Rubella antibody assay by the immunoperoxidase technique: comparison with the hemagglutination inhibition test for determination of immune status. The rubella immune status of 128 young women was determined with two assays for rubella antibody, the immunoperoxidase technique and the hemagglutination inhibition test. Comparison of the results of these techniques showed agreement in 125 cases (110 positive and 15 negative). Positive results were obtained for one woman only by the immunoperoxidase assay and for two women only by the hemagglutination inhibition test; all three of these women had a minimal titer of rubella antibody of 1:16. The sensitivity of the immunoperoxidase test was comparable to that of the hemagglutination inhibition test, and the specificity of the former test was verified. The peroxidase-labeled antibody technique is easier to perform than the hemagglutination inhibition test and is less time-consuming since sera do not require prior treatment and results can be obtained in as little as 90 min.


Delayed hypersensitivity to fungal antigens in mice. II. Molecular classes in immunogenic RNA extracts that transfer delayed hypersensitivity. The transfer of delayed hypersensitivity to Coccidioides immitis and Candida albicans antigens with immunogenic RNA extracts was studied in a mouse model. Sensitivity was measured by skin tests and footpad swelling responses. Immunogenic RNA converted normal spleen cells in vitro so that they produced antigen-specific delayed hypersensitivity in mice that were given injections of the cells. RNase reduced the rate of, but did not abolish, in vitro interaction of immunogenic RNA extracts with lymphocytes. Immunogenic RNA transferred sensitivity on direct intraperitoneal inoculation into mice. The transfer ability was resistant to RNase preparations active against both single- and double-stranded RNA. Sedimentation gradient fractions of the immunogenic RNA were assayed by intraperitoneal injection, and converting activity was found in two fractions, greater than 33S and 6S-13S. After treatment with RNase, all activity was shifted to the less than 6S fraction. Two fractions of the immunogenic RNA in its native state (greater than 33S and 6S-13S) were also able to convert spleen cells. The data indicate that the transfer of delayed hypersensitivity by immunogenic RNA preparations is associated with RNA but may not require the intact RNA molecule.


A canine distemper model of virus-induced anergy. For development of an animal model of virus-induced anergy, the effect of canine distemper virus (CDV) upon cell-mediated immunity in dogs was investigated. First, canine cutaneous reactions and in vitro lymphocyte responses to soluble protein antigens were characterized. Dogs immunized with picryl guinea pig albumin and with keyhole limpet hemocyanin (both in complete Freund's adjuvant) responded reproducibly to intracutaneous challenge with these antigens. Reactivity peaked in 20-40 days (maximal induration, 6-50 mm). Lymphocytes from these animals responded in vitro to stimulation with keyhole limpet hemocyanin or purified protein derivative. This stimulation was antigen-specific and was maximal on day 6 of culture. Infection with CDV depressed cutaneous reactivity and lymphocyte response in vitro to antigens and mitogens. This effect was transient in animals previously vaccinated with attenuated CDV; however, gnotobiotic puppies (susceptible to CDV) had prolonged depression of cell-mediated immunity and lymphopenia. Some of these animals developed neurologic symptoms and died. The findings indicate that CDV infection is a potentially useful model for study of virus-induced depression of T (thymus)-cell responses and support the hypothesis that there is more than one mechanism responsible for this phenomenon.


Vectorial characteristics of ventricular extrasystoles stimulated during cardiac catheterization. Ventricular extrasystoles (VES) from different areas of the ventricular muscle mass were obtained by mechanical stimulation of inflow and outflow regions of the right ventricle (RV) and apical and basal portions of the left ventricle (LV) during cardiac catheterization. Cube system vectorcardiogram (VCG) patterns of VES from each location were analyzed to determine the specificity of vector orientation from each site. Transverse plane VCG distinguished between nonseptal LVES and RVES, while a combination of transverse and either sagittal or frontal planes permitted further localization of septal VES to inflow or outflow regions of the RV and apical and basal areas of the LV.


Mobitz II atrioventricular block due to infra-Hisian block and bundle branch extrasystoles. An asymptomatic elderly male presented with complete right bundle branch block, left anterior fascicular block and Mobitz Type II second degree atrioventricular block. In addition, he was noted to have ventricular premature systoles. Electrophysiologic studies demonstrated two apparently different mechanisms for the second degree A-V block--infra-Hisian block and A-V block due to bundle branch extrasystoles arising in the affected right bundle branch. Concealed conduction of the bundle branch extrasystoles as the proximate cause of infra-Hisian block could not be excluded. However, both forms of A-V block were evidently dependent upon significant distal conduction system disease; this consideration was felt to warrant permanent pacemaker implantation.


Coexisting ventricular and blocked atrial parasystole. A rare instance showing non-conducted atrial parasystole coexisting with ventricular parasystole is presented and a related subject is briefly discussed. The importance of recognizing parasystole is again emphasized because the ordinary extrasystoles, particularly ventricular in origin, are frequently digitalis-induced, while parasystole, which superficially resembles the ordinary extrasystoles, does not seem to be related to digitalis.


Alpha-fetoprotein synthesis by murine lymphoid cells in allogeneic reactions. Surface-bound alpha-fetoprotein (AFP) was demonstrated by immunofluorescence on approximately 1/3 of splenic lymphocytes in chronic murine graft vs. host (GVH) reactions. Splenic lymphocytes were also shown to have a suppressed phytohemagglutinin (PHA) response compared to controls while lymph node cells from the same GVH animals revealed no surface AFP and had normal PHA responses. Splenic lymphocytes showed marked synthesis of AFP in the GVH and mixed lymphocyte culture (MLC) reactions by [14C]leucine incorporation and by radioimmunoassay in MLC supernates. Lymph node cells, however, demonstrated less synthetic activity and 14C counts in their membrane fractions were not markedly elevated.


Toward a theory of human disease.

Toward a theory of human disease. The importance of the idea of human disease is revealed by the attention that it receives in both the social and biological sciences. It is striking, thus, that despite its certrality and fundamental relevance to an understanding of man and his social institutions, no theory which exclusively addresses human disease has been developed. The purpose of this paper is to set forth a preliminary outline of a theory of human disease. In the paper, an exploratory approach is followed. That is, the requirements of and problem areas which a theory of disease should explain are touched on. The material draws from literature in both the social and biological sciences. Some attempt is made to link the material to contemporary questions in these fields.


Velocity measurements of particulate neuroplasmic flow in organized mammalian CNS tissue cultures. The movements of spherical particles in the range of 0.3 to 0.8 mum diameter within neurities of cultured embryonic mouse spinal cord fragments were observed and recorded by means of Nomarski optics and time-lapse photocinematography at high power. Particulate movements were measured by projecting the motion pictures onto a calibrated screen and recording the distances moved with time of linearly moving particles and making note of the direction (toward or away from the neuron soma) of movement. In all, 128 particles were measured in six cultures. These measurements were taken away from the neuron soma near the periphery of the neurites. Eight-three particles were noted to be moving toward the neuron at a mean velocity of 1.03 +/- 0.38 (SD) mum/sec while 45 anterograde moving particles were noted to move at 1.07 +/- 0.62 (SD) mum/sec. Statistical analysis of these veolcities revealed no significant difference between them.  Particles which were elongated and probably represented mitochondria moved more sluggishly and could not be measured accurately by the techniques employed. It appeared the spherical particles moving in a retrograde direction originated at the neurite tip apparently by pinocytosis. There was a suggestion that anterograde flow and retrograde flow may have been affected unequally by factors which develop in the observation chamber over a period of 2 hr or more. The most likely factor responsible was probably hypoxia.


Qualitative and quantitative studies on human myelin basic protein in situ with respect to time interval between death and autopsy. Normal human frontal lobe white matter obtained at autopsy was used to determine the extent of in situ post-mortem degradation of myelin  basic protein (BP). Effects of the following two factors were studied: 1) time interval between death and autopsy, and 2) freezing and thawing the tissue. Quantitative extraction of BP from the autopsy material showed only minimal loss of BP that could be attributed to the time interval between death and autopsy (up to 48 h). The purified BP from these samples was electrophoresed on acrylamide gels at pH 4.3 and it was found that the electrophoretic patterns were comparable to zero hour bovine BP samples. The BP obtained from the autopsy samples was found to be encephalitogenic in guinea pigs. When tested against rabbit anti-human-BP serum, the purified BP preparations gave a single arc in immunoprecipitin test. BP extracted and purified from tissue that was frozen once and processed before it could thaw showed yields, encephalitogenic activity and acrylamide disc gel electrophoretic patterns that were similar to those of BP from tissue that was never frozen. However, frozen tissue that was thawed and then incubated for 8 h at room temperature before processing yielded only 13-25% of the total extractable protein. This BP also was encephalitogenic and showed acrylamide banding pattern that was similar to BP from tissue that was never frozen. Samples of white matter were examined by electron microscope. Unfrozen autopsy material showed some separation of myelin lamellae. Myelin in sections of frozen and thawed white matter showed separation as well as disruption of the lamellae. Samples that were frozen, thawed and then incubated at room temperature for 8 h showed sporadic loss of dense line material in addition to lamellar separation and disruption. The results a) show that BP is quite resistant to autolytic changes and b) are consistent with the location of BP along the cytoplasmic surface of the myelin membrane.


