[Human rotavirus in cell culture: its isolation and passage]. Rotavirus was isolated from feces of patients and passaged in green monkey kidney cell subculture using the factors affecting the initiation of infection of tissue culture cells with human rotavirus. The effective factors were found to include the presence of low concentrations of trypsin in the infected culture and virus centrifugation of a cell layer which agreed with the data by Almeida et al. (1978) and Shoub and Bertran (1978) obtained in other cell systems. Immune electron microscopy was used to detect the virus in cell cultures and to prove its specificity.


[New aspects of diagnosis, treatment and follow-up of trophoblastic tumours (author's transl)]. Diagnosis, treatment and follow-up of gestational trophoblastic tumours has become more efficient through the introduction of new methods like angiography, computer tomography and, especially, the determination of specific chorionic gonadotrophin. Exact diagnosis, with differentiation of high- and low-risk patients allows an individual approach to treatment. The results of these new diagnostic and therapeutic methods were studied in a department with a relatively high incidence of gestational trophoblastic disease in a European region, where trophoblastic tumours are generally rare. (Since 1971 16 cases of trophoblastic tumour and 68 patients with hydatidiform mole were treated in the department of Obstetrics and Gynaecology, University of Graz.) Schedules were drawn up for the diagnosis, classification of risk and for treatment. This may help to get good results and to prevent errors in the future. Long-term determination of HCG beta in the serum and also comparative follow-up of LH and HCG in urine led to the formulation of further characteristics of gonadotrophin secretion after hydatidiform mole and treatment of trophoblastic tumours. On the basis of the results a regimen has been formulated which seems to be optimal for the detection of tumour after hydatidiform mole and for the registration of the effect of treatment in case of trophoblastic tumour.


[Immunology and oncology of paraproteins]. Since the first description by Apitz paraproteins were for a long time regarded as biologically abnormal proteins which normally do not appear in the human plasma. According to the modern biochemical knowledge this determination of the notion can no more be acknowledged, since analyses of amino acids did not reveal any differences in the composition of the complete paraproteins and the immune globulins. Apart from the complete paraproteins which consist either of gamma, my, delta, alpha or epsilon heavy chains on the one hand and of kappa or lambda easy chains on the other hand, also molecule fragments and isolated heavy or easy chains, respectively, appear. Like immune proteins paraproteins are formed by B-lymphocytes and their transformation forms, respectively, in which case the monoclonality represents their specific characteristic. Thus exist close relations to malignant changes of the B-lymphocyte system, in particular to the non-Hodgkin-lymphomas. Several functional peculiarities of the paraproteins, such as autoantibody effect, lymphocytotoxicity, aggregation ability and binding affinity to blood cells lead to multiform clinical phenomena. To this belong immune defects, nephropathies, haemocytopenias, amyloidoses and haemorrhagic diatheses. As evoking cause of the alteration of B-lymphocyte system with activation of one or several cell clones (e.g. in double paraproteinaemia) tumour viruses are taken into consideration. After an infection with oncogenic herpes viruses irreversible cell transformations in the lymphatic system have been proved. Thus it is doubtful, whether there are indeed true benign paraproteinaemias. One has rather to speak only of relatively benign forms of the course.


[IgG- and IgA-antibodies to the Epstein-Barr virus in the sera of patients with nasopharyngeal carcinoma in Cuba]. Sera from 24 patients with nasopharyngeal carcinoma (NPC) and from 60 normal subjects were examined for the presence of IgG and IgA antibody to various antigens associated with Epstein-Barr virus (EBV). The results indicate that NPC in Cuba, like in other countries, was accompanied by high titers of EBV-specific IgG antibody the levels of which differed markedly from those in normal subjects. Serological activity of the patients differed depending on the stage of the illness and its duration. Geometric mean antibody titers to the capsid antigen (VCA), D and R components of early antigen (EA) of EBV complex were higher in patients with extensive tumour process (III--IV stages) and in patients with the duration of the disease since the onset less than 3 years. Sera of the most patients contained EBV-specific IgA antibody which were practically completely absent in sera of the control subjects. Alongside with characteristic manifestations of responsiveness to EBV observed by other workers, patients with NPC in Cuba had specific features: higher antibody titers to VCA than in Caucasian subjects in the countries where this disease occurred sporadically, like in Cuba; high levels of antibody to EA, frequently exceeding those in patients with NPC from endemic zones (for instance in Chinese patients); prevalence of EBV-specific antibody to the R component of EA complex.


[Levels of humoral antibodies to Epstein-Barr virus in the population of Cuba]. Indirect immunofluorescence was used to study the levels of humoral antibodies to capsid (VCA) and early (EA) antigens of Epstein-Barr virus (EBV) in sera of 322 normal subjects living in the province of Habana and varying in ages from several months to 93 years. The results suggest that the population of Cuba, like in other countries, is widely infected with EBV, although the pattern of spread of this infection has some specific features. In particular, the infection rate of the pediatric population (3--4 and 5--9 years) is moderately high, 73% and 65%, respectively, whereas in adult population it is rather low (62--86%) despite the tropical location of the country. In all the age groups examined, geometric mean titers (GMT) of antibody to VCA were also lower than in comparable groups of population from other countries. The observed high GMT of VCA antibody in persons over 55 years and a considerable increase in the number of positively reacting sera and sera with high antibody titers (greater than or equal to 1 : 160) agree with the data by other workers and appear to be due to reduced immunological defence of the cellular type in elderly people. Antibody to EBV EA were found in all the age groups examined, although in a small per cent. The subjects with high antibody titers to this antigen (greater than or equal to 1 : 40) were found more frequently in the two youngest age groups (0--2 and 3--4 years) which appears to be due to large amounts of virus usually occuring in the period of primary infection. The analysis of infectious mononucleosis incidence for 5 years (1972--1976) in various age groups of Habana province population indicates a general low level of incidence. Two small peaks in 3--4 and 15--19-year groups corresponded to increased GMT values of antibody to EBV EA in these particular age groups.


[Plasma lipoproteins and apolipoproteins]. In a survey the plasmalipoproteins LDL, VLDL and HDL are characterized and their functions demonstrated. Metabolically they are connected together through the IDL. Their clinical importance lies in the disturbances of the lipoprotein metabolism, which are significant for hyperlipoproteinaemia and arteriosclerotic diseases. Atypical plasmalipoproteins are LP(a), pre-beta-1-lipoprotein and sinking-pre-beta-lipoproteins. The LP-X is of interest for the differential diagnosis of jaundice. The carrier proteins of the plasmalipoproteins, the apolipoproteins, are Apo A, Apo B, Apo C, Apo D, and Apo E. They are differently structured. Their concentration in the individual plasmalipoproteins are also responsible for their function in normal and pathological lipid metabolism.


[The effect of theophyllin on small intestinal structure and function of the diabetic rat (author's transl)]. In order to obtain some information about the role of cAMP in the regulation of cell turnover of the intestinal mucosa it was interesting to investigate whether chronic pharmacologically induced changes in the cellular cAMP levels could cause alterations in mucosal growth in the case of a well defined animal modell, involving increased cell proliferation rate, such as chronic experimental diabetes mellitus of the rat. Since it has been suggested that cAMP levels on the one hand are low in cell division and increased cAMP levels on the other hand inhibit cell division, the aim of the study was to induce a suppression of the cell proliferation rate in the intestinal mucosa by chronic theophyllin application, a well known PDE-inhibitor. The following results could be obtained: Chronic theophyllin application induces a hyperplastic alteration of the small intestinal mucosa of the rat, which is similar to that observed in diabetes mellitus. In diabetic animals theophyllin causes a further increase in hyperplasia. The morphological alterations of the intestinal mucosa are more pronounced than the functional changes. In experimental diabetes mellitus the radioimmunologically determined cAMP level in the intestinal mucosa is rather low. Chronic theophyllin application alone or in combination with experimental diabetes mellitus was unable to increase the cAMP-level continuously. This could be a result of an adaptive change of the cAMP regulating enzyme system. Therefore theophyllin induced mucosal alterations are probably due to systemic effects of this drug.


[Information regulation in the vegetative periphery]. The importance of the proteoglycans (PG) of the extracellular matrix in regulating the information reaching the vegetative periphery is demonstrated. Information brought to the vegetative periphery by autonomic nerves and the microcirculatory system are coded by the PG, thereby changing their biochemical structure. These changes (i.e. degree of polymerisation, capacity of ion-exchange and water-binding, electrostatical tonus) stimulate via the specific cellglycocalyx the cAMP-adenylcyclase-system of the cells in the vegetative periphery. In this way the information becomes decoded and is followed by the enzymatically steered answer of the cell. The center for all of these relations is the fibrocyte. The fibrocytes form the metabolic active center in the vegetative periphery and answer to "informative" changes in the extracellular matrix with a situation-dependent synthesis of PG. The possibilities of modulating the intercellular transfer of informations --- various cell contacts, temporary intercytoplasmic connections (fusomes), the role of mastcells.


[Effects of zinc-aerosols on the inhalation toxicity of cadmium (author's transl)]. Female rats were continuously exposed for 3 months to an aerosol containing 50 micrograms/m3 Cadmium-Oxyd and 1.25 mg/m3 Zinc-Oxyd. Our results were compared with those of Prigge (1977), who studied the CdO-toxicity under equal conditions. Inour investigations we studied with clinical and clinico-chemical methods a possible protective effect of ZnO on the Cd-toxicity, given simultanously. A protective effect of ZnO on the Cd-toxicity was evident in out investigations in form of a reduced deposition of Cd in lungs, in livers and kidneys. A reduction of the cadmium-induced hyperplasia of lungs was a remarkable sign for a protective action of Zn. There are some criterions, that Zn, given simultaneously in the studied concentrations, can inhibit the Cd-induced disorder of function in kidneys.


