Human leukocyte migration inhibitory factor (LIF). IV. 3',5'-cGMP protects LIF against inactivation by the esterase inhibitor phenylmethylsulfonyl fluoride. Recently reported experiments suggest that human leukocyte migration inhibitory factor (LIF) has properties of an esterase and a protease with substrate specificities directed against arginine esters and amides. Also reported previously, the synthetic phosphodiester bis-p-nitrophenyl phosphate (BNPP) but not various phosphomonoesters preserve LIF activity in the presence of the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF). In this paper I demonstrate that guanosine 3'5'-cyclic monophosphoric acid (3',5'-cGMP), a naturally occurring phosphodiester, at concentrations in excess of 10(-5)M also protects LIF against PMSF inactivation. The effect seems specific for the diester bond, its position in the nucleotide, and the guanine base. The possibility that LIF may be a multifunctional or an allosteric enzyme regulated by 3',5'-cGMP is discussed.


[Bronchopulmonary hamartomas, chondromas, fibromas and myxomas]. The observation of 23 bronchopulmonary hamartomas, 9 chondromas, one fibroma and one myxoma has provided insight into the particularities of these tumors. The group of hamartomas, tumors of "erroneous mixture of tissue", included 20 cases which can be considered a malformation of the entodermal bronchial anlage, and 3 cases which can be regarded as a malformation of the mesenchymal anlage. The first type consists of multiple cleft-like spaces surrounded by ciliated and cuboidal epithelium. There are no alveolar cells. Cartilaginous, fibrous, myxomatous and lipomatous tissue and lymphocytes are also found. The second type consists mainly of undifferentiated mesenchymal cells with tubules, lined by cuboidal epithelial cells or an intestinal type of mucus-secreting epithelium. There may be some immature alveoli, but no ciliated epithelium is found. In contrast to the hamartomas, the chondromas are not derived from a dysontogenetic malformation of the bronchopulmonary tissue but are tumors which develop directly from the bronchial cartilage and are for this reason mainly localized in the endobronchial region. A special form seen in one case is association of pulmonary chondromas, gastric leiomyomas or leiosarcomas and extra-adrenal paraganglioma, though the latter is not always present.


Fasting decreases triiodothyronine receptor capacity. Fasting decreases the ratio of hepatic nuclear to serum triiodothyronine (T3) by diminishing the binding capacity of nuclear T3 receptors. In combination with the lower serum T3 concentration caused by fasting, the decrease in receptor content results in a marked decrease in nuclear T3-receptor complexes. The changes in T3 receptor content and circulating T3 in fasted animals appear to be independent synergistic adaptations for caloric conservation in the fasted state. Unlike changes in hormonal level, the modification of nuclear receptor content provides a mechanism that may protect cells with a low caloric reserve independently of the metabolic status of the whole animal.


Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls. Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers ("null" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.


Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor. The conformation of [Leu5]enkephalin is produced by a Tyr-Gly-Gly-Phe beta bend stabilized by antiparallel hydrogen bonding between tyrosine and phenylalanine. On the basis of a comparison of the observed structure with the structure of known opiate agonists, three hydrophilic and two hydrophobic regions have been identified as contributing to the recognition of the molecule at the opiate receptor site.


Motor nerve sprouting and acetylcholine receptors. Sprouting of motor nerve terminals was evoked by functional denervation of skeletal muscles brought about by presynaptic blockade or disuse. The amount of sprouting, determined by morphometric measurement, was correlated with the level of extrajunctional acetylcholine receptors. Sprouting was inhibited by blockade of acetylcholine receptors with alpha-bungarotoxin. Extrajunctional acetylcholine receptors may play an important role in eliciting motor nerve terminal sprouting.


Opiate receptors for behavioral analgesia resemble those related to the depression of spinal nociceptive neurons. With naloxone as antagonist, a dose-ratio analysis of the depression by morphine of nociceptive neurons in the spinal cord reveals that this opiate depression of single unit activity has the same pharmacological properties as observed with morphine analgesia. This suggests that the opiate receptor, mediating the observed cellular depression, and those mediating analgesia are presumably the same.


Immunity to antigens associated with primate C-type oncoviruses in pregnant women. Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed.


Inhibition of bone resorption in vitro by a cartilage-derived anticollagenase factor. A cartilage-derived factor containing a specific collagenous inhibitor was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. Morphologic and quantitative histometric examination revealed that this factor modulates osteoclastic activities.


Dual actions of substance P on nociception: possible role of endogenous opioids. Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.


Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines. Peripheral lymphocytes from human volunteers boosted with tetanus toxoid were cultured after in vitro infection with Epstein-Barr virus. Forty-four continuous lymphoblastoid lines were established which continued to secrete human gamma globulin; seven of these secreted antibody to tetanus toxoid. Subcultures derived from limiting dilution experiments continued to secrete the antibody. Some of these antibody-secreting cells have been in continuous culture for more than 6 months.


Genetic mapping of xenotropic leukemia virus-inducing loci in two mouse strains. In genetic studies of C57BL/10 and BALB/c mice, inducibility of xenotropic murine leukemia virus from tissue cultures by treatment with 5-iododeoxyuridine shows single gene segregation ratios. In both strains, the virus-inducing loci are on chromosome 1, linked to the Dip-1/isozyme locus, but the two may not be at allelic sites.


Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture. The opiate etorphine depresses monosynaptic excitatory postsynaptic potentials (EPSP's) elicited in spinal cord cells by activation of dorsal root ganglion cells in murine neuronal cell culture. The depression is reversed by naloxone. Statistical analysis of the synaptic responses reveals that the opiate reduces EPSP quantal content at this synapse without altering quantal size. Therefore, the opiate action is presynaptic and affects transmitter release rather than postsynaptic responsiveness.


Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication. Mouse spinal neurons grown in tissue culture were used to study the electrophysiological pharmacology of the opiate peptide leucine-enkephalin. Enkephalin depressed glutamate-evoked responses in a noncompetitive manner independent of any other effects on membrane properties. The results demonstrate a neuromodulatory action of opiate peptide functionally distinct from the conventional neurotransmitter class of operation.


[Scanning electron microscopy study of the synovial membrane in rheumatoid arthritis]. A comparative study under the scanning electron microscope of rheumatoid synovial membranes, 5 arthrosic synovial membranes, one tuberculous membrane, and 3 normal synovial membranes showed the pathological changes in the synovial membrane due to rheumatoid arthritis: Inflammatory aspect of the synovial fringes, surrounded by turgid and proliferative villous processes. Granular appearance of the endo-articular surface like a "pebble beach". Dome-shaped synoviocyte layer, standing out well above the subjacent intimal layer, associated with small round cells, also with a raised margin, covering most of the endo-articular surface. Plasma membrane of the superficial synovial cells, covered with numerous and various differentiations and abundant microvillous processes. Reticular deposits or layers, covering the apical poles of the synoviocytes.


[Interpretation of and indications for bone scintiscans]. The interpretatiton of a bone radioisotope scan requires perfect knowledge of normal skeletal appearances, shadows outside the bones and the various methods of expression of bony lesions: generally hyperfixations but sometimes isofixations or even hypofixations. A bone scan permits one to make an overall assessment of multiple bony lesions, determine the extent of a lesion, detect bony complications of a disease or treatment and seek the bony origin of a pain.


[Lumbosacral arachnoepiduritis. Clinical and etiologic aspects]. A series of 120 cases of lumbo-sacral arachno-epiduritis was studied from the clinical and etiological points of view. The recruitment of the cases and their classification were based on purely radiological criteria. The clinical symptoms were various, non-specific and without correlation with the radiological type. The course was chronic with a change in the distribution of the symptoms. The influence of the method of examination was discussed in the 9 cases discussed after a first myelography without surgical operation. All the forms suggesting epidural lesions were post-operative and observed mainly in cases of laminectomy.


[Gamma heavy chain disease associated with rheumatoid arthritis. Spontaneous disappearance of the pathologic protein]. The authors report the chance discovery in a man aged 53 years with serum positive rheumatoid arthritis, of gamma 3 heavy chain disease. The originality of this case depended on the absence of any detectable lymphoid proliferation and on the transient character of the pathological protein. Only the course after a long follow up will determine whether there is no incipient lymphoid proliferation and whether the heavy chain disease has disappeared permanently.


[Interactions of salicylates and other nonsteroid anti-inflammatory agents]. The salicylates are frequently associated in every day treatment with other non-steroid anti-inflammatory drugs, which justifies a study of their interactions. Animal pharmacodynamics, although interesting, is of little practical interest. Pharmacokinetic research seems to indicate that aspirin reduces the bio-availability of other non steroid anti-inflammatory drugs, which has not yet been confirmed clinically. It is still premature to conclude, but the already established facts suggest the continuation of such studies.


[Male pseudohermaphroditism. Etiologic diagnosis. 2]. The cause of male pseudohermaphroditism : polydystrophy, gonadal dysplasia, agenesis or precocious abiotrophy of Leydig cells, defect of testicular stimulation by foetal hypophysis, testosterone, biosynthesis abnormalities 5 varieties of which are identified, 5 alpha reductase defect, testosterone or dihydrotestosterone insenstivity complete and incomplete forms, defect of secretion or action of Mullerian ducts inhibitor can be found in the majority of cases by clinical and para-clinical analysis. Practical management results from this diagnosis.


[Fetomaternal rhesus immunization in Algeria]. The frequency and modalities of immunisation in the rhesus system were studied in 847 rhesus negative. Algerian women, and in 247 foreign women. 33% of the Algerian women and 8% of the foreign women were immunised. The high muliparity still frequent in Algeria is one of the causes of this difference. The specificity of the antibodies, the mode of foetal involvement, and the antibody titre in relation to the number of pregnancies and the month of the pregnancy are indicated.


