[Representative enzymes of energy supplying metabolism in the normal and denervated human brachial biceps, deltoid and anterior tibial muscles (author's transl)]. Representative enzyme activities of energy supplying metabolism were measured in muscle specimens of brachial biceps, deltoid or anterior tibial muscle of patients with affections of the peripheral nerves. Simultaneously performed measurements of the same enzyme activities in the contralateral normal muscles served as a control. 5 patients suffered from a lesion of the brachial plexus, 7 patients had a paralysis of the axillary nerve, and 8 patients had a peroneal paralysis. In all denervated muscles no electrophysiological signs of reinnervation were present. The activities of glycogen phosphorylase, triosephosphate dehydrogenase, lactate dehydrogenase and alpha-glycerophosphate dehydrogenase were found to be highest in the normal brachial biceps muscle. Lower activities were measured in the normal deltoid and anterior tibial muscle. The oxidative enzymes, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase as well as hexokinase, showed no significant difference from the levels of the control. It is suggested that a probable factor determining the differences of the enzyme activities of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation between brachial biceps, deltoid and anterior tibial muscle, might be the pattern of impulse activity in the motor nerves of these muscles. The enzyme activities of glycogen phosphorylase, triosephosphate dehydrogenase, lactate dehydrogenase and alpha-glycerophosphate dehydrogenase, decreased rapidly during the first 2 months after denervation in the brachial biceps, deltoid and anterior tibial muscle, whereas the decrease was slight during the following months. The activities of the oxidative enzymes (3-hydroxyacyl-CoA dehydrogenase and citrate synthase) showed no significant change after denervation. The metabolic difference of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation between the three muscles was no longer maintained. The possible causes of the deeply decreased enzyme activities of glycogenolysis, glycolysis and alpha-glycerophosphate oxidation, as well as the causes of the unchanged oxidative enzyme activities and of the increased hexokinase activity after denervation in the human brachial biceps, deltoid and anterior tibial muscle, are discussed.


"Epi-" and intramedullary neurilemmoma of the spinal cord with denervation atrophy in the related skeletal muscles. The autopsy of a 68-year-old male who died of cardiac infarction revealed an ep - and intramedullary neurilemmoma of the spinal cord as an associated finding half a year prior to death. The patient had suffered from progressive weakness and sensory disturbances of the lower limbs together with muscular wasting for 6 months. Repeated neurological examinations had led to the diagnosis of an intraspinal space occupation which, however, could not be substantiated by myelography because of its surprisingly small size. The Schwann cell proliferation originated from the adventitia of the epi- and intramedullary vessels of the conus medullaris. The main tumor mass was epi-medullary and extended into the medullary parenchyma via the penetrating vessels forming intramedullary nodules. The special findings in the present case seem to support the hypothesis that intramedullary neurilemmomas originate from the perivascular nerve endings.


Electrocardiographic studies in female carriers of Duchenne muscular dystrophy. The incidence of electrocardiographic features "typical" for the Duchenne progressive muscular dystrophy (PMD) was investigated in 191 carriers: 136 mothers and 55 daughers. The typical PMD pattern was seen in 6.6% of the mothers, and a pattern similar to that observed in PMD in 2.9%. Among daughters of carriers the percentages were 16.4 and 1.8 respectively. The daughters obviously belong to a much lower age bracket (average 13.3 years) and therefore must be followed for the eventual disappearance of the "juvenile" ECG features, which, in this group, may reduce the incidence of the typical PMD electrocardiograms. The need for more thorough clinical appraisal of the myocardium in carriers is emphasized, especially in those with the "typical" PMD electrocardiograms, with the help of hemodynamic investigations.


[Trismus, trigeminal motor dyssynergy with brain stem lesions (author's transl)]. Paradox activity of masticatory muscles was observed clinically and electromyographically in 4 patients with brain steem lesions who had trismus. There was no activity in the elevators of the jaw on the side affected during voluntary biting, as if the muscles were paralyzed. There was strong activity of the elevators on the side of the trismus on opening the mouth, inactivity on the unaffected side, or inverse activity appeared on both sides. In view of the trigeminal anesthesia on the side of paradox activation, and the absence of pyramidal signs, a stretch reflex mechanism and abolition of inhibition can not be the only basis for these phenomena; so, a disturbance of bilateral synergism, in the sense of an internuclear lesion, is postulated. In one case of motor and sensory paralysis after the extirpation of a meningioma of the cerebellopontine angle, intensive paradox activity was observed, without trismus.


[Stellate ganglion block under EEG control in the treatment of complicated cervical migraine (author's transl)]. Complicated migraine is regarded as a cerebrovascular syndrome of functional character. In the case of a young man with cervical migraine associated with paroxysmal neurological disorders and persisting EEG abnormalities, stellate ganglion blocks were performed under EEG control. A transient amelioration of the pathological EEG pattern was observed after each stellate ganglion block and after several treatments the EEG was normal and the migraine attacks disappeared. The pathophysiology of the effect of stellate ganglion block on cerebral blood flow is discussed.


[The diagnostic value of brain scanning in children (author's transl)]. The results of brain scanning of children up to the age of 16 (192 patients) show that cerebral tumors could be accurately detected in 44 out of 50 cases (88%) and cerebellar tumors in 22 out 32 cases (69%). The characteristics of the individual kinds of tumors were discussed but classification by means of brain scanning is not yet possible, due to the limited experience with tumors of children. For in-patient studies, together with contrast methods, and for out-patient examinations with X-ray, EEG, and echoencephalography, brain scanning improves the diagnostic possibilities to a large extent.


Syndrome of the rectus abdominis muscle: A peripheral neurological condition causing abdominal diagnostic problems. Four cases of a painful abdominal syndrome are presented, the pain occurring in the distribution of the medial cutaneous branch of the 7th--12th intercostal nerves. The diagnosis presents difficulties because of severe abdominal pain. In 2 cases the clinical observations were corroborated by EMG findings. The symptoms, physical manifestations, mode of development and therapy are described. The term proposed for the condition is: Syndrome of the Rectus Abdominis Muscle.


[Eosinophil leucocytes in csf after myelography (author's transl)]. 2 cases one of polyneuropathy and one of funicular myelosis, in which myelography was performed, are reported. After the insertion of the contrast medium an increase of eosinophil leucocytes was observed. In one case an additional increase of IgG and IgA, as well as a penetration of macromolecular proteins and an increase of the total protein, was detected. The second case showed an increase in haptoglobulin in addition to the cellular reaction described. After removal of the contrast medium, the CSF became normal in both cases. These changes were on one hand interpreted as a functional lesion of the barrier, and on the other hand as a special cellular and humoral immune reaction. This could be distinctly detected in the lumbar CSF while in the suboccipital CSF there was only an indication of it. This emphasizes the assumption of a pathological reaction in the section of the cerebrospinal region that was in contact with the contrast medium (allergen-hyperergic reaction of the vascular fibrous tissue of the leptomeninges). No marked changes were observed in the serum.


Transitional forms of Arnold-Chiari and Dandy-Walker malformations. The morphological findings in 12 cases of Arnold-Chiari and 3 cases of Dandy-Walker malformations are described and compared to those in 2 cases of congenital hydrocephalus of unknown origin, 1 case of isolated meningo-myelocele and 2 cases of normal newborn brains. Lesions common to both types of malformation indicate a same time-related embryogenetic defect of the roofplate of the rhombencephalon, that does not allow the inferior vermis and the choroid plexus to turn inward into the fourth ventricle.


[The clinical picture and a consideration of the neurolinguistic structure (author's transl)]. Despite the variability of its behavioral manifestations Wernicke's aphasia is considered to be a unitary syndrome. According to the criteria of intelligibility, phonemic and semantic paraphasias in spontaneous speech, 4 forms of Wernicke's aphasia are differentiated: 1) with predominantly semantic paraphasias, 2) with semantic jargon, 3) with predominantly phonemic paraphasias and 4) with phonemic jargon. A severe deficit in language understanding is common to all 4 forms. In addition to phonemic and semantic paraphasias paragrammatism is an outstanding feature of the language production in Wernicke's aphasia. After a survey of views about the localization of the lesion and of earlier descriptive models a neurolinguistic explantation of the characteristic symptoms of Wernicke's aphasia is suggested.


Clinical and electrophysiological observations in patients with myotonic muscle disease and the therapeutic effect of N-propyl-ajmalin. Six patients with congenital myotonia and 4 patients with myotonic dystrophy have been examined clinically before and after the administration of N-propyl-ajmalin, an alkaloid frequently used as a cardiac antiarrhythmic drug. All patients but one reported a good to moderate improvement of their myotonic muscle stiffness. This was verified by measuring the time the patients needed to ascend a flight of stairs and by recording the speed of opening the hand. The amplitude of the compound muscle action potential decreased during repetitive nerve stimulation in myotonic patients. This decrease was not influenced by N-propyl-ajmalin. It seems to be due to the increased after-depolarization observed in myotonic fibres which causes partial inactivation of the Na-carrying system. From one patient a muscle biopsy was taken and intracellular potentials were measured with a microelectrode. Almost all muscle cells investigated showed myotonic activity which was completely abolished by addition of 10(-5) g/ml N-propyl-ajmalin to the bathing fluid. The development and duration of "warm-up" is illustrated and a possible electrophysiological basis is discussed.


Gallium-67-citrate scanning in primary cancer of the liver: diagnostic value in the presence of cirrhosis and relation to alpha-fetoprotein. Gallium-67-citrate and 99mTc-sulfur colloid scans were performed in 38 South African blacks with primary hepatocellular cancer. Selective uptake of the radinuclide by the tumor occurred in 27 patients (70%). In 12 out of 18 patients with associated cirrhosis, 67Ga was concentrated in the defect or defects visible on the 99mTc-sulfur colloid scan, but in the remaining 6 cases (33%), the 2 scans were identical and the defects may have been attributed wrongly to cirrhosis. Alpha-fetoprotein (AFP) was detected by immunodiffusion in the serum of 26 patients. Twenty-one of these showed selective uptake of 67Ga by the tumor as compared with 6 out of 12 patients in whom this protein could not be detected. We were therefore unable to confirm a previous finding of a greater uptake of the of the radionuclide in AFP-negative primary liver cancer.


