Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. Amyloid fibrils were studied from two different tissues of medullary carcinoma of the thyroid (MCT). The fibrils mainly consisted of a low molecular weight protein, AMCT, which was immunologically distinct and did not react with various antisera against known amyloid fibril proteins. A specific antiserum raised against the MCT amyloid proteins gave a reaction of identity with the degraded MCT amyloid fibrils from two patients, as well as with the isolated AMCT protein, but showed no reaction with other known amyloid proteins. The AMCT protein had a blocked N terminus, but the sequence analysis of a cyanogen bromide fragment revealed identity with human calcitonin in the 11 positions studied. Although the amino acid composition was similar, there were also distinct differences, and the mol wt of 5,700 daltons was considerably larger than that of calcitonin. For these reasons the AMCT protein may represent a prohormone of calcitonin.


Identification of additional antigenic sites on Dane particles and the tubular forms of hepatitis B surface antigen. Additional antigenic sites, distinct from those present on spherical 20 nm diam. particles of hepatitis B surface antigen (HBsAg), are exposed on the surface of Dane particles and tubular forms of HBsAg. The immunological relationship of these sites to e-antigen, an antigen detected earlier in HBsAg-positive sera from patients with chronic hepatitis, cirrhosis or acute hepatitis but not in healthy HBsAg-carriers, was established by immune electron microscopy and affinity chromatography. These findings suggest that e-antigen may be potentially useful in active immunization against hepatitis B.


Levodopa alone and in combination with a peripheral decarboxylase inhibitor benserazide (Madopar) in the treatment of Parkinson's disease: A controlled clinical trial. A combination of levodopa and the extracerebrally acting decarboxylase inhibitor benserazide (ratio 4:1) (Madopar), was compared with levodopa alone in a controlled double-blind clinical multicenter trial on 94 patients with Parkinson's disease. During 4 months of therapy levodopa + benserazide proved superior to levodopa on several accounts. Nausea and vomiting occurred with statistically significant less severity and frequency. Clinical improvement expressed through improvement in Webster rating occurred sooner and was all together greater. The treatment schedules did not differ with regard to other side effects, in particular involuntary movements and reduction in supine blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters.


An uncommon case of amyotrophic lateral sclerosis with isolation of a virus from the CSF. An atypical case of amyotrophic lateral sclerosis (ALS) is described, characterized by early manifestation, a long lasting course with asymmetry of the lesions, absence of bulbar symptoms in the presence of an otherwise very advanced symptomatology, and constant signs of an inflammatory reaction in the CSF which was the reason to initiate extensive virological studies, including procedures for virus isolation. A virus belonging to the TbE complex of arbovirus group B (tick-borne flavivures), was finally isolated from the CSF. About 70% of the ALS cases in Hamburg/W. Germany, examined for antibodies, apparently had contact with this virus. The antibody pattern found made it possible to explain this exceptional case.


[Cerebral vasoparalysis, arterial hypertension and brain edema (author's transl)]. The present studies were performed in order to determine whether "filtration edema" will develop as a consequence of cerebral vasoparalysis, vasoparalysis in combination with arterial hypertension or arterial hypertension alone. A series of dogs, anaesthetised with i.v. Chloralose-Urethane were exposed 1) to cerebral vasoparalysis, produced by hypercapnia (PaCO2 about 150 mm Hg) and hypoxaemia (PaO2 40-60 mm Hg); 2) to arterial hypertension and 3) to a combination of cerebral vasoparalysis and arterial hypertension. Following cerebral vasoparalysis and arterial hypertension, a significant decrease of total cerebrovascular resistance and moderate increase of venous resistance was observed. Regional cerebral blood flow (133Xe), intracranial pressure, as well as the pressure in postcapillary venous outflow (sinus sagittalis wedge pressure and confluence sinuum pressure) were increased. Neither normotonic vasoparalysis nor vasoparalysis in combination with slight arterial hypertension (MABP more than 90 min above 180 mm Hg) resulted in cerebral edema. In contrast, cerebral vasoparalysis in combination with severe arterial hypertension (MABP more than 90 min above 220 mm Hg) resulted in a statistically significant increase in the water content in the white matter without evidence of protein extravasation. Multiple small foci of Evans blue extravasates, however, were found in the cortex following arterial hypertension in combination with vasodilation, indicating a damage of the blood brain barrier. In these blue stained cortical areas the water content was significantly in creased. The following conclusions were drawn from the results. Vasoparalysis during normotension does not produce brain edema despite the slightly elevated hydrostatic pressure gradient between intravasal and extracellular space. Only considerable increase of this hydrostatic pressure gradient caused by a combination of vasoparalysis with severe arterial hypertension is able to produce brain edema in the white matter. In addition, acute hypertension may cause minor multifocal damage of the blood brain barrier in the cerebral cortex. It is concluded that so-called brain swelling, which has been described by several authors in states of cerebral vasoparalysis, is not predominantly caused by brain edema but by vascular congestion. The clinical aspects of the result are discussed.


Transfer factor therapy in patients with subacute sclerosing panencephalitis. Thirteen patients with subacute sclerosing panencephalitis (S.S.P.E.) at different stages of the disease were admitted for transfer factor treatment. The transfer factor was prepared from non-selected blood bank donors. The activity of the transfer factor was tested in patients with diseases other than S.S.P.E. and was found to be either clinically or immunologically active. Regardless of the number of transfer factor units applied a significant influence on the course of the disease was not apparant. The observed intermittant improvement of 3 patients was considered as spontaneous remission which is known to occur occasionally in S.S.P.E. The humoral and cellular immune response before and after transfer factor therapy did not reveal significant changes which could be correlated with transfer factor therapy.


The significance of perivascular infiltrations in multiple sclerosis. 143 autopsy cases of multiple sclerosis (19 acute and 124 chronic cases) were analysed histologically for the extent of active demyelination and the degree of infiltration within and outside the demyelinating lesions and in the leptomeninges. The results were compared with the duration of the illness. Infiltrations were found in 60% of all cases but more often (74%) in those with active demyelination. Inflammatory lesions outside demyelinating foci were observed in 27% of the total, and in 80% of them active demyelination was present. Inflammatory lesions in the meninges were present in 41% of the total and in 80% of these were accompanied by active demyelination. The duration of illness correlated with decreasing severity of active demyelination and of perivascular infiltration. Patients treated with cortico-steroids and/or immunosuppressive substances showed no or only moderate inflammatory lesions. The duration of illness in both these groups was significantly longer than the average of untreated patients. The significance of these pathological findings for the CSF cytology in multiple sclerosis is discussed.


Niemann-Pick's disease. Clinical, biochemical and ultrastructural findings in a case of the infantile form. A diagnosis of Niemann-Pick disease type A was made in a 6-month-old boy on the grounds of progressive psychomotor retardation, hepatosplenomegaly, typical foam cells in the bone marrow and a deficiency of sphingomyelinase in a liver biopsy. Typical ultrastructural changes in lysosomes were found in hepatocytes and in Schwann cells. In spite of the absence of gross morphological changes in the axons and in the myelin sheath of the peripheral nerve biopsy, the nerve conduction velocity in the patient was greatly reduced. The ultrastructural aspect of the lysosomal inclusion suggested the storage of a phospholipid. Biochemical analysis of the liver biopsy demonstrated an increased content of total phospholipid of which sphingomyelin made up for more than 60%. The significance of these data are discussed.


[An autopsy case of olivocerebellar and thalamic degeneration, diffuse sclerosis and hypertrophic neuropathy: infantile system degeneration? (author's transl)]. The brain of a 21-year-old man with imbecility and spastic tetraplegia since early childhood showed a diffuse sclerosis of the cerebral white matter and symmetrical degeneration of the thalamus and olivocerebellar system. The spinal nerve roots as well as proximal branches of the spinal nerves were hypertrophic and there was seen a marked fibrosis with some onion-bulb formations of Schwann cells. In spite of a possible relation to an unknown infection at the age of 3 months this case could preferably be regarded as a peculiar form of the combined system degeneration in the early childhood, including the cerebral white matter and peripheral nerves. An uncle of the patient had died of a similar nervous disease at the age of 20 years.


Primary leptomeningeal sarcomatosis. Clinicopathological report of six cases. 6 autopsy cases of primary leptomeningeal sarcomatosis are presented as a distinct nosological entity with a variable clinical picture and morphology in 5 males and 1 female. The clinical course from onset of symptoms till death ran for only a few weeks in most cases. 2 infants showed brain tumor symptoms and signs. 2 patients of advanced age presented a polyradiculoneuritic syndrome and 2 young adults had spinal cord compression symptoms and a mixed clinical form. In almost all cases, clinical symptoms and signs were for most of the course confined to one part of the neuraxis. The CSF was distinctly abnormal in all cases, showing elevated protein, depressed glucose and pleocytosis of variable extent. CSF sediment was investigated in 3 cases in all of which malignant tumor cells were found so a diagnosis of malignant meningeal tumor was made during life. Electron microscopy of CSF cells in 1 case confirmed the primitive character of the tumor cells. Complete autopsies revealed absence of any neoplasm outside of the CNS. Gross meningeal involvement was visible in all cases. Histologically, 3 tumor types were distinguished: polymorphic cell sarcoma, an undifferentiated form, and fibrosarcomatosis. Clinical data are analyzed in order to distinguish the condition from other neoplasms or infectious, especially tuberculous meningeal infiltrations. CSF cytology studies are considered the most useful step in clinical diagnosis. Neuropathological features are reviewed with stress on differentiation from malignant lymphomas of the CNS, diffusely spreading medulloblastoma, meningeal melanoblastosis and gliomatosis. The origin of meningeal sarcomatosis cells is briefly discussed. The use of the term "meningeal meningiomatosis" for this condition is deprecated.


Late effects of brain biopsy.

Late effects of brain biopsy. 303 patients underwent brain biopsy; 20 patients were available for a follow-up EEG examination, up to 16 years after the biopsy. 4 patients (20%) had focal fits starting within 6 months after the intervention. In the EEG of 15 patients (75%) 2 varieties of focal abnormalities appeared: "trepanation activity" which, for reasons discussed below should be regarded as an abnormality; and other focal features, including spikes, more often seen in patients with epilepsy. It is concluded that irritative brain lesions appear in a considerable number of patients after brain biopsy. The decision of performing this diagnostic procedure should be made after taking in consideration that: by enhancing the possibility of a correct diagnosis we may induce focal seizures in every fifth patient and irritative phenomena in three fourths of their EEG'S.