[Division of the pituitary stalk (mischotomy) for malignant exophthalmos after treatment of Basedow's disease with I 131]. The authors report a case of malignant exophthalmia occuring after treatment of Grave's disease with I 131. The exophthalmia was resistant to corticosteroids, thyroxin in large doses, reserpine, and the patient was treated by mischotomy (division of the pituitary stalk with interposition of polyethylene strips). There was progressive marked regression of the exophthalmia with return to work and normal social life.


[Splenic lesions during benign inoculation lymphoreticulosis]. The authors describe the fibro-granulomatous lesions with scar formation on a splenectomy specimen removed for familial spherocytosis, eight weeks after the onset of cat scratch disease. This original observation, apparently unique in the literature, is in favour of the blood spread of the agent responsible for benign inoculation lymphoreticulosis, and suggests a pathogenic theory for the unusual visceral manifestations.


[Volvulus of the ascending colon. Apropos of 5 cases]. The authors report five cases of volvulus of the right side of the colon, including 3 with complications, which required segmental colonic resection. They recall the diagnostic and therapeutic problems, emphasising the interest of barium enema, the necessity of early diagnosis, the high level of mortality and the treatment of choice which is right hemicolectomy.


[Shunt between Disse spaces and biliary canaliculi and its pathology]. The existence and permeability of communications between Disse spaces and biliary canaliculi has been finally accepted, in spite of the socalled obstacle of the water-tight junctions. The explanation of pigmented bile secretion by filtration and reabsorption has become plausible. Whilst other subtances excreted by the bile after having been filtered at the level of the sinusoidal wall need to enter the hepatic cell to be synthesised, stocked or to take up their final shape, the bile pigments, cell debris, cross the hepatic lobule through the shunt between the Disse space and the bile canaliculi, without passing through the liver cell. These facts require us today to reconsider the physiopathology of some liver disorders, especially those accompanied by jaundice.


[Intestinal hemorrhage due to blind loops. 3 cases and review of the literature]. The authors report 3 cases of intestinal bleeding either micro- or macroscopic induced by ulcers in blind loops. The blind loops developed in all 3 cases on side-to-side ileocolic anastomoses. In one of the patients, the ulcers were demonstrated by colonoscopy. The 3 cases reported are quite comparable to the 18 cases found in the world literature. These hemorrhages may become severe by their abundance or repetition, but a cure is easily obtained by resection of the intestinal blind loops and restoration of the continuity by end-to-end anastomosis.


[Idiopathic thrombopenic purpura in Algeria]. The study in Algeria over a period of 3 years of 90 cases of idiopathic thrombopenic purpura out of 409 hemorrhagic syndromes, showed the following peculiarities: the chronic forms are as frequent in the child as in the adult and we did not observe any subacute forms. Except in one case the use of prednisone at a dose of 2 mg/kg gave no result in patients who were not improved by a dose of 1 mg/kg.


[Ebstein's disease. Study of 5 personal cases]. Ebstein's disease is a frequently cyanotic form of congenital heart disease. The lesions consist of low implantation in the right ventricle of the tricuspid valves, often associated with an atrial septal defect. Our five cases (two men and 3 women) had a variable clinical presentation depending on the degree of the variable clinical presentation depending on the degree of the lesions. A fairly exceptional fact should be emphasised, which is that 3 of our patients brought to term or almost to term 3 pregnancies and gave birth to live children. Ebstein's disease should be suspected when a large heart with a rugby football shape is discovered on X ray and E.C.G., together with right atrial hypertrophy, frequent elongation of the P-R interval, low voltage and complete right bundle branch block. The diagnosis can be confirmed by angiocardiography and catheterisation. Angiocardiography shows a large right atrium and a distal right ventricle in the form of a small chamber with thin walls. Catheterisation is essential and detects the atrial septal defect in 80% of cases and a pressure gradiant intermediate between atrial and ventricular pressures, revealing ventricular morphology. Surgical treatment will be either palliative (cavo-pulmonary anastomosis) or curative: Hunter's operation (Lillehei-Hardy) implantation of the tricuspid on the atrio-ventricular ring. The prognosis is then worse.


[Mortality due to tuberculosis. Statistical concepts]. The mortality statistics due to tuberculosis drawn up by INSERM for the years 1968-1973 show the rate to be 0.86% in the Paris region. A study based on autopsy results of 7,400 adults gave a rate of 3.3%. The causes of this discrepancy are analysed.


[Fulminating refractory hypoxemia. Apropos of 3 cases including 1 case of tuberculosis]. The authors report 3 cases of refractory fulminant hypoxemia. The etiology was various, neoplastic lymphangitis, influenza and tuberculosis. The authors emphasize the role of tuberculosis in the onset of certain diffuse interstitial fibroses.


[Diaphyseal bone tuberculosis].

[Diaphyseal bone tuberculosis]. The authors report a case of diaphyseal bony tuberculosis, in which the diagnosis was not made for a long time as bony tuberculosis is considered exceptional and owing to the presence of a staphylococcus which oriented the diagnosis towards osteomyelitis. Bony tuberculosis certainly affects more easily immigrant patients, in whom one may see multifocal forms, but also affects those who, by their environment, might imagine they are protected, and it is not exceptional to see unifocal forms.


[Multi-focal tuberculosis].

[Multi-focal tuberculosis]. The authors present 16 cases of multifocal tuberculosis observed over a period of five years on a general medical unit. These cases almost all occurred in immigrants. (14 out of 16) with at least 2 localisations in 9 of them and sometimes 3 or more. The viscera usually affected were, in order, the liver, the lymph nodes, the lungs and pleura, the joints. They emphasise the mildness of the clinical symptoms, the rareness of lung involvement and, on the contrary, the constancy of hepatic involvement so that needle biopsy of the liver is essential in diagnosis.


[Tuberculosis and caustic eso-gastric burns. Critical reflections on one case]. The diagnostic problems which may be raised during caustic oesophago-gastric burns and concommittent tuberculosis, of which the symptoms may be masked by the richness of the initial clinical picture are discussed here. The authors emphasise the necessity of prophylactic anti-tuberculous treatment, before any surgery when there is any suggestion of tuberculosis even siabilised.


[Extrinsic allergic alveolitis of drug origin]. Extrinsic allergic alveolitis of drug origin is now a better known branch of respiratory pathology. The symptoms and course of these cases resemble in many ways those of extrinsic allergic alveolitis in general with a few differences. The list of drugs responsible is longer every day, and it is important to be aware of it. The diagnosis of these diseases is not always easy, as there are certain similarities between them and other long diseases either iatrogenic or not, but not immuno-allergic. Our physiopathological knowledge is based on already known data concerning allergic alveolitis, but includes many theories which still have to be verified. It is important for the clinician to be aware of this new type of respiratory disease as the treatment includes withdrawal of the responsible drug as soon as possible, failing which irreversible pulmonary fibrosis develops.


Atopic dermatitis, eczema herpeticum, infectious mononucleosis, and depressed cell-mediated immunity. An immunologic investigation was undertaken in a patient with atopic dermatitis and infectious mononucleosis complicated by eczema herpeticum. Humoral immunity was normal. The cell-mediated immune (CMI) response was temporarily depressed during the acute phase of the illness as measured by in vivo skin tests, and in vitro tests using T-lymphocyte population, macrophage inhibition factor, and lymphocyte transformation. It is postulated that the depression of CMI caused by infectious mononucleosis precipitated the development of eczema herpeticum in this patient.


A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis. Gaviscon tablets and the standard antacid proved equally effective in reducing the number of heartburn attacks. Chi-square tests revealed no significant difference between the two treatment groups at the end of weeks 1, 2, 3, or 4. Heartburn score was arrived at by multiplying heartburn incidence by heartburn severity. This heartburn score also indicated no significant difference between the two treatment groups at the end of the four weeks. Tabulation of the mean number of tablets consumed by patients in the two groups was made. There was no significant difference between the two groups in tablet consumption, indicating equal demand as well as equal compliance in the two groups. Esophagoscopy done before and after 28 days of treatment showed that Gaviscon and the standard antacid tablets were equally effective in each group. There was significant, and equal, decrease in the severity in the specific signs of esophagitis, friability, erosion, and ulceration in both treatment groups, as well as in such nonspecific signs as hyperemia, edema, and exudate. The validity and clinical acceptance of an alginic acid-containing agent, Gaviscon, which through a foaming action delivers a minimal dose of antacid directly at the site of acid irritation of the esophageal mucosa, has been confirmed in a multicentric, well-controlled randomized clinical trial.


Clofibrate-induced complications in renal disease: a case report. A young male nephrotic patient, who was given small doses of clofibrate for hyperlipaemia, developed muscle pain, stiffness and very high serum levels of muscle enzymes. The myopathy remitted completely after administration of clofibrate was stopped. He also displayed a transient mononeuropathy and rapid deterioration of previously stable renal function, so that he required maintenance dialysis. Clofibrate has particular dangers in patients with uraemia or hypoproteinaemia, and we recommend that it be used with great caution in patients with renal disease.


Malignant cystosarcoma phyllodes associated with scirrhous carcinoma of the breast: a case report. The presence of a malignant cystosarcoma phyllodes in one breast and a scirrhous carcinoma in the opposite breast in a premenopausal Black woman is described. Malignant cystosarcoma phyllodes is uncommon and its rare association with carcinoma of the breast is mentioned.


Hepatoma presenting as a bone tumour: a case report. Osseous metastases from hepatoma are rare. One patient who had a lesion in the upper humerus is presented.


Rotavirus and winter gastro-enteritis in White South African infants. In a microbiological investigation of winter gastro-enteritis in 23 White children rotaviruses were found in 14 (61%) and parvovirus-like particles in 1 (4%). Bacteriological examination of stools from 11 of these patients yielded one isolate of Salmonella eastbourne, but no enterotoxigenic or invasive bacteria were found. Rotavirus appears to be the main aetiological agent of acute winter gastro-enteritis in White infants.


