Induction of germination in Blastocladiella emersonii by cyclic AMP and inhibitors of cyclic AMP phosphodiesterase. Since K+-induced germination of Blastocladiella emersonii is accompanied by a rapid decrease of a specific cyclic AMP phosphodiesterase (cAMP PDE) activity and a transient cyclic AMP accumulation, the effects of this compound as well as of some inhibitors of cAMP PDE on the induction of germination were tested. Adenine and caffeine, competitive inhibitors of zoospore cAMP PDE, were able to elicit germination in substitution for K+. Cyclic AMP is a poor inducer, but a synergistic effect was evident when non-effective concentrations of K+ and cyclic AMP were added together to the medium. At the same concentration, cyclic GMP had no effect as compared with cyclic AMP. Lanthanum, a specific antagonist of calcium in several biological systems, completely blocked the germination induced by potassium.


Role of hemolytic factors of Sendai virus on human erythrocyte membrane fluidity. In order to establish whether the hemolytic activity of Sendai virus might be related to changes of the membrane fluidity of sensitive cells, membrane fluidity variations have been recorded in human erythrocytes ghosts in the presence of Sendai and PR 8 viral particles. A decrease of membrane fluidity is elicited by Sendai and Pr 8 virions and by non hemolytic Sendai virus after trypsinization; the effect on membrane fluidity of sendai virus is strongly reduced after pyridine treatment which abolishes hemolytic action.


Identification of a glycoprotein inhibitor of human serum, active towards the hemagglutinating activity of Sendai virus. Non-antibody hemagglutination-inhibiting activity of human serum is due, at least partially, to a glycoprotein inhibitor. This inhibitor was obtained from the whole serum or the fraction VI (Cohn) by means of methods of purification generally used for the preparation of the orosomucoid and was identified more precisely with an acid alpha 1-glycoprotein.


Decline in incidence of hepatitis A infection in Milan. A serologic study. The availability of serum samples collected in 1958 and in 1977 from healthy individuals of Milan, has provided an opportunity to compare the prevalence of anti-HAV and anti-HBs in the same area at a distance of about 20 years. The results obtained show a general drop of anti-HAV rate from 1958 to 1977. Difference in antibody prevalence was found to be significantly remarkable (35.7% versus 3.6%, P < 0.05 and 78.6% versus 26.9%, P < 0.01) in the youngest age groups examined (1-5 and 6-15 years old). Moreover the plateau of antibody acquisition was reached over 30 years of age in people selected in 1958 and over 50 years in 1977. No substantial difference was found in anti-HBs prevalence in sera collected in 1958 and in 1977 (29.2% versus 29.3%). The finding of a decline in hepatitis A infection may reflect the improvements in public health and hygienic conditions which occurred in our city in the last decades, whereas with regard to hepatitis B, the maintenance of the same incidence of infection may be due to different contributory factors.


[Observations on the diffusion of hepatitis A and B virus during an epidemic in a Sicilian town with a high rate of infection]. Epidemiological investigations were carried out during a viral hepatitis outbreak occurring in a Sicilian town of 30,000 inhabitants with poor sanitary standards, with the aim to study the mode of spread of HAV and HBV in conditions of high incidence of infections. HBsAg, anti HBs, anti HAV (RIA), HBeAg, anti HBe and anti HBc were investigated in serum samples from patients, their family contacts and from healthy individuals of different age groups. Morbidity was inferred from case notifications; search of unreported cases among school children, through the study of absenteeism, did not reveal further cases. In all 148 cases, occurred from August 1976 through July 1977 with a peak in January, 44% were under 5 and 93% under 10 years of age. All but 8 of 59 cases in which laboratory data were available were due to HAV. Anti HAV antibodies were highly prevalent in serum samples obtained in February through April 1977: 62% were positive in the 1 to 3 years age group, and more than 90% among school children. Prevalence of HBsAg was age and sex dependent, ranging from 4% to 15%; anti HBs was present in 8% of the children 1-10 years and in 30% or more in age groups 30-41 and over. It is suggested that direct contact between very young children was the main mode of spread of HAV, and inapparent cases the main source of infection, although ambient diffusion through water contamination could not ruled out. HBV was probably propagated mostly by intrafamilial spread with little overt pathology.


Galactose-1-phosphate uridylyltransferase activity in chronic lymphocytic leukemia. Galactose-1-phosphate uridylytransferase (E.C.2.7.12) activity was measured in both lymphoid and erythroid cells from patients with chronic lymphocytic leukemia (CLL). Decreased enzyme activity was found in both cell types using two assay methods. The results suggest the presence of an inhibitor of the enzyme in CLL patients. A correlation between decreased uridyl transferase activity and glycogen accumulation in CLL is postulated.


Serum lipoproteins in rats bearing Morris hepatomas of different degrees of differentiation. Serum lipoproteins were measured by ultracentrifugal means in rats bearing hepatomas of different degrees of malignancy (Morris hepatomas 16, 5123TC and 7777) to determine the effect of these hepatomas on serum lipoprotein levels. Serum lipoprotein patterns were altered, especially in rats bearing hepatomas 16 and 7777, which had elevated high-density lipoproteins. (They were not elevated in serum of rats bearing hepatoma 5123TC). This increase in high-density lipoproteins seems to be specific for chemically induced hepatomas since HDL2 is usually decreased in humans and animals with types of cancer not involving the liver. It appears that hepatomas can synthesize lipoproteins, and the serum levels of the host rats are altered depending on the hepatoma. Different biochemistries appear to be associated with each hepatoma. Cholesterol and fatty acid levels of unfractionated serum and of isolated lipoproteins also indicate abnormal lipid/lipoprotein metabolism associated with these hepatomas.


Influence of charge on the inactivation of membrane bound (Na+ + K+)-ATPase of Yoshida sarcoma cells by inhibitor proteins from cobra venom. Inactivation of (Na+ + K+)-ATPase of Yoshida sarcoma cells and beef brain microsomes by phospholipase A2 and a cytotoxin P6 from snake venom has been examined in relation to their activity to degrade phospholipids. Cytotoxin P6 which was most basic and devoid of phospholipase activity was most effective in inhibiting the (Na+ + K+)-ATPase of Yoshida sarcoma cells. Phospholipase A2 from Naja naja which was most active in degrading phospholipids was least effective in inhibiting (Na+ + K+)-ATPase in Yoshida sarcoma cells or in beef brain microsomes. Addition of trace amounts of cytotoxin P6 to the phospholipase considerably enhanced the inactivation of (Na+ + K+)-ATPase. The evidence suggests that the charge of the inhibitor protein and its specific structure play an important role in the inactivation of (Na+ + K+)-ATPase.


Influence of metaphos on the structuro-functional organization of mitochondrial membranes. It has been established by methods of spectrophotometry and spin probe that the organophosphorus pesticide metaphos, widely used in practice, is an inhibitor of NADH2 oxidase of the respiratory chain of the mitochondria and exerts an influence on the structural organization of the mitochondrial membrane. An effect of metaphos on the nature of the distribution and kinetics of NADH2-induced death of monoradical spin probes of various chemical structures was detected in a suspension of submitochondrial particles obtained from beef heart.


Phosphonoacetic acid: inhibition of transformation of human cord blood lymphocytes by Epstein-Barr virus. Phosphonoacetic acid disodium salt (PAA) inhibited the transformation of human cord blood lymphocytes by Epstein-Barr virus (EBV) at concentrations of 50-100 microgram/ml. At these concentrations, PAA had no effect on the multiplication of EBV transformed human lymphoblastoid cells or on the survival of human cord blood lymphocytes. The transformation of human cord blood lymphocytes by the B95-8 strain of EBV was measured by 3H-thymidine uptake, 5 days or more after infection. The degree of inhibition of transformation was correlated with the relation between the input of EBV and the concentration of PAA in the experiment. PAA inhibited the transformation even when added 24 h after EBV infection, but had no effect when added 48 h after EBV infection. The inhibitory effect of PAA could be overcome by its removal and normal 3H-thymidine uptake was restored even after 6 days of inhibition. The specificity of the inhibitory effect on EBV induced transformation of human cord blood lymphocytes is discussed.


Distribution of 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl free radical in normal and neoplastic animal tissues. The free radical 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) was injected i.p. in doses of 100 mg/kg bw into Syrian hamsters: untreated, partially hepatectomized and grafted with transplantable tumours as well as into mice with B16 melanotic melanoma or with an adenocarcinoma. One hour after application of the compound its content was determined spectrometrically in livers, kidneys, lungs and all tumours. The characteristic triplet signal of TMPO was registered in the hamster and mouse melanotic melanomas but not in all other animal tissues and tumours. This may be the result of an enzyme defect in the melanotic melanoma cells or of a retention of TMPO by melanin. It was also found that TMPO is metabolized predominantly in the livers of the animals.


