[Acute obstruction of the esophagus by mucilage]. The authors present the case of an 84 year-old woman with chronic constipation who suddenly developed acute obstruction of the lower oesophagus on taking a tablespoonful of mucilage without water. The obstruction was relieved by fiber endoscopy. There was no other previous lesion which might explain this complication. The patient was seen again later in good general health. The authors recall the clinical and radiological signs of acute obstruction of the oesophagus and discuss the physiopathology. They propose treating them exclusively by oesophageal fiber endoscopy.


[Basal cell epithelioma and multiple fibroepithelial Pinkus' tumors in the lumbosacral region. Discussion of the precipitating role of previous radiotherapy treatment. Apropos of 4 cases]. The authors report 4 cases of multiple tumors of the lumbo-sacral region with, on histology, a mixture of basal cell carcinomas and fibro-epithelial Pinkus tumours. They were struck by the fact that three of these four patients had received, in this region, radiotherapy numerous years previously. They discuss the role of this radiotherapy in the onset of the disease and the relative importance of this factor and of constitutional factors (Hamartomas). They recall the characteristics of multiple basal cell carcinomas and of Pinkus fibro-epithelial tumours, together with the close relationship between these two types of tumour.


[Bone marrow biopsy in the diagnosis of hematopoietic tuberculosis]. The authors report 6 cases of tuberculosis of the bone marrow, in which the diagnosis was made by biopsy. Three of these cases, included peripheral blood abnormalities, such as pancytopenia, whereas in the three other, nothing special was found on routine blood examination. All the patients, except one who died from intercurrent infection, became cured thanks to anti-tuberculosis treatment. Marrow biopsy thus permits early diagnosis, miliary tuberculosis, even when usual radiological and bacteriological investigations are negative.


[Primary malignant tumor of the liver in children]. Primary malignant tumours of the liver in children are rare. They occur in more than 50% of cases before the age of 2 years. The clinical signs are very often limited to a large mass in the right hypochrondrium. A search for alphafoetoprotein and arteriography are the most useful investigations for diagnosis. The pathology leads one to distinguish hepatoblastomas and hepatocarcinomas. The prognosis in these tumours remains poor for, in spite of progress in liver surgery, a cure is rarely possible. It is important for doctors to recognize the existence of this tumour pathology in order to give a chance for surgery to succeed in these young children. To illustrate this, 5 cases from Besançon are reported here.


[Waldenstrôm's macroglobulinemia. Developmental and prognostic study]. The course of 27 cases of Waldenström's macroglobuilinemia was observed during at least 2 years or until death. A worsening occurred in half of the patients, with 7 deaths before 2 years. 10 patients improved under therapy, with only two deaths later. The more frequent complications were infections, but other complications, haemorragic, neurologic, osseous and renal were also observed. A haemoglobin initial level higher than 9 g % and a significant decrease of lymphocyte blood count under chemotherapy seem to be of good prognosis.


[Morphologic manifestations of Waldenström's disease]. The authors describe the various cytological and pathological lesions found in lymph node, spleen, bone marrow and liver in Waldenströms macroglobulinemia. The significance of the discovery of PAS positive intranuclear vacuoles is discussed. The findings are completed by a description of the results obtained in immunofluorescence and under the electron microscope. Unusual forms and the differential pathological diagnosis are then discussed.


[Sarcomatous and leukemic forms of Waldenström's macroglobulinemia]. Four cases of sarcomatous or leukaemic types of Waldenström's macroglobulinemia are presented. They are characterized by tumoral and compressive localizations of lymph node or spleen, or by a hyper-leukocytosis with many circulating abnormal cells. These cells are different from the lympho-plasma cells regularly observed in Waldenström's macroglobulinemia, and can be assimilated to malignant immunoblasts. They have a proliferative aspect and seem to produce less macroglobulin and to recover some beta-glucuronidase activity. The sarcomatous and leukemic types of Waldenström's macroglobullinemia have a poor prognosis and may appear as terminal transformation of the disease.


[Waldenström's macroglobulinemia with preserved antierythrocyte and antilipoprotein antibody activity]. One case of Waldenström's macroglobulinemia is reported, in which the monoclonal IgM has an antibody activity against stored red cells, beta-lipoproteins and mammalian glomeruli. The antibody activity is observed with the purified IgM molecule, which cross reacts with the three antigens, and with the Fab piece. The study of the cross reactions shows that the antibody recognizes similar rather than identical antigens. This observation is to be added to the few cases already published of antibody against stored red cells, and of Waldenström's macroglobulinemia with antibody activity. The physiopathology of the occurrence of a M component with such an activity is discussed.


Pancytopenia and "caillary leak syndrome" with infectious mononucleosis. A 19-year-old man with documented infectious mononucleosis presented with pancytopenia and a megaloblastic bone marrow. He developed a "capillary leak syndrome" with an expanded plasma volume of 9,290 ml and normal right heart and pulmonary artery pressures. The patient had a dramatic recovery after corticosteroid therapy.


Meigs' syndrome. A case report.

Meigs' syndrome. A case report. A case of Meig's syndrome is reported and the rarity of this condition is emphasised. The need for exploratory laparotomy in patients with solid ovarian tumours associated with ascites and pleural effusion, and free of malignant cells, is stressed.


[Transmissible Gastroenteritis in Swine (author's transl)]. Transmissible gastroenteritis or TGE is a virus diarrhoea which occurs in pigs of all ages and is associated with high mortality rates in the young piglets. Growth of virus in the columnar epithelium of the small intestine causes atrophy of the intestinal villi, malabsorption, watery diarrhoea and dehydration. Faecal excretion of virus usually continues up to fourteen days after infection but chronic carriers have been found to occur. TGE is self-limiting on the majority of pig-breeding farms but the virus may persist in particular conditions and an enzootic form of the disease will appear in this case. In typical outbreaks, the diagnosis can usually be based on clinical symptoms. When the disease runs an enzootic course, a clinical diagnosis will be out of the question. TGE should be differentiated from colibacillosis and from another virus diarrhoea, the aetiology of which is not precisely known. A rapid and correct diagnosis may be established by direct fluorescent antibody studies of frozen sections of the small intestine in infected piglets. When sows have been spontaneously infected, their offspring will be protected by lactogenic immunity. The presence of TGE antibodies of IgA class in the milk is required to ensure complete immunity of the piglets lasting for weeks on end. Intramuscular inoculation of a commercially available vaccine in sows will only stimulate the production of antibodies of the IgG class in the milk. These antibodies will merely afford short-lived immunity. The vaccine cannot prevent symptoms of disease from appearing in piglets following infection with virulent TGE virus but it does reduce mortality


Progesterone in the uterus. V. Correlation of the in vitro progesterone metabolism with the progesterone binding in rat uterus. Incubations of rat uterine segments with varying 3H-progesterone concentrations were performed to study the hormone uptake by the tissue. The radioactivity of the uterus and the nutrient medium were plotted in form of a SCATCHARD plot. Additionally, the binding capacity of the uterine cytosol was measured. In both systems, the hormone was found to be associated with two components which differ from each other in their association constants. The progesterone metabolism occuring at a hormone concentration of 10(-6)M and more in the incubation medium is discussed with respect to the affinity and the capacity of the hormone binding components.


Dynamics of estrone glucosiduronate metabolism in dogs. Interest in the metabolism of estrogen conjugates has been increased by the recent demonstration that some of these conjugates can be hydrolysed in vivo, and are thus a source of physiologically-active circulating estrogens. In this report the metabolism of the quantitatively important conjugate estrone glucosiduronate has been studied in dogs, following the intravenous infusion of 3H-estrone glucosiduronate. Arterial plasma levels of radioactive estrone glucosiduronate and of the radioactive metabolites estrone, estradiol-17beta-3-glucosiduronate and estradiol-17alpha-3-glucosiduronate were measured. The metabolic clearance rate of estrone glucosiduronate (MCREG) was determined, as well as conversion ratios for estrone glucosiduronate to estrone (CREG.E), estradiol-17beta-3-glucosiduronate (CREG.E2betaG) and estradiol-17alpha-3-glucosiduronate (CREG.E2alphaG). Sequential values for the above mentioned conversion ratios were obtained and the relationship to time was analysed. Transfer constants for estrone glucosiduronate to estrone (rhoEG.E) were measured. The mean MCREG was 329 L/day/m2, SE 35. The values for CREG.E2betaG and CREG.E2alphaG did not become constant until 80 minutes following the start of infusion. The mean values at a steady state were: CREG.E.021, SE .002, CREG.E2betaG .068, SE .005, CREG.E2alphaG .022, SE .002. The mean value for rhoEG.E was .057, SE .006.


MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones.


Investigations on the level of circulating eosinophils throughout a 24 hour period in parasitic disease. Circulating absolute eosinophil levels were studied over a 24 hour period in a series of 10 patients with presumed parasitological disease. Seven of these ten had the distinct nocturnal increase and a percentage swing paralleling that found in normal subjects. Three patients had a reversed pattern. The latter were thought to have one or other form of filariasis. Two patients with loasis and a "physiological response" had suppression as anticipated to exogenous steroid. It is concluded that steroid administration will not separate parasitic from other causes of eosinophilia.


[Incorporation of radiolabel in vitro into proteins of rat hippocampus synaptosomes when elaborating defensive conditioned reflexes]. The influence of learning local protein synthesis was studied in the rat hippocampal synaptosomes. It is found that elaboration of two-way avoidance conditioned reflex causes a decrease in ability of hippocampal synaptosomes to include H3-leucin into proteins in experiments in vitro. It is suggested that cyclic adenosin 3'5'-monophosphate plays a definite role in controlling protein synthesis in the nerve endings during different influences including learning because its addition to the incubation medium activates sharply this process.


[Peptide-hydrolase activity in different areas of brain with introduction of hydrocortisone and ACTH]. A single introduction of hydrocortisone is established to evoke an increase in the total activity of acid peptide-hydrolase in most areas of the brain. A single administration of ACTH single and long term administration of hydrocortisone was found to increase the specific activity of acid peptide-hydrolase of the soluble fraction. The specific activity of neutral peptide-hydrolase of the soluble fraction increases with a single administration of ACTH and long term administration of hydrocortisone. A single and long term administration of hydrocortisone and ACTH cause an increase in the percentage of the soluble form of peptide-hydrolases of the total activity.