Somatic cell hybrids between Friend erythroleukemia cells and mouse hepatoma cells. Somatic cell hybrids between hepatoma and Friend erythroleukemia parental cells were studied for the expression of liver-specific and erythroid properties. Several independent clones were isolated using HAT selection and were shown to be true hybrids by isozyme and chromosome analysis. All displayed a complete extinction of hemoglobin and globin mRNA production, but a retention of albumin and transferrin secretion. The data suggest that erythroid differntiation is being actively inhibited by the hepatoma genome. Possible mechanisms that might explain these results are discussed in the light of current hypotheses regarding the mechanism of cell differentiation.


Transfer of the human genes coding for thymidine kinase and galactokinase to Chinese hamster cells and human-Chinese hamster cell hybrids. Cotransfer of two linked human genes, coding for the enzymes thymidine kinase (TK) and galactokinase (Gak) was demonstrated following incubation of Chinese hamster TK-deficient cells with isolated human chromosomes. The 5 colonies which were isolated all expressed a stable TK-positive phenotype. Cotransfer of the human genes coding for TK and Gak has also been observed in experiments in which isolated human chromosomes were incubated with TK-deficient human-Chinese hamster cell hybrids. These receipient hybrids had lost all human chromosomes at the time of incubation. From these experiments, four colonies were isolated, all expressing an unstable TK-positive phenotype. Using chromosome staining techniques, the presence of human chromosomes could not be demonstrated in either of the transformed clonal lines obtained with the Chinese hamster and the hybrid recipient cells. This indicates that incorporation of only the fragment of the human chromosome 17, bearing the genes for TK and Gak, has occurred in the recipient cells.


Adenosine kinase as a new selective marker in somatic cell genetics: isolation of adenosine kinase--deficient mouse cell lines and human--mouse hybrid cell lines containing adenosine kinase. A new selective system for isolating somatic cell hybrids, using adenosine kinase as the selective marker, has been developed. The selective medium for forward selection (to select for cells containing adenosine kinase) contains alanosine, adenosine and uridine. To survive in the presence of alanosine, cells must have adenosine kinase in order to utilize exogenous adenosine as the sole source of AMP. Uridine is added to the selective medium to prevent the toxic effects of adenosine on cultured mammalian cells. The selective medium for reverse selection (to select for cells lacking adenosine kinase) contains 2-fluoroadenosine, an analogue of adenosine, which is converted to a toxic nucleotide by the action of adenosine kinase. Mouse mutant cell lines deficient in adenosine kinase have been derived. Human--mouse hybrid cells containing the kinase have been prepared from one of these mutant lines. Karyotype data of these hygrid lines and their adenosine kinase-minus sublines are consistent with assignment by others of the human gene for adenosine kinase on chromosome 10.


T antigen and initiation of cell DNA synthesis in a temperature-sensitive mouse line transformed by an SV40tsA mutant and in heterokaryons of the transformed cells and chick erythrocytes. The role of SV40 gene A product in initiation of cellular DNA synthesis was investigated, using a mouse kidney line [mKSA207] transformed by SV40tsA207. mKSA207 cells were temperature sensitive for growth, lost SV40 T antigen (Tag) when incubated in low serum at 40degreeC, and accumulated Tag in the cytoplasm when fed 10% serum and incubated at the nonpermissive temperature (39.7degreeC). Following serum addition, the percentage of mKSA207 cells synthesizing DNA was essentially the same at nonpermissive (39.7 degrees C) and permissive temperatures (33.5degreeC). The cells entered S phase asynchronously at both temperatures, but most cells entered S within 16 h, and before Tag accumulated. mKSA207 synchronized by a double thymidine block also synthesized DNA at 39.7degreesC and entered a second S phase. Tag-depleted or Tag-synchronized mKSA207, when fused with chick erythrocytes (CE), activated CE DNA synthesis. At nonpermissive temperatures (39.7degreesC), 40% of CE nuclei in heterokaryons with Tag-depleted mKSA207 displayed 3H-thymidine--labeled nuclei 28--40 h after fusion, when only 12% of CE nuclei were Tag+. The experiments indicate that SV40 gene A product probably does not have a direct role as initiator of cellular DNA synthesis.


Cystosarcoma phyllodes.

Cystosarcoma phyllodes. Recurrence and metastases of a cystosarcoma phyllodes are poorly correlated with the histologic type and treatment used. There is some evidence, however, that the prognosis is more favorable for small tumors and minimal cellular atypism. Local excision seems to be associated with a higher incidence of recurrence of the tumor. Metastases can develop later from what appears primarily a benign, as well as a malignant, type. Mastectomy as primary treatment was not always effective in preventing the local recurrence of the tumor. If the tumor recurred after mastectomy, it gave rise to fatal metastases. The recurrence of the tumor after local excision is secondary to microscopic foci retained after enucleation. If a local excision is done, it should include a wide margin of mammary tissue around the tumor. Wide local excision, for small, slow growing and clinically benign tumors can be used as a first operation, with wider re-excision and later mastectomy if the tumor recurs. Large and rapidly growing tumors that suggest malignant disease should be treated primarily by mastectomy.


Preoperative occlusion of the hepatic artery with isobutyl 2-cyanoacrylate for resection of the "unresectable" hepatic tumor. The case of a child with an "unresectable" hepatic tumor is presented to introduce a new technique of preoperative selective tumor vascular occlusion by means of injection of isobutyl 2-cyanoacrylate on the morning of surgical resection. This technique provides a well demarcated, significantly smaller, and relatively avascular field, allowing for a safe and total removal of the hepatic neoplasm.


Granulocyte collagenase and elastase and the plasma protease inhibitors in human pus. Granulocyte collagenase and elastase was demonstrated in human pus using specific antisera. The enzymes were complexed by alpha1-antitrypsin and alpha2-macroglobulin but also were present as free proteases. All purulent exudates showed free elastolytic and collagenolytic activity.


Type IIa hyperlipoproteinemia and the HLA system. The comparative study of a control group made up of 340 healthy subjects, a group of 100 unrelated patients, all showing signs of type II hyperlipoproteinemia and a family of 15 members covering three successive generations, brings to light the highly significant increase of the recurrence of HLA Bw17 antigen and the increase in frequency of HLA Bw35 antigen.


Massive intramedullary globules in IgA monoclonal gammopathy associated with gastric carcinoma. The bone marrow of a patient with IgA monoclonal gammopathy associated with gastric carcinoma was massively infiltrated with extracellular globules of varying sizes from 2 to 110 micron. These exposed globules were not found in the metastatic lesions heavily infiltrated with plasma cells, but were exclusively confined to the bone marrow. They were indistinguishable from Russell bodies and composed of monoclonal immunoglobulin (IgA, lambda). Of interest is the fact that, despite a small number of plasma cells, there was an intramedullary extensive infiltration of exposed globules. The following conditions may be related to these changes. (1) The globules were not removed rapidly by effectual phagocytosis. (2) The environment of the bone marrow may be favorable for their remaining. In our case, however, the possibility that the plasma cells around the tumor were not of the same clonal origin as the marrow plasma cells cannot be ruled out. (3) The marrow plasma cells may produce immunoglobulin more vigorously, whereas their survival time be shorter than usual. As a result, these exposed globules released on the death of the cells accumulated massively in the bone marrow.


A radioimmunoassay of plasma unconjugated and conjugated estetrol. A radioimmunoassay for the measurement of both unconjugated and conjugaged estetrol in plasma has been developed. The antiserum obtained after 6 months of immunization with 6-oxoestetrol-6-(O-carboxy-methyl)oxim-BSA was used at a final dilution of 1:90,000 and showed almost no cross reaction with other steroids except for estriol at 1.24%. Esterol-glucosiduronate was synthesized by incubating with adrenalectomized rat liver homogenate and uridine diphosphoglucuronic acid. Then, plasma estetrol-glucosiduronate was measured in the same manner for unconjugated estetrol after hydrolysis with beta-glucuronidase. Sephadex LH-20 column chromatography (7X110 mm, benzene:methanol, 85:15) was employed for accurate assessment. The sensitivity was 10 pg and the smallest amount measurable was 40 pg/sample. The method bland was consistently negligible. The intra and inter assay precision was 11.8% and 14.2% for unconjugated estetrol and that for estetrol-glucosiduronate was 13.5% and 17.1%.


Serological evidence of bluetongue in game animals in Botswana. Using the Agar Gel Precipitin technique the sera of 397 African buffalo (Syncerus caffer) and 90 sera of other common game species were examined for bluetongue antibodies. Of the adult buffalo 283 out of 325 (87 per cent) were positive. Buffalo calves were positive in 25 out of 72 cases (35 per cent). Positive reactions were also recorded in lechwe (Kobus leche), tsessebe (Damaliscus lunatus), red hartebeeste (Alcelaphus buselaphus), gemsbok (Oryx gazella), sable (Hippotragus niger) and impala (Aepyceros melampus).


[Biochemical properties of aging of rat periodontium]. The content of proteins and nucleic acids and activity of acid and alkaline proteases, RNases, phosphatases and alpha-amylase were studied in the gum and alveolar bone or rats at the age of 1, 3, 6, 12, 18 and 24 months. It is found that a degree of periodontal atrophy strongly and directly correlates with the age of rats. The concentration of DNA and RNA in alveolar bone and of RNA in gum decreases with the age. The hydroxyproline content of periodontal tissues continuously increases till the age of 18th month and then considerably decreases. The activity of trypsin-like proteases, cathepsins and alkaline RNase in periodontal tissues increases reaching the maximum at the age of 6-18 months, and the activity of alkaline phosphatase decreases in the process of aging.


[Study of electron transfer in the NADH-vitamin K-cytochrome c system]. K-group vitamins, menadion and phylloquinone are shown to be able to transfer transmembrane electron from NAD.H onto cytochorme c localized inside lyposomes. Menadion reduces 60-70% of "endogenous" protein and phylloquinone--20--30%. FMN being added to the incubation medium increases considerably the rate of cytochrome c reduction, the quantity of "endogenous" protein remains unchanged.


