The pathogenesis and pathway into the central nervous system after intraocular infection of herpes simplex virus type I in rabbits. Herpes simplex virus (HSV) type I was injected into the right eye of 18-day-old New Zealand albino rabbits and the animals were killed on the fourth and eighth days after inoculation. Longitudinal section of the optic nerves and chiasma showed that both myelinated axons and neuroglial cells crossed at the chiasma. Semi-serial (1 micrometer) and ultrathin sections showed the presence of HSV in both astrocytes and oligodendrocytes, although no particles were seen in the myelinated axons; the infected cells were confined to the medial side of the right optic nerve. HSV travels centropetally along the optic pathway and slowly spreads laterally by cell-to-cell infection. The virus does not appear to kill the astrocytes and oligodendrocytes, and also does not directly damage the myelin sheath.


Methylprednisolone treatment in patients with brain tumors. A study was made in 10 patients with brain tumors of the effect of methylprednisolone sodium succinate (Solu-Medrol) on clinical neurological status, intracranial pressure, and periventricular elastance. Significant clinical improvement and reduction in periventricular elastance both ocurred within 24 hours of starting treatment, whereas intracranaial pressure was not significantly reduced until the 2nd day of therapy.


Elevations in cerebrospinal fluid norepinephrine during unilateral and bilateral cerebellar stimulation in man. Lumbar cerebrospinal fluid (CSF) norepinephrine concentrations determined by radioenzymatic assay in four epileptic patients were significantly higher during either chronic unilateral or bilateral cerebellar stimulation than those determined after a 7-day period without stimulation. The mean CSF norepinephrine levels noted during these two modes of cerebellar stimulation were not significantly different. The percentage of increase in CSF norepinephrine in one patient receiving 200/sec stimulation was 3 times higher than those noted in the three patients undergoing 10/sec stimulation. These evoked alterations in norepinephrine metabolism may relate to the reported modulation of spasticity and cerebral neuronal excitability during chronic cerebellar stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation.


Progressive multifocal leukoencephalopathy: failure of response to transfer factor and cytarabine. A 57-year-old woman with a 2-year history of neurologic symptoms was shown on brain biopsy to have progressive multifocal leukoencephalopathy. Although cell-mediated immune mechanisms were impaired, no underlying disease was found. The administration of transfer factor enhanced cell-mediated immunity, but the neurologic symptoms did not improve. Separate courses of glucocorticoids and cytarabine were associated with rapid neurologic deterioration.


Serum factor blocks neuromuscular transmission in myasthenia gravis: electrophysiologic study with intracellular microelectrodes. We studied the effects of normal and myasthenic sera on the miniature endplate potential (MEPP) and resting membrane potential (RP) of rat muscle in vitro by conventional intracellular microelectrode techniques. Normal sera had little or no effect on either the amplitude or frequency of MEPP or RP. On the other hand, MEPP amplitude was reduced in each of nine muscles during exposure to myasthenic sera; five of these muscles showed a significant difference, by student's t-test, from the values in a control solution. The half decay time of diminished MEPP remained unchanged. MEPP frequency and RP were not affected by myasthenic sera. The reduced amplitude of the MEPP was almost completely restored when the muscle was washed with a control solution for more than 30 minutes. These observations indicate that myasthenic sera contain factors that bind reversibly with the acetylcholine receptor and reduce postsynaptic responses to acetylcholine.


Histochemical labeling of beta-adrenergic receptors in the mouse central nervous system by 9-amino-acridin propranolol. A new fluorescent beta-adrenergic antagonist, 9-amino-acridin propranolol (9-AAP), was administered intravenously to living mice. In the cerebral cortex, the highest concentration of 9-AAP was noted in the hippocampal formation, where it distinctly labeled the hippocampal pyramidal cell layer and the granule cell layer of the dentate gryus. High uptake occurred in the pyramidal cell layer of the piriform cortex. In the neocortex, fluorescence was less dense and more diffuse but confined to the basal layers. A similar pattern was observed in the basal layers of the cingulate cortex, but an additional high-density dotted fluorescence labeled its layer II. In the cerebellar cortex, 9-AAP was localized within the Purkinje cell layer. In the spinal cord, the highest density of fluorescence was observed in the nuclear collections of alpha-motoneurons. The findings were similar to those observed in the central nervous system of the rat and support the reproducibility of the method. 9-AAP may be used in vivo as a fluorescent probe to map out the central beta-adrenergic receptor system.


[Results and prospects of therapy of type IV dyslipidemia with chenic acid]. Administration of 500 mg/day chenodeoxycholic acid for 60 days in a series of 44 patients with type IV dyslipidaemia led to gradual normalisation of triglycerides by the end of the treatment. Falls were greater in subjects with initially higher values, but were independent of age, sex, weight and type of diet. Further falls were obtained by repeating the treatment in some cases when prebetalipoproteins rose again. Decreases were already evident by the 5th day (about 24%) and could be obtained with only 4 mg/Kg/day. The rapid effect of the acid and its specific action on prebetalipoproteins were demonstrated by examination of lipid curves after a glyco-lipid load with and without pretreatment with chenic acid. Encouragement of the shunt of triacylglycerols towards the phosphoglycerides during hepatic synthesis of triglycerides is put forward as the most likely mechanism of action in endogenous hyper-triglyceridaemia. The chemical composition of bile is interfered with, which may explain why cholesterol lithiasis is significantly more common in type IV dyslipidaemia than in other forms and in controls, as shown by statistical analysis.


[Malignant insuloma. Evaluation of the response to treatment with streptozotocin, using selective arteriography of the celiac axis]. A patients with metastatic insulin-producing islet-cell carcinoma has been treated with Streptozotocin intravenously and studied by selective celiac angiography during treatment. A 50% decrease of the tumor's size has been demonstrated by this technique after a total dose of 19 grams of the drug together with return to normal of the serum-insulin and blood-glucose values. The usefulness of angiography in evaluating the tumor response to Streptozotocin and in managing chemotherapy is discussed.


Cytomegalovirus infections in renal allograft recipients: correlative studies with histocompatibility antigens. We studied 32 renal allograft recipients in order to determine whether or not any correlation could be demonstrated between the HLA and development of cytomegalovirus infection. There was a positive stastical correlation (P less than 0.01) of the development of cytomegaloviraemia and the number of HLA antigens mismatched in the recipient. There was no correlation between specific HLA antigens and predisposition to develop cytomegalovirus infection. The implication of our observations with regard to the pathogenesis of cytomegalovirus infection in renal allograft recipients is discussed.


Uncomplicated pregnancy following oral contraceptive-induced liver hepatoma. A patient who used oral contraceptives who had had a partial hepatectomy for benign hepatic cell adenoma became pregnant 3 years after surgery. No diagnosed liver complicaions resulted during the pregnancy or the postpartum period.


Postpartum cytomegalovirus infection. A hazard of multiple transfusions. A patient whose postpartum course included the defibrination syndrome and Bacteroides septicemia developed recurrent high fever. Cytomegalovirus infection was suspected on the basis of the clinical features and a history of massive blood transfusion, and was confirmed by subsequent observations. Recognition of this disease and its typically benign course averts the need for extensive diagnostic procedures, exploration, and empiric drug therapy trials.


Adrenocortical response to ACTH stimulation in postmature newborns. Diminished total plasma cortisol levels have been demonstrated in postmature neonates, suggesting that fetal glucocorticoids may be involved in the cause of postmaturity. This hypothesis was tested by adrenocortical stimulation in 32 newborns: 12 were postmature; 12 were postterm, but not postmature; and 8 were normal term neonates. The mean pre- and poststimulation total plasma cortisol levels were 3.9 and 50.9 microgram/100 ml, respectively, for the postmature newborns, 9.7 and 44.0 microgram/100 ml for the postterm, but nonpostmature newborns, and 9.8 and 37.1 microgram/100 ml for the normal term newborns. The differences in the poststimulation rise in plasma cortisol between the postmature and merely postterm infants or between the postterm and normal term infants were not statistically significant. The mean poststimulation cortisol rise in the postmature group exceeded that of the normal term group (P less than 0.05). The adequacy and promptness of response to adrenocortical stimulation eliminate the likelihood of adrenal insufficiency in postmature infants.


Lipofuscin in salivary glands in health and disease. Lipofuscin granules were observed in normal salivary glands (parotid, submandibular, and minor salivary glands). The pigment was confined mainly to the epithelial cells of the intralobular ducts, but isolated granules were also found in acinar cells and myoepithelial cells. In chronic sialadenitis pigment granules were found in the intralobular epithelial cells and in macrophages in the surrounding ionnective tissue. In benign epithelial tumors pigment granules were observed within neoplastic epithelial cells and in macrophages in the stroma, while malignant tumors displayed pigmented granules only in macrophages in the stroma.


Serum lipids and lipoproteins at birth in a biracial population: the Bogalusa heart study. The lipid profile, total cholesterol, triglycerides, and lipoproteins (beta-, pre-beta-, and alpha-) of cord blood, is presented for 419 black and white infants (94% of the eligible population) born during an 18-month period in Bogalusa, Louisiana. At birth, white neonates of both sexes had higher average levels than black neonates of total cholesterol and beta-lipoproteins. White girls among the four race-sex groups had the highest cord blood levels of total cholesterol, beta-lipoproteins, and alpha-lipoproteins. Neither stress at delivery, birthweight, socioeconomic status, nor season of the year had an observable effect on any of the lipid or lipoprotein levels. The magnitude and direction of the relationships between the respective lipids and lipoproteins in cord blood were similar to those we have observed in preschool and school-aged children in the same community. Total cholesterol was highly correlated with both beta- and alpha-lipoproteins; triglycerides were correlated with pre-beta-lipoproteins but inversely with alpha-lipoproteins. These observations suggest that basic biochemical relationships are already established at birth.