Kinetics of 111In-bleomycin and 111 In-chlorides in mice. Indium-111 as the chloride and chelated to bleomycin has been reported useful as a tumor-scanning agent. This report of the kinetics of these compounds compared in Yale-Swiss mice bearing a transplantable, in situ brain sarcoma. Indium-111-chloride, pH 1.5, gave a maximum tumor uptake of 18.5% dose per gram tumor, a maximum tumor-to-brain ratio of 17.0, and a maximum tumor-to-blood ratio of 4.4. Its renal blood clearance was a slow 0.0022 ml/min. Indium-111-bleomycin showed a maximum tumor uptake of 3.0% dose per gram tumor, a maximum tumor-to-brain ratio of 13.5, a maximum tumor-to-blood ratio of 6.8, and renal blood clearance of 0.254 ml/min. The labeling of bleomycin with 111In results in a tracer with localizing properties in this tumor model which are quite different from those obtained with 111In as chloride or that labeled to bleomycin would appear to have significant potential as agents for imaging tumors.


Histochemistry of the keratohyalin granules in human oral leukoplakia. The keratohyalin granules from 25 human oral leukoplakias, showing benign hyperorthokeratosis histologically, were examined employing a series of histochemical techniques. The tissues were fixed in 10% neutral buffered formalin, 80% methanol, or Carnoy's fluid. The keratohyalin granules stained intensely with Pauly's reagent, Congo red and Harris hematoxylin, indicating the presence of proteins. This was confirmed by abolishing the staining reaction by pretreatment with proteolytic enzymes. The keratohyalin granules also reacted with methyl green-pyronin by staining pink at their peripheries; this staining was abolished by pretreatment with ribonuclease, indicating the presence of ribonucleotides. The keratohyalin granules partially stained with toluidine blue and colloidal iron, indicating the presence of acid polysaccharides. The keratohyalin granules did not react with the Feulgen reagent, suggesting the absence of DNA. Our studies indicate that the keratohyalin granules in human oral leukoplakia are primarily protein(s) complexed with polyribonucleotides. The presence of a carbohydrate moiety suggests the possibility of a protein-polysaccharide component in the granules.


Microscopic anatomy of edentulous residual alveolar ridges. The histologic tissue changes of the residual alveolar ridges were studied in five edentulous patients ranging from 55 to 80 years of age. The material studied was obtained from cadavers. The following observations were made: (1) The epithelium was hornified. Acanthosis was found in all specimens. (2) In four of the specimens, the collagen fibers covering the residual bone crest showed a hyalinized area. (3) Mucoid collagen degeneration was seen in all specimens. (4) The most striking finding, common to all specimens, was the epithelial remnants. Resting and proliferating types were identified. (5) Chronic inflammation was found in all specimens. (6) Both osteoid and necrotic bone types were observed. (7) An outstanding characteristic of the residual alveolar ridge was the reinforcement of the internal structure of the bone by endosteal apposition.


Development of dermal ridges in the fetus. This paper describes a new technique to inspect dermal ridges on the dermal surface instead of the epidermal surface. The dermal surface was exposed by chemical treatment and stained with toluidine blue. Dermal ridges are observable by the metachromatic effect of the reagent, which might suggest a close relationship between morphological characteristics and quantitative variations of biochemical components in the connective tissue. Dermatoglyphic features were recognized in fetuses from the 14th gestational week. Morphogenesis of dermal components--that is, grooves, primary and secondary dermal ridges, furrows, papillae, and sweat ducts--was examined at various gestational stages. The general law in the developmental sequence of the ridges in different volar areas was also confirmed.


RNA-dependent DNA-polymerase activity in human milk. A simple method is described for testing milk specimens from nursing mothers for the presence of RNA-dependent DNA-polymerase activity. Positive results were obtained in five of 137 women (3.6%) without a family history of breast cancer, and in six of 31 women (19.3%) with a family history of breast cancer.


Ethnic aspects of cord serum alpha 2-macroglobulin levels in Chinese, Caucasians and Ghurkas in Hong Kong. Serum alpha 2-macroglobulin (alpha 2-M) levels were measured in cord sera of Chinese, Caucasian and Ghurka babies in Hong Kong by the antibody-agar radial immunodiffusion technique. The values for male babies of the three ethnic groups were 293 +/- 59, 323 +/- 79 and 303 +/- 72 mg./100 ml., respectively; those for female babies were 287 +/- 74, 315 +/- 74 and 317 +/- 7) mg./100 ml., respectively. Although a general similarity of cord serum alpha 2-M levels was evident at birth, it was noted that ethnic differences in the level of this serum protein only become apparent later in life. The value obtained for Caucasian cord serum alpha 2-M in Hong Kong was significantly lower than a published value for Caucasians elsewhere.


Isolation and preliminary characterization of temperature-sensitive mutants of measles virus. Twenty-four genetically stable temperature-sensitive mutants of measles virus were isolated after mutangenesis by 5-azacytidine, 5 fluorouracil, or proflavine. The restricted replication of all mutants at 39 C was blocked subsequent to cell penetration and could not be attributed to heat inactivation of virus infectivity. Complementation analysis was made possible through the use of poly-L-ornithine. The members of one complementation group exhibited wild-type RNA synthesis at the nonpermissive temperature and induced the synthesis of virus antigens. These mutants were found defective in both hemolysin antigen synthesis and cell fusion "from within," supporting the unitary hypothesis for these functions. The members of the other two complementation groups synthesized neither virion RNA nor detectable virus antigens at the nonpermissive temperature.


Biochemical properties of the bromodeoxyuridine-induced guinea pig virus. The biophysical and biochemical properties of the virus particles released by guinea pig embryo cells treated with 5-bromo-2'-deoxyuridine (BUdR) have been compared to those of the B-type mouse mammary tumor virus (MMTV) and the C-type Rauscher murine leukemia virus. The high-molecular-weight (60 to 70S) RNA of the BUdR-induced guinea pig virus (GPV) has a molecular weight of 8 X 106 when measred by mixed agarose polyacylamide gel electrophoresis. The virus particles isolated from the tissue culture medium of BUdR-induced guniea pig cells have the following properties in common with MMTV: (i) a buoyant density of 1.18 g/ml in sucrose and 1.21 g/ml in CsCl, and (ii) a DNA polymerase that prefers Mg2+ over Mn2+ in an assay using the synthetic template poly(rC):oligo(dG). No nucleic acid sequence homology between GPV RNA and the viral RNAs of the MMTV, murine leukemia virus, hamster sarcoma virus, or Mason-Pfizer monkey virus could be observed in a competition hybridization assay using the radioactive-labeled GPV 60 to 70S RNA. By this same competition by hybridization assay the frequency of GPV proviral sequences was estimated to be at least 83 per haploid cellular genome of guniea pig cells. No nucleic acid sequences related to be GPV RNA were detected in the DNA of normal tissues of mice, rats, cats, dogs, baboons, or humans by direct RNA-DNA hybridization using radioactive GPV60 to 70S RNA.


Purification and properties of spleen necrosis virus DNA polymerase. DNA polymerase was purified to apparent electrophoretic homogeneity from virions of spleen necrosis virus (SNV). (SNV is a member of the reticuloendotheliosis group of avian ribodeoxyviruses). The SNV DNA polymerase appears to consist of a single polypeptide with a molecular weight of 68,000. The SNV DNA polymerase has a preference for Mn2+ for DNA synthesis with an RNA template and Mg2+ for DNA synthesis with a deoxyribohomopolymer template. At the optimum concentrations of divalent cation, the relative rates of DNA synthesis by SNV DNA polymerase with different template.primers were similar to the relative rates of DNA synthesis by an avian leukosis virus DNA polymerase, with the exception of a lower relative rate of DNA synthesis by SNV DNA polymerase with SNV RNA. However, in contrast to DNA synthesized by the avian leukosis virus DNA polymerase with a SNV RNA template, DNA synthesized by SNV DNA polymerase with an SNV RNA template did not hybridize to the SNV RNA. SNV DNA polymerase has RNase H activity which is antigenically distinct from the RNase H activity of avian leukosis-sarcoma virus DNA polymerase.


RNA-directed DNA polymerase activity of reticuloendotheliosis virus: characterization of the endogenous and exogenous reactions. Reticuloendotheliosis virus (REV) contains an endogenously instructed, RNA-directed DNA polymerase activity. Both the endogenous and exogenous DNA polymerase activities exhibited up to 10-fold greater activity at the optimum concentration of manganous ion (0.025 mM for exogenous; 0.25 mM for endogenous) than at any concentration of magnesium ion. Antiserum to the DNA polymerase of an REV group virus (spleen necrosis virus) inhibited both endogenous and exogenous DNA polymerase activity of REV, whereas antiserum to the Rous sarcoma virus (Rous-associated virus-0) [RSV(RAV-0)]DNA polymerase did not. The DNA product of the endogenous reaction is associated with the high-molecular-weight RNA of REV and anneals with REV RNA but not with RNA from Rous sarcoma virus.


Characterization of endogenous RNA-directed DNA polymerase activity of reticuloendotheliosis viruses. Reticuloendotheliosis viruses (REV) contain an endogenous RNA-directed DNA polymerase activity. The endogenous DNA polymerase activity can be elicited in purified preparations of REV by treatment with nonionic detergents. The enzyme activity has a strong preference for manganous ions. Therefore, appreciable endogenous DNA polymerase activity can be demonstrated only if the reaction mixture contains appropriate concentrations of manganous ions. Enzyme activity can be inhibited by pretreatment with RNase or deletion of one or more deoxyribonucleoside triphosphates from the reaction mixture. In contrast, actinomycin D has little effect in initial DNA synthesis. The results from both velocity and equilibrium centrifugation indicate that the nascent chains of product DNA are associated with 60S viral RNA. The DNA product of the endogenous DNA polymerase reaction is hybridizable to REV RNA, but not to avian leukosis virus RNA.