[Clinical observations on hydrocephalus with special regard to the posttraumatic malresorptive form (author's transl)]. 100 cases of Spitz-Holter shunts performed for hydrocephalus over a period of 3 years were analyzed; 17 of these were of posttraumatic origin and are discussed in regard to pathogenesis, clinical symptoms, diagnostic methods, and therapy. Half of these 17 had severe traffic accidents. The rapidity and degree of ventricular dilatation were positively correlated with the duration of unconsciousness. When the unconsciousness had lasted more than 10 days hydrocephalus was recognized early, and the shunt was performed on an average 2 months after the trauma. Two thirds of the patients improved after the shunt operation. Pathogenetically we believe the important factors in the acute stages are increased CSF pressure, disturbed CSF dynamics, brain swelling and vascular circulation disorder; in the chronic stages, parenchymous atrophy. The following 3 types of posttraumatic hydrocephalus were differentiated on the basis of the clinical features: --symmetrical communicating internal hydrocephalus with malresorption, especially after subarachnoid hemorrhage, --communicating internal hydrocephalus alone, or in combination with external hydrocephalus resulting from atrophy, --internal occlusive hydrocephalus after trauma. The following posttraumatic clinical features were found to be indications that hydrocephalus may be present: in the acute stages inadequately long symptom resolution considering the severity of the trauma, secondary changes for the worse, an apallic syndrome which does not improve; in late stages, the presence of an Adams-Hakim syndrome charaterized by dementia, a spastic gait and loss of sphincter control. The most successful diagnostic methods were found to be pneumencephalography with 24 and 48 h delayed exposures, cisternoscintigraphy and continuous intracranial pressure monitoring in combination with the spinal infusion test. The most important intracranial shunting procedures and the indications for shunting are discussed.


[Paradoxical pupillary reaction to light -- a pupillographic study (author's transl)]. A report given of a 32-year-old female patient who exhibited a unilateral paradoxical pupillary reaction to light, but was obviously healthy in all other respects. All of the neuroophthalmological findings, including the infrared reflex-pupillographic results registered, are indicated and discussed in detail in the report. An analysis of the findings leads to the conclusion that this disturbance has a central, prenuclear location. Apart from a stenosis at the junction of the arteria vertebralis, which was determined angiographically, further examination did not reveal any pathological findings.


[Chronic pernicious course in multiple sclerosis with involvement of the optic nerves and total spinal sclerosis (diffuse spinal sclerosis) (author's transl)]. Four cases with the clinical diagnosis of chronic MS are presented, which, histologically, show large solitary demyelinated and gliotic areas involving almost the entire spinal cord over 12-25 segments as well as the optic chiasm. The abortive form of the neuromyelitis optical syndrome in MS is discussed. The additional involvement of the cerebral hemispheres suggests that the clinical and histological picture described is related to Schilder's disease.


Effects of threshold, low frequency, long lasting stimulation on single motor unit electrical responses from the extensor digitorum brevis muscle in normal and myasthenic subjects. The authors studied the recruitment of motor units of EDB muscle by long lasting threshold intensity stimulation at 1 c/sec of external popliteal nerve at the ankle in healthy subjects and in myasthenic patients. In the healthy volunteers, at steady intensity of threshold stimuli, maximum number of motor units never exceeded 5--6 electrical increments with a final incremental response of constant amplitude during 60 min of stimulation. In myasthenic patients, both an early exhaustion of threshold motor units and a marked facilitation phenomenon occurred with massive recruitment of incremental responses, while in a small number of cases no changes were observed. These data are discussed in the light of various morphofunctional hypotheses regarding the localization of the myasthenic impairment.


[Intracerebral hematoma with Nishimoto-Takeuchi-Kudo disease (Moyamoya disease): a contribution to the differential diagnosis of intracerebral hematoma (author's transl)]. A 40-year-old female was admitted with the diagnosis of an intracerebral hematoma. A bilateral carotid angiogram showed the typical signs of Nishimoto-Takeuchi-Kudo disease with a left temporal intracerebral expansive process. This disease must consequently be considered as another cause of an intracerebral hematoma. The pathogenetic and arteriographic aspects of this disease are considered.


[Cerebral involvement in the Sézary syndrome (author's transl)]. Two foci of histologically verified mycosis fungoides were found in the left parietal region of a 45-year-old man with involvement of the brain during an exacerbation of leukemia. There was perivascular and diffuse infiltration with lymphoma-like cells and occasional giant (Lutzner) cells but no involvement of the meninges. Both before and after operation the CSF contained a few atypical lymphocytes and mononuclear cells, one of which showed ultrastructurally the deeply clefted nucleus of Sézary cells. Atypical cells were confirmed morphologically in the peripheral blood, as well as by cytochemical (beta-glucuronidase) and immunological (rosettes with SRBC) markers, after the postoperative leucocytosis had subsided. It is suggested that this CNS involvement during a leukemic conversion phase of mycosis fungoides is consistent with the Sézary syndrome.


Changes in carotid flow velocity induced by direct percutaneous carotid angiography in man. Quantitative percutaneous flow velocity measurements are possible in carotid arteries. The results of the direct percutaneous angiography were measured by means of a Doppler directional flow velocity device and registered on a polygraphy. The results indicate an increase in the flow velocity of the injected as well as the non-injected carotid system. This implies that there are no local constrictions of the carotid artery following intervention and, furthermore, it implies a systematic effect of the puncture and injection itself, or of the contrast medium, on the whole cerebral circulation. A diffuse vasodilatation, at least in the cerebral circulation, is postulated. The possible implications are discussed.


Quantitative histometric studies and relation of number and diameter of myelinated fibres to electrophysiological parameters in normal sensory nerves of man. Quantitative histometric investigations were made in 6 radial and in 12 sural nerves of subjects without signs of a neuromuscular disorder. Nerve conduction velocities and amplitudes were studied on the same nerves. A linear relationship between the nerve fibre diameter and the conduction velocity of the fastest fibres was found. The conversion factor had a mean of 4.67, S.D. 0.16 in the radial nerves and an average value of 4.55, S.D. 0.19 in the sural nerves. Correlating the amplitudes of the compound nerve action potentials and the fibre number there was a linear proportionality between the log10 of number of fibres with a diameter of 11 mum and more, and the amplitude.


[Orbicularis oculi reflex after facial paralysis: decreased amplitude of reflex response and spreading to all hemifacial muscles after reinnervation (author's transl)]. After the acute stage of peripheral facial paralysis with nerve degeneration we find some signs of paresis after reinnervation due to insufficient motor recovery and associated movements due to faulty reinnervation. Electromyographical investigation of the orbicularis oculi reflex can be used for the objective evaluation of these two phenomena. This shows the following typical signs: 1. The amplitudes of the early and late reflex response are decreased on the affected side proportionate to the degree of paresis. 2. The response occurs in all reinnervated hemifacial muscles as a result of misdirection of fibres which originally innervated the orbicularis oculi muscle.


[The oculoauricular phenomenon: a new reflex, a new muscle -- m. retroauricularis (polygraphic EMG study) (author's transl)]. On forced lateral gaze the outer and upper part of both ears is turned backward (oculoauricular phenomenon). A new, as far as we know, skin muscle of the external ear is described and called "m. retroauricularis". The oculoauricular phenomenon is a reflex mechanism between the abducens (m. rectus externus) and facial (m. retroauricularis) nerves. The verification of the automatic and tonic coinnervation is made polygraphically (EMG, stimulodetection) and clinically (unilateral abolition in case of homolateral facial paralysis). The oculoauricular reflex is a physiological and bilateral phenomenon, often rudimentary in man. It serves in looking, hearing and miming. The bilateral mechanism of innervation in the brainstem via the medial longitudinal fasciculus corresponds to Bell's phenomenon as to the "anti Bell".


Editorial: Post-therapeutic radiation injuries of the nervous system. Reflections on their prevention. The introduction of the concept of Nominal Standard Dose and of Time, Dose Fractionation Factors ostensibly permits definition of tolerance doses for normal tissues in unequivocal terms. However, even with these refinements, tolerance doses remain, at best, guidelines, because radiobiologic effectiveness is governed not only by the effective dose, but also by individual factors, which will modify the response. Attention must be accorded to these biologic parameters, in order to prevent injury to healthy tissues. Of particular significance are the relative size or volume of the irradiated tissue, the possible presence of co-existing pathology in the exposed organ and the development of disease after tge termination of the treatment. Even if these factors are properly respected, the risk of radiation injury cannot entirely be eliminated. The radiotherapist is therefore obligated to use an approach which minimizes the exposure of the healthy nervous tissue, a goal which has become attainable with the advent of modern accelerators as radiation sources.


Proprioceptive feedback performance in patients with focal brain lesions. Utilization of proprioceptive feedback in a manual tracking task was studied in patients with circumscribed unilateral brain lesions. Patients with posterior right hemisphere disease showed severe impairment in performance as compared to those with lesions in other areas of the brain. Increasing the intensity of proprioceptive feedback facilitated the tracking performance of left hemisphere damaged patients while patients with right hemisphere lesions failed to improve. The results were interpreted as supporting the view that the posterior right hemisphere plays a particularly important role in the utilization of proprioceptive information to maintain the position of body parts in space.


[Investigations on the Variability of the phasic pupillary light reflex (author's transl)]. Infrared pupillography was used to determine physiological time parameters of the direct phasic light reflex in 101 normal subjects. These parameters include latency, contraction and redilatation times as well as total reaction time, measured in response to 4 different light stimulus intensities. A total of more than 4000 pupillary stimulations in these subjects was analyzed statistically. The study of these time parameters included determination of the mean, the standard deviation and three dimensional analysis of variance, with the following results: 1. The physiological time parameters are bilaterally symmetrical. 2. The most stable parameters with least variability in an individual subject were latency and contraction time. The redilatation time, however, showed marked intra-individual variability. 3. Variance analysis revealed a high degree of correlation among the different parameters to light stimuli of varying intensity. 4. There was a highly significant prolongation of latency and of contraction time with increasing age. 5. No sex dependent effect on physiological time parameters was found. In addition, no interaction among light stimulus intensity, age and sex could be detected. Possible applications of the method for clinical neurological examination are discussed.


On the occurence of vanillic acid in human brain and cerebrospinal fluid. 3-methoxy-4-hydroxyphenylbenzoic (vanillic) acid was previously shown to be one of the endogenous metabolites of adrenaline and noradrenaline. Using thin-layer chromatographic methods for identification and quantification of phenolic acids and phenolic alcohols, the authors identified vanillic acid in different regions of the human brain. The concentration of vanillic acid in the cerebrospinal fluid was also determined and compared to the concentration of 3-methoxy-4-hydroxyphenylethylene glycol. The identification of VA in the human brain suggests that the vanillic acid of the cerebrospinal fluid originates, at least in part, from the catecholamines in the brain. The authors discuss other possible origins of vanillic acid besides the noradrenaline catabolism of dopamine. As the concentration of vanillic acid in the cerebrospinal fluid was found to be greater than the concentration of 3-methoxy-4-hydroxyphenylethylene glycol, it might be important for clinical biological studies to measure vanillic acid in the cerebrospinal fluid as well as the other alcoholic and acid catabolites of the catecholamines.