Amyloid-like material in odontogenic tumors. Various types of odontogenic tumors (epithelial, mesodermal, and mixed tumors) were studied for the presence of amyloid material. Highman's Congo red and Wolman's standard toluidine blue methods were used for diagnosing amyloid. Of all types of odontogenic tumors studied, only the calcifying epithelial odontogenic tumors contained material that might be interpreted as amyloid-like.


Implant pellets I: effects of compression pressure on in vivo dissolution of delmadinone acetate pellets. A formulation containing 95% delmadinone acetate was compressed at three different pressures. These pressures resulted in a pellet density difference of 19%. In vivo dissolution profiles were determined for five lots of pellets. The pellets were implanted subcutaneously in rats, removed periodically, and assayed chemically for remaining steroid. The resulting data were fit, using the computer program NONLIN, to a dissolution model. The dissolution rate for the lot with the lowest density made at the lowest compression was statistically (p less than 0.05) different from the four other lots. A possible explanation for this increased dissolution rate could be that channeling occurs within the pellet, thereby increasing the effective dissolving surface. The results also indicate that equivalent dissolution rates between lots are reached at a certain compression and density.


Fast axoplasmic transport in the fibres of chromatolysed neurones. 1. The rate of fast axoplasmic transport in cat sensory nerves was determined in sciatic nerves above transections made low in the popliteal fossa some 6-165 days beforehand. The pattern and rate of movement of the crest of labelled components in the nerve fibres after injecting the L7 dorsal root with [3H]leucine was used to characterize fast axoplasmic transport. 2. The mean rate and S.D. found on the transected side was 424 + 33 mm/day compared with 432 +/- 34 mm/day for the control nerves. These rates were not significantly different and were similar to the rate of axoplasmic transport previously reported to be 410 +/- 50 mm/day. The results gave little support for the hypothesis that a speeding up of the rate of fast axoplasmic transport is the signal for the initiation of chromatolysis. 3. The amount of transport shown by the level of activity in the crests on the chromatolytic and control sides relative to the "pool" of radioactive materials remaining in the cell bodies of the ganglion were also similar. The significance of these findings was discussed with respect to changes in the cell bodies known to take place during chromatolysis and the stability of the axoplasmic transport mechanism in nerve fibres.


[Contribution to the scintigraphic diagnosis of malignant endothoracic tumors by 57Co labeled Bleomycin (author's transl)]. The authors report the results of the exploration by 57Co Bleomycin scinitigraphy in 97 thoracic tumors. The Bleo-57Co scintigraphy detects primary and secondary malignant tumors underevaluated by classical tests. In the thorax, the radioactive focus are easily detected on account of the light physiological fixation of the Bleo-57Co. It is particularly interesting in the mediastinal tumors where the picture is not covered by cardiovascular interference. Mediastinal, pleural and costal tumors have been explored. Pulmonary tumors give the best results, they fixe in 93% of the case. All the mediastinal tumors have capted the bleomycin but the authors insist on the fact that the fixation was very light even when the tumor was a large one. The exploration of pleural and costal tumors was less interesting. In conclusion, the Bleo-57Co scintigraphy, gives indications about the volume of the tumor and its spread in the organism. By this method, we can diagnose malignancy in tumor. It can be used to survey cancer patients which have been treated. Nevertheless the long half-life (270 days) and the lack of specificity of the Bleo-57Co for the malignant tumors, justify discussion about indications and the results of such an exploration.


Steroid effects on human endometrial glycoprotein biosynthesis. Human endometrium from the secretory phase of the menstrual cycle was incubated with 3H- and 14C-labelled glucosamine and [3H]leucine. Incorporation into secreted extracellular glycoprotein and accumulation of the label into the microsomal fraction were measured. When oestradiol or progesterone were added to the medium, medroxyprogesterone acetate (MPA), ethynodiol diacetate and chlormadinone acetate reduced incorporation of glucosamine and MPA reduced incorporation of leucine into glycoprotein. MPA reduced the amount of glucosamine in the microsomal fraction and also had an effect on amino acid transport within the endometrial cells, as indicated by intracellular alpha-aminoisobutyric acid space measurements. These results and the ratios of 3H and 14C in the microsomal fraction and secreted protein suggest that MPA has a primary effect in decreasing amino sugar incorporation and a secondary effect in reducing amino acid incorporation into glycoprotein.


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Comparison of histocompatibility antigens on cultured human tumor cells and fibroblasts by quantitative antibody absorption and sensitivity to cell-mediated cytotoxicity. Human tumor and febroblast tissue culture cells were compared to determine the suitability of fibroblasts as control cells in experiments on human tumor serology and cellular immunology. Fibroblasts expressed the same HL-A antigen profile as did melanoma cells. Furthermore, the quantitative expression of the determinants was similar on both cell types. In four of five pairs tested, the fibroblasts displayed similar sensitivity to effector cells generated by mixed lymphocyte culture as did the tumor cells from the same donor, but there were some differences in the effects of specific alloimmune effector cells at high and low effector-to-target ratios on the two types of target cells. Results indicated that fibroblasts are legitimate control target cells for studies in human tumor immunology, if screening assays are done to verify their antigenicity and sensitivity to cell-mediated cytolysis.


In vivo host immune to a tumor-specific transplantation antigen induced by Rous sarcoma virus. We examined the host immune response to a tumor-specific transplantation antigen (TSTA) induced by Rous sarcoma virus (RSV) In vivo. In contrast to previous in vitro studies, the present investigation demonstrated in vivo host immunity of the TSTA 10-55 days after tumor inoculation. Immunity to the TSTA appeared specific, since the homologous RSV tumor was rejected. whereas the heterologous tumor grew progressively. No generalized suppression of cell-mediated or hymoral immunity was shown, because tumor-bearing hosts  retained the ability to reject heterologous tumor cells and mounted a normal plaque response to sheep red blood cells. Although alpha-globulin levels were elevated, they did not appear to affect the host's immunity to the growing tumor or to heterologous antigens. Assoicated with the progressively growing tumor was the appearance in the serum of a fetal antigen with characteristics of an alpha-2 acute phase protein.


Tumor-bound immunoglobulins: an in vivo phenomenon of masked specificity. We examined the specificity of the lg "coating" on murine tumor cells grown in vivo. Cells were treated in vitro for release of cell-bound lg from ascites tumors. Such uncoated cells showed an increased expression of tumor-associated antigens and a parallel decrease in intensity of the lg coat, but displayed no changes in the expressions of other normal membrane antigens. This was shown by a complement-dependent cytotoxicity assay and radioimmunoassay. These changes were attenuated if the tumor originated from animals that had been irradiated before tumor inoculation. No alterations were found with corresponding cells propaged in vitro and submitted to the same treatments. Our findings and others suggest tumor-specific antibodies among the lg coats detected on tumor cells grown in vivo.


Temperature-dependent changes in activation energies of the transport systems for nucleosides, choline and deoxyglucose of cultured Novikoff rat hepatoma cells and effects of cytochalasin B and lipid solvents. The initial rates of transport of uridine, thymidien, purines, choline and 2-deoxy-D-glucose by cultured Novikoff rat hepatoma cells were determined as a function of temperature between 5 and 41 degrees C. Arrhenius plots of all transport systems exhibited sharp breaks in slope; between 17 and 23 degrees for uridine, thymidine and hypoxanthine-guanine transport and between 29 and 32 degrees for choline and 2-deoxy-D-glucose transport. The activation energies for the transport systems changed from 15-26 kcal/mole below the transition temperatures to 4-9 kcal/mole above the transition temperatures. Propagation of the cells in the presence of cis-6-octadecenoic acid which results in marked changes in the lipid composition of cell membrane, had little effect on the temperature characteristics of the various transport systems. Similarly, propagation of the cells for 24 hr in media containing Tween 40 or nystatin had no effect on the capacity of the cells to transport the various substrates or on the temperature dependence of the transport systems. The presence of ethanol, phenethyl alcohol or Persantin at concentrations that inhibited thymidine and 2-deoxy-D-glucose transport between 40 and 70% also did not alter the transition temperatures or activation energies for the transport of these substrates. Cytochalasin B, on the other hand, shifted the transition temperature for 2-deoxy-D-glucose transport to higher temperatures in a concentration-dependent manner, whereas it had no effect on the temperature dependence of thymidien transport.


Effects of (Na+ + K+)-ATPase-specific antibodies of enzymatic activity and monovalent cation transport. Antibodies have been obtained that specifically interact with the transport enzyme (Na+ + K+)-activated ATPase. The antigen used was purified (Na+ + Ka+)-ATPase from canine renal medulla. Purified gamma globulin from immunized animals, but not from control animals or preimmune serum, inhibited (Na+ + Ka+)-ATPase from canine renal medullar with reduction of activity to 33 +/- 4 (SD)% in concentration-dependent manner. Maximum inhibition occurred in less than 5 minutes at 37 degrees C. The Mg++ -dependent, nonouabain inhibited component of activity (Mg++ -ATPase) was unaffected. Fab fragments obtained by papain cleavage of the gamma globulin fraction had similar inhibitory activity and specificity. These antibodies also produced varying degrees of concentration-related inhibition of canine myocardial, calf brain, and human red cell ghost (Na++ + Ka+)-ATPase, but not Mg++-ATPase activity.


RELATIONSHIP BETWEEN THE Mason-Pfizer monkey virus and Hela virus: immunoelectron microscopy. Envelope antigens of the Mason-Pfizer monkey virus (MPMV) and the morphologically similar HeLa virus, which is continuously produced in some HeLa cell lines, were compared by indirect immunoferritin techniques. Antisera raised against MPMV and HeLa virus revealed cross-reacting antigenic specificities on the surfaces of both agents, and cross-absorption and end-point dilution techniques indicated the presence of identical envelope antigens. The results demonstrated a close relationship, if not an identity, between MPMV and HeLa virus.