[Role of hormonal receptors in the regulation of the corpus luteum (author's transl)]. Recent publications dealing with the hormonal regulation of the corpus luteum function have been reviewed. Hormones involved in this regulation are: LH and placental analogue hCG, FSH, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction in the luteal cells and the role of each hormone in the modulation of the cell responsiveness has been reviewed.


Agarose linked adenosine and guanosine-5'-monophosphate; a new general method for the coupling of ribonucleotides to polymers through their cis-diols. Condensation of the cis-diol of adenosine (1a) or guanosine (1b) with ethyl levulinate led to the acetal-esters 2a or 2b. Phosphorylation with phosphorous oxide trichloride converted them into their 5'-monophosphates. On alkaline hydrolysis the acetal-esters 2a,b as well as their 5'-monophosphates gave the carboxylic acid derivatives 3a,b and 4a,b, respectively. Condensation of these acid derivatives with aminohexyl-agarose (5) using water soluble N-ethyl-N'-(3'-dimethyl-aminopropyl)-carbodiimide hydrochloride as coupling reagent led to the new polymers 6a/6b and 7a/7b. This method of preparing resin linked adenosine and guanosine derivatives should be generally applicable to any ribonucleoside or ribonucleotide with a cis-diol. Because of the widespread occurence of these molecules, particularly as cofactors of enzymes, the new polymers might be useful tools for the purification of certain classes of enzymes by affinity chromatography.


Fetal limb deformities due to amniotic constrictions (a possible consequence of preceding amniocentesis). The nature and origin of circular constrictions and intrauterine amputations can be studied more effectively in the fetus than in the newborn. Two cases of fetal micro- and syndactyly secondary to ring constrictions are discussed with respect to morphological processes. The amniotic membranes display active chorionic proliferation in addition to amniotic rupture and passive string formation. Moreover, association between the origin of amniotic bands and preceding amniocentesis seems to be possible in one case though it is difficult to ascertain.


Uremic hyperlipidemia: the nature of the problem. Increased triglyceride and reduced HDL cholesterol levels are 2 risk factors for atherosclerosis with a high prevalence in chronic hemodialysis patients. Whether they have the same significance in these patients as in the general population is not known. Nonethless, therapy may be indicated because of the severity of the atherosclerotic disorder. The most appropriate drug, clofibrate, is renally excreted and can be used safely if the dosage is markedly reduced. No data exists in any population that such therapy is beneficial.


Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line. Inhibition of IMP dehydrogenase (EC 1.2.1.14) by ribavirin causes the normal human lymphoblast to excrete increased amounts of newly formed purine into the culture medium. In order for ribavirin to be active as an inhibitor of the dehydrogenase, this synthetic nucleoside must be phosphorylated. The effect of ribavirin on purine excretion has been determined with a normal lymphoblast line, and with lymphoblast lines deficient in hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyl-transferase, EC 2.4.2.8), in adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20), and in both hypoxanthine phosphoribosyltransferase and adenosine kinase. Resistance to the effect of ribavirin on purine excretion was associated only with those cell lines deficient in adenosine kinase activity. These cell lines have normal deoxyadenosine kinase (ATP:deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) activity. Therefore, the nucleoside kinase activity responsible for ribavirin phosphorylation is adenosine kinase.


ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. In the presence of ATP and a cytosolic factor, cholera toxin fragment A1 catalyzes the transfer of ADP-ribose from NAD to a number of soluble and membrane-bound proteins of the pigeon erythrocyte. Evidence is presented that suggests that the most readily modified membrane protein (Mr 42,000) is the adenylate cyclase-associated GTP-binding protein. Its modification by toxin is stimulated by guanine nucleotides. Adenylate cyclase activity increases in parallel with the addition of ADP-ribose to this protein and decreases in parallel with the subsequent reversal of ADP-ribosylation by toxin and nicotinamide. The protein is only accessible to toxin A subunits if the erythrocytes are lysed. When adenylate cyclase activity reaches a maximum, the number of ADP-ribose residues bound to this protein (about 1500 per cell) is similar to the reported number of beta-adrenergic receptors.


Oxygen-mediated heterogeneity of apo-low-density lipoprotein. Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions.


Heat-stable low molecular weight form of phosphodiesterases from bovine pineal gland. The 105,000 X g supernatant fraction of bovine pineal gland contains a phosphodiesterase activity that hydrolyzes both cyclic AMP and cyclic GMP. The rate of hydrolysis is 4-5 times greater with cyclic GMP as substrate than with cyclic AMP. Chromatography of supernatant fraction on Sephadex G-150 resolves phosphodiesterase activity into two fractions designated PDE I and PDE II. These are distinguishable on the basis of their molecular size, substrate specificity, and kinetic parameters. PDE I hydrolyzes cyclic GMP at a faster rate than cyclic AMP and has a molecular weight of 163,000. PDE II appears to be a smaller protein with a molecular weight of 24,400 and is specific for cyclic AMP. PDE I has apparent Km values of 83 and 53 micron for cyclic AMP and cyclic GMP, respectively, whereas PDE II exhibits an apparent Km value of 330 micron for cyclic AMP. With subsaturating concentrations of cyclic AMP as substrate, the phosphodiesterase activity of PDE I is inhibited by the addition of cyclic GMP. However, PDE II activity remains unaffected by cyclic GMP even at concentrations up to 125 micron. PDE II appears to be thermostable, losing only 20% of its activity on heating at 80 degrees for 2 min. Similar treatment completely abolishes the enzyme activity of PDE I.


Guanosinetriphosphatase activity dependent on elongation factor Tu and ribosomal protein L7/L12. Incubation of electrophoretically pure samples of the Escherichia coli 50S ribosomal protein L7/L12 together with elongation factor Tu leads to the hydrolysis of GTP. Addition of elongation factor Ts stimulates this reaction. Elongation factor G cannot replace elongation factor Tu for the ribosome-free GTPase reaction dependent on L7/L12. The data suggest that elongation factor Tu and the protein L7/L12 interact directly at the ribosomal A site.


Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A. Pseudomonas aeruginosa exoenzyme S is an adenosine diphosphate ribosyltransferase distinct from Pseudomonas toxin A. Exoenzyme S catalyzes the transfer of radioactivity from all portions of radiolabeled NAD+ except nicotinamide. Digestion of the radiolabeled product(s) formed in the presence of [adenine-14C]NAD+ and exoenzyme S with snake venom phosphodiesterase yields only AMP, suggesting that ADP-ribose is present as monomers and not as poly(ADP-ribose). Exoenzyme S does not catalyze the transfer of ADP-ribose from NAD+ to elongation factor 2, as do toxin A and diphtheria toxin, but to one or more other proteins present in crude extracts of wheat germ or rabbit reticulocytes and in partially purified preparations of elongation factor I. The ADP-ribosyltransferase activity of exoenzyme S is distinct from toxin A by several tests: it is not neutralized by toxin A antibody, it is destroyed rather than potentiated by pretreatment with urea, and it is more heat stable. These latter observations and the substrate specificity suggest that exoenzyme S is different from any previously described prokaryotic ADP-ribosyltransferase.


Nucleotide sequence homology at the 3' termini of RNA from vesicular stomatitis virus and its defective interfering particles. Vesicular stomatitis virus (VSV) and defective interfering (DI) particle RNAs were labeled at their 3' ends by using RNA ligase and cytidine 3',5'-bis[32P]phosphate. The RNAs were subjected to partial digestion with alkali and analyzed by oligonucleotide fingerprinting in two dimensions. VSV and DI particle RNAs have complete sequence homology for the first eight bases from the 3' end. The following four positions contain three mismatched nucleotides in which guanosine residues in one strand are replaced by uridine residues in the other. There is again complete homology for the next five bases (positions 13-17). The locations of purine residues within the sequence were confirmed by partial digestion with RNase T1 and RNase U2 and separation by size on 20% acrylamide gels. The latter method also indicated that sequences of VSV and DI particle RNAs diverge beyond the 18th nucleotide from the 3' termini.


Identification of epoxide hydrase as the preneoplastic antigen in rat liver hyperplastic nodules. A liver microsomal protein, previously referred to as preneoplastic antigen, from hyperplastic nodules of rats fed a diet containing 2-acetylaminofluorene has been identified as the enzyme epoxide hydrase [glycol hydro-lyase (epoxideforming), EC 4.2.1.63]. Purified preneoplastic antigen from hyperplastic nodules and purified rat liver microsomal epoxide hydrase are immunochemically identical on the basis of Ouchterlony double-diffusion analysis. In addition, the purified proteins have identical minimum molecular weights in sodium dodecyl sulfate/polyacrylamide gels, and both proteins catalyze the hydration of arene oxides to dihydrodiols. Chronic feeding of 2-acetylaminofluorene to rats results in a 5- to 7-fold increase in epoxide hydrase activity in rat liver. The induced level of the enzyme is maintained in developing hyperplastic nodules and hepatomas but not in the nontumor tissue after removal of the carcinogen from the diet.


Identification of the major polyadenylylated transcription products and the genes active in their synthesis in a rat insulinoma. Three RNA fractions with molecular weights of 200,000, 280,000, and 360,000, have been identified as the major polyadenylylated transcription products in a transplantable rat pancreatic islet cell tumor that synthesizes insulin. These three RNAs share sequence homology as demonstrated by comparisons of both partial and complete RNase T1 digestion products. The 200,000 and 280,000 molecular weight species hybridize primarily with three EcoRI restriction fragments of the rat genome having molecular weights of 1.4 X 10(6), 1.6 X 10(6), and 6.0 X 10(6). The 360,000 molecular weight species hybridizes preferentially with the 6.0 X 10(6) molecular weight DNA fragment.


