[Examination of the vulva of small girls. A too often neglected examination]. After a description of the methods of examination of the vulva, the authors discuss the most important findings. Among the organic diseases, are congenital abnormalities, vulvar coalescence, imperforate hymen, polyps, cysts and above all, trauma. Among the infections, one may note vulvitis or vulvovaginitis but also inclusions, of the clitoridian smaegma, and meatitis. Among the functional disorders, examination of the vulva is necessary for precocius puberty, amenorrhoea, and late puberty. Finally, it permits one to solve a certain number of false problems ; it is however often neglected and should form part of all complete pediatric examinations.


[Tiapride in anesthesiology].

[Tiapride in anesthesiology]. The psycho-motor sedative action of tiapride, which has been demonstrated in internal medicine, was studied in anesthesiology. A group of 253 patients hospitalized for urological (203 cases) or gynaecological (50 cases) operations were given standard premedication together with 100 to 300 mg of tiapride. Preoperative sedation and reduction of anxiety was excellent in 138 cases, moderate in 97 cases, and nil in 18 cases, under the influence of tiapride. Tiapride was perfectly well tolerated even in patients with debility, obesity, alcoholism and cardiac or respiratory insufficiency.


[Leri's melorheostosis. Apropos of 3 cases in children]. Three pediatric cases of Leri's melorheostosis are reported. Growth disorders and deformities of the limbs are often the first signs in children. X ray shows areas of very opaque condensation of the long bones parallel to the main axis of the bones parallel to the main axis of the bone, and on the epiphyses, small dense and irregular islets. The course is benign but there may be orthopedic complications.


[Desquamative interstitial pneumonia. Clinical, optic, ultrastructural, histo-immunoligical and enzymatic study of a case]. The desquamative intersitial pneumonia is a rare, sometimes curable from of diffuse interstitial fibrosis. A clinical, optical and ultrastructural, immunochemical and histo-enzymologic study of one case proved the macrophage nature of the intra-alveolar cells and suggested in the histo-genesis an immunological mechanism depending on lymphocytes.


[Original treatment of headache and migraine]. Headache and migrain are frequant motives for requesting advice of the general practitioner or specialist. They often participate in a general picture of "masked depression". Among the many propounded therapies, a place of choice should be made for Tiapridal, the more so that its antalgic effect is combined with an antiemetic and slightly anticompulsive action.


[Unusual digestive manifestations during rheumatoid purpura. Apropos of 2 cases]. We have observed two unusual forms of rheumatoid purpura with digestive symptoms in two young girls aged 16 years. In the first case, the signs of complete duodenal stenosis led to a surgical operation which led to the discovery of an infiltrated mesenteric band of adhesions containing numerous lymph nodes, with on the oedematous loops of small intestine, numerous ecchymoses. In the second case, the duodenal-jejunal radiological abnormalities suggested protein-losing enteropathy. especially as this patient like the first, had major hypoproteinemia without albuminuria. The Cr51 radioisotope test confirmed this quite exceptional diagnosis in this disease.


[Sinus node dysfunction with conduction disorders and lithium poisoning]. A case of lithium poisoning with lithium salts in a man of 66 years is reported. Sinus node dysfunction and conduction-tissue modifications were found. The responsibility of lithium in these disoredrs is discussed. The literature and the cellular mode of action of lithium are reviewed.


[Alcoholic coma by accidental poisoning in children]. Among comas of toxic origin, in children, alcoholic coma due to accidental poisoning is uncommon compared with comas due to drugs or household products. It is however important to make an early diagnosis, for this is a severe from of poisoning, liable to cause irreversible cerebral lesions if not treated very quickly. It almost always causes a flask coma, without localising signs, hypothermia and hypoglycemia, but hypoglycemic comas are not always of alcoholic origin, and only measurement of blood alcohol gives a definite diagnosis.


[New therapeutic indications for a dopamine antagonist, Piribedyl]. Evidence has been found for the view that piribedil stimulates peripheral and central dopamine receptors. Piribedil stimulates the nigro-striatal pathway and has been shown to be an effective antiparkinsonian agent. The stimulation of dopamine receptors in the meso-limbic and/or meso-cortical pathways lead to propose its use in the treatment of affective disorders (maia and depression). Piribedil stimulates dopamine receptors located in the tubero-infundibular pathway and reduces the secretion of prolactine, producing ablactation ; it increases the secretion of STH. Recent studies suggest that the peripheral effects of piribedil, mainly the increases in femoral and cerebral blood flows are also due to stimulation of peripheral dopamine receptors.


[3 recent cases of Noonan's syndrome].

[3 recent cases of Noonan's syndrome]. In the present state of our knowledge of cytogenetics, it seems logical to distinguish Noonan's syndrome from Turner's syndrome, thanks to the following arguments: Althought there are minor differences in the morphotype, the small size and the mental retardation are the same in both cases. However there are two lines of evidence: The first, inconstant, concerns the lesser intensity of the gonad changes, especially in the female sex, explaining the relative frequency of the familial forms of the syndrome, of Noonan, which are then trasmitted as autosomic dominants  with variable penetrance. The second, constant and formal until now, concern the chromosome abnormalities. Present in Turner's syndrome, which they help to define in both sexes, they are always absent in Noonan's syndrome, in boys as in girls.


[Clinical, bacteriological and pharmacokinetic study of Sisomicin in the newborn infant]. A study of the efficiency and tolerance of sisomicin in 19 children with severe bacterial infections led to the following conclusions: -sisomicin was efficient, particularly in association with beta-lactamin; -the local and systemic tolerance was good. The susceptibility of various bacterial strains was studied. The half-life of sisomicin given intramuscularly was : 4,0 +/- 1,8 hours in the new-borns under 10 days and 2,0 +/- 0,3 hours in older infants, when creatininemia was below 10 mg/l. No accumulation was found. The recommended daily dose of sisomicin by intramuscular route is 3 to 6 mg/kg, i.e. 1 to 2 mg every 8 hours in infants an 1,5 to 3 mg every 12 hours in new-borns.


[Action of Tiapride on wakefulness].

[Action of Tiapride on wakefulness]. A "blind" study of the action of tiapride on vigilance was carried out in 3 healthy volunteers using polygraph recordings and psychometric tests. A total of 48 recordings were made in order to study the effects during initial treatment, long-term administration of a dose of 299 mg/day, and the rebound period, we also studied the effect of a single dose of 400 mg of tiapride. No quanlitative or quantitative changes in the polygraph recordings were noted. The psychological tests showed reduction of highest scroes and lowering of the overal efficiency level, but diminished attention during treatment was not observed.


[Tiapride and alcoholic disorders of central origin. Apropos of 33 cases]. Thirthy-three alcoholics, aged between 31 and 82 years, were treated for 7 to 30 days with tiapride. The dosage was 600 mg/day (200 mg 3 times daily) by mouth or 100 to 800 mg/day I.M. Out of 27 cases of tremor treated, there were 25 favourable results, one average result and one nil result. Insomnia and character disorders, e.g. anguish, depression, nightmares, hallucinations, were improved during the first few days of treatment in 27 cases out of 30. Out of 12 cases of algo-paresthesia of the lower limb treated, the were 9 good or excellent results, 2 average results and 1 nil result. A favourable result was observed in 7 cases out of nine in vomiting, water brash (3 cases out of 4), and in 16 cases out of 20 in anorexia. No clinical or laboratory disturbance attributable to tiapride was noted in our patients whose general health was often very poor.


Small cell bronchogenic carcinoma: a distinct clinicopathologic entity. Since small cell carcinoma is a treatable disease, with surgery being beneficial in a few cases and with chemotherapy, radiotherapy, and immunotherapy contributing to prolonged survival in patients with inoperable disease, it is essential that the clinical and pathologic features of small cell carcinoma be quickly recognized in a newly presenting patient so that appropriate therapy may be offered.


Clinical biology of small cell carcinoma: relationship to surgical therapy. No prognostic factors could be identified that influence survival in patients with small cell carcinoma undergoing traditional therapy. These findings identified small cell carcinoma (1) as a distinct disease entity with reference to non-small cell carcinoma, (2) as a nonsurgical disease, and (3) as a disease demanding systemic treatment.


Long-term results in combined-modality treatment of small cell carcinoma of the lung. Fifty eight patients with small cell carcinoma of the lung were treated with a combined-modality regimen: chemotherapy with adriamycin, cyclophosphamide, and vincristine; BCG immunotherapy; radiotherapy to the lung primary and prophylactic cranial irradiation. Ninteen patients had limited disease, and 39 had extensive disease. There were 27 (48%) partial remissions and 23 (41%) complete remissions, and median survival was 51 wk. Initial performance status and extent of disease had a definite effect on survival. Only 1 patient developed CNS metastases on prophylactic cranial irradiation. Five of 19 patients (26%) with limited disease remain alive and in complete remission at 26-45+ mo. It is becoming clear from this and other recent studies that we can significantly prolong median survival in small cell lung cancer. However, even more important is the fact that limited-extent small cell lung cancer may be a potentially curable disease.


DNA viruses in urine after renal transplantation. Approximately 2 500 specimens from 96 renal transplant recipients were examined for virus particles. Electron microscopy of negatively stained preparations showed that only 3 virus groups were present, namely polyomavirus, adenovirus and herpesvirus. No RNA viruses or oncogenic RNA viruses (retraviridae) were detected. Over a 5-year period polyomavirus was excreted by 37,5% of patients. Both herpesvirus and adenovirus were excreted by approximately 11% of the patients. Although trace quantities of other viruses may have been missed, the absence of RNA virus suggests that immunosuppressive treatment activates these DNA viruses. The failure to detect RNA viruses suggests that they are absent or may require different means of activation.