Tissue sites of alpha fetoprotein synthesis by the rat during pregnancy and hepatoma growth. The tissue sites of alpha1 fetoprotein (AFT) synthesis by the rat during gestation and hepatoma growth were determined by specific incorporation of a radiolabeled amino acid precursor into AFP by tissue cultures in vitro. During gestation, AFP were produced by the yolk sac, the fetal liver, and in small amounts by the fetal gastrointestinal tract; there was no synthesis by maternal rat tissues. During growth of a transplantable hepatoma, only the hepatoma tissue synthesized AFP; the nontumor tissue of the host contained AFP but did not produce it.


Streptococcus pyogenes preparation OK-432: immunoprophylactic and immunotherapeutic effects on the incidence of spontaneous leukemia in AKR mice. An inactivated and lyophilized preparation of a low virulence strain (Su) of Streptococcus pyogenes (group A) was designated OK-432. When 2- and 5-month-old AKR mice were inoculated im with OK-432 twice weekly throughout their life-spans, spontaneous leukemias occurred later and at a lower incidence than in control groups. By virus neutralization and cytotoxicity tests and by immunoelectron microscopy, antibodies against virus and cell-surface antigens of transplanted AKR leukemia were not detectable in sera of nonleukemic mice of any group. Whereas sera from mice treated with OK-432 were the only positive for interferon, viremia was clearly demonstrated in control groups by reverse transcriptase assays of the plasma.


Tumor-associated antigens in human myeloma. Antiserum was generated in rabbits to the RPMI 8226 tissue culture line of human myeloma cells, and its reactions with fixed smears of bone marrow aspirates from patients with multiple myeloma, macroglobulinemia, benign monoclonal gammopathy (BMG), leukemia, and nonneoplastic plasmacyosis was assessed by indirect immunofluorescence. After absorption with preparations of bone marrow from normal individuals, the antiserum reacted to a significantly higher titer with a specific subpopulation of plasma cells in smears from 81% of patients having multiple myeloma and 50% of patients having BMG than with cells in smears of bone marrow aspirates from normal individuals or patients having leukemia or nonneoplastic plasmacytosis, or than with cells in smears of peripheral blood from patients having Hodgkin's and non-Hodgkin's lymphoma. Absorption of the antiserum with RPMI 8226 cells or with a bone marrow preparation from a patient with multiple myeloma but not the Jijoye line of Burkitt's lymphoma reduced reactivity for cells in myeloma bone marrow. The antiserum reacted at a lower titer with the Jijoye and EB-3 lines of Burkitt's lymphoma, the RPMI 4098 cell line of normal human lymphocytes, and culture lines of human melanoma and osteogenic sarcoma than with the RPMI 8226 cells or bone marrow from certain patients having multiple myeloma. Approximately 50% of the cells reactive with antiserum to RPMI 8226 cells in the bone marrow of patients with multiple myeloma were not producing immunoglobulin, as assessed by double immunofluorescence assay. The data suggested that a subpopulation of plasma cells in the bone marrow of patients with multiple myeloma possesses a tumor-associated antigen.


Tumor immunity induced by preimmunization with BALB/c mouse myeloma protein. Prior sc immunization of BALB/c mice with 1 mg isolated M component of MOPC-11 mouse myeloma resulted in significant relative immunity to subsequent sc or ip challenge with 10(4) living cells from the same plasmacytoma. However, challenges of 10(5) and 10(6) tumor cells overcame immune status engendered by preimmunization with M component. Despite evidence for the specificity of the immunity induced by one isolated M component as opposed to another, no clear cytotoxic antibody, cell-mediated tumor-cell lysis, or predominance of either humoral or cell-mediated immune mechanisms were demonstrated. These findings were compatible with a relatively slight tumor-specific antigenicity of M components expressed on tumor surfaces, compared with the tumor specificity of other tumor-related, cell-surface antigens.


Variations of some plasma components after closed fractures. 1) Variations in the serum concentrations of total proteins and the electrophoretic fractions, glycoprotein, mucoprotein, fibrinogen, erythrocyte sedimentation rate, calcium, phosphorus, alkaline, and acid phosphatases were analyzed until the 30th day following uncomplicated fracture of shafts of long bones of the limbs in 25 cases. 2) A significant fall of albumin with concomitant rise of alpha 1, alpha 2, and beta globulins were noted until 30th day. 3) Mucoprotein, glycoprotein, and fibrinogen showed parallel elevations with that of alpha and beta globulins. 4) The peak values of alpha 1 and alpha 2 globulins, mucoprotein, and fibrinogen were registered on the 10th day after trauma. Albumin showed maximum fall on the 10th day in all these cases. 5) Glycoprotein showed a peak value on the 5th day. 6) Total protein and gamma globulin remained almost unchanged throughout the studies. 7) Beta globulin showed higher values and paralleled more closely the fibrinogen and erythrocyte sedementation rates. 8) The elevations of beta globulin, fibrinogen, and erythrocyte sedimentation rate were higher, and persisted beyond 30 days in lower-limb fractures as compared to upper-limb fractures. 9) Serum calcium, phosphorus, alkaline phosphatase, and acid phosphatase were not significantly different following fractures and therefore did not reflect much physiologic variation. 10) The most significant changes in the levels of plasma fractions studied were conspicuous on the 10th day and lasted for about 1 month.


Comparisons of the immunological properties of two structural polypeptides of type C RNA viruses endogenous to old world monkeys. Immunologically very closely related type C RNA viruses are endogenous to the domestic cat and to an old world primate, the baboon. In the present studies, radioimmunological techniques have been developed for detection of the 15,000 and 30,000 molecular weight (MW) polypeptides of each virus. The much more pronounced type-specific antigenic determinants of the lower MW polypeptides made it possible to readily differentiate these viruses from each other as well as from a type C virus isolate from a second baboon species. Normal rhesus monkey tissues were partially purified and shown to contain a reactivity with MW and immunological properties similar to that of the baboon virus 30,000 MW polypeptide. Despite a similar degree of purification, antigenic reactivity like that of the baboon virus 15,000 MW polypeptide was undetectable even in the brodest immunological tests available for this polypeptide. The present findings indicate that the immunological properties of two structural polypeptides of closely related viruses endogenous to primate and feline species have undergone different rates of antigenic change in the course of evolution within their respective host cell genome.


Inhibition of friend murine leukemia virus production by low-ionic-strength medium. The effect of medium of low ionic strength on the release of virus from Friend leukemia cells has been studied. The release of infectious Friend leukemia virus is almost completely inhibited in medium of low ionic strength, as measured by a focus-forming assay (XC assay), by endogenous RNA-dependent DNA polymerase activity of released virus particles, and by electron microscope studies of the production of C-type particles. Friend leukemia virus-transformed proerythroblasts undergo extensive morphological changes in low-ionic-strength medium. The cells are viable in this medium, but they can no longer be stimulated with dimethyl sulfoxide to produce hemoglobin and increase virus production. Infectious virus is released between 30 and 120 min of resuspension of inhibited cells in normal medium. The rate of virus release after reversal of the inhibition is much greater than the rate of virus release during normal cell growth. The morphological changes occurring after dimethyl sulfoxide stimulation of Friend leukemia cells are compared with those resulting from resuspension in normal medium of cells inhibited by low ionic strength.


Initiation of DNA synthesis by the avian oncornavirus RNA-directed DNA polymerase: tryptophan tRNA as the major species of primer RNA. The major species of primer RNA required for the initiation of DNA synthesis by the Rous sarcoma virus RNA-directed DNA polymerase can be aminoacylated by tryptophan. Furthermore, an intact 3' terminus is required for the primer to function in the initiation of DNA synthesis.


Formation of an infectious virus-antibody complex with Rous sarcoma virus and antibodies directed against the major virus glycoprotein. Preparations of Rous sarcoma virus (RSV) can form an infectious viral-antibody complex with antibodies raised against the major glycoprotein, gp85, isolated from avian myeloblastosis virus and Prague-RSV subgroup C. Binding of anti-gp85 antibodies to RSV can be demonstrated by the inhibition of focus-forming activity after addition of goat anti-rabbit immunoglobulin and by a shift in density of virions treated with anti-gp85 serum. Group- rather than subgroup- specific regions of viral gp85 appear to be the site of binding for infectious complex.


Purification and serological characterization of the major envelope glycoprotein from AKR murine leukemia virus and its reactivity with autogenous immune sera from mice. The major envelope glycoprotein (gp71) from AKR murine leukemia virus (MuLV) was purified and its serological reactivity with heterologous and autogenous immune mouse sera was examined. Homologous and interspecies competition radioimmunoassays using antisera to Rauscher-MulV gp69/71 or Friend-MuLV gp71 or antisera to feline leukemia virus to precipitate 125I-labeled gp71 from various MuLV showed that distinct differences exist between Rauscher- or Friend-MuLV and AKR-MuLV glycoproteins. Characteristically the AKR-MuLV gp71, in contrast to FLV or RLV gp71, does not compete fully in homologous or interspecies radioimmunoassays with iodinated Friend of Rauscher glycoproteins. Purified 125I-labeled AKR-MuLV gp71, in contrast to the Rauscher- or Friend-MuLV glycoproteins, reacts with normal (autogenous immune) mouse sera in direct radioimmune precipitation assays. Competition experiments further demonstrate that this is a predominant immunological reactivity of normal mouse sera which had previously been detected by radioimmune precipitation assay against intact virions.


Comparison of the serology, transforming ability, and polypeptide composition of human papovaviruses isolated from urine. Four isolates of human papovaviruses (RF, GS, DW, and MG viruses) obtained from the urine specimens of renal allograft recipients in widely separated locations were compared with BK virus. Hemagglutination inhibition tests and plaque neutralization assays showed that all were antigenically related to BK virus. All isolates transformed baby hamster kidney cells, transformation being determined by the ability of the cells to plate in soft agar. Purified preparations of each isolate were iodinated with chloramine T and the polypeptide compositions were compared by electrophoresis of disrupted viruses in polyacrylamide gels containing sodium dodecyl sulfate. The gel patterns of all isolates were similar to that of BK virus. The tryptic digests of two major iodinated virion proteins, VP1 and VP3, were analyzed on an ion exchange column. The peptide patterns of GS, DW, and BK virus were identical; those of RF and MG virus closely resembled the patterns of the above three with only minor differences in some peptides. The results show that the four isolates and BK virus are antigenically closely related, have similar onocogenic potential, and are distinguishable from simian virus 40 and JC virus.