Fast excitatory postsynaptic currents in voltage-clamped mammalian sympathetic ganglion neurones. Fast excitatory postsynaptic currents (EPSCs) were recorded in voltage-clamped neurones of isolated superior cervical ganglion of the rabbit. The rise time, decay time and whole duration of EPSC, as well as miniature EPSC, were shorter than those of corresponding postsynaptic potentials. Characteristic impedance for EPSC was 5.5 +/- 1.1 M omega, and was a few times lower than for current evoked by iontophoretic application of ACh. The rise time of EPSC was 2.0 +/- 0.2 msec, the time constant of decay was 3.6 +/- 0.5 msec, and the mean amplitude of EPSC was -5.5 +/- 1.0 nA at the resting potential level (-53.8 +/- 1.4 mV) and at 36 degrees C. Amplitude of EPSC varied with membrane potential almost linearly at negative potentials, non-linearly at positive potentials, and nullified at -8.9 +/- 1.8 mV. The decay of EPSC was exponential over the most of its time course and the rate constant of decay (alpha) varied exponentially with membrane potential according to the relationship alpha(V) = B exp(AV), with A = 0.00716 +/- 0.00101 mV-1 and B = 0.46 +/- 0.07 msec-1. The voltage sensitivity of EPSC decay is interpreted in terms of voltage sensitivity in ionic channel lifetimes.


Classically conditioned heart rate responses in Macaca mulatta after beta-adrenergic, vagal and ganglionic blockade. Heart rates of 5 rhesus monkeys (Macaca mulatta) were monitored during classical conditioning trials consisting of a visual conditioned stimulus followed after 10 sec by an electric shock to the tail. Heart rates typically increased at the onset of the visual stimulus, and returned to baseline before shock delivery. Autonomic blocking agents were subsequently administered; their effects on resting heart rates, and on acceleratory and deceleratory phases of the biphasic conditioned heart rate responses were examined, both in the raw data, and with a statistical regression technique. Beta-adrenergic blockade by propranolol lowered resting heart rates and was found, after regression analysis, to reduce the heart rate increase phase, and to weakly enhance the subsequent heart rate decrease phase of the conditioned response. Vagal blockade by atropine sulfate elevated resting heart rate, and markedly reduced both acceleratory and deceleratory heart rate phases of the conditioned responses. Ganglionic blockade by chlorisondamine also elevated resting heart rates (less than atropine), and almost completely eliminated conditioned heart rate changes. Several sources of evidence suggest a predominant vagal tone over resting heart rates, as well as mostly vagal mediation (with some sympathetic contribution) of the biphasic conditioned rate response.


Immunopotentiation and anabolism induced by sodium diethyldithiocarbamate. Sodium diethyldithiocarbamate, DTC, enhances over a large range of doses macrophage listericidal capacity and T cell activities in terms of increased IgG-antibody forming spleen cells and delayed hypersensitivity levels. Such immunopotentiation is not associated with splenomegalia or increase in lymphocyte counts. Immunopotentiation requires a preexisting link between carbon disulfide and diethylamine, since both moieties were inactive if administered alone or on separate body sites. DTC demonstrates also an anabolic effect on mice emanciated by administering a B. melitensis cell-wall fraction. The role of DTC on hormonal production is discussed in relation to hormone-mediated action on T cell induction.


Thymic hormones.

Thymic hormones. The thymus produces several polypeptides, which induce lymphocyte differentiation in vitro and in vivo. Several of these polypeptides have been chemically characterized, and three of them have been sequenced and synthesised (alpha 1 thymosin, thymopoietin and the serum thymic factor). Thymic hormones do not act identically on all T-cell subsets: they alter preferentially post-thymic precursor cells, and among mature T cells cytotoxic cells and suppressor cells. Their mode of action at the cellular level involves binding to specific cellular receptors and interaction with adenyl cyclase. Preliminary clinical trials with crude extracts have provided promising results in immunodeficient and cancer patients. The differentiation of T cells from stem cells has been the matter of considerable investigation over the last two decades, since it has been realized that the thymus and its products, the thymus-derived cells (T cells) play a central role in the generation of effector cells in cell-mediated immunity and in the regulation of the various categories of immune responses. That the thymus could act by the intermediate of humoral substances was precociously suggested by MILLER and OSOBA before the observation that thymuses grafted within a cell-impermeable Millipore diffusion chamber restored the immunocompetence of neonatally thymectomized (Tx) mice (1). However, although this experiment was ultimately confirmed by using chambers with well-controlled impermeability (2), MILLER did not pursue the idea of the humoral function of the thymus. Probably, the striking results obtained by DAVIES (3) and other workers, indicating direct migration of functional T cells from the thymus and the poor results initially obtained in trying to reconstitute the immune system of neonatally Tx mice by cell-free thymic extracts contributed to this disappointment. A new impetus was given to the subject in the early 70's when in vitro tests of lymphocyte function became available and when purified extracts of the thymus proved capable of restoring antigen-specific and non-specific immunocompetence of Tx mice. More recently, completely defined synthetic thymic hormones have been obtained. The question is no longer to decide whether thymic hormones exist, but rather to elucidate their biological significance and potential clinical applications. The multiplicity of available factors has created some confusion. It will be the aim of these few pages to review critically the various factors reported in the literature, giving particular emphasis to their pharmacology and their potential use in the modulation of immune responses.


Development, reactivity and GFA immunofluorescence of astroglia-containing monolayer cultures from rat cerebrum. This report describes detailed protocols for the dissociation, seeding and growth in vitro of monolayer cultures derived from neonatal rat cerebrum. Primary cultures derived by using different seeding densities and in vitro ages were examined qualitatively and quantitatively for morphological composition in terms of two major cell classes (flat cells and process-bearing cells) and for the presence within these classes of glial fibrillary acidic protein (GFA) as detected by immunofluorescence histochemistry. Also examined was the reaction of the cells to serum withdrawal plus the administration of dibutyryl cyclic AMP in terms of the conversion of flat cells into process-bearing cells. Conditions are defined for the generation of in vitro cell populations, more than 90% of which are GFA-containing flat cells which can all be experimentally converted into cells with processes. These well-defined culture preparations will serve as useful models for future studies of astroglial behaviour.


Naturally-occurring neoplasms in the Mongolian gerbil, Meriones unguiculatus. 10 spontaneous tumours were observed. Several had not been previously reported for this species and 1 occurred in the youngest gerbil yet reported to have a spontaneous tumour. 7 of the 10 tumours originated from the female reproductive tract.


Effects of polybrominated biphenyl on a discrimination task in rats. Learning or performance of an operant discrimination task by laboratory rats in Skinner boxes was studied as a function of subchronic treatment with polybrominated biphenyl (PBB) (1.0 mg/kg, 3.0 mg/kg or 6.0 mg/kg for 20 days). Acquisition of the discrimination task was similar for experimental and control rats at each dose level. Response times were slower for the 1.0 mg/kg rats but were like controls for the 3.0 and 6.0 mg/kg animals. Extra responses occurring in the absence of auditory discriminative stimuli increased significantly for the 1.0 mg/kg rats (hyperactivity), were no different from controls for the 3.0 mg/kg rats and decreased significantly for the 6.0 mg/kg animals (CNS depression). The weights of PBB animals did not differ significantly from controls. Analyses of brains and plasma by electron capture gas chromatography yielded detectable levels of PBB as long as 10 months following the last PBB administration. PBB in brains and plasma varied directly as a function of dose administered.


Correlation of systemic and biochemical effects of PBB with behavioral effects. Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals.


Collagen synthesis in the developing chick heart. We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.


Role of cyclic AMP in myocardial cell function. A series of agents which stimulate the formation of cyclic AMP are well-known positive inotropic agents in the heart. This fact has suggested that cyclic AMP may indeed mediate the positive inotropic effects. The elucidation of precise in vivo mechanisms utilizing in vitro and isolated techniques is always difficult; in the myocardial cell, a very complicated and multicompartmented cell, all such in vivo-in vitro correlation must be viewed with caution. In this review, the authors has attempted to list possible cellular sites of inotropic intervention based on current concepts of excitation contraction coupling (which also are speculative). Recent evidence from in vitro experiments have suggested several sites which are apparently affected by cyclic AMP-mediated events and which are thought to be intimately related to the control of myocardial contraction. It is suggested that the myocardium be viewed as a multicompartmented system with several effector sites for cyclic AMP-mediated events, all of which have individual controls; this type of thesis would be necessary to explain the volume of experimental data which fails to show simple correlation between myocardial cyclic AMP levels and cardiac contractility. The difficulties in designing experiments to further elucidate these mechanisms and the possibility of "linked enzyme systems" are also discussed.


Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts. The concentration of ACTH, corticosterone, LH and testosterone in the plasma of rats have been measured in normal, thymectomized and sham-operated rats. A group of rats, thymectomized at birth, received two i.p. injections weekly of two thymic extracts, each prepared in a separate way. Neonatal thymectomy was followed by the appearance of a transitory wasting disease during which a hormonal unbalance was manifest. Plasma corticosterone and ACTH levels increased at first at 30 days after thymectomy and then decreased at 60 days. The levels of the different hormones returned to normal by 90 days. The injections of thymic extracts rectified all these perturbations. The plasma levels of testosterone and corticosterone of hypophysectomized rats were compared to those of hypophysectomized and thymectomized animals. Results suggested that the thymus has a direct action of the adrenal cortex and in indirect action on the testes. The indirect effect is probably mediated through the hypophysis.