[The rehabilitation of patients with cerebrovascular accidents]. A rehabilitation programme for patients with cerebrovascular accidents is outlined. The effectiveness of this programme was assessed in 220 patients transfered from Tygerberg Hospital to Goodwood Aftercare Hospital during the past 4 years. They were accepted after the acute phase and when the stroke were completed. The results or rehabilitation were judged by evaluating activities of daily living, namely eating, washing and dressing, and factors such as mobility and use of an affected hand, sphincter control, and ability to communicate. Other factors used to evaluate the rehabilitation programme were complications during treatment and eventual placing of the patient.


Metastatic hepatocellular carcinoma of the heart. A case report. A metastatic tumour growing in the heart more than 2 years after total removal of the primary hepatic growth is a rare event. Jaundice as a result of bile production by the metastasis is most unusual. The primary tumour did not recur in the regenerated liver. Features which may prove useful in making a clinical diagnosis are briefly considered. Death resulted from a thrombo-embolus from the right atrium lodging in the opening of the tricuspid valve.


Focal dermal hypoplasia (Goltz syndrome): case reports. Two Cape Coloured children, both with physical stigmata of Goltz syndrome, are described. Accurate diagnosis of congenital defects in the newborn allows optimal planning of surgical treatment and more accurate prognosis and genetic counselling.


Health needs of geriatric patients discharged from hospital. In a survey of the health needs of White and Coloured geriatric patients discharged from hospital it was found that community services were not effectively utilized to meet existing needs. While the White elderly suffered less financial hardship and had better access to medical care, they complained of more symptoms, more loneliness and more depression than their Coloured counterparts.


The radiological features of alcoholic ulcero-osteolytic neuropathy in Blacks. The radiological features in the bones and the angiographic changes in the vessels of the lower limbs of 15 chronic alcoholic men are discussed. The distal arteries demonstrate the features of neovascularization. Infective and resorptive changes in the bones of the forefeet are described. These features are related to chronic infection or to the toxic effects of the alcohol.


Surgical management of Cushing's syndrome. Twenty-seven operations for Cushing's syndrome were reviewed. Included were five cases of adenoma and 22 of adrenal cortical hyperplasia. Preoperative laboratory data, particularly the metyrapone test, were highly accurate in distinguishing adenoma from hyperplasia. Bilateral flank incisions are preferable to the transabdominal approach, with fewer complications, less postoperative ileus, and shorter hospital stays. The inability to inspect both glands simultaneously is of little consequence because biochemical testing data are sufficiently accurate to obviate the need for gross evaluation. The use of perioperative prophylaxis seems to be of importance for preventing thromboembolism in these hypercoagulable patients. The preoperative use of adrenal cortical blocking agents has not proved to yield significant advantages.


Surgical management of islet-cell adenoma in infancy. Persistent neonatal hypoglycemia is a potentially serious condition which should be recognized promptly, investigated thoroughly, and treated expeditiously. Islet-cell adenoma causing hypoglycemia in infancy is very unusual. Only 23 cases have been reported in the literature. This report documents eight cases of our own and summarizes diagnostic methods, proper medical preparation, and fundamental surgical management. Prompt surgical intervention is emphasized, as this will relieve hypoglycemia and may be important in preventing irreversible central nervous system damage. We are of the opinion that any infant with unremitting hypoglycemia, a high corrected insulin/glucose ratio, and failure to respond to maximum diazoxide therapy will require partial pancreatectomy. Identification of the adenoma at the time of operation is unlikely, and blind pancreatectomy and/or reoperation is not unusual.


Possible role of initiation factor activity in the action of interferon. Treatment of mouse L cells with homologous interferon results in the production of a protein which inhibits initiation factor activity. Characterization experiments indicate that the interferon in the preparation is responsible for the induction of an inhibitor protein. The impairment of initiation factor activity induced by interferon is specifically reversed by cAMP. An inhibitor protein may be separated from the initiation factor activity by glycerol density gradient sedimentation. The molecular weight of the inhibitor is about 50,000 dalton and sediments with protein kinase activity.


Effect of interferon on phagocytosis.

Effect of interferon on phagocytosis. The observation on the in vitro phagocytosis-enhancing effect of mouse interferon has now been confirmed in the same host system and expanded to the human system. Morphological and cytochemical evidence of the activated state of mouse macrophages has also been reported. The interferon-elicited enhanced state of macrophages has been demonstrated in intact animals. The exact mechanism of the macrophage-enhancing effect of interferon remains to be elucidated.


Effect of interferon on antibody formation. Virus-type interferon is capable of suppressing the antibody response both in vivo and in vitro. Interferon induced by antigen or mitogen (immune interferon) primarily in T lymphocytes also appears capable of suppressing the antibody response. Cyclic AMP has a regulatory effect on the induction of both virus-type and immune interferon. The immunosuppressive effects of virus-type and immune interferon may differ at the cellular or subcellular level.


Effect of interferon on togavirus and arenavirus infections of animals. The sensitivity of togaviruses to the effects of IF appears to permit successful exploitation of IF inducers, whereas the relative insensitivity of arenaviruses to IF in vitro appears to correlate with the complete lack of success of poly (ICLC) therapy in the monkey model. Noteworthy is the successful use of poly (ICLC) against fatal encephalitis caused by JE virus in monkeys. Additional studies appear to be warranted to characterize further the role of IF and/or IF inducers in other model infections prior to studies in man.


Effect of interferon respiratory infections of animals. Several animal models are available for the evaluation of interferon in respiratory virus infections. Considerable variability exists among the respiratory viruses with respect to sensitivity to exogenous interferon or induced endogenous interferon. Due to this apparent variability, combinations of interferon with immune serum and chemotherapeutic agents may provide a means of more efficient control of respiratory infections.


Use of interferon in cytomegalovirus infections in man. Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway.


[Control of lymphosarcoma or leukaemia in cats and of feline leukaemia virus (author's transl)]. A removal programme, specially designed for catteries or multiple cat households, to reduce the incidence of lymphosarcoma or leukaemia in cats and the spread of feline leukaemia virus (FeLV), is discussed. This removal programme includes annual testing of male stud cats, testing all contacts of FeLV-positive cats they had during the past two years, testing cats imported from abroad and isolation--or, if this is not possible, euthanasia--of cats found to be positive for FeLV-antigen. To detect the FeLV-antigen a simple indirect fluorescent antibody technique (FAT) was used to detect FeLV-antigen. During a period of four years, the following results were obtained when a removal programme was carried out by a large cat breeders' association in the Netherlands. The proportion of catteries, in which FeLV-positive cats were found to be present, decreased from 11.5 per cent in the former half of 1974 to 2.1 per cent in the latter half of 1977. The proportion of FeLV-positive cats and male studs decreased from 4.9 per cent to 1.2 per cent and from 5.9 per cent to 1.0 per cent respectively during this period. It is concluded that the recommended removal programme is a simple and successful procedure.


[Results of operative therapy for small-cell bronchogenic carcinoma (author's transl)]. In considering the results achieved through resection of small-cell bronchogenic carcinoma, the following factors are taken into account: age, localization, staging of the tumor, lymph node involvement, type of resection and adjuvant chemotherapy and radiotherapy. Furthermore, the fate of patients not operated provides a sound basis for comparison with the surgically treated group. In contrast to other authors, these results indicate that small cell carcinomas with limited dissemination have a relatively good prognosis following resection. The cooperative study undertaken in the German Democratic Republic, which included a very large patient collective, resulted in a similar conclusion.


Nature of tyrosinase inactivation in melanosomes. The decrease in tyrosinase activity following incubation of melanosomes isolated from mouse melanoma with dopa appeared to be related to the degree of in vitro melanization of melanosomes caused by incubation with dopa. The inactivation similarly occurred in the dopa-tyrosinase reaction system containing ascorbic aicd, although in the presence of ascorbic acid the dopa-quinone is immediately converted back to dopa and therefore melanin formation does not take place. The mode of inactivation of tyrosinase in melanosomes appeared to be similar to the reaction inactivation which is known to occur in the reaction of plant plant tyrosinase. Superoxide anion (O-2) and singlet oxygen (1O2) were estimated but undetectable during the dopa-tyrosinase reaction. Thus the inactivation of tyrosinase is not caused by the reaction products or the oxygen radicals.


Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium. Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus.


[Investigation of the NAD metabolism in the spleen of patients with Hodgkin's disease (author's transl)]. A correlation between the NAD metabolism and DNA synthesis, that means cell proliferation, was observed in the course of experimental studies using mouse tissues. The present studies revealed a similar correlation also in splenic tissues of patients with Hodgkin's disease. The enzymatic activities of NAD-pyrophosphorylase and NAD-glycohydrolase were measured in detail in isolated cell nuclei. NAD-pyrophosphorylase activity was particularly increased in patients with Hodgkin's disease. A decrease of enzymatic activity was seen following radiation therapy, and especially 24 hours after local irradiation of the spleen with 200 rd(60Co). These studies are in accordance with former results obtained in mice.