Dissociation of alpha beta DNA polymerase of avian myeloblastosis virus by dimethyl sulfoxide. The alpha beta DNA polymerase of avian myeloblastosis virus was treated with dimethyl sulfoxide to dissociate the enzyme subunits. The dimethyl sulfoxide treated enzymes were passed over phosphocellulose to purify and characterize the dissociated subunits as well as to remove the dimethyl sulfoxide. RNA-directed DNA polymerase, RNase H, and nucleic acid-binding activity were monitored, as well as the subunit structure (on sodium dodecyl sulfate-polyacrylamide gels) of the various enzyme species obtained. With 30% dimethyl sulfoxide, the majority of DNA polymerase and RNase H activities as well as the alpha subunit were displaced from the alpha beta DNA polymerase position on phosphocellulose (0.23 M potassium phosphate) to the alpha DNA polymerase position (0.1 M). The association of DNA polymerase and RNase H activities with the alpha subunit suggests that alpha is the enzymatically active subunit in alpha beta. In addition to alpha DNA polymerase, a minor polymerase species eluted from phosphocellulose at 0.4 M potassium phosphate. The dissociated beta subunit eluted from phosphocellulose at a wide range of salt concentrations (0.28 to 0.5 M potassium phosphate). The dissociated beta subunit bound 3H-labeled murine leukemia virus RNA and [3H]poly(dT)-poly(dA) approximately 20-fold more avidly than alpha DNA polymerase alone. In contrast to the results with the alpha subunit, there was no correlation between DNA polymerase and RNase H activity profiles and the elution profile of the beta subunit from phosphocellulose. These observations suggest the beta subunit is either enzymatically inactive or possesses limited DNA polymerase and RNase H activity when compared with the alpha subunit.


Group-specific antigen shared by the members of the reticuloendotheliosis virus complex. The polypeptides of reticuloendotheliosis virus (REV) were separated by gel filtration in the presence of guanidine hydrochloride. The eight peaks obtained by gel filtration were then analyzed by polyacrylamide gel electrophoresis and four appeared to contain single polypeptides. The material identified as p29 was used to prepare antiserum. This protein constitutes the major internal non-glycosylated polypeptide in the virion. Double immunodiffusion indicated that the antiserum was specific for p29. Using this antiserum, cross-reactivity was demonstrated between REV, chick syncytial virus, duck infectious anemia virus, and spleen necrosis virus. Antiserum to p29 failed to cross-react with Rous sarcoma virus. This indicates that p29 is a group-specific antigen shared by the viruses of the REV complex. A microcomplement fixation test was developed with this antiserum that will be useful in the quantitation of REV and the identification of other members of this newly defined group.


Mechanism of interaction of avian myeloblastosis virus reverse transcriptase with avian myeloblastosis virus RNA. The synthesis of DNA on avian myeloblastosis virus (AMV) RNA as the primer-template using AMV reverse transcriptase in vitro has been examined as a function of the concentrations of these components, as well as a function of the ionic strenth of the assay medium. The results are consistent with the hypothesis that two types of sites exist on the AMV RNA: inactive "dead-end" sites that merely bind the enzyme, and active binding sites that lead to DNA synthesis. Velocity sedimentation studies of reverse transcriptase reveal that the enzyme becomes a dimer (or oligomer) at low salt concentrations and it is at these concentrations that the two types of sites are evident on the RNA. At high salt concentration the enzyme, which exists primarily as a monomer, is inactive with AMV RNA, although it is active when poly(rA)dT10 is used as the primer-template. We have shown that inactive sites are not due to binding of the reverse transcriptase to nicked regions or to partially denatured RNA molecules. We deduce that inactive sites are those containing incorrect 4S primer molecules. These results are discussed in terms of the mechanism of the interaction of the reverse transcriptase with AMV RNA.


Relationships between intracisternal type A and extracellular oncornavirus-like particles produced in murine MOPC-460 myeloma cells. Oncornavirus-like particles of the "A" (both intracisternal and intracytoplasmic) and "B" or "C" (extracellular) types are produced by murine MOPC-460 myeloma cells. This communication describes a comparative study on tracisternal A and extracellular particles. Both types of particles contain an RNA-dependent DNA polymerase activity, traces of 35S and 70 S RNA in addition to larger amounts of degraded RNA, and proteins of approximately 76,000 and 45, 000 daltons. The 76,000-dalton proteins from intracisternal A and extracellular particles have the same cyanogen bromide peptides. Hybridization kinetic analysis indicates that the RNAs in the two particles are identical or very closely related and share partial homology with Moloney leukemia virus RNA. In contrast, the particles appear to have little or no relationship to murine mammary tumor virus as judged by several different criteria. Electron microscope studies indicate that the extracellular particles arise from the budding of core components through the plasma membrane. These results suggest that the intracisternal A and extracellular oncornavirus-like particles produced by MOPC-460 cells are closely related.


Reverse transcriptase activity per virion for avian myeloblastosis virus and Rauscher murine leukemia virus. We have measured reverse transcriptase enzyme activity per virus particle for samples of avian myeloblastosis virus (BAI strain) and murine leukemia virus (RAUSCHER) USing the synthetic template poly(rC)-oligo(dG). Absolute virus concentrations were determined directly by laser beat frequency spectroscopy. Enzyme activity per virion was determined from the slope of the activity plotted as a function of virus concentration. With this reverse transcriptase assay, the minimum activity (expressed as picomoles of dGTP incorporated/virion per hour) is estimated at (28.1 +/- 4.2) X 10(-7) for avian myeloblastosis virus and (1.1 +/- 0.2) X 10(-7) for murine leukemia virus. The sensitivity of this assay, which is determined by the level of incorporated radioactivity measurable above background, is 2.5 X 10(-4) virions for avian myeloblastosis virus (with dGTP specific activity of 8.9 Ci/mmol) and 88 X 10(-4) virions for murine leukemia virus (with dGTP specific activity of 6.52 CI/mmol). These results show that although reverse transcriptase assays can obviously be used to measure relative virus concentrations of equally purified samples of the same virus, they can be very misleading when used to compare the concentrations of different virus species.


Value of granulocyte examination for bacteria. Granulocytes from patients with suspected bacteremia and from dogs with staphylococcal bacteremia were examined by light microscopy for the presence of intracellular inclusions that resembled microorganisms. Quantitative blood cultures were done at the same time. Few granulocytic inclusions were observed during a two-hour screening period even when high levels of bacteremia were present. There was no correlation between the number of inclusions and the quantitative blood culture data. The inclusions appear to be artifacts of the staining procedure. This technique has questionable value in the diagnosis of bacteremia and may be misleading.


Effect of age and cigarette smoking on carcinoembryonic antigen levels. Serum carcinoembryonic antigen (CEA) levels were determined by the Hansen-Z-gel technique in 276 healthy volunteers, of whom 154 were smokers and 122 nonsmokers. The mean CEA level was significantly higher in smokers (2.7 ng/ml) than in nonsmokers (1.9 ng/ml) (P less than .001), and a significantly higher percentage of smokers had elevated CEA levels (P less than .05). In both groups, CEA levels were directly related to age. Seventy-six of the 154 smokers who entered the study ceased smoking. Their CEA levels were determined at one, three, and six months after cessation of smoking. Within three months after cessation, elevated CEA levels declined to within the range of nonsmokers and did not appear to be influenced by previous smoking habits. Both age and smoking history must be considered for accurate evaluation of CEA levels. A reappraisal of the diseases associated with elevated CEA levels that considers the influence of age and smoking may invalidate some of the correlations previously reported.


[Quantitation of basophil cell-line in human bone marrow (author's transl)]. Appropriately fixed basophil cell-line can selectively be visualized by anionic dyes as toluidine blue. Typical activities for Leder's esterase distinguish individual maturity stages. Both methods were successively applied to bone marrow smears from 22 healthy subjects in order to assess the basophil population among the total marrow leukocytes (lymphocytes, monocytes and granulopoietic cell-lines) and the portion of each basophil maturity stages. Total basophils represent 0.45+/-0.13% of marrow leukocytes. Basophil precursors capable of division (promyelocytes and myelocytes) comprise 46.7%, mitoses 3.7+/-1.76% of the total marrow basophil population. The frequency distribution of these subpopulations approximated a normal distribution pattern. No clear central tendencies could be encountered in the dispersion of other stages. The low peripheral basophil counts, the high incidence of divisible precursors and the considerable mitotic activity suggest a short half-life time for blood basophils.


Fibroblast surface antigen (SF): molecular properties, distribution in vitro and in vivo, and altered expression in transformed cells. We have recently described a cell type-specific surface (SF) antigen that is deleted in chick fibroblasts transformed by Rous sarcoma virus, SF antigen is a major surface component and makes up about 0.5% of the total protein on normal cultured fibroblasts. The antigen is shed from normal cells and is present in circulation (serum, plasma), and in vivo, also, in tissue boundary membranes. The molecular  equivalents of both cellular and serum SF antigen are distinct, large polypeptides, one of which (SF210, MW 210,000) is glycosylated and, on the cell surface, highly susceptible to proteases and accessible to surface iodination. Immunofluorescence and scanning electron microscopy have indicated that the antigen is located in fibrillar structures of the cell surface, membrane ridges, and processes. Human SF antigen is present in human fibroblasts and in human serum. We have recently shown that human SF antigen is identical to what has been known as the "cold-insoluble globulin" and that it shows affinity toward fibrin and fibrinogen. Our results also indicate that loss of the transformation-sensitive surface proteins is due not to loss of synthesis but to lack of insertion of the protein in the neoplastic cell surface. Both normal and transformed cells produce the SF antigen, but the latter do not retain it in the cell surface. The loss of SF antigen, a major cell surface component, from malignant cells creates an impressive difference between the surface properties of normal and malignant cells. The possible significance of SF antigen to the integrity of the normal membrane and its interaction to surrounding structures is discussed.


An epidemic of infantile papular acrodermatitis (Gianotti's disease) in Japan associated with hepatitis-B surface antigen subtype ayw. An epidemic of infantile papular acrodermatitis (I.P.A.) (Gianotti's disease) occurred in Matsuyama City, in south-east Japan in 1974-75. Patients ages ranged from less than one year to eight years. Hepatitis-B surface antigen (HBsAg) was detected by an immune adherence haemagglutination method in the serum samples of 48 of the 54 patients tested. HBsAg subtypes were determined by a haemagglutination-inhibition method. ayw antigens were identified in 42 patients and adr antigens in 3; it was not possible to determine subtypes in the remaining 3 patients because antigen titres were too low. Since subtype ayw and I.P.A. are extremely rare in Japan, the association of the disease with HBsAg subtype ayw is regarded as being most significant.


