Studies of age-related changes in the metabolism of eosin in the rat. Male rats of different age groups maintained normally on laboratory chow were injected with eosin (2,4,5,7-tetrabromo-11-carboxyfluorescein) after which the biliary excretion of the dye was studied. In 3 age groups below 42 weeks, the dye was excreted as 2 compounds which were identified by thin-layer chromatography as unchanged eosin (Rf 0.90--0.91) contributing about 80--90% and one conjugated compound of Rf 0.43--0.47 (14--9%) which was shown to be a glucuronide. Eosin metabolites could not be traced in 30 and 42 week-old rats. This finding is discussed in relation to: (i) age and enzymic activity, and (ii) bio-activated metabolites of this dye which may induce biochemical or toxicological and carcinogenic lesions.


[Spiradenoma, cutaneous cylindroma and familial multiple trichoepithelioma]. Multiple spiradenoma, trichoepithelioma and traits of cylindroma in three members of a family are studied. The relationships among these tumors are discussed. Spiroadenoma and cynlindroma have shown a close interrelation. Both conditions may exist with multiple lesions in genetic autosomal dominant inherited association with multiple trichoepitelioma.


Altered mechanism of glucagon-mediated hepatic glycogenolysis during long-term starvation in the rat. The effect of long-term starvation on glucagon-mediated hepatic glycogenolysis was investigated in the rat in vivo. Following glucagon (50 microgram/kg i.v.) fed rats showed rapid phosphorylase activation but no change in synthase-I activities. In contrast, rats fasted 72 hr (long-term fasting) showed rapid synthase inactivation but no significant phosphorylase activation. Rats fasted 24 hr (short-term fasting) demonstrated coordinated inactivation of synthase and activation of phosphorylase. Hepatic cyclic AMP responses were greater in fasted rats. Hepatic glycogen concentrations in rats fasted 72 hr were approximately 30% of fed levels. After glucagon, comparable decrements in hepatic glycogen and increments in plasma glucose concentrations were seen in fed and 72-hr groups. The diminished responsiveness of the hepatic phosphorylase system in rats fasted 72 hr was not attributable to altered cyclic AMP-dependent protein kinase or phosphorylase kinase activities. However, the diminished responsiveness could be ascribed to diminished total phosphorylase with nearly complete activation in the basal state. In fed and fasted rats, synthase decrements after glucagon correlated closely with basal levels of synthase-I. Thus, it is proposed that the enzymatic mechanism of glucagon-mediated hepatic glycogenolysis differs in fed and fasted rats. It is also proposed that partial hepatic glycogen reaccumulation during long-term fasting could be physiologically important for glucose homeostasis.


Hormonal regulation of membrane receptors and cell responsiveness: a review. Hormone receptors are those components of target-cells that specifically bind hormones and convey the hormonal message to the intracellular machinery. Such receptors can be localized inside the cell, such as the nuclear receptors of thyroid hormones and the nuclear and cytoplasmic receptors of steroid hormones, or on the outer surface of the plasma membrane, such as the membrane-bound receptors of polypeptide hormones and neurotransmitters. Extensive studies during recent years have shown that the interaction between hormone and membrane-bound receptor can affect the receptor characteristics in at least two ways. Firstly, receptor occupancy can modify, by way of cooperativity, the affinity of homologue receptors for the given hormone. Secondly, the binding capacity of a target cell appears to vary as a function of the preexposure of the cell to the hormone. The latter phenomenon has been related to the so-called states of subsensitivity, desensitization, or refractoriness, and might be responsible for the physiologic regulation of the target cell sensitivity and for the hormone resistance which accompanies various metabolic disorders. In this review we attempt to describe the major findings related to hormone desensitization or resistance of these hormones that have plasma-membrane-bound receptors. Data from the literature are presented independently for each hormone and when applicable, conflicting results are discussed in each section. The various theories which might explain hormone desensitization are outlined in the last section of this paper.


Properties of the erythrocyte receptors for influenza C virus. Properties of the receptor for influenza C virus were studied. Although the receptor for influenza C virus on chicken erythrocytes was destroyed by the homologous virion, neuraminidase activity could not be detected in any of the influenza C virus strains tested. The receptor activity of chicken erythrocytes for influenza C virus was diminished by formaldehyde treatment but not by periodate oxidation. There was a considerable variation in the pattern and the titer of hemagglutination of influenza C virus when human erythrocytes of different blood types were used; the virus agglutinated most type B erythrocytes but not type A erythrocytes. By using human type B erythrocytes, differences among strains of influenza C virus in the hemagglutinating activity were also demonstrated. These results showed that both the receptor for and the receptor-destroying activity of influenza C virus were completely different from those of influenza A or B virus and also that carbohydrates were not involved in the receptor for influenza C virus.


Conditions necessary for quantifying ethyl methanesulfonate-induced mutations to purine-analogue resistance in Chinese hamster V79 cells. We have investigated conditions necessary to quantify the relationship between exposure to a mutagen, ethyl methanesulfonate (EMS), and the frequency of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells. Maximal expression of potential mutants has been achieved by either subculturing at fewer than 5 X 10(5) cells/100-mm dish at 2-day intervals or by daily feeding of cultures. An expression period of 5 days (measure from 1 day after the initiation of treatment with the chemical mutagen) should be allowed, since at least 4 days of expression is required to reach to steady maximum of mutation frequency. It appears that there is no concentration dependence of expression time necessary to reach a plateau of mutation frequency with increasing concentrations of EMS up to 1.6 mg/ml. About 1.25 X 10(5) cells/100-mm dish or fewer should be plated for selection to avoid the loss of mutants which occurs at 1.5 X 10(5) cells/dish, presumably through cross-feeding (metabolic cooperation). The use of 6-thioguanine in hypoxanthine-free medium (supplemented with dialyzed fetal calf serum) appears to be a very stringent condition for selection. Mutation induction by EMS as a function of EMS exposure (EMS concentration X treatment time) increases linearly with concentration up to 12 h. For these treatment periods, the observed mutation frequencies for EMS are directly proportional to mutagen exposure regardless of the duration of the treatment.


Prolactin-screening tumors and hypogonadism in 22 men. We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.


Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. To define the metabolic defect in Tangier disease, we studied the kinetics of [125I]-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism.


Obstructive sleep apnea in family members. Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep.


Cellular immune response in genital herpes simplex virus infection. We studied the relations between the cellular immune response, pre-existing complement-fixing antibody and virus type with duration of virus excretion in genital herpes simplex virus (HSV) infection. Thirty-six patients (seven with HSV-1 and 29 with HSV-2) with genital herpes underwent serologic testing, sequential viral cultures and weekly determination of lymphocyte-transformation stimulation index with inactivated HSV antic n. The duration of virus excretion was shortest in those with pre-existing complement-fixing antibody, was unrelated to virus type, and was inversely correlated with the magnitude of the mean peak stimulation index (r = -0.69, P less than 0.001). Prolonged virus excretion occurred in patients with a delayed and diminished peak index. Recurrent episodes had a higher peak index (29.4 compared to 14.5) (P less than 0.02), an earlier development of the peak during recurrences (9.1 vs. 25.8 days) (P less than 0.01) and a briefer duration of viral shedding than initial episodes. Thus, the temporal course and magnitude of the stimulation index correlate with and may determine the duration of genital HSV infection.