Murine intracisternal type A particles: a biochemical characterization. Intracisternal A particle preparations from a murine neuroblastoma cell line (N18) and from a mineral oil-induced murine plasmacytoma (MOPC-104E) contain both an endogenous RNA-dependent DNA polymerase activity and high molecular-weight polyadenylic acid (poly[A])-containing RNA. The DNA polymerase activity is stimulated by oligo(dG)-poly(C) and oligo(dT)-poly(A) and to a lesser extent by oligo(dT)-poly(dA), in agreement with previous reports. The high-molecular-weight RNA is predominantly 35S and contains a poly(A) tract of approximately 220 nucleotides as judged by polyacrylamide gel electrophoresis. Small amounts of 70S RNA are also present. This RNA preparation contains RNA homologous to RNA from type-C particles, as judged by molecular hybridization experiments. However, since this RNA derives only in part from A-particles and in part from other cellular RNA, hybridization of A-particle endogenously synthesized DNA or reverse transcripts of A-particle RNA to purified type C viral 70S RNA may more accurately reflect the relationship of A-particle RNA to RNA from C-particles. None of these DNA transcripts hybridizes significantly to C-particle 70S RNA, although MOPC and N18 DNA transcripts share significant homology. Our interpretation of these results is that murine intracisternal A particles are not closely related genetically to the tested murine type C viruses, although an alternate possibility is that all the A-particle DNA transcripts are copied from only a small part of the genome, which is unrelated to C-particle RNA.


Variants of N-tropic leukemia virus derived from BALB/c mice. Clonal lines derived from cultures of NIH/3T3 cells infected with N-tropic leukemia virus from BALB/c mice differ in the amount and type of N-tropic virus they produce. Three biologically distinguishable N-tropic viruses were found: the large XC plaque-forming virus of hartley et al. (1969) (LP-N), A SMALL XC plaque-forming virus (sp-n), and a non-plaque-forming virus (NP-N). SP-N and NP-N are less infectious than LP-N. Upon prolonged passage in NIH/3T3 cells NP-N gives rise to highly infectious LP-N.


Observational study of alcohol consumption in natural settings. The Vancouver beer parlor. Observations of patrons in beer parlors in Vancouver, British Columbia, indicate that the rate of drinking is relatively constant. Total consumption and blood alcohol concentration depended primarily on duration of the occasion, which in turn was related to size of the drinking group.


Intracardiac repair of tetralogy of Fallot. Five-year review of 403 patients. During the 5 year period 1969 to 1973, 403 patients underwent intracardiac repair of tetralogy of Fallot. The patients ranged in age from 3 months to 41 years. Before operation, 86 per cent were cyanotic and 14 per cent were acyanotic. Forty-nine per cent had had at least one palliative procedure before total correction. Mahor associated anomalies included atrial septal defect in 24 per cent, patent ductus arteriosus in 2.5 per cent, coronary anomalies in 4 per cent, and left superior vena cava in 4.5 per cent. Seven per cent of the patients had pulmonary atresia. Pulmonary valvotomy was performed in 111 patients and complete excision of the pulmonary valve in 151. Patch graft reconstruction of the right ventricular outflow tract was performed in 57 per cent of the patients. In 11 patients a conduit was used to connect the right ventricle to the pulmonary artery. The over-all hospital mortality rate was 9.5 per cent, with the lowest rate (3.5 per cent) in the age group 6 to 10 years and the highest in the infant and adult groups (16.5 and 14.5 per cent, respectively). Three known late deaths occurred. A residual ventricular septal defect (VSD) was found in 3 per cent of the patients and an aneurysm of the pericardial patch in the right ventricular outflow tract developed in 7 patients. Intracardiac repair of the tetralogy of Fallot can be performed with reasonable risk and low morbidity. In our experience the optimal age for elective surgery is between 6 and 10 years.


Histocompatibility antigens in diabetic identical twins. 84 pairs of diabetic identical twins were HL-A typed. 22 were maturity-onset diabetics (diagnosed after age 45); all were concordant and they showed no disturbance of HL-A frequencies. Of the remaining 62 pairs of juvenile-onset diabetics, 31 were discordant (only one twin diabetic) and 31 concordant (both twins diabetic). The frequency of the W15 antigen was equally increased in both the concordant and discordant pairs; HL-A8 was increased only in the concordant pairs. The fact that W15 is increased in the discordant pairs shows that there is genetic predisposition to diabetes even in these twins; the fact that HL-A8 is not increased suggests that different alleles may underlie susceptibility in the two groups of twins.


Effect of gestational age on screening for neural-tube defects by maternal plasma-A.F.P. measurement. Maternal plasma or serum alpha-feto-protein (A.F.P.) concentrations were measured once between 8 and 22 weeks of gestation in each of sixty-two pregnancies which resulted in an infant with a neural-tube defect. Between 13 and 22 weeks of pregnancy twenty-two of the forty-one cases tested (54%) had A.F.P. values greater than three times the median value for unaffected pregnancies (which is equivalent to the 97th percentile of normal), and many of these values were very high indeed. However, before the 13th week of pregnancy only one of the twenty-one cases (5%) had an A.F.P. value more than three times the median for unaffected pregnancies, and this value was not very high. This indicates that in antenatal screening for anencephaly or spina bifida, A.F.P. should be measured in blood taken from the mother during the second trimester.


Recombinant WRL 105 strain live attenuated influenza vaccine. Immunogenicity, reactivity, and transmissibility. The immunogenicity, reactivity, and transmissibility of recombinant WRL 105 (H3N2) (A/Okuda/57XA/Finland/4/74) strain live attenuated influenza virus vaccine were studied in adult male volunteers in a residential community in rural England. Thirteen volunteers received a single dose of 10(7.0) E.I.D.50 recombinant WRL 105 vaccine administered as nose drops, and twelve volunteers received placebo. Nine (82%) of eleven volunteers with initial antibody titres of less than or equal to 1/96 showed a significant antibody response to vaccination, but there was no evidence of transmission of vaccine virus to those who received placebo. The incidence and nature of reactions were similar in those who received vaccine and placebo. The vaccine was shown to confer protection against natural infection with a strain exhibition antigenic characteristics equivalent to those of A/Scotland/840/74.


Hydrocarbon exposure and chronic glomerulonephritis. 63 adult patients with advanced renal failure were interviewed to evaluate their exposure to chronically contacted or inhaled toxic substances. Grading of exposure revealed that patients with biopsy-proven primary proliferative glomerulonephritis and patients with a clinical presentation consistent with glomerulonephritis had significantly greater exposure than patients with a variety of other renal diseases. Patients with proliferative or suspected glomerulonephritis also had significantly more exposure than age and sex matched controls without renal disease. Hydrocarbon solvents were the most frequent agents of exposure. Further studies to define a possible pathogenic relationship between hydrocarbon exposure and glomerulonephritis are warranted.


Secretin: A new role for an old hormone. Plasma-secretin levels were measured by radioimmunoassay during a 72-hour starvation period in nine healthy subjects. Immunoreactive secretin (I.R.S.) levels rose dramatically during starvation. The rises were several orders of magnitude greater than those after intraduodenal acid. The classic concept that the major function of secretin is the control of the exocrine pancreas is challenged by these results. The findings suggest that secretin is a hormone of importance during starvation, and its role in starvation may be related to its lipolytic properties.


Hearing acuity in young people exposed to pop music and other noise. An investigation by questionary, otological examination, and audiometry has been carried out on 505 students in higher education. Statistically significant hearing losses were found in the group that admitted frequent attendance at pop-music entertainment compared with a control group. Losses associated with vacation employment in loud noise or with gunfire exposure were also identified. Thses losses were unrecognised before investigation and indicate the need for preventive action.


IgM and IgG anti-milk antibodies measured by radioimmunoassay in myocardial infarction. Antibodies against milk protein were sought by a radioimmunoassay in 47 patients with myocardial infarction and in 50 control patients. There was no difference between the two groups in the frequency or in the quantity of IgM and IgG antibodies against milk proteins. These results do not support the suggestion that anti-milk antibodies are involved in the pathogenesis of coronary heart-disease.


Urea metabolism in an azotaemic woman with normal renal function. The blood-urea of a 43-year-old woman with normal renal function was 150 mg. per 100 ml. because she regularly consumed about 400 g. of protein daily. She had no symptoms of uraemia and her haemoglobin concentration was normal. Although she had a very large body-urea pool she degraded no more urea than healthy individuals on a normal diet. The failure of endogenous urea hydrolysis to increase in proportion to the blood-urea in renal failure has tentatively been ascribed to toxic effects of compounds retained with urea in renal failure; the findings in this azotaemic patient, who had neither signs nor symptoms of uraemia, cast doubt upon that explanation.


Comparison of 5-day, 1-day, and 2-day cyclical combination chemotherapy in advanced breast cancer. The results of 5-day cyclical combined chemotherapy for advanced breast cancer were compared in two trials with the less demanding 1-day and 2-day regimens. At all stages, except at 3 months, 5-day treatment was significantly more successful in providing regression and remission of tumours than the 1-day regimen. However, although the differences are not statistically significant, data from the second trial indicated that the 2-day regimen tended to be more effective than the 5-day regimen. The lower 95% confidence limit for the success of the 2-day treatment was 56.2% at 3 months.


Flatus retention is the major factor in diverticular disease. Retention of flatus is the main factor in the origin and progression of sigmoid diverticular disease. This hypothesis explains why the disease is confined to modern urban communities, and why the patient must avoid "windy" foods.


Weight/length classification of nutritional status. The use of somatic measurements for the assessment of nutritional status is briefly reviewed. Two classifications using weight and length being advocated at present--those of McLaren and Read (1972) and Waterlow and Rutishauser (1974)--were applied to data from three sets of children surveyed in hospital and field studies. The results obtained differed considerably. The system of Waterlow and Rutishauser tended to underestimate the problem. A simple chart has been devised to aid the practical application of the classification of McLaren and Read.


An outbreak of hepatitis associated with intravenous injection of factor-VIII concentrate. An outbreak of jaundice associated with three out of four batches of a commercial brand of freeze-dried factor-VIII concentrate occurred at the Bournemouth haemophilia centre between April and June, 1974. Seven cases of non-B hepatitis and four of hepatitis B occurred within 6 months of the first use of this product. Two patients contracted both types of hepatitis; thus nine patients became ill out of a total of twenty regularly seen at the centre, eighteen of whom received commercial factor-VIII concentrate.


Outbreak of food-borne type-A hepatitis in Greater Glasgow. In a fourteen-day period between December, 1974, and January, 1975, 12 out of 118 members of a Glasgow golf club, who had attended their annual dinner/dance at a popular hotel in Glasgow six weeks previously, developed acute icteric hepatitis. Epidemiological investigations suggest that the infection was due to contamination of the cream used in fruit salad and sherry trifle prepared by a pastry-cook at a time when he was incubating type-A hepatitis.