Binding to chromosomes of herpes simplex-related antigens in biochemically transformed cells. Association of herpes simplex virus (HSV)-related antigens with chromosomes was demonstrated in human and mouse cells biochemically transformed by HSV that had been irradiated with ultraviolet light. This was accomplished by using peroxidase-anti-peroxidase immunological staining with rabbit antisera that had high neutralizing titers against both HSV-specific thymidine kinase activity and virus infectivity. Antisera-against HSV did not react with chromosomes of uninfected cells nor did normal sera react with any of the constitutents of biochemically transformed cells. Methanol/acetic acid treatment of biochemically transformed cells eliminated their nuclear staining for HSV-related antigens. In vitro binding of HSV-related antigens to chromosomes was demonstrated by incubating soluble antigens from high salt extracts of HSV-infected cells with methanol/acetic acid-fixed chromosomes of biochemically transformed or uninfected cells, followed by exposure to antiserum against HSV and peroxidase-anti-peroxidase staining. There was no staining when soluble extracts from uninfected cells were substituted for those from HSV-infected cells. The results show that cells biochemically transformed and lytically infected by HSV, respectively, contain antigens, which like the Epstein-Barr virus-associated nuclear antigen (EBNA), bind to chromosomes in vivo and in vitro.


Different regulation of insulin receptors in intracellular (Golgi) and plasma membranes from livers of obese and lean mice. Insulin binding to Golgi and plasmalemma fractions from the liver of obese (ob/bo and db/db) and lean control mice was studied. The specficiity of binding in Golgi fractions (Golgi vesicles and Golgi cisternae) was identical to that observed previously in rat liver Golgi fractions and plasmalemma. Binding to plasmalemma was much lower in obese compared to lean mice, but binding to Golgi cisternae was either not changed (ob/ob) or slightly increased (db/db) in obese compared to lean littermates. These observations suggest that intracellular (Golgi cisternae) insulin receptors are regulated differently from those of the plasmalemma. We propose that insulin affects hepatic receptor content in two different ways. On the one hand plasmalemma receptor loss is accelerated, and on the other hand intracellular receptor production is increased. This model can explain in one framework the effect on insulin in reducing and prolactin in augmenting the level of their respective hepatic receptors.


Sites of integration of reticuloendotheliosis virus DNA in chicken DNA. The pattern of integration of spleen necrosis virus (SNV) DNA in DNA from a large population of SNV-infected chicken cells was studied by nucleic acid hybridization with iodinated viral RNA by the blotting technique of Southern. SNV DNA was found to be integrated at multiple sites in acutely infected chicken cells. Concomitant with the transition from acute to chronic infection, a shift in the pattern of integration was observed. The majority of integrated SNV DNA found in acutely infected cells was absent from chronically infected cells. This result is consistent with the hypothesis that the cell death that occurs after infection of avian cells with reticuloendotheliosis viruses is a consequence of the multiple integrations of the provirus. Viral DNA was also integrated at multiple sites in chronically infected cells. However, infectious viral DNA molecules in chronically infected cells migrated in a uniform manner in agarose gel electrophoresis after EcoRI digestion (which does not cut viral DNA), indicating that not all integrated SNV copies are equally infectious.


Isolation and characterization of a human serum cholesteryl ester transfer protein. Human plasma has been shown to contain an apolipoprotein that mediates the transport of cholesteryl ester from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) or low density lipoprotein (LDL). This activity, confined to the density greater than 1.063 g/ml interval, has been isolated from HDL and appears as a single migrating species by anionic or sodium dodecyl sulfate/polyacrylamide gel electrophoresis. It is unreactive to antibodies to the major HDL apolipoproteins. Antibodies prepared against this factor and immobilized on Sepharose remove the capacity of HDL and density greater than 1.21 g/ml fractions as well as whole plasma to transport cholesteryl ester from HDL. The system shows saturation kinetics with respect to plasma LDL and VLDL concentrations, and transport of cholesteryl ester was associated with reciprocal and equimolar back-transport of triglyceride from VLDL and LDL to the HDL fraction. The possible relationship of this apoprotein to apoprotein D is discussed.


Identification of the trypanocidal factor in normal human serum: high density lipoprotein. The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity.


Influence of cyclic AMP on DNA synthesis in slices of regenerating rat liver. DNA synthesis in slices of regenerating rat liver is inhibited by adenosine cyclic 3',5'-monophosphate [cAMP]. The number of cells synthesizing DNA as assayed by 2-14C-thymidine incorporation is reduced by 65% in the presence of 10(-3) M cAMP. The inhibition of cAMP is not specific; other adenosine compounds, N6,O2,-dibutyryl adenosine 3',5'-monophosphate, 5'AMP and adenosine have the same effect. Moreover, the concentration of cAMP in the cell required for this inhibition is much higher than the normal levels of cAMP in liver cells.


Cutaneous signs of internal malignant disease. An awareness of various dermatoses which reflect internal malignancy will facilitate the physician's ability to recognize or even anticipate malignant disease. There have been several previous reports on this subject. This review emphasizes the nonspecific cutaneous changes associated with malignancy. New skin markers of cancer are also discussed.


Paradoxical effects in sleep and performance of two doses of chlorpromazine. Twenty-four subjects were given placebo, 25 mg, and 75 mg of chlorpromazine on three separate occasions. Twelve subjects were treated in the morning and tested for performance during the day. Twelve other subjects received the drug treatments in the evening. Both groups had their EEG stages of sleep recorded during the subsequent night. The low dose of drug shortened the REM/non-REM cycle length in comparison to the high dose, and placebo values were intermediate. In performance tests, visual integration time was impaired by the high dose of the drug. Logical reasoning was slowed by the high dose of the drug in comparison to the low dose, with placebo values intermediate between the two.


The differential effect of lithium on noradrenaline- and dopamine-sensitive accumulation of cyclic AMP in guinea pig brain. Lithium (Li) in its narrow therapeutic concentration range was found to inhibit only the noradrenaline- and not the dopamine-sensitive accumulation of cyclic AMP in guinea pig brain. The results suggest a pharmacological distinction between the anti-schizophrenic drugs that inhibit dopamine-sensitive cyclic AMP accumulation and Li, an antimanic agent that inhibits specifically only the noradrenaline-sensitive cyclic AMP accumulation.


LSD and tryptamine effects on sleep/wakefulness and electrocorticogram patterns in intact cats. Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep.


Effects of L-tryptophan and ethanol on sleep parameters in the rat. Sleep parameters were monitored following (1) a single 2 g/kg oral dose of ethanol, (2) an oral dose of L-tryptophan (600 mg/kg), and (3) administration of both drugs simultaneously. Ethanol reduced REM and increased slow wave significantly. The effects of L-tryptophan were apparent only in the case of one parameter, REM latency. Administration of both drugs resulted in a significantly shorter REM latency than that observed for ethanol alone. Results are discussed in terms of possible changes in the biosynthesis of 5-HT.


The effect of L-dopa and propranolol on human CSF cyclic nucleotides. Human CSF cyclic AMP  and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without L-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of L-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40-50% reduction of CSF cyclic AMP and a 80-90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed.


[Insulinoma in the computer-tomogramm (author's transl)]. Documentation of insulinoma by computerized tomography and the diagnostic value of this new method compared with conventional radiography is discussed. The study of four cases demonstrates the capability of computer tomography to localize tumors in the pancreas.


Reduced adrenergic sensitivity in vivo in acute ethanol-fed rats. Prior studies indicate ethanol feeding induces adrenergic subsensitivity in vitro, as measured by cyclic adenosine monophosphate  (cAMP) response of tissues to norepinephrine (NE). In this report we show acute ethanol feeding induces a depressed level of adrenergic sensitivity in vivo, as measured by plasma cAMP response to isoproterenol. Two hours after intragastric feeding of ethanol (6 gm/kg) to rats, there was a decrease in plasma cAMP response to intravenous isoproterenol, compared to dextrose controls. This decrease was the same in animals with blood ethanol levels averaging 68 mg/dl or 193 mg/dl. This data is consistent with the hypothesis that ethanol induces adrenergic subsensitivity.


Effect of somatostatin analogues and 17-alpha-dihydroequilin on rat brain opiate receptors. Two somatostatin analogues (SA)  and 17-alpha-dihydroequilin (E) inhibited the stereospecific binding of 3H-naloxone in vitro to rat brain opiate receptors in the absence of sodium. The addition of sodium indicated the SA to be greater or similar in potency to somatostatin as opiate agonists and E to be an opiate antagonist. The results indicate that SA and certain steroids may affect endorphin containing neurons.


Inducing of automatism of Purkinje fibers with dibutyryl 3', 5' cyclic AMP. Dibutyryl 3', 5'-cyclic AMP induced automatic activity in Purkinje fibers of myocardial strip in the rat. The phenomenon was not affected by beta adrenergic blockade.