[Release of toxic agents from ceramic utensils]. Under the influence of acidic agents, ceramic glazes and decorations for ceramics may release certain toxicants, especially lead and cadmium. Both elements are essential constituents of ceramic colours and glazes; their release to acidic foods is technologically unavoidable, but it may be minimized by the utilization of appropriate decoration agents and techniques. In most industrial countries, the release of toxicants from utensils is severely limited, the maximum permissible values and the methods of test and analysis being in part very different and not always in agreement with the demands and conditions of practice. The problems related to the release of toxicants from ceramic utensils are treated from the aspects of ceramics, test techniques, analytics, toxicology and food law, with special regard to the necessity for a well-balanced compromise between the justified hygienic demands of health protection and the actual technological possibilities. The endeavours of the ceramic industry of the GDF to produce ceramic utensils releasing as little toxicants as possible are outlined.


[Evaluation of the cadmium content in sedimented and floating dust as factors in contamination of the biosphere]. In a territory being 3.500 km2, the cadmium deposits from the atmosphere were determined at 63 sites in 52 towns and communities. These determinations yielded a mean value ranging from 0.13 to 0.15 mg/m2 . 30 d. On the contrary, the mean value (-x) was 0.33 mg/m2. 30 d in the region of heavy-metal-emitting industries. The mean cadmium content in the aerosol was between 0.003 and 0.004 microgram m-3 and, respectively, 0.016 microgram m-3 in case of cadmium emission. It was calculated that the mean proportion of cadmium in the sedimentary dust was between 13 and 16 p.p.m. The cadmium burden, as estimated as cadmium sediment, correlated with the extent of the developmental area. The authors recommend for the present the following maximum permissible values: 0.05 microgram m-3 in the aerosol, and 0.15 mg/m2. 30 d. The cadmium content in the sedimentary dust may be considered to be a permanent burden applied via the food chain, whereas the content in the aerosol is of less importance to the total uptake in man. The calculation of the daily pulmonary uptake yielded a value of 0.075 microgram, from which an absorption of 0.038 microgram is estimated.


Transmission of hormonal stimulation by cell-to-cell communication. Rat ovarian granulosa cells and mouse myocardial cells respond to cell-specific hormones by cyclic AMP-dependent mechanisms. In coculture, these heterologous cells communicate by means of gap junctions. Exposure of the cocultures to a hormone specific for one cell type causes the heterologous cells to respond through a cell contact-dependent mechanism. These studies suggest that this cross-stimulation results from the intercellular communication of a mediator that is common to both cell types. The communicated mediator may be cyclic AMP.


Neuronal properties underlying processing of visual information in the barnacle. Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina.


Promoter-specific inhibition of transcription by antibiotics which act on DNA gyrase. Nalidixic acid, novobiocin and coumermycin specifically inhibit phage promoter-dependent transcription of the trp operon in phi 80 ptrp but not transcription from the authentic trp promoter. The nalidixic acid inhibition is not observed in an E. coli strain containing a nalAr mutation. These results indicate that DNA gyrase is involved in transcription.


Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis. A temperature sensitive mutant has been isolated for the first time from a replication defective acute leukaemia virus, AEV. In vivo, at 41 degrees C, the mutant shows a reduced leukaemogenic potential. In vitro, in erythroblasts transformed at 35 degrees C, haemoglobin synthesis can be induced by a shift to 41 degrees C. This indicates that the continuous expression of a viral gene product is necessary to maintain the undifferentiated state of the virus-transformed leukaemia cells.


Passive immunization against transmissible gastroenteritis virus in piglets by ingestion of milk of sows inoculated with attenuated virus. Pregnant sows were inoculated with the attenuated strain, TO--163, of swine transmissible gastroenteritis virus. Suckling piglets born from them received challenge inoculation with the virulent virus at 3 days after birth, and examined for ability to prevent infection and the immunoglobulin (Ig) classes of antibody in milk. A pregnant sow was inoculated intramuscularly with a dose of 10(8.0) TCID50 and intranasally with a dose of 10(9.3) TCID50 of attenuated virus. Piglets born from it suffered from diarrhea after challenge inoculation, but none of them died eventually. Their dam was also affected with diarrhea for 4 to 7 days after challenge inoculation of them. Another pregnant sow was inoculated twice with 10(9.3) TCID50 of attenuated virus, first by the intramuscular and secondly by the intranasal route. Of nine piglets born from it, one excreted soft feces after challenge inoculation, but all survived to grow normally. Their dam manifested no clinical symptoms at all after challenge inoculation of them. The higher the titer of virus inoculated into pregnant sows, the higher the neutralizing antibody titer in serum and milk of the sows after farrowing. The puerperal sow which had received two doses of 10(9.3) TCID50 each of attenuated virus by the intramuscular and intranasal route, respectively, presented the highest neutralizing antibody titer of all the inoculated sows. This titer was 2,048 in serum and 14,183 in colostrum immediately after farrowing. In that sow IgG was the main class of immunoglobulins in neutralizing antibody in milk. Even the IgA antibody titer of that sow was higher than that of any other sow which had been administered with virus of low titer. It was 392 and 19 3 and 9 days, respectively, after farrowing.


The use of polyethylene glycol in concentration and purification of several bovine viruses. The polyethylene glycol (PEG) precipitation method was used for the concentration and purification of eight bovine viruses. Good results were obtained from four viruses, parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus. No satisfactory results of concentration were obtained from bovine reovirus, bovine viral diarrhea virus, and infectious bovine rhinotracheitis virus. The failure of concentration of the four viruses seems to be ascribed rather to the resuspending of virus from the virus--PEG precipitate than to the precipitation of virus from infective culture fluid. This method can be applied as the initial step to the concentration of parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus from a large volume of material, since it is simple, rapid, and inexpensive.


Responses of the rat superior cervical ganglion in vitro to isoprenaline and bethanechol. The effects of isoprenaline were studied in isolated rat superior cervical ganglia. Intracellularly recorded excitatory postsynaptic potentials were depressed by isoprenaline in concentrations of 10(-5) to 10(-4)M. In 13 out of 17 cells, isoprenaline caused ganglionic hyperpolarization (mean, 4mV). Changes in the amplitude and contour of antidromic action potentials caused by isoprenaline could be accounted for by the increased membrane potential. A slight increase in membrane input resistance from 44--50.2 megohms (mean values) occurred in about half of the cells. Activation of an ion pump by isoprenaline was suggested by the finding that the hyperpolarization did not occur when the bathing solution contained ouabain (10(-5)M) or lacked Na+ or K+. Characterization of the isoprenaline effects by the use of alpha and beta adrenergic blocking drugs was not possible because of the direct depressant effects of the antagonists. The muscarinic agonist bethanechol (2.5 X 10(-5) to 2.5 X 10(-4)M) caused ganglionic depolarization and increased input membrane resistance (42--52 megohms) during depolarization in each of the cells tested. The ganglionic responses to bethanechol were prevented by atropine.