Analysis of the electron spin resonance spectrum of human liver tissue embedded in paraffin. The ESR spectra of the liver samples embedded in paraffin of newborn, adult, cirrhotic and control individuals always display the g approximately 2.05 signal and occasionally also the g = 4.3 line and the signal of free radicals. In adults, the amplitude of the g approximately 2.05 signal is negatively correlated with that of the g approximately 4.3 signal; in infants aged from three months to one year this correlation is positive. The copper content of the liver is in linear correlation with the amplitude of the g approximately 2.05 signal. The hyperfine structure of the part of the g approximately 2.05 signal recorded at low magnetic field may be of three types: it may correspond to Cu2+ centers of axial symmetry of type I, II or I + II. The parameters of the signal are the following: type I center, g = 2.35 +/- 0.05, g = 2.05 +/- 0.01, A < 100 gauss; type II center, g = 2.25 +/- 0.03, g = 2.05 +/- 0.01, A = 160 +/- 20 gauss. On the basis of the amplitude of the g approximately 2.05 signal, the copper content of the liver tissue can be estimated from paraffin blocks with an error of 30%, without losing the tissue embedded for histological examination.


Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study. In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.


Ultrastructural pathology of lymphocytes in neuronal ceroid-lipofuscinoses. Lymphocytes were studied by electron microscopy in five cases of neuronal ceroid-lipofuscinoses (NCL), one of infantile, three of late infantile and one of juvenile types. Each type of NCL revealed specific cytoplasmic inclusions, namely, granular bodies in the infantile form, curvilinear profiles in the late infantile form and fingerprint profiles within vacuoles in the juvenile type. Survey of the literature also confirmed the high correlation between subtype of NCL and type of lymphocytic inclusion. The electron microscopic examination lymphocytes offers easily available diagnostic informations.


The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity. Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions.


Complement fixing antibody to varicella-zoster virus in cancerous patients. The titer of complement fixing antibody to Varicella-Zoster virus was studied in sera from 161 cancerous patients and 161 healthy controls. Sera with antibody titers greater than or equal to 1/4 were 74 (45.9%) among cancerous patients and 120 (74.5%) among healthy controls. The difference between these two groups is statistically significant.


[Enzymes of purine metabolism in the nuchal muscle (M. complexus) of chick embryo]. The developmental patterns of enzyme activities related to GMP metabolism have been investigated in chick embryo musculus complexus (m. Complexus). Guanylate phosphatase activity increases conspicuously from 18th to 21st day, guanosine phosphorylase increases on the 21st day and the guanase shows a very low activity during the whole period considered. Xanthine oxidase was always found absent. The results suggest that during the first period of incubation GMP breakdown in chick embryo m. complexus might follow a catabolic pathway, while starting from the 18th day some guanine might be converted to GMP originating a new metabolic pathway as previously suggested for AMP metabolism.


[Interference of antioxidants E/O of some free radical "scavengers" with the activity of glucose-6-phosphatase after administration of carbon tetrachloride]. G-6-Pase activity was investigated in the microsomal fraction from rat liver in the presence of carbon tetrachloride and/or propyl gallate (PG), reduced glutathione (GSH) and superoxide dismutase. Results obtained "in vitro" demonstrated that CCl4 induced a 60% inhibition of the microsomal enzyme activity. Moreover, a marked inhibition of G-6-Pase activity was found also when propyl gallate and reduced glutathione were added, at different concentrations, to incubation mixture. In addition, these drugs were unable to interfere with the dangerous effect exerted on the enzymatic activity by the haloalkane. Additional experiments carried out "in vivo" with propyl gallate produced evidence that intraperitoneal administration of the antioxidant was followed by a significant inhibition of G-6-Pase activity, while the damaging action of CCl4 was unaffected. Some possible explanations of these results are reported.


[Histoenzymatic research and internal irradiation. V. Histochemical modifications in rat liver with the use of colloidal Au198]. The histochemical behaviour of succinic dehydrogenase, isocitric dehydrogenase, acid phosphatase and acetylglucosaminidase activities was studied in rat liver treated with Au198-colloidal. In these experimental conditions it was found that the hepatocytes present changes in the enzymatic activities examined, generally proportional to the doses employed. With lower doses of radionuclides, the histoenzymatic changes have a local character and are completely reversible after a month. With higher doses they take on a more extensive character. These findings suggest that Au198 could be used clinically with due precautions.


[DNA-protein interactions. Destabilizing activity of sheep pancreatic RNAase]. Evidence is presented that ovine pancreatic ribonuclease, a protein strictly homologous to bovine RNAase A but with one positive charge less, has a definite 'destabilizing' activity (quite similar to that of the bovine enzyme) on double-stranded DNA. This action of sheep pancreas RNAase has been measured by differential spectrophotometry and determining the thermal-transition profiles of the protein-DNA complexes.


[Activity of glucose-6-phosphatase during liver regeneration]. During hepatic regeneration a drop in the liver glycogen content along with a lower blood glucose level have been observed. These data are difficult to correlate with the rise of blood glucagon and the drop of insulin shown at the same times after partial hepatectomy. Therefore, liver glucose-6-phosphatase activity has been studied at 1.5, 4, 15 and 24 h, since that enzyme is involved in the release of glucose from the cell. 4 and 15 h after partial hepatectomy a remarkable decrease in glucose-6-phosphatase activity is observed. These results are discussed in view of the higher metabolic demand of regenerating liver.


[Demonstration by immunofluorescence and immunoperoxidase of an antigen of the measles type in the osteoclasts of Paget's disease of bone]. The intra nuclear and intra cytoplasmic inclusions described in osteoclasts in PAGET's bone disease are morphologically similar to those observed in subacute sclerosing panencephalitis. Immunological techniques using different specific immune sera demonstrate the presence of an antigenic structure of viral origin in osteoclasts in PAGET's bone disease. A measles or a measles like virus is most likely to be involved and may play a role in the etiology of the disease.


[Retroperitoneal tumors in children: clinical diagnostic problems (author's transl)]. Starting from two recent observations of retroperitoneal tumors in the pediatric age group (a nephroblastoma and a ganglioneuroma), the authors illustrate the main characteristics of these malignancies and emphasize the difficulties often encountered in differential diagnosis.


Protein degradation in health and disease. Introduction: the classification of proteinases. Twenty years after B.S. Hartley's 1960 review, on which the present scheme for classification of the proteinases is based, most of the new information that has been obtained appears fully consistent with Hartley's views. A slight amendment is proposed of the name of the four groups of these enzymes to 'serine', 'cysteine', 'aspartic' and 'metallo'-proteinases.


Regulation of protein breakdown in hepatocyte monolayers. Effects of potential modifiers on intracellular protein degradation have been measured in hepatocyte monolayers two days after the cells were isolated and plated. Modifiers were added after cells had been labelled with [3H]leucine and generally at the beginning of the degradation period. Protein degradation was inhibited by insulin, epidermal growth factor and serum as well as the protein synthesis inhibitors, leupeptin and weak bases. Degradation was stimulated by cyclic AMP, glucagon, beta-agonists, glucocorticoids and nutritional stepdown. The results from addition and competition experiments are consistent with all effectors acting on lysosomal proteolysis but differing in whether they alter amounts of proteinases, conditions favourable for proteinase function, or degree of autophagocytosis.


Human collagenases: comparative and immunolocalization studies. Four human collagenases derived from different tissues or cells were shown to have different physicochemical properties with regard to molecular size and protein charge. Such differences have been used to demonstrate that the collagenase activity of rheumatoid synovial fluids is of granulocytic origin. Immunolocalization studies have demonstrated that immunoreactive collagenase is present in a variety of human tissues. Its production by cells in normal tissues suggests a role in collagen remodelling processes, whereas its more frequent occurrence in diseased tissues suggests an important role in pathological collagen resorption. In nearly all the positive specimens examined the enzyme was restricted to a single cell or small groups of cells, or collagenous elements, suggesting microenvironmental rather than widespread collagenolytic activity.


Proteinases in connective tissue breakdown. Lysosomal cathepsins B and N complete the depolymerization of native fibrillar collagen in the phagolysosome after prior extracellular fragmentation by collagenase and other neutral proteinases. In vitro studies have confirmed that cathepsins B and N cleave native collagen only at the short non-helical telopeptides, which generate the intermolecular cross-links. This action occurs maximally at pH 3.5 and at 37 degrees C the released monomers denature spontaneously and are susceptible to further breakdown. In the phagolysosome the collagenous debris is already weakened and probably therefore, more easily disrupted by these cathepsins. Complete digestion would then be undertaken by the whole complement of proteases. The lysosomal glycosidases may assist this breakdown by degrading ground substance components which are normally tightly bound to collagen. In certain situations cells may instead generate an acidic pericellular environment that could permit the direct action of secreted lysosomal enzymes. This extracellular action may supersede the action of collagenase and the activity of these different enzymes would thus be regulated by changes in the nature of this microenvironment.


Natural history of perinatal cytomegaloviral infection. Epidemiological data presented here indicate that cytomegaloviral (CMV) infection is one of the most common perinatal infections found in human beings. Transmission to the offspring occurs in utero at birth and postnatally. Intrauterine infection results from primary or recurrent maternal involvement, the latter being more common in populations where infection is initially acquired during childhood or adolescence, such as in low socioeconomic settings. Congenital infection is usually subclinical with either type of maternal involvement but primary infection has a greater tendency to produce disease in the fetus. About 20% of the offspring infected in utero are damaged, infrequently with generalized disease, but more often with auditory involvement. The latter can develop in utero or postnatally and can be progressive. The major cause of recurrent maternal infection according to restriction enzyme analysis is reactivation of latent virus, which occurs in the face of substantial maternal humoral immunity, even with intrauterine transmission of virus. Reinfection by exogenous virus remains a lesser possibility for maternal recurrences. Even more commonly, CMV can be transmitted at birth from the infected maternal genital tract and postnatally through infected breast milk, especially in highly immune populations. With the possible exception of early pneumonia, these infections appear to be innocuous.