[Immunologic aspects of the pathogenesis and treatment of myasthenia]. In 30 myasthenic patients the state of the T and B systems of immunity was examined: Depending on the initial findings the immunodepressant therapy (gamma-irradiation of the thymus, intrathymic blockades with hydrocortisone, ultraphonophoresis of hydrocortisone into the thymus area, oral administration of imuran, and intramuscular injections of antilymphocytic immunoglobulin) was given. A relationship between the immunological changes and the disease stage was discovered: the index of the 3H-thymidine incorporation was found to be 67.9 at the stage of disease exacerbation, and 208.8 at the stage of remission; the complement titre reached, respectively, 46.64 +/- 5.28 and 112.0 +/- 6.0 units per ml. The different methods of the immunodepressant therapy produced different effects on the patients' state and the immunological shifts. The combination of hydrocortisone with imuran appeared to be the most sparing and sufficiently efficacious method of the therapy.


[Diagnosis of lesions of the ilioinguinal nerve using clinical and electromyographic methods]. On the basis of a study of 11 normals and 19 patients, the clinical and EMG features of iloinguinal nerve lesions are described. In lesions of this nerve there are EMG changes in the internal oblique abdominal muscles, which indicate an involvement into the pathological process of not only of the nerve conductors, but central structures. The EMG method may be recommended as a supplementary one for detecting subclinical forms of the disease, clarification of the diagnosis and determination of the degree of nerve lesions.


Serum trypsin inhibitory capacity and alpha 1-antitrypsin levels in liver cirrhosis and hepatoma. alpha 1-Antitrypsin levels were measured in sera of 134 patients with cirrhosis and in 64 with cirrhosis and hepatoma. S-TIC was determined in 105 patients with cirrhosis and in 54 with cirrhosis and hepatoma. The mean alpha 1-at and S-TIC values in patients with cirrhosis were 369.59 +/- 14.072 mg% and 1,808 +/- 0.05 mg/ml respectively. In patients with cirrhosis and hepatoma the mean alpha 1-at level was 406.595 +/- 17.834 mg% and the S-TIC mean values was 2.064 +/- 0.82 mg/ml. Although these values are higher than those found in the healthy controls, the differences are not statistically significant.


Changes of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis. Serum angiotensin I converting enzyme, identical with kininase II, was measured fluorometrically in patients with acute viral hepatitis (n=18), liver cirrhosis without (n=44) and with (n=19) ascites. In all groups of patients the enzyme was significantly elevated as compared to 44 healthy controls (p less than 0.001). No correlation could be found between angiotensin I converting enzyme activity and liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, total protein, albumin, bilirubin) or other parameters (serum potassium, serum sodium). High serum converting enzyme activity in chronic liver diseases might originate primarily from an altered pulmonary circulation and indicates higher conversion rate of angiotensin I by passage through the lungs as well as increased bradykinin degradation. The reason for the enzyme liberation in acute viral hepatitis is as yet uncertain.


[Determination of the individual sensitivity of human glial tumors to the action of chemotherapeutic preparations]. Individual sensitivity of 40 glial tumors (34 macroglial and 5 oligodendroglial tumors and 1 medulloblastoma) to 4 chemotherapeutical agents (fluorofur, 5-fluorouracil, methotrexate and sarcolysin) was studied in vitro on the basis of changes in the values of thymidine labelling index after 24-hour incubation of tumor-tissue fragments in a medium with the chemical agents. Each of the tumors studied possessed individual range of sensitivity to the chemotherapeutical agents distinguishing it from other tumors. None of the agents studied proved to more effective than others. The reaction of the tumor tissue to the effect of the chemotherapeutical agents did not depend on the proliferative activity of the tumor, while the degree of manifestation of the tumor reaction was often dependent on the concentration of the agents. An increase in the number of DNA-synthesizing cells in the tumor under the effect of the chemical agents was observed in rare cases.


Hepatocellular carcinoma associated with erythrocytosis. A nine year survival after successful chemotherapy and left lateral hepatectomy. A case of hepatocellular carcinoma associated with erythrocytosis is described. The patient was successfully treated with a combination chemotherapy of 5-fluorouracil, mitomycin C, cyclophosphamide and chromomycin A3, which was followed by a left lateral hepatectomy, and has survived for more than 9 years after the operation without any signs of recurrence. With the regression of hepatic tumor by the anticancer chemotherapy, the remission of erythrocytosis was observed, indicating that the tumor was producing erythropoietin. The data suggest also that erythrocytosis could be a marker for evaluation of chemotherapeutic effects in some patients with hepatocellular carcinoma.


[Intracranial cylindroma (cylindromatous epithelioma)]. A case with intracranial cylindroma is reported. Intracranial cylindroma possesses local destructive growth and may recur repeatedly and produce metastases; it is localized on the base of the skull in the chiasmal area or, more frequently, in the region of the trigeminal ganglion. Cylindroma of chiasmal localization develops from ectopic mucous glands of the nose or nasal sinuses, whereas cylindroma of the trigeminal ganglion arises from the glandular epithelium of the auditory tube. Intracranial cylindroma is sensitive to radiation therapy. In the case discussed, the cylindroma was localized in the chiasmal area.


An electron microscopic study of childhood dermatomyositis. Muscle biopsies from 12 patients with a typical clinical picture of dermatomyositis have been examined by electron microscopy. Endothelial cells of intramuscular blood vessels, their basal lamina, pericytes, muscle fibers, and satellite cells show degenerative or regenerative alterations. In nine patients, tubular arrays were noted in the cisterns of endoplasmic reticulum of endothelial cells, pericytes, lymphocytes, macrophages and satellite cells. Other types of inclusions were also observed. The pathogenesis of the disease is discussed.


Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog. The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animal were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves.


Crystalloid inclusions reminiscent of Hirano bodies in autolyzed peripheral nerve of normal wistar rats. In a study of experimental autolysis of peripheral nerves of normal Wistar rats, crystalloid inclusions similar to Hirano bodies were observed. They occurred in the nuclei and cytoplasms of Schwann cells and in myelinated axons. They first developed after a 12-h autolysis and increased in number and size with time. Their fine structure, localization, and morphogenesis are discussed in relation to the autolysis of the cellular organelles.


Herpes simplex type 2 encephalitis concurrent with known cerebral metastases. A 62-year-old woman developed neurologic deficits 7 months after pulmonary lobectomy for alveolar cell carcinoma of the lung. CT scan of the head demonstrated two metastases with marked peritumoral edema. Administration of Decadron, chemotherapy and 3,000 rad cranial radiation resulted in dramatic improvement of dysphasia and right hand paresis. Almost 2 months later, rhythmic, involuntary movements of the left hand developed. There was progression to multifocal seizures, grand mal seizures, postictal depression, status epilepticus, and coma, with death 9 days after onset of the movement disorder. Bronchoalveolar carcinoma was widely disseminated in lungs and bones, and as three metastases in brain. Bland "ischemic" necrosis in a pseudolaminar pattern was present in the neocortex. Innumerable Cowdry type A intranuclear inclusion bodies were seen in neurons, astrocytes, and oligodenodroglia. Immunofluorescence demonstrated Herpes simplex virus type 2 antigen and electron microscopy revealed virions with the morphology of the Herpes group. The case is significant for (1) the concurrence of intracranial metastases and Herpes simplex encephalitis, and (2) the causal agent, Herpes simplex virus type 2. The implication for the clinical neurocientist is the potential in a patient with systemic cancer, for the causation of neurologic complications by more than one factor or mechanism.


Sendai virus haemolysis: mechanism of the increased haemolysis obtained by pretreatment of the virus with antibody and complement. Sendai virus is haemolytic against erythrocytes from various species. Pretreatment of the virus with antibody and complement (C) resulted in a sixfold increase in the haemolysis. The viral haemolysin (HL) could be inactivated by heating the virus at 37 degrees C for 5 h. HL-inactivated virus became haemolytic again when pre-treated with antibody and C. This acquired haemolytic capacity corresponded to the enhanced haemolysis shown by intact virus. It is concluded that the enhanced haemolytic activity is due to a C-mediated indirect haemolysis and is not dependent on the fusion process. The possibility of cell damage in vivo from virus-antibody-C complexes is discussed.


Fractionation of connective-tissue-activating factors from the culture medium of silica-treated macrophages. The medium of cultured, SiO2-treated peritoneal macrophages contained a factor which enhances the incorporation of labelled proline to collagen and other proteins in granulation tissue slices, cells and polysomes. Simultaneously, the activity of alkaline RNase in the whole medium was decreased in comparison with the corresponding control. Polyvinylpyridine-N-oxide, PVNO, protected the macrophages against SiO2. Latex-particles and E. coli lipopolysaccharide decreased the RNase activity in the macrophage medium, but unlike SiO2 did not cause liberation of the collagen synthesis-stimulating factor. Fractionation of the medium by gel filtration chromatography showed the SiO2-pretreatment to have caused a very significant decrease in the aggregation state of RNase. The fraction from gel filtration chromatography that contained the SiO2-liberated factor stimulating collagen synthesis also contained the disaggregated RNase. There was no RNase-activity in the control sample. A homogenous protein (mol. wt. 14,300) was isolated with repeated gel filtrations from the medium of silica-treated macrophages. It increased the incorporation of 3H proline and 3H thymidine into cultured granuloma cells.


Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle. End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.