Controlled trial of urokinase in myocardial infarction. A European Collaborative Study. 341 patients with acute myocardial infarction have been treated in intensive or coronary care units. They were randomised into two groups, 172 receiving urokinase and 169 receiving a glucose infusion. Thereafter they were anticoagulated first with heparin and then for a year with oral anticoagulants. Despite a significantly faster regression of electrocardiographic alterations in the urokinase group there was no difference in mortality during the 1-year follow-up (29 deaths in the urokinase and 24 in the control group) and no difference in cardiac functional class between both groups.


Quality and quantity of survival in acute myeloid leukaemia. The quality of life in leukaemia is as important as its quantity. In fifty-one patients the quality and quantity of life were improved by less aggressive treatment than is usual. By not trying to induce complete remission at all costs, the mobidity and early mortality were reduced and at least an equivalence in survival was obtained.


Splenectomy for complications of chronic granulocytic leukaemia. 13 patients with chronic granulocytic leukaemia (C.G.L.) which was unsatisfactorily controlled underwent splenectomy. 3 out of 4 patients with hypersplenism did well, as did 5 out of 8 patients in whom the C.G.L. had undergone metamorphosis to a refractory phase. In a case of C.G.L. complicated by severe myelofibrosis the need for transfusion was reduced but survival was short. Splenectomy should be considered when C.G.L. in its chronic phase is complicated by hypersplenism, and may be considered as a part of the treatment after C.G.L. has undergone metamorphosis to a refractory phase. However, a favourable outcome is unlikely for patients over 65 years, and in the presence of coexistent illnesses, rapidly progressive metamorphosis to an acute phase, or severe bone-marrow failure from any cause. In C.G.L., elective splenectomy early in the chronic phase must be clearly distinguished from splenectomy performed at a later stage when the disease is not well controlled.


New familial defect in microbicidal function of polymorphonuclear leucocytes. A family is described in which a defect in intracellular killing affected two, and probably three, siblings of both sexes. From an early age they have had recurrent severe infections. During these episodes their white-blood-cell count became very high. This familial disorder seems to differ from previously reported syndromes of abnormal leucocyte function.


IgA deficiency, epilepsy, and phenytoin treatment. In a prospective study of thirty-two children with seizures treated with phenytoin (diphenylhydantoin), five had low levels of serum-IgA before treatment. All of these were among the fifteen who had had febrile convulsions in infancy. IgA levels fell significantly during 6 months treatment in the fourteen patients studied sequentially. Treated children with low serum-IgA had normal numbers of lymphocytes with surface IgA. This suggests that phenytoin causes failure of terminal differentiation of B lymphocytes, and is the first known cause of this, the commonest mechanism of immunoglobulin deficiency.


Acute changes in thyroid function in patients treated with radioactive iodine. Serum triiodothyronine (T3) and thyroxine (T4) were measured in thirteen unselected hyperthyroid patients before and at frequent intervals after iodine-131 treatment. There was an abrupt rise in  T3 from a pretreatment mean of 250 ng/100 ml to a maximum of 365 ng/100 ml at 24 hours. Total T4 rose from a mean of 18.7 mug/100 ml to a maximum of 22.3 mug/100 ml at 24-48 hours. These findings may explain why an occasional patient develops acute thyroid crisis after radioiodine treatment.


Relevance of "significant bacteriuria" to aetiology and diagnosis of urinary-tract infection. 28 of 74 female domiciliary patients who presented with urinary-tract symptoms did not fulfil the usually accepted laboratory criterion required for confirmation of urinary-tract infection (i.e., a urinary bacterial viable count in excess of 100 000/ml). The progress of the disease was similar in non-bacteriuric and bacteriuric patients. In addition, a significant proportion of the bacteriuric group did not show the response to therapy expected from the results of in-vitro tests of antibiotic sensitivity and urinary antibacterial activity. To explain these findings, it is postulated that bacteria may not be primary pathogens in uncomplicated urinary-tract infection even where "significant bacteriuria" is demonstrated.


Trial of digoxin in mania.

Trial of digoxin in mania. A suggestion that mania is associated with an increased membrane transport of sodium has been investigated in a double-blind trial of a specific Na-K A.T.P.ase inhibitor (digoxin) in twelve female inpatients with mania. Digoxin had no effect.


Defective essential-fatty-acid metabolism in cystic fibrosis. Cystic fibrosis (C.F.) is characterised by low serum levels of essential fatty acids (E.F.A.). However, the fatty-acid pattern does not totally resemble that of dietary E.F.A. deficiency. The differences suggest a reduction in the desaturation of E.F.S. It is not known whether this defect is the primary lesion in C.F. or is the result of tissue damage in the disease. It is proposed that C.F. patients might have increased linoleic-acid requirements, and possibly specific requirements for its desaturation products.


Acute folate deficiency in surgical patients on aminoacid/ethanol intravenous nutrition. Acute folate deficiency with pancytopenia and megaloblastic haemopoiesis developed in four patients after abdominal operations; all four responded to folic acid over 3-9 days. Three of them had been given intravenous nutrition with amino-acid/ethanol before the blood changes developed. A prospective study of twenty-five surgical patients with gastrointestinal diseases revealed a high frequency of acutely developing negative folate balance. Megaloblastic haemopoiesis and consequent blood changes were found in five patients. Treatment with intravenous nutrition correlated strongly with a fall in serum-folate and megaloblastic haemopoiesis. Some surgical patients develop acute folate deficiency which may proceed to megaloblastic arrest of haemopoiesis. Patients receiving intravenous nutrition containing ethanol are especially prone to this complication, which may be life-threatening if untreated. It is not yet known whether other forms of intravenous nutrition carry a similar risk.


Methicillin-resistant staphylococci 1965-75. Methicillin resistance in Staphylococcus aureus has been one of the major problems of gram positive infections in hospitals in the Zurich area. Up to 1971, about 20% of staphylococcal disease was caused by these peculiar organisms. Since 1972, however, a gradual decrease in the number of methicillin-resistant organisms has been observed, with an unprecedented low of 3% in 1975. The nearly 700 methicillin-resistant cultures that have isolated since 1965 exhibited, with rare exceptions, conventional group-II patterns of lysis in phage-typing and similar antibiotypes. It is suggested that all these isolates are derivatives of a strain which has long existed in the staphylococcal population. The reasons for the changes in the frequency of this strain as an agent causing staphylococcal disease are unclear. The use of penicillinase-resistant beta-lactam antibiotics in hospitals does not seem to play a major role in the distribution and spread or in the disappearance of this strain.


The Lancet - Saturday II October 1975. Sodium iothalamate as an aid to diagnosis of intracranial lesions by computerised transverse axial scanning. The diagnostic accuracy of computerised transverse axial tomography in conjunction with enhancement of tissue density by sodium iothalamate was assessed in 438 patients, 256 of them having intracranial tumours and 182 having other intracranial disorders. THE 80 X 80 matrix and 20 ml intravenous sodium iothalamate were used in 174 patients, the 160 X 160 matrix and 20 ml sodium iothalamate in 126 patients, and the 160 X 160 matrix and 60 ml sodium iothalamate in 138 patients. The diagnostic accuracy rose from 87% in the first group to 100% in the final group. The proportion of patients showing enhancement of tumour tissue density improved from 64% in the first group to 96% in the third. In the non-tumour patients, excluding those in whom the underlying disease caused no alteration of brain structure or tissue density, the overall accuracy was 96%, being unaffected by the modifications of technique. The enhancement of tissue density in brain abscesses, some cerebral infarcts, and angiomas could be readily distinguished from that seen in tumours.


Treatment of deep-vein thrombosis with intermittent streptokinase and plasminogen infusion. 17 consecutive patients who presented with extensive deep-vein thrombosis, confirmed by phlebography, were included in this study. Of 12 patients who received streptokinase and plasminogen infusion, complete lysis of thrombi was obtained in 8 and partial but extensive lysis in 4. In contrast, thrombi remained unchanged in each of 5 patients who received the same doses of streptokinase infusion only.


Simultaneous investigation and treatment of suspected acute adrenal insufficiency. The increase in plasma-fluorogenic-corticosteroids in response to a single injection of tetracosactrin depot was measured in eleven patients with suspected acute renal insufficiency who were treated simultaneously with prednisolone and deoxycorticosterone acetate (D.O.C.A.). Acute adrenal insufficiency was excluded in seven patients within 24 hours. There was no response in the remaining four patients, and prolonged corticotrophin stimulation tests confirmed the diagnosis of Addison's disease.


Acute effects of smoking tobacco and a tobacco substitute on lung function in man. The acute effects on airway function of smoking one cigarette of a tobacco substitute 'New Smoking Material' (NSM), one cigarette of conventional tobacco, and one cigarette containing 70% tobacco and 30% NSM, were studied in 6 healthy nonsmokers and 6 healthy smokers. None of the cigarettes produced any change in three tests of small-airway function (flow-volume curves, closing volume, frequency dependence of compliance). However, smoking either one conventional tobacco cigarette or the 30% NSM/70% tobacco cigarette produced an acute fall in specific airways conductance, of similar degree with both cigarettes, whereas the 100% NSM cigarette produced no such change.


Ischaemic heart-disease: possible genetic markers. National death-rates from ischaemic heart-disease are significantly correlated with population frequencies of histocompatibility antigen HLA-8 and haplotype 1-8. Serum-cholesterol levels may also be correlated with population frequencies of HLA-8. Inexplicably high death-rates from ischaemic heart-disease and high levels of serum-cholesterol in Finland may be due to the combined effects of HLA-8 and W15. It is suggested that HLA-8 (and possibly W15) are linked to genes which predispose to hypercholesterolaemia and ischaemic heart-disease. These findings provide some support for i-munogenetic hypotheses for vascular disease in man.


Potentiation of levodopa effect by intravenous L-prolyl-L-leucyl-glycine amide in man. L-prolyl-L-leucyl-glycine amide (P.L.G.) has melanocyte-stimulating-hormone-inhibitory hormone (M.I.F.) activity. When injected intravenously as a bolus of 200 mg, it greatly potentiated the effect of an oral levodopa dose upon motor performance objectively measured by a battery of tests. This amelioration in motility was accompanied by improvement in intellectual functioning.