[Procedure for extracting polyphosphoinositides from rat liver tissue and peculiarities of their metabolism]. The content of the rat liver triphosphoinositides and diphosphoinositides was determined in fresh tissue by the extraction with acid chloroform methanol mixture. The content was 7.7 +/- 0.5 mug P and 6.4 +/- 0.5 mug per 1 g of the tissue for triphosphoinositide and diphosphoinositides, respectively. The rapid enzymatic posthumorus changes are shown for the phospholipid content in the liver tissue; 5 min after the amount of triphosphoinositides increased by 19%, diphosphoinositides -- by 13% and that of total phospholipids -- by 11%; subsequently after 30 min after the content of di- and triphosphoinositides decreases below the initial values and that of other phospholipids returns to the initial level. The rate of 32P incorporation into polyphosphoinositide fractions increases rapidly during 1 hour and considerably exceeds that of all other phospholipid fractions studied.


[Localization of viral antigen in cell cultures infected with the IBR-IPV virus]. Using the immunofluorescence method and fluorescein-isothiocyanate-labelled antibodies against the IBR-IPV virus the dynamics was followed up of the production of the viral antigen in primary cell cultures of calf kidney and a permanent cell line of calf kidney infected with IBR-IPV strains isolated in this country. To avoid nonspecific reactions in the fluorescence-and-serologic demonstration of the viral antigen a method was employed for the contrast staining with Evans blue. A positive reaction consisting in the specific fluorescence of the membrane enveloping the nucleus appeared at the earliest four hours after the infection of the cell cultures. No differences were found between the studied IBR-IPV virus strains so far as the place and time of appearance and the development of the viral antigen in the infected cell were concerned with the use of the two types of cell cultures.


[Some properties of strains of the transmissible gastroenteritis virus of swine (TGE) isolated in Bulgaria]. Strains of the swine transmissive gastroenteritis (TGE) virus were isolated for the first time in Bulgaria in 1972. The dynamics was followed up of some strains' propagation in primary cell cultures of kidney tissue and subcultures of the thyroid of pigs. The intracellular virus reached highest titers at the 24--48th hour in the kidney cells, and at the 24--36th hour in the thyroid cells, while the extracellular virus was subjected to inactivation by the 2nd hour after infecting the cultures, by the 4--6th h its titer dropped up to 50 per cent of its initial value, and by the 24th h it was completely inactivated. The viability of the virus was tested after freeze-drying and after it had been stored at 4degreesC and--20degreesC. It was found that chloroform fully inactivates the virus at 4degreesC for 24 hours. The same results were obtained with the use of sodium desoxycholate. The strains isolated in this country form plaques, and with some strains the plaques are of a varying size. Halogenic desoxyuridines (IUDR, BUDR), as well as 8-azoridine do not suppress the multiplication of the tested TGE strains even in high concentrations. Inhibitory effect has 5-bromurazyl which in given concentrations affects the titer of the virus and the size of the plaques formed. Two Bulgarian and two reference strains have lowered their plaque-forming titer by 2 log after being treated with rifamycin-B or rifampicin.


Formaldehyde-ozone-induced fluorescence and ACTH immunoreactivity in basophil tumours of the pituitary. The ACTH cells of human foetal pituitary displayed intense formaldehyde-ozone-induced fluorescence characteristic of peptides or proteins with NH2-terminal tryptophan. Fourteen pituitary tumours were examined histochemically. Of these, two displayed formaldehyde-ozone-induced fluorescence. These two tumours were the only ones to exhibit ACTH immunoreactivity.


[Alpha-1-antitrypsin deficiency in children: liver ultrastructure and speculations (author's transl)]. Fourteen liver biopsies from twelve young patients with liver diseases associated with homozygous, PiZZ phenotype, alpha-1-antitrypsin deficiency in their sera were examined by electron microscopy. In all these biopsies characteristic homogeneous material was found in some hepatocytes and corresponded, when observed on adjacent semithin sections by light microscopy, to the deposit stained by periodic acid Schiff reaction. The accumulation in perinuclear spaces resulted in intranuclear invaginations, but the major deposit was located in lumens of the endoplasmic reticulum. The limiting membranes were rough and smooth but the extent of the latter was so large that only this type of reticulum seemed peculiarly involved in the accumulating process. On the contrary, Golgi complexes did not seen obligatorily involved by this process because, when observed, they appeared almost normal even in heavily overloaded liver cells. At least for the PiZZ phenotype, the abnormal substance would be an asialo form of normal alpha-1-antitrypsin. Thus the subject of this study is the morphologic translation of an impairment in the synthesis of a glycoprotein. In the light of data concerning the synthesis of such proteins our findings lead us to suggest: The ultrastructural patterns observed in alpha-1-antitrypsin deficiency cannot give the expected morphologic evidence of the biochemical data which locate the first binding steps of monosaccharide residues in the rough endoplasmic reticulum. The absence of sialic acid could not result from an enzymatic defect primarily located in Golgi complexes but could be secondary to an impairment in the binding of one monosaccharide residue which improves subsequent fixation of sialic acid, in the smooth endoplasmic reticulum. Finally it seems necessary to emphasize that the relationship between the abnormal substance and various important non specific lesions is largely unknown and that we don't know the significance of polymorphous dense bodies observed in ductular cells during the cholestatic period.


[Comparative light and electron microscopic studies of oncocytic pituitary adenomas (author's transl)]. In a collection of 108 surgically removed, light and electron microscopically studied pituitary tumors, 19 adenomas (17.6%) could be found of which oncocytic tumor cells constituted more than 50%. These showed histologically, in conformity with the criteria of oncocytes, a fairly broad cytoplasm with finely granular or, in part, finely vacuolar structures and distinct cell membranes. The nuclei were predominantly round and moderately rich in chromatin but also in part, pyknotic. In paraffin-embedded sections the tumors could not be distinguished with certainty from chromophobe or moderately granulated acidophil adenomas. In plastic-embedded sections they could be identified by the typical filmy and finely granular feature of the cytoplasm which was distinctly different from conglomerations of secretory granules. Ultrastructurally they were characterized by many densely packed mitochondria. These were, in part, hydropically swollen. Furthermore, 5 tumors exhibited increased hormone-synthesizing organelles, 2 of which induced an acromegaly. Probably the oncocytic pituitary adenomas are secondarily transformed chromophobe or moderately chromophil tumors which must be regarded as independent, for the most part endocrinologically inactive pituitary tumors. In addition to these purely or almost purely oncocytic tumors further 12 adenomas (11.1%) with oncocytic parts constituting between 10 and 50% of the tissue were in our collection. Of these, 5 were moderately or distinctly acidophil adenomas with clinical symptoms of acromegaly; 2 were, for the most part, mucoid cell adenomas with Nelson's syndrome.


[Paracrystallic, intraplasmatic inclusion bodies in human hepatocytes: a structural analytic study (author's transl)]. Electron micrographs from intraplasmatic inclusion bodies of human hepatocytes are described; these paracrystallic aggregations consist of helically arranged filaments. All the observed periodic structures within these bodies can be indicated as originating from the same compound by the use of the Frauenhofer diffraction pattern. Concerning the genesis of these characteristically structured bodies two possibilities are discussed: 1. A special polymeric form of fibrinogen and fibrin built up in vivo. 2. Polymerization of a monomeric enzyme, for example, glutamate dehydrogenase, to paracrystallic bodies by fixation-dependent cross-linkages.


Ultrastructures of glosso-palatal fusion after treatment of meclozine-hydrochloride. The behavior of the epithelial cells on the tongue and palatal processes during glosso-palatal fusion induced by Meclozine-hydrochloride was investigated with light and electron microscopes. Microscopical observations revealed that; at two or three days after the administration, the palatal processes were approximating to the tongue, and the superficial cells on the lateral sides of tongue became swollen and to have inclusion bodies, and in the epithelium on the medial sides of palatal processes, some inclusion bodies appeared too. At the time of contact, the superficial epithelial cells of tongue tended to degenerate markedly, and these degenerating cells were dissociated from the epithelium, and concurrently, superficial layer of the palatal epithelium became to have a lot of inclusion bodies. Between the two tissues, attachment devices developed just after the contact, and then, the cells in the intervening epithelial lining fell into a degeneration gradually. As well known, Meclozine-hydrochloride is one of important miner tranquilizers. From the findings mentioned above, it seemed to be possible that a heterotopic fusion caused with this drug is a result of a destruction of embryonic epithelium on tongue and palatal processes at a certain stage of development.


Ultrastructural localization of plasma lipoproteins in human intracranial arteries. The fine-structural localization of apoB, the major protein constituent of both the low and very low density plasma lipoprotein fractions, was described in human middle cerebral and basilar arteries. Using an immunoperoxidase technique together with electron microscopy, apoB was localized only in arteries with atherosclerotic involvement and to the following regions in these arteries: 1. on the outer aspects of extracellular spherical structures with diameters of 250 to 700 A found predominantly in lipid cores and between bands of collagen fibers of advanced atherosclerotic lesions; 2. on the surface of reduplicated elastica; 3. along collagen fibers and; 4. on aggregates of extracellular spherical lipid globules. These results suggest that the extracellular spheres may represent the fine-structural morphology of deposited low and very low density lipoproteins and that free apoB may be bound to lipid globules, elastica, and collagen fibers.


The presence of complement fixing antibodies to Rous sarcoma virus (Schmidt-Ruppin strain) in patients with various forms of neoplasia. The presence in men of antibodies to Rous sarcoma virus, an oncogenic virus of avian origin, was demonstrated. The highest antibody incidence was found in patients with various forms of cancer (34.4%, as against the value of 12% recorded in blood donors); these patients also showed an increased antibody level - 1/64 titers were detected in 43 out of 7 patients. The possibility of a human infection with animal oncogenic viruses is discussed, without excluding the hypothesis of a paraimmune reaction.