Angiotensin-converting enzyme in sarcoidosis. Using a spectrophotometric assay with L-hippuryl-L-histidyl-L-leucine as substrate, s-angiotensin-converting enzyme (SACE) was determined in 85 sarcoidosis patients, 116 healthy controls and 150 patients with various non-sarcoid diseases. The controls showed no sex or age variation and had SACE levels of 24.4 +/- 6.2 U/ml (mean +/- 1 S.D.), giving a normal range (mean +/- 2 S.D.) of 12.0-36.8 U/ml. In contrast, the sarcoidosis patients had SACE values of 38.4 +/- 14.4 U/ml, with the highest values in cases with active sarcoidosis and duration of disease longer than two years (49.0 +/- 12.7 U/ml). A total of 41% of the sarcoidosis patients had elevated SACE, in the chronic active group 85%. Patients with renal failure, Hodgkin's disease and other malignant lymphoma had low SACE, whereas patients with lung cancer and tuberculosis had normal SACE values. Among 266 patients with non-sarcoid diseases and healthy controls, only two had slightly elevated SACE, but so far we have not found SACE above 40 U/ml in other than sarcoidosis patients. An elevated SACE is rather specific in sarcoidosis and seems to be a useful supplement to existing diagnostic measures.


Relationship between biochemical and clinical features in an English Anderson-Fabry family. The relationship between biochemical parameters and clinical symptoms in angiokeratoma corporis diffusum universale (Anderson-Fabry's disease) has been studied in an extensive English family. The biochemical parameters measured were alpha-galactosidase activity in urine and in single hair roots and the urinary glycosphingolipid excretion per 24 h. The clinical symptoms evaluated included the occurrence of pain, the prevalence of skin lesions, an abnormal ECG, cornea verticillata and other features. Nine male patients and 13 female carriers were studied. No correlation between biochemical parameters and the severity of the clinical symptoms could be found either in the hemizygotes or in the heterozygotes. The urinary alpha-galactosidase activity in all the heterozygotes lay within the normal range. All the obligate heterozygotes (mothers and daughters of hemizygotes) could be detected by analysis of hair roots. Additional heterozygotes were recognized on the basis of clinical symptoms and hair root analysis.


Interaction of human lymphocytes and viruses in vitro. Interaction between phytohaemagglutinin (PHA) stimulated human lymphocytes and two DNA viruses (adenovirus type 5 and herpes simplex virus type 1) considered to be closely connected with lymphoid tissues has been studied. The fate of the same viruses was investigated also in non-stimulated separated lymphocytes for comparative purposes. To elicit this interaction infectivity titrations, immunofluorescent technique and electron microscopy were used. The production of viral antigens was investigated by complement fixation. It has been shown that in PHA-stimulated lymphocytes from peripheral blood of healthy donors adenovirus type 5 is capable to replicate in its infectious form. Prolongation of the interval between stimulation and infection of cells significantly influenced the dynamics of replication. Non-stimulated lymphocytes produced antigens but no infectious particles.


Detection of antibodies to cytomegalovirus, herpes simplex virus and rubellavirus with the micro-enzyme immunoassay. Serum samples of pregnant women (200), non-pregnant women (100) and children (36) were tested for the presence of antibodies to cytomegalovirus (CMV), herpes simplex virus (HSV) and rubellavirus with the micro-enzyme immunoassay (micro-EAI), the indirect immunofluorescence antibody (IFA) technique and the haemagglutination-inhibition (HI) test. Micro-EIA gave the highest positivity rate: 78% for CMV, 86% for HSV and 85% for rubellavirus compared to 67% (CMV) and 84% (HSV) of the IFA technique and 79% (rubellavirus) of the HI test, respectively. Among IFA and HI positive sera the occurrence of micro-EIA negative ones was 6% for CMV, 4% for HSV and 9% for rubellavirus. It is concluded that the introduction of micro-EIA will improve the diagnostic and screening work of virus laboratories.


Cells containing Epstein--Barr nuclear antigen (EBNA) in peripheral blood. The anti-complement immunofluorescence (ACIF) method was used to demonstrate EBNA in B lymphocytes separated from the peripheral blood of patients with infectious mononucleosis (IM) or other diseases. In the acute phase of IM of Epstein-Barr virus (EBV) origin, 0.5--1% of the B lymphocytes proved to be positive in 6 of the 8 patients tested. In two of the positive cases the test was repeated 20 and 26 days, respectively, after clinical symptoms had appeared; the result was negative in both cases. No EBNA-positive cells were found in the peripheral blood of 17 patients with Hodgkin disease, 3 with systemic lupus erythematosus and 2 with lymphosarcoma. It is supposed that EBNA-positive cells appear in detectable amount exclusively in the acute phase of EBV infection.


Interaction of peripheral and cerebellar inputs to red nucleus neurons. In chloralose anesthetized cats responses of red nucleus neurons to cerebellar cortical or peripheral stimulation are described. Interactions between cerebellar (conditioning) and peripheral (test) stimulations were studied at various interstimulus intervals. Peripheral stimulation alone typically evoked a complex response consisting of an early (15 ms latency) burst, a period of depression of activity (inhibition, lasting up to 300 ms) and a late, long-lasting (on an average 300 ms) excitation. Cerebellar cortical stimulation resulted in a similar pattern of response; but it was composed predominantly of only two phases, an initial inhibition followed by a prolonged late discharge. With conditioning- testing intervals in a range of 10-150 ms, depending on the cell, there was a conspicuous depression of the sh0i.t-latency test excitation, followed by a prominent potentiation of this component. An occlusion of the inhibitory or late excitatory responses occurred when conditioning-testing stimuli were applied with an interval shorter than 0.5 s. It is suggested that the early excitation and the subsequent late components are generated in the red nucleus by independent mechanisms. The initial depression of the early test response is explained as an effect of Purkinje cell inhibition, and the later potentiation as a result of temporary blockage of the cerebellar cortex to afferent input.


Reversibility of changes in evoked spinal response following graded spinal cord compression. The spinal evoked response obtained in cats at a site immediately rostral to the site of a graded spinal cord compression is described. They usually show an earlier decrease in amplitude than cortical SEP's and the appearance of a particular positive potential. The degree of reversibility after decompression is variable and is not correlated with histological damage.


Pathological actin in vestibular hair cells of the waltzing guinea pig. Vestibular type 1 hair cells in the waltzing guinea pig contain needle-shaped inclusion bodies which grow in an uncontrolled fashion associated with the destruction of the cell. The needles are shown to be composed by filaments of actin, a protein identified in the electron microscope by its ability to bind subfragment 1 of myosin. Whereas actin filaments in stereocilia are oriented down towards the cell body, filaments in the needles point up towards the cuticular plate. The hereditary lesion appears to be associated with a defective control of polymerization of actin into filaments.


Therapeutic embolization of juvenile angiofibroma. Therapeutic embolization of juvenile angiofibromas was performed in 15 boys, aged 12--18 years, 11 of whom subsequently underwent surgery. Intraoperative blood loss was reduced from an average of 2,400 ml in nonembolized patients to 800 ml after embolization. Angiography is of value to confirm the diagnosis prior to excision and to delineate the extent of the tumor. Embolization may be performed at the same sitting as a presurgical adjunct or possibly as a definitive or palliative therapeutic method. The embolization procedure is discussed in detail, emphasizing techniques and potential hazards of such procedures.


The use of sand substitution to solve the free silica problem in foundry atmospheres. Field tests were carried out to compare the air quailty in a gray iron foundry before and after changing the molding material from the standard silica based sand to the mineral olivine. Olivine is a magnesium iron silicate (Mg, Fe) SiO4 which occurs in nature and contains little or no free silica. Data were collected using standard OSHA approved methods to determine the total dust and the respirable limit for the alpha-quartz particle loading levels. Additional samples were taken using a cascade impactor and filter tape samplers. The foundry was surveyed once before the substitution of olivine and three times after the changeover. The study demonstrates that the partial substitution of olivine can reduce the concentration of free silica to acceptable health levels. However, contamination from processes using silica sand must be controlled.


Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart. Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.


Unexpected decrease in plasma high density lipoprotein cholesterol with weight loss. High density lipoprotein (HDL) cholesterol is inversely related to coronary heart disease prevalence. Despite the fact that obese patients have lower plasma HDL-cholesterol concentrations, there are few prospective studies on the effect of weight loss on HDL-cholesterol. Consequently, plasma lipoprotein levels were measured in 15 obese females before and after a 10 week weight loss program. Mean weight loss was 8.6 +/- 3.9 kg (P less than 0.001). Total plasma cholesterol and low density lipoprotein-cholesterol did not change significantly. Plasma triglyceride levels decreased (P less than 0.05) as did HDL-cholesterol (P less than 0.02). A subgroup of 11 of the subjects had repeat lipid measurements 8 months after the start of treatment. Mean weight loss at this time was 12.8 +/- 0.8 kg (P less than 0.01). No subject had returned to her pretreatment weight but mean weight loss was not significantly different from the 10 week value. At 8 months all lipid values, including HDL-cholesterol, had returned to their pretreatment value. By multiple regression analysis HDL-cholesterol decreased with increasing relative weight but also decreased with increasing rate of weight loss. These results suggest that negative caloric balance produces a decrease in HDL-cholesterol that in prospective studies may obscure the inverse relationship between HDL-cholesterol and indices of obesity.


Intralipid clearance and lipoprotein pattern in men with advanced alcoholic liver cirrhosis. Twelve male patients with advanced alcoholic cirrhosis of the liver were found to have markedly low serum lipid and lipoprotein concentrations. Serum triglyceride and cholesterol concentrations were about 50% of matched control values. The very low density lipoprotein-triglyceride concentration was only one-third of control values and the cholesterol concentrations in very low density and low density lipoproteins were far below control values. The mean high density lipoprotein cholesterol concentration was not significantly decreased, but in three of 12 patients extremely low values were found. These findings may reflect a failure of lipoprotein synthesis secondary to a bad nutritional state and metabolic disturbances in this advanced stage of liver cirrhosis. By means of the intravenous fat tolerance test with Intralipid it could be shown that substantial amounts of triglycerides could be cleared from the plasma in these patients. However, studies on the long-term Intralipid clearance capacity have to be performed before any general recommendations about the inclusion of fat emulsions in parenteral nutrition of these patients can be made.