Plasmapheresis in the management of acute systemic lupus erythematosus? Eight patients with systemic lupus erythematosus (S.L.E.) have been treated with plasmapheresis. In four patients in whom immunochemical studies indicated high levels of circulating immune complexes, the removal of 5-8 litres of plasma weekly produced a striking clinical and immunochemical improvement. The four other patients, with only minor complement disturbances and no direct evidence of circulating immune complexes, could not be shown to benefit from plasmapheresis and one patient in this group died of cerebral lupus despite intensive treatment with cytotoxic drugs. It is concluded that plasmapheresis may be of value as an adjuvant to the treatment of acute S.L.E.


Immunosuppression and plasma-exchange in the treatment of Goodpasture's syndrome. Seven patients with Goodpasture's syndrome induced by anti-glomerular-basement-membrane (anti-G.B.M.) antibody were treated by a regimen of intensive plasma-exchange, cytotoxic drugs, and steroids. In the three patients retaining some renal function at presentation, this regimen led to suppression and eventual termination of antibody synthesis with improvement in renal function. In four patients, all anuric at presentation, antibody to G.B.M. persisted with variable reduction in the circulating levels. No return of renal function occurred in this group, all of whom had extensive changes on renal biopsy. Pulmonary haemorrhage, life-threatening in one patient, was rapidly controlled in all five patients in whom it was a presenting feature. In addition to its effect on antibody levels, plasma-exchange, using volume-replacement with plasma-protein fraction (P.P.F.), resulted in substantial depletion of complement and fibrinogen, mediators possibly contributing to the antibody-induced injury.


Pituitary function in patients receiving intermittent cytotoxic and corticosteroid therapy for malignant lymphoma. Diurnal variation in plasma-cortisol was studied immediately before and after intermittent steroid therapy in seven patients receiving monthly courses of quadruple chemotherapy for Hodgkin's or non-Hodgkins lymphoma over a period of 6 months. The serum-thyroid-stimulating-hormone (T.S.H.) response to intravenous T.S.H.-releasing factor was also measured before and during the first course and before the second and fourth courses. The morning plasma-cortisol concentration fell significantly over 6 months when measured immediately before the start of each course. The mean evening cortisol concentration also fell over this period. In most patients the T.S.H. response showed a downward trend during treatment, although in two patients the response returned to normal whilst they were still undergoing therapy.


Blood-cadmium levels in normotensive and untreated hypertensive humans. Administration of cadmium to laboratory animals causes hypertension. Necropsy specimens of the liver and kidneys of human patients who had had hypertension were previously reported as showing elevated cadmium concentrations. In the present study living normal humans were found to have a blood-cadmium level of 3-4 +/- 0-5 ng/ml, while a matched group of living untreated hypertensive humans had a blood-cadmium of 11-1 +/- 1-5 ng/ml. All of the normal subjects had blood-cadmium levels below 8-0 ng/ml, while 13 of the 17 hypertensive patients had blood-cadmium levels over 8-0 ng/ml.


Ultrasound monitoring of fetal movements. A method for assessing fetal development? Human fetal movements in utero have been analysed by conventional compound B-scan ultrasound techniques. With practice, movements of specific parts of the fetus can be readily recognised, and even as early as the 6th week after conception gross movements of the whole embryo are visible. Monitoring of fetal movements as an indication of normal or abnormal fetal development appears to have been neglected, and future studies in this important area of antenatal paediatrics are suggested.


Increase in serum-lipids during treatment of hypertension with chlorthalidone. Fasting concentrations of serum cholesterol and triglyceride were measured before and during therapy in 63 patients with uncomplicated primary (essential) hypertension. The patients were divided into two groups, and diet therapy was applied equally to both groups. One group of 31 patients received no other therapy; the other 32 received chlorthalidone in addition to diet. Diet therapy consisted of no added sodium, caloric restriction if overweight, and consumption of foods low in lipids. On diet therapy alone serum-cholesterol fell by 11 mg/dl (P less than 0-02 vs pretreatment value) and serum-triglyceride was unchanged. When chlorthalidone was prescribed in addition to diet, serum cholesterol rose by 12 mg/dl and triglyceride by 36 mg/dl (P less than 0-005 vs pretreatment value for both). Serum-lipids were similar in the two groups before treatment; during therapy both serum cholesterol (P less than 0-05) and triglyceride (P less than 0-005) concentrations were higher in the chlorthalidone group. Thus, despite the prescription of lipid-lowering and calorie-restricted diets, serum-lipids became slightly raised when chlorthalidone was used as the sole drug in the treatment of hypertension.


Thrombotic side-effects of lower-limb phlebography. In 20 of 61 patients with initially normal phlebograms, uptake of 125I-labelled fibrinogen subsequently increased. In 4 (7%) cases, independent examinations (pulmonary scintigram or a new phlebogram) demonstrated a thromboembolic or thrombotic process. These results suggest that thrombosis and embolism may be caused by phlebography.


Dopamine acetylcholine imbalance in Parkinson's disease. Possible regenerative overgrowth of cholinergic axon terminals. Parkinson's disease is characterised by an imbalance between acetylcholine and dopamine which probably results from the degeneration of a dopaminergic nigrostriatal pathway. A new hypothesis is proposed to explain the development of this imbalance. Applying the concept that degeneration of nerve-fibres in the central nervous system can lead to collateral sprouting of uninjured fibres, it is suggested that the death of dopaminergic nigrostriatal neurons results in sprouting of axons of cholinergic interneurons in the caudate nucleus. This overgrowth could result in the cholinergic innervation of neuronal membranes vacated by degenerated dopaminergic terminals. Thus, the apparent changes in the activity of dopaminergic and cholinergic systems can be accounted for by faulty regeneration in the central nervous system.


Genetic risks of vinyl chloride.

Genetic risks of vinyl chloride. A study of pregnancy outcome among wives of workers exposed to vinyl-chloride monomer (V.C.M.) indicated that, in comparison with controls, there was a significant excess fetal loss in the group whose husbands had a primary exposure to V.C.M., whereas no differences between the groups were observed before the husband's exposures. The difference in fetal death-rates for the post-exposure comparisons was a reflection of a greater fetal loss associated with the wives younger-aged husbands. The significant excess did not seem to be the result of bias from interviewers, respondents, nor from women who had experienced chronic abortions weighting the results. These findings, in conjunction with the demonstration of a mutagenic response via microbial test systems and with observations of significant excesses of chromosomal aberrations among workers exposed to V.C.M., raise scientific and public-health concern for the possible genetic risks of V.C.M. to man.


Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism. Carbohydrate metabolism and vitamin-B6 status were assessed before and after pyridoxine administration in 46 women taking combined oestrogen-progestagen oral contraceptives (O.C.). 18 women had evidence of tissue depletion of vitamin B6, although all the women had abnormal tryptophan metabolism, including increased urinary xanthurenic acid (X.A.) excretion. In the women with vitamin B6 deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction in plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes in carbohydrate metabolism were not found in the 28 non-vitamin-B6-deficient women. These results indicate that carbohydrate intolerance in women on O.C. is unlikely to be mediated by the formation of a complex of X.A. with insulin, as has formerly been proposed. Since the synthesis of the tryptophan metabolite quinolinic acid, an inhibitor of the heptaic enzyme phosphoenolpyruvate carboxykinase, may be enhanced by the administration of pyridoxine, it is suggested that this metabolite might be the important factor in the improvement of glucose tolerance in the vitamin-B6-deficient women. This conclusion is supported by the improvement in glucose tolerance observed in 6 women on O.C. and in 4 patients with glucocorticoid excess who were not vitamin-B6 deficient, when they were given tryptophan to augment the synthesis of quinolinic acid.


A fatal encephalopathy in chronic haemodialysis patients. A distinct neurological syndrome in twelve chronic haemodialysis patients is described. This syndrome is currently the leading cause of death in one Denver dialysis unit. The hallmarks of this syndrome are progressive speech difficulties, mental changes, and a markedly abnormal electroencephalogram which may be present months before the clinical signs appear. Additional clinical features including seizures, myoclonus, asterixis, apraxia, focal neurological signs, and psychiatric symptoms may also be observed. Neuropathological changes are slight and non-specific. The aetiology of this syndrome is unknown but the clinical and pathological features suggest a toxic/metabolic disorder. To date, this disorder has been refractory to several therapeutic measures.


Pressure changes in varicose veins.

Pressure changes in varicose veins. Pressures in the superficial leg veins of 24 patients with varicose veins and 6 normal controls were studied. In the controls there was no rise in pressure in the veins on increasing the intra-abdominal pressure, but in the patients with varicose veins pressure rose significantly. Squatting was no better than sitting in preventing transmission of intra-abdominal pressure to the leg veins. It was concluded that the difference in the positions adopted for defaecation is not the cause of the wide variation in the geographical distribution of varicose veins.


Possibly avoidable deaths in hospital in the age-group one week to two years. In a complete analysis of all infant deaths in hospital between the ages of 1 week and 2 years, over a two and a half year period in Sheffield 21 children (26%) were found to have died from treatable diseases. 15 (71%) of these children were admitted moribund but had shown no difference in preadmission clinical features from a group of children admitted with similar diseases but surviving. The essential difference between the infants who died and those who survived was in the adequacy of medical care before admission.


Inhibition of frusemide-induced hyperreninaemia by growth-hormone release-inhibiting hormone in man. In a study of the effect of somatostatin (growth-hormone release-inhibiting hormone) on plasma-renin in healthy volunteers, plasma-renin activity was measured by radioimmunoassay after the intravenous administration of somatostatin and also during frusemide-induced hyperreninaemia. While somatostatin was being given, basal values of renin were unchanged. Injection of frusemide alone produced hyperreninaemia; but, under somatostatin, renin release was inhibited by 45%. The results indicate that somatostatin is a potent inhibitor of renin and exerts its effect independent of sodium excretion, which was unchanged under somatostatin. Conceivably, somatostatin plays an important role in the regulation of endogenous renin release.