Perinatal infections: prevention of long-term sequelae. All the congenital infections and most of the natal and postnatally acquired infections of man are associated with disease of the central nervous system and long-term sequelae in the survivors. The most important perinatal pathogens in this regard are group B streptococcus, Escherichia coli and other coliform bacteria, cytomegalovirus, Toxoplasma gondii and herpes simplex virus. All these agents are the subject of active and, in some instances, promising investigation. The strategies for prevention are discussed here. Recent clinical trails of two cytomegalovirus vaccines (Towne 125 and AD 169) are considered in detail.


The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method. Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.


Substrate-specificity of uvr excision repair. The substrate specificity of the uvr endonuclease, the product of the uvrA, uvrB, and uvrC genes is reviewed. It is suggested that the relatively well-defined substrate specificity of this repair enzyme is useful as a guide in determining the nature of the DNA-lesion caused by a given mutagen.


[Research on substances with antiviral activity. X. 1-substituted-2-(methylamino) naphtho/2,1-b/furan hydrochlorides]. Some 2-(methylamino)naphtho [2,1-b] furans hydrochlorides 1-substituted were synthetized and investigates for antiviral activity in vitro against Herpes simplex virus type I (VHS-I) and parainfluenza virus type 3 HA-I/CR-8 stock.


Malignant fibrous histiocytoma of bone.

Malignant fibrous histiocytoma of bone. Eleven cases of malignant fibrous histiocytoma of bone observed during recent years are reported. An analysis is presented with regard to sex, age, site, symptoms, radiography, macroscopic and microscopic aspects. The differential diagnosis is discussed on the basis of these criteria. Because of the small number of cases and limited follow up, it was not possible to come to any definite conclusions concerning prognosis and treatment. Treatment was surgical in almost all the cases.


[Markers of hepatitis virus A and B infection in subjects undergoing a hiring examination in a large business]. The prevalence of some hepatitis-A and hepatitis-B markers has been studied in 495 individuals (male 291, female 204) attending a preemployment medical examination at a great factory in Northern Italy between November 1978 and April 1979. A 2.0% and 13.7% incidence has been respectively found for HBsAg and anti-HBs in the whole population. A statistically significative difference has been recognized between people coming from Southern and Northern Italy, as well as between first-employment subjects and workmen or countrymen. A higher incidence of anti-HBc has been detected in men, in older age groups, and Southern immigrants, without any statistically significative difference related to their previous activities. Anti-HAV antibody has been found in 57.9% of whole population, with a greater incidence in younger people and in southern immigrants. First-employment group showed a lower incidence of anti-HAV, notwithstanding the great number of southern immigrants in this group.


The protonation of the 5-thymyl radical in single crystals of thymine derivatives: e.s.r. and INDO evidence. For the 5-thymyl radical, minor couplings additional to beta-protons bonded to C6 and C7 are observed in single crystals of 1-methylthymine. Hyperfine coupling tensors are given of the N3 nitrogen (+3.5/0.0/0.0 G) and of the exchangeable proton (-4.1/-2.5/-0.9 G) bonded to it. In single crystals of thymine . anhydrate, thymine . monohydrate and 5,6-dihydrothymine these additional couplings are unresolved, but are also present. INDO-calculations were performed to reproduce consistently both beta-coupling constants and additional couplings from N3 and H(N3). Comparison of experimental and calculated values to the conclusion that the 5-thymyl radical is protonated at 04 in all single crystals of thymine derivatives investigated.


Decreased repair of gamma-irradiated adenovirus in Xeroderma pigmentosum fibroblasts. The ability of gamma-irradiated adenovirus to produce viral structural antigens (Vag) was examined in several normal and Xeroderma pigmentosum (XP) fibroblast strains. The fibroblast cultures were infected with either irradiated or nonirradiated adenovirus and at 48 hours after infection, cells were examined for the presence of Vag using immunofluorescent staining. Survival of Vag synthesis for gamma-irradiated adenovirus had a D37 value of 47 +/- 4 x 10(4) rad following the infection of seven normal fibroblast strains. The survival of this viral function was found to be significantly less following infection of the XP strains. D37 values for Vag synthesis expressed as a percentage of that obtained on normal strains were obtained for a representative strain from each of the XP complementation groups: group A, 57 per cent; group B, 61 per cent; group C, 61 per cent, group D, 59 per cent; group E, 73 per cent; and variant, 75 per cent. These results indicate that XP cells have a reduced repair capacity for some type of gamma-ray-induced DNA damage.


Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.


Myxoid variety of malignant fibrous soft tissue histiocytoma. Three cases of the myxoid variety of malignant fibrous histiocytoma (I.F.M.) of the soft tissues are reported. This condition should be recognised as a separate entity differing from other benign pseudosarcomatous or malignant lesions of the soft tissues in that the myxoid component is present not as an occasional background, but as an integral constituent of the neoplasm. This indicates a more favourable prognosis as compared with other varieties of malignant fibrous histiocytoma.


Sarcoma in Paget's disease (11 cases).

Sarcoma in Paget's disease (11 cases). Eleven cases of sarcoma in Paget's disease of bone are presented, together with an extensive review of the literature. These neoplasms are rare but not exceptional, and mostly affect male subjects in the seventh decade of life. The sites most frequently affected are the pelvis, femur and humerus. In 30 per cent of cases these neoplasms are multifocal. Radiographically the lesions are nearly always osteolytic. The radiographic diagnosis may, however, be quite difficult, especially in the presence of the severe (but benign) osteolyic lesions that sometimes occur in Paget's disease. Morphologically these tumours are mostly highly polymorphic sarcomas. The cases in this series were diagnosed histologically as osteosarcoma, grade 3 fibrosarcoma, and malignant fibrous histiocytoma; but there are no prognostic differences between the various histological types. The prognosis is very serious, only about 3 per cent of patients surviving for five years from the time of diagnosis. Therapy, unfortunately nearly always palliative, is based on amputation or disarticulation after sections biopsy in cases where the disease is localised to the limbs, and on radiotherapy in cases not amenable to surgery.


[The metabolic effects of contraception with oestrogen-progestogen products (author's transl)]. A synthesis has been attempted to explain the metabolic action of oestrogen-progestogens: and their action on carbohydrates, triglycerides, cholesterol, lipoproteins and coagulation has been reviewed. Carbohydrate tolerance can evolve in different ways, depending on the case. On the one hand hyperglycaemia, which is provoked by taking carbohydrates by mouth in a primitively pathological way, can be improved while on the other hand there can be diminution in carbohydrate tolerance in other cases. Two factors, however, remain constant, hyperinsulinism and resistance to insulin. There is no way of predicting how carbohydrate tolerance will behave. That is why pills that contain oestrogens and progestogens, even if they are "mini-dose" pills, are contra-indicated for women who have pancreatic diabetes. Pills with a high oestrogen content raise the triglycerides, while those which have a higher progestogen content tend to raise the blood cholesterol levels. High-density lipoprotein tends to be raised with an oestrogenic milieu and lowered with progestogens or with pills that have a strong progestogen content.


Horse muscle acylphosphatase: a more rapid purification procedure and crystallization. A crystalline acyl phosphatase has been obtained from horse muscle. The enzyme purified by a modified procedure which allowed to obtain a larger yield with respect to a method previously developped in this laboratory, was homogeneous by disc electrophoresis on polyacrylamide gel. Crystals of this enzymatic protein have been obtained by the addition of ammonium sulphate to around 52% saturation.


Life span changes in the presence of alpha-melanocyte-stimulating-hormone-containing cells in the human pituitary. Since recent circumstantial evidence has suggested possible functions of alpha-MSH in intrauterine growth and labour, the presence of this hormone in the human pituitary was determined by means of the indirect immunofluorescence procedure during development and adulthood. Cross reaction of the antibodies with other peptides was measured after which they were purified by solid phase absorption. Experiments on the rat pituitary showed that staining of alpha-MSH- and ACTH-containing cells could be obtained well until 48 h after death. In the pars distalis the ability of ACTH-containing cells to take up stain increased during the period of post-mortem storage. In the youngest human fetus studied (15 weeks) only alpha-MSH-containing cells were found in the pars intermedia and no ACTH-containing cells were observed. In the other fetal pituitaries a distinct pars intermedia containing more alpha-MSH cells than ACTH cells was found. In the pars distalis of the fetuses more ACTH- than alpha-MSH-containing cells were observed. From birth to 19 years, progressively fewer alpha-MSH containing cells could be detected in the 'zona intermedia' and pars distalis, while in adults only a few such cells were found in either area. Irrespective of age, sex, cause of death or therapy, alpha-MSH-containing cells were found in all pituitaries throughout life. The number of ACTH containing cells gradually increased in the zona intermedia and pars distalis and reached a high adult level in the latter structure. In the pituitaries of seven anencephalics, no alpha-MSH-containing cells were present. The presence of alpha-MSH in the fetal pars intermedia, the change in the ratio of the alpha-MSH/ACTH cells during the course of development, and the absence of alpha-MSH in anencephaly all support the possibility that human fetal pituitary alpha-MSH is involved in both intrauterine growth and fetal adrenal function and thus also in parturition.