[Activity of glycolysis enzymes in kidneys, blood serum and urine with toxicity of certain segments of the nephron]. The activity of hexokinase, glycose-6-phosphatase, phosphofructokinase, fructose diphosphate aldolase and ketose-1-phosphate aldolase was studied in kidneys, blood serum and urine or rats, the proximal and distal areas of their nephron being affected with the chemical substances. A pronounced decrease in the activity of the mentioned enzymes in the renal tissue was greater with afection of the nephron proximal area. The activity of the mentioned enzymes in urine, vice versa, increases sharply and in blood serum it was almost unchanges (exception for keto-1-phosphate aldolase). The pronounced enzyme uria may reflect the deep changes in epithelium cells of canals, especially of proximal ones where the enzymes under study are mainly localized.


An electron microscopic study of experimentally-induced HEV encephalitis. A gnobiotic piglet, was inoculated intracerebrally with hemagglutinating encephalomyelitis virus (strain VW572). Mononuclear cells formed vascular cuffs and were disseminated in the brain parenchyma. A few neurons were surrounded by the same kind of cells. Virus particles morphologically similar to coronavirus particles were found in the cytoplasm of both chromatolytic light neurons and hyperchromic dark neurons. The particles were in vesicles of distended endoplasmic reticulum and in the hypertrophied Golgi apparatus.


Hypervitaminosis D and metastatic pulmonary calcification in a cow. The history, clinical signs and post mortem findings in a cow with metastatic pulmonary calcification and calcific arteriosclerosis after vitamin D3 treatment are described.


[Immunoprophylaxis of infectious bovine rhinotracheitis]. The live attenuated vaccine against infectious rhinotracheitis (LAV), the live trivaccine against infectious rhinotracheitis (LT), the concentrated etanolsaponin vaccine against infectious rhinotracheitis (CESV) and the ethanol-saponin vaccine against infectious rhinotracheitis (ESV) can all be used as immunoprophylactic means in the control of infectious rhinotracheitis in cattle. The first two live vaccines are applied to calves in infection foci, and the two inactivated vaccines are used with cows. The comparative testing of CESV and ESV in experimental conditions on calves has shown that the first possesses higher immunogenicity--used in a twice lower dose it produces several times higher level of the neutralizing antibodies against the infectious rhinotracheitis virus. The use of LAV and LT in the practice under the conditions of established infections of infectious rhinotracheitis in calves has given good results. The immunization of calves at the immediate menace of this infection has lowered the morbidity rate, and death cases were no longer observed. The use of CESV and ESV with pregnant cows on a prophylactic basis against infectious rhinotracheitis has also given good results manifested in the full suppression of abortions.


[Virus-neutralizing antibodies in the colostrum and milk of brood sows vaccinated with an ethanol vaccine against Aujeszky's disease virus]. The experiment was carried out with five pregnant sows vaccinated with an etanol vaccine against the Aujeszky's disease virus. Studies was the level of virus-neutralizing antibodies in the blood, colostrum and milk serum of the sows as in the serum of their piglets. Virus-neutralizing antibodies were contained in high titers both in the blood, colostrum, and milk serum of the sows and in the serum of the offsprings. The titer of the passively acquired antibodies in the blood serum of the sucklings proved directly dependable on the titer of the colostral antibody level of their dams. The use is suggested of colostral sera for the evaluation of the immune status of sows in the breeding herds that are disease-free and vaccinated against the virus of Aujeszky's disease.


Asteroid bodies: derivatives of the cytosphere. An electron microscopic contribution to the pathology of the cytocentre. An electron microscopic study of asteroid bodies in granulomatous diseases of man, in particular in sarcoidosis and foreign body reactions, has led to the following conclusions. 1. Asteroid cytoplasmic inclusions are composed of organic proteineous structures. The body and arms of the stars consist mainly of longitudinally orientated, partially helically wound, collagen free, microfilaments with a diameter of approximately 50 A. Microtubules participate in their composition to a lesser degree. The filaments intertwine in various directions within the corpus of the stars. 2. Deeply osmiophilic compact structures, considered to represent condensation forms of protein, are consistently present within the body of the stars. These structures are partially granular and partially ring-shaped; in the latter case, transverse sections of tubules are noted. Since it is disputed whether they constitute procentrioles or postcentrioles, they are best referred to as paracentrioles. 3. The asteroid bodies are derivatives of the cytosphere, thus relating, in the broad sense, to the microfilamentous and microtubular apparatus of the cell. 4. The asteroid bodies in multinucleated giant cells participate in the spatial compartmentalization of the cytoplasmic content and nuclei. The sphere, aided by the centrioles, induces the formation of the mitotic spindle and, in addition, function as an organizing system of the cell. 5. The light microscopical periastral clear zone does not correspond to a fluid space. Rather, it consists of closely packed accumulations of laminated and whorled myelin figures, which are derived from the degradation of lipoid substances.


[Gene frequencies of both forms of galactosaemia in the western Hungarian province of Vas (author's transl)]. The two enzymes of galactose metabolism, namely galactokinase and galactose-1-phosphate uridyltransferase (Gal-1-PUT), were measured in 3653 subjects aged 7 months to 84 years in der to obtain the incidence of the gene deficiency causing galactosaemia in the Western Hungarian province of Vas. To date nothing is known about these frequencies in this particular region. It was of special interest whether these enzyme defects are to be found more frequently in gypsies than in a comparable population of West Hungary. The frequency of homozygous Gal-1-PUT deficiency amounts to 1:23,500; the respective incidence of galactokinase deficiency is 1:64,000. Both enzyme deficiencies in this province are not higher than in other countries. Considerable differences were established in the gene frequencies in individual areas and for various groups of subjects with variations from 1:30,000 to 1: 127,000 for galactokinase deficiency and from 1:5,300 to 1:81,000 for Gal-1-PUT deficiency. Neither gene deficiency occurred more frequently in gypsies than in the general population. This study demonstrates that the results of such analyses are relevant only to the investigated region and the greatest possible number of subjects must be taken in order to draw reliable conclusions.


Cholesterol metabolism in man.

Cholesterol metabolism in man. Recent investigations on cholesterol metabolism in man have led to new insights into diseases associated with abnormal accumulations of cholesterol in plasma (hypercholesterolemia), arterial tissues (atherosclerosis) and biliary tract (gallstones). Regulation of cholesterol synthesis under the influence of dietary and plasma cholesterol, may play a crucial role in determining biliary and tissue concentrations of this sterol. Plasma concentrations, on the other hand, appear to be controlled by complex mechanisms for secretion, transformation and removal of plasma lipoproteins. The recent identification of specific cellular receptors for uptake of plasma lipoproteins represents a significant advance for the understanding of regulation of both plasma and tissue concentrations, and possibly of the basic mechanisms underlying accumulation of cholesterol in atherosclerotic plaques.


Sarcoidosis therapy with cortisone and ACTH--the role of ACTH therapy. Out of 58 sarcoidosis patients 55 were treated successfully with a prednisolone therapy lasting one to two years. The high initial dosis of 40 mg daily has been maintained for at least 3 months. In case of intolerance or inefficiency of corticosteroid therapy a treatment with synthetic ACTH either in combination with corticosteroids or only ACTH was applied to 23 patients. The positive experiences of other authors were confirmed. Synthetic ACTH (1 mg) injected intramuscularly every third day did not cause any side-effects. ACTH can be employed not only in combination with corticosteroids, but it can also substitute them in special clinical cases.


Effect of AMP on acute carbon-tetrachloride hepatotoxicity. The effect of carbon-tetrachloride poisoning and the protection caused by AMP were studied. A single dose of CCl4 has resulted in a rapid development of a fatty liver, a considerable increase in serum enzymes, glutamic oxalacetic and pyruvic transaminases as well as serum-alkaline phosphatase. Total serum protein showed a tendency to decrease accompanied by a decrease in A/G ratio. Administration of adenosine-5-monophosphate prevented the increase in serum-alkaline phosphatase and increased the A/G ratio. There was, however, a slight but significant decrease in serum GOT and GPT within the 24-hrs. period of study, but it remained still higher than that of the control. AMP lowered liver fat without complete protection against the development of fatty liver.


[Influence of hemodialysis, heparin and protamin on the pre-beta fraction of lipoproteins in patients with chronic kidney failure]. The spectrum of lipoproteins in the serum and the blood clotting time was examined in 19 dialyzed and 5 non-dialyzed patients with chronic renal failure. Compared were the values obtained in hemodialysis with intermittent and regional heparinization and the changes after the application of heparin in hemodialysis and beside it. In non-dialyzed and dialyzed patients in interdialyzation period were studied the changes of given parameters which occur after heparin and protamin application. Out of the results of this examination it follows that: 1. the most significant factor causing the changes of lipoprotein spectrum in the serum during hemodialysis is heparin. 2. the effect of protamin upon the lipoprotein spectrum during hemodialysis cannot be explained only by the neutralisation of heparin effect. 3. beside heparin and protamin in the spectrum changes of lipoproteins during hemodialysis also other factors are participant that are concerned with hemodialysis.


[Constellation of lipoproteins in patients with hyperlipoproteinemia and in rabbits fed a cholesterol diet with reference to vascular permeability]. By feeding of rabbits with cholesterol a hyperlipoproteinaemia (HLP) was created and the changes of the cholesterol and triglyceride (TGL) level were compared with the changes of the portions of the pre-beta- and beta-lipoproteins. The electrophoresis with a gel of agar-agarose are more suitable for the densitometric evaluation than electrophoresis with cellulose acetate films. Tests with Evan's blue of the angiopermeability of rabbits feeded with cholesterol showed that the permeability of the cutaneous vessels decreased strikingly during test period, while a change of the permeability of the aorta was not to be proved under the conditions of our tests. HLP patients had been treated with clofibrinic acid, nicotinic acid derivatives and metabolism basic diet for 3 years. The cholesterol and TGL values as well as the pre-beta-/beta-lipoprotein quotients have been determined before and after treatment. The pre-beta-/beta-lipoprotein quotient has proved as suitable complementary parameter for pursuit of the therapeutic result with HLP patients. The changes of the quotients corresponded well with the found changes of the HLP types. The decrease of the TGL content of HLP patients of the type IV or IIb being treated with metabolism basic diet or clofibrinic acid may be estimated (with nearly constant cholesterol level) from the per cent decrease of the pre-beta-/beta-quotient.