[Parameters of collagen biosynthesis in cotton pellet granuloma of rats on iron deficiency (author's transl)]. Rats of Wistar strain, of same age, were kept on iron free diet up to nearly absolute iron deficiency in iron depots. Afterwards granuloma was produced by implantation of cotton pellets subcutaneously. For characterization of the collagen biosynthesis in the granuloma the neutral salt soluble collagen and the activity of the prolyl hydroxylase were measured in the granuloma 4, 8 and 12 days after cotton pellet implantation. At the same time "collagen-like" protein was determined in the serum of the animals. The enzyme activity was statistically significant lower in the granuloma of animals on iron deficiency than in the granuloma of the comparable groups on normal diet. Statistically significant higher concentration of neutral salt soluble collagen was found 8 and 12 days after cotton pellet implantation in the group on iron free diet. There was no significant difference as to the serum levels of "collagen-like" protein in serum.


Peroxidase activity in human granulocytes, inter- and intra-individual variations. A kinetic method for quantitation of peroxidase activity ('myeloperoxidase', E.C. 1.11.1.7.) in human granulocytes has been evaluated. The enzymic activity was determined at 37 degrees C, PH = 7.0. Substrates: 2-methyxo-phenol (1.25 mmol/l) and H2O2 (0.1 mmol/l). When applied on granulocytes from solitary blood samples from healthy, normal subjects the detected peroxidase activity varied considerably from one person to another (CV = 40-50%). Sequential determinations of the peroxidase activity in granulocytes from selected healthy, normal subjects demonstrated substantial intra-individual variations. Analysis of variance confirmed that the intra-individual variations (CV = 36%) exceeded all other variance components involved.


Studies on the pre-alpha-lipoprotein of human serum. I. characterization of an albumin-containing lipoprotein. In this study an albumin-containing lipoprotein is isolated by column affinity chromatography and electrophoresis. Its electrophoretic mobility is faster than that of albumin in agarose gel. Immunologically it reacts with anti-albumin and anti-apolipoprotein-A-I. No reaction is obtained against antibodies to any of the other previously known lipoportein families: Apo-AII, Apo-B, Lp(a), Apo-C, LpX, Apo-D or Apo-E ('the arginine rich peptide'). It differs from purified albumin in having higher amounts of glycine, serine and glutamic acid. Moreover, the molecular weight is estimated to 80,000 as compared to 67,000 for albumin.


Effects of corticotrophin and choriogonadotrophin on urinary cyclic adenosine 3',5'-monophosphate. The actions of exogenous corticotrophin (ACTH) and human choriogonadotrophin (HCG) were assessed by measuring cyclic adenosine 3',5'-monophosphate (cAMP), 17-ketosteroids (17-KS), 17-ketogenic steroids (17-KGS), androsterone (A), etiocholanolone (E), dehydroepiandrosterone (DHEA) and pregnanetriol (P3) in 24 h urine. ACTH was infused intravenously into six healthy women. A dexamethasone (DXM) suppression test was also performed, and continued when HCG was injected intramuscularly. The effects of intramuscular injection of ACTH and administration of DXM on urinary cAMP, 17-KS and 17-KGS were also studied in an adrenalectomized and ovariectomized patient. ACTH, 250 microgram (25 i.u.), increased excretion of cAMP in the healthy women and also in the patient. In the six controls there was a simultaneous normal increase in 17-KS, 17-KGS, A, E, DHEA and P3 excretion. DXM did not cause the excretion of cAMP to fall below the basal level in any of the subjects examined but the excretion of all the steroids studied decreased significantly. The only effect of HCG was to increase P3 excretion. The results indicate that the increment in cAMP is probably related to an extra-adrenal effect regulated by ACTH.


High density lipoproteins (HDL) and physical activity: the influence of physical exercise, age and smoking on HDL-cholesterol and the HDL-/total cholesterol ratio. 220 trained men, examined the day before participation in a cross country ski-race, had significantly higher HDL-cholesterol and HDL-/total cholesterol ratio than untrained men, but did not differ signficantly from untrained women. HDL-cholesterol was significantly higher in skiers above 60 years than in skiers of younger age. Tobacco smokers ahd lower HDL-cholesterol and HDL-/total cholesterol ratio than non-smokers, but the differences were only significant in skiers, not in controls. HDL-cholesterol was positively correlated to total cholesterol in skiers. The HDL-cholesterol level may possibly contribute to the lower morbidity of CHD in men who are physically active during leisure time.


Comparison of the reactions of neutral granulocyte proteases with the major plasma protease inhibitors and with antiplasmin. Reaction mixtures of human serum and increasing amounts of granulocyte collagenase, elastase and chymotrypsin-like enzyme were studied by crossed immunoelectrophoresis utilizing antibodies against alpha1-antitrypsin, alpha1-antichymotrypsin, and antiplasmin. The increasing complex formation of alpha1-antitrypsin and alpha 1-antichymotrypsin with the different granulocyte proteases was not accompanied by any changes in the electrophoretic mobility or precipitate pattern of antiplasmin until the protease binding capacity of serum was saturated. The antiplasmin component in the reaction mixtures of human serum and granulocyte collagenase or elastase was not precipitated by antibodies against the proteases. The results indicate that none of the granulocyte proteases are bound by antiplasmin and that these enzymes do not activate plasminogen in serum.


Studies on the pre-alpha-lipoprotein of human serum. II. Evidence for the presence of an albumin-apo-A-I complex. By combined column affinity chromatography and preparative electrophoresis, a lipoprotein was isolated from the electrophoretically defined pre-alpha-region. The isolated fraction, designated Fraction II1, demonstrated one band after electrophoresis in agarose, in polyacrylamide, and in sodium dodecylsulphate containing polyacrylamid. Double diffusion experiments disclosed the presence of albumin and apolipoprotein-A-I within the fraction. After reduction with mercaptoethanol and subsequent electrophoresis in sodium dodecylsulphate containing polyacrylamide gel, two bands appeared. One of the bands had an electrophoretic mobility similar to albumin monomer (mol.wt 67,000), the other had the same electrophoretic mobility as apolipoprotein-A-I with a mol.wt of 28,400. It is suggested that Fraction II1 contains an albumin-apolipoprotein-A-I complex.


Adenylate cyclase activity in human liver membranes and its inhibition by adenosine and adenine nucleotides. The production of adenosine 3',5'-monophosphate (cyclic AMP) in a membrane preparation from human liver homogenate has been studied. Cyclic AMP production was enhanced by glucagon, guanylyl 5'-imidodiphosphate (GMP-PNP), or fluoride, or combinations of these. Adenosine, adenosine monophosphate (AMP) and adenosine diphosphate (ADP) at a concentration of 10(-3) mol/l antagonized the effects of all stimulants. These data suggest that inhibitory effects are exercised at the catalytic moiety of the adenylate cyclase system, or at the transducer function between hormone receptor and catalytic unit. In contrast, adenosine at a concentration of 10(-5) mol/l antagonized glucagon- but not fluoride-stimulated adenylate cyclase activity.


Muscle metabolism during and after strenuous intermittent running. Muscle and blood metabolites, plasma insulin and cyclic adenosine 3',5'-monophosphate (cAMP) levels were investigated in five male runners before and after strenuous intermittent running exercise of short duration. Immediately after the exercise, the mean muscle creatine phosphate level (CrP) had fallen by 74% (P less than 0.02) and 30 min later the initial level was regained in only one subject. Other immediate results were increases in mean muscle lactate (460%, P less than 0.005), glucose (130%), glucose-6-phosphate (G6P, 320%) and fructose-1,6-diphosphate (FDP, 32%). Muscle ATP and glycogen concentration had decreased by 31 and 23% (P less than 0.05), respectively. However, ATP, glucose, G6P and FDP changes were not significant owing to the great individual variation. This may have been due to the different training programmes of the runners. Immediately after the exercise mean plasma insulin was 210% (P less than 0.01), blood glucose 71% (P less than 0.005) and plasma cAMP concentration 260% (P less than 0.01) higher than the pre-exercise values. After running urinary excretion of cAMP was 29% higher than before the exercise. It is concluded that exhaustive, short-term exercise activates the liver adenylate cyclase system so giving rise to an increased level of blood glucose, which is an important source of energy during this type of exercise.


Multiple sclerosis: local synthesis of electrophoretically restricted measles, rubella, mumps and herpes simplex virus antibodies in the central nervous system. An imprint electroimmunofixation (IEIF) technique was used to study measles, rubella, mumps and herpes simplex virus antibodies in serum and concentrated cerebrospinal fluid (CSF) from ten patients with multiple sclerosis (MS). Electrophoretically restricted virus-specific antibodies were detected in sera or CSF from nine of the ten patients. Comparison of the antibody patterns in matching serum and CSF samples indicated that electrophoretically restricted populations of antibody against one or more of the four viruses were produced locally in the central nervous system of nine patients. No association between the locally produced antibody populations the oligoclonal IgG of the CSF could be demonstrated. The virus-specific antibodies studied thus seem to constitute only a minor fraction of the total IgG of the CSF from MS patients.


[The state of hormone and chemotherapy in breast neoplasms]. Several decisive developments have emerged during the past few years in the hormonal treatment and chemotherapy receptors should make for a more selective and successful application of hormone therapy. In the field of chemotherapy, highly active substances have been developed. Two groups of routine treatment may be defined: the first employs combinations of cytoxan, methotrexate, 5-fluorouracil and prednisone, and the other, combinations of these agents with the highly active adriamycin. With these combinations, remissions lasting an average of over one year, with significantly prolonged survival, can be achieved in about two thirds of patients. It remains uncertain whether initial addition of hormone treatment to the chemotherapy is of definite advantage. Modern chemotherapy appears to have been especially beneficial in altering the course in patients with poor prognosis. The newest development is the use of chemotherapy postoperatively, i.e. so-called adjuvant chemotherapy. For the present this should only be done within controlled studies and in patients with histologically proven axillary lymph node metastases.


Trisodium phosphonoformate, a new antiviral compound. Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs.