[Effect of Polyakov's "prints" on the catalytic properties of an enzyme substrate system]. Silicagels, formed in presence of an enzyme (histidine decarboxylase from Micrococcus sp. n.), substrate (L-histidine-HCl-H2O) and inhibitor (imidazole) (so-called Polyakov's "print") exhibited specific catalytic properties in the reaction of L-histidine decarboxylation. The "prints" of the enzyme, inhibitor and substrate increased the activity of the enzyme-substrate system studied. The increased activity was probably due to the specific adsorption of imidazole ring of the substrate molecule by the "print".


[Fluorimetric ultramicrodetermination of the dansyl derivatives of cyclic 3'5-AMP by thin-layer chromatography]. A new fluoriemtric ultramicromethod was developed for quantiative determination of cyclic 3',5'-AMP as derivative of dansyl chloride using silica gel thin-layer chromatography. In presence of dansyl chloride cyclic 3',5'-AMP formed a fluorescent complex. A spot of dansyl derivative of cyclic 3',5'-AMP was photographed on a reversible colour film, after which the colour intensity of the spot on the film was determined directly by a special densitometer. Content of cyclic 3',5'-AMP was studied in different regions of rat brain. The in fluence of some psychotropic drugs on the level of cyclic 3',5'-AMP was studied using this method. The method was highly sensitive and reproducible and enabled to determine 10(-10) -- 10(-11) M cyclic 3',5'-AMP.


[Solubilization of cytochrome c in ischemic liver tissue]. Dynamics of cytochrome oxidase inactivation was studied in ischemic liver tissue using tetramethyl paraphenylene diamine (TMPD-oxidase) and cytochrome c (cytochrome c oxidase) as substrates. The cytochrome c ovidase activity was determined in presence of low concentrations (0.03%) of Triton X-100 (the total activity) and without the detergent (the free activity). Within 60 min after the restriction of oxygen supply to the liver tissue TMPD-oxidase was inactivated almost completely, at the same time cytochrome c oxidase maintained its activity. The free enzymatic activity became equal to the total activity; this phenomenon demonstrated an increased permeability of the external mitochondrial membrane for cytochrome c. The decrease in the TMPD-oxidase activity was considered to be due to the cytochrome c solubilization. This assumption was supported by the experiments, in which the addition of cytochrome c into the incubation mixture restored the enzymatic activity to the initial level. Hypotonic solutions and treatment of mitochondria with phospholipase A were found to simulate the impairment of the organelles in ischemic liver tissue. Increased peroxidation of unsaturated fatty acids in presence of ascorbic acid and ferrous ions was not accompanied by solubilization of cytochrome c.


[Stimulation by cyclic adenosine-3'5'-monophosphate by Na+, K+-activated ATPase from rabbit kidney]. Cyclic 3',5-AMP in vitro increased the activity of Na+, K+-ATPase, isolated from cortex and medulla of rabbit kidney. Maximal stimulating effect was observed in kidney cortex at 10(-6) M concentration and in medulla at 10(-4) M concentration of 3',5'-AMP. Under these conditions the enzymatic activity was increased by 24.6 +/- 4.1% and 27.9 +/- 7.7%, respectively. These data suggest that Na+, K+-ATPase, activated by cyclic 3',5'-AMP, is directly involved in the mechanism of Na+ transport in cells of osmoregulating organs.


[Ultramorphometry of cells in a hamster embryo fibroblast culture following transformation by Rous sarcoma virus]. Changes in mitochondria, ergastoplasma and the polyribosomal apparatus of FHE (fibroblasts of hamster embryo) cell culture were studied in the kinetics of their malignification with Rous sarcoma virus. Considerable alterations were revealed in the organization of protein-synthetising cytoplasmic organells, manifested in the pronounced enhancement of nonspecific protein synthesis and reduction of ergastoplasma. This process starts immediately after the infection and shows a character approximating the exponents. On the part of the mitochondrial apparatus no differences between the experiment and control were revealed.


[Effect of ACTH on the excretion of acid glycosaminoglycans in urine and on the content of haptoglobin in blood serum of rats in acute aseptic inflammation]. In aseptic inflammation an increase in excretion of acid glucosoaminoglycans with urine of rats was an earlier evidence for destructive processes in the main substance of connective tissues than an increase in content of haptoglobin in blood serum. The increase in content of haptoglobin in blood serum was probably caused by beginning reparative processes in the centre of impairment. The centre of inflammation, caused by subcutaneous administration of turpentine simultaneously with repeated injections of high doses of ACTH, was maintained in the rats longer than in animals, which were not treated with ACTH. In the case the most distinct increase in excretion of glycosoaminoglycans with urine was observed; content of haptoglobin was also increased in blood serum.


[A kinetic analysis of the growth of transplanted tumors and their metastasis]. Under study were kinetic regularities in development and incorporation of tritium labelled thymidine into cells of two experimental metastasizing tumors -- Zajdela ascites hepatoma and Walker carcinosarcoma, transplanted intratesticulary. Primary tumors and their metastases in regional lymph nodes show certain differences relative both to the rate of the process and intensity of the DNA synthesis, and relative number of cells with incorporated labelled thymidine.


A new serum lipoprotein associated erythrocyte antigen which reacts with a monoclonal IgM. The stored human red blood cell SHRBC antigen. A monoclonal IgM (IgM) was found to react with stored human red blood cells (SHRBC) and human low density lipoprotein (LDL). IgM Re Fab fragment was reactive. SHRBC antigen was present, in a hidden state, in all fresh human ABO erythrocytes studies; it was not present in fresh or stored animal RBC. Cross reactivity of SHRBC and LDL antigens against IgM Re and IgM Re Fab was demonstrated. In contrast with SHRBC antigen, LDL antigen has no species specificity and was also found in rabbit and rat LDL. Furthermore, cross-reacting soluble inhibitors were also found in human saliva, and in a small molecule fraction issued from human and rabbit serum. The IgM Re also reacted with human and animal glomerular membrane. These findings are suggestive of two closely related but not identical antigens: a human specific SHRBC antigen and a LDL-associated, SHRBC-like antigen, which is a secreted, non-human specific substance. The former is part of the human RBC structure, the latter is a soluble molecule which may be found in saliva and in serum where it may be free or bound to LDL; it also binds to glomerular membranes.


[A modified method for phosphoribosyl pyrophosphate synthesis]. A modified method for synthesis of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and ATP in presence of ribose phosphate pyrophosphokinase (RPPPK) was developed. RPPPK was isolated from extracts of acetone powder of rabbit liver tissue, using alcohol fractionation of proteins. The protein fraction, containing RPPPK, was isolated at 35% saturation with 96% ethyl alcohol. The identification of the synthesized preparation of PRPP was carried out in enzymatic reaction with adenine- and inosine phosphoribosyl transferases, using labelled adenine and guanine. The obtained product of reaction (AMP and GMP) were precipitated with lantane chloride.


[Mechanism of changes in oxidative phosphorylation in the kidney in nephropathy caused by post-transfusion complications]. A decrease in cytochrome c oxidase activity was observed in kidney tissue within 40 min after the transfusion of incompatible blood; at the same time, the succinate dehydrogenase activity was not altered. Opposite ratios (as compared with normal kidney) of the enzymatic activities were found within 24 hrs after a heterohemotransfusion. An addition of 5 M succinate to the kidney homogenate in vitro or administration of the substance at a dose of 8 mg per 100 g of body weight in vivo caused an activation of free oxidation and a decrease of phosphorylation. The addition of 50 M succinate, combined with hexokinase and NADH2, into the homogenate distinctly increased both the rate of tissue respiration and the coupled phosphorylation.


[Effect of hydrocortisone on lipid composition of blood serum lipoproteins in the development of experimental atherosclerosis]. Single administration of hydrocortisone into rabbits with experimental atherosclerosis increased the content of atherogenous classes of lipoproteins (Low Density Lipoproteins (LDL) and Very Low Density Lipoproteins (VLDL) in the animals with distinct atheromatosis. Content of the lipoproteins was decreased in animals, which had no atheromatous alterations in aorta under the effect of atherogenous diet. Within 5 hrs after the single administration of hydrocortisone in rabbits with pronounced atheromatosis of aorta relative content of cholesterol was increased in the VLDL fraction. In rabbits, resistant to development of atheromatosis, composition of VLDL was not altered. Under the effect of hydrocortisone the LDL fraction fo lipid composition was altered in the direction of relative increase in triglycerides content. In the LDL fractions subfractions were observed, which were similar to the VLDL in their cholesterol/triglycerides ratios. The data obtained suggest that in blood plasma transformation of the lipoproteins was impaired under the effect of hydrocortisone. Hydrocortisone influenced the spectrum and lipid composition of lipoproteins in blood serum independently of the degree of hypercholesterolaemia.


[2 types of oncornavirus viroins in epithelial cells from human milk]. Virions of types B and C similar to previously known mammal oncornaviruses were found in tissue cultures prepared from epithelial cells sedimented from the milk of a lactating woman with mammary cancer (HEC-31) and the milk of two clinically normal women (HEC-33 and HEC-34). In HEC-33 culture type C particles were predominant quantitatively. All the three milk specimens gave an identical precipitation line with antiserum for the milk of the mammary cancer patient as well as sequences forming molecular hybrids with DNA product of oncornavirus type D. At the same time, no positive immunologic reaction was obtained with the test system for oncornavirus type D from HEp-2 cells.


[Development of poliovirus infection in laboratory animals of different species]. The capacity of vaccine and virulent strains of poliomyelitis virus to multiply in laboratory animals of different species was studied. Virus reproduction was judged by formation of photoresistant virus progeny in response to inoculation of the animals with photosensitized virus. Multiplication of virulent poliomyelitis virus strains observed in the majority of animal species examined (monkeys, newborn and adult cotton rats, newborn and adult white mice, chickens, chick embryos) resulted in active formation of photoresistant virus population and in some cases was accompanied by clinical symptoms of the disease. Multiplication of vaccine strains was observed in a smaller number of animal species and was limited, as a rule. Among non-primate animals, newborn cotton rats were most susceptible to poliovirus infection. Newborn guinea pigs were the only species of laboratory animals in which no multiplication of any of the six strains under study could be detected.