Structural changes on Entamoeba histolytica trophozoites after cryopreservation in liquid nitrogen. Trophozoites of Entamoeba histolytica cultures which had been deep-frozen in the presence of 5% DMSO, along with untreated cells and cells treated with DMSO (5%), were examined for fine-structural changes. After deep-freezing in liquid nitrogen only a few amoebae exhibited normal nuclear and cytoplasmic structure. One frequently observed but unspecific finding pertaining to recovered cells is the separation of the cytoplasm into large vacuolated (coarse-granular) and electron-optically fine-granular (hyaline) zones. The glycogen which normally lies in the cytoplasm is always eluted. In many cases numerous short RNP helices are scattered unevenly in the vesicular plasma, but they are also found in larger masses adjacent to the membranes of still intact and already damaged nuclei. Moderately damaged nuclei have a poorly folded membrane and their chromatin is markedly denatured. More heavily damaged nuclei have a membrane which has partly fibrillated or ruptured and then formed conspicuous folds, where the nuclear membrane has ruptured nucleoplasmic remnants of chromatin and button-like bodies appear to pour into the surrounding cytoplasm. The final destruction of the cell is marked by coalescing autolytic zones, first in the vacuolated and later in the fine-granular cytoplasm. Finally only remnants of the nuclear membrane and of the membranes of numerous vacuoles remain. It is assumed that most of the changes in the cytoplasm are of a secondary nature and are caused by the early functional disturbance of the nucleus.


Carcinoma of the lung: the view today.

Carcinoma of the lung: the view today. The present epidemic of carcinoma of the lung is a consequence of society's indulence of cigarette smoking. Most of the progress in treatment has resulted from more accurate staging of the cancer at the time of diagnosis and the selection of the safest therapy. Future progress hinges on the public health measures to stop smoking, and to a much lesser degree on earlier diagnosis and advances in radiotherapy and chemotherapy.


[Organic lesions after application of hashish in rats and rabbits (author's transl)]. Toxic lesions were found in liver, kidney and brain of rats and rabbits after oral application of hashish for 7 or 30 days. The brain tissue showed hyperemia and edema. The cerebral cortex, brain stem and cerebellum contained ganglion cells with eccentric nuclei and an icreased number of nucleoli. Different stages of cell lesions could be distinguished by nuclear vacuoles, pyknosis and karyolysis. The cytoplasma was loosened and showed numerous vacuoles. In the kidney we found, besides interstitial hemorrhage, cloudy swelling of the proximal tubules with vacuolous degeneration and nuclear pyknosis and karyolysis in all stages. The glomeruli were often enlarged with thickening of Bowman's capsule and surrounding cellular infiltration with cell fragments. The liver cells showed irregularities of nuclei and vacuolated nuclei, plasma vacuoles and cell necrosis. Infiltrations of round cells at the portal-biliary areas were usually combined with an activation of the Kupffer cells and intracellular bile stasis.


[Failure in the treatment of carcinoma of the colon and rectum in connection with the operative technique (author's transl)]. Colonic and rectal anastomoses are more subject to leakage than anastomoses in other parts of the gastrointestinal tract. The mortality is high. Many aetiologic factors are connected with the operative technique. The great role of collagenase in the colon which increases during an infection is a cause for an anastomotic break-down.


[Cryosurgical treatment of malignant tumors in the cerebral hemispheres]. In 35 patients with deep-lying and medial gliomas (25 cases of glioblastoma multiforma, 10 cases of dedifferentiated astrocytoma), stereotactic cryodestructions were performed after preceding biopsies. Diagnosis was made in the usual manner, mainly by means of angiography. Sites of action were the tumour mass proper and the blood supply zones. In some cases, partial removal of the tumour was carried out in the usual way before or after cryodestruction. There are 3 kinds of further development after cryodestruction: regression, slow progression and rapid progression. Progression was found in 14 patients; 9 patients died within 2 weeks after the operation. In their cases, cryodestruction was by far insufficient. Dedifferentiated astrocytomas showed more a regressive behaviour than multiform glioblastomas. The possibility of local chemotherapy was also utilised.


[Indicators of immunity in children vaccinated with live poliomyelitis vaccine]. Serological examination of 1057 children, residents of Leningrad, vaccinated with poliomyelitis vaccine at the appropriate calendar dates according to the scheme, showed the presence of antibodies to the polioviruses in 81.5-99.1% of the cases. There were more serologically negative children against the virus type III, and much less--against the virus type II. The value of the mean geometrical titres somewhat decreased with the advance of the children's age and the time lapse after the vaccination and revaccination. The greatest antibody titres determined were against the poliovirus type II, and the least--against type III. No antibodies against the viruses of types I and III were revealed in case of deficiency against the poliovirus type II. The number of children with the absence of antibodies against the poliovirus of all the types was insignificant.


[Experimental study of combined staphylococcal, streptococcal and adenovirus infections in tissue culture]. Associated adenoviral, staphylococcus, and streptococcus infection was studied in the cultures of cells HEp-2 and PAO. Under conditions of monoinfection the cell culture largely inhibited the reproduction of staphylococci, and failed to influence the streptococci. In double and triple associated infections staphylococci overcame the inhibitory action of the cell culture. The pathogenic properties of cocci (plasma coagulation, hemotoxic properties) grown in the cell culture both under conditions of monoinfection, and in associations, failed to change. In double and triple associated infections adenoviruses did reproduce, but in lower titre than in monoinfection. Under conditions of mixed infection cocci penetrated and reproduced in the cell cytoplasm more intensively than in monoinfection. The cytopathic action was determined by viral associate, and was identical by its character to adenoviral monoinfection. A statistically significant increase in the activity of aldolase and transaminase enzymes was noted in mixed infection. The changes in the enzyme activity proved to depend on the character of the associations studied.


The effect of cyclic AMP on the maturation and degranulation of mast cells. In short-term tissue cultures dibutyryl cAMP inhibits the cortisone-induced degranulation of mast cells. The effect of methylxanthine was found to be similar but developed at a slower rate. The increase of cAMP level also affected the maturation of mast cells, as the ratio of cells of mixed granulation increased, compared to the alcian blue- and safranin-present model inhibited degranulation.


Absence of positive feedback effect of oestrogen on LH release in patients with testicular feminization syndrome. The response of serum LH to exogenous oestrogen administration was studied in 5 patients with testicular feminization syndrome (TFS). The serum LH levels were elevated in all the patients, while serum testosterone levels were within the normal male range. Serum FSH levels were elevated in 4 patients and normal in one patient. Intravenous administration of 100 microgram of LH-RH provoked a further increase in both LH and FSH. Following intravenous injection of 20 mg of conjugated oestrogen (Premarin), the LH levels were serially determined until 120 h in TFS patients, 5 normal males, and 10 normal females during the mid-follocular phase (D7-9). Both TFS patients and normal males showed no LH release following oestrogen injection in contrast to normal females who displayed a significant increase in LH with a peak at 48 to 56 h after the injection. These results seem to suggest that the insensitivity of the hypothalamus to androgen in TFS patients do not affect the sex differentiation of the hypothalamus. The possible role of oestradiol conversion from testosterone in the hypothalamus is discussed.


The effect of cyproterone acetate on the pituitary-adrenal axis in hirsute women. The functioning of the hypothalamo-pituitary-adrenal axis was assessed in 10 adult women with idiopathic hirsutism treated for 2 weeks with the anti-androgen cyproterone acetate in a dose of 50 mg b. d. daily and in 4 patients treated for at least 3 months. Basal plasma ACTH and cortisol levels and the cortisol response to 8 h ACTH infusion were comparable before and during short-term treatment. The plasma ACTH and cortisol responses to insulin induced hypoglycaemia before and during anti-androgen therapy also were of the same order of magnitude. In the 4 patients treated for at least 3 months also no suppressive effect of the anti-androgen on basal plasma cortisol levels was observed. From these data the conclusion seems warranted that short-term cyproterone acetate treatment in the given dose not significantly influences pituitary-adrenal function in adult women with idiopathic hirsutism.


Suprahypophyseal dysfunction in a patient with asexual ateleiosis. The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.


Fasting plasma cyclic AMP levels in an adult diabetic and non-diabetic group. Fasting plasma cyclic adenosine monophosphate (cAMP) was measured in 50 mature-onset diabetic patients and in 111 non-diabetic patients. Methods used to determine plasma cAMP are described. The addition of sepharose agar beads to the bovine adrenocortical binding protein has considerably improved the sensitivity and simplified the radioligand-receptor assay of cAMP. No statistical differences in plasma cAMP were noted in relation to sex in either group, to the presence of diabetes mellitus or to age or weight in the non-diabetic patients. Plasma cGMP levels are now being studied to determine if these may prove better indicators of insulin activity than plasma cAMP.


[Histotopic of glycosidases in the oviduct of the quail (Coturnix coturnix japonica) (author's transl)]. The activities of 6 glycosidases (n-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-fucosidase and alpha-mannosidase) in the oviduct of the quail (Coturnix coturnix japonica) were studied with histochemical methods. Alpha-galactosidase and alpha-fucosidase showed a weak to moderate activity in the surface epithelium and in most of the glands of the oviduct. A Distinct reactivity of beta-glucuronidase was observed in the surface epithelium of the whole oviduct and in the glands of the uterovaginal-region. A moderate to distinct reactivity of n-acetyl-beta-glucosaminidase cound be demonstrated in the epithelium and in the glands of all regions of the oviduct. The comparatively highest activity of this enzyme was found in the glands of the magnum and in the surface epithelium of the uterus. The possible functions of the glycosidases in the oviduct are discussed briefly.