[Primary malignant tumour of the liver associated with the ingestion of oral contraceptives (author's transl)]. A 42-year-old woman, who had been taking oral contraceptives for 10 years, developed a primary carcinoma of the liver. The diagnosis was made by biopsy under laparoscopic control. Twenty one cases have already been reported in the literature. The aetiological role of contraceptives in the development of generally benign (approximately 200 published cases) and sometime malignant hepatic lesions, has not been definitely proven. The regression of certain benign tumours when contraceptives are stopped is the essential argument. In some patients, the association of benign lesions and of hepatic carcinoma suggests a single pathogenesis. The early recognition of such lesions justifies their being sought routinely in patients taking oral contraceptives (palpation of the liver, questioning concerning pain in the hepatic region). A national register will be required in order to determine their exact prevalence.


[Determination of umbilical cord blood Ig and its correlation with prenatal infections (author's transl)]. IgG, IgM and IgA were measured in 120 funicular blood samples. At the same time, these determinations were assayed in the mothers. In the serum samples of the newborn, IgA and IgM were found to have levels over 20 mg/100 ml. Antibodies against rubella virus, cytomegalus virus, Listeria monocytogenes and Toxoplasma gondii were measured in order to investigate a possible intrauterine infection. All Ig determinations were performed through the radial immunodiffusion method.


Comparison of suture materials for intestinal anastomosis. Ninety end-to-end entero-anastomoses were prepared in 45 dogs by inverted single row knotted sutures. Half of the anastomoses were carried out on the small intestine, the other half on the colon. Of the two non-absorbable materials that of the polyester type proved to be the best. Of the absorbable materials Dexon can be recommended for intestinal anastomoses, but on the colon Dexon is not reliable. Plain catgut is not recommended for this kind of anastomoses.


[Blood coagulation disorder in islet cell adenoma]. Coagulation physiologic tests were carried out and plasminogen activity and concentration were measured in the case of 6 patients (5 islet cell adenomas and 1 islet cell carcinoma). Except a reduced plasminogen activity in the postoperative phase no other unequivocally pathologic data were found. This phenomenon can probably by attributed to the enhanced plasmin inhibitors of the human plasma. The problem of so-called hypercoagulaemia of these patients can be clarified only after the investigation of the half-lives of the various coagulation factors.


Effect of ACTH-stimulated glucocorticoid hypersecretion on the serum concentrations of thyroxine-binding globulin, thyroxine, triiodothyronine, reverse triiodothyronine and on the TSH-response to TRH. The responses of serum concentrations of TSH, thyroxine (T4), triiodothyronine (T3) and of reverse triiodothyronine (rT3) to i. v. administration of 0.4 mg THR were examined prior to (and after) i. m. administration of ACTH (2 mg Synacthen Depot) in 7 euthyroid women using estrogen-containing oral contraceptives and in 8 controls, with the following results: (1) an increase in endogenous glucocorticoid secretion is associated with a depression of the TSH response to TRH; (2) TSH formed in decreased amounts is still capable of stimulating thyroid secretion; (3) the increased serum corticoid levels fail to affect the secretory response of the thyroid to TSH; (4) control of the pituitary-thyroid axis remains normal in the presence of increased serum thyroxine-binding globulin (TBG) levels. In a further series the serum levels of TBG, T4, T3, rT3 and cortisol under the effect of ACTH-induced endogenous glucocorticoid hypersecretion were studied in 6 normal untreated controls, in 6 normal women using oral contraceptives and in 10 untreated hyperthyroid patients. During four days subsequent to treatment the serum TBG levels decreased, maximum decrease being found in the users of oral contraceptives, minimum decrease in the controls. Serum T4 was found to decrease during 2 to 4 days, serum T3 parallel with an increase in serum rT3, for 1 to 2 days, subsequent for ACTH loading. In the euthyroid cases also the serum TSH levels showed a transitory decline. It is concluded that in case of endogenous hyperproduction of glucocorticoids (1) T4 leads to T3 monodeiodination decreases and T4 leads to rT3 conversion increases parallel with the changes in the serum cortisol levels; (2) TBG synthesis is inhibited by endogenous glucocorticoids; (3) the changes in serum TBG levels are accompanied by a decrease in the serum T4 concentrations.


The role of the ATP--adenylate cyclase--cAMP system and its pharmacological regulation in the development of gastric hypersecretion and ulceration. The role and pharmacological regulation of the ATP-adenylate-cyclase--cAMP system were studied in the mucosa of the gastric fundus, and in the forestomach, of pylorus-ligated rats to elucidate the development of gastric hypersecretion and ulceration. (1) cAMP content of the tissue of the fundus mucosa and of the forestomach decreased before the significant increase of gastric H+ output and ulcer development; (2) the gastric H+ outputs depended on the breakdown of ATP in the fundus mucosa; (3) the gastric H+ secretion was inhibited in a dose-dependent way by theophylline, epinephrine and cimetidine; (4) the inhibition of gastric H+ secretion by epinephrine , theophylline or epinephrine plus theophylline associated with a significant increase in the mucosal cAMP of the gastric fundus (5) the significant increase in gastric H+ secretion due to histamine associated with a significant decrease in fundic mucosal cAMP; (6) the gastric H+ secretion could be inhibited dose-dependently by ADP, AMP, cyclic 2', 3'-AMP and cAMP; (7) the inhibition of gastric H+ secretion by cimetidine developed without and with histamine application in pylorus-ligated rats; (8) the histamine on gastric H+ secretion could not be stimulated further with theophylline (9) no significant correlation was found between the mucosal cAMP level and the gastric H+ secretion and/or between the decrease of mucosal cAMP content and gastric H+ secretion. It has been concluded that in pylorus-ligated rats (1) the gastric H+ secretion is an ATP-dependent process; (2) the cAMP system has an inhibitory effect as regards the development of gastric hypersecretion and of ulceration; (3) histamine and cimetidine show no close correlation with the cAMP system; (4) an extracellular and intracellular feed-back mechanism system exists between th ATP-membrane-bound ATPase-ADP and the ATP--adenylate cyclase--cAMP systems in the background of the development of gastric hypersecretion and ulceration.


A comparative molecular--pharmacological study of drugs inhibiting Na+--K+-dependent ATPase separated from human gastric fundic mucosa. (One receptor system and more drugs). The inhibitory effects of atropine, epinephrine, cyclic 3', 5'-AMP (cAMP), the prostaglandins E1 (PGE1) and E2 (PGE2) pentagastrin, histamine and ouabain have been studied on the activity of Na+--K+-dependent ATPase obtained from human gastric fundic mucosa. This study compares the sensitivity of the enzyme to a variety of drugs, applying the law of one receptor and more drugs. It was found that (1) the doses of drugs necessary to produce 50% inhibition to Na+--K+-dependent ATPase activity (affinity, pD2 value) significantly differ from each other C (atropine, 9.50; epinephrine, 8.60; cAMP: 11.30; PGE1, 9.30; PGE2, 9.45; pentagastrin, 9.45; histamine, 9.70 and ouabain, 9.50); (2) the intrinsic activities of drugs to Na+--K+-dependent, ATPase in comparison with ouabain (alpha=1.00) differ: atropine, PGE1, PGE2 and histamine, 1.00; pentagastrin, 0.87; cAMP, 0.48 and epinephrine, 0.41; (3) the inhibitory effects of different drugs, on Na+--K+-dependent ATPase system, depend on the magnitude of enzyme activity from human gastric fundic mucosa. It has been concluded that (1) the sensitivity of these drugs to the Na+--K+-dependent ATPase system and to the adenylate cyclase system, both obtained from human gastric mucosa, significantly differs from each other; (2) the main effect of pentagastrin and histamine on human gastric secretory function differs from the function of Na+--K+-dependent ATPase system; (3) the role of Na+--K+-dependent ATPase system and of adenylate cyclase can be separated pharmacologically from the point of view of human gastric H+ secretion.


In vivo and in vitro effects of LH-RH on cAMP content of anterior pituitary in rats. Changes in the cAMP content of anterior pituitary of male rats were studied after in vivo administration of LH-RH or in vitro incubation in the presence of LH-RH. Although a significant rise was observed 5 min after in vivo injection of LH-RH, the cAMP level increased after only a two-hour lag period in vitro. Maximum level was reached in vivo with 1 microgram LH-RH/100 g b.w., but there was no maximal production in vitro even in the presence of 5 x 10(-6) M LH-RH. A summary of the available observations on the effect of LH-RH on pituitary cAMP level is given in the present paper.


Central and peripheral adrenergic mechanisms in endotoxin fever and newborn guinea pigs. In 0--3 day-old guinea pigs cerebroventricular pretreatment with alpha-methyl-p-tyrosine failed to modify the course of fever induced by E. coli endotoxin administration into the cerebral ventricles. Central or intraperitoneal administration of phentolamine or central administration of propranolol were also ineffective. Intraperitoneal propranolol, however, prevented both the first and the second temperature rise after endotoxin, while the transient fall in temperature that usually occurs between them still ensued. Central noradrenergic mechanisms seem to play, at most, a minor role in the mediation of endotoxin fever, while the integrity of peripheral beta adrenergic receptors is indispensable for the febrile response to occur.