Vulnerability of cell-surface receptors to autoimmune reactions. A previous hypothesis in which myasthenia gravis was explained by an immune response to acetylcholine receptors has been validated, and is here extended to cell receptors in general. Receptors on target cells, being accessible to circulating trophic hormones or transmitters, must also be accessible to antibodies which compete with the natural mediator for access to the site. To detect anti-receptor antibodies, physiological assay systems would be more sensitive than conventional immunological assays. Autoimmune responses to receptor sites would require a genetic predisposition to failure of immunological tolerance such as occurs in various autoimmune diseases. This hypothesis is supported by recent findings in hyperthyroidism and a type of insulin-resistant diabetes mellitus, and is applicable to other endocrinopathies, diseases in which dysfunction at receptor sites can be postulated, and regulatory functions within the immune system itself.


Kaposi's sarcoma: a byproduct of tumour rejection. It is suggested that Kaposi's sarcoma is the result of a chronic immunological reaction between antigenically altered or transformed lymphoid cells and normal lymphocytes. In the course of this local graft-versus-host type activity, an angiogenesis factor is liberated and intense proliferation of mesenchymal and endothelial cells ensues. During the G.V.H.-like activity, an oncogenic virus is either transferred to or induced in the cells responsive to the angiogenesis factor. Thus, the stage is set for neoplastic transformation of these cells in an environment which is conducive to the progressive growth of the virally transformed vasoformative mesenchyme.


Clinical applications of bone-marrow culture. The use of in-vitro culture methods for studying human haemopoietic cells has advanced greatly since 1970. These methods have contributed to our understanding of the mechanisms controlling granulopoiesis though the physiological role of colony-stimulating factor needs further clarification. In leukaemia they offer an approach to the study of possible causal factors and to the characterisation of leukaemic-cell defects. Results already obtained support the concept that the bone-marrow in acute myeloid leukaemia consists of coexisting populations of normal and leukaemic cells, with a leukaemic clone predominating in relapse and normal clones regenerating in remission. For the individual patient, in-vitro methods may prove useful in assessing prognosis and in confirming the completeness of remission; the detection of early relapse may then indicate the need for changing or re-instituting therapy. Further studies may aid the classification of the "preleukaemic" states and may help in the identification of the various causes of neutropenia.


Late complications of sterilisation by laparoscopy and tubal ligation. A controlled study. The frequency of late sequelae in 454 patients sterilised by laparoscopy and diathermy or by abdominal tubal ligation was compared with that in 154 controls whose husbands had had a vasectomy. Results showed an increase in menstrual loss and pain with menstruation in the sterilised groups, especially if this had been done by diathermy and division under laparoscopic control.


Some particularities of hepatitis B-antigen subdeterminants. From 200 acute viral hepatitis patients serum samples were collected successively, at various intervals. In 192 patients one single hepatitis B-antigen (HB-Ag) subdeterminant ("ad" in 37.6% and "ay" in 62.4% of the cases) occurred and persisted during the entire course of the disease. The remained 8 patients (4%) showed an alternation of HB-Ag subdeterminants. The possible causes of this alternation are discussed in detail.


[Analysis of the stimulus formation and excitation conduction systems by electrostimulation and intracardiac registration of the ECG (author's transl)]. A program for investigating the stimulus forming and excitation conduction systems of the human heart by programmed stimulation and intracardiac lead, with its most important clinical indications, is presented. The parameters to be determined for function analysis of the individual structures, such as the corrected sinus node recovery time, conduction rates and functional and effective refractory periods are discussed with their electrophysiological principles and their clinical information value.


[Cytostatic therapy of tumors under conditions of partial synchronisation with particular reference to malignant tumors of the testicle (author's transl)]. Cytostatic therapy under conditions of "partial synchronisation" is reported. 12 patients with extensive metastases of malignant testicular tumors and 5 other patients with other rapidly growing metastasizing tumors were treated. They had all previously undergone extensive operation, irradiation and some also treatment with cytostatics. Vincristine/ifosfamide and bleomycin/ifosfamide were given as stosstherapy and trofosfamid (Ixoten) as maintenance therapy. There was complete remission of the lung metastases in 8 of the metastasizing testicular tumors. Retroperitoneal and supraclavicular metastases became operable. In 2 patients there was a partial remission lasting 4-6 months. Complete remission could be obtained in the other patients.


Infective transmission and characterisation of a C-type virus released by cultured human myeloid leukaemia cells. A C-type virus isolated from long term cultures of myeloid cells from a patient with acute myelogenous leukaemia is infectious for a wide variety of cells. The establishment of chronically infected cells enabled us to characterise the virus by biological, immunological, and biochemical tests. The virus is closely related to the simian sarcoma-associated virus isolated from a woolly monkey fibrosarcoma.


Disease-inducing activity of different parts of bovine encephalitogenic protein in guinea-pigs. The encephalitogenic activity of different parts of bovine encephalitogenic protein (BEP) has been tested in guinea-pigs, mainly at a dose equimolar to 32 mug of intact protein. A high activity was found with complete protein and with region 89-169; both peptide 43-115, tyr (modified at the tyrosine residue 67) and HNB-89-169 (modified at the tryptophan residue 115) showed a moderate but clear-cut activity, whereas that of peptide 1-42 was very faint. No qualitative differences in the disease induced by the different peptides could be found; in only one animal out of 139 were clinical signs observed without evidence of histological disease. Slight histological changes, similar to those seen at EAE, were found in four out of 19 animals injected with Freund's complete adjuvant only.


Fractionation of protein carried by axoplasmic transport. II. Comparison in the rat of proteins carried to the optic relay nuclei. Proteins carried in the fast (200 mm/day) axoplasmic flow of retinal ganglion cells in albino rats were labeled with intraocular injections of radioactive L-methionine. Transported proteins which accumulated in the lateral geniculate nuclei (LGN) and superior colliculi (SC) 4 1/2 hours after injection were extracted with media of increasing solubilizing power. Over 70 percent of the transported material is soluble only in media possessing detergents such as Triton X-100 and sodium dodecyl sulfate. Specific activities of the transported proteins exceeded 7000 dpm/mg. With specific activities this high, further fractionation could be carried out under conditions of high resolution. Separations of solubilized proteins on polyacrylamide gels, either with or without detergents, showed that a large number (60-100) of polypeptides are transported. Using a double labeling procedure which employed L-[35S]methionine and L-[methyl-3H]methionine, material transported to the LGN was compared with that transported to the SC. No statistically significant differences were seen in the polypeptides transported by the retinal ganglion cells to the two major optic relay nuclei.


Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone on the cardiovascular system of patients with parkinson's disease. The effects of carbidopa combined with levodopa (carbidopa/levodopa) and levodopa alone on the cardiovascular system of patients with Parkinson's disease were evaluated. Thirty-eight patients who had been on stable doses of levodopa underwent a complete cardiac examination, including measurement of recumbent and erect blood pressure and 24 hour ambulatory electrocardiographic monitoring. Patients were classified with respect to the presence or absence of clinically significant heart disease and ventricular arrhythmias. Nineteen of the 38 patients (50 percent) had heart disease, and 12 (32 percent) had significant ventricular arrhythmias. Eleven of the 12 with arrhythmias had underlying heart disease. The incidence of arrhythmias did not correlate with the dose of levodopa. The patients were subsequently randomly assigned to treatment groups receiving either carbidopa/levodopa or levodopa alone. There was no significant difference in the severity of ventricular arrhythmias or in the incidence of orthostatic hypotension in the group assigned to carbidopa/levodopa compared with the group receiving levodopa.


Temporomandibular degenerative joint disease. Part II. Diagnostic procedure and comprehensive management. The diagnostic procedure is given in the detail necessary to arrive at an accurate diagnosis of temporomandibular degenerative joint disease (TDJD). The differentiating clinical findings of degenerative joint disease (DJD) and rheumatoid arthritis of the temporomandibular joint (TMJ) are described. Principles and modalities of comprehensive management of TDJD are presented in the manner and sequence needed to allow practical clinical application. Methods of treatment are applied to the management of patients with acute and chronic TDJD. The surgical procedure for TDJD, intracapsular high condylectomy with a preauricular incision, is described in the detail required for individual application. Case reports are presented to illustrate the comprehensive management of TDJD.


[Quantitative study of alpha 1 antitrypsin and alpha 2 macroglobulin in the sputum]. A quantitative study of alpha-1-antirypsin and alpha-2-macroglobulin in the sputum showed an increase in both during attacks of asthma and in patients with chronic obstructive bronchitis. The levels were much lower in asthma patients during remissions, in emphysema and in patients with chronic simple bronchitis, without associated bronchospasm. The parallel variations in levels of alpha-1-antitrypsin, albumin and transferrin in the sputum, contrasts with the course of secretory IgA and are in favour of a transudation process of alpha-1-antitrypsin across the respiratory mucosa.


F antigen. III. Immunological and biological properties. Relationship of the isoforms of F antigens from A2G and CBA inbred mouse strains have been worked out in detail in respect to their immunogenicity. Mice from several inbred strains have been shown to possess the ability of forming anti-F upon stimulation with xenogeneic F antigens from certain species. An immunoelectrophoretic method for sensitive quantitation of the antigen is described. During human ontogenesis the antigen appears very early. It could never be detected in serum except in cases of acute liver disease. A small fragment set free under denaturing conditions showed the ability of inhibiting precipitation of the complete antigen by antibody. The F protein seems to be a vehicle for this small fragment possessing haptenic properties and probably being responsible for the universal cross-reactivity.


[Mechanisms of inactivation of aminosides. Relationship to phenotype in Gram negative bacilli]. Aminosides are antibiotics essential in the treatment of gram negative bacilli infections. Phenomena of resistance related to them are amongst the best documented. For enterobacteria encountered in clinical practice, the process is usually a plasmid mediated inactivation mechanism, the dispersion of which in a hospital context may be appreciated. Precise knowledge of the modes of inactivation and the molecular sites involved has led to the production of semi-synthetic aminosides which escape the action of these enzymes. A classification of hospital bacteria according to their type of resistance is possible by virtue of the study of phenotypes and may make it possible to define the true need of these new substances.


[Surgery of pain in the lung apex cancers]. When invasion of the brachial plexus occurs, tumours of the lung apex result in intolerable pain. On the basis of 13 cases, the authors show that surgical excision, whilst only palliative, is associated with immediate total or quasi-total disappearance of pain in all patients. This effect lasted for two to eighteen months. Operation gives marked relief in a painful situation not helped by medical treatment.