[Virological study of simian hemorrhagic fever]. The results of a comparative study of different routes of inoculation of simian hemorrhagic fever (SHF) virus to Macaca monkeys are presented as well as the results of virological examinations of sick animals. Only the parenteral route of inoculation has been found to be effective. After virus penetration, a long-term viremia and generalization of the infection are observed. The virus is found in the brain, the spinal cord and bone marrow, the spleen, the liver, the kidneys, the cerebrospinal fluid, the urine and nasopharyngeal washings. By the fluorescent antibody technique the virus-specific antigen is demonstrated in the capillary endothelium, neurons and glial cells of the brain, and in the reticulo-endothelial and macrophagal elements of parenchymatous organs.


[Use of the immunofluorescence test in the differential diagnosis of acute and latent adenovirus infections in adult]. Regular laboratory and clinical examinations were carried out in 150 patients with acute respiratory diseases and 25 normal subjects from family foci in whom adenovirus antigen was found in the epithelial cells of the nasal mucosa by means of the immunofluorescence test upon admission. By combinations of various laboratory methods adenovirus infection was confirmed in all the subjects under study. In preparations obtained from normal subjects, predominantly nuclear localization of adenovirus antigen was observed. In patients, localization of the antigen varied. Detection of cells with nuclear localization of adenovirus antigen, the regularity of this localization and the duration of this finding suggest latent infection, whereas findings of cells with cytoplasmic localization of the antigen and an increase in the number of such cells in the course of the disease suggest active adenovirus infection.


[Preparation of immune serums for the identification of rhinoviruses]. Six schedules of immunization of rabbits, guinea pigs and rats for production of antirhinovirus immune sera were studied. Sera with virus-neutralizing antibody titers of 1:1000 to 1:50,000 were obtained in rabbits immunized into popliteal lymph nodes. The resulting sera had high titers of antibody to cell components and neutralized the cytopathic effect induced by heterologous strains. Sera from which cell components had been absorbed showed strict type-specificity in the neutralization and indirect immunofluorescent tests. A mixture of sera has been shown to be useful for identification of rhinoviruses by the immunofluorescent procedure.


[The role of cyclic AMP and Ca in the altered permeability of tumour cells grown with a deficiency of Mg]. Yoshida-Ascites tumour cells grown with a deficiency of Mg show an increased passive permeability. This results in an accelerated efflux of Na+. The uptake of aminobutyric acid is decreased, while its release is unchanged. The uptake and release of alpha-methylglucopyranoside are unchanged. In the cells grown with a deficiency of Mg, the concentration of cyclic AMP is slightly increased. The addition of dibutyryl cyclic AMP results in similar but smaller changes in the cellular concentration of cations, to those found in Mg deficiency. It is suggested that the effects of Mg deficiency result from the action of cyclic AMP and/or an increase in the Ca concentration of the cell.


[Biochemical investigations of cancer cachexia: I. Tumour induced changes of glycogenolysis and gluconeogenesis of Walker carcinoma bearing rats (author's transl)]. Rats (weight 150-200 g) bearing Walker-carcinoma showed tumour size dependent hypoglycemia, diminished mobilization of glycogen following glucagon stimulation and elevated values of the enzyme activity of glucose-6-(P)-ase. A further hormonal stimulation of this enzyme activity towards the values observed in normal rats after betamethasone stimulation was not possible. The values of the enzyme fructose-1,6-di-(P)-ase in liver of tumour bearing rats equalled those found in normal controls and did not show any rise after application of betamethasone. The serum levels of free fatty acids did not show any difference between normal controls and tumour bearing rats, and displayed an equal rise after intensive stimulation of peripheral lipolysis.


Attempts to induce tubular deformations and subsequent mixed tumours from organotypic cultures of mouse renal mesenchyma. With the aim of expanding knowledge on the pathogenesis of nephroblastomata, an embryological organ culture system (Grobstein, 1956) was tested for its applicability to in vitro carcinogenesis experiments by using murine sarcoma virus (MSV-M) and 3-methylcholanthrene (MCA). Treatment of CBA/H-T6 mouse metanephrogenic mesenchyma with MSV-M at the pretubular stage neither disturbed the glomerulogenesis nor induced rapid malignant transformation. Treatment of the same tissues with MCA considerably inhibited the glomerulogenesis but failed to also reduce rapid malignant transformation. However, one MSV-M, one MCA and two untreated cultures showed malignant transformation after prolonged survival in vitro and produced different histological types of tumours upon transplantation into newborn CBA/H-T6 mice.


[Transplantable sebaceous adenoma of the mouse with virus particles studied by electron microscopy (author's transl)]. Histology and ultrastructure of a sebaceous adenoma of the mouse -- derived from i.p.-injection of 0.1 ml DNA, isolated from cells of a transplantable mouse-leukemia -- were studied. The original tumour and all transplanted tumours display the same tissular differentiation. In all tumours virus particles were found. Structure and behaviour of the intracytoplasmic A-particles resemble those of the mouse mammary tumour virus while the C-particles found extracellular were identical with the leukemia viruses of the mouse. It might be suspected that mammary tumour virus and leukemia viruses are either non specific or that a new virus is present in the sebaceous adenoma.


35S incorporation into sulfated mucopolysaccharides from embryonic, normal, and neoplastic liver cells. The incorporation of 35S into the sulfated mucopolysaccharides from hepatoma, normal and embryonic liver cells has been studied by means of anion exchange chromatography of the isolated mucopolysaccharide. Comparatively to liver cells, while showing a higher labeling of low sulfated mucopolysaccharides the hepatoma cells incorporate much less 35S into the heparin fraction.


[Pathogenesis of neural lesions in Marek's disease. II. Transmission of neural lesions by spleen cells from ill donors (author's transl) ]. Viable spleen lymphocytes of 13 chickens with clinical and histological signs of Marek's disease were transferred by intravenous injection to 46 chickens 4-10 days old, X-rayed 24 hours before inoculation. Histologically Marek-like neural lesions were almost regularly observed in the chickens after 6-14 days. Chickens having received destroyed spleen lymphocytes of Marek-donors were free of nerve infiltrations. There were also no neural lesions detectable within 14 days after application of pathogenic Marek's disease virus alone, or in combination with viable spleen cells from healthy donors immunized against Marek's disease. These results exclude that the formation of neural lesions 6-14 days following the spleen cell transfer is solely induced by the virus.


Reactions of essential sulfhydryl residues of dehydrogenases with nicotinamide-(S-methylmercury-thioinosine) dinucleotide. Nicotinamide-(S-methylmercury-thioinosine) dinucleotide was formed by reaction of nicotinamide-(6-thiopurine) dinucleotide with methylmercury chloride.  The compound exhibits coenzyme properties in the test with LDH (Km=1.5 X 10(-4) M, Vmax=12500) and LADH (Km=1.7 X 10(-4) M, Vmax=27) and inactivates YADH and GAPDH. From incubations with LDH and LADH the mercury containing coenzyme could be regarded by column be qualified for the X-ray structure analysis of the coenzyme-enzyme complex for some dehyrogenases based on the proportion of the heavy metal.


The ultrastructure of macrogametes of Eimeria ferrisi Levine and Ivens 1965 in Mus musculus. Macrogametes of Eimeria ferrisi occurred in epithelial cells of the cecum and colon of Mus musculus and were studied by electron microscopy. Young stages were identified as macrogamonts by the presence of wall-forming bodies. At first an outerlimiting membrane and remnants of the inner membrane complex of the former merozoite pellicle were present; the latter was later lost but in mature macrogametes 3 limiting membranes were observed. Type II wall-forming bodies appeared before type I; the former developed in expanded cisternae of the endoplasmic reticulum whereas the latter were smaller in size and appeared in the ground substance of the cytoplasm. After formation of the oocyst wall the bodies of the 2 types were no longer visible. The presenceodies of the 2 types were no longer visible. The persistence of micronemes in mature macrogametes and the presence of numerous layers of rough endoplasmic reticulum during wall formation have not been previously reported.


Electronic structure and spatial arrangement of C2v-coordinated ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin. The electronic term scheme of ferric iron in metmyoglobin, metmyoglobin fluoride, and methemoglobin is evaluated by a Hamiltonian which involves the Coulomb repulsion of the 3d electrons, their interaction with the C2v-coordinated ligands, and spin-orbit coupling. The adjustable parameters of the theory were determined by a least squares fit to experimental EPR, susceptibility, and far-infrared data reported in the literature. According to these results, the structural properties of the ferric ion and its neighboring ligands were discussed by means of group theoretical arguments: An increasing out of plane position of the ferric ion is found in the sequence metHb--metMb--MbF which corresponds to an increasing binding strength with the axial ligands.


[Ischemic contractures of muscle and nerve lesions (author's transl)]. Reporting 14 own cases symptomatology and treatment of the common ischemic syndromes of the extremities (Volkmann's contracture, thumb adduction contracture respectively contracture of the intrinsic hand muscles and anterior tibial syndrome) including the regularly concomitant nerve lesions are discussed. Edema and compression beyond the primary ischemia are essential factors in pathogenesis of nerve and muscle lesions. The electromyographic examination is helpful in diagnosis, prognosis and treatment of the severe sequelae of nerve and muscle. Since late diagnosis yields poor therapeutical results, early recognition of ischemic states and prophylaxis are most important.


Interaction between dehydrogenases and a new NAD -isomer. A new NAD -isomer was prepared, in which the D-ribose of the adenosine moiety was substituted by the enantiomeric L-ribose. As compared to nicotinamide-adenine-dinucleotide (NAD) and NADH the coenzyme isomer (D,L)-NAD and its dihydroform (D,L)-NADH are far less tightly bound to lactate dehydrogenase and alcohol dehydrogenase from horse liver. In the presence of the second substrate (D,L)-NAD and (D,L)-NADH act as hydrogen acceptor and hydrogen donator, respectively, with lactate dehydrogenase and alcohol dehydrogenases from horse liver and yeast. Compared to NAD and NADH the Michaelis constants are always increased, the catalytic constants (V/Et) were found to be decreased except for the dihydroform reacting with alcohol dehydrogenase from liver.