[Comparative electron cytochemical and biochemical study of ATPase and beta-glycerophosphatase activity in thymocytes, leukocytes and erythrocytes]. A study was made of the effect of procedures (freezing-thawing prior to incubation, prefixation with formaldehyde and glutaraldehyde, incubation with DMSO) on the activity of ATPase and beta-glycerophosphatase in leucocytes and erythrocytes of man, and of the effect of these procedures and of homogenization on ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity by 15%. A repeated freezing-thawing results in a 15% decrease of ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity in rat thymocytes, in a 2% decrease in human leucocytes, and in a 21% increase in human erythrocytes. Beta-glycerophosphatase activity in leucocytes and in erythrocytes increases thereby by 89 and 38%. Incorporation of 5% DMSO into the medium increases ATPase activity in human leucocytes and erythrocytes by 17 and 16%, while thymocytes this activity drops by 27%. Beta-glycerophosphatase activity increases thereby in leucocytes by 26 and in erythrocytes by 11.5%, resp.


[Effect of long-term suppression and long-term stimulation of ACTH secretion on the ultrastructure of tanycytes[]. The ultrastructure of the tanycyte ependyma in males of Wistar albino rats (160--180 g of weight) was studied under experimental long-term suppression of ACTH secretion and its long-term stimulation. The former effect was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phsophate; the stimulation of ACTH secretion was achieved by bilateral adrenalectomy. The long-term suppression of the hypophyseal adrenocorticotrophic function was followed by the ultrastructural markers of an increased transport and secretory activity in the tanycytes (mainly in beta-tanycytes, i. e. the ependyma lining floor of the third ventricle): the increased amount of microvesicles in the Golgi area and in the vicinity of the particular membranous cavity system (MCS, according to the authors' definition), the appearance of some figures of exocytosis, the elevated amount of lipid inclusions. On the contrary, the long-term stimulation of ACTH secretion was followed by the ultrastructural changes of the opposite character. The data obtained are in agreement with the previously established fact that there is a negative correlation between the tanycyte activity and the hypophyseal adrenocorticotrophic activity. It is supposed that this correlation is regulated by a feedback mechanism and attest to the involvement of tanycytes in the inhibitory control of ACTH secretion. A possible substrate inhibiting ACTH secretion by the tanycytes is discussed.


[Effect of agents disrupting microtubules on the distribution of receptors on the surface of cultured cells]. Substrate-attached normal mouse fibroblasts, transformed mouse fibroblasts (L-strain) and epithelial cells (MPTR strain) were incubated with two ligands that are cross-linking different group of the surface receptors: concanavalin A and cationic ferritin. Surface-attached ligands were revealed by the indirect immunofluorescent methods. The incubation of control cells with these ligands induced a patching of corresponding surface receptors, and a clearing of these receptors from the surface zones located on the lamellar cytoplasm near the cell edges actively protruding pseudopodia. Effects of three antitubulins (colcemid, colchicine and vinblastin) on the ligand-induced redistribution of receptors were examined and compared with the previously described effects of these drugs on the distribution of active cell edges.


[Surgical treatment of malignant neoplasms of the pancreatoduodenal zone]. The experience with surgical treatment of 866 patients with malignant neoplasms of the pancreato-duodenal zone is analyzed. Radical operations were carried out upon 220 (25.4%) patients, palliative ones-upon 459 (52.8%) and laparotomies-upon 187 (22.7%) patients. The authors draw the conclusion that a one-stage pancreato-duodenal resection is the operation of choice for cancer of the Vater's papilla, distal portion of the common bile duct and of the head of the pancreas. Extended pancreato-duodenal resections with excision of a segment of the portal or the superior mesenteric veins are indicated when adhesion of tumor and the venous wall makes the only contraindication to the radical operation.


Experimental reovirus hepatitis in newborn chicks. The avian reovirus "UM 1-203" originally isolated in the United States from chickens with tenosynovitis was pathogenic for the newborn chick infected by parenteral inoculation. It induced plurivisceral lesions, which became particularly intense in the liver. The intense local multiplication of the virus provoked a necrotizing hepatitis; viral titers were maintained around an E.I.D.50 of 10(8)/0.2 ml of organ suspension in chicks killed between the 3rd and 5th days after inoculation. As a specific cellular response to the viral multiplication, numerous polykaryocytes formed and increased in number, then regressed and disappeared from the hepatic parenchyma. By histologic and electron microscopic examination at progressive times after infection, the virus was recognizable in the polykaryocyte cytoplasm. In chicks that survived longer (killed the 5th and 6th days after inoculation), regeneration of the hepatic parenchyma occurred and seemed to develop from groups of dense hepatocytes that either lacked the virus or survived the acute phase of infection.


Epizootiology of bovine rotavirus infection. Published information on rotaviruses as pathogens, the source of virus infection and the method of transmission of infection under normal conditions are reviewed. The antigenic differences between rotavirus isolates from children, calves, pigs, foals and mice are discussed. Bovine rotaviruses isolated in the USA and the UK were shown to be closely related antigenically and the US vaccine strain protected calves from challenge with the UK rotavirus. Nineteen normally reared calves, with 20 or more ZnSO4 units of serum delta globulin, were susceptible to rotavirus inoculation at two days of age. They developed diarrhoea, showed body weight loss but recovered. Three calves with less than 10 ZnSO4 units of serum delta globulin developed diarrhoea and died. In a serological survey of 654 adult cows and calves from three herds, between 2 per cent and 37 per cent of individuals in a group had low rotavirus antibody titres and were probably susceptible to rotavirus infection. These were found in all age groups of animals studied, whether or not the group had suffered a recent rotavirus epizootic. It was not possible to predict whether an epizootic would develop on the basis of a serological survey.


Antibody titres to lamb rotavirus in colostrum and milk of vaccinated ewes. Ewes were vaccinated two to three weeks prior to mating with a formalin-treated preparation of lamb rotavirus. The colostrum and milk produced by vaccinated ewes after the subsequent pregnancy were shown to contain significantly higher titres of antibody to the virus than did mammary secretions from non-vaccinates. The virus neutralising antibody activity was associated with IgG in both colostrum and milk. However, IgG concentrations in the mammary secretions of vaccinates and non-vaccinates did not differ. It is suggested that vaccination of the dam may be of value in protecting the suckled neonatal lamb against rotavirus infection.


Haemorrhagic gastroenteritis in the dog associated with Clostridium welchii. Two cases of peracute haemorrhagic enteritis in the dog are reported. Gram-positive bacilli, which were shown in one case to be Clostridium welchii were found adhering to the necrotic epithelial surfaces in parts of the gastrointestinal tract in both cases. Large numbers of C welchii were recovered from the intestines of both dogs.


A serological survey on the prevalence of infectious bovine rhinotracheitis in Buckinghamshire, Berkshire and Oxfordshire. Of the 2368 cattle sera from herds in Buckinghamshire, Berkshire and Oxfordshire examined for infectious bovine rhinotracheitis antibody by an indirect haemagglutination test, 162 (6.8 per cent) proved positive. Positive titres were more prevalent in older cows and they tended to show higher titres. There was little evidence of infection in the bulls tested. The percentage of positive animals in Berkshire and Oxfordshire was 4.7 compared with 10.5 in Buckinghamshire. The infection was not known to be associated with any clinical disease.


Investigations on the presence of enteroviruses in drinking water. Out of 220 tap-water samples examined, 3.64% were found to contain enteroviruses. The 11 isolates included 3 attenuated poliovirus, 2 Coxsackie A4 and 6 untyped strains. The necessity of improving the treatment of drinking water, especially by disinfection, is outlined.


Immunoelectrophoretic study on the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note II. Analysis of KB cell host antigens. It could be demonstrated by immunoelectrophoretic analysis that the host antigen incorporated in the envelopes of Sendai virus cultivated in KB cells (Sendai/KB) is characteristic of these cells and does not occur in the envelopes of the same virus grown in the embryonated hen egg (Sendai/egg). This host antigen appears from the first passage in KB cells and is constantly maintained over subsequent passages. The glycoproteins released by Triton X-100 disruption from Sendai/KB envelopes have a concomitant antigenic specificity for both virus and host. In the case of Sendai/egg virus, exclusively virus-specific macromolecules are also released.


[Pyruvate oxidation and S35-lipoic acid fixation by breast tumor homogenates]. The rate of pyruvic acid oxidation by human mammary gland tumor homogenates is several times lower compared with that by homogenates of the adjacent non-involved tissues. This dependence is especially manifest with malignant tumors, although in this case both in the involved and non-involved tissues the pyruvate oxidation is slower than in benign tumors. In the in vitro experiments the rate of S35 lipoic acid binding by the precipitated in 10000 g fractions of the homogenates in question was the highest for malignant tumors and 3.36 times lower for the adjacent tissues. In benign tumors these values and their correlation were much more lower.


[2 aspects of immunity in experimental flavivirus infections]. Experimentally, two aspects protective and damaging, of the immune response were demonstrated in the course of development of infection in mice inoculated with tickborne encephalitis (TBE) virus, Langat, yellow fever, dengue type 2 or West Nile viruses. The experiments were carried out in animals in which the functions of T- and B-lymphocytes, were temporarily inhibited with cyclophosphane (CP). It was demonstrated that the protective or damaging role of the immune response depended on the method of inoculation of the animals, the virus properties, and characteristics of the mouse strain. The conditions optimal for the development of immunopathological reactions in one infection (TBE) were not identical for those in another infection even when caused by an antigenically related virus (LANGAT). In mice of the AKR strain the possibility of producing a therapeutic effect upon treatment with CP of the animals inoculated with TBE virus was demonstrated.