Quantitative electromyography in the detection of the carriers in Duchenne type muscular dystrophy. The quantitative EMG technique was used to detect Duchenne muscular dystrophy carriers. The tests were carried out, measuring the parameters of M.U. potentials (the duration, the phase, and the 0 index according to Van den Bosch, modified by Gardner-Medwin), and using the Willison analyzer, in a group of carriers and normal subjects. Ten M.U. potentials from the deltoid, biceps brachii and quadriceps muscles were photographed and measured in each subject, and the right and the left biceps were examined with the Willison analyzer. An high detection rate was obtained by manual EMG, measuring traditional values such as mean number of phases, A.P. duration and 0 index. The Willison analyzer was significant in 2 known carriers. The total EMG detection rate was higher than the CPK tests both in the known carriers and the possible carriers. It is concluded that the quantitative EMG technique is an useful and specific test to detect carriers of the gene of Duchenne muscular dystrophy.


Biochemical findings in multiple sclerosis. III. Immunoglobulins of restricted heterogeneity and light chain distribution in cerebrospinal fluid of patients with multiple sclerosis. Several biochemical parameters, the most important of which are total IgG, kappa and lambda light chain distribution and thin layer isoelectric focusing, were determined in the cerebrospinal fluid of 36 multiple sclerosis patients. Their ages and the evolution period of their disease are widely spread and no sex differentiation was made.


Morphological signs as indications of function of cells in the cerebrospinal fluid. It is suggested that a continual cell exchange exists between blood and the subarachnoid space. These cells can live for a shorter or longer time there and fulfil their function depending on local conditions. In addition to phagocytosis, morphological evidence of local cellular and humoral immunological reactions have been demonstrated and how far they concour with current views on the functional state of spinal fluid cells has been examined. Peripolesis and emperipolesis, transformation of lymphocytes as well as various cell processes, as signs of function, are illustrated by light transmission and scanning electron microscopy as well as by immunological methods in various inflammatory diseases of the central nervous system.


[Dyscephalia-cataracta congenita-hypotrichosis (DCH) syndrome (Ullrich-Fremerey-Dohna, Hallermann-Streiff, Francois). Report of a case showing extrapyramidal hyperkinesia and dementia (author's transl)]. In a 43-year-old man dyscephalia, cataracta congenita, and hypotrichosis were the outstanding features. These signs were first described in 1953 by Ullrich and Fremerey-Dohna as a clinical entity. Since 1958 the DCH syndrome was published under the synonyms of "Francois syndrome" and of "Hallermann-Streiff syndrome". However, as these authors did not add any essential details relevant for the classification of the syndrome we prefer to retain the term "Ullrich-Fremerey-Dohna syndrome". In our case in addition to the above mentioned and well known manifestations, extrapyramidal hyperkinesia of the choreoanthetotic type and servere mental deficiency accompanied by mild cerebral atrophy (revealed by pneumencephalography) were found.


[Hyperinsulinism. Neurological and psychiatric aspects (author's transl)]. A case of a patient with hyperinsulinism due to insulinoma associated with neurological and psychiatric disturbances including EEG alterations is reported. The hunger test as well as the i.v. tolbutamid test proved to be of diagnostic importance. In addition, the electroencephalographic studies combined with blood sugar analyses before and after 50 g glucose, orally, showed a reversibility of the EEG alterations together with normalization of the blood surgar levels. These results point to the possibility of differentiating biochemical from structural cerebral lesions associated with hyperinsulinism.


Iodinated bleomycin: an unsatisfactory radiopharmaceutical for tumor localization. Cobalt-57-bleomycin is a clinically useful tumor-localizing agent, but attempts to label bleomycin (BLEO) with other radionuclides have been made because of the long physical half-life of 57Co. As an alternative labeling approach, we iodinated BLEO both directly on the imidazole ring and indirectly by reaction with N-succinimidyl 3-(4-hydroxy, 3-iodophenyl) propionate. Directly iodinated BLEO retained antibacterial activity, but in tumor-bearing rats it showed a lower tumor-to-blood ratio (2.3) at 2 hr than did 57Co-BLEO (11.8). The antibacterial activity of the indirectly labeled BLEO was markedly reduced and this material showed a tumor-to-blood ratio of 0.55 at 2 hr. The radioiodinated bleomycins are not suitable substitutes for 57Co-BLEO as tumor-imaging radiopharmaceuticals.


The Paneth cell population of the small intestine of the rat-effects of fasting and zinc deficiency on total count and on dithizone-reactive count. The distribution of Paneth cells in the rat small intestine was found to be approximately one per crypt in the duodenum, two to three per crypt in the jejunum and four to six per crypt in the ileum. The ileum has more Paneth cells containing dithizone-reactive zinc than the duodenum and jejunum. Zinc deficiency had no significant effect on the total Paneth cell count but no dithizone-reactive Paneth cells were found in any area of the small intestine examined in zinc-deficient animals. Fasting for 3 days had no significant effect on the Paneth cell count but after a 4-day fast there was a significant rise in the total Paneth cell count accompanied by a fall in the percentage of Paneth cells containing dithizone-reactive zinc in all areas examined.


Effects of lipids on bioavailability of sulfisoxazole acetyl, dicumarol, and griseofulvin in rats. The effects of hexadecane, oleyl alcohol, polysorbate 80, trioctanoin, and triolein on the bioavailability of sulfisoxazole N1-acetyl, dicumarol, and griseofulvin were investigated. Compared to administration of the drugs in water, the rate of absorption of the drugs was either decreased or not changed by the lipids. The extent of absorption of sulfisoxazole acetyl and dicumarol was significantly increased by polysorbate 80 and triolein and not affected by hexadecane or oleyl alcohol. Tricotanoin increased the extent of abosrption of sulfisoxazole acetyl but had no effect on the absorption of dicumarol. Compared to the aqueous vehicle, the extent of absorption of greiseofulvin was decreased by hexadecane, oleyl alcohol, and triolein, increased by polysorbate 80, and not affected by trioctanoin. The extent of absorption of sulfisoxazole acetyl was not affected by the amount of triolein in which it was administered nor by emulsification of triolein prior to administration.


Immunopharmacologic properties of WY-16,922, a new orally effective antiallergic agent. In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, longs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.


Effects of ethanol on the permeability of toad urinary bladder epithelium. Ethanol (9%) decreases the potential difference across the toad bladder when present at the mucosal surface, the short-circuit current was unchanged. The electrical resistance decreased indicating a change in ion movements across the bladder. Unidirectional 22Na and 36Cl flux measurements showed an increase in the movement of Cl, but no change in Na. The vasopressin-induced increase in Na transport (natriferic response) was also unaffected by the presence of ethanol. It is suggested that ethanol may be altering the apical tight junctions and affecting an anion selective pathway. The hydro-osmotic response of the toad bladder to vasopressin was decreased by 70% in the presence of 3% ethanol. The hydro-osmotic action of cyclic adenosine monophosphate was also inhibited by ethanol, indicating an action subsequent to the endogenous formation of this nucleotide. Tritiated water fluxes (in the absence of an osmotic gradient) were reduced by 30% in the presence of 3% ethanol. The vasopressin-induced increase in diffusional water flow was similarly reduced. Osmotic water movements across glutaraldehyde and N-ethylmaleimide-"fixed" vasopressin-stimulated bladders were also decreased in the presence of ethanol. However, 3% ethanol had no effect on osmotic water transfer across artificial collodion membranes. Ethanol, therefore, probably interacts with the bladder membrane. The Ktrans (permeability coefficient) of ethanol and water is increased by vasopressin. suggesting that their movement is through similar pathways. It is suggested that ethanol empedes the flow of water across the toad bladder by facilitating a physicochemical interaction between the membrane "pore" and the water molecules.


Immunological heterogeneity among the M-associated protein antigens of group-A streptococci. Different serotypes of group-A streptococci share common antigens that are closely associated with the type-specific determinant of M protein. By the use of selected human sera containing antibody to these M-associated antigens, we have shown that group-A streptococci can be divided into three categories. The majority of the opacity-factor-negative respiratory serotypes possess a shared M-associated antigen or antigens, to which high titres of antibody are common in patients with rheumatic fever, or patients recovering from upper respiratory infections with certain opacity-factor-negative serotypes. The antibody in these sera has a demonstrable but limited affinity for the M-associated antigens of strains belonging to a second category of M types, the majority of which are opacity-factor-positive serotypes of "throat" or "skin" origin. A third group, consisting mainly of opacity-factor-negative pyoderma serotypes, gave variable results and seemed to be intermediate between the other two categories. Complement-fixation-inhibition tests and absorption studies showed a marked degree of cross-reactivity between the M-associated antigens of the three categories.


Loss of protective antigen, histamine-sensitising factor and envelope polypeptides in cultural variants of Bordetella pertussis. Five Bordetella pertussis strains of phase I were grown in conventional casamino-acid medium and in media modified by adding high concentrations of MgSO4 or nicotinic acid. Cells grown in high-magnesium media (in the C-mode) had only about 4% of the protective antigen (PA) and 6% of the histamine-sensitising factor (HSF) of cells from the normal medium. Envelopes from C-mode organisms when examined by SDS-PAGE showed a loss of 28K and 30K polypeptide bands. Similar parallel losses of PA, HSF and 28K and 30K bands were found with cells from the high-nicotinic-acid medium. A medium with a high concentration of nicotinamide gave cells with normal amounts of PA, HSF and 28K and 30K bands. Growth in high concentrations of Na2SO4 caused partial losses of PA, HSF and 28K and 30K bands, while a high-succinate medium gave cells with somewhat diminished PA and HSF but without appreciable attenuation of the 28K and 30K bands. Because of the close correlation between the presence or absence of PA, HSF and 28K and 30K envelope polypeptides, it is suggested that the latter may represent or be closely associated with the components responsible for PA and HSF activities.