[Histochemical study of the effect of phosphoroorganic esters Z-50 (fenchlorfos) and Z-51 (bromophos) on cholinesteras activity in the course of the muscle phase in experimental trichinellosis in mice]. The studies were carried out on mice between the 14th and 19th days, i.e., in the period of maximum penetration of T. spiralis larvae in the host's muscles. Phosphoro-organic esters were given orally to experimental animals in oil solution, at the following doses: Z-50 -- 150 mg per kg of body weight and Z-51 -- 100 mg per kg of body weight. The influence of esters on the activity of cholinesterases was investigated with the Koelle-Friedenwald method, modified by Gomori. The aim of the study was to establish the joint activity of the migrating Trichinella larvae and phosphoro-organic esters on the organism of the host. Z-50 and Z-51 penetrate in therapeutic doses the striated muscles rather weakly. 24 hrs after these compounds were given, acetylcholinesterase (AChE) activity was inhibited in motor end-plates in about 30%, and in muscle fibres infected with T. spiralis larvae in about 60-70%. Pseudocholinesterase (PChE) activity was stronger inhibited than AChE. 24 hrs after applying Z-50 and Z-51 PChE was inhibited in about 90%. Of the two phosphoro-organic esters being examined Z-51 stronger inhibited the cholinesterases activity than Z-50. It was found that the efficiency of phosphoro-organic esters in the course of trichinellosis depends on its ability of infiltration into the host's muscles and on the degree of inhibition of the active cholinesterases in the motor end-plates. Attention was drawn to the fact that increased activity of cholinergic system is one of the main factors in the patholgenesis of the second phase of trichinellosis, i.e., the migration and penetration of the larvae in the muscular fibres of the host.


A clinical nursing study: failure to thrive in a child with Down's syndrome. A five-year-old child with Down's syndrome and severe failure to thrive, given a program of individually tailored developmental nursing care, showed substantial improvement as evidenced by changes in seven of nine criteria chosen for measurement. When investigation of the child and his family suggested that the failure to thrive was the result of masked deprivation, a study was designed to measure the effect of a 17-day program of developmental nursing care on specific parameters of growth and behavior-height, weight amount of sleep, caloric intake, active mobility, awareness of the environment, prelanguage vocalizations, self-stimulation behavior, and play activity with toys. Data on these criteria were gathered before, during, and after the nursing care program. Findings supported the assumptions that there would be an increase in height, weight, amount of sleep, active mobility, awareness of the environment, prelanguage vocalizations and a decrease in self-stimulation. Findings did not support the assumptions that there would be an increase in caloric intake and play activity with toys. The study supported the use of nursing care as the primary therapeutic modality for children with this condition and illustrated an approach to systematic evaluation of the effects of nursing care.


Thyroid metabolism in the recessive sex-linked dwarf female chicken. 2. Binding of thyroid hormones by serum proteins. Serum protein profiles were studied together with serum binding sites and capacity for L-thyroxine in dwarf and non-dwarf White Leghorn and White Rock breeds at ages 1 wk., 4 wks. and in laying hens. Serum protein profiles varied with breed, strain and age. The percent gamma-globulin fraction was greater (P less than .05) in dwarf 1 wk. old and laying hens of the White Leghorn breed when compared with the normals. The only difference found in the White Rock breed was a decreased level of albumin in dwarf laying hens. There were no significant differences in the capacity or sites of binding of L-thyroxine to serum proteins although greater amounts of L-thyroxine were bound to globulin fractions in the dwarf. The data were interpreted to suggest that changes in serum protein profiles may have been the result of hypothyroidism at the cellular level but there was no reason to suspect abnormal binding of thyroid hormones to be the cause of that hypothyroidism.


Region of immunoglobulin light-chain mRNA transcribed into complementary DNA by RNA-dependent DNA polymerase of avian myeloblastosis virus. The mRNA coding for a kappa-type immunoglobulin light (L)-chain and its complementary DNA (cDNA) hybridize with a Crt1/2 of 2.6 x 10(-4) moles of ribonucleotide x liter-1 x sec, forming well-matched duplexes (melting temperature Tm equals 89 degrees). The molecular weight of the cDNA is about 280,000 (840 nucleotides) as determined by alkaline sucrose gradient centrifugation and from the extent of protection of the mRNA by the cDNA from ribonuclease digestion. The cDNA anneals with kappa-type mRNAs of the same and different subgroups with comparable Crt1/2 values, but not with a lambda-type mRNA. Thus, one kappa-type cDNA can be used to quantify the mRNAs coding for all kappa-type L-chains. The values of cDNA hybridized at saturation with various kappa-type mRNAs indicate that: (1) the cDNA is complementary to the entire constant region and to about half of the variable (V)-region; (2) V-regions of similar amino-acid sequence are coded by a similar nucleotide sequence; (3) the nucleic acid probe to one V-region may anneal and quantify V-region genes of members of the same subgroup.


Specific binding of tryptophan transfer RNA to avian myeloblastosis virus RNA-dependent DNA polymerase (reverse transcriptase). The ability of tryptophan tRNA (tRNATrp) to initiate reverse transcription of the 70S RNA of avian RNA tumor viruses suggested that the reverse transcriptase (RNA-dependent DNA polymerase; deoxynucleosidetriphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7) might have a specific binding site for the tRNA. A complex of tRNATrp and the avian myeloblastosis virus reverse transcriptase has been demonstrated using chromatography on Sephadex G-100 columns. Of all the chicken tRNAs, only tRNATrp and a tRNA4Met bind to the enzyme with high enough affinity to be selected from a mixture of the chicken cell tRNAs. The ability of tRNATrp to change the sedimentation rate of the enzyme indicates that tRNATrp is not binding to a contaminant in the enzyme preparation. Treatment of the enzyme with monospecific antibody to reverse transcriptase prevented binding of tRNA as well as inhibited the DNA polymerase activity of the enzyme. The ability of reverse transcriptase to utilize tRNATrp aa a primer for DNA synthesis, therefore, appears to involve a highly specific site on the enzyme.


Transformation of cultured human embryonic fibroblasts by oncornavirus-like particles released from a human carcinoma cell line. A fibroblast-like cell culture was established from a stomach biopsy of a patient with metastatic adenocarcinoma. One of the cultures, at the 6th passage level, left unattended for a month at 37 degrees, produced numerous foci of epithelioid cells. Upon subculturing, an epithelioid cell line, designated HCCL (human carcinoma cell line), was established. The HCCL cells released particles possessing the characteristics of oncornaviruses: density 1.175 g/ml, cores with a density of 1.22-1.26 g/ml, high-molecular-weight RNA (60-70S) and RNA-instructed DNA polymerase activity (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7). Inoculation of particles released from HCCL cells into cultures of human embryo muscle fibroblasts resulted in the appearance of foci of transformed cells.


Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis. Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of RNA-directed DNA polymerase (reverse transcriptase). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)-(dG)12-18 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently, diagnosis 2 and 4 months after initial evaluation revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.


Adjuvant effect on maintenance and escape from tolerence. When mice are injected with deaggregated human gamma globulin (HGG), and HGG-tolerant state ordinarily is produced and persists despite subsequent challenges with an immunizing dose of HGG in saline or with an immunizing dose of HGG in Mycobacterium adjuvant. Subsequent administration of an immune elimination dose of radiolabeled HGG, at 27 days and 47 days does not break the tolerant state. Of special interest is the observation that when complete adjuvant containing increasing amounts of mycobacterial components was administered in conjunction with antigen very early in the tolerance induction phase 5 days after TID, it appears to prevent tolerance production. Mice challenged 5 and 17 days after the tolerance-inducing inoculation exhibit a statistically significant increase in circumvention of tolerance when compared with individuals challenged on the 7 and 17 day schedule. This increased circumvention of tolerance, as evidenced by 5 day challenge mice, seems to be related both to the mycobacterial content of the adjuvant and murine strain.


Immunological recognition of specific antigenic determinants in UV- and gamma-irradiated phage DNA. Thermally denatured DNA of coliphage T1 after treatment with uv-light (2537 A) and 60Co-gamma rays acts as a hapten with antigenic determinant groups specific for radiation-induced alterations of the macromolecule. After conjugation to methylated bovine serum albumin the DNA becomes immunogenic in rabbits. Antibodies against irradiated DNA do not react with unirradiated single-stranded DNA. Antigen-antibody complexes were demonstrated by CsCl-density gradient centrifugation. The decrease in buoyant density of the DNA is proportional to the amount of antibody protein bound to the antigen. By this means photoproducts as well as alterations due to ionizing radiation in DNA were detected independent of the type of antigen-antibody complex, i.e. precipitating or soluble aggregate.


Responsiveness of lymphoid precursors to polyclonal B-cell activators. We have shown previously that in the differentiation of fetal liver cells to mature B cells in irradiated hosts, these cells sequentially gain responsiveness to the polyclonal B-cell activators dextran-sulphate (DxS), lipopolysaccharide (LPS), and purified protein derivative from tuberculin (PPD), in that order. In this paper we show that both fetal liver cells and adult bone marrow cells responded with proliferation to DxS, but not to LPS OR PPD. However, neither fetal liver nor bone marrow cells gave rise to detectable numbers of high-rate antibody-secreting cells on short-term stimulation by polyclonal B-cell activators. The lack of LPS and and PPD responses of fetal liver and bone marrow cells could not be ascribed to the presence of inhibitory cells, and the DxS-induced response in these cell populations was not dependent on adherent cells. However, LPS could inhibit the DxS response of fetal liver cells, possibly indicating that DxS-responsive cells are precursors to B cells. Direct evidence was provided that DxS activated B-cell precursors in bone marrow. Thus, this cell population became responsive to LPS after DxS prestimulation, as measured by DNA synthesis. Bone marrow cells, sequentially stimulated with DxS and LPS, contained increased numbers of cells with surface immunoglobulin, although no significant increase in numbers of antibody-secreting cells was obtained. These data indicate that DxS had the capacity to increase the rate of differentiation of B-cell precursors. Finally, we show that the sequential appearance of responsiveness in B-cell differentiation to polyclonal B-cell activators is not due to lack of accessory cells during early stages in maturation.


Biological significance of Fc receptor-bearing cells among activated T lymphocytes. Lethally irradiated mice injected with syngeneic thymocytes and immunized with protein antigens develop specific helper T cells. If injected with semiallogeneic thymocytes, such mice generate H-2 antigen-specific cytotoxic T cells. Most spleen cells from these chimeric mice possess Fc receptors. The present results demonstrate that the development of Fc-receptor-bearing cells in thymocyte-injected irradiation chimeras seemingly is due to the physiological conditions in the mice rather than to the specific immunization. As a corollary, both helper T cells and cytotoxic T cells did not have Fc receptors, at least not in their effector state. Thus, Fc receptors on T cells would seem irrelevant to their immune function.