[Enzymatic and ultrastructural changes in isolated liver mitochondria from mice infected with several group A arboviruses]. Inoculation of white mice of varying body mass with pathologic strains of eastern and Venezuelan equine encephalomyelitis viruses and their attenuated variants (DNC-20/6 and No. 2621), promising as vaccine candidates, resulted in an increase of enzymatic activity and ultrastructural changes of isolated mitochondria from livers of the animals. The attenuated strains of the viruses were shown to induce temporary changes in both aspects of the study which became normal by the end of the study. There was a certain correlational dependence between the enzymatic activity and ultrastructural changes in isolated mitochondria associated with the use of energy in virus reproduction.


[Electron microscopic study of the An-750 strain of Powassan virus isolated in the Soviet Union]. Electron microscopic examinations of brains of white mice inoculated with the An 750 strain isolated for the first time from adult mosquitoes and with the prototype LB strain of Powassan virus were carried out. The method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. Sizes of virions and their localizations in the brain cells were determined. Virus particles were found in large and small neurons as well as in glial elements. Subcellular changes in neurons associated with virus multiplication are described. The causes of differences in sizes of virions measured in ultrathin sections are discussed.


[Hormones and cytostatic drugs in cancer chemotherapy]. From the practical experience the possibilities and the areas of application of the tumour chemotherapy and their value in the complex treatment of tumours are described. After representation of the cytostatic drugs available and description of their principal mechanism of action as well as their clinical pharmacology the indications, side-effects and contraindications for the usual cytostatic drugs are described. The possibilities of the application of the tumour chemotherapy in the clinical and out-patient field are particularly entered. Nowadays, by combinations of several cytostatic drugs and additional application of hormones satisfactory results of therapy may be achieved, which were not yet achievable 10 and more years ago. The proportion of tumours, which may be cured by chemotherapy alone, is still insignificant. The pharmacotherapy of tumours is at present put into earlier stages, e.g. into the postoperative phase as an adjuvant treatment. Finally, some practicable schemata of the therapy for solid forms of tumours are given, which are suitable for use in general practice, without putting in a claim for being regarded as therapy standards.


Role of the vagus nerves and catecholamines in the production mechanism of the myocardial failure induced by arteriovenous fistulas. Myocardial adenine nucleotides (nicotinamide adenine nucleotides included), glutathione, catecholamines (DOPA, dopamine, noradrenaline, adrenaline) and some enzymes in correlation were investigated in dogs with cardiac failure induced by bilateral iliac arteriovenous fistulas, and unilateral (left) heart vagotomy was also studied for its influence on the changes in the myocardial amounts of these compounds occuring in this pathological circumstance. The cardiac failure in arteriovenous fistula was characterized by the following myocardial metabolic aspects: (I) no change in the amount of proteins (although an important cardiac hypertrophy was present); (II) decreases in the amounts of adenine nucleotides (especially ADP and ATP), without significant variations in the adenosine concentration, accompanied by increases in the concentrations of nicotinamide adenine nucleotides (in both their oxidized and reduced forms) in the heart mitochondria; (III) no change in the amounts of oxidized and reduced glutathione and in the activity of NADH2-dependent glutathione reductase; (IV) a very significant increase in the activity of MAO without significant influences on the levels of the studied catecholamines. The partial vagal denervation of the heart was found to attenuate substantially the changes in the amounts of adenine nucleotides and nicotinamide adenine nucleotides in the myocardial mitochondria and to facilitate the action of MAO on noradrenaline leading to a significant decrease in its myocardial level.


The influence of diazepam and thiouracil upon the carcinogenic effect of diethylnitrosamine in gerbils. N-diethylnitrosamine (DEN) was simultaneously administered with diazepam (DZP) or thiouracil (TU) once weekly for life to gerbils (Meriones unguiculatus). Additional DZP or TU treatment increased significantly average survival time and inhibited the development of cholangiocarcinomas, although cholangiomas were still observed in these groups. Tumor type and incidence in the nasal cavities were not influenced by DZP or TU. However, in comparison to DEN alone tumor latencies were prolonged.


[Studies of the activity of various dehydrogenases in the desert rat (Meriones unguiculati) nephrons]. Researches about the Activity of some Dehydrogenases in the Nephrons of Desert Rats (Meriones unguiculati).--Our desert rats Meriones unguiculati (Mongolian Gerbils) show--also when held under the same experimental conditions as our other laboratory rodents (Wistar rats and white mice)--a somewhat different enzyme histchemical behaviour of these nephrons. The essential difference in the Meriones is that their distal convolutions display on the whole stronger enzyme activities compared as well with the proximal convolutions of the same kidneys, as with the distal convolutions of Wistar rats.


Morphological and histochemical observations on the intestinal epithelium of Ascardia galli (Nematoda: Ascaridida). The intestinal epithelium of Ascardia galli has been studied with various cytological and cytochemical techniques. It consists of large epithelial cells resting on a thick collagenous basal lamina. Their luminal surface is provided with microvilli. The intestinal cells store considerable amounts of glycogen and neutral lipids. Some intracellular granular inclusions, which stain for proteins, phospholipids and lipoproteins, are distributed throughout the cytoplasm. The brush border is composed of microvilli whereas the outer surface coat consists of saliva resistant PAS-positive material. The detailed histochemical analysis of surface material has revealed that it is composed of nonacetylated acid mucopolysaccharides rich in hyaluronic acid with carboxylate polyanions. The brush border shows intense activities of acid phosphatase and glucose-6-phosphatase, moderate of ATPase, and lipase, weak of 5'-nucleotidase. Acid phosphatase-positive intracellular structures are seen in the intestinal epithelium which form distinct aggregations.


Experimental muscular amebiasis in hamsters as a biological model. Trophozoites of Entamoeba histolytica maintained in vitro in Pavlova's medium were inoculated by deep intramuscular injection into the proximal left hindleg of hamsters. Thioglycollate medium was utilized as a successful vehicle to induce the infection. The invasion of the muscular tissue by the vegetative forms caused the formation of abscesses with great destruction of muscular fibers. The lesions were limited to the muscular tissue of the femoral area. The number of trophozoites, the medium of thioglycollate as a vehicle, the volume of the inoculum and the trauma caused by the needle were important elements in the evolution of the muscular amebic abscesses. A limited trial of the amebicidal activity of metronidazole utilizing the amebic intramuscular infection was also performed.


Morphological, histochemical, and biochemical studies on the gut of Haemonchus contortus Rud., 1803). A study has been made on the structure and chemical composition of the gut of Haemonchus contortus (Rud., 1803). The oesophagus has typically a triradiate, cuticle-lined lumen. The intestinal epithelium is provided with a well-developed brush border which contains periodic acid-Schiff-positive mucoproteins. The intestinal epithelium stores glycogen and lipids. It stains diffusely for phospholipids and general proteins and also for terminal-NH2 group. The presence of Fe2+ and Fe3+ containing pigments and activities of acid and alkaline phosphatases, glucose-6-phosphatase, and 5'-nucleotidase have been observed in the intestinal epithelium. Biochemically pH optimum for intestinal acid phosphatase has been found to be 4.8. The brush border shows positive reactions for acid phosphatase and glucose-6-phosphatase, and negative reactions for alkaline phosphatase and 5'-nucleotidase, and negative reactions for alkaline phosphatase and 5'-nucleotidase. The presence of enzymes in the brush border is related to extracellular digestion and absorption of nutrients.


Cyclic-AMP content in Escherichia coli B/b as affected by N1-(delta 2-isopentyl)adenine. N6-(delta 2-isopentenyl)adenine, like other cytokinins, does not detectably modify Escherichia coli growth, but strongly affects cellular levels of cAMP. A substantial delay of the highest level of intracellular cAMP, a reduction to about one half of such maximum level, and a slight increase of cAMP secreted into the medium are reported.


Further investigations on the antioncogenic activity of A/PR8/34 (HON1)- influenza virus on polyoma virus induced tumors in newborn Wistar rats. The oncogenic activity of polyoma virus in newborn Wistar rats can be significantly reduced by simultaneous vaccination with the A/PR8/34 (HON1) strain of influenza virus. The antioncogenic activity (AOA) of influenza virus suspensions was neutralized by the addition of homologous influenza antibodies, indicating that AOA was due to influenza virus and not to any non-viral material possibly present. The AOA of influenza virus was found to decline with storage at 4 degrees C and to depend critically on the relative doses of influenza virus and polyoma virus inoculated per animal. Simultaneous inoculation of animals with influenza and polyoma virus reduced significantly the antibody response to polyoma virus in all experiments, suggesting that influenza virus reduced the multiplication of polyoma virus. By contrast, the antibody response to influenza virus was significantly enhanced by inoculation with polyoma virus in some experiments, only. Influenza virus was found to reduce markedly the adsorption of polyoma virus on rat embryo fibroblast cells, suggesting that AOA could be at least partially due to interference of influenza virus with polyoma virus adsorption on target cells.


[Inactivation of viruses in water by anodic oxidation (author's transl)]. The inactivating effect of anodic oxidation on viruses performed in an experimental electrolytic polarization unit was investigated with 11 different viruses suspended in tap and superficial water. Furthermore attempts were made to define the influence of factors important in experimental and water respect. Using concentrations up to 10(4) infectious units per ml representing a multiple quantity of the virus demonstrable in contaminated environmental waters all the viruses investigated could be inactivated reliably and rationally when suspended in tap water, more easily however in water of improved conductivity, by passing the current leading unit once. Anodic oxidation represents a fast and rational not denaturating method for decontamination of virus containing waters. Varying conditions of a water as well as bacterial contamination, so far remaining within naturally occurring scope, have only little or no influence on the inactivating effect on viruses. The applicability of the method is discussed briefly.