The role of beta receptors in the regulation of renin release. The effect of the primarily beta 2 type adrenergic receptor stimulating terbutaline (10(-7)--10(-5) M) and of the beta 1 and beta 2 type adrenergic receptor stimulating isoproterenol (10(-7)--10(-5) M) was studied on renin release from incubated slices of renal cortex. Renin release and cAMP content of the slices were significantly higher in the presence of both terbutaline and isoproterenol. A logarithmic dose--response relationship was shown to be present between the beta mimetics and the renin concentration in the medium, and the cAMP content of tissue slices. In equal doses isoproterenol was about 1.5 times more potent than terbutaline. No change was seen in the renin content of the tissue slices. The results supports the view that beside the beta 1 type adrenergic receptors of the renal cortex--even if to a lesser extent--the beta 2 type adrenergic receptors, too, are involved in the regulation of renin release.


Vitamin C, high density lipoproteins and heart disease in elderly subjects. Plasma vitamin C, total and high density lipoprotein (HDL) cholesterol and cortisol levels were measured in a random sample of 337 elderly subjects living at home in S. Wales; measurements of relative body weight and information about fruit intake, smoking habits and symptoms of cardiovascular disease were also collected. There was a sex difference, over all age groups, in plasma vitamin C and in total HDL cholesterol levels. Plasma vitamin C was strongly correlated with fruit intake in both sexes. Both HDL cholesterol and low and very density lipoprotein (LDL + VLDL) cholesterol levels tended to increase with increasing plasma vitamin C but this reached significance only for the LDL + VLDL fraction. In addition, HDL cholesterol was negatively correlated with Quetelet's index in the women. Symptoms and medication for heart disease did not correlate significantly with plasma vitamin C or with HDL cholesterol levels, but reported angina showed a weak positive association with total cholesterol in the men, and there was some evidence of increased cortisol levels in subjects with heart disease.


Glomus tumors of the temporal region: surgical therapy. A series of 23 patients with glomus tumors of the temporal region, treated surgically at the ENT Department, University of Zurich, Switzerland from 1970 to 1977, is presented. A system of classification as to tumor size is described with tympanic, tympanomastoid, infralabyrinthine and intracranial tumors categorized as types A, B, C, and D respectively. A majority of tumors, 12 of 19 were infralabyrinthine (type C), and a surgical approach featuring permanent anterior displacement of the facial nerve, an cavity obliteration, has been employed with the aim of total tumor extirpation. There were five males in this series, with a mean age 22 years younger than for the females and all having infralabyrinthine (type C) tumors. The most frequent clinical presentation included pulsatile tinnitus, hearing loss, and observable tumor mass in the ear. Fifteen of 23 patients had significant hearing loss, of varying types on the tumor side, with one presenting as sudden hearing loss, and another as progressive unilateral sensorineural loss over several years, in the absence, initially, of tinnitus. Ten of 23 patients with type B, C, and D tumors had cranial nerve involvement, seven and tenth being the most frequent. Because of slow growth and tendency to multicentric origin, final conclusions cannot be made regarding treatment in such a recent series of cases. However, the impression gained suggests that radiotherapy is less effective than complete surgical excision, and that partial excision is to be avoided.


Glomus jugulare tumors with intracranial extension. A glomus jugulare tumor with posterior fossa extension needs the expertise of the neuro-otologic surgeon and neurosurgeon to obtain total tumor removal. A one-stage combined otologic and neurosurgical procedure is presented for removal of base of skull tumors posterior to the carotid artery. Twelve cases of this type of tumor have been seen at The Cleveland Clinic. Two cases are presented in detail to illustrate the applicability of this procedure. In cases with infection around the temporal portion of the tumor, tumor extension around or anterior to the carotid artery, or extensive involvement of the posterior fossa, the procedure should be performed in two stages.


Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input. Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.


Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides. Convulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased level of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity.


Acute generalized polyneuropathy accompanying lithium poisoning. A woman with typical symptoms of lithium toxicity had, in addition, severe generalized sensorimotor peripheral neuropathy, which cleared completely as the recovered. Electrodiagnostic studies suggested axonal lesions; autopsy ten months later revealed no residual abnormalities. Previous studies have shown that lithium can affect peripheral nerve function, but this is the first reported case of peripheral neuropathy in association with lithium toxicity.


The ultrastructure of Spirulina platensis in relation to temperature and light intensity. The ultrastructure of Spirulina platensis, a cyanobacterium with a helical morphology, has been studied in relation to temperature and light intensity. An increase in temperature gives rise to a more tightly coiled trichome, an increase in sheath material formation and a decrease in cyanophycin (above 17 degrees C) and polyglucan (above 20 degrees C) granule concentration. An increase in light intensity leads to an increase in gas vesicle concentration while the phycobilisome content decreases. Furthermore, cylindrica bodies have been observed with a somewhat different ultrastructure from those found in other species of cyanobacteria. The occurrence, size and ultrastructure of polyhedral bodies, photosynthetic lamellae, mesosomes, lipid deposits and an unknown kidney-shaped inclusion in relation to temperature and light intensity are described.


Persistence in humans of antibody after immunization with four alphavirus vaccines. Immunization with attenuated VEE virus vaccine resulted in persistence of neutralizing antibody for 12 years. Immunization with inactivated WEE vaccine converted 83% of the subjects, killed EEE vaccine converted 27% and killed Chikungunya vaccine induced no significant titers. Antibody formed as a result of immunization with inactivated vaccines was of short duration, i.e. less than 1 year. Attenuated VEE was responsible for some heterologous antibody rises to the other three alphaviruses. Among the inactivated vaccines WEE and Chikungunya vaccines produced one heterologous rise each to EEE virus.


[Serological survey for virus and Mycoplasma infections (author's transl)]. The Authors describe the two years follow up of complement fixing antibodies vs 4 viral antigens (Herpes simplex, Herpes zoster, Cytomegalovirus, respiratory syncytial virus, Mycoplasma pneumoniae). They evaluate the seasonal trend and the eventual clinical correlations on 3267 sera and 254 spinal fluids from hospitalized patients.


Angiotensin-converting enzyme in sarcoidosis: a British study. Serum angiotensin-converting enzyme (ACE) activity was measured in 18 healthy controls, 26 patients with active sarcoidosis, 13 patients with inactive sarcoidosis and seven patients with extensive tuberculosis. The serum ACE activity showed no significant difference between male and female in the control or sarcoidosis groups. There was no correlation between ACE activity and age except in the female active-sarcoid group. ACE activity in the active-sarcoid group was significantly higher than in the control, inactive-sarcoid and tuberculosis groups. The ACE activities at Stages I, II and III of the disease were not significantly different.


[Foot-and-mouth disease in buffaloes (Bubalus bubalis, Linnaeus, 1758): search of antiantigen antibodies and isolation of the virus]. The immune response to virus-infection-associated (VIA) antigen was studied in 379 Indian buffalos (Bubalus bubalis). These animals were vaccinated three times a year with commercial acetylethyleneimine (AEI)--inactivated foot-and-mouth disease vaccines under field conditions. Two months after the last vaccination, antibody against virus-infection-associated (VIA) antigen was found in 23 per cent. Foot-and-mouth disease virus -- (FMDV) type C "Waldmann" was isolated from oesophageal/pharyngeal fluid of 7 samples buffalos.


[Immunological monitoring of patients with carcinoma of the lung. Study method and preliminary research]. It is by now an established fact that the status of the immune system stands in some relationship with the onset and evolution of malignancy. To clarify this relationship the authors investigated the immune system of patients with pulmonary carcinoma, with special regard to the functions of the T and B lymphocyte lines. After suitable explanation of their experimental protocol, which involved immunological monitoring and the study of relationships between immunological changes and the extent and histological type of malignancy, and also the effects of any treatments being administered, the authors describe the results obtained in 18 preoperative patients. The study revealed an overall diminution of cell-mediated immune activity: less strongly positive DNCB skin tests, reduced capacity for making E rosettes, reduced blast transformation with PHA. With B lymphocytes the EA rosette test was often depressed, whereas antibody titers were normal or even above normal, and the pokeweed blast test was invariable above normal values. These preliminary results show that at the time of diagnosing malignancy, the greater aggressiveness characteristic of the less differentiated cellular types, or of stages of diffuse malignancy, is associated with overpowering of cell defenses and (within certain limits) enhancement of the humoral response.


[Three different tumors in a case of synovial sarcoma of the hand]. Examining a 74 year old female patient with a nodular goiter, a tumor of the left thenar eminence with a concurrent radiolucent swelling in the adjoining second metacarpal was found. The diagnosis was a struma nodosa with regressive marginal changes, a hypervascularized monophasic synovial sarcoma of the wrist joint, and an enchondroma of the second metacarpal bone. Following the amputation of the forearm, no radiotherapy or cytotoxic therapy was performed. After a follow-up time of one year no metastases were detected.


Effects of phthalazinol (EG 626) on arterial lipolytic enzyme activities in the rat. Phthalazinol (EG 626), a thromboxane A2 antagonist and cyclic AMP phosphodiesterase inhibitor, has been shown to prevent the atherosclerosis induced in cholesterol fed rabbits. In an attempt to clarify the antiatherosclerotic mechanism, the effects of this compound on the lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) of rat aorta were examined in vivo. Administration of EG 626 (100-200 mg/kg, per os, daily, 1-2 weeks) affected neither the aortic lysosomal cholesterol esterase nor the acid phosphatase activity, whereas the lipoprotein lipase activity was signficantly decreased by the treatment. These results suggest that with an elevation in HDL-cholesterol, a decrease in lipoprotein lipase activity after ingestion of EG 626 might contribute, at least to some extent, to the prevention of arterial lipid accumulation.