Generation of new mouse sarcoma viruses in cell culture. Endogenous nontumor-producing type C viruses from C3H mice were used to generate rapid, solid tumor-inducing variants in cell culture. The new mouse sarcoma viruses induce undifferentiated sarcomas with a short latency period upon inoculation into newborn NIH Swiss mice. Transforming viruses appear only transiently, at a time when the virus-infected cells show morphologic alterations; both before and after this time, transforming viruses cannot be detected. These results show that variants of endogenous type C virus which contain transforming genes (oncogenes) can arise during spread of the endogenous virus in fibroblast lines in vitro as well as in susceptible tissues in vivo.


Growth inhibition of transformed cells with succinylated concanavalin A. Succinylated concanavalin A reversibly inhibits the growth of SV40 transformed mouse 3T3 cells and thus causes an accumulation of the cells in the G1 phase of the cell cycle. In a soft substrate (methylcellulose) succinylated concanavalin A also restores in transformed cells the growth behavior typical of untransformed cells.


Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver. A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.


The biology of oxygen radicals.

The biology of oxygen radicals. The reactive superoxide radical, O2-, formerly of concern only to radiation chemists and radiobiologists, is now understood to be a normal product of the biological reduction of molecular oxygen. An unusual family of enzymes, the superoxide dismutases, protect against the deleterious actions of this radical by catalyzing its dismutation to hydrogen peroxide plus oxygen.


Opiate effects after adrenocorticotropin or beta-endorphin injection in the periaqueductal gray matter of rats. Injections of adrenocorticotropic hormone (ACTH) into the periaqueductal gray matter of drug-naive rats resulted in a dose-dependent opiate abstinence syndrome characterized by fearful hyperreactivity and explosive motor behavior. Injecting shorter chains of ACTH caused attenuated forms of this behavior. Injections of beta-endorphin at this same site caused opposite behavior: sedative, analgestic, and catatonic. If the effects of morphine are mediated by two classes of receptor) and the other which is not stereospecific and naloxone-insensitive--the endogtor)--and the other which is not stereospecific and naloxone-insensitive the endogenous ligand of the second receptor may be ACTH. The neuropeptides ACTH and endorphin may be part of an integrated neuromodulatory system, and the opiate abstinence syndrome may be the result of an altered interaction between the two receptor systems.


Rod-cone dysplasia in Irish setters: a defect in cyclic GMP metabolism in visual cells. An abnormality in retinal guanosine 3,5-monophosphate (cyclic GMP) metabolism is demonstrated in the inherited rod-cone dysplasis of Irish Setter dogs. Affected visual cells are deficient in cyclic GMP phosphodiesterase activity and have elevated levels of cyclic GMP. The biochemical abnormalities observed in affected retinas of Irish Setters are similar to those in the retinas of mice with inherited retinal degeneration before visual cell degeneration begins. A defect in cyclic GMP metabolism may be characteristic of early-onset degenerative diseases of the retina, possibly including those that affect humans.


Mitochondrial thyroid hormone receptor: localization and physiological significance. Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor.


[Pulmonary embolism in general medicine. Characteristics and diagnostic elements]. Natural history of pulmonary embolism observed during a 4-year period in a non-discriminayory Department of Internal Medicine, with reference to 7,843 admissions : 2 per cent of patients, 9 per cent of deaths, 22 per cent of post-mortem examinations. Value of various paraclinical examinations, more especially ECG, lung scintigraphy and determination of blood gases.


[A simple evaluation of osteoporosis: study of the architecture of the upper extremity of the femur by pelvic radiography]. From the study of the architectural features of the system connecting the neck to the femoral diaphysis on pelvic radio-grams, osteoporosis can be classified into seven stages (7 to 1) of increasing severity. It is thus possible to estimate the risk of fracture, the latter being over 50 per cent from stage 4 onward. The cortex-diaphysis relationship (RCD) follows a parallel course but is less reliable. The investigation of a control group of 20 subjects and 37 patients with osteoporosis, aged 50 to over 80, shows the value of this method, with which it is moreover possible to check the evolution of the disease and the effects of treatment.


[The heart of the nonagenarian].

[The heart of the nonagenarian]. Clinical, radiological and electrocardiographic abnormalities found at cardiovascular examination of 140 patients in their nineties admitted into hospital, were listed and a systematic comparison was established between 36 subjects in their nineties in a home for the aged and subjects in their eighties in the same home. Comparison with previous similar series.


[Effect of tiapride on the side effects of cerebrospinal fluid depletions in spinal puncture, pneumoencephalography and air myelography]. The authors report their experience of the treatment post-cerebrospinal fluid loss syndrom, following subtraction by lumbar puncture, pneumoencephalography and air myelography. The study of 70 patients, divided in two equal groups, one receiving classic therapy, one receiving tiapride, a new molecule of original conception, lead to emphasize the interest of this drug. Tolerance in general is good, despite the administration of high doses and effects on the syndrom are positive and remarkable in preventive and curative treatment.


[Vascular manifestations of Touraine's great aphtosis (Behcet's syndrome)]. Among the systemic manifestations of Behçet's syndrome, venous and arterial involvements are discussed. Venous thrombosis is a common manifestation and may be considered as a cardinal sign in the diagnosis. Venous and arterial thrombotic complications may be regarded as agents of morbidity and mortality. The pathogenesis of the occlusive process is still some what obscure, although vasculitis and impaired local vascular fibrinolytic activity play a part in it. Therapeutic measures using fibrinolytic enhancing agents may prevent and control the thrombotic complications of the disease.


[Frequency of association of cardiac and urinary abnormalities]. In 680 cases of congenital heart disease, the authors discovered 49 uropathies (i.e. 7.2%) diagnosed thanks to a film of the urinary apparatus taken during angiocardiography. These uropathies were encountered mainly during ventricular septal defects, pulmonary stenosis and Fallot's tetralogy. The diagnostic value of the film during angiocardiography is great as it revealed 22 out of 49 uropathies (i.e. 44.9%) clinically silent until then.


[Epidemiologic study of 850 children with burns requiring hospitalization]. This study concerns 850 cases of burns in children. It showed the predominance of burns in boys between the ages of one and 3 years. Most domestic accidents (96.5%) were due to boiling water (55.9%), the second cause was burns due to a flame (11.7%). Most accidents arrived at meal times. The area of burnt skin was as follows:--in 222 cases, less than 5%;--in 365 cases, between 5 and ten percent;--in 152 cases, bwtween 10 and 25%;--in 111 cases, more than 25%.


[Non-addictive properties of tiapride (1347)]. Possible addiction to tiapride was sought in a 10 kg Beagle dog and an ordinary 12 kg dog using the substitution method suggested by J.J. Deglarez. Tiapride at a dose of 30 mg/kg was not able to interrupt the state of hyperexcitability triggered off by sudden morphine withdrawal. On may consider that tiapride is completely lacking in addictive properties.


[Nervous and digestive manifestations in chronic alcoholism. Their treatment by tiapride]. Triapride has proved to be effective for the treatmentof neurological and digestive disorders associated with chronic alcoholism. The clinical and physiopathological aspects of this disease are discussed briefly. Tiapride has a significantly effective action on tremor and muscular pains in moderate cases of alcoholism.--It corrects changes in hebanour and mood.--It improves appetite stimulating the desir for food and reducing the overall functional symptomatology. Tiapride is well-tolerated and vigilance is not modified.


Bronchial adenoma--benign or malignant?

Bronchial adenoma--benign or malignant? Bronchial adenomas grow slowly and are potentially malignant. Of the 45 cases reviewed, 36 were carcinoids, six were adenocystic carcinomas, two were mixed tumors, and one was mucoepidermoid carcinoma. The carcinoid group is subdivided into histologically typical 27(75%), atypical 9 (25%), and metastasizing 9 (25%) adenomas. There were 32 lobectomies, seven pneumonectomies, one sleeve resection, and two tracheal resections for adenocystic carcinoma. Ten-year survival rate was 88% for typical carcinoids, 66% for atypical carcinoids, and 44% for metastasizing carcinoids. In the cylindroma group, one patient was lost to follow-up, one died postoperatively, and one developed recurrence of the tumor eight years later. The only patient with mucoepidermoid carcinoma is alive without evidence of recurrence nine years after operation.


Pleiotropic drug resistance in cystic fibrosis fibroblasts: increased resistance to cyclic AMP. In previous studies, cystic fibrosis (CF) fibroblasts were demonstrated to be resistant to the cytotoxic effects of ouabain, dexamethasone, and the sex hormones, dihydrotestosterone, 17beta-estradiol, and progesterone. We now show that CF fibroblasts also exhibit greatly increased resistance to the cytotoxic effects of exogenous dibutyryl cyclic AMP (cAMP), as well as to isoproterenol and theophylline, drugs which are known to increase endogenous levels of cAMP. CF cells were also shown to have normal amounts of (3H)cAMP binding to protein kinase as well as normal amounts of cAMP-stimulated protein kinase activity. Phosphodiesterase in CF cells was also found to be stimulated by cAMP to the same degree as in normal cells. These findings suggest that there is no detectable protein kinase deficiency in CF cells. cf cells thus appear to be unlike some cAMP-resistant mutants described by others which are defective in protein kinase activity and cAMP regulation of phosphodiesterase levels. The cross-resistance of CF fibroblasts to ouabain, steroid hormones, and cAMP may provide a unique opportunity to study the biochemical events involved in the metabolism of these drugs as well as the basic biochemical defect in a common human genetic disease.


Pregnancy and breast cancer.