Nuclear medicine and cancer research in the People's Republic of China. This article reports the experience of the author's recent visit to China where he witnessed nuclear medicine facilities. Among other things, the author observes that most imaging equipment and radionuclides are made in China and that many good textbooks of nuclear medicine are available in Chinese. Precautions on radiation safety are very much stressed. Chinese medicinal plants are always added in order to improve the therapeutic effects of classical chemotherapeutic agents or to lessen their possible side effects. Their scientific value cannot be evaluated, nor can it be for the "anti-cancer pills" that are sold freely. The author encourages studies of different patterns of cancer problems in different geographic localities, as he gave indications for a few geographic areas.


SV40 T-antigen expression in cultured fibroblasts from patients with Down syndrome and their parents. Expression of simian papovavirus 40 (SV40) T-antigen following in vitro infection was studied in skin fibroblasts from patients with Down syndrome (DS) and their parents to determine whether the increased susceptibility to SV40 infection reflected the cytogenetic defect or the leukemia risk associated with this syndrome. As a group, fibroblasts from patients with DS showed elevated T-antigen expression 72 hrs after infection compared to that of a healthy control population. However, among 24 patients tested, the cell lines of only 11 showed statistically significant increases in T-antigen expression. A cell line from a patient with concurrent DS and acute myelogenous leukemia had a normal value. T-antigen expression did not correlate with the percentage of cells trisomic for chromosome 21 in 18 cell lines examined or with the number of copies of this chromosome in disomic and trisomic cell strains cloned from three mosaic patients.Collectively, cell lines from parents of trisomy 21 patients also showed increased susceptibility to SV40 infection; however, in five families tested, a consistent pattern of genetic transmission of elevated T-antigen expression from parent to offspring was not observed. Q-banding of cell lines in one family showed that elevated T-antigen expression is not a marker of parental nondisjunction. Variation in susceptibility to human interferon, an antiviral agent, did not account for variation in T-antigen levels among these cell lines. Thus, the abnormalities of T-antigen expression in DS appear independent of the hyperdiploid state and are not a sensitive indicator of cancer risk.


Brief clinical observations: the Neu-Laxova syndrome--a distinct entity. We report a stillborn girl with a complex syndrome of microcephaly, lissencephaly, severe subcutaneous edema, atrophic muscles, camptodactyly, syndactyly of toes and fingers, hypoplastic genitalia, and numerous structural changes of the brain and eyes. Similar cases have been reported by Neu et al [1], Laxova et al [2] and Povysilova et al [3]. The above-mentioned syndrome complex is a distinct genetic syndrome, for which we propose the eponym "the Neu-Laxova syndrome." Affected patients resemble each other strikingly and there is usually no doubt about the diagnosis. The Neu-Laxova syndrome is apparently transmitted as an autosomal recessive trait.


The utility of a rapid assay for human chorionic gonadotropin in the management of trophoblastic disease. The diagnosis and treatment of trophoblastic disease depend upon the reliable measurement of human chorionic gonadotropin (hCG) in serum or urine. The double-antibody hCG beta-subunit assay for serum hCG combines great sensitivity, specificity, and precision but requires 36 hours to yield results. This investigation sought to increase the efficiency and total assay volume capabilities of our laboratory through the development of rapid hCG assay to augment the slower beta-subunit system. Two separate rapid hCG assays were examined--a double-antibody radioimmunoassay and a radioreceptor assay. The double-antibody assay took 5 hours to complete, while the radioreceptor assay could be completed with 3 1/2 hours. One hundred serum samples from patients with trophoblastic disease were assayed for hCG in the beta-subunit radioimmunoassay and in both rapid assay systems. No differences in results produced by the rapid double-antibody and the hCG beta-subunit assays were noted; however, results from the radioreceptor assay were significantly different (p less than 0.05) from those obtained in the beta-subunit system.


Visuospatial dysgnosia.

Visuospatial dysgnosia. Spatial dysgnosia may occur in patients with various forms of brain disease, including tumors, vascular accidents, Alzheimer's disease, multiple sclerosis, and developmental aberrations. Patients with lesion in the nondominant hemisphere, particularly at the junction of the occipito-temporoparietal regions, may manifest predominantly visuospatial dysgnosia--a loss of the sense of "whereness" in the relation of himself to his environment and in the relation of objects to each other. Visuospatial disturbances caused by lesions in the dominant hemisphere may be masked by other gnostic symptoms. Patients with more extensive lesions, especially those involving similar areas in both hemispheres, may also exhibit other cognitive disturbances associated with vision.


Temporal firing sequences of antagonistic muscles. The purpose of this study was to assess the relationship between paired agonist/antagonist muscle firing times and accompanying time to peak EMG amplitudes with a 75 degree ballistic right forearm flexion task during experimental conditions of A) no external limb resistance, B) 3.1 Kg., and C) 9.8 Kg. of premovement limb resistance. In addition, total reaction time and movement time values were compared relative to the experimental conditions. Twelve male subjects practiced the flexion task for three days until criterion measures stabilized. Following five control measures on each of the next two days, 10 trials each of conditions A, B, C appearing in random order were administered. Results indicated that as external limb resistance increased (from A to B to C), movement time decreased by 30 msec., total reaction time increased by 52 msec., while biceps latency remained unchanged. There were significant (p less than0.05) increases in triceps latency, biceps and triceps time to peak EMG amplitude only with respect to the greatest external resistance (condition C). It is speculated that coordination may be defined in terms of the temporal firing sequences within an agonist/antagonist muscle group.


Continuity of care in the delivery of mental health services. The authors report on the help-seeking experiences of people referred to community settings for aftercare on discharge from a state mental hospital in western Massachusetts. They present results that bear on three questions relevant to public policy issues in the mental health field: 1) the proportion of patients who comply with referrals to aftercare agencies, 2) the social and psychological characteristics of patients who comply with these referrals, and 3) the impact of receiving aftercare on the probability of rehospitalization.


Health consequences of the snow disaster in Massachusetts, February 6, 1978. On February 6, 1978, the largest New England blizzard of the century struck eastern Massachusetts. On request, four days later, the Center for Disease Control provided epidemiologic assistance. On-site disaster assistance provided decision-makers with immediate health surveillance information useful in helping the area return to normal. No outbreaks of infectious diseases and no significant increase in the number of deaths were observed in the week following the blizzard. Some of the deaths which occurred immediately after the blizzard might have been prevented if traffic had been banned earlier.


Antigenic analyses of two axenized strains of Entamoeba histolytica by two-dimensional immunoelectrophoresis. Antigens in extracts of two strains of Entamoeba histolytica (HT-31 and HK-9) were studied by two-dimensional immunoelectrophoresis (2D-IEP) and 32 and 20 different antigenic components were detected, respectively. Cross-reactions between heterologous systems showed a large number of shared antigens between the two strains. Extracts were fractionated by Sephadex G-200 chromatography. Of the fractions obtained, fraction II of both strains was found to have the most reactive antigenic components. Precipitin patterns of fraction II from HT-31 and HK-9 with sera from patients showed similar 2D-IEP profiles and suggested that in this fraction antigens common to both strains exist which elicit antibody in individuals with E. histolytica infections.


Adenoid cystic carcinoma: factors influencing survival. We have reviewed our experience with 264 patients treated for adenoid cystic carcinoma of salivary origin. This study updates a previous report from our hospital and includes all patients treated during a 30 year period who were eligible for a minimum follow-up of 10 years. The tumor arose in minor salivary (mucous) glands in two thirds of the patients; half had received treatment elsewhere, and both sexes were equally represented. Actuarial survival curves and "cure" rates calculated by the direct method confirm that clinical staging provides a reliable prognostic guide. We are unable to demonstrate that the microscopic appearance of the tumor exerts a predictable effect on treatment results. Although some patients lived for many years after resection despite local recurrence and distant metastases, prolonged survival was unusual in patients with stage 3 lesions, particularly in those with sinus or submaxillary gland primaries. Based on the site of origin of the tumor and its clinical stage, it is now possible to select which patients with adenoid cystic carcinoma have the most ominous prognosis and perhaps plan a more appropriate operation. More importantly, these data may help focus on the subpopulation at greatest risk, which is vital to the design of any prospective study to assess the value of adjunctive irradiation and chemotherapy.


Granular cell myoblastoma of the head and neck: review of the literature and 10 year experience. The literature on granular cell myoblastoma (Abrikossoff's tumor) is reviewed and 16 new cases are presented. The etiology of this tumor remains uncertain, although a neurogenic origin appears likely. Individual tumors are usually small, nodular, and nonulcerating. There appeared to be no predilection for either sex in our series, and most tumors occurred between the third and sixth decades of life. Pseudoepitheliomatous hyperplasia is frequently associated with granular cell myoblastoma, and this combination must be distinguished from squamous cell carcinoma. Wide local excision, the treatment of choice, should be curative, although the incidence of multicentricity may exceed 15%. Thus, despite the usually benign nature of granular cell myoblastoma, its propensity for local invasion, multicentricity, and associated pseudoepitheliomatous hyperplasia should alert surgeons to its potential hazards, to the probability of recurrence if it is only marginally excised, and to the possible later development of similar lesions.


Chronological versus skeletal age, an evaluation of craniofacial growth. Skeletal and chronologic ages of both female and male populations were compared relative to the degree of concurrence between the two age-indices at the various age levels. Maxillary and mandibular cephalometric measurements were similarly compared for both sex groups. Individual's comparisons of facial changes were made relative to their respective chronologic and skeletal ages. The significance of a skeletal vs. chronologic age discrepancy and its relationship to the timing of facial growth was demonstrated. Clinical implications were discussed.