Correlation between inhibition of (Na+, K+)-membrane-ATPase and positive inotropic activity of cardenolides in isolated papillary muscles of guinea pig. Concentrations of 17 cardenolides, cardenolide glucuronides and sulfates producing half-maximal inhibition of (Na+, K+)-membrane-ATPase from different organs and animal species were determined in vitro. In addition the concentrations that increased the contractility of guinea pig isolated papillary muscles to a particular level were investigated. Comparisons between ATPase-inhibiting and positive inotropic cardiac activities showed extensive parallelism: the correlation coefficients after log/log transformation were between 0.92 and 0.97. The same close correlations are found if dissociation constants of cardenolide receptor complexes and concentrations causing 86Rb-uptake inhibition in human erythrocytes are examined. The concentrations necessary for inhibition of (Na+, K+)-membrane-ATPase of the guinea pig heart and the concentrations required to achieve a defined positive inotropic effect in guinea pig papillary muscle showed a log/log correlation coefficient of 0.97 (P less than 0.001). In both tests the potencies covered more than three orders of magnitude. The results support Repke's hypothesis on the digitalis receptor.


Kainic acid-induced lesion of dopaminergic target cells in the striatum: consequences on the dynamics of cerebellar cGMP. The bilateral intrastriatal injection of kainic acid (2 microgram/caudate) caused a marked decrease in the activity of striatal dopamine-sensitive adenylate cyclase. This probable loss of target cells for dopamine was associated with a parallel decrease of the cGMP level in the cerebellar cortex, which was maximal (80% loss) by 24 h and prevented apomorphine from raising cerebellar cGMP levels. On the contrary harmaline and isoniazid both increased the levels of cerebellar cGMP in kainic-lesioned rats to the same extent as in control rats. The results indicate that dopamine mechanisms in the striatum are involved in the regulation of cerebellar cortex cGMP.


[Neurological complications of Argentinian hemorrhagic fever]. The Argentine hemorrhagic fever (AHF) is an infectious disease, endemo-epidemical, of viral etiology, produced by the Junin virus and limited to the Buenos Aires Province, South of Córdoba, East of La Pampa, and South of Santa Fe. It generally assails rural workers at harvest-time, especially during corn-harvest. The incubation period of the disease does not exceed 12 days. A feverish syndrome with asthenia, adynamia, myalgias, migraine, photophobia, epigastralgia etc., appear. The patient has a facial erythema, petechias on the skin, enantema on the palate, conjunctive micropolyadenopaty injection. The laboratory shows a low erytro, leukopenia with aneosinophilia, thrombopenia and a urine with albuminuria and virous cells. After the fourth day, hemorrhage and a neurological case appears. The laboratory tends to normalize and cast appears in the urine. The most striking neurological signs are the following: muscular hypotonia, proprioceptive hyporreflexia or arreflexia, marinesco reflex, shakings, difficulty to stand and walk, oscillations in consciousness level, and ocular disturbances. The cytochemical test of the C.L. Rachis in the usual ways of the AHF is within its normal characteristics; on the other hand there are modifications in the nervous cases: the total proteins are nearly always increased and the cells augmented with a great predominance of mononuclear cells. The electroencephalogrammes were always abnormal, varying from a brief disorganization up to a diffusive and permanent slowness. The half of which additionally presented paroxisms generalized by slow waves. The pathological anatomy over  the central nervous system makes us think that the lesion would not primitively neuronal but that the action of the virus would be indirectly done through the capillar wall. This capillar lesion is produced by multiple focuses. The neuronal destruction with necrosis by microinfarcts is minimum. The symptoms and neurological signs are present in 10% of the clinical cases; the death-rate in the nervous clinical cases having reached 50% of them. The premature treatment allows the death-rate to diminish and the cases that survive have not many after effects.


[Virological studies in acute polyradiculoneuritis, LGBS type. Various findings in relation to Coxsackie A4 virus]. Studies of isolated virus in LCR and necropsy material were made (medulla roots and rachi ganglia) in acute cases of polyradiculoneuritis. Landry-Gullain-Barré-Strohl type. Serological studies with prepared sera were also made (at three week intervals). The results were discussed based on the isolation of a Coxsackie A virus in four cases and the corresponding serological findings.


Hormonal response to stress in the squirrel monkey (Saimiri sciureus). The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females.


Uptake and release of norepinephrine by slices of rat cerebral cortex: effect of agents that increase cyclic AMP levels. Cerebral cortical slices from rats were incubated in physiologic saline, and the uptake, release, and K+-stimulated release of norepinephrine were measured. Dibutyryl cyclic AMP, the phosphodiesterase inhibitors aminophylline and papaverine, and adenosine (which stimulates adenyl cyclase) all caused a variable increase in uptake of norepinephrine at concentrations ranging from 10(-7) to 10(-4) M. Prostaglandins E1 and E2 appeared to have no effect on uptake, but this may be because the alcohol required to dissolve them had an inhibitory effect on uptake. None of these compounds appeared to affect basal or K+-stimulated release of norepinephrine. These agents therefore seem to have an effect opposite to that of the tricyclic antidepressants (which inhibit uptake of norepinephrine). Since norepinephrine's postsynaptic effects are usually inhibitory in the cortex, the stimulatory effect of the drugs tested on the presynaptic uptake of norepinephrine may explain the stimulant and epileptogenic effects of these drugs.


Diagnostic significance of myeloperoxidase assay in neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome). In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the leukocyte homogenate; application of phosphate buffer (pH7.0) and borate buffer (pH7.6); employment of 9mM, 28mM, and 55mMp-phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10, 60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses.


Unit activity in the cat visual cortex in the sleep--waking cycle. Changes in spontaneous unit activity in the primary visual cortex during the sleep-waking cycle were studied in chronic experiments on dark-adapted cats. In the cell poulation studied activity in states of wakefulness and of paradoxical sleep did not differ significantly either in mean discharge frequency or in pattern. Activity of most cells in a state of slow sleep differed significantly from that in states of wakefulness and paradoxical sleep by the development of a "burst-pause" pattern in the unit discharges.


Corneal ultrastructural changes in Fabry's disease. A case of Fabry's disease is reported. The findings of the corneal alterations with the light microscope as well as with the electron microscope are described. The diffuse corneal haziness seems to be due to small intracellular osmiophilic inclusions of the epithelium. There seems also to be a relation between the giant inclusions in the corneal epithelium, not yet described, and the clinical presence of punctiform grey opacities. The pathogenesis of the whorl-like opacities remains unsolved.


Clinical, genetic, and histologic features of the trichoonychodental (TOD) syndrome. A syndrome of scanty, fine, curled hair, thin dysplastic nails, taurodontic molars, hypoplastic-hypomature enamel, dysplasia of dentin, and hypohidrosis segregating as an autosomal dominant trait is described in a Japanese family. The patients received repeated doses of tetracycline during odontogenesis which fortuitously assisted in interpreting the pathogenesis of the dentin defect. The condition was previously described as familial congenital ectodermal dysplasia by Westerholm and as odontogenesis imperfecta by Siirilä and Heikinheimo. It is suggested that the name trichoonychodental (TOD) syndrome is a better descriptive term for the condition.