Quantitative separation of antigen-specific murine antibodies by anti-allotype chromatography. The use of Sepharose-conjugated murine anti-Iga or anti-Igb allo-antisera allowed the quantitative separation of immunoglobulins of the two allotypes. After fractionation of mixtures of anti-(T,G)-A--L antisera obtained from congenic strains differing in immunoglobulin allotype, it was possible to measure the antigen-binding capacity of specific anti-(T,G)-A--L antibodies in each allotype fraction. Analysis of artificial mixtures of immune sera obtained from homozygous Iga and Igb animals showed that this method is quantitative and internally consistent. This method of affinity chromatography was used in the analysis of specific anti (T,G)-A--L antisera from tetraparental mice.


Antibody-dependent cell-mediated cytotoxicity: heterogeneity of effector cells in human peripheral blood. We have compared antibody-dependent cell-mediated cytotoxicity (ADCMC) of human peripheral blood leukocytes (PBL) in three model systems. target cells were 51Cr-labeled mouse mastocytoma cells, chicken erythrocytes (CRBC), and human erythrocytes (HRBC) coated with appropriate heterologous or isologous antisera. Effector cells were characterized on the basis of their adherence, phagocytosis, radiosensitivity, and sedimentation velocity(s) at 1 g. In predominantly mononuclear (Ficoll-Isopaque-purified) PBL preparations (MPBL) HRBC were lysed by an adherent, phagocytic population of cells that was markedly radio-resistant. Sedimentation velocity analysis further established that these effector cells were restricted to rapidly sedimenting fractions (s greater than 4.5 mm/hr). On the other hand, mastocytoma cells were lysed by a population of MPBL that was nonadherent, nonphagocytic, and relatively radiosensitive. These cells mainly restricted to slowly sedimenting fractions (s greater than 4.5 mm/hr) following 1 g velocity sedimentation. CRBC appeared to be susceptible to lysis by both types of mononuclear effector cell. In some experiments, enriched populations of polymorphonuclear leukocytes (PMN) were isolated. These cells were found to lyse both HRBC and CRBC very efficiently, whereas mastocytoma cells were lysed very little if at all by the same effector populations. Taken together, these results suggest that antibody-coated mastocytoma cells are lysed uniquely by effector cells in human peripheral blood with the physical properties of lymphocytes, whereas antibody-coated HRBC are lysed by both monocytes and PMN, but not by lymphocytes. Antibody-coated CRBC would appear to be lysed by all of the three effector cell types tested.


Cell-mediated immunity to a serologically defined (SD) HL-A antigen panel in kidney-transplanted patients. The graft-directed, cell-mediated immunity in kidney-allografted patients was examined with a seriologically defined (SD), donor-unrelated panel of antigenic material in clinical steady state, soon after transplantation, and during acute rejection episodes. The SD antigens were selected from the panel on the basis of predictions hypothesized from the SD match of donor and recipient. The cell-mediated immunity was measured by the direct leukocyte migration agarose test (LMAT). Positive reactions in kidney-transplanted patients were induced particularly by one preparation (antigen 52) and were unpredictable on the basis of SD classification. The investigation shows that other antigenic determinants, different from SD antigens, probably play an important role as inducers of cell-mediated, graft-associated immunity in kidney-transplanted patients.


A surface antigen marker for human monocytes. Antisera have been raised in rabbits aginst human peritoneal macrophages. After absorption with tonsil cells the sera reacted, by direct and indirect immunfluorescence, with phagocytic mononuclear cells from a variety of tissues and, in addition, stained a small population of nonphagocytic non-T, non-B mononuclear cells present in blood, spleen, and marrow but absent or very rare in tonsil and thymus. The antisera may define a human monocyte-macrophage cell surface differentiation antigen (HuMA) and can be used to deplete or enrich reactive cell population.


The effect of lipopolysaccharide on the primary immune response to the hapten NNP. We have studied the effects of lipopolysaccharide (LPS) on the primary in vivo immune response to the hapten (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP), with special reference to the avidity and affinity of the early appearing 19S and 7S antibodies. Comparisons were made of the immune response to NNP in groups of mice given either antigen alone, LPS alone, or antigen plus LPS. The avidity of antibodies induced by LPS plus antigen were similar to that found after injection of antigen alone, in spite of the fact that the antibodies were more numerous. However, when comparing the avidity of antibodies produced in animals given only LPS with those given LPS plus antigen, the latter group was often found to have fewer low-avidity 19S-antibody-producing cells. The affinity of 7S antibodies was also similar in the two groups given antigen or antigen plus LPS. Kinetic studies of the effect of LPS on the primary immune response to NNP showed that synergy was observed only before or after the peak response in groups given antigen alone. It is concluded that LPS under synergy conditions acts preferentially on specific antigen-sensitive cells, which are distinct from those that are activated to polyclonal antibody synthesis by LPS alone. Possible mechanisms for the adjuvant effect of LPS are discussed.


Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. IV. Isolation of two groups of naturally occurring, idiotypic molecules with specific antigen-binding activity in the serum and urine of normal rats. In the rat the major histocompatibility locus antigens are determined by the Ag-B locus. In the present article evidence is presented that the sera and urine of normal adult rats contain naturally occurring antibody-like molcules with reactivity to allogeneic Ag-B antigens. Such molecules can be shown to contain both antigen-binding capacity for the relevant antigens and the idiotypic markers signifying such specific reactivity. The molecules could be shown to be composed of two groups of molecules, one around 7S IgG in size and the other around 35,000 in molecular weight. Only the smaller molecules were found in the urine. From other data we know that the 7S molecules are produced by B lymphocytes and the 35,000-molecular-weight molecules by T cells. Purified natural anti-Ag-B factors, when inoculated into rabbits or chickens, lead to the production of specific anti-idiotypic antibodies that will selectively inactivate rat T lymphocytes with the capacity to react against the relevant Ag-B antigens while leaving other reactivity intact. We thus conclude that the present system allows the purification of naturally occurring idiotypic B- and T-cell products with antigen-binding specificity for further biochemical and functional analysis.


Secondary responses of human lymphocytes to alloantigens in vitro. The secondary response of human lymphocytes following restimulation with alloantigens has been studied. If fresh stimulating cells are added to a mixed leukocyte culture (MLC) at a time when the peak of proliferative and cytotoxic activity has passed, a rapid reactivation occurs. The secondary response in MLC demonstrates specificity such that restimulation with the original sensitizing cell (or one presumably sharing the LD genetic determinants responsible for triggering MLC) induces a greater proliferative response than a third-party cell. On the other hand, the secondary cytotoxic response is directed towards the SD antigens of the original sensitizing cell regardless of which cell is used for restimulation. Possible mechanisms of cellular interactions are considered to explain these results.


Inhibition by anti-beta2-microglobulin antisera of responder cells and not of stimulator cells in the mixed lymphocyte reaction. Specific antisera directed against beta2-microglobulin (B2m) have been shown to inhibit completely the mixed lymphocyte reaction (MLR). However, the mechanism of inhibition has been unclear. In the present study, further experiments were performed to determine the effect of anti-B2m on both the stimulator and responder cells in an MLR. The experimental design used was that of a xenogeneic MLR, using mouse and human lymphocytes. The ffect of anti-human B2m was studied in this system. Anti-human B2m inhibited the xenogeneic MLR only when human lymphocytes were used as responder cells and did not inhibit the MLR when they were used as stimulator cells...


Some epidemiological and clinical aspects of hepatitis B antigen and its subtypes. The close association between hepatitis B antigen (HBAg) and the infectious agent of hepatitis B is clear. Many investigations have shown HBAg to be a useful tool for epidemiological studies of hepatitis B. The relation between HBAg and the postulated hepatitis B virus (HBV) is as yet not clear. In light of recent results a possible candidate could be the so-called Dane particle, which has HBAg reactivity on the surface, but possesses an antigenically distinct core. The core has been shown to have associated DNA polymerase activity. The particles which carry HBAg reactivity have surfaces which are antigenically complex. One common specificity a and 2 pairs of mutually exclusive determinants have been recognized namely d and y and w and r but further possible specificities are under investigation. Four different phenotypes have been described, adw, adr, ayw and ayr. Present evidence indicates that adw, adr and ayw are the phenotypic expression of 3 different transmissible strains of HBV. Studies on the epidemiology of these subtypes have shown 3 different geographic patterns. In the USA and Northern Europe both Dw (adw) and YW (ayw) are common, but in the Eastern Mediterranean and Middle East Yw is practically the only type found. In the Far East DR (adr) is the dominating subtype. Investigations have been done to determine whether there are any clinical differences in hepatitis caused by the different tubtypes. No certain differences have been shown.


Cellular elements in the urine in health and in acute infectious diseases, especially with respect to the presence of haematuria. A study with application of millipore procedure and Papanicolaou staining. The excretion of cellular per litre of urine amounted in healthy persons to, in round figures, one million epithelial cells (2.5 cells per visual field) in both sexes, one million leukocytes in males, one million erythrocytes in females and 0.5 million in males. The maximal excretion was calculated to be 5-6 million per litre. In acute infections the number of epithelial cells and leukocytes in the urine rose to more than the double. Pathological microscopic haematuria, judged by exceeding of the maximal value for normal excretion during the acute phase (24 or more erythrocytes per visual field), occurred in no case of mycoplasma infection, in about 4% of measles, mononucleosis, serous meningitis and hepatitis cases, in about 8% of mumps and streptococcal infections, and in more than 20% of influenza A2 cases. Statistical significance or probable significant existed between influenza and other diseases. The haematuria was unrelated either to the general degenerative or to the specific inclusion-provocative reaction within the renal and urinary tract epithelium. The cause is sought in an involvement of glomeruli with increased diapedesis. The special position of influenza may be explained by the marked haemorrhagic reactions produced by this infection. In one case persistent haematuria combined with increased content of inclusion-bearing cells occurred after influenza. Immunoglobulin deposition in glomerular mesangium may perhaps be one explanation of this haematuria.