[Post-operative hyperaldosteronism and related endocrine perturbations (author's transl)]. Electrolytes disturbances during operative period are believed to be related to an hyperaldosteronism produced by anaesthetic management and surgery. Effects of ethrane anaesthesia and surgery on hydroelectrolytic metabolism and endocrin function were investigated in 11 patients submitted to an abdominal surgery. Plasma and urinary levels of aldosterone were increased (x3) significantly (p less than or equal to 0.001) during operation, then decreased gradually in post-operative period, and return to normal values when Na/K ratio is reversed in urines. Relationship between hyperaldosteronism and other changes in endocrine function are established by determination of following hormones: A.C.T.H., cortisol, plasma renin activity (P.R.A.) catecholamines in plasma and urinary levels of 17-ceto, 17-hydroxysteroids and catecholamines. Ethrane anesthesia give a good neurovegetative stability since plasma catecholamines levels are not affected significatively. Plasma aldosterone level is correlated with urinary aldosterone and plasma renin activity. Plasma A.C.T.H. is much more increased at the operative time and decreases rapidly instead of plasma cortisol which decreases more slowly. Relationship of this hyperaldosteronism with anesthetic management, surgical stress intestinal transit disturbances, other endocrine function changes is discussed.


[Anaesthesia. Resuscitation problems arising from the surgical treatment of chemodectomas in the carotid fork (author's transl)]. Chemodectomas in the carotid fork are rare and usually benign tumours. Their removal by surgery creates certain problems in terms of operating technique since they are, anatomically, awkwardly situated. An additional problem arises from loss of blood resulting from their removal and possible cardiac disturbance which might affect the functioning of the carotid sinus should the tumours have been situated in this region. Furthermore, the possible eventuality of having to clamp the internal carotid for a short or even long time, should the operation require it, presupposes a perfect knowledge of the patient's cerebral circulation. Hence, therefore, the necessity of a verification of this circulation by centrolateral carotid arteriography to confirm the permeability of the circle of Willis and a potentially good supply of blood when the blood in the region of the tumour is restricted. It is equally necessary to have a complete record of the general state of the patient's cardiovascular, circulatory, respiratory, renal and neurological conditions. These must, within certain limits, be deemed satisfactory before the decision to operate is taken. Indeed, it is these conditions that will determine the per-operative as well as the post-operative condition of the patient.


[Quantitative analysis of low concentrations of cristobalite in thin layers by x-ray diffraction]. A new x-ray diffraction procedure for the determination of cristobalite in the presence of amorphous silica is described. The standards are obtained by deposition of thin layers of watery suspensions of cristobalite and amorphous silica mixtures on silver or lead disks or cellulosa filters. Six calibration curves are then calculated to reduce weight and sampling errors. Six mcg of cristobalite mixed with 594 mcg of amorphus silica is the lowest detectable limit. The method may be used for the analysis of both raw materials and respirable dust.


[Possibility of siliceous pollution in goldsmith workshops]. The AA. carried out a research in order to determine the entity and the localization of siliceous dust pollution in goldsmith-field in the industrial area near by Valenza Po, Northern Italy. The research put attention just on the microfusion process and it was carried out among factories that attend to this process continuously. In fact the "scagliola" is used only during microfusion. It is a sort of mixture containing a high quantity of quartz and cristobalite used for the moulding. Dangerous dusts are caused by the mentioned "scagliola" during stripping and mixing. The use of right technical precautionary measures can surely eliminate the risk.


[Urinary kallikrein in cadmium-exposed workers]. The urinary kallikrein activity was determined in a group of 20 young workers exposed to cadmium and to lower concentrations of lead and other toxic agents. Two of them were suffering from labile hypertension. The urinary kallikrein activity of exposed workers was found to be reduced by more than 80% in comparison with a control group.


[Radiological diagnosis of primitive hepatic tumors in infants (author's transl)]. Six primitive hepatic tumours (two benign and four malignant) collected over a period of seven years, are studied. The symptoms were mild or absent in many of the cases, and all were discovered after investigation of hepatomegaly or abdominal mass. The importance of the co-ordinated use of radiological and gammagraphical findings is pointed out.


[Ultrastructural study in four cases of cutaneous xanthomas in children (author's transl)]. Three cases are associated with a Reclinghausen disease. Histological findings show typical xanthoma. Electron microscopical study indicates: --numerous intracytoplasmic lipid inclusions of various type (droplets, crystals, concentric lamellar bodies, ceroid granules) in dermal cells (histiocytic foam cells, endothelial cells, Schwann cells, fibroblasts and most cells); --large intranuclear inclusions in some histiocytes containing few lipids droplets; these figures could be compared to a slice of "petrified wood"; their significance is as yet unknown (Liesegang rings?).


[Atopic dermatitis: a histologic and radioautographic study (after 3H-thymidine labelling) of epidermal and dermal lesions (author's transl)]. Skin lesions of atopic dermatitis (A. D.) have been studied histologically and radioautographically after in vitro incorporation of tritiated thymidine. The histopathologic aspects of epidermis in the different types of skin lesions are reviewed. The dermal infiltrate is mononuclear and not very abundant in all types of lesions. An enlargement of the epidermal proliferative compartment has been noticed. Labelled cells are distributed as follows (mean +/- standard deviation) : 46 +/- p. 100 in the basal layer; 37 +/- 6 p. 100 in the epibasal layer; 16 +/- 7 p. 100 in the upper layers. The basal and epidermal labelling indices have been found significantly increased in exudative and lichenified lesions as compared to xerotic areas and normal epidermis. The labelling index of the "round" cell infiltrate in the dermis was significantly higher than in irritant patch test reactions (p less than 0.001) but significantly lower than in allergic positive patch test reactions (p less than 0.001). This increased cell proliferation in the dermal infiltrate does not allow definite conclusions about immunopathogenesis of the disease: indeed, a large number of mediators, involved in the inflammatory reactions of A. D. lesions, can modulate cell proliferation.


[Study of a series of 158 parotidectomies and histological problems in mixed tumors of salivary glands (author's transl)]. About a homogeneous statististic of 158 parotidectomies, authors study repartition parameters of parotid gland tumors. They insist on particular surgical and evolutive problems in relation to histology sometimes very difficult.


[Importance of corn extract components for the biosynthesis of polymyxin B by B. polymyxa strain 1538]. The effect of some components of corn-steep liquor, such as biotin, organic nitrogen, inorganic phosphorus and other mineral elements on biosynthesis of polymyxin B by B. polymyxa, strain 1538 was studied. It was found that biotin and organic nitrogen had the most significant effect on the antibiotic accumulation. The effect of inorganic phosphorus and other mineral elements on accumulation of polymyxin by B. polymyxa, strain 1538 was less significant.


Streptomycin resistance in a streptomycin-producing microorganism. Cell-free extracts of Streptomyces bikiniensis contain an adenosine 5'-triphosphate-dependent kinase which inactivates streptomycin (Sm) and dihydrostreptomycin by phosphorylation. The products have been identified as streptomycin 6-phosphate and dihydrostreptomycin 6-phosphate. Activity was not present in logarithmic-phase cells, which were susceptible to 25 mug of Sm per ml. In stationary-phase cells, activity appeared 12 h before detectable Sm in the medium. These cells were resistant to more than 200 mug of Sm per ml. Certain S. bikiniensis isolates selected from cultures treated with acriflavine or ethidium bromide lost the ability to produce Sm and became susceptible to 10 mug of Sm per ml throughout their growth. Cell-free extracts of the dye-treated isolates did not inactivate Sm and lacked streptomycin kinase activity at all stages in development. Ribosomes from resistant cells bound the same amount of [(3)H]dihydrostreptomycin as ribosomes from susceptible cells, and there was no correlation between the uptake of [(3)H]dihydrostreptomycin and resistance. The Sm-inactivating enzyme was identified as streptomycin-6-kinase. These results suggest that phosphorylation by streptomycin-6-kinase is a major factor in resistance in S. bikiniensis.


Effects of amphotericin B and its methyl ester on the antiviral activity of polyinosinic:polycytidylic acid. Since the macrolide polyene antibiotics, amphotericin B (AmB) and its methyl ester (AmBME), augment interferon production by polyriboinosinic:polyribocytidylic acid [poly(I):poly(C)] in vitro, experiments were undertaken to determine how AmB and AmBME affect the antiviral activity of poly(I):poly(C) and interferon. AmBME increased the direct antiviral activity of poly(I):poly(C) 10(2)-to 10(4)-fold in L929, Flow 6000, and T98G cells. Viral replication, measured by either direct plaque formation or virus yield, was markedly reduced. Serum interferon levels in mice induced by poly(I):poly(C) were enhanced by concomitant treatment with AmB. However, the therapeutic effects of poly(I):poly(C) in encephalomyocarditis and Semliki Forest virus infections were not augmented by combined treatment with poly(I):poly(C) and AmB. In vitro, the antiviral effects of exogenous interferon were markedly inhibited by AmB and AmBME. This inhibition may have contributed to the adverse effects of the macrolide polyenes in encephalomyocarditis and Semliki Forest virus infections in vivo. These findings further substantiate the effectiveness of macrolide polyenes in augmenting cellular penetration of macromolecules. However, therapeutic application may be limited by the complex interactions which occur between compounds administered in vivo.


Pharmacokinetics of E-5-(2-bromovinyl)-2'-deoxyuridine in mice. The pharmacokinetics of the newly developed anti-herpes agent, E-5-(2-bromovinyl)-2'-deoxyuridine, was compared with that of the standard anti-herpes drug 5-iodo-2'-deoxyuridine. Both compounds were administered to mice at 100 mg/kg by either the intraperitoneal, subcutaneous, or oral route. The active blood drug levels achieved by E-5-(2-bromovinyl)-2'-deoxyuridine were considerably higher than those attained by 5-iodo-2'-deoxyuridine (serum peak concentrations: 40 to 100 and 4 to 10 mug/ml, respectively). Active blood drug levels could still be found 320 min after oral administration of E-5-(2-bromovinyl)-2'-deoxyuridine.