[Peripheral nerve injury due to total replacement of the hip-joint (author's transl)]. Report on peripheral nerve lesions due to total replacement of the hip-joint based on the literature and the authors' own experience. In 15 patients our diagnosis was made on clinical and electromyographic evidence. 16 endoprostheses had been inserted. The femoral nerve was involved on 12 occasions, the sciatic in 5, the glutei in 5, the obturator in 2, the lateral cutaneous femoris in 2 and the posterior cutaneous in 1 instances. One has to count on about 1% of such lesions. This type of paresis has to be distingushed from pseudopareses for which electromyography was proved very effective. Damage due to overstretching is probably the main cause. Treatment with thorough physiotherapy and faradic stimulation is needed. When this is done the prognosis is generally favourable. In some cases, however, these complications may limit the success of the operation and postoperative disability may be worse than before.


In vitro transformation of chicken bone marrow cells with avian erythroblastosis virus. An in vitro transformation of bone marrow cells has been demonstrated for two strains of avian erythroblastosis virus (AEV-R and AEV-ES4). The transformed cells were indistinguishable from in vivo transformed erythroblasts in morphology and staining characteristics and could be propagated to large numbers. The transformation efficiency could be greatly increased by the addition of dimethylsulfoxide (DMSO). The number of foci appearing in the presence of DMSO was proportional to the virus concentration.


[Isolation of "pregnancy-zone" proteins using immuno absorbents and study of possible enzyme activities]. The purification of the pregnancy zone protein by means of immunoadsorbents is described. The pregnancy zone protein antibody was isolated from an absorbed rabbit antiserum and coupled with CNBr-activated sepharose. The pregnancy zone protein was isolated from pregnancy serum by the specific antibody cross-linked with sepharose. Contaminating serum proteins were eliminated by "inverse" immunoadsorption using antibodies against these proteins coupled with sepharose. An immunoelectrophoretically pure pregnancy zone protein was obtained. By means of a combination of immunoprecipitation and enzyme reaction in agar gel could be excluded that the pregnancy zone protein possesses activities of the following 11 enzymes: ceruloplasmin, leucine amino peptidase, alkaline phosphatase, carboxylic  esterase, lactate dehydrogenase, malate dehydrogenase, glycerophosphate dehydrogenase, glucose-6-phosphat-dehydrogenase, cholinesterase, acetyl cholinesterase and oxytocinase.


[Formation and persistence of latex-agglutination-inhibiting IgG- and IgM-antibodies in rabbits inoculated with poliomyelitis, Coxsackie and encephalomyocarditis viruses (author's transl)]. The formation and presistence of virus specific IgG- and IgM-antibodies produced in rabbits after a single dose of poliomyelitisvirus, coxsackievirus or encephalomyocarditisvirus were tested comparatively by latex-agglutination-inhibition test, hemagglutination-inhibition test and neutralization test. The animals were immunized either intravenously alone or with Freund's complete adjuvant. The IgM-antibodies were only detectable for a short time by the three tests. In the IgG-fraction and in the unfractionated serum the neutralizing antibodies persisted without any loss in titer during the period observed, whereas the latex-agglutination-inhibiting and hemagglutination-inhibiting antibodies showed a significant decrease. The hemagglutination-inhibiting antibodies required 23 weeks (Figure 5), the latex-agglutination-inhibiting antibodies 7 weeks (without Freund's complete adjuvant; Figure 1 and 3) or about 16 weeks (with Freund's complete adjuvant; Figure 2, 4 and 5) respectively to decline to 25% of their maximum titer.


Studies on the energetic metabolism of Shigella flexneri x Escherichia coli hybrids devoid of penetration ability. III. Catalase and phosphatase activity. The catalase and phosphatase activity of avirulent by keratoconjunctival test of guinea pigs lac+, kcp- hybrids that have lost their ability of penetrating in the epithelium, received from virulent strains Shigella flexneri (Sh. flexneri 222 5a and Sh. flexneri M42-43) and donor strains Escherichia coli (E. coli K-12, P4x and E. coli H) was investigated. It was established that there is no any dependence between the lost of virulence of the hybrids and the level of the catalase activity. During the study of the phosphatase activity it was established, that in comparison with the recipient virulent shigella strains, the investigated avirulent lac+-hybrids revealed higher values of the enzyme activity.


[Aeromonas punctata subsp. caviae as the causative agent of acute gastroenteritis (author's transl)]. Since in the past, Aeromonas hydrophila had been isolated from all cases of human infection described. A. punctata and the anaerogenic sub-species were considered as apathogenic. From the case described, a close association between acute diarrhea with vomiting and the identification of A. punctata subsp. caviae becomes evident so that a conditional pathogenicity of this sub-species must be assumed. The question is discussed whether a preceding disturbance of the intestinal habitat in the presence of a particular susceptibility of the gastrointestinal tract promoted gastro-enteritis. Infection may have been brought about by the ingestion of surface water contaminated by sewage. Attention is again drawn to the fact that in the case of enteritis occuring during the open-air bathing season, faeces samples should also be examined for their Aeromonas content which may be performed by a simple indophenol or so-called cytochrome oxidase reaction of the aerobic flora in feces by rubbing off colonies into a corresponding test strip.


Serologic examination of birds from the area of Southern Moravia for the presence of antibodies against arboviruses of the groups alfa, flavo, Bunyamwera supergroup, and the virus Yaba 1-Lednice 110. I. Domestic fowls. 196 geese, 141 ducks, and 100 hens from 9 localities of the South Moravian region (District of Breclav) were examined by means of the haemagglutination-inhibition test (HIT) for the presence of antibodies against 12 arbovirus antigens of the groups Alfavirus (Western Equine Encephalitis (WEE), Eastern Equine Encephalitis (EEE), Semliki, Sindbis, Chikungunya, O'nyong-nyong), Flavovirus (Tick-borne Encephalitis (TBE), Dengue and West Nile Virus (WN), Bunyamwera Supergroup (Tahna and Beta Calovo), and the Yaba 1-Lednice 110 Virus. In tested fowls antibodies were mostly found against Yaba 1-Lednice 110 Virus, namely 3.6% in geese and 17.7% in ducks. Antibodies against Calovo Virus were found in only 1 of the tested ducks. All sera of hens were negative. Antibodies against arboviruses of the Alfa-and Flavovirus groups were not detected.


Receptor for 5alpha-dihydrotestosterone from Streptomyces hydrogenans. Streptomyces hydrogenans exhibits binding activity for 5alpha-dihydrotestosterone (17 beta-hydroxy-5alpha-androstan-3-one) in vivo. A cell free homogenate from the microorganism binds 5alpha-dihydrotestosterone in vitro as well. The association constant is 10(8) M-1 at 4 degrees C. Progesterone, but neither testerone nor cyproterone, competes with 5alpha-dihydrotestosterone for binding. The binding fraction from Streptomyces hydrogenans permits a simple assay for 5 alpha-dihydrotestosterone in biological samples.


[An experimental study of mixed tularemia and Omsk hemorrhagic fever infection in muskrats]. Musk-rats were infected simultaneously and at three-day interval with tularemia and Omsk hemorrhagic fever (OHF); the course of this mixed infection under the mentioned conditions were studied. Virological, microbiological and morphological data indicated that infection of musk-rats with OHF and tularemia caused development of mixed infection in them. A more severe course of mixed infection was associated with enhanced vascular affections caused by the action of the OHF virus. An inhibition of tularemia caused by the OHF development was noted in the course of mixed infection.


Glucocorticoid therapy for acute myocardial infarction. Several uncontrolled early studies established that corticosteroid administration to patients with ischemic heart disease and cardiogenic shock was relatively safe. Whether or not the glucocorticoids were of benefit or not remained unclear when mortality was used as an index of efficacy. Hemodynamically, glucocorticoids may decrease peripheral vascular resistance, increase cardiac output and coronary blood flow, but leave myocardial contractility unchanged. The mean arterial pressure may vary unpredictably. The increase in coronary blood flow may certainly be advantageous in treating patients with acute myocardial infarction. The decrease in infarct size recently reported, if confirmed in man, would also be desirable. However, there is a paucity of good data concerning the effects of corticosteroids in man postinfarction. In addition, through unproved mechanisms, the corticosteroids decrease the extent and severity of myocardial ischemic injury. While these fundamental actions may not result in improved mortality, ongoing studies suggest that minimization of ischemic injury may ultimately prove to be most rewarding in the prevention of cardiogenic shock.


Stimulatory effect of FSH in vitro on the extracellularly active cyclic AMP phosphodiesterase in the prepubertal rat ovary. Intact prepubertal rat ovaries were incubated with radioactively labelled adenosine 3',5'-cyclic monophosphate (cAMP) in Krebs bicarbonate buffer containing glucose. The rate of degradation of cAMP was determined by measuring the radioactivity in the medium after precipitation with Ba(OH)2 and ZnSO4. The fate of the nucleotide was followed by measuring the products in the incubation medium. Paper chromatography was used for the separation and identification of these products. It was found that cAMP was degraded to AMP, which in turn was degraded to inorganic phosphate (Pi) and adenosine. An uptake of labelled products was also observed. NIH-FSH-S9 (10 and 100 mug/ml), but not NIH-LH-B8 (0.1-100 mug/ml), increased the degradation of cAMP. Concomitantly, an increased accumulation of labelled adenosine and Pi as well as an increased uptake of labelled products were seen. Kinetic studies with low concentrations of cAMP (0.125-0.025 mumol/l) revealed an apparent Km value of 0.12 mumol/l for the phosphodiesterase (PDE) activity. FSH significantly changed the slope of the curve in the Lineweaver-Burk plot by increasing the PDE activity. The increased PDE activity in the presence of FSH is discussed in relation to earlier findings of differences in action betweeh LH and FSH on the cAMP system in the prepubertal rat ovary.


[The effect of arecoline on the structure of sleep and wakefulness in hens]. In chronic experiments on hens, studies have been made on the role of cholinergic mechanisms in regulation of the cycles "awakefulness-sleep". A cholinomimetic, arecoline, was used which stimulates M-cholinoreceptive brain neurons. Arecoline was injected intramuscularly in a dose 0.2 mg/kg of body weight. It was shown that cholinergic mechanisms are involved into the formation of "awakefulness-sleep" cycles in hens. Activation of these mechanisms facilitates paradoxical stage of sleep and expecially such its components as rapid eye movements, the decrease of tonus in neck muscles and, presumably, ponto-geniculo-occipital discharge. Arecolin affects not only the structure of paradoxical sleep, but both the awakefulness and mechanisms of slow-wave sleep stage.