[Results of the research on the preparation and testing of live oral smallpox vaccine in tablet form]. The authors sum up the results of decade of investigations on the elaboration and trial of live oral smallpox vaccine in tablet form. A conclusion was made that due to mild reactogenic properties, satisfactory immunogenicity and weak allergy producing properties, the mentioned preparation, along with a possibility of express and mass use, can posses future prospects under conditions of final smallpox eradication.


[Experimental study of cellular immunity after administration of inactivated and live virus vaccine]. Experiments were conducted on guinea pigs with the use of cell migration inhibition test of the peritoneal exudate; stimulation of a definite level of cell immunity in response to the administration of both live and of inactivated vaccine virus was shown. The results obtained are used for the interpretation of the action mechanism of the inactivated preparation in two-stage smallpox vaccination.


[Comparative study of lipid A from pertussis microbes differing in the toxicity of their O-antigens. I. Chemical composition and stability of the bond between lipid A and the specific polysaccharide in B. pertussis lipopolysaccharide]. Data presented in this work indicated that antigens, contrastive by toxicity, obtained by Boiven's method and O'Neill and Tood's method from two strains of Bordetella pertussis differed by stability of lipid A binding with the specific polysaccharide. The influence of duration of the lipopolysaccharide hydrolysis on the fatty acid content in lipid A, and of heptose in the specific polysaccharide was demonstrated. Lipid A fatty acid composition was studied. It is supposed that bound fatty acids are presented as C14 and C19--C22. There was a correlation between the antigen toxicity and the stability of lipid A bond with the specific polysaccharide. Stability of the lipopolysaccharide complex bond depended on heptose and lipid A content and on the composition and the amount of fatty acids in the lipid A preparations.


[Stable paper indicator systems for rapid identification of microorganisms]. The authors prepared under experimental-industrial conditions paper indicator systems for the express identification of microbes, including carbohydrate discs (by the method of Nikitin et al.), and newly worked out types for the determination of the activity of cytochromoxidase, urease, indol formation, and indicator amino acid decarboxylases (lysin, ornithin, arginine). The use of paper indicator discs proved to be expedient for rationalization of laboratory diagnosis of bacterial intestinal infections.


[Changes in the level of cyclic nucleotides in brain tumors]. Cyclic 3-5-adenosine-monophosphate and 3-5-guanosinemonophosphate concentrations were studied in the bioptate of brain tumors, examined during neurosurgical operation and in normal brain tissues. The correlations between cyclic nucleotides in the tumors appeared to be significantly decreased in comparison to the intact tissue, being a characteristic signs for all types of tumors. There were significant fluctuations in the level of cyclic nucleotides both in the tumours and nontumorous brain tissues. There were no correlations found between the level of cyclic adenosine-monophosphate and cyclic guanosine-monophosphate on the one hand and the duration of the disease, localization of the tumor, degree of the brain oedema and the type of narcosis on the other.


Studies on adenosine triphosphatase activity of rat cardiac myosin in isoproterenol-induced cardiac hypertrophy. Ca2+- and K+ -activated ATPase activity of cardiac myosin from normal and hypertrophied rat hearts was investigated. Cardiac hypertrophy was induced by isoproterenol treatment. A nearly 40% increase in heart mass was seen after seven consecutive days of isoproterenol injection (5 mg/kg) as determined by either heart weight expressed as per cent of body weight or by dry heart weight and total protein content. The measurement of ATP hydrolysis revealed that cardiac myosin from isoproterenol-treated rats had a significant decrease (P less than 0.01) in Ca2+-activated ATPase activity at low ionic strength (0.05 M KCl) in the presence of 5 and 10 mM Ca2+. In contrast, in a high ionic strength medium (0.50 M KCl) the K+- and Ca2+-activated ATPase activity of myosin prepared from hypertrophied myocardium remained unchanged. Comparative analysis of protein present in the light chains of myosin showed no alteration in the proportion of LC1 to LC2 in the myosin from hypertrophied hearts, however, a decrease in the absorption of myosin in the u.v. region was observed. On the basis of our results one can hypothesize that there may be some conformational change in the myosin molecule from hypertrophied myocardium, thereby modifying both Ca2+-sensitivity and ATPase activity at a low KCl concentration.


Ultrastructural organization of giant neurones of the mollusc Lymnaea stagnalis under different environmental temperatures. The ultrastructure of identified giant neurones of the visceral ring of Lymnaea stagnalis ganglion alters with the seasonal change of the animal and, experimentally, from the inactive physiological state (winter time or at +4 degrees C) to an active one (spring-summer time or at +18 degrees C). The ultrastructural organization of the active animal's neurones is characterized by morphological alteration pointing to an increased metabolic activity, viz., an increased number of nucleoli, an enlarged surface of nuclear membrane and an increase in the nuclear membrane pores, appearance of a zone of free ribosomes near the nuclear membrane, changing the structure of cytosomes, abundant granular endoplasmic reticulum, increase in the number of mitochondria.


Lysosomal enzyme secretion in rat ventral prostate. Secretagogue action of testosterone and dibutyryl cyclic AMP. Rat ventral prostate slices, when incubated in vitro, secrete protein, lysosomal enzymes and newly phosphorylated components in a time- and temperature-dependent manner. Testosterone and dibutyryl cyclic AMP immediately stimulate secretion and 32Pi incorporation. Acid phosphatase and beta-N-acetylhexosaminidase are secreted as acidic isoenzymes presumably contained within primary lysosomes.


Repeated isologous transplantation of islets of Langerhans in the diabetic rat. The metabolic response to repeated isologous transplantation of isolated pancreatic islets was studied in 11 streptozotocin-diabetic AGUS rats. The islets were isolated with collagenase and transplanted intra-portally in batches previously found to be quantitatively insufficient for reversal of the diabetic state. Primary transplantation caused a slight improvement whereas retransplantation with the same number of islets three weeks later was followed by normalization of blood glucose, plasma insulin, urine volume and urine glucose per 24 hours during a three-month observation period. Repeated isologous transplantation of isolated pancreatic islets has an additive effect on the metabolism in that two insufficient tissue doses correct streptozotocin induced diabetes in the rats.


Effects of human chorionic gonadotrophin on the release of cyclic AMP and progesterone from the sheep ovary at different stages of the oestrous cycle. The rate of release of cyclic AMP by sheep ovaries containing a corpus luteum was determined at different stages of the cycle before and up to 60 min after an intra-arterial (ia) injection of 500 IU human chorionic gonadotrophin (hCG). The median cyclic AMP concentration in arterial plasma and of ovarian venous plasma following hCG stimulation was 93.2 and 98.0 pmol/ml, respectively. The ovaries of ewes examined at Days 1 and 2 of the cycle showed no response to hCG, whereas in 2 sheep at Day 3, hCG caused a slight response, and in 13 sheep examined between Days 5-18, hCG caused a marked increase in cAMP release. In 5 of the sheep in which both ovarian veins were cannulated, only the ovary with a corpus luteum responded to hCG with an increased secretion rate of cyclic AMP and progesterone. The results indicate a lack of responsiveness in the newly formed corpus luteum to hCG.


Maturational changes in sheep ovarian follicles: gonadotrophic stimulation of cyclic AMP production by isolated theca and granulosa cells. Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 microgram NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3',5'-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4-6 mm in diameter) and small (1-3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.


Cyclic AMP and cyclic GMP accumulation by isolated hamster granulosa cells stimulated by LH and FSH. Cyclic AMP and cyclic GMP accumulation in hamster granulosa cells as a function of gonadotrophin dose (LH or FSH) and time (0-30 min) was determined. The pattern of acute cyclic AMP accumulation was similar in LH and FSH stimulated granulosa cells, except that the cells were more sensitive to FSH than LH. There was a positive dose response relationship of cyclic AMP accumulation in LH and FSH stimulated cells. LH appeared to partially inhibit FSH stimulated cyclic AMP synthesis. Cyclic GMP accumulation was distinctly different in LH and FSH stimulated cells. An inverse dose response relationship of cyclic GMP to dose LH was observed, with only the lowest dose of LH (0.005 IU/ml) stimulating cyclic GMP synthesis. FSH at 0.005 IU/ml did not stimulate cyclic GMP synthesis, but at higher doses generated cyclic GMP in a positive dose-related manner. The results suggest that specificity of hormone action in granulosa cells may be governed in part by differential on cyclic AMP and cyclic GMP in these cells.


Calcitonin heterogeneity in lung cancer and medullary thyroid cancer. An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Exdogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (greater than or equal to 30 000 molecular weight (MW) to fraction V (approximately 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i.e. fractions I and IIA). Following in vitro incubation of the serum, the typical MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.


Clinical studies of "big ACTH": its physico-chemical characteristics. The big ACTH fractions available from human plasma and pituitary glands and from porcine pituitary glands were physico-chemically characterized by gel filtration, disc electrophoresis and isoelectric separation. In the case of healthy human subjects, big ACTH fractions were isolated by gel filtration from plasma samples taken during states of acute ACTH hypersecretion such as the lysine-8-vasopressin, insulin or metopyrone tests though none of these fractions were isolated from plasma sampled under normal conditions. Even with no stimulation of ACTH secretion, patients with Cushing's disease gave plasma samples that contained an isolable big ACTH fraction, but such a fraction was hardly isolated from plasma taken from patient with Addison's disease. Both human pituitaries and porcine pituitaries contained an isolable big ACTH fraction. By a gel filtration analysis the molecular weight of the big ACTH was estimated to be higher than 20 000. Disc electrophoresis with an acrylamide gel indicated that big ACTH is strongly basic while small ACTH is more acidic than pH 8.3. Isoelectric separation revealed that the isoelectric point of human big ACTH is higher than pH 10.0 while that of small ACTH is about pH 6.8.