Pregnancy and breast cancer. Breast cancer in association with pregnancy and lactation is rare, but presents a therapeutic problem of considerable magnitude. The outlook for such patients is less favorable than that of nonpregnant, nonlactating women, probably because the stage of the disease is more advanced when it is discovered. The most significant factor in the poorer prognosis is physician delay in diagnosis and therapy. When mastectomy is carried out early in pregnancy, the operation can be as effective as in nonpregnant women of the same age groups. It is emphasized that when pregnancy and breast cancer are found concurrently, prompt therapy for the cancer should be undertaken. Interruption of pregnancy in nondisseminated breast cancer is of little value. If pregnancy is near term when the diagnosis of disseminated breast cancer is made, the desire of the husband and wife for a child should be considered. A modest delay in therapy to allow for delivery probably has no deleterious effect. Castration should be withheld and used only for the patient with metastatic disease. There may be a place for prophylactic castration in the treatment of disseminated disease, but its role is yet to be clearly defined. Subsequent pregnancies in a patient with axillary spread at the time of mastectomy are contraindicated, because of the high rate of treatment failure and decreased rate of survival. In patients desiring future pregnancies following mastectomy, a period of observation of at least 2 years seems wise. At the end of that period, if clinical evaluation, laboratory values, roentgenographic studies, and isotopic bone scanning are negative for disseminated disease, subsequent pregnancies seem safe. Prompt evaluation of any breast mass found during pregnancy and lactation should be carried out by needle or operative biopsies under local anesthesia. Although the prognosis of the pregnant or lactating woman with breast cancer is generally favorable, numerous long-term survivals are encountered in those women who undergo prompt mastectomy early in pregnancy. The former pessimistic outlook for such patients seems unjustified. With modern methods of diagnosis and treatment, therapy can be effective and successful.


The effect of splanchnic viscera removal upon canine liver regeneration. The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor.


Interventions in atherosclerosis: a review for surgeons. For the surgeon, atherosclerosis is defined by a variety of aneurysmal, occlusive, or ulcerated lesions in major arteries. These end-stage lesions often require operative treatment. However, just as advanced atherosclerosis presents complex clinical phenomena, so its earlier stages display many underlying mechanisms promoting lesions. To arrest or control atherosclerosis, the disease must be approached with knowledge about diverse biological processes. These include ceullar and systemic aspects of lipoprotein metabolism, reactions and metabolism of endothelium and smooth muscle cells of the arterial wall, and interaction of platelets with the arterial intima. The chronic nature of this process is such that surgeons are involved intimately with overall management as well as with surgical procedures. We will review underlying biological processes of atherosclerosis as related to interventions in patients with clinically apparent disease.


Intrathoracic neural tumours.

Intrathoracic neural tumours. The experience of one regional thoracic surgical unit in managing intrathoracic neural tumours over a 25-year period is presented. Neural tumour was diagnosed in 55 patients, of whom 41 were asymptomatic. In 11 patients complete resection was not achieved--the reasons for this and its effect on the outcome of the patient are discussed. There were 52 posterior mediastinal and three lateral chest wall tumours. The pathological distribution was as follows--benign nerve sheath tumours (neurofibroma, neurilemoma) 39, ganglioneuroma 13, and neuroblastoma 3. One neurofibroma recurred as a neurosarcoma six years after its apparently complete resection and was removed by an extensive resection at reoperation. One neuroblastoma recurred within the spinal canal four years after incomplete excision at thoracotomy--this patient died subsequently of widespread metastatic neuroblastoma. No other tumour is known to have recurred.


Cellular immunity to cytomegalovirus in a patient following bone marrow transplantation. Cell-mediated immunity to cytomegalovirus (CMV) was studied in a bone marrow transplant patient with evidence of active CMV infection. The lymphocytes from this patient were found to specifically recognize and respond in vitro by transformation to CMV-infected Wistar-38 fibroblasts and by production of macrophage migration inhibition factor to CMV antigen. In addition, plasma and spinal fluid from the patient were found to contain blocking factor that specifically inhibited the lymphocyte response in the above assays. Biochemical, biophysical, and immunological studies indicate that the blocking factor may be an antigen-antibody complex.


[Poly (ADP-ribose), ADP-ribosylation of proteins and regulation of cell activity]. The nature of a before unknown biological activity of NAD as a substrate in protein modification reaction is considered. Upon enzymatic digestion of NAD its adenosinediphosphate ribose (ADPR) part is transferred to acceptor proteins. ADPR in its mono- or polymeric form is covalently linked to proteins at the expense of NAD's high energy bound. Negatively charged ADPR, in association with a protein, is able to alter the charge, conformation and biological activity of the latter. The reaction is important in structural rearrangements of chromatin, in the synthesis and repair of DNA, in cell growth and differentiation and in the mechanisms of actions of actions of bacterial toxins.


[Autonomous hyperparathyroidism--diagnostic values of laboratory parameters (author's transl)]. The diagnostic parameters of HPT in 22 patients with recurrent urinary stone disease and high levels of PTH were investigated with particular reference of their practical value and reliability. Among the diagnostic parameters PTH and ionized calcium in serum and calcium/creatinine ratio, TRP p. c. and c-AMP in urin after overnight fasting have the best reliability.


[Disc-electrophoresis of proteins and infrared spectroscopy of Rous sarcoma tissue]. A study of sarcoma was carried out in the process of its development in the chicken muscular tissue. Simplification of the protein composition and IR-spectra of the tumour are established which is manifested in an increase in the content of albuminous proteins and in a decrease in some globulin fractions, in disappearance of two IR spectrum bands as well as in changes in relative optical density of the bands at 1560 and 1380 cm-1.


[On 14C-nicotinate penetration into cellular and subcellular structures of animals following adrenalectomy and hormone administration]. The experiments on the Wistar line rats and mongrel dogs showed that gravitational overloading, surgical and chemical adrenalectomy, injections of certain hormones and actinomycin D affect essentially the permeability of blood cells and liver mitochondria to 14C nicotinic acid. An assumption is advanced that the transport of 14C nicotinic acid to biological structures occurs with participation of complex mechanisms, the function of which is regulated by hormones and is coupled with the processes of protein synthesis.


Prevention of avian lymphoid leukosis by induction of bursal atrophy with infectious bursal disease viruses. Five groups of genetically susceptible chickens were inoculated at hatching with lymphoid leukosis virus; four of these were given infectious bursal viruses of varying virulence at 14 days of age and one group was not inoculated (control). All chickens in the control group developed evidence of lymphoid leukosis by 180 days. Two groups given relatively virulent bursal disease viruses, which destroyed bursal lymphoid cells, did not develop lymphoid leukosis. Treatment with avirulent vaccines had no visible effect on bursal morphology and did not significantly alter the incidence of lymphoid leukosis in two other groups, although the time of development was delayed. Results of our study show that viral-induced destruction of the bursa of Fabricius eliminates the development of lymphoid leukosis but that infection without bursal destruction has little effect on lymphoid leukosis.


Studies on cross protection induced in calves by rotaviruses of calves, children and foals. Inoculation at birth with a live attenuated strain of a bovine rotavirus isolated in the USA (scourvax-reo) induced protection in five gnotobiotic calves seven to 21 days later against a UK isolate of pathogenic bovine rotavirus. However, no protection was induced in three calves challenged three to five days after vaccination. There was a close antigenic relationship demonstrated between the two bovine rotavirus isolates. In contrast only one of three gnotobiotic calves inoculated with foal rotavirus, and one of three with human rotavirus, were protected against bovine rotavirus challenge. Protection in these two calves correlated with high heterologous immunofluorescent antibody titre (320 or greater), although the neutralising antibody titres was less than 20.


[Comparative studies of the virulence of some Aujeszky's disease viral strains]. Clinical, virological, morphological, and immunofluorescence investigations were carried out on 22 pigs experimentally infected with two strains--a virulent one (V) of a 10(-3) titer, and a slightly virulent one (K) of a 10(-7) titer--of the virus of Aujeszky's disease as well as on contact pigs. Results revealed variations in the clinical and morphological manifestation of the disease in the individual groups. They were shown to be due to the strains of the virus that varied in virulence and tissue tropism. In the strain B-infected animals there were clinical symptoms characteristic of the disease, and the morphological changes in the central nervous system were of the nonsuppurative encephalitis type. The pigs infected with the K strain of the virus showed no clinical symptoms, while the contact animals manifested only respiratory troubles as well as interstitial pneumonia. It was demonstrated that the strains of slight virulence had weak nervotropic and pronounced pneumotropic characters. Complex virologic, morphologic and immunofluorescence investigations can be used for the diagnosis of the atypical forms of Aujeszky's disease and for the differentiation of the virulent from the slightly virulent strains of the virus.


[Attempts to demonstrate and identify avian adenoviruses by an immunofluorescence method]. A specific conjugate of a hyperimmune serum, obtained from rabbits with the use of the reference Phelps-CELO strain, was employed in a direct immunofluorescence method to investigate more than 320 lamelles with cell cultures infected with 4 field CELO virus strains and the reference Phelps-CELO strain. It is stated this method is specific and prompt for the early diagnosis and identification of adenoviruses (CELO viruses).


[Action of actidion on the replication of the transmissible gastroenteritis virus]. Explored was the possibility of inhibiting the replication of the virus of the transmissive gastroenteritis by means of actidione. It was found that in certain concentrations the antibiotic completely inhibited the replication of this virus. In individual strains the process of replication was not influenced by the various concentrations applied. It was demonstrated that when the antibiotic was added to the infected cell cultures during individual phases its varying concentrations influenced the virus replication. When actidione was added to the cells at the time of virus adsorption it did not inhibit the synthesis of the virus. Similar were the results when the cells were cultivated 24 hours with specified concentrations of actidione prior to their infection with the virus.