Glycoproteins from the aorta.

Glycoproteins from the aorta. This review deals with the data on isolation techniques, structure, physicochemical properties and biological function of glycoproteins isolated from the aorta. Some glycoproteins extracted at low ionic strengths (soluble glycoproteins) are immunologically distinct from serum glycoproteins. The designation "structural glycoprotein" was proposed for glycoproteins associated with the collagen elastin matrix. These glycoproteins are solubilized by dissociative and reducing buffers. A selective hydrolysis of the insoluble collagen prior to their extraction was also reported. The molecular weights are in the range of 53 - 72.000 and 35.000 - 27.000 daltons for the soluble and the structural glycoproteins respectively. The aorta glycoproteins are rich in polar aminoacids. The primary structure of glycoproteins from aorta is not yet established. The electrophoretic mobility and sugar content of some glycoproteins extracted at low ionic forces change with the maturation and sex. The biosynthesis of a soluble glycoprotein (glycoprotein B) and of structural glycoproteins by aortic smooth muscle cells was demonstrated "in vitro". The structural glycoproteins appear as microfibrillae in electron microscopy. Their self-aggregation may be due to hydrophobic interactions. The association of microfibrillar glycoprotein with elastin in connective tissues and in the culture medium of aortic smooth muscle cells suggests the role of glycoprotein-elastin interactions in morphogenesis.


[Circadian rhythms in man. Their incidence in endocrinology (author's transl)]. The authors, after a classification of the main biological rhythms, mention the parameters of the circadian rhythm deduced by mathematical analysis of so-called "Cosinor". They then devote their study to the main hormones, the secretion of which depends on circadian periodicity. They emphasize the effect that their biorhythm has on the value of plasma concentrations depending on the time of sampling. They suggest standardisation of this time in drawing up international norms.


Technique for measurement of inert gases in liquids by gas chromatography. A method for quantitative analysis of inert gases in liquids by gas chromatography is described. The technique comprises an equilibration system for partial extraction of dissolved gases from liquids and a gas chromatograph equipped with helium ionization detector. The method is particularly devised for determination of solubility coefficients of gases in liquid materials, e.g. water, aqueous solutions, blood, tissue homogenates, and for simultaneous measurement of several inert gases dissolved in liquids. Coefficients of variation for serial analyses of individual samples were less than or equal to 3%. The method is applicable to studies of blood-tissue transfer of respiratory and inert gases.


A nuclear protein-modifying enzyme is responsive to ordered chromatin structure. Poly (ADP-ribose) polymerase, a nuclear protein-modifying enzyme, binds to the internucleosomal linker region of chromatin, although it modifies certain core nucleosomal histones in addition to histone H1. The activity per unit of DNA chromatin changes with the nucleosome repeat number. It reaches a maximum on chromatin of 8-10 nucleosomes in length. As the complexity of chromatin with respect to nucleosome repeat number and compactness increases, a decline and stabilization of specific activity is noted. The difference in specific activity is maintained through resedimentation and dialysis of particles. It does not appear due to differences in polymer chain length or differential degradation of poly (ADP-ribose). The data suggest a relationship between ADP-ribosylation and chromatin organization and vice versa.


An electron microscopic method for the mapping of proteins attached to nucleic acids. An electron microscopic method for demonstrating the presence of and mapping the positions of proteins specifically bound to nucleic acids is described. The nucleic acid-protein complex is treated with dinitrofluorobenzene under conditions such that dinitrophenyl (DNP) groups are attached to nucleophilic groups on the protein, with only a low level of random attachment to the nuclei acid. This product is treated with rabbit anti-DNP IgG. The position of the protein-(DNP)n(IgG)m complex on the nucleic acid strand can be observed by electron microscopy by protein free spreading methods and, in many cases, by cytochrome-c spreading. If necessary for visualization by the latter method, the size of the labeled region can be increased by treatment with goat anti-rabbit IgG. High efficiency of electron microscopic labeling is achieved. Examples studied are: the adenovirus-2 DNA terminal protein, a protein covalently bound to SV40 DNA, DNA polymerase I bound to DNA, E. coli RNA polymerase bound to T7 DNA, and proteins UV crosslinked to avian sarcoma virus RNA.


Fused rocket and rocket immunoelectrophoresis adapted for demonstration and quantitation of the A antigen of Marek's disease virus-infected cell cultures. Preliminary results have shown that the rocket immunoelectrophoresis technique can be used as a method for quantitation of the A antigen of Marek's Disease virus-infected cell cultures.


Chromosome of the mature virion of simian virus 40 contains H1 histone. In addition to free SV40 minichromosomes in the compact form, complete virions were obtained from the nuclear extract of productively infected cells. Capsid proteins VP1, VP2, and VP3, as well as histones, were observed on  electrophoregrams of proteins prepared from virions. In contrast to the widely accepted view, histone H1 was found in virions in stoichiometric amounts with respect to other histones. The same is true for virions isolated by a conventional method. Free minichromosomes present in infected cells contain all histones and practically no viral proteins.


Purification of a DNA nicking-closing enzyme from mouse L cells. A DNA nicking-closing enzyme has been purified from the nuclei of mouse L cells to 90% homogeneity. The denatured and reduced form of the enzyme has a molecular weight of 68,000 which is in agreement with the molecular weight of the native enzyme as determined by gel filtration and by sucrose sedimentation velocity assuming the protein is globular. Therefore, the active form of the enzyme is a monopolypeptide. Its isoelectric point is pH 4.2 +/- 0.2. The nicking-closing activity does not require a cofactor and does not involve any sulfhydryl group. The enzyme requires 0.2 M NaCl and pH in the range of 6.5-7.5 for optimal activity.


The relationship of SV40 replicating chromosomes to two forms of the non-replicating SV40. SV40 replicating chromosomes were extracted from infected cells using a detergent free extraction method. This procedure also extracts 2 forms of the non-replicating chromosome, one of which corresponds to the well characterized 50-55S SV40 minichromosome. The other is a more compact structure which has a sedimentation coefficient of 80-85S. The replicating chromosomes sediment between the 2 conformations of the mature chromosome. Electron microscopy of the replicating chromosomes suggests an overall conformation that resembles the 50-55S form of the mature chromosome rather than that of the 80-85S structure. Nucleosomes are present on both sides of the replication forks. When the replicating chromosomes were incubated in an in vitro DNA synthesis assay all regions of the SV40 genome were synthesized and a significant fraction of the replicating chromosomes completed replication. The progeny chromosomes co-sedimented with the 50-55S chromosomes which were present prior to the incubation. The sedimentation coefficients and relative amounts of the two forms of the mature chromosome were unaffected by the incubation.