Binding of gonadotrophin releasing hormone (GnRH) by bovine anterior pituitary plasma membranes and purified GnRH receptor protein (GnRH.R). [125I]-(GnRH) concentration dependence binding curves using isolated bovine anterior pituitary plasma membranes, intact and solubilized, and purified GnRH receptor protein, are compared. In all instances the concentration dependence binding curves had a stepwise character here interpreted as multisigmoid, with several steep increases and plateaus. These curves are compatible with the existence of several binding sites for GnRH. Purification of the GnRH receptor protein (GnRH.R) resulted in about 500 000-fold increase of binding activity and yielded a single protein species on polyacrylamide gel electrophoresis in SDS, of estimated molecular weight 60 000. Similarity of GnRH binding by the purified protein with that of intact and solubilized plasma membranes suggested that a single protein was responsible for the binding in each instance. Thus heterogeneity of GnRH binding is likely attributable to phase transitions of a single receptor protein into different allosteric forms. The data suggest that positive cooperativity is involved in the studied system.


Action of KI and several iodocompounds on [3H]uridine incorporation into thyroid RNA. The present studies were performed in order to further clarify the action of iodine and iodocompounds on the incorporation of labelled uridine into thyroid RNA. KI decreased RNA labelling but did not alter total [3H]uridine uptake or [3H]inulin distribution space. KI also inhibited the increase in RNA labelling produced by 8 mM glucose. T4 was more potent on a molar basis than KI in impairing uridine incorporation. TETRAC, TRIAC and isopropyl-T3 also decreased RNA labelling, while T2 and isopropyl-T2 were ineffective. KI did not alter the distribution of the uridine derivatives, UMP, UDP and UTP, as determined by the distribution of [3H]uridine in these compounds by paper chromatography, suggesting that the action of KI does not take place at the step of uridine phosphorylation. Like its effect on TSH, KI also impairs the stimulatory effect of exogenous cAMP and cGMP on RNA labelling, suggesting that its action is exerted beyond the step of cyclic nucleotide formation. Iodine and iodocompounds may exert their inhibitory action on RNA labelling at the step of nucleotide polymerization.


Some histochemical observations on the myocardial metabolism in experimental conditions. Part I. In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes.


[Quantitative investigations of the zonal distribution of SDH, G6Pase and malic enzyme activity in liver parenchyma (author's transl)]. In native cryostat tissue sections of adult female albino rat liver the activities of succinate dehydrogenase (E. C. 1.3.99.1), glucose-6-phosphatase (E. C. 3.1.3.9) and malic enzyme (E. C. 1.1.1.40) were histochemically demonstrated and planimetrically determined. The areas of the enzymes with a maximum activity in the periportal regions, namely SDH and G-6-Pase, were respectively 34% and 41% of the whole parenchyma. Malic enzyme showed a maximum activity in the perivenous region, which consisted of about 53% of the total parenchyma. The zonal distribution of enzyme activities is related only to the terminal vessels; in the vicinity of the preterminal vessels an irregular distribution pattern was found. The results further support the assumption of the bifunctionality of liver parenchyma.


[Accumulation of phosphate ions in biological materials, phosphate ion diffusion and electron microscopical investigations of phosphohydrolases (author's transl)]. Isolated unfixed nuclei of mouse liver accumulate different amounts of phosphate ions dependent on pH, temperature and concentration of phosphate ions. At 37 degrees C and pH = 7.2, 8.5 X 10(9) binding places and a stability constant of 2.0 +/- 0,5 . 10(4) l/mol were calculated, the data at 30 degrees C and pH = 6.5 are 4 X 10(9) Nucleus-1 and 6 X 10(3) l/mol. Nuclei fixed by formaldehyde-ethanol or glutaraldehyde do not accumulated phosphate ions. Under conditions of nearly undisturbed diffusion phosphate ions taken up by the nuclei and precipitated by the help of lead ions are detected electron microscopically in the nuclear envelope, preferently in intracisternal space. Nucleoprotein structures do not show enrichments of crystals. These structures are also not stained after precipitation of phosphate ions under conditions of diminuation of diffusion. A possible mode of phosphate binding in cell nuclei and the influence of adsorbed phosphate ions on localization of enzymatic activities are discussed.


Sensory denervation of the plantar lumbrical muscle spindles in pyridoxine neuropathy. Male albino rats treated with excessive amounts of pyridoxine developed an impairment of neuromuscular function. The equatorial region of the plantar lumbrical intrafusal muscle fibres was studied in the electron microscope and the calibre of the nerve fibres was determined in semi-thin sections of the posterior tibial nerves. Degeneration of the primary sensory endings coincided with the onset of ataxia, and in more advanced stages of the neuropathy as well as after a 2-month treatment-free period the equatorial region was denervated. There was a corresponding decrease in the number of large nerve fibres. It is considered essential that primary sensory endings of lumbrical muscle spindles should be included in studies of distally accentuated sensory neuropathies.


Ultrastructural localization of rabies virus antigens in infected trigeminal ganglion of hamsters. The trigeminal ganglion of hamsters infected with CVS strain of rabies virus was investigated by electron microscopy with peroxidase-labeled antibody. Major localization of virus antigens were the following three types of structures; rabies virion, cytoplasmic inclusion, and ribosomal granules consisting of Nissl body. Rabies virions in neurons were mostly found within the cluster of such ribosome-rich regions suggesting a close relationship between the two in the synthesis of virus antigen. The cytoplasmic inclusion appeared to be derived from ribosomal or allied particles with virus-specific antigens. The significance of results obtained is briefly discussed.


Effects of terbutaline on the pressure volume relationship in fetal rabbit lung. The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation.


Ultrasonography and computer tomography in orbital diagnosis. With special reference to dysthyroid ophthalmopathy. A report is given on a series of 162 patients referred for ultrasound examination (US, A-mode) due to orbital disease. 101 also had computerized tomography (CT, Emi scanner Mark I, 160 X 160 matrix, 8 mm sections), the results of which were emphasized in a recent publication (Gyldensted et al. 1977). The present approach is primarily clinical. With histopathological confirmation in only 40% of the cases, it is difficult to give exact values for diagnostic accuracy, but it appeared to be above 90% for CT, and close to this value for US (depending on, of course, how specified the diagnostic predictions were). Dysthyroid ophthalmopathy (DO, orbital Graves' disease, endocrine exophthalmos) was the most frequent cause of unilateral protrusion (24 cases). In some such cases "tumour-positive" CT scans represent a diagnostic pitfall, unless the examiner is familiar with the clinical features of DO. In the present series, for example, one of the DO cases had transcranial exploration of the orbit. The two--indeed valuable--non-invasive methods (CT and US) should be assessed in combination, and also combined with the classic clinical evaluation of the patient.


Pigment changes of the retina in chronic progressive external ophthalmoplegia (CPEO). A study was made of the retinal functions in 4 patients with chronic progressive external ophthalmoplegia, general myopathy, EEG anomalies and pigment changes of the fundus oculi (ophthalmoplegia-plus). Three of them exhibited typical, granular pigmentations in a linear or reticular arrangement at the periphery. All four showed slight to moderate pigment epithelial defects in the maculae, mostly only discernible with fluorescence angiography. In all 4 cases, a slight decrease of the visual acuity, a mildly abnormal ERG, mild concentric restriction of the field of vision and, in two cases, an abnormal dark-adaptation curve led to the conclusion of a mild diffuse, widely disseminated receptor affection of the retina (both rods and cones). The EOG appeared normal in 3, and at the lower limit of normal in 1 case. On the basis of a detailed study of the literature we can conclude that the retinal lesions in chronic progressive external ophthalmoplegia may vary from benign pigmentations without functional impairment to genuine 'retinitis pigmentosa' with all gradations of rod-cone or cone-rod dystrophy. Emphasis is laid on the possibility of a correlation between the mitochondrial abnormalities encountered in ocular myopathy and ophthalmoplegia-plus on the one hand, and the retinal abnormalities on the other, with special reference to a possible disorder of the utilization of pyruvate in the citric-acid cycle and a loose coupling of the oxidative phosphorylation.


The process of wound healing of the avascular outer layers of the retina. Light- and electron microscopic studies on laser lesions of monkey eyes. The process of wound healing of the avascular outer layers of the retina is studied on a series of Laser lesions of the monkey, Cercopithecus aethiops. The extent of the retinal lesions is limited to the pigment epithelium and photoreceptor cells, whereas Bruch's membrane and the vascular inner layers of the retina intact. The retinal lesions are not seen to be invaded by cells from the choroid, nor from the retinal vessels. During the first three days after irradiation the pigment epithelial cells in a zone, about 75 micrometer wide, around the lesions appear to be changed into bi- or multinucleate cells with the additional nuclei situated in apical cytoplasmic protrusions which extend towards and into the lesions. During the second and third days after irradiation the lesions are invaded by two kinds of cells which both appear to arise through the off-budding of the nucleus-containing apical protrusions of the pigment epithelial cells around the lesions: (a) phagocytic cells which disintegrate the damaged tissue and, as this process is completed 4--9 days after irradiation show evidence of melanogenesis; and (b) regenerated pigment epithelium which form a single layer of cells along Bruch's membrane, but show no evidence of phagocytosis or intracellular disintegration of the damaged tissue. Within the lesions both these kinds of cells show mitotic figures the third day after irradiation.