Acute phase proteins in children with protein-calorie malnutrition. The serum concentrations of the acute phase proteins, C-reactive protein, caeruloplasmin and haptoglobin were significantly higher in children with protein-calorie malnutrition than in age-matched controls, while the concentrations of alpha1 antitrypsin, alpha2 macroglobulin, transferrin and complement component C3 were significantly lower. During rehabilitation and treatment with antibiotics, C-reactive protein disappeared from the serum in most of the patients whilst the levels of caeruloplasmin and haptoglobin returned to normal values. On the other hand the serum concentration of alpha1 antitrypsin, alpha2 macroglobulin, transferrin and C3 showed significant increases. It is suggested that C-reactive protein and haptoglobin may provide useful indices of the presence or absence of infection in children with malnutrition.


Comparative trial of thiacetazone with isoniazid and paraaminosalicyclic acid (PAS) with isoniazid in the treatment of pulmonary tuberculosis in Nigerians. A comparative trial of a combination of thiacetazone 150 mg with isoniazid 300 mg in a once daily dose and that paraaminosalicyclic acid 12 gm uith isoniazid 300 mg daily in divided doses was carried out on 72 specially selected patients with pulmonary tuberculosis over a period of 12 months. The result of the trial showed that patients treated with thiacetazone/isoniazid combination responded equally favourably to therapy as the patients treated with PAS/isoniazid combination. The result of sputum conversion was similar in both groups. Radiological changes after treatment showed a significant similarity in both groups. It was observed that the thiacetazone/isoniazid combination is no more toxic than the PAS/isoniazid combination. There was no case of blood dyscrasia during the trial. Of the 72 patients who started the trial, a total of 19 (26 per cent) patients defaulted before the end of the third month. However, the remaining 53 patients (74 per cent) completed the trial, and the final analysis was based on this number. It was concluded that thiacetazone (150 mg/day) was of similar efficacy when compared with PAS (12 gm/day) as a companion drug for isoniazid (300 mg/day) in producing sputum conversion, and radiological changes in Nigerian tuberculosis patients and is therefore to be preferred because of its relative cheapness and once-a-day administration.


Post-prostatectomy impotence.

Post-prostatectomy impotence. With the help of the principles of rapid eye movement sleep and nocturnal penile tumescence, 14 patients who underwent transurethral prostatectomy were studied by monitoring the electroencephalograph, electro-oculograph and penile plethysmograph activity preoperatively and postoperatively. No instance of complete loss of penile erection was found postoperatively. The need for objective rather than subjective data is emphasized.


Enhancement of encephalitogenic activity by the formation of myelin basic protein-brain acidic protein complex. Encephalitogenic protein fraction (BEC) was isolated from bovine brain tissue by extraction with salt-ethanol mixture at neutral pH, instead of employing dilute mineral acid. The fraction BEC was separated into two fractions. An acid-soluble protein was encephalitogenic and the major component was very alike to the basic protein of myelin (Al). The other was acid-insoluble acidic protein that was not encephalitogenic even at a dose of 100 mug. The acidic protein formed an insoluble complex with Al rotein which was purified by Eylar's method. Encephalitogenic activity of the complex was higher than Al protein in young guinea pigs when injected with complete Freund's adjuvant.However, this enhancement of encephalitogenic activity was not observed in aged guinea pigs. The complex showed higher blastogenic activity than Al protein alone with peripheral blood lymphocytes from guinea pigs immunized with Al protein and complete Freund's adjuvant. These results show that an adjuvant-like acidic protein is present in brain tissue and the complex with Al protein enhances the induction of experimental allergic encephalomyelitis (EAE).


Experimental allergic encephalomyelitis (EAE) in mice. I. Induction of EAE with mouse spinal cord homogenate and myelin basic protein. The condition of experimental allergic encephalomyelitis (EAE) induction was investigated in several mice strains. SJL and C3H/He strains were found to be susceptible. A single immunization with mouse spinal cord, complete Freund's adjuvant (CFA) and pertussis vaccine produced clinical signs of EAE in SJL and C3H/He strains after 11 to 18 days. Isogenic spinal cord produced EAE in C3H/He strain. A single immunization with myelin basic protein from bovine spinal cord in CFA and pertussis vaccine produced EAE in SJL strain. EAE susceptibility of SJL strain correlated with the amount of mycobacteria used for sensitization. It was necessary to give pertussis vaccine intravenously in all cases.


[Acid mucopolysaccharides in human blood and bone marrow cells shown by fluorescence microscopy (author's transl)]. In lymphocytes, monocytes and basophil granulocytes of patients with mucopolysaccharidosis specific fluorescence of acid mucopolysaccharides exists after fixation of blood smears with 9-aminoacridin-hydrochloride and subsequent staining with pseudoisocyanine at pH 4.2. A total of eleven children with various types of mucopolysaccharidosis were investigated. Specificaly stained granula were demonstrated in 5 to 49 percent of all lymphocytes and monocytes. Acid mucopolysaccharides were for the first time also shown in red-cell precursors of the bone marrow of children with mucopolysaccharidosis.


Combined therapy in carcinomas of the female breast. Of 606 female breast cancers treated, 364 of them in stage I, II and III, only 7 cases were in stage I. All stage II and III cases in good general condition received radical preoperative irradiation to the entire breast volume and the regional lymphatic areas over a period of 4 wk, followed 4 wk later by a radical mastectomy. No postoperative irradiation was administered. The biological basis of this therapeutic policy is explained in detail and the 5-yr disease-free survival of patients in relation to stage of disease, treatment method, histology of the primary tumor, histologic nodal metastatic status, postradiational status of the breast primary, the menstrual status of the patient, and the general metabolic status is discussed. It is explicitly shown by meticulous histological study of the breasts and the axillary lymph nodes removed at surgery that radical irradiation per se is inadequate to sterilize the breasts and that subsequent radical surgery is essential. Furthermore, two-thirds of the stage III cancers, which would have been considered inoperable by conventional criteria, were rendered operable by preoperative irradiation, with a near 50% 5-yr disease-free survival.


One drug (phenytoin) in the treatment of epilepsy. Thirty-one, previously untreated, adult outpatients with idiopathic or focal grand-mal and/or focal minor seizures were treated initially with phenytoin. Serum-phenytoin concentrations were monitored to achieve an optimum range of 10-20 mug/ml if necessary. With a mean duration of follow-up of 14-7 months, only three (10%) patients have required the addition of a second drug, although without the guidance of serum concentrations sixteen (54%) might have been treated with a further drug. In the optimum serum-phenytoin range only 1 grand-mal attack occurred in this series, compared with a mean pre-treatment grand-mal seizure-rate of 1-1/month. Serum phenytoin declined slowly in fourteen (45%) patients. These observations suggest that many epileptic patients  could be satisfactorily treated with one drug instead of the polypharmacy which they usually receive.


Doxorubicin/B.C.N.U. chemotherapy for multiple myeloma in relapse. A combination of doxorubicin ('Adriamycin") and B.C.N.U. (1,3 di[2-chloroethyl]-1-nitrosourea) (30 mg/m2 of each intravenously every 3-4 weeks) was used to treat thirteen multiple-myeloma patients who did not respond or were in relapse after remission produced by alkylating-agent/prednisone therapy. All cases were staged according to total-body myeloma-cell number and followed quantitatively for response to therapy. Seven of the thirteen patients responded (54%). Two had complete clinical remissions and a greater than 75% reduction in tumour-cell mass lasting 12 and 16 months. Five others had partial remissions with lesser degrees of tumour-mass reduction and bone pain and improved haemoglobin and serum-albumin concentrations. Toxicity was limited to occasional myelo-suppression, mild alopecia, and nausea. The results indicate the usefulness of doxorubicin/B.C.N.U. for myeloma patients who have relapsed during previously effective alkylating-agent therapy.


Coronary arteriographic findings in type-II and type-IV hyperlipoproteinaemia. Coronary arteriography was performed in 46 patients with type-II and type-IV hyperlipoproteinaemia. Type-II patients had a high prevalence of main left coronary disease and of distal coronary atherosclerosis, while type-IV patients usually had disease localised to the proximal coronary tree. These differences may be related to the differing plasma-lipoprotein patterns in these two syndromes.


Enhanced antibody responses in active chronic hepatitis: relation to HLA-B8 and HLA-B12 and porto-systemic shunting. Titres of antibodies to rubella, measles, smooth muscle, nuclei, and Escherichia coli were examined in relation to the presence of particular histocompatibility antigens in 57 patients with active chronic hepatitis, 8 of whom were HBsAg positive. With the exception of antibodies to E. Coli, the HBsAg-negative patients with HLA-B8 or HLA-B12 had higher titres than those with neither, and antibody titres were highest in the 7 cases with both these histocompatibility antigens. In contrast, E. coli antibody titres were not related to the presence of particular histocompatibility antigens but correlated closely with the degree of portosystemic shunting. None of the HBsAg-positive patients possessed HLA-B8, and titres of all the antibodies were significantly lower than in the HBsAg-negative cases. The increased antibody response in HBsAg-negative patients is likely to be due to a genetically determined increase in immunological responsiveness for which HLA-B8 and HLA-B12 are markers. The results obtained in healthy family members also suggest that this defect in immunoregulation is under polygenic control.


Renin/angiotensin system in hypertension after traumatic renal-artery thrombosis. Hypertension was found in four patients after unilateral renal-artery thrombosis following blunt abdominal trauma. In one patient, who was followed up from the time of injury, renin hypersecretion and secondary aldosteronism developed within a few days, and hypertension was present 12 weeks later. Increasing haemoglobin and raised blood-erythropoietin concentrations were also found. In the three other patients, hypertension was found casually within 3 years of trauma. In all patients, unilateral renin production by the affected kidney was significantly increased. Nephrectomy of the diseased kidney corrected hypertension and endocrine abnormalities in all patients. The delayed onset of hypertension despite early activation of the renin/angiotensin/aldosterone axis accords with the course of events observed in experimentally induced hypertension in rats, and suggests that several weeks or even months are required for hypertension to develop after sudden renal-artery occlusion in man. Slowly acting mechanisms, probably initiated by hypersecretion of renin, may be responsible for the hypertension.