Chemical synthesis of 5'-pyrophosphate and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. CD study of the effect of 5'-phosphate groups on the conformation of 3'-5' GpG. A simple, two-step method is described for the synthesis of the 5'-pyro- and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. The readily accessible 2'(3')-5' ApA, ApG, GpA and GpG were converted in one step to the corresponding 5'-phosphoramidate derivatives which were then transformed to the 5'-pyro- and triphosphates. CD spectra of 3'-5' pn GpG (n = 0,1,2 or 3) derivatives, measured at pH 1, indicated stabilization of the (syn) G+p (anti)G conformation by the 5'-phosphate groups.


Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA). A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.


Substrate dependence of the mechanism of EcoRI endonuclease. The mechanism of EcoRI endonuclease is substrate dependent. At 37 degrees dissociation of the enzyme-Form II DNA intermediates of ColE1 DNA and bacteriophage G4 RFI DNA is negligible. Therefore, both DNA strands with in the EcoRI sequence are cleaved during a single binding event. However, double strand cleavage of SV40 DNA occurs without dissociation of the enzyme in only 75% of the catalytic events. This mechanistic difference presumably reflects sequence differences about the EcoRI sites of these DNA's.


[Examinations to cAMP-levels in plasma (author's transl)]. Plasma cAMP levels were measured by a competetive protein binding method in nine healthy volunteers every 30 minutes over a period of 24 hours under standardized conditions. No circadian variation was observed. Upright posture after 32 hours bedrest increased cAMP significantly.


Intestinal giardiasis, steatorrhoea and peripheral nerve dysfunction. Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed.


Isolation of an avian erythrocyte protein possessing ADP-ribosyltransferase activity and capable of activating adenylate cyclase. An ADP-ribosyltransferase was purified approximately 500-fold from the supernatant fraction of turkey erythrocytes. The enzyme hydrolyzed [carbonyl-(14)C]NAD to ADP-ribose and [carbonyl-(14)C]nicotinamide at a low rate. Nicotinamide formation from NAD was enhanced by arginine methyl ester > D-arginine approximately L-arginine > guanidine; lysine, histidine, and citrulline were ineffective. Incubation of [adenine-U-(14)C]NAD and arginine methyl ester or arginine with the purified enzyme resulted in the formation of new compounds that contained (14)C, reacted with ninhydrin, and quenched background fluorescence of thin-layer plates viewed in ultraviolet light. Their mobilities on thin-layer chromatograms were indistinguishable from those of ADP-ribosylarginine methyl ester and ADP-ribosylarginine formed during incubation of choleragen with NAD and arginine methyl ester or arginine, respectively [Moss, J. & Vaughan, M. (1977) J. Biol. Chem. 252, 2455-2457]. The purified transferase also catalyzed the incorporation of label from [adenine-(14)C]-NAD into lysozyme, histones and polyarginine. When the (14)C-labeled lysozyme was incubated with snake venom phosphodiesterase, the radioactivity was released and, on thin-layer chromatograms, exhibited a mobility indistinguishable from that of 5'-AMP, as would be expected of an ADP-ribosylated protein, but not of a poly(ADP-ribosylated) product. The purified transferase activated rat brain adenylate cyclase and, as is the case with choleragen, activation was absolutely dependent on NAD. The presence in the avian erythrocyte of a protein that, like choleragen and Escherichia coli heat-labile enterotoxin, apparently activates adenylate cyclase and possesses ADP-ribosyl transferase activity is consistent with the view that the mechanisms through which the bacterial toxins produce pathology are not entirely foreign to vertebrate cells, at least some of which may possess and employ an analogous mechanism for activation of adenylate cyclase.


Nearest-neighbor interactions of the major RNA tumor virus glycoprotein on murine cell surfaces. Formaldehyde-fixed Staphylococcus aureus and monospecific antiserum to gp70, the major envelope glycoprotein of murine leukemia virus, were used to immunoadsorb gp70 from Nonidet P40 extracts prepared from surface-radioiodinated murine cells. The labeled gp70 molecules in these cells were linked to a protein of approximately 15,000 daltons via native disulfide bonding. Prior treatment of cells with the reversible, bifunctional, crosslinking reagent dimethyl-3,3'-dithiobispropionimidate, followed by immunoadsorption and two-dimensional diagonal electrophoresis, revealed apparent homodimers and homotrimers of the 85,000-dalton complex. Identical treatment of purified type C RNA tumor virus from murine cells also revealed homodimeric and homotrimeric species, demonstrating similar self-associating tendencies of this glycoprotein in both intact virus and the plasma membrane of nonproducing murine cells. One cross-linked product consistently detected on the surfaces of murine cells was not present after crosslinking of a representative strain of murine leukemia virus.


Detection of an early surface change during oncogenic transformation. Fluorescamine, which can label surface components of cells grown as monolayers in culture, has been used to probe alterations in chicken embryo fibroblasts infected with a temperature-sensitive  mutant of Rous sarcoma virus, Prague A, LA24. The fluorescence of bound fluorescamine on cells at the permissive temperature (35 degrees) was found to be about 1/3 that of cells cultured at the nonpermissive temperature (41 degrees). During development of the transformed phenotype, i.e., after transfer of the cells from 41 degrees to 35 degrees, the decrease in surface fluorescence was observed to be an early event occurring within the first  4-8 hr after temperature shift. This alteration took place on a time scale similar to that of changes in 2-deoxyglucose transport and an increased rate of DNA synthesis, but before any major morphological changes. The change was related to cell transformation rather than to growth differences of the cells at the two temperatures. Further, it was found that fluorescamine was not monitoring the loss of LETS glycoprotein from the surface or the loss of any other surface components that could be detected by lactoperoxidase-catalyzed iodination of surface proteins. When fluorescamine-labeled components were resolved by polyacrylamide gel electrophoresis, significant differences were seen between components from cells cultured at 35 degrees compared with those from cells cultured at 41 degrees. Based on these results, possible mechanisms accounting for the fluorescence differences are suggested.


Post-transcriptional suppression of globin gene expression in cells transformed by avian erythroblastosis virus. Cells transformed by avian erythroblastosis virus were grown in vitro for up to 5 months. After a few days in culture, synthesis of hemoglobin was undetectable and could not be induced by dimethyl sulfoxide. As shown by globin cDNA hybridization to nuclear and cytoplasmic RNA carried to Crot values of 10(5) moles of nucleotide per liter X sec, globin genes in these cells are transcribed into pre-mRNA, but no trace of globin mRNA appears in the cytoplasm. The implications of this observation for schemes of post-transcriptional regulations and viral transformation are discussed.


Control of microtubule assembly-disassembly by calcium-dependent regulator protein. The Ca2+-dependent regulator (CDR) protein of cyclic nucleotide phosphodiesterase is a low molecular weight, acidic, Ca2+-binding protein which has been implicated in a number of Ca2+-dependent enzymatic functions. Indirect immunofluorescence has revealed that CDR is specifically associated with the chromosome-to-pole region of the mitotic apparatus during metaphase-anaphase in a pattern distinctly different from that of similar cultured cells stained with antitubulin. This characteristic localization in the mitotic half-spindle suggested a role for CDR in the control of microtubule assembly-disassembly during mitosis. Thus, CDR was examined for its effects on microtubule polymerization in vitro. It was determined that stoichiometric concentrations of CDR and a homologous Ca2+-binding protein, skeletal muscle troponin C, both inhibited and reversed microtubule assembly in a Ca2+-dependent manner. CDR-dependent inhibition of in vitro microtubule assembly occurred at physiological Ca2+ concentrations (approximately 10 micron) that, in the absence of CDR, caused only a slight reduction in polymerization. At Ca2+ concentrations in the low physiological range (less than 1 micron), no inhibition was observed. These biochemical results, together with the immunofluorescent localization of CDR in the mitotic half-spindle, provide evidence that Ca2+ is an endogenous regulator of microtubule disassembly through the activity of CDR.