Effect of heat treatment on the performance of tryptose-sulfite-cycloserine agar for enumeration of Clostridium perfringens. Dissolving dehydrated tryptose-sulfite-cycloserine agar by only boiling or microwaving was found to inhibit Clostridium perfringens colony development in pour plates when compared with C. perfringens recovery in tryptose-sulfite-cycloserine agar prepared by autoclaving.


Evaluation of beta-subunit chorionic gonadotropin as an aid in diagnosis of trophoblastic disease. The advent of the radioimmunoassay of Beta subunit chorionic gonadotropin (BhCG) has eliminated a major problem in following the patient with gestational trophoblastic neoplasia (GTN). Whole hCG cross reacts with luteinizing hormone (hLH) causing difficulties when GTN patient titers fall to levels coincidental with pituitary levels of hLH. The use of the Beta subunit of hCG in radioimmunoassay has eliminated this problem because there is essentially no cross reaction between the B-subunit of the hCG and hLH. A review of the use of this sensitive assay in the management of patients with GTN is presented.


Glutaraldehyde inactivation of exotic animal viruses in swine heart tissue. Glutaraldehyde, 0.2%, in a 1:100 (wt/vol) ratio, inactivated four animal viruses (foot-and-mouth disease, swine vesicular disease, African swine fever, hog cholera) in swine heart tissues during 11-day exposures at 22 to 26 degrees C.


Microbial cleavage of various organophosphorus insecticides. Bacteria able to utilize Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, Trithion, dimethoate, Dylox, methyl parathion, and Vapona as sole phosphorus sources were isolated from soil and sewage. Individual isolates used from 3 to 10 of these insecticides as sole phosphorus sources. The extent of growth of two Pseudomonas strains in media containing diazinon and malathion was in the range expected from the amount of insecticide supplied, and their proliferation resulted in disappearance of the chemical. Resting cells of the pseudomonads derived from cultures grown on diazinon or malathion but not orthophosphate caused extensive destruction of these two organophosphates in the presence or absence of chloramphenicol. Extracts of the two bacteria derived from organophosphate-grown cultures catalyzed the disappearance of Aspon, Azodrin, Dasanit, diazinon, malathion, Orthene, parathion, and Trithion but not dimethoate, Dylox, methyl parathion, and Vapona. Results from gas chromatographic analysis suggested that the extracts formed dimethyl phosphate from azodrin, dimethyl phosphorodithioate from malathion, diethyl phosphorodithioate from Trithion, and diethyl phosphorothioate from Dasanit, diazinon, and parathion. Dimethyl phosphate, dimethyl phosphorothioate , dimethyl phosphorodithioate, diethyl phosphate, and diethyl phosphorothioate were not used by the pseudomonads as sole phosphorus sources.


Raffinose increases sporulation and enterotoxin production by Clostridium perfringens type A. Replacement of starch with raffinose in Duncan and Strong sporulation medium improved percent sporulation in six of eight strains tested. Enterotoxin concentration in cell extracts was increased in the case of four of five known enterotoxin-positive strains. With strain NCTC 10240, levels of 0.3, 0.4, and 0.5% raffinose produced the highest enterotoxin concentration 300 to 320 micrograms of enterotoxin per mg of cell extract protein. At a level of 0.4% raffinose the highest enterotoxin concentration in cell extracts of NCTC 10240 occurred after 8 h of growth in Duncan and Strong medium. Enterotoxin produced in the presence of starch or raffinose by three separate strains all migrated at similar Rm by polyacrylamide gel electrophoresis.


Method of soil column preparation for the evaluation of viral transport. A method for packing soil columns to investigate viral transport phenomena is described. The columns were 10 cm in diameter and ranged from 33 to 100 cm in length. Field conditions of the soil, including bulk density and profile, were reproduced in columns. Ionic gradients resulting from sequential applications of wastewater and distilled water affected the movement of poliovirus I (Chat) through soil. Compared with 33-cm- and 66-cm-length columns, lower concentrations of infectious virions were observed in the percolates from 100-cm soil columns. These results may be attributed to the greater pore volume in the longer columns (the greater volume of soil contained in these columns), whereas the volume of liquid applied was constant for all columns.


Survival of poliovirus within organic solids during chlorination. Poliovirus in fecal homogenates was used to determine the protection against inactivation by chlorination afforded virus that was occluded within particulates. Virus that was closely associated with or occluded within small fecal particulates was protected. A fourfold increase in combined residual chlorine was required to achieve the same degree of inactivation for occluded virus as for free or secondarily adsorbed virus. A combined chlorine residual of 6.6 mg/liter was necessary to achieve 50% inactivation in 15 min at pH 8.0 and 22 degrees C in a particulate suspension containing occluded virus compared to 1.4 mg/liter for free virus. These differences were found to be relatively small compared to differences due to the presence of dissolved organics or between free and combined chlorine residuals. The results suggest different mechanisms of protection due to adsorption and occlusion.


Granular cell basal cell carcinoma. A distinct histopathologic entity. In two cases of basal cell carcinoma with prominent granular cell features, light microscopic examination showed a tumor with the general configuration of a nodular basal cell carcinoma. Focally, there were masses of cells with eosinophilic, granular cytoplasm and large cytoplasmic inclusions, strongly suggestive of granular cell myoblastoma. Ultrastructural observations in one case showed numerous lysosome-like organelles that were similar to those described for granular cell myoblastoma, but were identical to those described for the granular cell variant of ameloblastoma, a tumor that frequently resembles basal cell carcinoma. Additional features included tonofilaments and desmosomes, both of which support an epithelial origin for the granular cells in this rare variant of basal cell carcinoma.


Metastatic ductal carcinoma of the parotid gland in a patient with sarcoidosis. A 38-year-old man with a history of sarcoidosis and ductal carcinoma of the parotid had metastasis to the pleura and skin. This skin metastasis resembled carcinoma of the breast. There is a possibility of sarcoidosis with its depressed cellular immunity predisposing to malignancy.


Cytomegalovirus and blood transfusion in neonates. A fatal case of neonatal cytomegalovirus (CMV) infection attributed to exchange transfusion is described. The incidence of CMV transmission by exchange and other neonatal transfusion was studied, and the use of CMV antibody-free blood for these procedures was shown to be effective in preventing CMV infection in neonates.


Toxic effects of dietary polybrominated biphenyls on mink. Serial levels of fireMaster FF-1, a commercial mixture of polybrominated biphenyls (PBB), and tissues from chickens and a cow that had previously consumed PBB were fed to mink to ascertain the chronic effects of the commercial and "metabolized" form of this compound on mink. Diets that contained 6.25 ppm (or more) PBB were lethal to adult mink within 10 months. One to 2.5 ppm dietary PBB fed for 9 months had an adverse effect on litter size, kit weight at birth, and kit survival. The data suggest that the PBB derived from contaminated beef and poultry was more toxic than the original PBB. The clinical signs of PBB poisoning in mink were food rejection, weight loss, and unthrifty appearance, and fatty infiltration of the liver. Based on these findings, mink must be considered highly susceptible to PBB toxicity. PBB residue levels 60 times the amount in the diet were found in the adipose tissue of the PBB-treated animals.


Collagenase production by rheumatoid synovial cells: morphological and immunohistochemical studies of the dendritic cell. The dendritic cells of dissociated, adherent rheumatoid synovial cell cultures are recognised by their distinctive morphological features--compact cytoplasm around the nucleus and long, branched cytoplasmic extensions. Such cells usually composed approximately 10% of the total adherent cell population but could vary from as few as 2% to as many as 40% with different synovial specimens. Histological studies have shown the cells to contain many mitochondria and large, spherical cytoplasmic inclusions which often distort the dendritic extensions. Although lysosomes were observed, no evidence for phagocytic activity was obtained. Immunolocalisation studies by means of a monospecific antibody to human collagenase have shown that the dendritic cell attached to a collagenous substratum produces and releases this enzyme in vitro. In contrast collagenase was detected in only a few of the fibroblast- and macrophage-like cells, and it was always intracellular. It is proposed that the dendritic cell may have an important role in the pathophysiology of the rheumatoid joint, particularly with regard to collagenase-mediated cartilage destruction.


Calcium infusion: a new provocative test for insulinomas. Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas.


New aspects of androgens, prolactin, and ACTH interaction in men. Some endocrine effects of prolactin (PRL), ACTH, and corticosteroids in testicular function were evaluated by measuring, in normal men, the effects of short-term experimental stimulation and suppression of either plasma PRL levels or adrenal function on plasma androgen profile. PRL levels were increased by administration of metoclopramide or sulpiride or suppressed with bromocryptine. Long-acting testosterone (T) was injected at 8 a.m. on one day in a control period and during a 9-day period of metoclopramide administration. PRL increase was accompanied by a rise in plasma 17-hydroxyprogesterone and T, whereas PRL suppression induced an increase in 5 alpha-dihydrotestosterone (DHT) plasma levels. Peripheral converions of T into DHT and androstenedione, noted after T injection, decreased during concomitant metoclopramide administration. Plasma testicular androgen levels were lowered after long-acting ACTH injections as well as after 24-hr cortisol administration, but the metoclopramide-induced PRL increase appeared to prevent the suppressive effects of ACTH on plasma T. A low-dose dexamethasone treatment did not modify testicular androgen levels. Experimentally induced hyperprolactinemia may have a stimulatory effect on testicular androgen secretion as well as a lowering action on 5 alpha reduction and oxidative T metabolism in man. On the other hand, ACTH-induced androgen suppression seems to be mediated through high circulating levels of corticosteroids; furthermore, PRL and corticosteroids might have reciprocal influences that modulate their effects on testicular function.