[Effect of denervation on carbohydrate metabolism in the liver]. Activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and content of glycogen in liver as well as content of sugar in blood were studied after denervation of dog liver tissue. Activities of these enzymes were increased and content of glycogen in hepatocytes was decreased within 1-2 weeks after the denervation. Within a month the enzymatic activities and content of glycogen in liver tissue approached the control levels; these patterns were similar to control ones within the subsequent periods of examination (3-months--1 year). Content of sugar in blood was the same within all the periods of study (3 days--3 months).


[Lipoprotein lipase fractionation of very low density serum lipoproteins from healthy subjects and persons afflicted with atherosclerosis]. In vitro experiments showed that blood sera of the patients with atherosclerosis contained rather often the fraction of very low density lipoproteins (VLDL) with sf 100-400 S, which were cleaved by the lipoprotein lipase at the decreased rate as compared with that of normal people. The decrease in cleavage of the VLDL fraction was usually observed in patients with the increased concentration of the lipoprotein fraction in blood sera. These data suggest that separate constituents occurring in the VLDL fraction (sf 100-400 S) may be nonuniformly increased in hyperlipoproteinemia.


[Reaction between cGMP and cAMP in their effect on muscle carbohydrate metabolism]. cGMP (10(-4)-10(-7) M) did not affect the activity of phosphorylase and glycogen synthetase from chicken sceletal muscles; but the cGMP prevented completely an effect of cAMP on the enzymes. This blocking effect was specific for cGMP (GMP did not exhibit the effect) and for cAMP (influence of calcium on the enzyme was not eliminated by cAMP). Possible mechanisms of the cGMP effects studied are considered: 1) stimulation of cAMP hydrolysis, 2) antagonism at the level of proteinkinase system. cGMP (10(-4)-10(-7) M) did not stimulate the phosphodiesterase activity at millimolar concentration of its substrate--cAMP.


[Biochemical features of the liver of high and low cancer mouse strains and primary spontaneous hepatomas]. Sex differences in development of spontaneous liver tumors were studied in mice of CBA strain. Content of mitochondrial proteins, activities of cytochrome oxidase, glucokinase, hexokinase as well as subcellular distribution of hexokinase were also studied in primary hepatomas and in normal liver tissue of the mice of CBA and C3HA strains. Liver tumors occurred in males of CBA strain 7-fold more frequently than in females. Activities of hexokinase, glucokinase, cytochrome oxidase and content of mitochondrial proteins were distinctly alterep both in primary spontaneous hepatomas and in transplantable strains. But, contrary to the transplantable tumors, in spontaneous hepatomas hexokinase, associated with mitochondria, was not found. Decrease in activities of glucokinase and cytochrome oxidase was observed at the early stages of development of CBA strain in males as compared with females of CBA and males of C3HA strains, i.e. distinct decrease in several functional patterns of liver tissue was observed. Subcutaneous administration of orthoamine azotoluene into mice of the C3HA strain caused alteration in activity of these enzymes from liver tissue, which was typical for hepatomas, already at the early steps of development.


[Serum lipoproteins in the generalized form of type III glycogenosis]. Distinct accumulation of glycogen, anomalous in structure, and absence of amylo-1,6-glucosidase activity were observed in studies of material obtained by biopsy from liver and muscle tissues of a patient with generalized form of glycogenosis type III. Anamalous glycogen (limitdextrin) was also found in erythrocytes. Concentration of lipoproteins, especially of low density lipoproteins 12.20 S and 0-12 S, was increased in blood serum. Spectrum of lipoproteins acquired a tendency to normalization simultaneously with clinical improvement after intravenous administration of glucose and treatment with cholesterolamine per os.


[Spin label study of plasma lipoproteins]. Lipoprotein structure was studied by means of EPR-spectroscopy of spin probes--iminoxyl derivatives of stearic acid and of androstane--in blood plasma of 40-59 years old men. The mode of wrapping of external monolayer of lipoprotein particles, the type of their intermolecular interactions were similar to corresponding characteristics of bilayer in biological and model membranes. Correlation was observed between concentration of separate lipoproteins in blood plasma and the structural parameters of the probe distribution in hydrophobic and polar regions of the lipoprotein preparations. The phenomena observed might be related to capacity of the high density lipoproteins to accept cholesterol from cell membranes with transfer of cholesterol into liver tissue, where it is subsequently metabolized, as well as to the property of the very low density lipoproteins to transfer cholesterol into tissues, particularly, into vascular walls.


[Detection of autoimmune lipoprotein--antibody complex in human plasma and aortic wall]. An immune complex of lipoprotein-antibody was found in human blood plasma and in tissue liquid of aorta, impaired by atherosclerosis. In the majority of cases the antigen component of the immune complex was lipoprotein of very low density. After dissociation of the complex at acid pH, immunoglobulin G was isolated, which was identified by double immunodiffusion in agar gel; the immunoglobulin reacted in RBS both with autological and, in some cases, with isological lipoproteins.


Immunization against swine influenza in the Yale University Community. Nineteen percent of the approximately 30,000 members of the Yale community aged 18 through 59 received swine influenza monovalent vaccine (A/New Jersey/1976) during the three days of a mass immunization program in Nov. 1976. Based on 1508 card questionnaires received, 71.2 percent of the vaccine recipients experienced a sore arm, 23.4 percent headache, 13.4 percent chilliness, and 9.7 percent feverishness or fever. The sore arm was judged as severe in 5.9 percent as was the headache in 4.2 percent. Other reactions were regarded as severe in less than 2 percent. All reactions were reported more commonly by women than mean and all decreased with age.Serologic tests carried out at the start of the immunization period revealed that influenza A/New Jersey/1976 antibody was absent from 78.6 percent of the recipients; almost all persons under 25 lacked this antibody. A significant antibody rise occurred in 78.3 percent of those receiving a single dose of monovalent vaccine. Somewhat better antibody responses occurred in 36-59 year olds than in those age 17-25 (84.9 vs 75.5 percent); the geometric mean antibody titer was also much higher (1:136.8 vs 1:31.2). However, the presence of pre-existing homologous antibody did not significantly improve the antibody response to the vaccine. Cross-reacting antibody rises to A/Victoria/1975 were found in 16.2 percent of the recipients of monovalent vaccine.


[Carotid body tumors and their operative problems (author's transl)]. Exstirpation of a neck tumor as an outpatient procedure became troublesome (bleeding). The surgeon had not realised the nature of the tumor.


[Selection of newborns with birth injuries for after care in a special session]. Selection of birth-traumatical injured newborns for follow-up with special care.--Premature newborns most will be in a special care during infancy and childhood. For all the mature infants this way is to expensive. We publish a compilation of abnormal neurological findings suitable for selecting with high risk of birth traumatical induced brain damage. The risk-group contains about 5% of all mature newborns. This number is small enough for a high expense within the bounds of the common care for mother and child.


[Clinical aspects of trophoblastic tumors]. Trophoblastic tumors are among the rare diseases in this country. The most important clinical aspects are demonstrated by references and personal experiences in the treatment of trophoblastic tumors. In many countries (SU, USA, GB, Japan) the treatment of trophoblastic tumors has been centralized.--The therapeutical strategy is based on histology, stage and other important prognostic factors. Most important is chemotherapy with antineoplastic substances. Surgery and radiation are to be used only under appropriate indication. After treatment the control of the HCG-values by radioimmunassay is of high importance for the early diagnosis of relapse.--All facts demonstrate, that also in the GDR a stronger centralization of the treatment of trophoblastic tumors should be attained.


[Basic studies on chronic polyarthritis as a collagen-autoimmune disease]. Clinical and experimental data establishing a hypothesis about rheumatoid arthritis (RA) as a collagen auto-immune disease are reviewed, beginning with the demonstration of rheumatoid synovial collagenase, the demonstration of collagen antibodies in the serum and the synovial fluid of patients with RA, the demonstration of collagen inclusion bodies and collagen-anticollagen immune complexes in synovial fluid cells and the synovial fluid of patients with RA, and leading to the in vitro demonstration of the inflammatory effect of such complexes, and the induction of experimental arthritis by these complexes. Each section contains tabular summaries of various investigations. Finally, a relation between these observations and the conclusions deduced from them and the appearance of rheumatoid factors in RA and the pathogenic effect of rheumatoid factor - gammaglobulin aggregates is considered.


[Noradrenaline and glycogen content and the activity of several enzymes of carbohydrate metabolism in normal, embryonic, and partly denervated livers and in hepatomas of the rat]. The noradrenaline and glycogen contents as well as hexokinase, glucokinase and glucose-6-phosphatase activities were determined in normal, embryonic and partially denervated (bilateral dissection of the Nervus splanchnicus or Nervus vagus) rat liver and in two transplantable hepatomas. In embryonic liver and hepatomas a strong decrease or complete loss of noradrenaline and glycogen levels and glucokinase and glucose-6-phosphatase activities is demonstrable as compared to the livers of adult animals, while the hexokinase activity is enhanced. Following bilateral splanchnicotomy the glycogen content and hexokinase activity are enhanced; the glucose-6-phosphatase activity is reduced, and the liver does not contain any noradrenaline. Bilateral vagotomy causes decrease of the glycogen content, of the hexokinase and glucokinase activities and an enhancement of glucose-6-phosphatase activity. The results lend support to the idea of antagonistic action of the sympathetic and parasympathetic nervous systems upon several partial reactions of carbohydrate metabolism of liver. In addition, it can be assumed that the alterations of the carbohydrate metabolism demonstrable in hepatomas as compared to normal liver are not solely attributable to disturbance or breakdown of the nervous regulation.