Reduction of menstrual blood-loss by prostaglandin-synthetase inhibitors. Six patients with menorrhagia due to dysfunctional uterine bleeding and one patient with an intrauterine contraceptive device were treated with prostaglandin-synthetase inhibitors in an attempt to reduce their excessive menstrual blood-loss. Mefenamic acid (six patients) or flufenamic acid (one patient) taken during menstruation for 2-3 cycles reduced menstrual loss in each patient. These preliminary observations suggest a new treatment for a common gynaecological problem and could imply that prostaglandins are involved in the aetiology of excessive menstrual blood-loss in such patients.


Evidence of stem-cell competition in children with malignant disease. A controlled study of hypertransfusion. In a prospective, randomized controlled study, 30 children who were receiving chemotherapy for malignant disease and who were anaemic and neutropenic, were randomized: 18 to receive transfusion to a Hb of 10-12 g/dl (group A) and 12 to receive moderate hypertransfusion to a Hb of 14-16 g/dl (group B). Children in group B had a significantly more rapid rise in polymorph count, lower incidence of infection, and lower incidence of interruption to chemotherapy. The findings of this study provide evidence for the existence of a common stem cell in human marrow, at least for erythroid and myeloid cell lines, and demonstrate that the concept of "stem-cell competition" derived from animal experiments has a human counterpart which is clinically significant.


alpha1-Macroglobulin and reduced basement-membrane degradation in diabetes. Thickening of the capillary basement membrane is the fundamental morphological alteration of diabetic microangiopathy. Leucocyte neutral proteases can degrade basement membrane in vivo. The activity of a purified neutral protease from granulocytes is inhibited by alpha2-macroglobulin. It is suggested that the reported increase in the concentration of alpha 2-macroglobulin in the blood of diabetic patients inhibits the activity of leucocyte neutral proteases which normally degrade basement membrane. The resultant decreased rate of breakdown would contribute to the increase in basement-membrane material seen in diabetes.


Breast cancer and preceding clinical benign breast disorders. A chance association. A review of 1059 patients seen in office consultation from 1970 to 1975 for breast disorders revealed that patients with clinically benign disorders were six times as numerous as those with breast cancer. Only 11% of patients with breast cancer had had a previous benign breast-biopsy specimen and on average they were 20 years older than the peak age for benign clinical disease. Of the 163 patients with a previous benign breast-biopsy specimen only 14 (9%) had breast cancer compared with 13% in women without such a history. It is concluded that clinical benign breast disorders do not predispose patients to cancer, and such women should not be singled out for special study.


Effects of insulin, glucagon, and insuling/glucagon infusions on liver morphology and cell division after complete portacaval shunt in dogs. Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not in the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggests new lines of inquiry about the pathogenesis and/or treatment of several human disease processes.


Antibody-dependent cell-mediated cytotoxicity against melanoma cells induced by plasmapheresis. Patients with disseminated melanoma were treated by repeated plasmapheresis using a continuous-flow blood-cell separator, as part of a study to investigate methods of removing factors from tissue fluids which block cell-mediated immunity. Using 51Cr release cytotoxic assays, it was found that plasmapheresis resulted in removal of serum blocking activity. Post-plasmapheresis sera taken from several patients also increased cell-mediated cytotoxicity by induction of antibody-dependent cell-mediated killing. This effect may have resulted from removal or alteration of circulating immune complexes in the serum. It is not known whether cytotoxic activity induced in this way improves the patient's immune response against their tumours. However, the procedure is well tolerated and these preliminary in-vitro results indicate that this form of therapy could act as an adjunct to other forms of treatment of advanced melanoma.


Prediction of azathioprine intolerance in transplant patients. One cause of transplant rejection is curtailment of immunosuppressive therapy due to leucopenia. To determine those patients most apt to develop leucopenia due to azathiprine the granulocyte response to intravenous injections (i.v.) of hydrocortisone was evaluated in 10 patients who had rejected their grafts at least six month previously. 5 patients who had rejected their grafts with concomitant severe leucopenia had an inadequate response to hydrocortisone, while in the other 5, who had tolerated the drug, the response was similar to that of normal controls. Based on these observations, all the transplant candidates underwent the hydrocortisone stimulation test the results of which were correlated with their subsequent clinical course. All medical decisions were based on events other than the steroid test. 8 leucopenic patients underwent splenectomy. 6 improved their granulocyte response to hydrocortisone and tolerated azathioprine after transplantation. 2 patients who underwent splenectomy and an unoperated leucopenic man were unresponsive to the hydrocortisone test, did not tolerate azatioprine after transplantation and rejected their grafts. 4 candidates with normal responses to i.v. hydrocortisone received transplants uneventfully. In all 13 patients transplanted since the beginning of this study, the hydrocortisone test correctly predicted their tolerance to azathioprine.


The macrophagen in human rapidly progressive glomerulonephritis. Glomeruli from 18 "normal" patients and from 35 patients with glomerulonephritis have been maintained in tissue-culture and examined by time-lapse cinemicroscopy and electron microscopy. At least two distinct cell types with features of epithelial and mesangial cells emerge in the outgrowths from normal and non-crescentic glomeruli. 4 patients with rapidly progressive glomerulonephritis formed a distinct subgroup. Glomerular culture revealed that their crescents contained large numbers of macrophages. This suggests that, contrary to belief, the crescents in rapidly progressive glomerulonephritis consist of accumulated macrophages rather than proliferated epithelial cells.


Double-blind trial of glycerol therapy in early stroke. The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke. Administration continued for up to 6 days. A standard scoring system was used for neurological evaluation. There was no difference in mortality or in improvement in neurological score between the two groups.


Thymine-requiring bacteria associated with co-trimoxazole therapy. Since 1971 thymine-requiring (thy-) pathogens have been isolated from the urine of 8 patients with renal calculi, and from the sputum of 1 patient with chronic chest infection. The patients had been treated with co-trimoxazole for several months before the isolation of the mutant pathogens. There was persistent pyuria in the patients with renal calculi, and purulent sputum in the patient with chronic chest infection. The mutants were identified by their inability to grow on diagnostic sensitivity test agar (D.S.T., Oxoid) which is deficient in thymine. It was found that wild-type bacteria can produce growth factors for the metabolism of the mutants in vitro, and the urine of the patients contained by thymine-like compounds. These findings indicate that thy- mutants may develop in renal calculi during co-trimoxazole therapy. Therapy should be changed to a more suitable antimicrobial as soon as possible after diagnosis of mutant infection.


Prognostic significance of serum lysozyme in adult acute myelogenous leukaemia. Pre-treatment sera from 88 adult patients with acute myelogenous leukaemia have been assayed for their lysozyme content. All 19 patients who presented with a serum-lysozyme level below 15 mug/ml failed to acheive haematological remission from intensive chemotherapy. Serum-lysozyme levels above 85 mug/ml were found in 10 patients, all of whom went into remission. Remissions in this group were, however, shortlived. Of the 59 patients with lysozyme levels between 15 and 85 mug/ml, 39 achieved haematological remission and 12 survived longer than 60 weeks. These findings suggest that estimation of serum-lysozyme may help to identify those patients who are unlikely to respond to the intensive-chemotherapy protocols currently advocated and who could therefore be spared exposure to them.


Molecular defects in haemophilia A and von Willebrand's disease. A model is proposed for the synthesis of the factor VII/von Willebrand factor protein. The defect(s) in von Willebrand's disease are related to abnormalities of the protein subunit and/or its carbohydrate content, while in haemophilia the abnormality is related to a deficiency or abnormality of the X-dependent enzyme or protein which is involved in the generation of procoagulant activity of the factor VII/von Willebrand factor multimer.


E.M.I. scan in the management of head injuries. The E.M.I. scan has much simplified the management of head injuries. The conventional investigations have been supplanted by a safe non-invasive technique, in which lesions of the brain can be demonstrated. Thus high density intracerebral or extracerebral haematoses are readily diagnosed, even when they are in unusual sites. Wherever their location, they appear in sharp contrast to the low density of cerebral contusions or chronic subdural haematomas. The safety of the procedure recommends its sequential use in patients who fail to improve or who deteriorate; and repeated examinations can be useful in monitoring the response to therapy. Under clinical supervision, the quantity and quality of information the method yields during a single comprehensive study is such that it should became the definitive investigation in the victims of cerebral trauma.


The organisation of breast-cancer services. An investigation of breast-cancer services in the West Midlands Regions has shown little concentration of diagnostic and treatment facilities or expertise. Delays were identified which were attributable to patients, general practitioners, hospital doctors, and administrative processes. It is suggested that the service could be improved by more effective education both of patients and of doctors, and by a more structured system of care for breast-cancer patients. An efficient system is an essential prerequisite for a screening service.


[Combinations of routine laboratory tests in diagnosis of malignomas (author's transl)]. The question if combined routine-laboratory-tests could improve the search for malignomas in man was checked by comparison of 519 patients with carcinoma and 460 patients with other diseases. In order to do so a combination of four (erythrocyte sedimentation rate, alkaline phosphatase, red blood-picture, relative alpha-2-globuline-increase) and five (additionally alpha-1-globuline-increase) was put up. For either group the found constellations - consisting of normal and pathological items - and their sensibility and specificity were set up. To find out their diagnostical value the likelihood-ratio was determined. Those combinations with exclusively pathological results of all four respectively five laboratory reports and the linked symptoms "anemia - relative alpha-2-globuline-increase" showed to be of high differential diagnostical value. In these groups the probability of malignoma was found to be 4,6:1, 8:1, 3,2:1. The serum protein dispersion of a group of patients with benigne and maligne diseases of the digestive tract was additionally checked by means of the paper-electrophoresis. Those changes that showed a relative increase of all globuline-fractions combined with a decrease of serum albumins under 45% was almost exclusively found in patients with malignomas. All-together this paper shows that certain pathological laboratory-tests--if found together in one patient--give a grave indication for the presence of malignoma.


[Value and limitations of oral exfoliative cytology in the diagnosis of malignancies]. The literature on oral exfoliative cytology in the diagnosis of malignant lesions is reviewed and the techniques most commonly employed for the removal of material, fixing, staining and observation are described, along with the usual diagnostic criteria. Evaluation of prior comparative cytological and histological assessments of the diagnostic reliability of the means is followed by an account of the difficulties encountered when comparing results so as to form a final opinion on its possible applications. It is felt that, while exfoliative cytology cannot take the place of biopsy in making a definite assessment of the nature of a lesion, the literature shows that it is widely applied in addition of clinical evaluation of oral lesions.