[Usage of the gel filtration method for the determination of urinary proteins (author's transl)]. The urinary proteins determination was carried out after purification by gel filtration over Sephadex rosin. The proteins eluaded react with Biuret-reagent to establish the coloured copper-proteins complex. If proteins concentrations is inferior, the proteins can be determinated by the copper-proteins complex isolation with second gel filtration and titrating Cu++ with reactives: dietildithiocarbamate or the PAR (4-(2pyridyl-azo)resorcinol monosodium salt).


[Occurrence of pleural mesothelioma. Chronic fibrosing pleurisy and calcified pleural plaques in Turkey in relation with environmental pollution by mineral fibers (author's transl)]. The incidence of pleural mesothelioma (PM), chronic fibrosing pleurisy (CFP) and calcified pleural plaques (CPP) has been studied in Anatolia (Turkey) in relation with environmental pollution by mineral fibers: 1) In central Anatolia, where asbestos deposits have been described, the frequency of CFP and CPP was in the range 2-25%; several cases of PM have been encountered. 2) One area (Cappadoce) is free of asbestos, but contains another kind of mineral fiber: zeolite. In this area, an outbreak of PM has been described in some villages. Among the 600 inhabitants of Karain, 28 cases of PM occurred for the period January 1975-June 1979.


[Fibre interaction with red blood cells or alveolar macrophages "in vitro" (author's transl)]. Haemolytic activities and effects on alveolar macrophages (AM) of various fibres were studied. UICC asbestos fibres and attapulgites either untreated or acid-leached were used. Amphiboles and commercial attapulgites were both cytotoxic on AM, but attapulgites and chrysotile were only haemolytic. Chrysotile fibres induced a release of B galactosidase; when acid treated these fibres were cytotoxic and less haemolytic. Acid treated amphiboles were more haemolytic than untreated.


[Danger of delayed diagnosis in severe meningeal suppurations (author's transl)]. The necessity of unequivocal diagnosis is sometimes a fatal cause of delay in the medical or neurosurgical treatment of meningeal suppurations.


[Oral contraceptive and trisomy 21. A retrospective study of 730 cases (author's transl)]. A retrospective study of 730 cases of trisomy 21 and of 1 035 cases of abnormal children without a detectable chromosomal aberration, allows the study of the frequency of use of oral contraceptives by their mothers. The statistical analysis shows no notable differences for mothers 30 years old and younger. Among the mothers 30 to 38 years old, there is an excess of pill-taking by mothers of trisomy 21 children. For this second category of mothers (30 to 38 years) this excess is significant (a) when the delay between the cessation of pill-taking and the conception of the child is six months or less ; (b) when the duration of pill-taking has been longer than one year ; and (c), when those two factors are present simultaneously. Moreover, the frequency of males is significantly reduced in trisomy 21 children when their mother have taken the pill. As a whole, for the subsample of mothers 30 and older, a correlation is observed between the three factors analysed, pill-taking, sex ratio, and trisomy 21. In view of the fact that decrease of the sex ratio and the increase of the frequency of trisomy 21 both are correlated with maternal aging in the general population, it seems remarkable that a correlation between these two variables and the use of oral contraceptives is observed only when the women had already passed the first half of their reproduction period.


[Analysis of 228 cases of multiple sclerosis (author's transl)]. The authors report some observations about 228 cases of multiple sclerosis with secure diagnosis subdivided in severe (34,6 %), common (29,8 %) and benign after the tenth year of illness (35,6 %). These observations are in agreement with classical statistic reports concerning the natural disease history : higher female incidence (64 %), average age at onset about 29,5 years, 4 main first signs (ocular [42,5 %], motor [41,5 %], ataxia [36,3 %], sensory [35 %] and remitting course [82,5 %]). Follow up study of 81 "benign" forms after the tenth year of the disease allows us to look at the freqwuency of "secondarily worsening" forms (25,7 %) and "benign remaining" ones until the twentieth year (10,1 %).


[Angiofollicular lymph node hyperplasia. About an exceptional meso-sigmoid localization (author's transl)]. The authors report the first angiofollicular Lymph-Node Hyperplasia (Castleman'tumor) case with a meso-sigmoid location. They carry out a general review of the literature on 315 observations and insist on the anatomic and evolutive aspects allowing a better understanding of the histogenesis of the lesion. The inflammatory theory, actually acknowledge by most of the authors, also seems to them the most plausible.


[Alcoholism, colic diverticular disease and metabolic disorders (author's transl)]. 70 patients with colic diverticular disease and 50 control subjects were compared. Sexes and ages were matched in the two groups. Significant higher frequencies of alcoholism (P < 0,00001), hyperlipidemia (P < 0,0001), impaired oral glucose tolerance test (P < 0,001), hyperuricemia (P < 0,01) and atherosclerosis (P < 0,000001) were noted in the diverticular group. Hypothesis about pathogenesis of diverticular disease are suggested.


[Screening of deafness at birth (author's transl)]. The authors studied different parameters of the hearing test proposed to detect deafness among new-borns. These parameters belong to the technic of the test itself (intensity of stimulus, repetition of the test five minutes later, during the day and the following days, characters of the reactions) and to the infant (gestational age birth weight age, disease). They found that the noise in the resuscitation room and in the usual incubators is high and perhaps injurious. Following their own experience and the results published in France and abroad, they think that the test is difficult and cannot be generalised for the moment to all newborns.


[Double blind study of tiapride in neoplasia-related pains (author's transl)]. The antalgic effects of tiapride used by intravenous way have been evaluated in a randomized study on 30 patients with neoplasia-related pains. We noticed a partial or a complete positive response in 60 % of the cases when tiapride is given at a dose of 300 mg/day. The average efficient period was about four hours. Tolerance was good.


[Are serum acid phosphatase levels of diagnostic significance in prostatic cancer? (author's transl)]. The abnormal serum level of "prostatic" acid phosphatases, stresses a cellular alteration but without an own specificity allowing to certify that it is related to a prostatic affection. One could expect that during the following years thanks to the immunological and electrophoretic methods one can be able to detect in serum specific enzymes issued from a tissue which is in a definite physiopathological state.


[Coronary spasm during exercise test (author's transl)]. We thought chest pain associated with ST segment elevation during exercise test in patients with not significant coronary lesions could be related to coronary spasm. Three patients with mild coronary obstructive lesions underwent coronary arteriography during exercise test. In two patients this hypotesis was supported by angiographic documentation of the coronary spasm.


[Adrenal cortical adenoma and arterial hypertension. Adrenal vizualisation by scintillation with 131 I 19 iodo cholesterol (author's transl)]. A case of adrenal cortical adenoma and arterial hypertension is reported. We emphasize interest of scintillation scanning with 131 I 19 iodo cholesterol, worth of routine examination when seeking for these tumors.


[Dense bone metastases and hypophosphatemic osteomalacia during the course of prostatic cancer (author's transl)]. In patient bearing an advenced prostatic carcinoma with bony metastases, a major hypophosphoremia had led to the detection of an osteomalacia. As far as we know, three observations of the same syndrome have been published previously. As a pathogenic hypothesis, we propose that this tumor secret a substance which inhibit the action of vitamine D. Hypophosphoremia could result from an hyperparathyroid due to hypocalcemia.


[Does hyperuricemia involve a specific cardiac or renal risk? (author's transl)]. Hyperuricemia, commonly found in hypertensive patients, is a daily problem for the practitioner, especially those induced by diuretic therapies. The most divergent opinions are being given about the cardiovascular potential risk of hyper-uricemia. This article raises the problem of the use of those substances which change the metabolism of uric acid, whether they are hyper- or hypo-uricemic. It serves to remind that one must not prescribe hypo-uricemic diuretics to patients whose uricemia is increased, because they may involve serious risks, especially renal ones.


[Adult teratoma of testicular and inguinal localization (author's transl)]. The purpose of the report is to present a patient in whom two adult teratomas presenting all the morphological benign features developed. The first teratoma is situated in the testis, the second is in the homolateral inguinal region. This association is very exceptional. Only a same case was found in literature. Several hypothesis about the mechanism of such lesions are discussed.


[Experimental model of cerebral ischemia preventive activity of Ginkgo biloba extract (author's transl)]. Unilateral embolization of the brain was performed in rats by intracarotid injection of 4 000 radioactive microspheres (50 mu). Local blood flow in hippocampus, striatum, hypothalamus and remainder of the brain were determined using the iodoantipyrine technique. Embolization resulted in a decreases in blood flow and modificationof the distribution of microflow. Furthermore, embolization produces changes in energy metabolism : particularly a fall in ATP and glucose levels and an increase in lactate level. Subsequently, severe vasogenic edema developed. There was a correlation between the number of microspheres injected and the amount of edema. Pretreatment using an extracted of Ginkgo biloba leaves partially suppressed the effect of embolization. An improvement of the flow in the ischemic areas associated with an improvement of the energy metabolism explain the decreases of the edema.