The vibration perception threshold in gastrectomized patients with low serum B12. A clinical and biothesiometric follow-up after intensive B12 therapy. In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy.


Efficacy of zoster immunoglobulin in prophylaxis of varicella in high-risk patients. During a period of 2 1/2 years 190 children have been prophylactically treated with zoster immunoglobulin in norway. Information on 130 (68%) of these children was obtained. This group included patients suffering from leukemia, lymphoma, and other malignant disorders, and patients with autoimmune diseases, with impaired immune mechanisms or with for other reasons increased frequency of infections, as well as premature and weak newborns, and infants born to mothers who developed varicella during the last 4 days before delivery. Of the patients who received zoster immunoglobulin within 3 days after exposure, 2.9% developed weak symptoms of varicella. When zoster immunoglobulin was administered 4-5 days after exposure, 37.5% contracted varicella, and when given more than 5 days after exposure, 50% developed the disease. The 9 neonates with possible intrauterine exposure are not included in these figures.


Studies on a patient with in vivo evidence of type I glycogenosis and normal enzyme activities in vitro. Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-1,6-glucosidase (EC3.2.1.33); glycogen phosphorylase (EC2.4.1.1); fructose-1,6-diphosphatase (EC3.1.3.11). The urinary excretion of 2-oxoglutaric acid was greatly increased in this patient and in a case of enzymologically proven type I glycogenosis. Abnormal 2-oxoglutaric aciduria has not been previously reported in the glycogen storage diseases. The results are discussed in relation to the possible nature of the underlying biochemical defect in patients of this type.


Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo. The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-ACTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH.


Transmission and scanning electron microscopic observations of mouse adrenocortical adenoma cells (Y-1) in non-stimulated and stimulated states. ACTH sensitive murine adrenocortical adenoma cells (Y-1) were examined by transmission and scanning electron microscopes under non-stimulated and stimulated conditions. They showed the ultrastructural characteristics which were fairly different from those of the original adrenocortical cells of LAF1 mice. The smooth-surfaced endoplasmic reticulum (sER) were poorly developed, and the mitochondrial cristae showed lamellar rather than tubular or tubulo-vesicular type. Administration of ACTH induced rounding-up of the Y-1 cells with slight increase in sER, BUt no mitochondria with vesicular inner structure appeared. The effects of dbcAMP on the morphology of the Y-1 cells were similar to those of ACTH except that the rounding-up occurred more rapidly and uniformly.


Correlation of alkaline phosphatase staining of cortisol-producing adrenocortical tumors with dexamethasone suppression and ACTH stimulation. The histochemical activity of alkaline phosphatase (Al-Pase), the induction of which is one of the effects of ACTH on the adrenocortical cells, was examined in 10 adrenocortical tumors causing Cushing's syndrome and in 65 adrenal cortices. All of the compact cells in every gland, and almost all, about half, or a small proportion in the four tumors showed Al-Pase activity. These tumors decreased in steroidogenesis after the administration of dexamethasone. No compact cells exhibited the activity in six tumors, none of which was "dexamethasone-suppressible". Three of the seven attached glands examined were halfway between those of typical Cushing's syndrome and those of other than Cushing's syndrome from the viewpoint of compact/clear cell morphology. All of the tumors that had Al-Pase-positive clear cells increased in steroidogenesis after ACTH administration. These results suggested that Al-Pase activity of tumor cells was also ACTH effect and that a decrease in steroidogenesis of tumors after dexamethasone administration was due not to fluctuations but to suppression of intrinsic ACTH.


Titration of herpes simplex virus antibodies in human sera by the enzyme-linked immunosorbent assay (ELISA). 100 sera from healthy adults were titrated simultaneously for herpes simplex virus (HSV) antibodies by ELISA and neutralization. The ELISA was performed on microtitre plates where approximately 100 ng of detergent solubilized and chromatographically purified HSV glycoproteins was bound covalently to the plastic bottom of each well. The optical density (OD) values obtained by the use of the peroxidase-1.2phenylendiamindihydrochloride system showed good correlation with the neuratlizing antibody titres. Sera with very low neutralizing titres were clearly positive in ELISA.


Effect of human leucocyte migration inhibitory factor (LIF) on 3', 5'-cyclic AMP levels of peripheral blood leucocytes. The possible involvement of 3', 5'-cyclic AMP (cyclic AMP) in the mechanism of action of leucocyte migration inhbitory factory (LIF) was tested. LIF-treated human peripheral blood leucocytes were incubated at 37 degrees C for various times between 0 and 22 h. The concentrations of cyclic AMP in these cultures did not differ from those in controls. Furthermore, LIF did not affect the cellular release of cyclic AMP. Neither when testing purified neutrophils, which are the prime targets of LIF action, an effect of LIF was found. Cyclic AMP levels decreased with time of incubation, whether testing mononuclear cells (92 per cent lymphocytes), purified neutrophils (98 per cent), or buffy coat cells (72 per cent neutrophils; 22 per cent lymphocytes). However, a transient and as yet unexplained increase in the cyclic AMP levels of the latter mixed population of cells was manifested within 10 to 30 min of incubation.


Cadmium feeding: apparent depression of atrioventricular-his-Purkinje conduction system. Male rats were exposed to 0, 10 and 130 p.p.m. cadmium administered in 0.5% saline drinking water for 71 days. Biweekly records of ECGs, Hct, body weight and blood levels of cadmium were made. Rats exposed to 130 p.p.m. cadmium showed slower growth rates and declining Hct indicative of acute cadmium poisoning. At the end of the experimental period, carotid artery blood pressures and whole heart cadmium levels were determined. Although no significant blood pressure changes were observed in the experimental groups, the cadmium content of the hearts of the higher dose group was significantly higher than in the hearts of the lower dose group. The PR interval of the ECG was lengthened progressively and to the same extent in both experimental groups with continued cadmium feeding. These experiments offer evidence that the accumulation of even moderate amounts of cadmium will be manifested in marked changes in cardiac conduction without overt signs of cadmium poisoning.


The effect of smoking on selected coronary heart disease risk factors in middle-aged men. Associations between smoking and selected factors supposed to promote coronary heart disease (CHD) were studied in 1832 healthy men, 809 of whom were smokers. Triglycerides were 7% higher in smokers; the heaviest smokers had the highest levels. Unfavourable changes were not seen in the other parameters in smokers. There was no trend indicating an influence of smoking on total and HDL cholesterol in the individuals who had abstained from smoking for a few hours just before the examination. Body mass index and weight, blood pressure and resting heart rate were lower in smokers, whereas heart volume, glucose tolerance, thyroid function and ECG findings did not differ significantly in smokers and non-smokers. The present study indicates that smoking promotes the development of CHD independently of the commonly accepted CHD risk factors.


The tropical amblyopia syndrome (or tropical nutritional amblyopia) in the Mid-Western State of Nigeria. One hundred and seven patients from the Mid-Western State of Nigeria with the tropical amblyopia syndrome are reported. Ninety-five patients (88.8%) had the amblyopia syndrome mainly; twelve patients (11.2%) had amblyopia and other manifestations of the tropical ataxic neuropathy. The young, aged 10-20 years, represented by sixty-six patients (61.8%), are predominantly affected by the uncomplicated syndrome. Thirteen patients (12.1%) showed muco-cutaneous evidence of avitaminosis. Fifty patients (46.7%) had temporal pallor of the optic discs, bilaterally, another fifty (46.7%) had normal discs, two (2.8%) showed pink discs. Generalized field constriction is the common field defect, though central or centro-caecal scotoma can occur. Red/green defect was present in seven patients. It is a disease of the poor or those living on a basic monotonous diet consisting mainly of cassava (mannihot) and its derivatives. It is a significant cause of defective vision in Mid-Western Nigeria.


Herpes type-2 virus antibody status in groups of patients with neoplasm in Ibadan. Various studies have associated Herpes Type-2 (HT-2) virus with carcinoma of the cervix, especially the squamous cell type. In the present study, prevalence of HT-2 virus antibodies was found to be significantly higher in patients with squamous cell carcinoma of the cervix than in cases with squamous cell carcinoma of sites other than the cervix, and other pelvic and extrapelvic malignancies (P less than 0.001). It was concluded that no association could be found between Herpes Type-2 virus and malignancies of sites other than the cervix.


An evaluation of the GCA respirable dust monitor 101-1. The GCA RDM 101-1 has been evaluated using aerosols of coal, Arizona road dust, silica, potash, and rock (copper ore) particles. The effects of the dust mass concentration, particle size distribution, and dust material on the instrument response were investigated. The instrument was found to measure the mass concentrations of respirable dust aerosols up to about 16 mg/m3 for coal and rock dust and about 20 mg/m3 for silica, potash, and Arizona road dust, providing there is not appreciable mass in the size range below approximateley 0.7 micrometer aerodynamic diameter.


A dust generator for laboratory use.

A dust generator for laboratory use. A dust generator has been developed to produce dry dust from powderous materials for instrument calibration and laboratory studies. The powder is fed at a constant rate via a chain conveyor into a fluidized bed where the particles are deagglomerated and aerosolized. The powder feed rate is raviable from 1.2 to 36 mm3/min and the air flow rate from 9 to 30 Lpm. Aerosols of coal, silica, potash, rock, and Arizona road dust have been successfully generated for calibrating optical particle counters and aerosol mass monitors.