[Possibilities of the cytological differentiation of the adrenal medulla by a new light-microscopic technic]. A simple new histochemical technique for the differentiation of adrenaline and noradrenaline storage cells is described. In both groups of cells two more types: clear cells and dark cells can be distinguished. The new technique is based on a special interaction taking place between the product of the reaction noradrenaline-glutaraldehyde and the metachromatic cationic dye. The relationship between clear- and dark cells observed by the described new technique and by electron microscopy by the other authors is also discussed.


External detection of axoplasmic flow using radionuclides. In order to investigate the possibilities of studying the axoplasmic flow in vivo by means of radionuclide scanning 75Se-methionine was injected into the L6, L7 or S1 spinal ganglia of cats and the spread of the isotope recorded with a gamma camera. -2. After 4 hours the area of isotope distribution extended 1-2 cm cranially and caudally in the spinal cord and a further movement of 1-2 cm was noted during the following 2-5 days. -3. Scanning of removed specimens of the spinal cord, roots, ganglia and nerves confirmed the intramedullary uptake and in addition revealed an uptake in the dorsal root. Determination of the specific radioactivity showed the presence of the isotope in the ventral root and spinal nerve also, however, sufficient for scintigraphy. -4. Microautoradiographic studies with 3H-methionine demonstrated isotope uptake in axons of the dorsal roots and root entry zone of the spinal cord. Hence, the spread of the isotope was likely to have occurred by axoplasmic flow. This seems to provide a basis for further in vivo studies of this phenomenon.


Cryosurgery of advanced vulvar carcinoma. An advanced epidermoid carcinoma of the vulva was treated with cryosurgery when radical surgery was refused. The cryosurgery was well tolerated in an elderly patient with arteriosclerotic heart disease, and local tumor control was achieved. Availability of sophisticated instrumentation for the destruction of tumors by freezing leads to broader indications for and increased use of this mode of therapy for vulvar and other malignancies.


Alterations of alpha2-globulin and the clinical response in patients with prostatic cancer following cryotherapy. Evaluation of alterations in the level of alpha2-globulin in the serum of 18 patients with prostatic cancer prior to and following cryotherapy of their primary prostatic tumor and the clinical response of these patients disclosed: (1) a progressive increase in the level of alpha2-globulin and the incidence of patients with significantly elevated levels of alpha2-globulin, i.e., greater than or equal to 1.30 g/100 ml, with a progression of the stage of their malignancy; (2) a decrease in the levels of alpha2-globulin in the serum of 14 of 18 (78%) patients following cryotherapy, and (3) a favorable clinical response in 11 of 14 (79%) patients with prostatic cancer showing a decrease in alpha2-globulin following cryotherapy. While limited to the study of a relatively small patient population, the present results suggest a prognostic potential for alpha2-globulin, particularly as applied to stage identification in prostatic cancer. Pending confirmation by evaluation of a larger patient population, it may even provide objective criteria for monitoring the clinical response of an individual following cryotherapy of the prostate.


Anergy in pregnancy and malignant disease: the role of the immunosuppressive alpha-globulin. Both tumour and trophoblast produce an immunosuppressive protein which is believed to be a prostaglandin (PG) antagonist. Substances which digest this protein (protease) or enhance the synthesis of PG (levamisole) can reverse the immunodepression in cancer patients. The relevance of these observations to cancer immunotherapy is discussed.


Immune response of guinea-pigs to chemically abbreviated prepatent Metastrongylus apri infection. The effect of chemical abbreviation of the primary infection dose (PID) of 160 infective larvae of Metastrongylus apri on the immune status of the guinea-pig host was studied. The criteria used for assessing the status of immunity consisted of clinical manifestations following administration of a challenge infection dose (CID) of 800 infective larvae of M. apri, the rate of worm recovery 15 days post-CID and the rate of mortality following administration of CID. Among the guinea-pigs of the main experimental group, where 15-day-old PID was abbreviated by two parenteral doses of levamisole, a strong immunity to CID given 35 days post-PID was built-up. Against this, all the guinea-pigs of a control group, which did not receive PID, died between 16 and 22 days post-CID. The increase in serum gamma-globulin level of the guinea-pigs, where the PID was abbreviated chemically, suggested that the rise of this globulin fraction in the serum could be in some way related to the resistant state of guinea-pigs.


[Paroxysmal tachycardia due to a latent Wolff-Parkinson-White syndrome]. The authors studied 35 cases of Bouveret type paroxysmal tachycardia with normal baseline ECB, without any signs of Wolff-Parkinson-White syndrome. In more than half the patients, it seems that it may be stated that the paroxysmal tachycardia is related not to a reciprocal intranodal rhythm, as is said classically, but to a reciprocal rhythm using in the anterograde direction the normal pathways and in a retrograde direction a direct atrio-ventricular bundle in which only retrograde conduction is possible. This explains the absence of any patent preexcitation pattern on tracings in sinus rhythm. The authors particularly stress the value of a sign recorded at the onset of an attack of tachycardia: transient slowing of the rate of the tachycardia when functional bundle branch block is present can only be explained by the existence of a latent preexcitation bundle on the side of the "slowing bundle branch block".


Inhibition of RNA-directed DNA polymerase by aurintricarboxylic acid. Commercial-grade aurintricarboxylic acid (ATA) inhibits poly(A), poly(C) and viral RNA-directed DNA synthesis by detergent-disrupted virions of Moloney murine leukemia virus. Paper chromatography of crude ATA yields two active components, which appear to behave identically, and at least two inactive components. The concentration of ATA needed to inhibit polymerase activity is proportional to the concentration of viral protein. The inhibition is neither attributable to contaminating heavy metal ions in the ATA preparation nor to chelation by ATA of Mn2+ or Zn2+, the necessary co-factors. Inhibition of the polymerase reaction by ATA greatly increases the Km for the primer [oligo(T)/oligo(dG)], while it only slightly lowers the Vmax and does not affect the Km's for the template [poly(A)/poly(C)] or the substrate (TTP/dGTP). Thus, ATA seems to reduce specifically the affinity of the polymerase for the DNA primer molecule.


Elastin fibers in scar tissue.

Elastin fibers in scar tissue. Scar tissue, obtained from humans, was stained for elastin fibers by a new staining method. Elastin fibers were noted at sites where they must have been formed de novo. The morphology and the distribution of elastin in various types of scars are described. Practically no elastin was found in keloids.


[Surgical considerations on the duration of heparin therapy in deep venous thrombosis]. The authors report their experience of the medical treatment of deep venous thrombosis. Certain surgeons have attempted venous thrombectomy at the acute stage, but many have abandoned this technique which appears perfectly sound. The authors have continued to rely on heparin treatment by intravenous injection ; the introduction 5 years ago of phlebographic methods for following the evoluton of thelesions has led the authors progressively to prolong the duration of heparin treatment. The results of this approach to therapy are illustrated in several cases by phlebograms.


Effects of compound 48/80, a histamine-releasing agent, on accumulation and release of cyclic AMP in various regions of rat brain in vitro. The effect of compound 48/80 in various rat brain regions - by means of incubating brain sclices with compound 48/80 - on cyclic AMP accumulation and release of the nucleotide into the incubation medium was studied. In all regions tested, accumulation of cyclic AMP occurred within at least 10 min. In the cortex, brain stem and cerebellar regions these increases of cyclic AMP could be blocked by propranolol, a beta-adrenergic antagonist. Diphenhydramin, an antihistaminic agent, was without effect in these regions, but could partially block the compound 48/80-induced rise of cyclic AMP in the hypothalamus. Propranolol had in this region only a moderate blocking effect. Release of cyclic AMP, induced by compound 48/80, occurred in all regions tested and could not be effectively blocked by propranolol or diphenhydramin.


The specificity of the fluorescent antibody test using the sera of rabbits inoculated with strains of myocobacteria. Sera from experimentally infected rabbits were used to test the specificity of the fluorescent antibody test. It was possible using mono-specific sera to differentiate antigenically Mycobacterium phlei, M fortuitum, M smegmatis, M avium, M intracellulare, M bovis (BCG) and M johnei. The cross-reactivity within the M avium and M intracellulare group was such that one antigen from these groups would detect infection within that group and exclude M johnei infection. The M phlei growth factor independent strain M johnei 316F was shown to be antigenically distinct from a M phlei dependent strain 9N96. There was loss of specificity when M avium infection was superimposed on a previous M johnei infection and when M johnei infection was superimposed on M avium infection.


[First experiences with amniocentesis from genetic indications]. Genetically indicated amniocentesis was performed in 93 patients in the first half of pregnancy and in 36 in the second half. To the common and recognized indications several obstetric indications were added. Six (4.7%) fetal abnormalities were diagnosed by karyotyping and determination of alpha1-fetoprotein (AFP), i.e. a child with trisomy 21 and a boy with XXY Klinefelter syndrome, both in mothers aged over 40, a partial trisomy 3 in a pregnancy with a balanced anomaly, 2 boys with X-linked hereditary disease and an anencephalic. In 4 cases (3.1) abortion was performed at the parents' request. Three pregnancies ended in spontaneous abortion. In 54 cases in which amniocentesis was performed in the first half of pregnancy the babies have now been born. One was found to have a congenital heart defect and the remainder were healthy. In the cases which had undergone genetic screening during the second half of pregnancy 3 neonates displayed anomalies not detectable by karyotyping or AFP determination, one of which was hydrocephalus. The abortion rate was 0.8%.


Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Growth hormone release-inhibiting hormone (somatostatin), a hypothalamic peptide that inhibits the release of growth hormone and also the secretion of insulin glucagon, and gastrin, was found in the rat stomach and pancreas in a concentration similar to that in the hypothalamus, as measured by radioimmunoassay. Somatostatin was also found in the duodenum and jejunum, but in a smaller concentration. Gel filtration of the extracts of the pancreas and stomach on Sephadex G-25 yielded two immunoreactive peaks, one corresponding in each case to the somatostatin tetradecapeptide. The hormone was not detected in other viscera or the ovaries. The results imply that somatostatin may be synthesized in the pancreas and the stomach in addition to the brain, and may be involved in local regulatory mechanisms for pancreatic and gastric secretion as well as secretion of growth hormone.