Relation between postphlebitic changes in the deep veins and results of surgical treatment of venous ulcers. 41 patients with venous ulceration, investigated by ascending phlebography, had operations to ligate incompetent calf perforating veins. Recurrent ulceration developed within five years of operation in all 23 patients with evidence of deep-vein damage on the initial phlebograms. Only 1 of the seventeen patients with normal deep veins had a recurrent ulcer during the same period of follow-up. Thus local surgery to the perforating veins in postphlebitic limbs was shown to be ineffective.


Radiotherapy in treatment of acute rejection of human renal allografts. 36 patients who received a renal transplant and who subsequently underwent a rejection episode were randomised into two groups. The first group received a standard form of rejection therapy consisting in high doses of steroid drugs, and the second group received in addition 600 rads of radiotherapy to the graft. After three years (minimum follow-up twelve months) the groups were compared with respect to patient and graft survival and level of transplant function. No benefit was obtained by the group receiving radiotherapy.


Antilymphocyte globulin in the treatment of advanced Sézary syndrome. Two patients with Sézary syndrome, refractory to conventional treatment, were given cyclophosphamide and antilymphocyte globulin (A.L.G) Both patients showed improvement. One patient subsequently died from widespread varicella and the other relapsed later. It is concluded that A.L.G. may be effective in this condition.


Childhood seizures: a 25-year follow up. Social and medical prognosis. Over 200 children from a group of 628 were followed up after 25 years. The children were identified as having had at least one seizure. Particular attention was given to the long-term prognosis in relation to medical, social, and educational problems. Although nearly two-thirds of the sample suffered minimal ill-effects, the problems of the remainder were considerable. 10-1% had died. Of the survivors 11-2% were confined to institutions, and 6-6% were invalids at home. Just under a quarter had chronic epilepsy. While overall the educational achievement of the sample was good, there was also a considerable number of educational problems. Continuing epilepsy was associated with greatly reduced educational and occupational achievement compared with the group in remission. The study reveals the considerable cost of epilepsy to the community in both human and material terms. It also reveals why epilepsy is regarded as a frightening illness.


Clinical chemistry reporting. Problems and proposals. The completed report is the most obvious interface between the laboratory and the clinician. An unattractive, uninformative, or confusing report may fail to do justice to an excellent analytical service. Unfortunately, relatively little effort has been expended on achieving the best possible report, and individual enthusiasm and initiative has led to widely diverse practices in reporting. There is an urgent need for standardisation of report formats and it is suggested that all reports should include guidance on abnormality, be in cumulative format, and contain a realistic statement of analytical reliability.


Bladder cancer in rubber workers. Do screening and doctors' awareness distort the statistics? The use of recognised carcinogens in the rubber industry before 1950 led to the introduction of screening progammes offering urinary cytology to workers who had been exposed. Publicity given to the introduction of these programmes and to individual claims for compensation have increased medical practitioners' awareness of a relationship between work and the industry and the subsequent development of bladder cancer. In this study 27 rubber workers and 88 controls registered in 1966 and 1967 with bladder cancer have been followed. A comparison of their death-rates and of the relative frequency of bladder cancer recorded on the death certificates should indicate whether cytological screening or doctors' awareness might explain a recent rise in the bladder-cancer death-rate in this industry. Since the proportions of rubber workers and controls who died before 1976 were similar (74% and 73% respectively) and bladder cancer was mentioned with similar frequence on their death certificates (80% and 83% respectively) neither screening nor doctor's awareness would appear to have an important influence.


Behaviour in a medical clinic of patients with well-controlled bronchial asthma. Patients with well-controlled bronchial asthma coming to a university health services clinic exhibited often irritating and sometimes unusual social behaviour. For example, they were more likely to arrive late for an appointment, or not to show up for it at all, than non-allergic healthy patients, patients with perennial rhinitis, patients with seasonal rhinitis, or patients being investigated for cardiac disease. Such behaviour may be just as much a sign of bronchial asthma as is coughing or wheezing.


Man in transit: Biochemical and physiological changes during intercontinental flights. Fifteen members of the passengers and crew of a plane flying from Buenos Aires to London have been studied, before, during, and after the 20-hour flight. Even allowing for circadian variation, there were clear rises in the urinary excretion of noradrenaline in the first part of the flight, and of both noradrenaline and adrenaline in the 2 days afterwards.


Brain damage in National Hunt jockeys.

Brain damage in National Hunt jockeys. Five National Hunt jockeys have been found to have post-traumatic encephalopathy- three with epilepsy and two with significant intellectual and psychological deterioration. Closer supervision is needed.


Treatment of duodenal ulcer with cimetidine. In a small open trial nineteen patients with active duodenal ulceration shown by fibreoptic endoscopy were treated with a 6-week course of cimetidine 1.6 g daily. Seventeen had healed ulcers on repeat endoscopy at 6 weeks. Seven of these have relapsed symptomatically within a month of withdrawal of cimetidine. No statistically significant change in the haemoglobin, white-blood-cell count, urea and electrolytes, or liver-function tests was associated with treatment. Plasma-creatinine showed a very small but significant rise but the mean level remained within the normal range. The significance of this is not clear.


Immunoglobulins within human small-intestinal Paneth cells. Human duodenal, jejunal, and ileal samples obtained at necropsy and by peroral and surgical biopsy, were studied by light microscopy using the unlabelled antibody enzyme method for imunocytochemical staining of lysozyme and immunoglobulins. Paneth cells contained IgA and IgG, but not IgD IgE, or IgM. Staining intensity indicated that IgA and IgG were present in amounts greater than in other epithelial cells. There was pronounced variation in the immunoglobulin content of Paneth cells. Rat Paneth cell containing IgA and lysozyme and are capable of the phagocytosis and degradation of microorganisms. These observations suggest that human Paneth cells may have similar functional capabilities.


Transfer-factor therapy in multiple sclerosis. The effect of transfer factor prepared from relatives of patients with multiple sclerosis (M.S.) and from unrelated donors on the clinical course of M.S. has been studied in fifteen male and fifteen female patients. Some patients were given transfer factor and some placebo (physiological saline). Results of three independent clinical examinations by different neurologists and subjective assessments by the patients showed no difference between those given transfer factor and those given placebo.


Cystic fibrosis heterozygosity in the pathogenesis of allergy. 47% of cystic fibrosis (C.F.) heterozygotes had positive prick skin tests of 1 or more of 9 antigens and 53% had histories of allergic disease, both occurring significantly more often than in a control group. Since 1 in 20 of the population are C.F. carriers, this would contribute to allergy in the community.


Possible dual role for vasoactive intestinal peptide as gastrointestinal hormone and neurotransmitter substance. Vasoactive intestinal peptide (V.I.P.) has been found in high concentrations both in the gastrointestinal tract and, unexpectedly, in the central nervous system. Immunocytochemical studies have demonstrated V.I.P. in nerve-fibers. These findings challenge the concept of V.I.P. as a simple gastrointestinal hormone and suggest a possible neurotransmitter function.


Effect of "fractionated" insulins on total plasma insulin binding capacity and insulin requirements in severe diabetes. Serial observations of insulin requirement and total plasma insulin binding capacity have been carried out on six xevere diabetics whose treatment was changed from standard soluble and isophane (NPH) insulins to "fractionated" preparations (Nordisk Insulin Ltd). No correlation was found between initial insulin dose and binding capacity, but changes in these two functions during the study period were closely correlated, both for the group as a whole and for individual patients in whom falls in insulin dose occurred. It is concluded that highly purified insulins could be valuable in the treatment of insulin-resistant cases, that their use is frequently associated with a gradual reduction in insulin dose, and that estimation of total plasma insulin binding capacity may indicate which patients are most likely to benefit from fractionated insulin. No sudden change in insulin requirement was seen on changing to purified insulin preparations.


Breast and thyroid cancer and malignant melanoma promoted by alcohol-induced pituitary secretion of prolactin, T.S.H. and M.S.H. In interview data from the U.S.A.'s Third National Cancer Survey, alcohol ingestion was associated with a higher occurrence of cancers of the breast, thyroid, and amlignant melanoma. Data from other studies support the first two associations. A unifying hypothesis to explain these seemingly diverse associations suggests that alcohol stimulates anterior pituitary secretion of prolactin, thyroid-stimulating hormone (T.S.H.), and melanocyte-stimulating hormone (M.S.H.). Under the stimulations of these hormones, the three target tissues exhibit increased mitotic activity and hence an increase susceptibility to the development of a malignancy. A wide variety of findings from other studies indicate plausibility for this hypothesis. The implications could be grave. In addition to alcohol, several common drugs acting in similar manner could be cancer promoters, including: resperine, methyldopa, phenothiaznes, d-amphetamine, tricyclic antidepressants, and antihistamines. Over 20000 (25%) ofall new breast-cancer cases each year in the U.S.A. could be preventable if this hypothesis is correct.


Predicting outcome in individual patients after severe head injury. Clinical data available in the first few days after severe head injury have been collected prospectively on 600 patients from Glasgow and the Netherlands and stored on computer; the patients in the two countries were similar in initial severity and in their outcome on a defined scale at 6 months. Calculated predictions of outcome were made in 200 randomly selected cases, using Bayesian statistics to compare the data from each patient with those from the 400 remaining cases whose outcome was known. Confident predictions (greater than 0-97 probability) were made in 44% of cases within the first 24 hours of coma, and in 52-61% when data up to 3 days were available. The higher confidence-rate occurred when prediction was limited to two outcomes (death or survival). Comparison of predicted with actual outcomes showed that 96-98% of confident predictions were correct. More logical clinical decisions should be possible when these predictions are available.


Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis. Parathyroid hormone, injected daily in low dosage, exerted anabolic effects on the human skeleton, just as it does in the rat. Four postmenopausal women with primary osteoporosis were treated for six months with a synthetic fragment of human parathyroid hormone (hP.T.H. 1-34), given as a daily injection of 100 mug. This treatment caused a remarkable acceleration of bone turnover, indicated both by isotopic tracer and histological methods. At this normocalcaemic dose level, the increases in bone formation outweighed increases in resorption. Three of the four patients showed more positive calcium balances, and mean increases in calcium and phosphorus balances were statistically significant for the group as a whole, the changes being principally due to increased intestinal absorption of both elements. Many modifications of the present method of hormone administration are possible which could further increase the preponderance of anabolic effects. These results suggest that low doses of hP.T.H. 1-34, alone or in combination with other agents, may prove useful in the treatment of osteoporosis.


Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Treatment of 63 oophorectomised women with oestrogen for five years prevented the reduction in bone mineral content observed in 57 women treated with a placebo preparation. When onset of therapy was delayed for three to six years there was a highly significant increase in bone mineral content mainly during the first three years of treatment. During the next two years there was no further increase in bone mineral, while the placebo-treated groups continued to lose bone at about 1% per annum. In association with the changes in bone mass, the expected biochemical effects of oestrogen therapy also persisted for at least three years, and were compatible with a prolonged increase in parathyroid activity but a reduction in bone turnover.


Place of azathioprine for Crohn's disease. The clinical effects of azathioprine have been compared with those of corticosteroids in a group of 112 patients who have come under the care of a single unit between 1963 and 1975. There is no clear evidence that azathioprine alters the course of the disease in the long term; it is of value in obtaining a remission, particularly when the disease affects the large intestine.


HLA-B27 and frozen shoulder.

HLA-B27 and frozen shoulder. Histocompatibility antigens were determined in 38 patients with frozen shoulder and 216 normal blood-donors. HLA-B27 was significantly more common in patients with frozen shoulder (42%) than in the controls (10%). The distribution of the other 19 histocompatibility antigens was similar in the patient and control groups. This result may be associated with the suggested immunological pathogenesis of the condition.


Controlled trial of 1apha-hydroxycholecalciferol in chronic renal failure. 24 patients with chronic renal failure (glomerular filtration-rate (G.F.R.) 5-25 ml/min) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol (1alpha-H.C.C.) 1 mug daily for eleven weeks. This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks. It also induced a significant reduction of the raised serum levels of parathyroid hormone. No significant changes were induced in plasma-phosphorus, plasma-alkaline-phosphatase, or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone. The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group. The fall in G.F.R. over eleven weeks was 2-5 times greater in the 1alpha-H.C.C. group than in the placebo group, but this difference was not significant. It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium.


Isolated temporary pharyngeal paralysis in childhood. Three children developed dysphagia and rhinolalia indicating isolated paralysis of the ninth and tenth cranial nerves. They recovered completely after three to four weeks. The clinical features suggested an infectious aetiology.


Renin dependency of blood-pressure. Analysis by angiotensin II antagonist P113 in hypertensive patients treated with salt depletion and propranolol. The effect of infusion of the angiotensin II antagonist P113 on blood-pressure (B.P.) has been studied in 10 patients with various forms of hypertension under four different conditions: before and after salt depletion and with or without propranolol treatment. The fall in B.P. after P113 infusion significantly correlated with log P.R.A. (plasma-renin activity), irrespective of diagnosis or treatment. P113 infusion caused a consistent fall in B.P. only after sodium depletion. The changes in B.P. after P113 infusion and those induced by propranolol correlated only during sodium depletion, when P.R.A. values rose. It is concluded that sodium depletion induced "renin dependency" of B.P. in all patients. The decrease in B.P. renin dependency after propranolol therapy suggests that suppression of P.R.A. is one of the antihypertensive mechanisms underlying the action of this drug.


Fertility patterns after discontinuation of use of oral contraceptives. Investigation of the fertility-rate after discontinuation of use of oral contraceptives shows that the monthly rate consistently follows an oscillatory pattern. This pattern appears to be unique to women who have discontinued the use of oral contraceptives. It may result from synchronisation of a previously unrecognised natural cycle, rebound changes in the reproductive system following steroidal contraception, or an infertile period associated with early intrauterine mortality.


Protection by pertussis vaccine. Little cause for concern. It was estimated from a survey of 418 children aged three weeks to twelve years with bacteriologically confirmed whooping-cough that about 95% of vaccinated children are protected by current vaccine. Protection could be increased even further by the greater use of adsorbed rather than plain vaccine and by closer adherence to a vaccination schedule. The lower incidence of infection, resulting from widespread acceptance of this highly effective vaccine, would also greatly reduce the exposure of infants who are too young to be immunished themselves; and eradication ow whooping-cough would be in sight.


Disorders of bone and fracture of the femoral neck. Evaluation of computer image analysis in diagnosis. The quantity of bone and osteoid has been measured in undecalcified sections of iliac-crest biopsy specimens taken from patients with fracture of the femoral neck. A control group of bone samples was obtained from post-mortem material. The 'Quantimet 720' image-analysing computer system was used to measure the area of bone and osteoid. An eye-piece graticule was used to measure the proportion of bone-surfaces covered with osteoid, and there was good correlation between the results obtained by these two methods. Little difference was found between the proportion of bone in the fracture and control groups, but the fracture group contained many more individuals with an increased proportion of trabecular osteoid measured with the quantimet and of osteoid-covered surfaces measured with an eyepiece graticule.


Variable response to long-term 1alpha-hydroxycholecalciferol in haemodialysis osteodystrophy. Ten uraemic patients on regular haemodialysis were treated with 1alpha-hydroxycholecalciferol (1alpha-H.C.C.) for 5 to 14 months. Five patients who had histological osteitis fibrosa with or without osteomalacia responded well, with resolution of musculoskeletal pain, return of raised serum-alkaline-phosphatase concentrations to normal, resolution of radiological subperiosteal erosions, and improvement in histological signs of osteitis fibrosa and osteomalacia. In these patients 1alpha-H.C.C. proved a safe and effective drug. Five other patients did not improve. Characteristically these patients started with moderately severe histological osteomalacia and minimal, if any, osteitis fibrosa. Proximal myopathy was a prominent symptom and serum-alkaline-phosphatase was normal in four of them. Treatment with 1alpha-H.C.C. resulted in early troublesome hypercalcaemia, and repeat bone histology 5--11 months later showed no improvement. It is suggested that in these patients lack of 1,25-dihydroxycholecalciferol may not have been wholly responsible for the observed osteomalacia, hence 1alpha-H.C.C. alone was ineffective. Phosphate depeltion may have been an important contributing factor.


Premenstrual tension and functional infertility. Aetiology and treatment. 17 women with premenstrual symptoms received bromocriptine (CB 154) and placebo in a double-blind crossover manner. 5 because pregnant and 10 who completed 2 cycles showed significant improvement in breast symptoms, oedema, weight gain, and mood with bromocriptine. Prolactin concentrations were suppressed. In 34 women with premenstrual symptoms, who had been warned of possible increased fertility, bromocriptine 2-5 mg twice daily from the 10th day of the menstrual cycle for 1--11 months gave marked or complete relief. 45 women attending the infertility clinic took 2-5 mg bromocriptine twice daily for 186 cycles; 23 became pregnant, 2 had marked relief and 20 complete relief from premenstrual symptoms. The relief of premenstrual symptoms by bromocriptine may be due to suppression of prolactin concentrations, which may be a major factor in premenstrual syndrome.


Treatment of early cancer of the breast: Histological staging and role of radiotherapy. The clinical progress of 350 patients with early cancer of the breast was reviewed. In a five-year follow-up after simple mastectomy routine postoperative radiotherapy conferred no demonstrable benefit on those with histologically negative lymph-nodes. When the regional nodes were involved in the malignant process, radiotherapy led to an increased mortality in the early stages, but did reduce the incidence of local recurrence.


Circulating hormone concentrations in women with breast cancer. Multiple plasma-hormone concentrations were measured in sequential plasma-samples from six women with breast cancer and were compared to concentrations in six control women matched for age, years since menopause, and parity. All hormone concentrations in all the women studied were within normal limits. However, within the normal range the plasma-testosterone concentrations in each cancer patient were significantly higher than in each matched control.


Pancreatic-polypeptide response to food in duodenal-ulcer patients before and after vagotomy. In 21 normal fasting subjects basal serum-pancreatic-polypeptide (H.P.P.), as measured by a specific radioimmunoassay, was 43 +/- 4 pmol/l (mean +/- S.E.M). This basal concentration was of the same magnitude as that of other gastrointestinal peptide hormones. In normal subjects the H.P.P. response to food was bisphasic. A rapid eightfold increase, reaching a maximum 20--30 min after beginning of the meal, was followed by a secondary, prolonged increase. H.P.P. did not return to basal concentration within five hours. 14 duodenal-ulcer (D.U.) patients were studied before and after truncal vagotomy. Before operation the D.U. patients had higher basal H.P.P. concentrations than the normal group (110 +/- 40 pmol/l) whereas their H.P.P. response pattern to food was similar to that of the normal subjects. After vagotomy the primary rapid increase in H.P.P. concentration was eliminated and the secondary, prolonged response was significantly reduced (P less than 0-005). The results indicate that H.P.P. is a digestive hormone under vagal control.


Anorectal disease in patients with non-haematological malignancy. A frequent and previously uncharacterised association of anorectal inflammatory disease in seven of twenty-two patients undergoing therapy for nonhaematological malignancy is described. Sepsis and secondary pulmonary infection were distant complications of the anorectal lesions. The degree of granulocytopenia induced by chemotherapy appears to be the major predisposing factor. Management includes early surgical intervention, and preventive measures specific for this patient population.


Enzyme inducation as a possible cause of increased serum-trigylcerides after oral contraceptives. Serial studies on twenty patients before and during oral-contraceptive therapy demonstrated a significant positive association between serum gamma-glutamyl-transpeptidase (G.G.T.) activity and triglyceride concentrations, both of which rose after treatment. The association between serum G.G.T. and triglyceride, and their increase after treatment with oral contraceptives, may reflect hepatic microsomal enzyme induction of both the rate-limiting enzymes of triglyceride synthesis, and G.G.T.