The isozyme pattern of cyclic AMP-dependent protein kinase and the distribution of a cervicovaginal antigen in experimental carcinoma of the cervix uteri of mice. Tissue-sections from 12 methylcholanthrene-induced carcinomas of the cervix uteri of mice were tested for the presence of an antigen normally confined to the cervicovaginal epithelium. The antigen was detected in 10 of the 12 tumours investigated with indirect immunofluorescence, and in all 7 tumours studied with the more sensitive method of mixed hemagglutination. The concentration of the antigen was generally higher in the well-differentiated areas of the tumours, but it was also found associated with solitary tumour cells, apparently invading the stroma. The presence of CVA in the tumours suggests an origin of the tumour cells from the cervicovaginal epithelium. The cyclic AMP dependent protein kinase (EC 2. 7. 1. 37) in the tumour cytosols was studied by chromatography on agarose and DEAE-cellulose. The enzyme showed the same properties as that from normal vaginal epithelium. The tumour cells thus contain an apparently normal complement of this enzyme, which is believed to be responsible for most of the intracellular actions of cyclic AMP.


Human malignant lymphomas in vitro. Characterization of biopsy cells and establishment of permanent cell lines. A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a "true" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.


The first tick-borne encephalitis virus isolates from Norway. Five virus strains with close serological relationship to the tick-borne encephalitis (TBE) complex have been isolated from Ixodes ricinus ticks. The ticks were collected in early June 1976 at three different locations in Sogn & Fjordane County, Norway. One of the virus-yielding pools was composed of ticks collected between the cabins on a tourist camping ground.


Metabolic adaptation to hypoxia. Redox state of the cellular free NAD pools, phosphorylation state of the adenylate system and the (Na+-K+)-stimulated ATP-ase in rat liver. The effect of hypoxia (30 min 10% or 8% O2) on the phosphorylation state and redox state of the cytosol and mitochondria of rat liver were studied. Measurements were made both from normal animals and animals which had been exposed to the reduced partial pressure of oxygen (50.5 kPa or 40.8 kPa of air) for one or seven days. Cytostolic free NAD was reduced in the liver both in acute hypoxia and in hypoxia after one or seven days, i.e. the lactate/pyruvate and sn-glycerol-3-phosphate/dioxyacetonephosphate ratios increased markedly. A marked reduction in the mitochondrial free NAD pool occurred only in acute hypoxia and only a slight reduction was observed in animals kept at 40.8 kPa for one or seven days, as evaluated from the hepatic hydroxybutyrate/acetoacetate ratio. Liver ATP concentration decreased rapidly in acute hypoxia without any significant recovery during one or seven days at 40.8 kPa. The hepatic ATP/ADP X Pi ratio decreased significantly, with a simultaneous decrease in the total adenine nucleotide concentration. A tendency was observed for the ATP/ADP X Pi ratio to return to normal after seven days, i.e. the values in acute hypoxia were significantly smaller than those noted in hypoxia after seven days, demonstrating an adaptation of the energy metabolism during prolonged hypoxia. Hepatic (Na+-K+)-stimulated ATP-ase activity was not affected by hypoxia.


The effect of vigorous physical activity at work on serum lipids with a special reference to serum high-density lipoprotein cholesterol. Serum lipid concentrations of lumberjacks whose occupational physical activity is most vigorous were compared with those of electricians. The lumberjacks had significantly higher serum HDL-cholesterol and significantly lower triglyceride and free fatty acid concentrations but there were no significant differences in total cholesterol levels. The favourable effect of vigorous physical activity at work on lipid metabolism is, however, epidemiologically not seen, obviously due to negative risk factors in lumberjacks' life.


The relationship between cortical recruiting responses and ponto-geniculo-occipital waves during paradoxical sleep in the cat. In an earlier study it was found that during paradoxical sleep (PS) thalamo-cortical recruiting responses (RRs) and rapid eye movements usually did not appear simultaneously. As shown elsewhere, ponto-geniculo-occipital (PGO) wave activity and rapid eye movements are during PS closely related to each other in time. Similarly, in the present study it was observed that during paradoxical sleep in cats in which the center median nucleus of the thalamus was being stimulated at a rate of 7--9 Hz PGO waves in the geniculate nuclei did not in the rule occur in the presence of RRs recorded from the motor cortex. This effect was most pronounced with respect to series of PGO waves which usually occur at a rate of 4--7 Hz. On the basis of these experiments it was concluded that PGO waves and RRs are reciprocal events and mutually exclusive. Considering to the well-known fact that RRs represent synchronization, this negative correlation between RRs and PGO waves indicates that the desynchronizing tendency typical to paradoxical sleep is most pronounced during the occurrence of PGO waves.


Oxidative and lysosomal capacity in skeletal muscle of mice after endurance training of different intensities. The activity of certain enzymes of energy metabolism (cytochrome c oxidase, citrate synthase, malate dehydrogenase, and lactate dehydrogenase) and of lysosomes (beta-glucuronidase, beta-N-acetylglucosamindase, arylsuphatase, ribonuclease, deoxyribonuclease, acid phosphatase, and cathepsin D) was assayed from m. rectus femoris of mice trained 5 days per week, 1 hr per day for 4 weeks according to 4 different programmes: I. running speed 20 m/min, horizontal track, II. 25 m/min, horizontal track, III. 20 m/min 8 degrees uphill inclination, and IV. 25 m/min 8 degrees uphill inclination. Oxidative capacity increased and anaerobic capacity decreased without distinction between the different traning programmes. Of acid hydrolases assayed the activities of beta-glucuronidase and cathepsin D were increased independently of training intensity. Simultaneous histochemical observations on beta-glucuronidase and arylsulphatase activities in the contralateral m. rectus femoris showed more intense staining in red as compared to white muscle fibres. It is suggested that training affected the red fibres and that the applied level of loading was probably too low to cause major involvement of white fibres.


Cell population kinetics and dose-time relationships for post-irradiation injury of the brachial plexus in man. Collected data on radiation-induced lesions of the brachial plexus were analyzed on the assumption that this reaction arises from depletion of some unidentified cell population in the irradiated tissues. A multi-probit search program was used to derive best-fitting cell kinetic parameters in a composite multi-target model for cellular radiation lethality and repopulation. From these parameters, a comprehensive iso-effect table, for a wide range of treatment schedules including daily treatment as well as fractionation at shorter and longer intervals, was constructed. The table provides a useful set of tolerance dosage limits for late effects in irradiated peripheral nerve.


Familial lecithin: cholesterol acyltransferase deficiency complicated with unconjugated hyperbilirubinemia and peripheral neuropathy. The first reported cases in the Far East. Three Japanese patients with lecithin: cholesterol acyltransferase (LCAT) deficiency, the offspring of a consanguineous marriage, are described. In addition to the characteristic clinical and laboratory findings of the disease, our patients had hitherto unreported manifestations, namely unconjugated hyperbilirubinemia, peripheral neuropathy and marked hypocholesterolemia. Although the mechanism of the unconjugated hyperbilirubinemia is not clear, the role of impaired hepatic bilirubin uridine-diphosphate-glucuronyl transferase activity combined with another unknown factor(s) was postulated. Non-random assortment was observed between LCAT deficiency and haptoglobin types, as previously reported. The discovery of Japanese patients with LCAT deficiency indicates that the distribution of this hereditary metabolic disorder is not confined to the Western hemisphere.


Small cell carcinoma of the lung: serum calcitonin and serum histaminase (diamine oxidase) at basal levels and stimulated by pentagastrin. Investigations were performed to evaluate the incidence of increased serum calcitonin and histaminase in 79 patients with untreated small cell carcinoma of the lung (SSC). In addition, serum calcitonin was measured following pentagastrin stimulation in 19 of these patients. Serum calcitonin was elevated in 54 of 79 patients (68%), 20 patients (25%) having a level usually associated with the diagnosis of medullary carcinoma of the thyroid (MCT). The levels of histaminase, on the other hand, did not differ from the distribution in normals. In three of 19 patients undergoing the pentagastrin stimulation test, calcitonin was significantly increased. Thus, serum calcitonin is frequently elevated in patients with SCC and a positive pentagastrin test is not pathognomonic of MCT.


Mathematics of the inverse solid-phase radioimmunoassay. Use of a simplified, idealized model allows a mathematical treatment of the inverse solid phase radioimmunoassay. Equations are presented for calculation of the following values: bound/free antibody ratio (R) in the state of equilibrium; the equilibrium constant (K), the concentrations of the directly non-measurable values (Abf; AbfAg: Abs and Ag) as well as the concentration of the antibody tested [Abf]0. The model has the same parameters as the test system, thus the equations may be used in planning of the test in the laboratory.


Antibodies to rubellavirus, herpes simplex virus and Toxoplasma gondii in serial serum samples of pregnant and non-pregnant women. By testing serial serum samples of 213 pregnant women for rubellavirus, of 196 for herpes simplex virus and of 134 for Toxoplasma gondii, it was found that during pregnancy there was a fall in the humoral antibody level. Presence and titre of antibodies were lower in sera of pregnant than of non-pregnant women. Alteration of the humoral antibody level during pregnancy may influence serological studies aimed at clarifying the role of infections in fetal malformations. Serial serum samples (4 samples from each pregnant woman involved) should be tested for obtaining reliable data regarding the frequency of infections during pregnancy.