Pyrimidine synthetic enzymes of the rat testis and epididymis following unilateral vasectomy. The de novo pyrimidine synthetic enzyme, aspartate carbamyltransferase, and the two pyrimidine salvage enzymes, uridine and thymidine kinases, of the rat testis and epididymis were measured 1, 2, 4, 6, 8, and 10 wk following unilateral vasectomy. Vasectomy had no effect on organ wet weights and on testicular and epididymal asparate carbamyltransferase and thymidine kinase activities. Increases in the uridine kinase activity of the caput epididymidis at 2 wk and of the cauda epididymidis from the second to the sixth weeks were the only significant enzymatic changes observed.


Effect of calcium concentration, isoproterenol, and McN-2165 on fetal rat heart rate and cyclic AMP level. The fetal rat heart in organ culture was used to study the interaction of calcium with the cardioactive agents. McN-2165 is an agent that produces negative chronotropism and elevation in cyclic AMP levels in this preparation. A concentration of 2.76 mM calcium ion antagonized the negative chronotropic action and prevented the cyclic AMP elevation produced by this agent. Positive chronotropic actions of isoproterenol were prevented by decreasing the calcium level below 1.84 mM.


The action of nicotine on the pituitary-adrenal cortical axis. Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow.


Effects of betamethasone on the stimulation of corticosterone secretion in rats. The effects of betamethasone on the elevation of rat plasma corticosterone levels by nicotine (400 microgram/kg s.c.), urethane anaesthesia and psychological stress have been studied. Betamethasone pretreatment (5 mg/kg given in the drinking water over 24 hr) initially suppressed the response to all three stimuli but, after 24 hr, only the response to urethane remained totally suppressed. Nicotine administered at this time to the urethane anaesthetised rats caused an increase in plasma corticosterone, apparently by stimulation of the autonomic nervous system. The results suggest that, following betamethasone, there is a prolonged delay in the recovery of the specific mechanism through which urethane stimulates pituitary-adrenal function rather than a total blockade of the effects of all stressful or chemical stimuli on ACTH secretion.


Effects of streptomycin on the cortical neurons in the cat. Data concerning the effects of streptomycin application on the brain cortex are very scarce and nonconcordant, despite routine intra-thecal administration of this drug. Experiments peformed in 15 adult cats permitted us to observed that application of streptomycin sulphate on the brain cortex leads to a real cortical depression, demonstrated by the disappearance of spontaneous spikes, lack of cortical fast activity and lack of hippocampal theta activity. The direct cortical response disappears too and sometimes even the transmission towards the deep structures of neuronal activation induced by high intensity or repetitive stimuli. The depressing activity of streptomycin resembles to a spreading depression, with an effect limited only to the hemisphere where the drug is applied. The difference between our results and those of other authors can be explained by the different degree of purity of the streptomycin used in the experiments.


Comparison of the inhibitory effects of acetylsalicylic acid and trifusal on enzymes related to thrombosis. Triflusal is a new antithrombotic agent, structurally similar to acetylsalicylic acid (ASA), which has been shown to possess a different pharmacological profile, suggesting a different mechanism of action for both compounds. To confirm this hypothesis we have studied, comparatively, the inhibition by  triflusal and ASA of the activity of several enzymes involved in the equilibrium of platelet haemostasis, namely, prostaglandin-synthetase system (PG-synthetase), cyclo-oxygenase, thromboxane-synthetase and cAMP-phosphodiesterase. Results indicate that trilfusal is 60% less potent as inhibitor of cyclooxygenase (biological method) and of prostaglandin biosynthesis (spectrophotometric method ) than ASA. On the contrary, triflusal is five times more potent than ASA as inhibitor of cAMP phosphodoesterase. Inhibition of thromboxane-synthetase by both compounds is negligible and without physiological significance. These results suggest a mechanism of action of trifusal that might explain the different pharmacological profile between triflusal and ASA as antithrombotic agents.


Hypocalcemia. Differential diagnosis and mechanisms. There is much individual variability in the clinical manifestations of hypocalcemia. The rapidly of the development of hypocalcemia will determine whether or not symptoms will be present. Signs and symptoms of hypocalcemia consisted of tetany (Chvostek's and Trousseau's signs), seizures, diminshed to absent deep tendon reflexes, papilledema, mental changes (weakness, fatigue, irritability, memory loss, confusion, delusion, hallucination), and skin changes. Etiologic factors for hypocalcemia in man include (1) decreased calcium absorption or increased loss from the gastrointestinal tract; (2) parathyroid hormone deficiency; (3) skeletal resistance to parathyroid hormone; (4) ineffective parathyroid hormone; (5) decreased production or increased degradation of 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol; (6) increased complex formation with calcium; (7) increased skeletal uptake of calcium; (8) hypomagnesemic state; and (9) direct inhibition of bone resorption. Measurement of total and ionic calcium, magnesium, parathyroid hormone, vitamin D metabolites (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol), and nephrogenous cyclic adenosine monophosphate are especially helpful in the laboratory evaluation of the hypocalcemic patient.


[Congenital cardiopathies in a tropical environment. Study of 259 cases seen at Abidjan from 1969-1976]. The authors report the study of 259 cases of congenital heart disease observed at Abidjan between 1969-1976. The average age of the patients was 7-8 years ranging from the newborn to 41 years. The principal malformations encountered in their order of frequency were: ventricular septal defect 38.6 p. 100, atrial septal defect 13.8 p. 100, Fallot's tetralogy 8.8 p. 100, pulmonary stenosis 8.1 100, patent ductus arteriosus 7.7 p. 100, atrioventricular canal 7.7 p. 100, transposition of the great arteries 3.8 p. 100, coarctation of the aorta 2.3 p. 100. There were associated malformations in 31 cases. 42 patients were catheterised at Abidjan, 28 were operated, 12 at Abidjan. These statistics are compared to those already reported of congenital heart disease in tropical and western countries. There is little difference in the distribution of the various cardiac malformations. Two congenital malformations appear to be less frequent in the Tropics: coarctation of the aorta and aortic stenosis.


[Study of the renin-angiotensin system in 2 cases of Wilm's tumor with severe arterial hypertension]. Two children who presented with Wilm's tumour and severe hypertension are described. The hypertension, which was secondary to excessive renin secretion, regressed after unilateral nephrectomy. In one child the total quantity of renin in the tumour was high and the peripheral plasma renin was also increased. The latter was unaffected by posture or a low salt diet and on angiography there was no compression of the renal arteries. Electron microscopy of the tumour cells showed numerous intra-cytoplasmic granules. In the other child the peripheral renin was only moderated elevated and could be stimulated by changes in posture or a low salt diet. Angiography demonstrated a large tumour that was compressing the renal artery on that side. No renin was detected in the tumour. In this child the inappropriate secretion of renin was probably due to renal parenchyma close to the tumour causing reno-vascular hypertension. The anti-hypertensive effect of propranolol given pre-operatively was excellent.


Plasma cells with inclusions containing iron. Iron inclusions in plasma cells of the bone marrow of an individual suffering from megaloblastic anemia due to folate deficiency were examined by electron microscopy. It seems that the iron is introduced into the plasma cell by micropinocytosis. The speculation of possible transfer of iron from the reticulum macrophage to the plasma cell is raised.


Isoantigens A, B, H in normal skin and tumors of the epidermal appendages. Isoantigens A, B, H(O) in biopsy specimens of 26 normal skin and in 35 adnexal tumors were studied by the red cell adherence (RCA) test of Davidsohn. Isoantigens were detected in the stratum corneum, stratum granulosum, stratum spinosum, acrosyringium, keratogenous zone of hair follicle, eccrine duct, and eccrine gland. The apocrine gland and duct consistently had negative test results for isoantigens. Seventy percent of all tumors tested contained isoantigens and included syringoma, hidrocystoma, syringocystadenoma papilliferum, spiradenoma, eccrine poroma, dermal duct tumor, clear cell hidradenoma, and cylindroma. We interpreted the presence of isoantigens in adnexal tumors as being evidence of immunologic maturity with differentiation toward eccrine structures. The RCA test is a new, sensitive, immunologic technique that can complement enzyme histochemical stains and electron microscopy in the study of the histogenesis of adnexal skin tumors.


Membranous nephropathy. Its association with multicentric angiofollicular lymph node hyperplasia. Multicentric angiofollicular lymph node hyperplasia of the plasma cell type with systemic manifestations developed in a 51-year-old man. One year later, the nephrotic syndrome due to typical immune complex mediated membranous nephropathy developed. Elevated titers to Epstein-Barr viral antigens suggesting reactivation of a latent infection were present. The patient has required conservative medical management only. The association of membranous nephropathy with angiofollicular lymph node hyperplasia lends further evidence to the postulate that the disorder is a manifestation of chronic immune stimulation by a foreign antigen.


Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: thermal sensitivity and rabbit virulence markers. Eleven cloned North American pseudorabies virus (PRV) strains and the European vaccine strains K and BUK were characterized by their thermal sensitivity and rabbit virulence markers. Heat sensitivity of the strains and isolates ranged from the highly heat resistant strain K, to the extremely heat labile strain BUK and isolate Be. The inactivation curves of each virus were transformed to the logarithmic scale and their standardized slopes and predicted virus survival values at 30 minutes were plotted against each other. The result was a distribution of points that represented a thermal sensitivity spectrum (TSS). Virus strains were subsequently categorized into 1 of 3 groups according to their position in the TSS. Viruses were also categorized into three groups according to their ability to clinically infect rabbits, their ability to produce pruritus and the time required to kill. When individual strains were described according to their marker profiles, 5 of 9 possible marker combinations were revealed. The 2 vaccine strains were each described by separate profiles. Virulent field isolates were characterized by 1 of 3 different profiles.