Distribution of a bombesin-like peptide in human gastrointestinal tract. The bombesin group of hormonal peptides produced in the amphibian skin have powerful actions on the mammalian gastrointestinal tract. In man a bombesin-like material was found in an endocrine cell which is widely distributed in the gastrointestinal mucosa. This has tentatively been identified as belonging to the non-enterochromaffin cell groups. The large number of cells containing a bombesin-like peptide suggests that this substance may be important in human physiology.


Comparison of antibody responses and reactivity of "Alice" and WRL 105 strain live influenza vaccines. Groups of 45 adult volunteers were vaccinated intranasally with a single dose of either "Alice" or WRL 105 strain live influenza vaccines. Seroconversion rates against A/Scotland/840/74 were significantly greater following administration of WRL 105 but seroconversion rates against A/England/42/72, A/Port Chalmers/1/73, A/Finland/4/74, A/Victoria/3/75, and A/England/864/75 did not differ significantly between the two vaccines. Poor antibody responses were elicited by both "Alice" and WRL 105 strains against A/Victoria/3/75 and A/England/864/75. No severe reactions followed the administration of either vaccine.


A nutrition rehabilitation centre for children with xerophthalmia. A nutrition rehabilitation centre for treatment of children with xerophthalmia was established in Madurai, India. Treatment was based on provision of locally available food, rich in protein and beta-carotene and cheap enough for the families concerned to buy at home. This diet alone, with general medical treatment for other diseases, was sufficient to reverse conjunctival xerophthalmia and corneal xerosis. Children with more severe xerophthalmia received additional vitamin A. The records of 296 children followed up for between two months and three years were analysed. The results of treatment at the centre seemed as good as those produced by more expensive, and usually unobtainable, hospital treatment. Participation of the mother in buying, cooking, and sharing the food given to her child was of some educational value.


Cytology of nasal secretions: further diagnostic help. Nasal cytograms, as an aid to diagnosis of pathological conditions of the nose and paranasal sinuses, have not been adopted by the majority of otolaryngologists. This situation exists because of technical problems with the preparation of a slide and the difficulty in finding someone competent and interested in its interpretation. The work of the Bryans has provided an analysis of the cytology of nasal secretions. Adopting their methods, we have been using the nasal cytogram in clinical practice and find it helpful in determining appropriate therapy for problems encountered in otolaryngological practice. In the authors' experience, profuse nasal mastocytosis is a consistent finding in cytograms from patients having varied symptoms that are associated with hypersensitivities that are not accompanied by positive objective findings. This is especially true in patients with constantly recurring headaches and those with a chronically obstructed nose. Once many mast cells are found by the cytogram, attempts are made to relieve these patients by selective dietary restrictions. These attempts are often successful. The nasal cytogram is also used to help explain periodic symptom flares in the long term allergy patient undergoing immunotherapy for inhalants, by identifying superimposed viral and bacterial infections.


[Tumor antigens in the diagnosis of gastroenterological diseases (author's transl)]. History, biochemical properties, techniques and normal range of carcino-embryonic proteins and their applications in clinical diagnosis are reviewed in detail. The importance of alpha1-fetoprotein, colon embryonic antigen, fetal sulfoglycoprotein, alpha2H-globulin and Regan-isoenzyme of alkaline phosphatase is discussed for carcinomas of the gastrointestinal tract, other malignant tumors and benign gastroenterological diseases. The results of prospective studies in cancer high risk patients and the indications for the determination of carcino-embryonic proteins in gastroenterology were described.


[Hemodynamics after prindolol and digitalis in acute myocardial infarction (author's transl)]. In 20 patients with acute myocardial infarction hemodynamic controls were performed after digitalisation and following i.v. injection of 0,4 mg of Prindolol. Circulatory changes were most pronounced 5-15 min after Prindolol injection and consisted of decrease in heart rate of 7%, mean arterial blood pressure of 6%, cardiac output of 10,5%, stroke volume index of 5,1% and left ventricular work of 18%. An increase of pulmonary wedge pressure of 17%, pulmonary pressure of 9%, mean right atrial pressure of 16% and peripheral arterial resistance of 6% were calculated. In 5 cases a favourable effect on extrasystoles and in 2 cases on sinus tachycardia were observed. Not infrequently, during the initial phase of acute myocardial infarction, a hyperadrenergic state may be noted. Prindolol may be indicated, when circulatory changes or arrhythmias are suspect to be the result of this hyperadrenergic stimulation. A simultaneous digitalisation may inhibit a more intensive cardiodepression.


[Plasma level studies of quinidine retard, their significance for dosage and onset of effect]. A new sustained-action preparation of quinidine-bisulfate (BM-Chinidin Retard) was investigated in 21 patients. After a single oral dose of 1 g peak plasma levels are reached within 3-4 hours with an unsubstantial decrease during the following 4 hours. After 2 g in three divided doses within 12 hours maximal plasma levels are found after 14-16 hours, but an effective level is reached as early as 4 hours after the first dose. With 1 g Chinidin retard given in two doses within 24 hours, varying plasma concentrations are reached after 24 hours, reaching a maximum after 48 hours and decreasing to a medium level thereafter. The minimal concentrations measured were 23 percent lower than the maximal concentrations suggesting that during longterm application rather stable plasma levels are achieved. The effectiveness of the preparation was demonstrated in patients with atrial fibrillation and flutter, supra-ventricular and ventricular premature beats. Longterm treatment was attempted in all patients. Quinidine effectiveness and plasma concentrations were constant throughout the observation period. Side effects were rare: inappetence, vertigo, and headache were observed transiently in 4 patients without necessitating a change in medication. ECG-alterations occurred as described for quinidine-prepartions in general.


[Antiarrhythmic treatment of ventricular ectropic arrhythmies with Disopyramide]. Disopyramide (D.) is a new antiarrhythmic agent, which is not related chemically to any of the known substances. Animal experiments have shown a close similarity to quinidine action. Side effects are mainly due to anticholinergic effects. Pharmacokinetic studies with radioactive labelled D. have demonstrated that 80 per cent are elimated via the kidneys and 15 per cent through the gut. Gastrointestinal reabsorption in 90 per cent. We have studied the antiarrhythmic properties of D. in ventricular ectopic arrhythmias in twenty male patients. There were 13 myocardial infarctions, 5 cardiomyopathies, one severe oartic regurgitation with prosthetic valve replacement, one case with VPB of unknown aetiology. In ten cases the influence of D. on ventricular excitation threshold in implanted pacemakers was studied. The effects were correlated with Disopyramide-plasma levels. D. was effective in suppressing VPB. It was successful in 67 per cent, in 30 per cent the effect was unsatisfactory. Pacemaker-threshold remained unaltered. Side effects included constipation. Two deaths were observed. Their relationship to the adminstration of D. is not definitely proved. Nevertheless should the drug because of its negative inotropic action be employed with caution in cases with congestive heart failure.


[Quantitative determination of glia-specific proteins in the cerebrospinal fluid of patients with MS (author's transl)]. 150 cerebrospinal fluids from MS patients (85 cases) and patients with different neurological diseases (65 cases) were investigated for their glia-specific content. The demonstration was made quantitatively by means of modified passive hemagglutination tests. The brain-specific glycoprotein was examined for its possible endogenous antigen and/or antibody properties in the cerebrospinal fluid (csf). It could only be demonstrated in the CSF as antigen. CSF with a quantitatively detectable glia-specific protein content- recognizable by a significant increase in titer - were set in relation to other CSF parameters such as cell count, total protein and globulin ratio, and investigated for possible relationships to the clinical syndromes mentioned and their development. A firm correlation was found between the glia-specific protein content and the total protein content of the CSF with retained equivalence.


[The effect of disopyramide phosphate in extrasystole at rest and on exercise (author's transl)]. The antiarrhythmic action of disopyramide phosphate was compared to placebo in a randomized double blind trial at rest and under physical exertion in two groups each of 10 patients with extrasystoles. The exercise was carried out on the bicycle ergometer in a recumbent posture in stages of 25 watts at 2 minutes each without a break to the limit of the individual. The extrasystoles were counted at fixed registration periods. It was shown that the number of extrasystoles in the disopyramide group was significantly lower in comparison to the placebo group (P less than 0.05).


[Experience in the treatment of islet adenomas (author's transl)]. The clinical picture of insulinomas is discussed with reference to the literature and 27 of our own cases. The neurological symptoms are usually more prominent, so that the diagnosis is delayed. The average delay between the onset of the disease and its recognition was 4 years. Whipple's triad is characteristic of insulinoma. Of the chemical laboratory investigations, the hunger and tolbutamide tests are the most reliable for the diagnosis. Because of the danger of brain damage, there is an absolute indication for operation. Conservative treatment is burdened with numerous side effects so that it is only considered as a temporary measure or for inoperable patients. In the overwhelming majority of cases, enucleation of the tumors from the pancreas is successful. The cure rate after successful operation is about 80%.


[Experiments with splenohepatoplasty in the rat]. The physiopathological premises for various methods of hepatic revascularisation are described and results wiht splenohepatoplasty in 40 rats are presented. This operation involves insertion of the upper pole of decapsulated spleen in the left hepatic lobe to create a new parenchymal supply and regenerate the liver cell. The clinical, functional and anatomopathological data are discussed. The experimental value of the procedure is asserted, though it is felt that no sure demonstration can be given of the establishment of newly formed vascular connections between the two organs.


[Use of 48/80 in the diagnosis and therapy of allergic asthma]. A review of the relevant literature is followed by the presentation of experimental and clinical results obtained with intradermal administration of the histamine releaser 48/80. The value of this substance in the diagnosis and treatment of bronchial asthma is stressed.


[Esophagocolonoplasty in the palliative treatment of cancer of the esophagus]. Treatment of cancer of the upper and middle thirds of the oesophagus is discussed. Should the condition be handled in radical or palliative fashion? In the light of the discouraging results obtained by most workers with radical therapy, palliative measures are favoured. Possible operations are listed and a personal case of palliative ileocolonesophagoplasty of about a year's standing and another operated on only two months previously are reported and preoperative and postoperative documentation given.