Polysaccharides, proteins, nucleic acids, enzymes and sulfate uptake of the gastric epithelial cells of Xenodon merremii Wagler, 1824 (Ophidia): an histochemical and autoradiographic study. Several histochemical tests were applied to the lining and glandular gastric epithelium of Xenodon merremii. Our observations, after discussion and interpretation, conducted to the following conclusions: 1. the surface epithelial cells, the neck cells, the body cells and the pyloric cells showed neutral polysaccharides, arginine, tyrosine, cysteine, acid phosphatase, AMPase and esterase. 2. besides these substances, in the surface epithelial cells was found tryptophan and in the body cells tryptophan and RNA.


[Functional topography of somatic muscles in euciscus idus]. The intensity of tissue respiration and anaerobic glycolysis, as well as the activity of succinic oxidase, cytochrome oxidase, lactate dehydrogenase and ATPase in skeletal muscles of the ide L. idus significantly increase from head to tail. Cranio-caudal gradients of the intensity of tissue respiration and the enzymic activity are especially evident in the red muscle, namely m. lateralis superficialis. In white m. lateralis magnus, the gradient of glycolytic activity is most pronounced. Biochemical and morphological peculiarities of muscles are discussed in relation to functional profile of the latter.


Histochemical localization of hydrolytic enzymes in the buffalo spermatozoa. A histochemical study was made of the localization of alkaline and acid phosphatase, 5-nucleotidase and ATPase in the ejaculated buffalo spermatozoa. Most of these hydrolytic enzymes were localized in the mid-piece, and post-nuclear cap. Acid and alkaline phosphatase activities were also present in the acrosome. The presence of hydrolytic enzymes at these sites is discussed and correlated with the permeability and transport processes across the membranes of spermatozoa as well as with the process of energy production and fertilization.


Thyroid C-cells in normal and goitrous gland: a histochemical study. 16 cases of goiter were examined for C-cells and 4 cases with normal thyroid gland. C-cells identification was based on masked metachromasia. There was stated both in toxic, atoxic goitrous tissue two forms of C-cells. The first characterized by positive metachromatic reaction and weak argyrophinty, the second type of C-cells were orthochromatic and argyrophilic. Metachromatic C-cells characterized as a rule by high alpha glycero phosphate menadione reductase as well succinic dehydrogenase and cytochrome oxidase.


Intracranial hemangiopericytoma: ultrastructural evidence of its leiomyoblastic differentiation. Two intracranial hemangiopericytomas revealed subcellular features of the neoplastic elements comparable to those observed in normal and neoplastic smooth muscle. These included intracytoplasmic and submembranous fusiform dense bodies associated with bundles of filaments, tapered configuration of cells with grouping of cytoplasmic organelles at nuclear poles and deposition of intercellular basal lamina-like material. These observations are consistent with the pericytic origin but opposed to the ofttimes postulated meningothelial derivation of the neoplasm.


Some effects of intracerebral lead implantation in the rat. Pellets of lead acetate were implanted into the forebrains of adult rats which were sacrificed at intervals between 4 days and 4 weeks thereafter. Parenchymal  necrosis and a number of reactive changes including edema and macrophage invasion were observed. Lead deposits were found in the extracellular spaces and within macrophages but only to a slight extent within glial or meningeal cells. Vascular changes were quite remarkable and included proliferation and the appearance of fenestrated blood vessels as well as some with tubular bodies and striking increases in the number of pinocytotic vesicles.


Differential morphological reaction of experimental CNS tumour clones in vitro to dibutyryl cyclic AMP or serum-free medium, resp. Six clones from methylnitrosourea (MNU) or ethylnitrosourea (ENU) induced tumours obtained in the nervous system of the rat were cultured in serum-free medium or treated with dibutyryl cyclic AMP (db cAMP) in vitro. All clones originated from longterm cultures. Three clones forming sarcomas after syngeneic transplantation showed only very slight changes following treatment, whereas the three glioma clones showed striking alterations. They formed long processes or showed rounding of their perikarya. In serum-free medium the cellular shape is intermediate between that seen in normal conditions and the seen in db cAMP treated cultures. The altered cultures resemble the primary cultures of the respective tumours. The relationship of these alterations to tumour types are discussed.


Chemotherapeutic effects of some alkylating derivatives of nitrosourea on the development of tumors transplacentally induced in rats by ENU. The application of BCNU, CCNU and MeCCNU has been shown to greatly reduce the number of tumors induced in rats by transplacentally administered ENU and to inhibit the full development of tumor proliferation. Moreover, no neurinomas appeared after treatment with CCNU. The application of GCNU proved to be much less effective. Our statistics in the form of tables showing these findings are included and discussed.


Mononucleosis-associated subacute sclerosing panencephalitis. A thirteen-year-old girl died of subacute sclerosing panencephalitis (SSPE) which occurred as part of a complex encephalitic illness related to acute infectious mononucleosis. The cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) fluorescent antibody (FA) titer was 1:64. Electron microscopic examination revealed 17 nanometer (nm) diameter paramyxovirus-like nucleocapsids in brain sections and 90 nm diameter herpes virus-like enveloped particles in negatively stained brain tissue extracts. Indirect FA staining of cerebral cortex sections demonstrated both measles and EBV antigenic material. EBV antigenic material has not previously been demonstrated in brain tissue. The proportion of B lymphocytes among the patient's peripheral blood lymphocytes was significantly increased as compared to normal controls, while the T lymphocyte percentage was normal. It is suggested that defects in cellular immunity associated with infectious mononucleosis may have been responsible for activation of latent measles-like virus. This is the tenth reported case in which two viruses have been associated with SSPE. This is the third instance in the authors' experience in which acute EBV infection has occurred coincident with the development of SSPE.


[Niemann-Pick disease (Crocker's type C): ultrastructural study of a case (author's transl)]. The authors report electron microscopic findings in brain, bone marrow and liver biopsies in a case of juvenile Niemann-Pick disease (Crocker's type C). The diagnosis was supported by clinical data increase of blood sphingomyelin and vacuolated histiocytes in bone marrow and liver. Neurons and glial cells were filled with two types of cytosomes: classical multilamellar bodies and unusual pleiomorphic bodies. The latter type probably showed some lipofuscinic component. The relationship between type C and classical Niemann-Pick disease is discussed.


Ultrastructure of the Gunn rat substantia nigra. II. Mitochondrial changes. The substantia nigra of hyperbilirubinemic (Gunn) rats was studied using light and electron microscopic techniques. PAS-positive inclusions were observed within the neuronal somata of animals 2 to 12 weeks old. Incubation of tissue sections in 0.5% diastase inhibited most of the positive PAS reaction, thus indicating the intraneuronal presence of glycogen. Electron microscopic examination of the tissue substantiated the histochemical data. Mitochondria in neuronal somata contained collections of osmiophilic granules, 200-300 A diameter, in their intracristal (intermembrane) space. These granules were typical of beta-glycogen particles. In increasingly older animals (from 2 to 12 weeks old) progressively fewer collections of intramitochondrial glycogen were observed. In these same animals there was, however, a concomitant increase of osmiophilic granules, 400-600 A diameter, located in the cisternae of granular endoplasmic reticulum. These granules corresponded to alpha-glycogen. After 12 weeks of age, only occasional glycogen granules were seen in either the mitochondria or endoplasmic reticulum. It is suggested that the intramitochondrial glycogen represents an alternate means by which the neuron is able to manufacture ATP following the disruption of oxydative phosphorylation caused by bilirubin. Furthermore it is suggested that with the recovery of oxydative phosphorylation the intramitochondrial collections of glycogen are transferred to the endoplasmic reticulum where glycogenolysis might possibly occur.


Glycerokinase in brain and liver of low birth weight newborns. Glycerokinase activity was measured in brain and liver tissue of decreased low birth weight newborns. No glycerokinase activity was found in the brain. In the liver a relatively high activity of glycerokinase was ascertained even in very immature newborns.


Considerations on treatment of nephroblastoma. A study of 36 cases. Thirty-six patients with nephroblastoma in Stages I, II and III treated at Radiumhemmet between 1966 and 1973, were analysed. The tumors were classified into three different histological types. All 10 patients in Stage III have developed metastases. All patients in Stages I and II (5 out of 26) who developed metastases had poorly differentiated (histological Type III) tumours. The indications for postoperative irradiation and chemotherapy for the different stages and histological types of the tumour are discussed.


Ulcer formation and histochemical changes in rat-stomach mucosa induced by acetylsalicylic acid. Numerous papers have emphasized the damaging effect of salicylic acid compounds on the stomach mucosa. The investigations here reported aimed at examining the effect on gastric and duodenal morphology of a moderate dose of aspirin. Oxidative enzymes were evaluated histochemically. To rats in groups of 16, aspirin tablets, placebo tablets, or the same with additional 1 cc of 0.1 N HCl, were administered twice a day for 6 weeks. Approximately 160 mg/kg/24 hrs. were ingested. Microscopy revealed severe hyperaemia along with focal gastritis in the aspirin treated animals. Chronic gactric ulcers were observed in 18 rats in the aspirin treated groups, particularly in the group where HCl was added. Ulcerations in the area of the pyloricgland occurred in the latter group only. A reduction in mucopolysaccharides was demonstrated and involved the acid as well as the neutral ones. NADH-reductase and cytochrome oxidase were inhibited not only in the surface cells but also in those in the deeper layers. The reduction in oxidative enzymes in otherwise undamaged areas suggests an interference with the cellular metabolism, probably processes in the respiratory chain which might lead to reduction in energy-rich phosphate bonds.


Occurrence of reo-like calf viruses in young children with acute gastroenteritis. Diagnoses established by electron microscopy and complement fixation, using the reo-like virus as antigen. In the course of a six-month-study of acute gastroenteritis in children of ages up to six years, a reo-like virus was found in 54 per cent of the faecal specimens obtained at an early stage of the disease, using electron microscopy as screening test. By means of a concentrated complement fixation antigen, composed of a related calf diarrhoea virus cultivated in tissue culture, the rise in titre was found to be significant in 96 per cent of the patients whose faeces contained the reo-like virus. Antibodies were present in the remaining 4 per cent without rise in titre. In 10 per cent of the cases with gastroenteritis infection was caused by adenovirus or Salmonella. A probable aetiological agent was found in 71 per cent of the patients. It applies to 33 per cent of all cases caused by the reo-like virus that they were nosocomial infections.