Post-operative stereotactic Curie-therapy using the iridium-192 GammaMed contact irradiation apparatus combined with radio-sensitizers in treating multiform glioblastomas. Experimental investigations on the dimethyl-amino-stilbous carcino-sarcoma of the rat have led to a modified interstitial post-operative Curie-therapy of gliomas in the brain hemispheres following treatment with radio sensitizers. After treatment with the thymine-analogous radio-sensitizers 5-brom-2-desoxyuridine (BUDR) and 5-brom-2-desoxycytidine (BCDR) and desoxyguanosine as well as the anti-metabolites 5-fluor-uracile (FU) and methotrexate (Mtx), there is greater incorporation of the thymine analogues in the DNS of the tumour cells. More than any other combination, BUDR and Mtx effectively sensibilizes the tumour cells. Syncavit and actinomycine-D are also effective. After radio-sensitizing the post-iridium-192 contact irradiation apparatus on 133 patients with gliomas. This treatment lengthened postoperative survival times.


Glioblastoma multiforme: morphology and biology. Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct "primary" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.


Megavoltage therapy of glioblastoma multiforme. Supervolt radiation therapy produced no improved survival rates in the treatment of glioblastoma multiforme as compared to orthovolt therapy. Survival times of more than one year or two years must still be considered a rarity. The application of computer techniques to the calculation of dose distributions greatly enhances the optimization of treatment planning. Tumour doses of 5,000 to 7,000 rad are considered necessary, and are dangerously close to the dose levels tolerated by brain tissue. Improvements could conceivably be expected from a) combinations of chemotherapy and radiation therapy, b) intra-arterial application of radiating substances with tumour affinity, c) neutron therapy. Whether or not such measures will in the future produce improved therapeutic results remains to be seen.


Multicentric glioblastomas. Methods of diagnosis and treatment. Although multicentric glioblastomas are relatively rare, their occurrence is not an extreme rarity. A multicentric lesion should always be thought of when the symptoms cannot be related to a single focus and when the special investigations do not confirm a single lesion. In our opinion the brain scintigram and the computer tomogram offer the best diagnostic possibilities at present. If the preoperative diagnosis has been made, then an indication for operation can be justified only if multiple tumours can be removed through one approach and, what is even more important, at one sitting. The cases demonstrated prove that this procedure can be successful. If, on the other hand, only one of several tumours is excised, then a fatal outcome is almost certain.


Protein heterogeneity in rat CNS myelin subfractions. Microsomal fraction-free myelin from forebrain and spinal cord of young and mature rats, when subjected to hypo-osmotic shock and slow speed centrifugation, yielded a myelin pellet and a supernatant fraction (SN 4). Fraction SN 4 consisted of small vesicular profiles in which the major myelin proteins were reduced whereas high molecular weight material such as Wolfgram protein, myelin-associated glycoprotein and CNP were substantially increased over myelin. A close correlation of the SN 4 fraction to the myelin-like fraction of Davison and coworkers was suggested. The myelin pellets were subfractioned on zonal sucrose gradients to yield bell-shaped particle distributions. Besides shifts in densities of the maxima between myelin of young and mature forebrain and spinal cord, a decrease was observed from the light to the heavy gradient end in basic proteins, and an increase in Wolfgram protein and other high molecular weight proteins. Proteolipid protein took an intermediate position. Light fractions from adult spinal cord displayed CNP activities below those of the total homogenate. This result, together with the very high CNP activities in fraction SN 4 casts some doubt on CNP being a marker for compact myelin; rather it appears that CNP is a marker for the process of myelin formation.


Retardation of brain myelination by malnourishment and feeding low protein irradiated diet in rats. The effect of feeding low protein diet, and the low protein irradiated diet on the deposition of myelin in the brains of rats over two generations showed that malnourishment lowered the CNP enzyme activity when compared to the normal (high protein) diet fed control rats during early postnatal period. Irradiated low protein diet, when fed within 21 days of irradiaton (15 Krads Gamma radiation, 60Co rays), produced still lower CNP enzyme activity. This also enhanced other effects of retarding the brain development, by lowering the protein and lipid contents of the brain during a period from the 4th to 25th day of postnatal development. This suggests the possibility that feeding irradiated low protein food to malnourished developing mammals could cause serious problems like mental retardation.


On the accessibility and localisation of cerebrosides in central nervous system myelin. Cerebrosides are concentrated in the myelin sheath where they account for about 20% of the total lipid of the membrane. The present paper is concerned with the role and localisation of these glycolipids in the myelin lamellae. Isolated central nerve myelin preparations have been treated with two probes to investigate cerebroside accessibility in the membrane. The action of galactose oxidase on the galactose headgroups of cerebrosides is followed and quantitated by recovery of the modified glycolipid and resolution of either the 6-aldehydo sugar or galactose remaining by gas-liquid chromatography. With isolated myelin preparations only some 40--50% of the cerebroside galactose is attacked by galactose oxidase at 20 degrees C. With periodate at 20 degrees C over 90% of the galactose headgroups are oxidised in 3 h while the figure is 50--55% over the same time period at 4 degrees C rising to 85% after 22 h. With multilamellar liposomes of mixed myelin lipids only some 20--25% of the available cerebroside is oxidised at 4 degrees C, the reaction being complete in 2 h. The results are discussed in relation to the dispositon of cerebroside in the myelin lamellae. A major location on the external face of the membrane system (intraperiod dense line) is favoured. A role for cerebroside in myelin in terms of increasing the stability and resistance of the lipid phase to ion movement is suggested.


Virus infection in demyelinating diseases. Several animal and human demyelinating diseases of the central nervous system (CNS) are associated with RNA or DNA viruses. These viruses infect CNS cells lytically or persistently. They mainly belong to the group of envelope viruses which derive their envelope partly from the host cell membrane. The process of virus release may result in the appearance of new antigens of virus-infected cells or the incorporation of cell membrane material into the viral envelope. These changes may lead to an immune response which selectively injures the CNS. These alterations of host cell membranes and host cell functions, together with the immune mechanism, are central to many of the hypotheses regarding virus-induced demyelination. The role of virus infection in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, visna and mouse hepatitis virus infections, is discussed in relation to the demyelinating process of these diseases.


Early and late CNS-effects of corona virus infection in rats. The mouse hepatitis virus strain JHM was injected intracerebrally into newborn and weanling rats. Three types of diseases were observed: 1. Acute panencephalitis: Almost all suckling rats became moribund within 6 days. Histologically severe panencephalitis with demyelinating foci was noticed; the foci were similar to those found in mice. Virus was easily detectable in the oligodendroglial cells and neurons both by immunofluorescence and electron microscopy. Infectious virus could be isolated. 2. Subacute demyelinating encephalomyelitis (SDE): Three weeks after infection of weanling rats, about 35% of the animals developed paralysis. Neuropathologically, demyelination with a striking predilection for white matter was observed in the brain stem, optic nerve and spinal cord. Virus was detectable by electron microscopy in degenerating oligodendroglial cells only, which corresponded to the results obtained by the immunofluorescent techniques. Infectious virus could be recovered. 3. Chronic progressive paralysis: Inoculated weanling rats without SDE developed 6 to 8 months later a slowly progressing paralysis of the legs. Hydrocephalus and myelomalacia were present. Viral "footprints" could not be detected.


A search for the "multiple sclerosis virus"--lack of effect of brain extracts on myelin development in chickens, mice and rats. Attempts were made to transmit possible infectious agents from tissue of MS patients into three animal species, under conditions designed to enhance the development of such an agent. Myelination was monitored by measuring CNPase activity and myelin basic protein. Although no significant effects were observed, the usefulness of a new assay for CNPase was demonstrated. Nude mice were found to have a lower level of CNPase than their heterozygous littermates.


Chemical and statistical studies of contaminants in urban lungs. Lungs taken at autopsy from 100 urban residents were studied to determine concentrations of 21 trace metals, dust, free silica and hydroxyproline. Medical, occupational and environmental histories were collected so that correlation studies might be done. The potential value of this data as a baseline for further studies of occupationally diseased lung tissue was assessed by evaluating the results of an analysis of variance. The personal histories were used as the criteria for classifying the observations (lung concentrations) into groups for the statistical analysis.


Nitrogen-containing compounds in foundry mold emissions. Nitrogen compounds have been identified in the decomposition products from several commonly used foundry sand binders. These compounds include nitrogen oxides, hydrogen cyanide, ammonia, simple aromatic amines, and isocyanates. The concentrations of these compounds in foundry mold emissions do not appear to be directly related to the nitrogen content of the organic binders. Measurable concentrations were observed in some cases, indicating the necessity for periodic, monitoring in the foundry. Adequate ventilation will permit the use of these binders. The substitution of nitrogen-free binders suggests another possible control strategy.


Exposure of firefighters to toxic air contaminants. A personal sampling apparatus for firefighters was developed to sample the fire atmosphere for CO, CO2, O2, NO2, HCI, HCN and pariculate content. Two fire companies made ninety successful sample runs during structural fires. CO presented a potential acute hazard and particulate concentrations were high. HCN was detected at low levels in half the samples. HCI was detected in only eight samples but on two occasions exceeded 100 ppm. CO2 and NO2 levels and O2 depression do not appear to represent significant hazards.


Hapten-specific respiratory hypersensitivity in guinea pigs. Respiratory hypersensitivity to small chemical determinants (haptens) was produced in guinea pigs by repeatedly exposing the animals to aerosols of hapten-ovalbumin conjugates. In this way, reactivity toward p-azobenzenearsonate and p-tolyl isocyanate was induced. Carrier (ovalbumin)-specific respiratory reactions were not produced. Hapten-specific respiratory hypersensitivity was accompanied by the production of hapten-specific antibodies. The method for inducing hapten-specific hypersensitivity can be applied to screen various industrial chemicals for their sensitizing abilities toward the respiratory tract.