Cobra venom factor: evidence for its being altered cobra C3 (the third component of complement). Evidence is presented that cobra venom factor, the anticomplementary protein in Naja naja venom, is modified cobra C3 (the third component of complement). Antiserum to the cobra venom factor cross reacts with human C3. A protein in cobra serum reacts strongly with antiserum to the venom factor and the former protein, like human C3, is converted by incubation of cobra serum with endotoxin, hydrazine, or simple storage at 37 degrees C. Incubation of cobra venom factor with cobra serum destroys the C3 cleaving activity of the venom factor in human serum, whereas human C3b inactivator is ineffective. Thus, the cobra venom factor appears to be a form of C3 (perhaps C3b); its potent action in human serum probably derives from its lack of sensitivity to human C3b inactivator.


Induction of mitosis in mature neurons in central nervous system by sustained depolarization. DNA synthesis and mitosis have been induced in vitro in fully differentiated neurons from the central nervous system by depolarization with a variety of agents that produce a sustained rise in the intracellular sodium ion concentration and a decrease in the potassium ion concentration. Depolarization was followed in less than 1 hour by an increase in RNA synthesis and in 3 hours by initiation of DNA synthesis. Apparently normal nuclear mitosis ensued, but cytokinesis was not completed in most cells; this resulted in the formation of binucleate neurons. The daughter nuclei each contained the same amount of DNA as the diploid preinduction parental neurons; this implies that true mitogenic replication was induced.


Nonanastomotic hepaticogastrostomy for palliative decompression. A simple, low risk technique has been used in two patients with high malignant obstruction of the common hepatic bile duct for the creation of a biliary enteric fistula.


The safety of dexamethasone and hydroxyethyl starch in the multiply leukapheresed donor. A total of 23 leukaphereses were performed on five normal, healthy donors for the purpose of providing granulocyte transfusions to septic leukemia patients with granulocytopenia. Dexamethasone 7.25 to 7.50 mg was given orally 10 to 12 hours prior to each donation, and an average of 304 ml of hydroxyethyl starch (HES) was given intravenously during each procedure. During the period of observation for each donor, there was no significant change of total leukocyte and platelet counts, total bilirubin, alkaline phosphatse, LDH, SGOT, creatinine, BUN, and uric acid determinations. Changes in the concentrations of serum protein, albumin, cholesterol, and glucose were thought to be due to hemodilution. Partial thromboplastin and prothrombin times remained within normal limits following collection procedures. Hemoglobin levels decreased transiently following the first three leukaphereses in all donors, but fell progressively to 11.8 gm/dl in one donor undergoing seven procedures in a 35-day period. Dexamethasone and HES in these doses can be given safely to multiply leukapheresed donors.


Rhinitis of pigs: A gross staining method for macroscopic examination of the nasal mucosa. A phloxine-alcian blue (PhAB) method has been used to stain the porcine nasal mucosa for macroscopic examination. Applied to either fresh or fixed specimens it stains respiratory epithelium dark blue and non-cilated epithelium, including the metaplastic epithelia of rhinitis, bright pink. The PhAB technique is simple, inexpensive and dependable, and is suitable for routine application in the post mortem room. Stained and fixed specimens may be preserved virtually indefinitely.


Antigen site densities and ultrastructural distribution patterns of red cell Rh antigens. The ultrastructural distribution pattern and antigen site density of the major Rh antigens (C, c, E, e, and D) on red blood cell ghosts sensitized with WITH IgG Rh antibodies were determined using electron microscopy and ferritin conjugated rabbit anti-human IgG. The ferritin particle distribution pattern of all the Rh antigens studied was random and ranged from relatively isolated monodispersed clusters containing less than eight ferritin particles to large localized aggregates or masses of 20 or more ferritin particles. Evidence is presented to indicate that most of the antigen clustering was due to the conjugate during staining of the cell bound IgG on the stroma preparations. The conjugate-induced antigen clustering was influenced by both the titer of the conjugate and the staining time. Whether a similar degree of antigen mobility exists in the native membrane remains to be determined. Estimates of the number of cell bound IgG molecules (number of antigenic determinants) based on ferritin particle scoring of IgG Rh antibody sensitized red blood cells under nonsaturating conditions were in the range of 20,000 to 32,000 for each of the Rh antigens. These findings are consistent with the view that the Rh antigen complex is associated with a single membrane component.


[New methods of identifying chromosomes]. The data are considered on the possibility to identify chromosome after differential inhibition of their spiralization when staining the preparations with acrichin derivatives with the subsequent application of fluorescent microscopy as well as with staining by Giemza after treatment of the preparations with hot salt solutions, alkalies or proteolytic enzymes. Materials of the Paris Conference on the human chromosome nomenclature 1971 are described briefly and recommendations of the Committee on standardization of the mice genetic nomenclature are given.


Trials with chlorpyrifos (Dursban) as a systemic insecticide against the cattle louse. Data for louse control are presented chiefly on chlorpyrifos (Dursban) 0, 0-diethyl 0-(3, 5, 6-trichloro-2-pyridyl) phosphorothioate and fenchlorphos in one trial and chlorpyrifos and famphur in three trials. These animal systemics were tested on 168 dairy calves in four herds located in three regions of the North Island, New Zealand. Louse control, following single backline, dermal applications, showed 80%, 87% and 100% with dosages of chlorpyrifos at 5 mg, 13 mg and 20 to 200 mg per kg, respectively, and 100% and 93% with dosages of famphur at 20 mg per kg, respectively. Poor louse control (24 to 58%) with fenchlorphos was expected since this compound requires two applications 14 days apart. Ovicidal effect was demonstrated with chlorpyrifos and famphur. Minor scurfing and hair loss occurred on some calves with all compounds, but hair coats were normal 28 days after treatment. Calves given 100 mg to 200 mg per kg chlorpyrifos showed signs of organophosphate toxicity from 5 mins to 90 mins post-treatment but were normal thereafter.


[Formation of giant cells in oral squamous cell carcinoma during bleomycin treatment: enzymehistochemical, electronmicroscopic and ultrahistochemical investigations (author's transl)]. During treatment of keratinizing squamous cell carcinomas with bleomycin tumor cells are devitalized by keratinization, while simple necrosis plays a minor role. Connected with this process is a marked resorptive granulomatous inflammation with numerous macrophages which is followed by a fibrous organization. In the border region of the keratinized tumor areas many multinucleated giant cells appear. The nature of these giant cells was the subject of controversy. Enzyme histochemical, electronmicroscopic, and ultrahistochemical investigations in three cases of advanced squamous cell carcinoma of the oral cavity prove that the giant cells which are formed during bleomycin treatment are not multinucleated tumor cells, but multinucleated macrophages. The enzymatic pattern is similar to macrophages with a high content of acid phosphatase and aminopeptidase. The ultrastructure of the giant cells is characterized by lysosomes with acid phosphatase activity, pinocytotic vesicles, and cytoplasmic projections on the cell surface with signs of macroendocytosis. The tumor cells show an epithelial differentiation with desmosomes, tonofibrils, and keratohyaline granula. The giant cells are formed by fusion of mononucleated (monocytogenic) macrophages. The fusions seem to be related to the functional status of the cells. It is possible, that the macrophages and the giant cells have an additional immunologic function. This is suggested by the frequent association of giant cells with lymphocytes. The importance of these facts for the evaluation of the action of bleomycin and the consequences for its therapeutic use are discussed. A combination with methods causing a dedifferentiation of the tumor or suppression of the immunologic defense seems to be problematic.


Demonstration of hepatitis B surface antigen by orcein staining in paraffin sections of cirrhotic liver. Blood and liver from 44 and 30 patients, died in cirrhosis and other diseases, respectively were tested for the presence of HBSAg. Blood samples obtained at autopsy and in seven cirrhosis cases also before death were tested for HBSAg by counter-electrophoresis. Detection of HBSAg in hepatocytes was carried out in paraffin sections by the modified orcein staining technique of Shikata et al. Ten of 14 HBSAg seropositive and 2 of 30 HBSAg seronegative cirrhotic patients had orcein positive hepatocytes, which were not found in any liver specimen from the 30 non-cirrhotic seronegative patients. The orcein positive substance localized in the cytoplasm of hepatocytes, less often it was also seen in a few Kupffer cells. The hepatocellular carcinoma cells present in part of the livers studied did not contain any orcein positive substance. Histological changes in the cirrhotic livers showed morphological indication of the presence of HBSAg, except on staining with orcein. The modified orcein staining technique is a simple, handy procedure for use in any routine pathological laboratory and has the additional advantage of detecting HBSAg also in stored paraffin blocks.


[Preliminary investigations of the serum alpha-1-fetoprotein level in mature and premature newborn infants (author's transl)]. Semiquantitative determination of the serum AFP concentration was carried out in 170 newborn infants (mature and premature) by means of crossover electrophoresis on admission to hospital and at 1 to 2 weekly intervals thereafter. The infants were divided into 3 groups according to their birth weight and also grouped according to gestational age into 3 further groups. The serum AFP level was correlated with the age in weeks of the infants for each group separately. Mature newborn infants with a birth weight of over 2500 g show a rapid fall in serum AFP titre; AFP is no longer detectable after the 9th week of life. In premature infants with a birth weight of 1500 to 2500 g, the fall in AFP titre is delayed and reaches zero between the 7th and 13th week of age. There is a markedly slower decrease in serum AFP concentration in the group of immature infants with a birth weight of under 1500 g; the limit of detectability lies between the 13th and the 17th week of age. An almost identical pattern is revealed when the infants are grouped according to gestational age. The possibility of diagnosing the small for date babies and severe liver disease by means of the serum AFP titre is discussed.


[Antigen-inducing activity of blood preparations from leukemia patients]. The evidence of appearance of specific surface antigen in the blood leukocytes of monkeys inoculated with cell-containing or cell-free materials from patients with leukemia (different variants of acute leukemia, chronic myelo- and lympholeukemia) with various clinicohematological characteristics is presented. The results of comparisons of the electron microscope and immunofluorescent examinations of experimental and control monkeys showed that the majority of the experimental animals with positive immunofluorescent tests were shown by the electron microscope examinations to have virus particles type C.