Sodium-stimulated active transport of aminoisobutyric acid by reconstituted vesicles from partially purified plasma membranes of mouse fibroblasts transformed by simian virus 40. Plasma membrane fractions isolated from mouse fibroblast BALB/c 3T3 cells transformed by simian virus 40 were partially purified by treatment with dimethylmaleic anhydride followed by extraction with 2% cholate. The extracted proteins were combined with exogenous phospholipids and eluted through a Sephadex G50 column. Reconstituted vesicles thus obtained were shown to possess the ability of Na+-stimulated transport of alpha-aminoisobutyric acid. The simultaneous addition of NaSCN and alpha-aminoisobutyric acid to these vesicles produced a transient accumulation above the equilibrium level (overshoot, active transport). The Na+-stimulated transport of alpha-aminoisobutyric acid was sensitive to the accompanying anion and to the temperature of incubation. The results demonstrate that partially purified membrane proteins of mouse fibroblast cells can be incorporated into the liposomes that have the characteristics of Na+-stimulated and electrochemically sensitive active transport of alpha-aminoisobutyric acid.


Molecular genetics of herpes simplex virus: demonstration of regions of obligatory and nonobligatory identity within diploid regions of the genome by sequence replacement and insertion. The DNAs of herpes simplex virus (HSV) 1 and 2 consist of two components, L and S, each composed of unique sequences bracketed by inverted repeats. In this study we have probed the structure of the reiterated regions of the S component in marker rescue experiments involving transfection of cells with mixtures of intact HSV-1 mutant viral DNA and individual DNA fragments generated by restriction endonuclease digestion of wild-type HSV-1 or HSV-2 DNAs. The results were as follows: (i) HSV is diploid for the wild-type sequences that rescue two temperature-sensitive (ts) mutants. DNA fragments from both reiterated regions of the S component of HSV-1(F) DNA can rescue tsLB2 and tsD mutants. (ii) Identity of the entire reiterated sequence at both ends of S is not obligatory because only one end of the S component of wild phenotype virus HSV-1(1061) rescues tsD even though both ends rescue tsLB2. (iii) Genes in both reiterated sequences can be expressed. We produced, by marker rescue experiments, recombinants with heterotypic ends of the S component, and these specified corresponding polypeptides characteristic of both HSV-1 and HSV-2. (iv) The reiterated sequences of the S component may contain a region of obligatory identity. Thus, several recombinant clones produced by rescue with HSV-2 DNA contained identical HSV-2 DNA insertions within both reiterated regions of the HSV-1 S component. Consistent with this conclusion, the termini of the S component in the heterodiploids described in iii were identical by restriction enzyme analysis. (v) The observation that HSV DNA can be expanded by at least 5 x 10(6) by means of insertion in the S component suggests that it can be a vehicle for exogenous DNA.


Abelson antigen: a viral tumor antigen that is also a differentiation antigen of BALB/c mice. We report here the serologic detection of a cell surface antigen common to cells transformed by the Abelson murine leukemia virus (A-MuLV) and to normal hematopoietic cells from certain strains of mice. Serum from C57BL/6 mice hyperimmunized with syngeneic A-MuLV lymphoma cells was cytotoxic for the immunizing cells; this reaction was used as the serologic test system for recognition of A-MuLV antigens. Absorption analysis using 40 tumors and 21 cell lines revealed that two serologic specificities were detected by this test system: (i) FMR antigen(s) related to the Moloney MuLV helper (the virus from which A-MuLV was originally derived), and (ii) an antigen expressed on all cells transformed by A-MuLV. The A-MuLV-specific antigen was also present on uninfected cells from BALB/c bone marrow, spleen, and fetal liver but not from adult liver, thymus, lymph nodes, or peripheral blood. Abelson antigen was not expressed on bone marrow or spleen cells of 12 other mouse strains. In light of the original isolation of A-MuLV from a BALB/c mouse infected with Moloney virus, it is possible that Abelson antigen is a serologic marker for a gene of BALB/c mice, normally encoding a cell surface molecule, that was incorporated into the Moloney virus genome during the generation of A-MuLV.


Cells nonproductively transformed by Abelson murine leukemia virus express a high molecular weight polyprotein containing structural and nonstructural components. Cell clones nonproductively transformed by the replication-defective Abelson strain of murine leukemia virus (AbLV) were analyzed for type C viral antigen expression by competition immunoassay. AbLV-transformed mink non-producer lines were found to express a 110,000- to 130,000-molecular weight polyprotein containing murine leukemia virus gag proteins p15 and p12 covalently linked to nonstructural AbLV-coded component(s) of around 80,000-100,000 molecular weight. This polyprotein lacked detectable antigenic cross-reactivity with other virion-coded gag gene proteins such as p30, p10, the viral reverse transcriptase (RNA-dependent DNA polymerase), or the major viral envelope glycoprotein, gp70. By analogy to earlier data on feline and avian sarcoma viruses, these results suggest that a portion of this polyprotein might represent the AbLV src gene product and that in translation it is initially linked in precursor form to gag structural proteins. Superinfection of mink cells nonproductively transformed by AbLV--with either a wild mouse amphotropic type C virus isolate, 4070-A, or with the endogenous cat virus, RD114--led to production of pseudotype virus containing high concentrations of the AbLV-coded precursor polyprotein.


Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line. Receptors for calcitonin, as assayed by the specific binding of 125I-labeled salmon calcitonin and stimulation of cyclic AMP formation, were found in 8866 cells derived from a human lymphoid line. The affinity of calcitonin from different species and of various analogues of human calcitonin for the binding sites and their ability to stimulate cyclic AMP formation were closely related to their hypocalcemic activity and presumably reflected biological properties of the hormones. Besides calcitonin, prostaglandin E1 and beta-adrenergic catecholamines stimulated cyclic AMP formation in these cells. The calcium ionophores, A23187 and Br-X-573A, did not influence the specific binding of 125I-labeled salmon calcitonin. A23187, however, suppressed basal and calcitonin-stimulated formation of cyclic AMP in the presence of at least 0.6 mM calcium in the incubation medium. Br-X-537A did not require extracellular calcium to suppress basal and calcitonin-stimulated formation of cyclic AMP, suggesting that the release of calcium from internal stores may regulate adenylyate cyclase activity in 8866 cells.