Management of hypercholesterolemia: evaluation of practical clinical approaches in healthy young adults. A work site-located clinic screened 6,000 employees (91 percent participation) and identified 146 hypercholesterolemic subjects (100 percent initial participation, 12 percent subsequent dropout rate). The subjects, aged 20 to 50 years, were randomly classified into four groups: Group A, treatment in a lipid intervention clinic with diet for 6 weeks, then diet plus clofibrate for the subsequent 18 weeks; Group B, diet treatment from a clinic nutritionist with the cooperation of the subject's private physician; Group C, referral for treatment by a private physician; and Group D, no intervention. Initial mean cholesterol was 294 mg/100 ml. At 24 weeks, all intervention groups had decreases in serum cholesterol (Group A, 12 percent; Group B, 15 percent; Group C, 17 percent; P less than 0.001). The control group (D) had a small decrease in cholesterol (4 percent). Decreases in cholesterol were correlated with weight loss and decrease in fasting serum triglycerides but not with the use of clofibrate. Serum cholesterol can be reduced in healthy young adults by several practical methods.


Malignant fibrous histiocytoma: an ultrastructural study of six cases. The ultrastructures of six malignant fibrous histiocytomas were studied. The lesions were composed of different proportions of fibroblastic- and histiocytic-appearing cells. Intermediate, undifferentiated, and foam cells also were present. Three of the lesions had some "fibroblasts" that had intracytoplasmic bundles of filaments with focal densities (myofibroblastic cells). Malignant fibrous histiocytoma is considered a sarcoma that has an undifferentiated mesenchymal cell origin, that differentiates along a broad fibroblastic and histiocytic (fibrohistiocytic) spectrum, and that usually has a predominant "fibroblastic" component.


Extracellular hydrolytic enzymes of rabbit dermal tuberculous lesions and tuberculin reactions collected in skin chambers. To evaluate extracellular hydrolytic enzymes in an in vivo system, plastic chambers were glued over rabbit dermal BCG lesions in various stages of development, after the central epithelium was removed with a scalpel. They were filled with tissue culture medium and left in place 2 days. The following enzymes in the fluid were assayed: collagenase (an enzyme secreted but not stored in macrophages); lysozyme (both secreted and stored); DNase and RNase (released on cell death and possibly regurgitated but not secreted); and, as a control, lactic dehydrogenase (released only on cell death). Tissue sections were prepared and studied histologically for the type of cell infiltrate, for beta-galactosidase (our marker enzyme for macrophage activation), and for necrosis. At 11 and 18 days of age the BCG lesions were largest and the number of activated macrophages in the chamber beds was highest. At this time the levels of the five enzymes assayed in the chamber fluids reached their peaks, tuberculin hypersensitivity was well developed, and the bacilli components would still be plentiful. In general, the chamber fluids from 11- and 18-day BCG lesions contained higher enzyme levels than chamber fluids from tuberculin reactions. Active collagenase was only detected in fluids from such BCG lesions. Evidently, the serum in the chamber fluids was sufficient to inhibit the lower amounts of collagenase probably released from smaller BCG lesions and tuberculin reactions (and from the 2-week polystyrene lesions that were also evaluated). These studies demonstrate that in chronic inflammatory reactions, both acid-acting and neutral-acting hydrolytic enzymes are released extracellularly. Tissue components would be hydrolyzed locally wherever the acid-acting hydrolytic enzymes encounter a drop in pH and wherever the concentration of neutral-acting hydrolytic enzymes exceeds the concentration of their inhibitors.


Energy relationships between cytosolic metabolism and mitochondrial respiration in rat heart. Isolated rat heart was perfused with Langendorff's retrograde perfusion method, while the oxygen consumption and the left ventricular pressure were monitored continually. The steady-state contents of metabolites in the cardiac tissue, freeze clamped under various work-load conditions, were determined and the concentrations of free cytosolic ADP and AMP were calculated from the near equilibrium in creatine phosphokinase and adenylate kinase reactions. Increasing respiratory rate with increasing load was accompanied by a fall in the cytosolic free [ATP]/[ADP][Pi] but little change in the mitochondrial free [NAD+]/[NADH]. The free energy of ATP hydrolysis was calculated from the concentrations of the adenine nucleotides and compared with the values computed from the measured turnover number for cytochrome c and redox state of the mitochondrial NAD couple according to a mathematical model. The agreement between the two values was good over a wide range of metabolic conditions, which provides further support for the proposed near-equilibrium model of mitochondrial respiration with control exerted at the cytochrome oxidase-oxygen reaction.


Homeostatic regulation of cellular energy metabolism: experimental characterization in vivo and fit to a model. Measurements in isolated liver cells, cultured kidney cells, protozoa (Tetrahymena pyriformis), and yeast (Candida utilis) indicate that homeostatic regulation of cellular energy metabolism is of common origin. In every case near equilibrium is maintained between the transfer of reducing equivalents from the intramitochondrial NAD couple to cytochrome c and the phosphorylation of cytosolic ADP to ATP. Under conditions of constant energy demand, changes in the intracellular phosphate concentration cause an adjustment in the [ATP]/[ADP] to maintain a constant [ATP]/[ADP][Pi] and constant respiratory rate. The regulation of mitochondrial respiration occurs as part of the reactions by which reduced cytochrome c is oxidized by molecular oxygen. At similar values for the [ATP]/[ADP][Pi] the respiratory rate increases with increasing reduction of cytochrome c. A model for mitochondrial respiratory control is found to give a good fit to the data in all of the different types of cells tested.


Intestinal contribution to secretion of very low density lipoproteins into plasma. To resolve the question of the magnitude of the intestine's contribution to circulating very low density lipoproteins (VLDL), measurements of intestinal, hepatic, and total VLDL--triglyceride were made on the same animals or on animals studied under comparable conditions. Animals were examined in the fasted state and during infusion of a fat-free meal. Intestinal VLDL secretion was determined through timed collections of lymph from the mesenteric lymph duct; hepatic and total VLDL secretion rates were estimated by the accumulation of plasma VLDL after injections of Triton WR 1339. Results indicate that the intestine contributes only a minor portion (11%) of the amount of triglyceride entering into the plasma compartment in the fasted state. Although intestinal triglyceride production is increased by 50% (p less than 0.01) in fed rats, the overall contribution of the intestine is not significantly altered in fed rats and represents only 14--17% of total body VLDL secretion. Thus, although intestinal VLDL secretion can be modified experimentally, its total impact on endogenous triglyceride production in normotriglyceridemic rats is small.


Purification of distinct plasma membranes from canine renal medulla. Two types of plasma membrane were purified from canine distal renal medulla by the techniques of differential and zonal density-gradient centrifugation followed by free-flow electrophoresis. One group of plasma membranes was identified as basal-laterally derived based on a 30-fold enrichment of Na-K-ATPase, a 20-fold enrichment of vasopressin-stimulated adenylate cyclase, and a 33-fold enrichment of [3H]vasopressin binding sites. The second type of plasma membrane was free of these markers, but had a cholesterol and phospholipid composition similar to them. Alkaline phosphatase also had a similar distribution in the two fractions. This lighter membrane fraction contained a membrane-bound cyclic AMP-dependent protein kinase as well as substrate for this kinase. In addition there was a 26-fold enrichment of specific activity of an anion (SO32-)-activated ATPase which was insensitive to mitochondrial ATPase inhibitor protein, in contrast to the mitochondrial fraction of the tissue. Based on the relative preponderance of collecting duct tissue in the distal medulla and the yield of membrane protein, these membranes are tentatively identified as containing apical membranes of the collecting duct.


Potentiation of the cerebrovascular response to intra-arterial 5-hydroxytryptamine. Infusion of 5-hydroxytryptamine (5HT) into the internal carotid artery of normal baboons was not accompanied by alteration of gray matter cerebral blood flow. In animals pretreated with depot estrogen and progesterone (dosage equivalent to oral contraceptive preparations), infusion of 5HT produced a marked decrease in gray matter blood flow. A similar decrease in flow was obtained when the 5HT was infused with a concentrate of beta-lipoprotein. Steroid substances appear to enhance the cerebrovascular constrictor responses to 5HT. A further series of six experiments has shown that the monoamine oxidase inhibitor tranylcypromine similarly produced constrictor responses to 5HT. It is possible that the steroids, the beta-lipoprotein, and the tranylcypromine produced constrictor responses to 5HT by the same mechanism (inhibition of cerebrovascular monoamine oxidase).


Fasting, adrenalectomy, and gluconeogenesis in the chicken and a carnivorous bird. Previous studies showed that livers from carnivorous birds have a higher gluconeogenic capacity and higher levels of gluconeogenic enzymes than livers from granivorous birds. In this work we compare the effects of fasting and adrenalectomy on gluconeogenesis. Fasting in the chicken elicited increased rates of incorporation of 14C from alanine into blood glucose, increased gluconeogenesis in liver slices, and increased activities of four gluconeogenic enzymes: glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, alanine aminotransferase, and aspartate aminotransferase. These responses in the chicken resemble those observed in fasted rodents. In marked contrast, fasting in black vultures induced decreased rates of incorporation of alanine label into circulating glucose, decreased gluconeogenesis in liver slices, and no change in any of the four enzymes studied. This unusual response to fasting in the carnivorous bird is probably related to the high-protein-low-carbohydrate content of the diet. Fasted adrenalectomized birds (granivorous and carnivorous) had reduced rates of in vivo glucose synthesis, decreased liver gluconeogenesis, and lower activity of glucose-6-phosphatase and aspartate aminotransferase, without change in phosphoenolpyruvate carboxykinase and alanine aminotransferase activities.


Angiotensin-converting enzyme in developing lung and kidney. Angiontensin-converting enzyme (ACE) catalyzes rapid conversion of angiotensin II (AII). This enzyme has been identified in the vascular endothelium of nearly every tissue. Inasmuch as AII is the biologically active component of the renin-angiotensin system, and since age-related differences exist in the renin-angiotensin system, it was of interest to determine converting enzyme activity during development. ACE activity was quantified by measuring the optical density of hippuric acid liberated from hippuryl-L-histidyl-L-leucine (HHL) following incubation with the 20,000 X g supernatant of tissue homogenates. Pulmonary ACE activity of near-term fetal rats was not different than 1-day-old animals. Therafter, ACE activity increased during the first 6 wk postpartum in a biphasic manner. A similar age-dependent increase in converting enzyme activity was observed in rat kidney, mouse kidney, and mouse lung. Substrate affinity of all enzymes measured was similar, suggesting that the age-related increase in activity was due to increased enzyme content. The low activity of ACE in the newborn might function to limit AII production.