[Heterogeneity of protein hormones in radioimmunoassay]. Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasma and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. These immunoreactive forms may be added to already well known elements of hormonal heterogeneity: formation of aggregate, polymerisation, links to transport proteins, microheterogeneity by silent mutation. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight (big hormone) usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight forms is still little known. There may be breakdown products, biologically active products or biosynthetic products. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, stimulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms of enteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones: secretin, vasoactive intestinal polypeptide and enteroglucagon, have similar structure and mode of action; however, the existence of a specific receptor is a sign of their functional differentiation at molecular level.


[Contribution to the isolation and study of the molecular weight of human factor VIII]. The authors describe some properties of highly-purified factor VIII concentrates isolated from human plasma. The fraction containing "factor VIII-complex" (factor VIII procoagulant activity, factor VIII related antigen and von Willebrand factor) is homogeneous by analytical ultra-centrifugation and its sedimentation coefficient is (see article). By gel filtration in high ionic strength buffer a low molecular weight fraction (LMW) with factor VIII procoagulant activity stronger than plasma's one has been isolated. This LMW fraction contains neither factor VIII related antigens nor von Willebrand factor. Its molecular weight determined by gel filtration is approximately 250,000.


[The antigenic properties of human prolactin (author's transl)]. The antigenic properties of human prolactin (HPr) were studied using various methods of radio-immuno assay. The homologous system, the difficulty of which resides in the preparation of the tracer, easily permits measurement of physiological levels. In this systems, blood prolactin in the monkey, has an antigenicity comparable with that of human prolactin, whereas growth hormone and human chorionic somatotropin have feeble or nil antigenic relationship with HPr. Human, sheep and pig prolactins have variable antigenic cross-reactions depending on the immune serum used. These antigenic cross reactions may be applied to the isolation of amniotic prolactin Human blood prolactin has several components of different molecular weight, but antigenicity comparable with that of pituitary HPr.


[Prevention of hepatitis A by polyvalent immunoglobulins. Study in a child population]. A longitudinal study in a residential centre for the treatment of children with primary tuberculosis.


Bovine leukemia virus: an exogenous RNA oncogenic virus. Short-term cultures of bovine leukemic lymphocytes release virus particles with biochemical properties of RNA oncogenic viruses. These particles, tentatively called bovine leukemia virus (BLV), have a high molecular weight RNA-reverse transcriptase complex and a density of 1.155 g/ml in sucrose solutions. Molecular hybridizations between BLV/[3H]cDNA and several viral RNAs show that BLV is not related to Mason-Pfizer monkey virus, simian sarcoma associated virus, feline leukemia virus, or avian myeloblastosis virus. These results were confirmed by hybridization between BLV 70S RNA and [3H]cDNA synthesized in the various viruses tested. The high preference of BLV reverse transciptase for Mg++ as the divalent cation suggests that BLV might be an atypical mammalian leukemogenic "type C" virus. DNA-DNA hybridization studies using BLV [3H]cDNA as a probe strongly suggest that the DNA of bovine leukemic cells contains viral sequences that cannot be detected in normal bovine DNA.


Synthesis of murine leukemia virus proteins associated with virions assembled in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Murine leukemia virus particles assembled in actinomycin D-treated cells were detected by determination of reverse transcriptase [RNA-dependent DNA polymerase (nucleotidyltransferase)] activity and by radioimmunoassay of the major virion protein, p30. The levels of enzyme activity and p30 protein were both 30-40% relative to the control over an 8 hr period, whereas after 3 or 4 hr infectivity was reduced by 95%. Thus, virions produced in the absence of RNA synthesis represent a fairly homogeneous population of defective particles. Although RNA synthesis is not necessary for virus assembly, protein synthesis is required. Treatment of cells with 10 mug/ml of cycloheximide reduced virus production by 80-85% within 2 hr, and by greater than 95% at later times. As might be expected from this finding, viral protein synthesis accompanies virus assembly in actinomycin D-treated cells. Newly synthesized proteins associated with the defective particles were identical with those found in standard virions and were present in the correct proportions. The results demonstrate that viral mRNA persists in cells in which RNA synthesis is blocked and continues to direct viral protein synthesis with a functional half-life of approximately 6-8 hr. Since viral mRNA is not packaged in virions even when viral RNA synthesis is shut off [Levin et al. (1974) J. Virol. 14, 152-161], we propose that murine leukemia virus-infected cells contain two nonequilibrating pools of intracellular viral RNA molecules, one associated with polyribosomes and one which is encapsidated into extracellular particles.


Immunologic and fine structure evidence of avidly bound host serum proteins in the surface coat of a bloodstream trypanosome. Intact, washed Trypanosoma lewisi bloodstream forms, isolated from rats, were agglutinated specifically by antisera against rat whole serum, albumin, alpha2-macroglobulin, and IgG. However, trypsinized bloodstream and intact culture forms lacking surface coat were not agglutinated by these antisera. Trypsinized bloodstream forms, incubated in dilute rat or heterologous host serum proteins, were agglutinated with specific antisera. The characteristic surface coat of intact bloodstream forms was absent from trypsinized cells; however, trypsinized and serum-incubated bloodstream forms reacquired a surface coat similar to that of intact cells. Gel-diffusion and immunoelectrophoretic results showed that rat albumin, alpha2-macroglobulin, and IgG were present in the surface coat of bloodstream forms. Results of quantitative rocket immunoelectrophoresis demonstrated that the adsorbed rat serum proteins constituted by weight about 5% of the trypanosome total surface coat protein.


Antisera against electrophoretically purified tubulin stimulate colchicine-binding activity. Several rabbit antisera have been prepared against reduced and alkylated, electrophoretically purified tubulin isolated from chick brain. These antisera give a single precipitin line in Ouchterlony double diffusion plates when tested against partially purified tubulin, and label specifically microtubule- and tubulin-containing structures, such as mitotic spindles, cilia, and vinblastine-induced crystals, in a variety of cells. The same antisera also display the unique ability to stimulate the colchicine-binding activity of tubulin preparations from chick brain and Chinese hamster ovary tissue culture cells. This specific stimulation of colchicine binding activity is also obtained with the gamma globulin fractions purified by ammonium sulfate precipitation of these antisera.


Evidence for circularization of the avian oncornavirus RNA genome during proviral DNA synthesis from studies of reverse transcription in vitro. The RNA-directed DNA polymerase (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase EC 2.7.7.7) of avian oncornavirus requires a tryptophan tRNA (tRNATrp) primer molecule located close to the 5' end of the viral RNA genome for the initiation of DNA synthesis in vitro. In this communication we demonstrate that the DNA product, transcribed from avian myeloblastosis virus (AMV) 35S RNA containing only tRNATrp as primer, is located also at the 5' end of the RNA genome. More importantly, we demonstrate that these 5' terminal DNA transcripts contain nucleotide sequences complementary to the 3' end of the genome. We have interpreted these results to mean that the genome. We have interpreted these results to mean that the 3' and 5' termini of the AMV 35S RNA genome become juxtaposed with each other either before or immediately after DNA synthesis has begun. These results are discussed in regard to the mechanism for synthesis of the circular forms of oncornavirus proviral DNA.


Pheasant virus: new class of ribodeoxyvirus. Cocultivation of cells derived from embryos of golden pheasants or Amherst pheasants with chicken embryo cells infected with Bryan strain of Rous sarcoma virus resulted in the detection of viruses which appear to be endogenous in these pheasant cells. The pheasant viruses (PV) were similar to avian leukosis-sarcoma viruses (ALSV) in their gross morphology, in the size of their RNA, in the presence of a virion-associated RNA-dependent DNA polymerase (DNA nucleotidyltransferase; deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7), and in their growth characteristics. PV also serves as a helper for the glycoprotein-defective Rous sarcoma virus. However, PV was shown to be different from both ALSV and reticuloendotheliosis virus in the following properties: (i) PV does not have ALSV group specific antigens; (ii) the protein composition of PV is different from those of the other two groups of viruses; (iii) PV fails to complement the defective polymerase of alpha type Rous sarcoma virus; and (iv) PV RNA shows no detectable homology with nucleic acids of the other two groups of viruses. Thus, PV appears to be a new class of RNA viruses which contain RNA-dependent DNA polymerase.


Biochemical characteristics of rat C-type virus WF-1. The non-oncogenic rat C-type virus WF-1, isolated from a Wistar-Furth rat embryo cell line, was characterized biochemically. The purified virus has a buoyant density of 1.15 to 1.16 g/cm3 in sucrose, RNA-dependent DNA polymerase (reverse transcriptase) activity, and RNA with a sedimentation coefficient of 62 to 68 S. The viral RNA is single-stranded, and, upon treatment with heat, yields components with sedimentation coefficients of 36 S, 18 to 20 S, and 4 to 12 S.


[Radioimmunologic determination of alpha fetoprotein in diagnosis of primary tumors of the liver]. The plasma level of alpha1-fetoprotein in 35 hepatic patients with a "cold" area showed by liver scanning has been detected by means of the radioimmunoassay technique. High levels (more than 320 ng/ml) of AFP were found in 4 cases of primary carcinoma of the liver; low concentration of AFP was found in 1 case of hepatoma. In 4 cases of liver metastasis the plasma levels of AFP were very low; the highest concentration (10 ng/ml) was found in a patient with a cancer of the colon. Low levels of AFP were found in all the cases (26) of hepatic cirrhosis, whereas high level of AFP was detected in 1 case of chronic hepatitis. The detection of alpha1-fetoprotein by the radioimmunoassay technique may be of value in the differential diagnosis between hepatoma and cirrhosis.


[The effect of donorspecific antigen type for active enhancement of renal-allografts in the histoincompatible inbred rats (author's transl)]. 49 kidneys of male LBNF1-rats were transplanted into male Lewis-rats. BN-rats were used as a source of antigen. Control animals survived 16.1 +/- 1.8 days. 5 recipients were preteated with donorspecific living cells, 7 with semisoluble and 5 with low dosage of soluble antigen. The living cell-pretreatment showed the best effect for the active enhancement, the soluble antigen the least. The pretreatment with 6 mg protein/kg bw. caused the sensibilization of recipients. At the time of transplantation lymphcytotoxic antibody titers were detected in all recipients with pretreatment of living cells, but no titer in other groups. Renal allografts with elevated postopertive titer were rejected rapidly.