Growth factors from murine sarcoma virus-transformed cells. Murine sarcoma virus-transformed mouse fibroblasts produce polypeptide growth factors and release them into serum-free medium. These factors stimulate cells to divide in monolayer cultures and also to form colonies that grow progressively soft agar. Three major peaks of activity are seen, with apparent molecular weights of 25,000, 12,000, and 7000. The sarcoma growth factors are heat-stable, trypsin-sensitive, and active in nanogram quantities when tested for growth stimulation of untransformed rat and mouse fibroblasts. All three molecular species are also capable of competing for membrane epidermal growth factor (EGF) receptors when tested with 125I-labeled EGF. They differ from mouse EGF, however, in their molecular weights, in their inability to react with anti-EGF antibodies, and in their ability to convert cells to anchorage independent (agar) growth. For the above reasons, we conclude that the sarcoma growth factors are a new class of polypeptide tropic factors that confer on fibroblasts in vitro properties associated with the transformed phenotype.


Ontogeny of synaptic phosphoproteins in brain. The ontogeny of two endogenous substrates for cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) has been studied in rat and guinea pig cerebrum. These endogenous substrates, referred to as proteins Ia and Ib, have been shown in other studies to be specific to nervous tissue and to be enriched in the synaptic membrane and synaptic vesicle fractions of adult brain. In the present study, proteins Ia and Ib were shown to increase markedly during the time of major synaptogenesis in rat cerebrum and guinea pig cerebrum, in which the morphological development of synapses is predominantly postnatal and prenatal, respectively. Similar results were obtained either by measuring endogenous phosphorylation of proteins Ia and Ib in the synaptic membrane fraction or by measuring phosphorylation of extracted proteins Ia and Ib with added protein kinase.


A Drosophila mutant with a temperature-sensitive block in nerve conduction. A mutant, napts (no action potential, temperature-sensitive), is described in which axonal conduction fails at high temperature. Synaptic transmission at the larval neuromuscular junction is unimpaired. Larvae and adults are rapidly paralyzed at restrictive temperatures; they recover rapidly when the temperature is decreased. The mutant gene is recessive and is located on the second chromosome at map position 56.


Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats. The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin II formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.


Effects of the acute administration of ethanol on the sleep of the rat: a dose-response study. Seven-hr sleep recordings were performed on rats following intraperitoneal injection of saline or one of four doses of ethanol (1.1, 1.5, 2.0 or 2.5 g/kg). Total minutes of REM sleep and percentage REM sleep were decreased in a dose-dependent manner. Percentage nonREM sleep increased with progressively higher doses. The decrease in REM sleep appeared to be related to a decrease in the number of REM sleep episodes and an increase in the length of the REM-nonREM cycle. Other variables such as mean length of REM sleep episodes and REM sleep efficiency were unchanged. An analysis of the first and second 3.5 hr of the recording showed that ethanol continued to have marked effects on REM and nonREM sleep during the second 3.5 hr, when blood levels were declining. Ethanol produced decreases in sleep latency, but total sleep time was unchanged.


Foreign-body reaction to silicone gel in axillary lymph nodes after an augmentation mammaplasty. A radical mastectomy was performed for a breast adenocarcinoma occurring 10 years after a subpectoral augmentation mammaplasty with silicone gel-filled prostheses. A foreign-body reaction to silicone was seen in two of the axillary lymph nodes resected.


Proteoglycans and collagenase in hypertrophic scar formation. The collagen fibers of the nodules and whorl-like figures in hypertrophic scars are "coated" with proteoglycans, mainly chondroitin-4-sulfate. The latter was shown to prevent collagenase from breaking down collagen. This suggests that the presence of great amounts of chondroitin-4-sulfate in hypertrophic scars may contribute to the overabundance of collagen deposition which is characteristic of this abnormal healing process.


Ultrastructural changes in the placenta of the ewe after fetal pituitary stalk section. Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.


Computed transaxial imaging using single gamma emitters. Emission computed tomography (ECT) studies were performed on test objects and dogs. Conjugate views were obtained for 60 to 120 projections equispaced around 360 degrees by rotation of the subjects in front of a gamma camera. A convolution reconstruction algorithm in which gamma ray attenuation corrections are included in the backprojection step were used to reconstruct the emission images. Reconstructions of x-ray transmission data provided data for gamma ray attenuation corrections of the emission images of 99mTc-pyrophosphate uptake in dogs. Reconstructed images of test objects show spatial resolution uniformity, and attenuation corrections enable estimation of relative activity densities to within 10--15% rms errors, thus demonstrating quantitative imaging capabilities of emission CT.


[Postnatal development of the epithelium of the small intestine of guinea-pigs (author's transl)]. This investigation deals with the histochemical, biochemical and electron microscopical development of the postnatal epithelium in the small intestine of guinea-pigs. Immediately after birth the enterocytes of the whole small intestine are rich in glycogen. Within 48 hours the glycogen in broken down by intralysosomal digestion and glycogenolysis or disappears from the villus epithelium by extrusion of the absorptive cells. The first loss of glycogen occurs in the jejunum; at the latest it leaves the lining epithelium of the ileum so that a proxoim-distal gradient exists. Afterwards for maximal 14 days fat ist taken up from the mother's milk only by the enterocytes of the jejunum without any signs of endocytosis; the bigger part of the fat leaves the cells by exocytosis and enters the intercellular space. Most of the lipid reaches the lymphatics or is absorbed by marcophages; only small amounts are found in the blood capillaries. The number of the enterocytes engaged in the absorption and passage of fat depends on its quantity in the lumen of the small intestine. During the first days of life everywhere in the small intestine the ultrastructure of the enterocytes is characterized by 2 types of mitochondria (large and small ones with different internal structure). Furthermore in the ileum the absorptive cells contain more lysosomes and a more extensive inframicrovillous membrane system than in jejunum. The membrane system consists of aggregated tubules, vacuoles and vesicles; they are situated below the microvilli and sometimes communicate with the lumen of the gut. The big mitochondria are broken down in the lysosomes or appear in the lumen of the small bowel following extrusion of the enterocytes. The lysosomes are involved in autophagic (digestion of glycogen and cell organelles) as well as in autophagic processes (hydrolysis of molecules from the mother's milk and foreign food). These substances are probably incorporated by means of the inframicrovillous membrane system. With respect to the microvillous hydrolases (lactase, alpha-D-glucosidases, peptidases, alkaline phosphatase) histochemical and biochemical assays were carried out with the same artificial substrate. The results depend on the method employed and the enzyme investigated. Using histochemical techniques and indolyl, naphthly, naphthol AS or naphthylamine derivatives as substrates the activity of peptidases and alkaline phosphatase correspond to that in adult guinea-pigs already at the time of birth; alpha-D-glucosidases (glucoamylase, saccharaseisomaltase) become mature at the end of the first, and the development of lactase is finished after the second week of life. For the biochemical investigations (fluorometric measurements of naphthol and naphthylamine) of microvillous enzymes with naphthyl and naphthylamine substrates a new technique of homogenisation using freeze-dried cryostate sections is successfully employed...