Serum somatomedin A in growth retarded children. The levels of serum somatomedin A were determined in 59 growth retarded Japanese children by a radioreceptor assay. Low levels were found in 10 children with growth hormone (GH) deficiency and 7 children with relative GH deficiency with means of 0.26 +/- 0.48 +/- 0.04 U/ml, respectively. Serum somatomedin A levels in 42 retarded children with normal growth hormone levels were within the range of normal adults, and did not correlate with degree of short stature. Significant increases of somatomedin A after hGH administration were found in children with growth hormone deficiency but not in children with normal growth hormone. These results show that determination of somatomedin A in serum corelates well with the state of growth hormone secretion, and is of great importance in the selection of patients for treatment with human growth hormone.


Changes in cyclic nucleotides of rat thyroid by chronic administration of LATS and TSH. The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5'-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.


Peripheral cryoglobulinemic neuropathy in a patient with Gaucher's disease. Cryoglobulinemia with peripheral cryoglobulinemic neuropathy is reported in a patient with Gaucher's disease. To the best of our knowledge, a similar relationship has not been previously described. The question whether the cryoglobulinemic neuropathy in this patient is related to Gaucher's disease, or is a mere coincidence, is discussed.


[The age dependent distribution and activity of enzyme metabolism in the humeral epiphysis]. In the chondrocytes of the humerus epiphysis and of the articular cartilage of newborn, 8-, 30-, and 60-day-old albino rats, cytochrome c oxidase, arylsulfatase and carbonate dehydratase activity was found. In the transformation zone, the column cartilage and the proximal hypertrophic cells of 30- and 60-day-old animals, cytochrome c oxidase and arylsulfatase are distinctly present. The reaction of carbonate dehydratase is most pronounced in these cell regions of 8-day-old animals. In the mineralization zone we found only small activity of the investigated enzymes. The cells of the opening zone of all age groups demonstrate an additional activity. In the articular cartilage the cytochrome c oxidase is very distinct. The carbonate dehydratase follows with variable reduction and finally the arylsulfatase with only small activity.


Comparative histochemical study of the enzyme changes in the ovary and uterus of mammals with special references to steroidogenesis. A comparative study of the enzymes delta5-3beta-HSD, cytochrome oxidase and peroxidase has been made in the ovaries and uterus of mammals (mouse, guinea pig, cat and dog) during various reproductive phases. The granulosa cells of developing follicles, hypertrophied interstitial cells of thecal origin and the luteal cells show intense delta5-3beta-HSD and cytochrome oxidase activity. Peroxidases are found to be present in the corpus luteum and the epithelial cords of thecal origin. delta5-3beta-HSD and cytochrome oxidase activity is localized to the endometrium and myometrium of mature and pregnant uterus of mouse and guinea pig, while peroxidase is seen only in the decidua and endometrial glands of pregnant animals. The significance of these enzymes is discussed in relation to the cellular basis of luteinization and steroid hormone synthesis.


Progression of a structural scoliosis during treatment with growth hormone. A case report. A diagnosis of panhypopituitarism was made in an infantile male at the age of 22. Skeletal age was estimated to be 14 years. Thyroxin, corticosteroid and later testosterone was administered. Growth hormone was given initially over a period of ten weeks and later for two and a half years. The standing height increased from 143 to 158.5 cm. During periods of growth induced by growth hormone a progression of a thoracic scoliosis from 15 degrees to 62 degrees was observed. In this case growth hormone or the associated substances seem to be the more probable cause of the progression of scoliosis than growth rate per se.


Cyclic AMP and insulin release.

Cyclic AMP and insulin release. The role of cyclic adenosine-3',5'-monophosphate (cAMP) for insulin secretion has been investigated. In isolated islets of Langerhans from the rat, glucose increases cAMP concomitant with insulin secretion. Stimulation of these two parameters is likewise reversible in parallel. The minimal and maximal concentrations of glucose eliciting cAMP and insulin responses are similar. Isomers and epimers of glucose influence insulin and cAMP in a parallel fashion as do sulfonylurea compounds (tolbutamide and glibenclamide). On the contrary, the time-dependent potentiation of glucose-induced insulin secretion is not accompanied by gross changes in cAMP. Reciprocally, in the absence of glucose islet cAMP can be markedly elevated by other agents (methyl xanthines, cholera toxin) without major insulin responses. The results indicate that metabolism of cAMP in the beta-cell is intimately linked to the glucose (and sulfonylurea) action on insulin secretion, although other factors influenced by the hexose are also necessary for the release process. The finding that the cAMP response is impaired in fasting, during the neonatal period and in diabetes mellitus (in the Chinese hamster) suggests an important role for the nucleotide in physiological and pathophysiological states characterized by decreased insulin release.


Immunohistochemical identification of actomyosin-containing (myoepithelial) cells in non-neoplastic and neoplastic tissues. Actomyosin-containing cells in both non-neoplastic and neoplastic tissues of the salivary gland, lung, breast and some other organs were studied by immunofluorescent microscopy using antiactomyosin rabbit serum. In the breast, myoepithelial-like cells with positive immunofluorescence in the cytoplasm were observed not only in sclerosing adenosis and fibroadenoma but also in scirrhous and medullary-tubular duct carcinomas. No positive cells were observed in medullary carcinomas with lymphoid infiltration. The actomyosin positive cells were also seen at the outer layer of tubules of "mixed tumors" and of cell nests in adenoid cystic carcinoma and in myoepithelioma of the salivary gland, but not in the metaplastic squamous cells or in the cells of myxomatous and chondroid areas of "mixed tumor". In carcinoma of the lung, actomyosin-positive cells were observed in adenoid cystic carcinomas and adenocarcinoma of the bronchial gland type, but they were not seen in squamous cell carcinomas or papillary adenocarcinomas. It was concluded that the actomysoin-containing cells with structural appearances of myoepithelial cells in a variety of tumors were neoplastic myoepithelial cells.


A freeze-fracture study of tubular myelin in fetal rabbit lung. A freeze-fracture replication study was undertaken to clarify the relationship between intracellular lamellar bodies of type II alveolar epithelial cells and intra-alveolar contents in late gestation rabbit fetuses. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes devoid of membrane-associated particles, while the limiting membrane of intracellular lamellar inclusion bodies was studied with membrane-associated particles of 150A diameter. The intra-alveolar contents were comprised of two components; spherical bodies, and tubular elements. Spherical bodies were identical to the internal contents of the lamellar bodies and also were devoid of membrane-associated particles. Tubular elements mostly appeared rectangular on cross-fractured faces, but triangular and hexagonal forms could also be seen. These tubules rested on the surfaces of the spherical bodies and appeared to be formed of the outer lipid monolayer of spherical bodies. The present observations suggest that the tubular element of the alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid.


Brain tumors induced in hamsters by intracerebral inoculation of SR-RSV-infected embryonic brain cells. Brain tumors were induced in Syrian hamsters by intracerebral inoculation of brain cells which were obtained from 12-day old syngeneic hamster and infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) in vitro. A total of 212 tumors were developed in all 25 recipients within 19 to 125 days after transplantation. On the basis of light and electron microscopic study, they were classified into four main groups: astrocytoma (45.8%), pleomorphic glioma (50.0%), sarcoma (3.8%), unclassified (0.4%). The morphological features of these tumors were described, and the advantages of this brain tumor model were discussed.


An autopsy case of cholangiocarcinoma with hypercalcemia. Au autopsy case of cholangiocarcinoma which showed clinically hypercalcemia and hypophosphatemia without bone metastases is presented in this report. Although parathyroid hormone (PTH)-like substance of 520 ng/g. dry weight was measured in neoplastic tissue by the radioimmunoassay, membrane-limited secretory granules as those of parathyroid gland were not found in the fine structure. The significance of an existence of secretory granules in ectopic PTH producing tumor is discussed.


Crystalline structures in human pancreatic beta cell adenoma. An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.


Protein kinases in rat testes. Subcellular distribution of the enzyme and endogenous substrates. The subcellular distribution of cAMP dependent and independent protein kinases (Pr K) has been studied in rat tests. The enzymatic activity was preferentially located in the cytosol. In all fractions mature animals have higher specific activity. The localization of endogenous protein substrates of Pr K was investigated using cytosol as an enzymatic source. The best endogenous substrate for the cAMP dependent Pr K seemed to be localized in the microsomal fraction. The rate of protein phosphorylation in the  testicular subcellular fractions was examined by in vitro incubation with 32P-orthophosphate. The nuclear fractions have the highest specific radioactivity.


Mitochondrial production of hydrogen peroxide in Saccharomyces cerevisiae. Intact mitochondria isolated from bakers' yeast and showing respiratory control by ADP, released H2O2 to the suspending medium at rates of 1.2.2.2 nmol/min per mg of protein depending on the mitochondrial metabolic condition. Release of H2O2 from mitochondria increased 1.3 times in swollen mitochondria and 1.2 times after osmotic shock, i.e., when the outer membrane was damaged. Under physiological conditions, yeast cytochrome c peroxidase, mainly  located in the intermembrane space, utilized about 53-55% of the H2O2 generated by the respiratory chain at the inner membrane, partially preventing H2O2 diffusion to the cytosol. Apparently, the outer mitochondrial membrane was highly permeable to H2O2. It is claimed that the risk of cell injury due to H2O2, O-2 and HO is slightly higher in the stationary phase than in the logarithmic phase of growth.