Patients' views of placement facilities: a participant-observer study. The authors report a study in which five student nurses from a psychiatric hospital observed and talked with released patients in their new environments-family care homes, adult and boarding homes, nursing and health-related facilities, and their own family homes. Overall, these ex-inpatients seemed responsive to the physical and social features of their new environments. Some of the aspects most often noted as beneficial may have implications for inpatient facilities in terms of architecture, decor, clear differentiation of subunits, and greater exchange of information between inpatient and field staff.


The prevalence of encephalomyocarditis virus neutralizing antibodies among various human populations. The prevalence of encephalomyocarditis virus (EMC) antibodies among selected human populations in various regions of the world was determined by the plaque reduction neutralization method. Antibody rates among children ranged from 1.0 to 33.9%, while those among adults varied from 3.2 to 50.6%. No differences between sexes were found in the frequency of EMC infection. The pattern of age-specific antibody rates observed among the study populations suggests that EMC infection occurs primarily during childhood. There appeared to be no association between the presence of EMC antibodies and potential exposure to rats. Sera from diabetic, suspected encephalitis, and myocarditis patients were also examined for EMC neutralizing antibodies. The prevalence of antibodies among these groups was not significantly different from that of control populations in the same geographic regions. No association was demonstrated between EMC infection and these three diseases. The results of this study indicate that EMC infection in man is fairly common but that most human cases are probably asymptomatic and/or unrecognized.


Serological evidence of infection of Tacaribe virus and arboviruses in Trinidadian bats. Sera from 39 species of bats collected in Trinidad between 1972 and 1974 were tested against some or all of 18 arboviruses in hemagglutination inhibition (HI) and/or suckling mouse neutralization (N) tests. A few sera were HI-positive with Mucambo, eastern equine encephalitis (EEE), Oriboca, Restan, Manzanilla, Guama, Bimiti, and Catu. No sera were HI-positive with Mayaro, Caraparu or Maguari. Many ser inhibited one or more of the group B hemagglutinins: Ilheus, St. Louis encephalitis (SLE), dengue 2, and yellow fever (YF), positives occurred in nearly every species of bat, being most frequent with Ilheus. In N tests, a few or single sera were found to protect against Ilheus, Nepuyo, Guama, Bimiti, and Cocal, while none protected against EEE, SLE, YF or Catu. Many sera positive in HI test with Ilheus, SLE or YF failed to neutralize the respective virus. Tacaribe neutralizing antibody was demonstrated in Artibeus jamaicensis and A. lituratus, the sources of past virus isolation, in the fruit bats Sturnira lilium and Vampyrops helleri, and in the vampire bat Desmodus rotundus. Sera from 19 other species gave either negative or inconclusive results. No convincing evidence of Tacaribe antibody was found in 29 human sera, 20 from bat collectors.


Relevance of laboratory colonies of the vector in arbovirus research--Culicoides variipennis and bluetongue. Relevance for laboratory colonies of Culicoides variipennis (Coquillett) in arbovirus research was determined during colonization by comparing a vector-competence characteristic for the parent (P) field and subsequent colonized generations. Three colonies established in 1972-1973 were used to determine whether each was representative of the field population from which it was derived for oral infection to 2 to 4 serotypes of bluetongue virus (BTV). Two colonies that were based on small numbers of females ovipositing did not represent the field population. Both appeared homogeneous to oral infection with different serotypes, and one was resistant to infection whereas the other was susceptible. The third colony, which was based on about 150 P females that had oviposited, was more representative of the field population: 1) oral susceptibility to BTV for the F6 was not greatly different from that of the P generation, and 2) the colony retained some heterogeneity for response to oral infection with different serotypes of BTV. The number and percentage of P females ovipositing and the numerical growth factor from the P to F1 were used to estimate whether a laboratory colony was apt to represent the field population from which it was derived.


Heterogeneity of Culicoides variipennis field populations to oral infection with bluetongue virus. A standard colonized population (000 line) of Culicoides variipennis (Coquillett) was used as the control for comparing the infection rate (IR) responses of different field populations of the vector to oral infection with several strains of bluetongue virus (BTV) that belonged to four serotypes. Three field populations from Colorado and Oregon tested concurrently in 1969 were differently susceptible to three BTV strains representing three serotypes. The IR's of each of the three populations varied greatly for the three serotypes, and the lowest IR for each of two Colorado populations was for a different serotype. The IR's of different populations to the same BTV strain varied greatly, and the lowest and highest IR's for two serotypes with adequate virus concentration occurred in different populations. Two Kentucky field populations in 1971 were completely resistent to oral infection with a BTV strain; in 1972, one population remained resistant and the other became moderately susceptible. The IR's of different field populations in 1971 to a single BTV strain ranged from 0 to 68%. The IR's of an Idaho population to three BTV strains representing three serotypes showed that a susceptibility rate (SR) could be calculated if the IR's were similar for one and for two infective blood meals. The average SR of this population was 42%; the SR's to each serotype were 32%, 40%, and 54%, with the highest response for the serotype that included the BTV strain collected during the BT outbreak from which the vector population was also collected.


Intracellular demonstration of growth hormone in human mammary carcinoma cells. Intracellular growth hormone has been demonstrated in human mammary carcinoma cells by using an unlabeled antibody enzyme technic with horseradish peroxidase and antihorseradish peroxidase complex. Intense reaction was seen in both male and female mammary carcinoma cells. Positive staining was observed in nuclei and cytoplasm and on cytoplasmic membranes.


Alterations in plasma lipid concentrations in normal and hyperlipidemic patients with morbid obesity before and after jejunoileal bypass. In a study of 193 massively obese patients plasma lipoprotein concentrations were elevated in 94 patients and were within normal limits in 99 patients. Jejunoileal bypass, in addition to causing weight loss, lowered plasma lipids in both groups to normal or below normal levels.


Calcium localization in normal rachitic, and D3-treated chicken epiphyseal chondrocytes utilizing potassium pyroantimonate-osmium tetroxide. Normal, rachitic, and vitamin D3-replete chicken growth plates were studied utilizing the potassium pyroantimonate-osmium tetroxide procedure. A marked membrane and mitochondrial calcium was revealed in all specimens in the maturing and early hypertrophic zones which disappeared as heavy matrix mineralization began. The most significant difference shown in the specimens was in the marked intracellular lipid content of chondrocytes in all zones of the rachitic and D3-replete growth plates. There was negligible lipid present in normal specimens. It is suggested that as most of the mechanisms postulated as necessary for calcification are present in rachitic chicks, perhaps the increased intracellular lipid pool results from the formation of abnormal lipids for insertion into the plasma membrane and thus prevents normal calcium transport. Chains of intracellular vesicles were also visualized in maturing and hypertrophic chondrocytes. These were more often seen in rachitic growth plates and in increased numbers in the early D3-replete specimens. The etiology is unknown at the present time.


In vitro antiviral efficacy of ribavirin against feline calicivirus, feline viral rhinotracheitis virus, and canine parainfluenza virus. Ribavirin had marked in vitro activity against feline calcivirus, strain 255, and canine parainfluenza virus, but showed only slight antiviral effect on feline viral rhinotracheitis virus. Antiviral activity was manifested by partial to complete suppression of viral cytopathic effect and of viral replication, depending on concentration of ribavirin in the culture medium and dosage of viral inoculum. Concentrations of ribavirin as small as 3.2 microgram/ml and 1.0 microgram/ml showed some activity against feline calcivirus and canine parainfluenza virus, respectively.


Cross reaction between bovine enterovirus and South African Territories I5 foot-and-mouth disease virus. A bovine enterovirus (E76T) isolated from a 2-year-old bull produced serologic cross reactions to South African Territories (SAT) I5 foot-and-mouth disease virus when inoculated into guinea pigs and cattle. Cross-reacting serum titers to SAT I5 virus of 1:320 by the plaque-reduction neutralization test and 1:20 by the radial immunodiffusion test occurred in 2 steers after they were inoculated with the E76T virus. In 1 steer, maximal cross-reacting titers appeared related to a 2nd exposure to the viruses or to a hyperimmune state. Ultracentrifugation and 2-mercaptoethanol studies indicated that the cross reactions were due to immunoglobulin M antibody. Sera from guinea pigs immunized with the E76T or the SAT I5 virus cross reacted with the heterologous virus by postinoculation day 7. Cross-reacting titers had decreased markedly by postinoculation day 35, whereas the homologous virus titer remained constant. Cross reactivity of the E76T virus was primarily with the SAT I5 virus, and to a lesser degree with SAT II3. Cross reactions did not occur with representatives of the 5 other antigenic types of foot-and-mouth disease virus.


Tetanic fade and post-tetanic tension in the absence of neuromuscular blocking agents in anesthetized man. Frequency and time dependent changes in neuromuscular transmission were examined in 30 patients undergoing elective minor surgical procedures not requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopenthal and maintained with N2O-O2 and fractional does of meperidine or fentanyl. Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-millisecond duration. Tetanic trains of 10-second duration ranging from 10 Hz to 400 Hz were used. From analysis of present data, criteria for normal responses to 10-second tetanic trains of varying frequencies were established. At a frequency of 30 Hz, the tetanic response is fully maintained and followed by post-tetanic potentiation; at a frequency of 50 Hz, both tetanic and post-tetanic responses are maintained; at a frequency of 100 Hz, there is tetanic fade, followed by a post-tetanic depression of the single indirect twitch responses. It is concluded that frequency and duration of indirect stimulation are the most important factors in using tetanic maintenance and post-tetanic events in assessment of recovery from neuromuscular block.