Effect of the common bile acids on the fibrin/fibrinogen fragments in rheumatoid synovial fluid. A possible clue to the ameliorating effect of jaundice in rheumatoid arthritis. Fibrin/fibrinogen degradation products observed in rheumatoid synovial fluid exhibit resistance to plasmin proteolysis. In the present study, the influence of the common bile acids on the plasmin digestion of these degradation products in 16 rheumatoid synovial fluids were quantitated immunologically by radial immunodiffusion, and qualitatively estimated by crossed immunoelectrophoresis. Addition of chenodeoxycholic acid, deoxycholic acid, and their taurine and glycine conjugates in concentrations of 3.33 mumole/ml of a mixture of rheumatoid synovial fluid and plasmin resulted in complete plasmin degradation. Cholic acid and its taurine and glycine conjugates were effective only in concentrations of 4.44 mumole/ml. A detergent, such as Triton X-100, had little or no effect on the plasmin digestion. Other proteins capable of influencing fibrinolytic activity, such as plasminogen and the inhibitors alpha1-antitrypsin and alpha2-macroglobulin, were not affected by the two detergents. The bile acids are thought to influence the fibrin/fibrinogen degradation products by unfolding the protein at a molecular level, by virtue of their properties as steroid detergents, leaving the fibrin/fibrinogen degradation products susceptible to plasmin digestion.


Immunologic differentiation of proteins in the surfactant system of the lung. Immunoelectrophoresis revealed the following four protein components in the lung surfactant system of guinea-pigs: albumin, transferrin, IgG, and an organ-specific protein migrating in the beta-globulin range. These proteins probably take part in the formation of the hypophase of the alveolar lining layer and thereby influence the surface properties of the alveolar air-liquid interface.


Differential fluorescent staining of human chromosomes with daunomycin and adriamycin--the d-bands. Human chromosome preparations were treated with a group of anthracycline antibiotics. Well-defined, orange-red fluorescent bands were observed on chromosomes after the slide was stained with daunomycin and adriamycin but not with nogalamycin. The characteristic differential bands appeared to be similar to the banding patterns obtained by the quinacrine techniques. Interaction of these antibiotics with DNA could provide information on the general mechanism of fluorescent banding. Further, these bands (D-bands) appeared to be more stable than the Q-bands and may have some usefulness for routine clinical cytogenetic analysis.


Treatment of obstructing cancer of the colon and rectum. A review was made of 128 patients who had obstructing cancer of the colon and rectum. About one-third of the patients had metastatic disease at the time of presentation. Primary resection carried an initial higher mortality rate than staged resection, but at one year and three years, no statistical difference can be found between the two procedures. There are high morbidity and mortality rates with all forms of treatment. A controlled comparative trial of primary and staged resection is recommended in the treatment of obstructing cancer of the colon and rectum.


Mediastinoscopy and bronchial carcinoma: experience with 600 mediastinoscopies. Of 600 mediastinoscopies carried out from 1966 to 1973, 479 were performed to assess the operability of a pulmonary carcinoma. Of these, 206 (43%) were positive and 273 (57%) were negative. Of the 161 patients found positive during an initial period, 147 were refused operation; the remaining 14 were considered suitable candidates for operation, either because only one homolateral lymph node site was involved or because there was a concomitant osteoarthropathy. The tumour was irresectable in one of these 14 patients who died after 3-5 months; curative resection was possible in one and palliative resection in 12 patients. These 12 patients all died within a year. Of the 184 patients found negative during an initial period, 149 were treated by operation. The tumour proved irresectable in seven (5%), while curative resection was possible in 113 (76%) and palliative resection in 29 (19%) patients. Comparison with the period 1957-63, when in the same hospital resection was performed after a negative Daniels' (scalene node) biopsy, shows that the tumour was irresectable in 25 (20%) of the 124 patients with a negative biopsy, while curative resection was possible in 43 (35%) and palliative resection in 56 (45%) patients. During a second period, patients with a positive mediastinoscopy were in principle refused operation. Of 89 negative patients, 81 were treated by operation. No tumour was found to be irresectable; curative resection was possible in 63 (78%) and palliative resection in 18 (22%) patients. An operation for bronchial carcinoma was performed on 167 patients between September 1970 and September 1973 after a negative mediastinoscopy in 95, and without mediastinoscopy in 71 patients, either because of a peripheral tumour (70) or because of a tumour relapse after two years (1). The resection was palliative in 11% of the 71 cases, but in only one patient with a peripheral tumour could a mediastinoscopy have been positive. Finally, an operation was performed on one patient with a positive mediastinoscopy and a tumour relapse after six years. A survival study was made of the first 100 patients with pulmonary carcinoma, operated on between September 1970 and March 1972 and with a follow-up from a minumum of two years to a maximum of 3-5 years. The early mortality averaged 10% and was higher after pneumonectomy than after lobectomy. The late mortality was 16% after curative lobectomy, 38% after curative pneumonectomy, and 83% after palliative pneumonectomy. The survival after 2 to 3-5 years was 63%.


[Renaut's bodies and familial neuropathy of the Dejerine-Sottas type. Apropos of 2 anatomo-clinical cases]. The authors report the pathological and clinical findings in two cases of familial Dejerine-Sottas neuropathy, including the peripheral nerve lesions of an unusual type producing extensive sub-perineural separation. In one case, there was onion bulb hypertrophy of the schwann layer and definite demyelinisation and above all, endoneural nodular structures known as Renaut bodies. The presence of Renaut bodies has not, to our knowledge, yet been reported in Dejerine-Sotta's disease. It is rare but well known during other neural diseases, which are often familial and in various pathological circumstances, such as syringomylia, diabetes and hypothyroidism. The fibroblastic origin of these structures has been proved. Their possible pathogenic role and their significance are  still the object of discussion.


Expression and segregation of HL-A antigens in D98/AH-2 by lymphocyte and fibroblast hybrids. Somatic cell hybrids between D98/AH-2 and fibroblasts or peripheral blood lymphocytes were analysed for the expression of HL-A antigens. The hybrids express the antigens of the donor lymphocytes or fibroblasts as well as other HL-A specificities from D98/AH-2, a HeLa derivative on which no HL-A could be detected by direct cytotoxicity. Segregant hybrid clones could be used to determine HL-A haplotypes and define the linkage relationships between these haplotypes and the PGM3 alleles expressed in the hybrids. An analysis of the HL-A antigens on D98/AH-2 and other HeLa derivates was done using absorption and a modified cytotoxicity assay.


Extracellular cross-striated banded structures in human connective tissue. Extracellular cross-striated banded structures have been found in the connective tissues of a variety of organs. Rarely have they been found in conditions such as: hyperplastic parathyroid, follicular adenoma of the thyroid, metastatic hemangiopericytoma in the lung, sarcoidosis of lymph node, and two biopsies of nerve as reported here. The shape and size of the structure varies, as well as its periodicity, which is usually in the range of 1000 to 15000 A. An unusual exception to this general rule is the banded structure in the follicular adenoma of the thyroid where the periodicity is 270 A. These structures are quite different from native collagen or experimentally reconstituted long-space collagen, both by staining reaction with phosphotungstic acid or uranyl acetate and lead nitrate, and in their ultrastructural morphology.


Histochemical demonstration of hyaluronic acid in human dermal mast cells. Acid mucopolysaccharides in mast cell granules were histochemically studied in the lesion of urticaria pigmentosa and in the dermis of normal human skin. Alcian blue and azure A were used to stain mucopolysaccharides. Bromphenol blue was employed for detection of basic proteins. In a further attempt to identify various polyanions, staining was carried out with alcian blue containing various concentrations of electrolytes. Methylation, saponification, and digestion with streptomyces or testicular hyaluronidase, chondroitinase ABC, sialidase, or desoxyribonuclease were also employed. The results obtained are most likely to suggest the presence of hyaluronic acid in mast cell granules.


[Fetal tumor antigens].

[Fetal tumor antigens]. A wide spectrum of fetal antigens is found not only in fetal cells but also in tumor cells. These substances are termed onco-fetal antigens. One group out of these antigens has developed special diagnostic interest and importance, first of all the carcino-embryonic antigen (CEA) in adenocarcinomas of the gastrointestinal tract. Another class of fetal antigens consists of tumor-assoicated membrane-antigens against these the organism may develop a cytotoxic reaction and in the long run, may repulse the tumor like an incompatible graft. The verification of this second group was possible by means of various cross reactions. These latter fetal antigens eventually may be utilized for purposes of immunological prophylaxis and therapy.


Studies on the effect of Fenchlorphos on postirradiation changes of serum proteins and nucleic acids content in rat liver. The effect of Fenchlorphos on postirradiation changes of serum protein levels and nucleic acid content in rat liver were investigated. It was found that this compound significantly decreases postirradiation changes in serum proteins, properdin level and nucleic acid content in rat liver. An important role of these phenomena in radioprotective action of Fenchlorphos is suggested.


[Radiotherapy of brain metastases].

[Radiotherapy of brain metastases]. Experiences are reported obtained with radiation therapy of brain metastases in 121 patients during the last 15 years. The treatment to lesser extent aimed at prolongation of survival but much more at the attempt to alleviate troubles and to spare pain. The indication thus involved medical points of view as well as ethical ones. The radiotherapy of cerebral metastases comprises the whole cranial volume and requires a focal dose of minimally 4000 R within four weeks. In 53% of the patients, the regression of neurological symptoms was considerable, in 18% even complete, partly beginning already after a few days of treatment. The number of recurrences was small. Under conditions of rigorous indication, the radiation therapy of brain metastases offers a rewarding palliative measure.


[Studies on the relationship between dental plaque and the hard tissues of healthy and diseased teeth]. 1. Dental plaques were detected in all the teeth under investigation, with the exception of impacted teeth. 2. The appearance of the plaques is regular. They occur chiefly in certain zones of the tooth crown and in retention areas. The film thickness ranges from 10 to 60 mum. 3. No alterations of the structure or of the primary texture of the hard tissues were observed on healthy and periodontally diseased teeth. The plaques infiltrate but slightly into the surface. 4. Carious teeth have a different appearance. The plaques infiltrate more or less deeply. They even penetrate into the macroscopically free zones of the enamel as well as of the dentine. The infiltrate is diffuse, especially in regions where the relationship between mineral and organic constituents is distrubed.


[The effect of health educational measures on the state of oral hygiene. 1. Relationship between intensity and effectiveness]. The effectiveness of health educational measures increases with the time spent for them. A health education which motivates the patients towards personal activity is unequivocally superior to passive forms of health education such as information, instruction and demonstration.