Human ecto- and endocervical epithelial cells as targets for herpes simplex type two infection in vitro. An in vitro method was used to compare the herpes simplex virus type 2 (HSV2) susceptibility of human ecto- and endocervical epithelial cells as well as the induced cellular alterations. HSV2 caused a productive infection and morphological alterations both in ecto- and endocervical epithelial cells, but the cytopathogenicity, virus production and development of HSV2 antigens showed a greater sensitivity of ectocervical cells to HSV2 infection. The cytopathogenicity and production of infectious virus did not depend on the antibody pattern of the target cell donor patients. Basically similar morphological alterations were seen in ecto- and endocervical cultures and the various morphological types of altered cells are described.


Adenosine 3',5'-cyclic monophosphate in perfused rat hearts exposed to isoprenaline and dopamine. Isoprenaline and dopamine increased cyclic AMP (cAMP) content and contractile activity of isolated perfused rat hearts. The changes of cAMP levels depended on the mode of drug administration. Isoprenaline (4 x 10(-10) mol) administered to the perfused heart as a relatively concentrated bolus, caused a substantial, rapid and transient increase of cAMP. Isoprenaline (2 x 10(-10) mol and 4 x 10(-10) mol) and dopamine (10(-7) mol) diluted in 40 ml of perfusate which was continuously recirculated through the heart, caused a gradual increase of cAMP content which approached an apparent steady state. cAMP accumulation occurred at isoprenaline concentrations above 10(-9) M and at dopamine concentrations above 10(-6) M. Both agents also increased cAMP labelling from 14C-adenine in the perfusate, probably indicating increased cAMP synthesis. Isoprenaline at 2 x 10(-8) M and 10(-7) M increased labelling more than content of cAMP. Isoprenaline and dopamine also increased phosphorylase a activity. An association between increased cAMP contents and increased contractile activity was revealed by both the time-response and the dose-response curves of hearts exposed to isoprenaline and dopamine. Since both agents stimulate adrenergic beta-receptors in cardiac muscle, the results are concordant with the hypothesis that cAMP is involved as a mediator of the inotropic response to adrenergic beta-stimulation.


Toxicity and metabolism of methyl n-butyl ketone. MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.


Pseudomesotheliomatous carcinoma of the lung. A variant of peripheral lung cancer. Six cases of primary lung cancer that closely mimic malignant pleural mesothelioma clinically and anatomically are compared with four proven cases of malignant pleural mesothelioma. Findings on roentgenograms of the chest, clinical history, and gross examination of the lung specimens are not helpful in distinguishing between these two neoplasms. Microscopic examination of the hematoxylin and eosin-stained tissues is often inconclusive. Tissues were stained with hematoxylin and eosin, PAS with and without diastase treatment (DPAS), mucicarmine, alcian blue, toluidine blue, and colloidal iron with and without digestion by testicular hyaluronidase. Among these histochemical methods, DPAS was found to be particularly useful in distinguishing the primary lung cancers from the mesotheliomas. All primary lung cancers except one showed DPAS-positive material (mucin) in both the cytoplasm of the cancer cells and within the lumina of neoplastic glands. In contrast, none of the mesotheliomas showed the presence of DPAS-positive material. Histologically, all lung cancers were glandular. Five were classified as bronchiolar carcinoma, the remaining one as poorly differentiated adenocarcinoma. In two of the bronchiolar carcinomas, a small subpleural primary focus was demonstrated. This finding suggests a possible origin of these cancers as a small subpleural tumor that became widely disseminated via the subpleural lymphatics. This form of primary lung cancer possesses sufficient gross and microscopic characteristics that recognition should be given to it as a variant of primary lung cancer, with emphasis on differentiating it from pleural mesothelioma.


Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients. We have studied insulin binding to circulating mononuclear cells obtained from 31 untreated, adult, nonobese, nonketotic diabetic subjects with fasting hyperglycemia, 40 normal subjects and four patients with fasting hyperglycemia secondary to chronic pancreatitis. Our results show that the mononuclear cells of untreated adult diabetic patients have a decreased ability to bind insulin when they are compared to cells obtained from normal subjects. The binding affinity for insulin was the same for both groups of cells, and the decreased binding could be accounted for by a 45 per cent decrease in the number of available insulin receptor sites per cell. Treatment with chlorpropamide (one to three months, average dose equals 375 mg/day) was associated with a marked reduction in hyperglycemia and an increase toward normal in insulin binding to mononuclear cells. In conclusion, (1) mononuclear cells from nonobese, nonketotic, untreated adult diabetic patients with fasting hyperglycemia demonstrate a decreased ability to bind insulin due to decreased numbers of insulin receptors per cell; (2) treatment with an oral hypoglycemic agent is associated with a diminution in hyperglycemia and a return toward normal of insulin binding.


Circulating immune complexes and complement sequence activation in infectious mononucleosis. The role of immune complex formation was investigated in a patient with infectious mononucleosis complicated by an urticarial rash. Circulating cryoprotein immune complexes were identified during the urticarial phase of the illness, and disappeared during recovery. These complexes were composed of immunoglobulins G (IgG), M (IgM) and A (IgA), complement components C3, C4 and C5, Epstein-Barr (EB) virus capsid antibody and particles resembling EB virus. The IgG subtypes identified in the immune complexes were the complement fixing IgG-1, IgG-2 and IgG-3. The C3 activator of the properdin complex was detected in serum obtained during that acute phase but not after recovery. Thus, the transient appearance of circulating complement-fixing immune complexes was associated in this patient with activation of both classic and alternate complement pathways. The findings suggest that these complexes may be involved in the rash associated with infectious mononucleosis.


Effects of fasting and theophylline on alanine-stimulated glucagon secretion in neonatal and infant sheep. Plasma concentrations of glucose, alanine, and glucagon were measured after 24 hour fasting in newborn and infant sheep and in response to infusion of alanine alone and concurrently with theophylline. The plasma glucagon response to alanine was minimal in newborn sheep; in contrast, alanine produced a brisk response in plasma glucagon concentration in infant sheep. Glucose concentrations were unchanged in both groups. Theophylline enhanced blood glucagon and glucose responses to alanine in newborn animals but had minimal effects on the response of the infant sheep. These data, considered with earlier data in fetal sheep, suggest a progressive maturation of pancreatic islet alpha-cell glucagon secretion in the sheep during the postnatal period and suggest that the blunted glucagon response observed in the neonate is related to immaturity of the glucagon secretion mechanisms rather than deficient synthesis of the hormone. This immaturity may be related to impaired synthesis and/or enhanced degradation of cyclic adenosine monophosphate (cAMP) or to diminished responsiveness to cAMP.


Trachoma in a rural Haitian community.

Trachoma in a rural Haitian community. We selected 43 patients, aged 15 days to 57 yesrs, for intensive study after screening 975 people for clinical evidence of trachoma in rural Haiti. Trachoma was present in Haiti with low endemicity and was followed by relatively mild sequelae. Laboratory studies confirmed the disease through demonstration of conjunctival inclusion bodies by immunofluoresence and serotyping of antibody in sera or eye secretions, or both. Of 23 patients (age 1 to 36 years) with active trachoma, all had serum antibody to chlamydia (range 1:10 to 1:640), nine had eye secretion antibody (range 1:10 to 1:1280), and one was inclusion positive. The remaining 20 patients (age 15 days to 57 years) had the following diagnosis: atypical follicles (eight), conjunctivitis with or without mucopurulent discharge (ten) innactive pannus only (one), and severe anemia (one). Only 16 of the 20 were tested for serum antibody and all were positive (1:10 to 1:5,120), 11 of 20 had eye secretion antibody (1:10 to less than or equal to 1:640), and one was inclusion positive. Serotyping attempted on 22 patients yielded 16 patients with antibodies specific for type A, one patient with type B, and five who were not typed.


Clinical and laboratory evaluation of epidemic keratoconjunctivitis due to adenovirus types 8 and 19. During a community outbreak of epidemic keratoconjunctivitis due to adenovirus types 8 and 19, we compared the clinical and laboratory characteristics of the two viruses. Much of the disease was mild and the keratoconjunctivitis associated with adenovirus type 8 was indistinguishable clinically from that associated with adenovirus type 19. Adenovirus type 8 was isolated only from the conjunctival sac, whereas adenovirus type 19 was frequently cultured from the nose, throat, and conjunctiva. The two adenovirus types were never isolated from the same individual. In a prospective study of ten individuals exposed to known cases, adenovirus type 19 was isolated from two without clinical disease.


Pathogenesis of bronchopulmonary dysplasia following hyaline membrane disease. The pathologic changes in the lungs of 112 infants dying from hyaline membrane disease (HMD) and 64 infants dying from other causes in the years 1967 to 1972 have been reviewed in order to obtain information about the pathogenesis of bronchopulmonary dysplasia (BPD). The results from the infants with HMD showed that: a) From the fourth or fifth day, the surface tension of lung extracts fell, inclusion bodies became more plentiful, and air saccules with patent airways could be inflated with air, even when severe changes due to BPD were present. b) There was a highly statistically significant correlation between the most serious lesions of BPD--damage to airways followed by excessive repair and fibrosis--and the use of high (greater than 35 cm H2O) peak airway pressures during mechanical ventilation in life. c) Damage due to oxygen breathing could not be reliably identified although some of the lesions, particularly edema and fibroplasia in intersaccular septa, may have been caused by oxygen. d) Evidence of pulmonary hypertension was present in infants surviving for more than a month with severe lung damage, and the ductus arteriosus was always open. We conclude that the most important factor in the pathogenesis of BPD following HMD is mechanical trauma to the lung from the use of excessively high peak airway pressures during mechanical ventilation.