Colostral immunity in piglets from sows vaccinated with inactivated Aujeszky disease virus vaccine. Neutralizing antibodies against ADV were transmitted from sows, vaccinated with inactivated ADV adjuvanted with DEAE dextran, to their offspring via colostrum. The suckling piglets were protected by colostral immunity against contact infection with ADV at week 1 p.p., however, they were not protected against i.n. infection (10(8) TCD50). At 2 and 3 weeks p.p. all the piglets were protected against both contact infection and i.n. infection. At 4 weeks p.p. 50 per cent of the litter were protected against i.n. infection, in spite of very low antibody titres (1:2--1:4). The colostral antibodies did not interfere with active antibody response when the piglets were vaccinated with the inactivated vaccine from 2 weeks p.p. onward. Lymphocytes from suckling piglets of a vaccinated sow showed in vitro reactivity (enhanced 3H-thymidine incorporation) against ADV and BHK antigen, both contained in the vaccine used for the immunization of the sow.


Biological properties of mouse interferon bound to a high molecular weight carrier: Blue Dextran 2000. Mouse C-243 cell interferon (IF) binds to Blue Dextran 2000 (BD). The BD-IF complex could be precipitated by polyethylene glycol. When 0.05 to 0.2 per cent solutions of BD were used for binding IF, the recovery of IF activity in the sediment was complete. The BD-IF complex was shown to have high antiviral activity, it was stable for months at 4 degrees C but it was inactivated by heating at 37 degrees, 56 degrees and 65 degrees C as native IF. The rate of clearance of IF bound to BD from the mouse peritoneal cavity was found to be significantly slower than that of native IF. The BD-IF complex was highly immunogenic for rabbits and sheep. Furthermore, the BD-IF complex was neutralized to a greater extent by specific antibodies than native IF.


Latent infection of cattle with bovid herpesvirus 2. In a series of experiments, 10 calves were infected by different routes with bovine mammillitis strain of bovid herpesvirus 2 (BHV2). Nine of the calves developed lesions and BHV2 was isolated from 8 calves. At intervals, after clinical recovery, the calves were given a course of corticosteroid by intravenous injection. Subsequently 7 calves developed lesions and from 3 calves BHV2 was reisolated. The shortest interval between initial infection and reisolation of virus was 10 weeks. In one calf virus was recovered on 3 occasions, at intervals of 20, 44 and 74 weeks post-infection. It is probable that BHV2 can occur as a latent infection in calves and that BHV2 should be included among the herpesviruses known to remain latent.


Studies on avian infectious bronchitis virus (IBV). II. Propagation of IBV in several cultured cells. The growth of ten strains of avian infectious bronchitis virus (IBV) in several cultured cells was examined. The cultured cells used were chick kidney (CK), chick embryo (CE), HeLa and BHK-21 cells. The results obtained can be summarized as follows. 1. All the strains showed similar growth curves in CK cells. Progeny viruses appeared in the culture medium 4 to 6 hours after inoculation and peak virus titers of 10(6.5)--10(8.5) TCID50 per 0.1 ml were obtained after 36 hours. A cytopathogenic effect (CPE) was detected within 24 hours. No distinct CPE and low multiplicities were observed on culturing at 30 degrees C. 2. All strains replicated in CE cells, although only small amounts of virus were produced. No CPE was observed. 3. Only Beaudette-42 and Holte strains grew in BHK-21 cells. 4. No IBV strains grew in HeLa cells.


Virus isolation and serum antibody responses after infection of cats with transmissible gastroenteritis virus. Brief report. Transmissible gastroenteritis virus was administered orally to cats. No clinical disease resulted but infectious virus was isolated from faeces for up to 22 days after infection and serum antibody was detected by neutralisation and immunofluorescence tests.


Possible pitfalls in the study of IgG receptors produced by herpesvirus-infected cells. Brief report. The presence of specific antibodies to human herpesviruses in certain purified human IgG preparations from commercial sources may produce misleading results when such preparations are used in studied on the IgG receptors produced by virus-infected cells.


Isolation of an adeno associated virus from sheep. Brief report. An adenovirus and a spherical virus 20--24 nm diameter were isolated from ovine faeces. The small virus replicated in the nucleus, and was associated especially with the nucleolus. It haemagglutinated guinea pig and human erythrocytes, was thermostable and required an adenovirus for replication. It is concluded that this represents the first recorded isolate of an ovine AAV.


[HBS Ag-positive hepatocellular cancer (pathomorphologic study)]. Pathomophological and histochemical analysis of 7 autopsy cases of primary hepatocellular carcinoma was performed. Direct immunofluorescence with an anti-HBsAg serum and staining with orsein according to Shikata's method revealed the presence of HBsAg in hepatocytes of the cirrhotic tissue and in tumour cells. Cirrhotic nodes were found to have numerous HBsAg-positive cells, whereas in the tumour tissue the number of such cells was insignificant and they were found only in highly differentiated areas. In all cases, highly differentiated hepatocellular carcinoma was combined with active large nodular cirrhosis.


Nuclear bodies in nerve cells of two patients with normal-pressure hydrocephalus. Biopsy specimen fragments from two patients with normal-pressure hydrocephalus were studied using ultrastructural methods. Simple nuclear bodies were found in all layers of the cortex and white matter, whereas complex ones were only seen in the fifth and sixth layers and in the underlying white matter. There may be a relationship of these nuclear bodies, either to the neuroglial proliferation observed in both patients or to the existence of a viral infection of the CNS.


Ocular manifestations of familial high-density lipoprotein deficiency (Tangier disease). Corneal clouding is one of the manifestations of Tangier disease, an inherited disorder in which cholesterol-rich lipids are deposited in various tissues of the body. The cause of the corneal clouding is unknown. This study documents the clinical course and conjunctival biopsy findings of a 60-year-old man who was one of the earliest patients to be recognized with Tangier disease and in whom progressive corneal clouding developed in adult life. Noteworthy in the biopsy specimens were birefringent lipid particles that were predominantly present in degenerating pericytes of the conjunctival vessels.


Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney. Affinity chromatography was used to isolate aminoglycoside receptors from inner ear tissues and kidney. Neomycin was immobilized on glass beads and served as the stationary phase in column chromatography. Fractionation of an organic tissue extract on this matrix demonstrated two components with high affinity for neomycin: phohphatidyl inositol phosphate and phosphatidyl inositol diphosphate. The toxicity of aminoglycosides is explained on the basis of a drug-interaction with these lipids.


Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase. The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.


Infectious bursal disease viral infections. II. The relationship of age, complement levels, virus-neutralizing antibody, clotting, and lesions. Experimental infection with infectious bursal disease virus (IBDV) reduced the complement (C) titer in 8-week-old chickens on days 3, 5, and 7 postinfection. Since the C titer was much lower in normal 2-week-old chickens than in normal 8-week-old chickens it could not be determined whether there was a reduction in titer during the infection process. Virus-neutralizing antibody rose rapidly following infection in both 2- and 8-week-old chickens. Hyper-immune serum given during infection in an attempt to produce immune complexes did not increase disease severity in either 2- or 6-week-old susceptible chickens.


Effects of avian reovirus on Marek's disease (MD). I. Suppression of MD development. The effects of an avian reovirus on the development of acute Marek's disease (MD) were studied by exposing chickens to Reo-W isolant of avian reovirus before infecting them with an oncogenic MD herpesvirus (MDHV). Four separate trials were made in a similar manner, 2 trials with an experimental line of White Leghorn (WSU-VS) highly susceptible to MD, and 2 trials with a commercial strain of meat-type (C-MT) chicken. MD mortality and/or incidence of gross MD lesions were consistently reduced by preexposure to avian reovirus. The suppression was more apparent in the WSU-VS than in the C-MT birds, and appeared greater with exposure to reovirus via the respiratory route than with the alimentary route.


Growth kinetics of embryo- and organ-culture adapted Beaudette strain of infectious bronchitis virus in embryonated chicken eggs. Three Beaudette strains of infectious bronchitis virus (IBV) [two chicken-embryo trachea-culture-adapted (E71CET10 and E71CEK10CET30) and one embryo-adapted (E72)] were propagated in 10-day-old embryonated chicken eggs (CE) to investigate growth and lethality patterns. The E72 and E71CEK10CET30 viruses were similar in growth pattern as to logarithmic phase and maximum virus production, but 95% of the CE mortality with E72 virus occurred between 20 and 32 hours whereas with E71CEK10CET30 60% mortality occurred between 36 and 84 hours. The yield of the E71CET10 virus was minimum, with little lethality.


Transmission of acute respiratory disease (rhinotracheitis) of turkeys. Clinical signs of acute respiratory disease of turkeys were transmitted to susceptible day-old poults by direct contact, litter contact, and drinking water. Attempts failed to transmit the disease by air (cage-to-cage) or by oral and nasal inoculation with feces, nasal exudates, or nasal turbinate extracts. The disease was not transmitted by inoculation with white blood cells. Chicks were not affected by the disease, but young quail developed signs of respiratory disease when exposed to contaminated drinking water. Thus, acute respiratory disease in turkeys appears to be of an infectious nature, and the infectious agent(s) probably exist in the heavily contaminated environment used to house young commercial turkey poults.


Growth of infectious bursal disease virus with plaque formation in chick embryo fibroblast cell culture. The WA69 isolant of infectious bursal disease virus (IBDV) induced cytopathic effects and plaque formation in chick embryo fibroblast (CEF) cultures after serial passages in embryonated eggs and then in CEF cultures. The plaque-forming agent was cloned (designated WA69 clone) and identified as IBDV on the basis of serologic response in inoculated birds and its antigenic relationship to other known IBDV isolants. The WA69 clone replicated rapidly in CEF cultures, reaching peak titers at 48 hours postinoculation, and the virus caused only minimal histologic lesions of the bursa when inoculated into 3-week-old chicks from a specific-pathogen-free flock. The growth of IBDV in CEF cultures with plaque formation may provide a simple in vitro system for virological and serological studies of IBDV.