Duck virus hepatitis: serial passage of attenuated virus in ducklings. The safety of three attenuated virus vaccines of proven efficacy against duck virus hepatitis was assessed by controlled laboratory studies which involved the serial transmission of the virus through groups of two-day-old ducklings known to be susceptible to the disease. Each vaccine was initially derived from a different source. Enhancement of virulence which resulted in deaths from the disease in test groups of ducklings occurred in each instance.


Detection and changes of nucleotide pyrophosphotransferase activity in cultures of Streptomyces griseus strains on solid media. The occurrence of nucleotide pyrophosphotransferase (ATP: nucleotide 5'-phosphate pyrophosphotransferase, EC 2.7.4) and the changes in its activity were studied during differentiation in cultures of two Streptomyces griseus strains grown on the surface of a solid medium. One of the strains does not sporulate and produce nucleotide pyro photransferase in submerged culture. Nucleotide pyrophosphotransferase could be detected, though in much differing amounts, in surface cultures of both strains.


[Retroperitoneal perforation of a duodenal ulcer (author's transl)]. A case or retroperitoneal perforation of a duodenal ulcer is presented. Firstly was erroneously diagnosed as an acute appendicitis, and operated upon. The result were good but four successives surgical gests became necessary : first, to treat a very severe parietal infection ; after that, to resolve one very impressive gastro-intestinal hemorrhage and lastly, to treat the duodeno-cutaenous fistula and the duodenal ulcer. The published cases in the recent literature are very scanty but similar to ourselves. The difficulties of promp diagnosis, the erroneously planned first operation in seriously ill patients would be the main causes of the very high mortality.


[Hematological observations in patients following immunostimulation through intrapleural application of Corynebacterium parvum]. The Ludwig Lung Cancer Study Group aims to investigate the role of immunotherapy as adjuvant treatment modality in operable non-small cell bronchial carcinoma. The participants are 12 european clinics and institutes. With a proven accrual of 350 patients per year the group offers a sharp tool in clinical oncology with regards to bronchial carcinoma. The accrual phase of the first trial was closed on February 2, 1979 with 475 patients, starting a new protocol on February 5, 1979. The ongoing randomized clinical trial aims to determine if intrapleural administration of corynebacterium parvum (c. p.) can increase the tumor recurrence-free interval or increase survival. Furthermore the study aims to identify high and low risk patient subgroups after biological and immunological investigations. The possibility of giving c. p. intrapleurally in humans was investigated in a phase-I-toxicity study. A dose of 7 mg has been adopted for the clinical trial since this dose combines a measureable systemic effect (increase of leucocyte and monocyte counts) with acceptable toxicity. The main morbidity was fever, flu-like symptoms and chest pain.


[Prognostic significance of the cyclic AMP concentration in acute leukemias]. In patients with acute leukemia (myeloblastic, lymphoblastic, undifferentiated) proliferation kinetics and cyclic adenosine-3', 5'-monophosphate (cAMP) concentration of the leukemic cells were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly faster turnover and lower cAMP-levels than those who failed to respond to treatment.


[Isolation of Enterovirus 70 during an outbreak of acute hemorrhagic conjunctivitis in Algeria in 1973]. The Enterovirus 70 was isolated in Algeria in 1973 during an outbreak of acute hemorrhagic conjunctivitis. The main epidemiological features were similar to those previously described in other countries: involvement of the adults especially, mainly those living in communities, irrelevance of the different socio-economical levels of the population. The spring waters may have played a role in the transmission of the disease. The virological study draws the attention on the optimal conditions for the isolation of the virus and shows that the strains are antigenically related to those isolated in Morocco during 1971. The Enterovirus 70 was associated with adenoviruses and it was not possible to evaluate the respective role of the two groups of viruses in the determinism of the epidemic. The detection of the residual antibodies in sera collected in 1974 indicates that 58% of a group of 50 adults have antibodies against the Enterovirus 70. It is not yet possible to ascertain whether those antibodies are specific or only reflect an antigenic crossing between the Enterovirus 70 and one or several already known enteroviruses.


[Nephroblastoma and whole-body hemihypertrophy. Relation to Wiedemann-Beckwith's syndrome]. A child with hemihypertrophy presented with Wilm's tumor at 3 years of age. History included neonatal hypoglycemia and the discovery of hepatomegaly and renal dysplasia. This case report emphasizes the close relation of body hemihypertrophy to Beckwith's syndrome, as well as the high degree to which both predispose to certain tumors.


[Hematopoiesis and changes in the RES of the spleen pulp in fibrosarcoma-bearing rats]. The transplantable fibrosarcoma of the Rat gives birth to different modifications in the splenic structures, and a strong perturbation is found within the enzymatic activities. The macrophages have an altered acid phosphatase activity. This is in marked contrast to the increase in number of the alkaline phosphatase polymorphonuclear cells, which are originated from myeloid areas in the red pulp. Lymphoïd-reticular cells, possessing one 5'nucleotidase activity, seem to be responsible, possibly, by forming numerous clonal systems during the development of this fibrosarcoma. The role of this separate system is discussed.


Na+/K+-dependent adenosinetriphosphatase activity in the skin, kidney and muscle in Xenopus laevis (Daud.) adult specimens under different experimental conditions. Xenopus laevis adult specimens were exposed to environmental changes simulating those undergone by these animals in their natural "habitat". After keeping groups of animals under dry conditions, some of them were returned to water. In both cases some parameters were compared with those of control animals kept in water. A lower activity in the Na+/K+-dependent ATPase of the epidermis and striated muscle was detected in "dry" animals with respect to the control ones or those rehydrated whereas the same ATPase activity in the kidney was higher in "dry" animals than in those from the other groups.


[Hormone dependence of 5'-nucleotidase histochemically detected during the development of the epididymis of the rat after birth]. 5'nucleotidase activity of the apical border of the epididymal epithelium appears towards the end of the second week during postnatal development. This activity is in correlation with the activity of testicular hormone. Bilateral castration modifies it and testosterone restores this activity.


Origin of mitochondrial enzymes. V. The polypeptide character and the biosynthesis of rat liver cytochrome c oxidase polypeptides by mitochondria. Isolated rat liver mitochondria were labeled in vitro with L-[14C]leucine. Sixty percent of the incorporated radioactivity was found to reside in subunits 1, 2, and 3 of cytochrome c oxidase with apparent molecular weights of approximately 33,000, 25,000, and 20,000, respectively. The results indicate that these are the predominant products of protein synthesis under the conditions employed. The enzyme complex, as derived by immunoprecipitation, was found to contain four additional polypeptides with apparent molecular weights of 17,000, 12,500, 7000, and 3500. A comparison of electrophoretic profiles of the rat liver and beef heart enzyme reveals that the apparent molecular weights of all polypeptides are remarkably similar.


Lipid protein interactions in mitochondria. VIII. Effect of general anesthetics on the mobility of spin labels in lipid vesicles and mitochondrial membranes. We have studied the effect of general anesthetics on the mobility of two stearic acid spin labels (5-doxyl stearic acid and 16-doxyl stearic acid) in bovine heart mitochondria and in phospholipid vesicles made from either mitochondrial lipids or commercial soybean phospholipids. The general anesthetics used include nonpolar compounds (alcohols, halothane, pentane, diethyl ether, chloroform) and the amphiphatic compound, ketamine. All anesthetics tested increase the mobility of the spin labels in phospholipid vesicles to a limited extent up to a concentration where the ESR spectra become those of free spin labels. On the other hand, anesthetics have a pronounced effect on mitochondrial membranes at concentrations as low as those known to produce general anesthesia; the effect is lower near the bilayer surface (5-doxyl stearic acid) and very strong in the bilayer core (16-doxyl stearic acid). The effects of anesthetics are mimicked by the detergent, Triton X-100. We suggest that the discrepancy between the action of anesthetics in mobilizing the spin labels in lipid vesicles and in membranes results from labilization of lipid protein interactions.


Detection of conformational changes in complex III of the respiratory chain by a maleimido spin label. Changes in the conformation of Complex III (CoQH2-cytochrome c reductase) of the mitochondrial respiratory chain were detected upon oxidoreduction using the nitroxide spin label, 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl. EPR spectra of the spin label show a transition from a greater to a lesser degree of immobilization when the labeled enzyme, reduced either with ascorbate or sodium dithionite, is oxidized with potassium ferricyanide or ferricytochrome c. These observations are interpreted to indicate that Complex III is more compact in the reduced state at least in the locality of the spin label. An apparent increase in the concentration of total spins during oxidation of the complex suggests change in the interaction between the spin label and other paramagnetic centers and not an oxidation of spin label, itself, since reduced free spin label could not be reoxidized. Addition of antimycin A had no effect on the EPR spectrum of the spin-labeled enzyme, indicating that this inhibitor does not initiate a conformational change in the region of the spin label. Experiments in which N-ethyl-[2-3H] maleimide was bound to Complex III show that binding occurs primarily to a subunit with a molecular weight of 45,000. Although no qualitative differences were observed, it was found that less radioactivity appears in samples reduced with dithionite than in those reduced with ascorbate. This difference appears to be caused by decomposition products of dithionite.


Presence of tolyl-specific IgE and absence of IgG antibodies in workers exposed to toluene diisocyanate. Independent immunoenzymatic and radioimmunoassay techniques indicated the absence of tolyl-specific IgG antibodies in sera from 25 workers with long-term exposure to toluene diisocyanate (TDI). Five of these workers were clinically hypersensitive to TDI and displayed significant titers of tolyl-specific IgE antibodies in their sera.