Immunopathogenicity and oncogenicity of murine leukemia viruses. II. Infection of mice and rats with Scripps leukemia virus. The pathologic consequences of infection of newborn mice and rats with MuLV (Scripps leukemia virus--SLV) were observed. Serum MuLV p30 concentrations of most strains were elevated 20 to 100 times that of controls while MuLV gp70 levels were elevated only 1.1 to 14.8 times, probably reflecting in part the higher concentrations of gp70 in control sera but also indicating the lack of parallelism in regulation of synthesis of these two viral antigens. Infected mice of most strains developed immunologic diseases, including antinuclear antibody and glomerulonephritis, but not Coombs' antibodies. The nature and severity of the immunologic disease varied considerably, depending upon the genetic character of the host. Most infected animals developed lymphatic leukemias, but four strains showed partial to complete resistance to SLV oncogenesis: BALB/c (nude); C57 Bl/6; (NZB times NZW) F1, and (NZW times BALB/c) F1.


Synthesis of secretory component by colonic neoplasms. The secretory component (SC) polypeptide chain of secretory immunoglobulin A can be considered as a differentiation marker in that it is normally synthesized in the non-mucus-containing columnar epithelial cells, but not goblet cells, of the large intestine. With this in mind, we have studied the expression of SC in 36 colonic adenocarcinomas and 15 polyps (adenomatous and villous) by the fluorescent antibody technique. As in the normal mucosa, the synthesis of SC in tumors found in non-mucus-containing columnar cells and was absent from goblet cells. However, in several well-differentiated carcinomas it appeared that columnar cells contained both SC and mucin; these cells could be analogous to the normal mucosal precursor of both cell types. SC was synthesized throughout all adenomatous polyps and villous adenomas with the exception of some atypical nonmucinous areas of adenomatous polyps. Secretory component synthesis by carcinomas was associated with mucus production, although goblet cells did not contain SC. The presence of SC also correlated with the degree of differentiation. Secretory component was absent from half of the carcinomas as well as from atypical nonmucinous areas of polyps, and this could represent one of the earliest changes associated with the development of malignancy.


Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. In livers from fasted rats perfused with bicarbonate buffer containing bovine albumin and erythrocytes, adrenalectomy decreased glycogen levels and glucose production, impaired the incorporation of 14C from [14C]lactate into glucose or glycogen, and decreased the activity of the active (I) form of glycogen synthase. Cortisol treatment restored gluconeogenesis after 1  h and glycogen synthesis after 2 h. Adrenalectomy did not alter the production of glucose or lactate or the levels of gluconeogenic intermediates in livers from fasted rats perfused with fructose, but reduced the formation of glycogen from this substrate. Adrenalectomy increased the levels of lactate and decreased the levels of P-pyruvate and subsequent intermediates in the gluconeogenic pathway. These changes were reversed by cortisol treatment. It is concluded that glucocorticoids support gluconeogenesis and glycogen synthesis in livers from fasted rats primarily by facilitating a reaction(s) located between pyruvate and P-pyruvate in the gluconeogenic pathway and by promoting the conversion of inactive to active glycogen synthase.


Heart functional responses to pressure overload in exercised and sedentary rats. Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.


Viral encephalopathy mimicking functional psychosis. Encephalitis, particularly herpes simplex encephalitis, frequently presents as a disorder with puzzling psychiatric symptoms before frank evidence of central nervous system involvement is apparent. The author describes three cases of encephalitis characterized by abrupt onset of bizarre psychological disturbance in the absence of gross neurologic dysfunction. Each patient was initially diagnosed as schizophrenic but later became critically ill and recovered only after a long and chaotic hospital course. The author warns psychiatrists and staff on psychiatric impatient units against mistakenly diagnosing cases of early encephalitis as functional psychoses.


Effectiveness of educational and administrative interventions in medical outpatient clinics. This study examines the popular belief that increased educational supervision and increased administrative support in university outpatient clinics will improve physician performance, which in turn will improve the process and outcome of patient care. Positive effects on house officers' attitudes and better functioning of clinics with respect to follow-up, information retrieval, and prescribing practices were demonstrated. However, no differences in the process and outcome of care were identified by faculty judges using implicit criteria.


Coarctation of the aorta. Roentgenographic assessment after operative correction. Persistent abnormalities in the cardiac silhouette and aortic arch are frequent in the late follow-up of patients operated upon for coarctation of the aorta. These abnormalities for the most part can be correlated with age at operation, the presence of a coexistent uncorrected congenital anomaly, or a persistent hemodynamic defect. This group of patients requires continuing clinical and roentgenologic assessment, as these abnormalities are frequently the hallmarks of additional significant cardiovascular disease despite correction of the primary congenital defect.


External and interstitial radiation therapy of carcinoma of the oral tongue. A review of 32 years' experience. In 204 patients with squamous cell carcinoma of the oral tongue treated with radiation therapy, the most significant prognostic factors appeared to be the presence of neck lymph node metastasis on presentation and the status of the disease three months after treatment. The most common site of failure was the primary lesion, either alone or with neck disease. External irradiation alone was seldom successful. Use of peroral cone irradiation or interstitial implants, either alone or in combination with external irradiation, achieved good local control in early lesions. When the primary tumor was uncontrolled by radiation therapy, salvage with surgery was rare. When failure occurred in the neck alone, radical neck dissection was successful in the majority of cases.


Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results. One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy.


Mediastinal Hodgkin's disease.

Mediastinal Hodgkin's disease. A group of five patients with Hodgkin's disease, nodular sclerosing in type, localized to the mediastinum (Stage IA) is reported. We believe that this presentation sometimes known as "granulomatous thymoma," warrants management in a manner somewhat different from that of the more common presentations of Hodgkin's disease. Nodular sclerosing Hodgkin's disease involving only the mediastinum affects a younger age group in whom the disease may be asymptomatic. Making the diagnosis may necessitate a thoracotomy, but an attempt should be made to obtain tissue short of thoracotomy, as by mediastinoscopy. An extensive attempt at surgical extirpation is not necessary because the disease is very radiosensitive and radiocurable. The combination of Stage I Hodgkin's disease, nodular sclerosing in form, limited to the mediastinum favors an excellent prognosis.


Elective irradiation with the electron beam after mastectomy for breast cancer. From 1963 to 1970, 380 patients have received elective treatment with the electron beam after radical mastectomy for breast cancer. One hundred and twenty-nine patients received treatment to the supraclavicular and internal mammary lymph node areas only, and 251 patients received treatment to the chest wall as well as to the areas of peripheral lymphatic drainage. Analysis of the results shows the value of elective irradiation of occult deposits of disease since the incidence of local recurrences is significantly less than would be anticipated in this group of patients.


Treatment selection in primary breast cancer. Pathologic considerations. Minimal breast cancer is defined as including in situ lobular carcinoma, noninvasive intraductal carcinoma, and invasive carcinoma forming a mass no greater than 0.5 cm in diameter. Intraductal, intralobular, and microinvasive carcinomas of this degree of development are classed together, and are associated with at most a 10% probability of having associated axillary lymph node involvement. Lesions of this classification have been shown to have a five year survival rate of 97% and a ten year rate of 95%, when they are treated surgically.


Treatment, results and prognostic factors in stage I and II sarcomas of the corpus uteri. One-hundred and four cases of Stage I and II uterine sarcomas treated at Rosewell Park Memorial Institute over a 27 year period are reviewed. Included are 30 cases of mixed mesodermal tumor, 27 cases of carcinosarcoma, 25 cases of endometrial stromal sarcoma, and 22 cases of leiomyosarcoma. Prognostic factors were found to include histologic classification, stage, uterine size, depth of myometrial invasion, and type of treatment. Endometrial stromal sarcomas had the best over-all prognosis. Radiation therapy alone was inadequate treatment, but was of adjunctive value to surgery in terms of increasing survival and decreasing pelvic recurrences in patients with endometrial stromal sarcoma, mixed mesodermal tumor, and carcinosarcoma. Patients with leiomyosarcoma did not benefit from adjunctive radiation therapy.


Irradiation of endometrial cancer in patients with medical contraindication to surgery or with unresectable lesions. In 124 medically inoperable patients with endometrial cancer, the five and ten year actuarial survival rates were 68% and 57%. In 26 patients with technically unresectable endometrial cancer, 26% actuarial survival rates at both five and ten years were seen. Pelvic control at death was 89% in Stage Ia, 78% in Stage Ib, 82% in Stage II, and 62% in Stage III. Sophisticated intracavitary therapy alone or in conjunction with external irradiation appears to give better uterine control rates than does external irradiation alone.


Experience with twice-a-day fractionation in clinical radiotherapy. Theoretical reasons have led to the treatment of 24 patients with advanced, rapidly growing squamous cell carcinomas of the head and neck, and 17 patients with inflammatory carcinoma of the breast with twice-a-day fractionation. After initial reduction in dose in both series, acute reactions and sequelae are similar to those in conventionally treated patients. The relative control rates are better than would be expected from conventional irradiation.


Volume and time factors in interstitial gamma-ray therapy. The two suppositions which have dictated time-dose and volume relationships in interstitial gamma ray implantation have been examined in the light of recent publications. The first of these assumptions, that total dose reduction is required when the dose rate exceeds 6,000-7,000 rads in seven days, does not appear to be substantiated by clinical experiences. It appears that total dose is the critical treatment parameter and that dose rate may be increased by a factor of two or three without requiring alteration of the total dose. Although the second classical assumption, "volume increase requires dose decrease," has been shown throughout radiation therapy experience to be generally correct, it should not be applied rigidly to interstitial gamma-ray therapy. In fact, recent experiences seem to indicate that compensation with respect to volume is not an absolute necessity. Larger lesions require, if anything, higher doses than small ones. To obtain a high percentage of controlled, lesions there must be no dose reduction, regardless of increased volume treated.


Low energy radionuclides for permanent interstitial implantation. An analysis of 318 permanent implants was carried out in an attempt to establish the effectiveness of iodine 125 as compared with radon 222 and iridium 192; and to derive dose-response curves for iodine 125. Analysis of the clinical results obtained with iodine 125 in comparison with radon 222 and iridium 192 in selected anatomical sites demonstrated that iodine 125 has a higher therapeutic ratio than the other two radionuclides. A tumor control rate of at least 80% with iodine 125 implants might be expected after a good geometrical dose distribution, with a planned initial minimum tumor dose of at least 14,000 +/- 2,000 rads. Rapid tumor shrinkage ensures a more or less steady or even increased dose rate over a period of several weeks and improves the local tumor control. Tumors with a longer cell cycle are especially susceptible to irradiation with radionuclides of long half-lives.