Effect of lead ingestion on vitamin D3 metabolism in Japanese quail. Immature female Japanese quail were given either lead acetate or sodium acetate in the drinking water for 15 days. In vitro kidney production of 1, 25- and 24-25- dihydroxyvitamin D3 from tritiated 25-hydroxyvitamin D3 was measured. At all 3 dose levels of lead acetate (0.32, 3.2 and 32 mg Pb/ml), in vitro kidney production of 1,25-(OH)2D3 was increased significantly compared to control levels treated with sodium acetate. Lead treatment had no significant effect on plasma calcium and inorganic phosphate levels.


[Neurological disorders and perhexiline maleate therapy. Clinical study of 10 cases. Neuropathological, pharmacocinetic and biochemical studies (author's transl)]. Ten new cases of perhexiline induced peripheral neuropathies are reported. The authors emphasize the possible association of other neurological disorders: cerebellar symptoms in one case, complex tremor in two other cases, marked decrease of photomotor reflexes in one case and disgeusia in another one. The pharmacocinetic study of 4 cases revealed the presence of a low metabolism of the drug in one of them. Polymorphous inclusions have been seen in Schwann cell and endothelial cell cytoplasm in the three patients with electron microscopic study of the nerves. The pathological study of one case showed the demyelination of spinal cord posterior columns. In another case, who died from hepatic coma, the biochemical study of cerebral lipids revealed the low values of cerebrosides and sulfatides in cerebellum and cerebral white matter.


[Change in recurrent inhibition when standing in normal subjects and spastics (author's transl)]. In normal subjects and patients with diseases of the upper motor neurone, recurrent inhibition directed to soleus motoneurones was studied in three different postures: sitting (control situation), standing when leaning backward on a wall, standing independently without the support of a wall. In normal subjects, this recurrent inhibition was not modified when standing with the support of a wall, while it was enhanced when standing without such a support.


["Functional and anatomical organization of associative" cortical areas 7, 21 and 22 in monkeys. A study of the cortical projections from the pulvinar by means of HRP tracing technique (author's transl)]. The thalamic projections to the parietal and temporal associative areas (Brodmann's areas 7, 21 and 22) have been revealed by means of the retrograde axonal transport of horseradish peroxidase (HRP). The medial pulvinar (PM) was found to send afferents to the three studied areas. Labelled neurones of the PM appeared to be grouped in terms of their cortical target; indeed, neurones of origin of projection fibres to areas 7, 21 and 22 were respectively localized in the dorso-lateral, ventro-lateral and ventro-medial part of the PM. Although the multimodal sensory nature of the PM has been demonstrated by electrophysiological works, the function of PM neurones and the significance of their topographical repartition remain unknown. However PM could be involved in the transmission of specific sensory informations to the three associative areas 7, 21 and 22. Such an hypothesis is discussed according to the hitherto available data.


Plasma cholesterol esterification and plasma lipoproteins in bile-duct-ligated dogs. To study the lipoprotein changes in cholestasis while the capacity for plasma cholesterol esterification was normal, the common bile duct was ligated in dogs and plasma investigated 8 h and 48 h later. The plasma concentration of cholesteryl esters was slightly increased, concomitant with a tendency toward an increase in the activity of lecithin:cholesterol acyltransferase (LCAT). The content of cholesteryl esters in the main lipoprotein classes was normal. Marked alteration in the low density lipoproteins (LDL) and the high density lipoproteins (HDL) took place and were essentially similar 8 h and 48 h after bile duct ligation. In LDL, (density 1.006--1.019 g/ml) and LDL2 (density 1.019--1.063 g/ml) an increase in the content of polar lipids was observed, and in LDL2 heterogeneity in particle size was demonstrated by gelfiltration on 2% agarose and by electron microsopcy. Large myelin structures, flattened disc-shaped particles, and particles with the appearance of normal LDL2 were present. HDL isolated after operation was characterized by a decreased protein/lipid ratio and an increased content of phospholipids. By gelfiltration on Sephadex G-200 and by electron microscopy changes in particle size were observed, with the presence of disc-shaped particles with a tendency in form rouleaux. These results demonstrate that marked lipoprotein changes occur as early as 8 h after bile duct-ligation in dogs and indicate that a deficient LCAT mechanism is present in cholestasis even with normal or high plasma LCAT activity.


Upper extremity deformities associated with the orofacial clefts. A material of 89 cases of upper extremity deformities, among the 3225 cleft patients born during the period 1950-75, and treated in the Finnish Red Cross Cleft Centre is presented. About two-thirds of the patients had an isolated cleft palate--half of the male and nearly all of the female patients. The percentage of upper extremity deformities appearing with the different types of the orofacial clefts was, for clefts of the primary palate 2.0: specifically for cleft lip 0.8, cleft lip--palate 2.6, and cleft lip and palate 3.6; and for clefts of the secondary palate 3.5: specifically for cleft palate 3.7, submucous cleft palate 1.6; and for the branchial arch syndrome (lateral cleft) 5.2; the total average being 2.8 percent. About one-third of the patients were dwarfs, most of them diastrophic dwarfs. Syndactyly was somewhat more common among cleft patients, 0.3%, than in the average population. Polydactyly, 0.1% was about as common as the average. Ectrodactyly was more common among cleft patients, 0.4%, than either syndactyly or polydactyly that are considered the most common hand deformities among the general population. The syndactyly cases were more complicated than the average, among them 4 cases of Apert syndrome were noted. About three-fourths of the 89 patients had multiple deformities.


Morphological significance of associated epithelial cords and ductlike structures in certain tumors of the pancreatic islets. The association of epithelial cord cells and ductlike structures in 2 cases of pancreatic islet tumors is presented. The first case was characterized by multiple pancreatic nodes of beta cell insulinoma in a 35-year-old woman. The second case was a Zollinger-Ellison syndrome in a 10-year-old male child with perforated duodenal ulcer due to an islet cell tumor of an aberrant pancreas in the omentrum. Stress is laid upon the striking continuity of the tumorous endocrine and exocrinelike histological formations reproducing the morphological pattern of ducto-insular relationships in histogenesis and islet regeneration.


Silicosis in diatomaceous earth factory workers in Sweden. Kieselguhr is a greyish-white powder which is made by heating lake ooze containing diatom skeletons to a temperature of about 1000 degrees C. It contains quartz, cristobalite and tridymite. Working with kieselguhr can induce silicosis. In Sweden six cases of silicosis caused by exposure to kieselguhr have been reported to the Worker's Protection Board. The time of exposure was relatively short. New cases have not appeared in the last 20 years. It seems, nevertheless, important to document this unusual form of silicosis, as diatomaceous earth is readily available and the manufacturing process is simple. Demand for kieselguhr has increased and new factories are to be established which may result in new cases of silicosis.


Angiotensin-converting enzyme and lysozyme in silicosis and asbestosis. Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source.


[Incidence and specificity of circulating immune complexes in infectious mononucleosis (proceedings)]. Occurrence of immune complexes in infectious mononucleosis has been investigated by the 125I Clq binding assay. Increased serum Clq-binding activity was found in 87% of the 23 patients studied during the acute stage of the disease. The serum Clq-binding material detected has properties identical to those of immune complexes. IgG antibodies dissociated from the complexes at acid pH and F (ab)'2 fragments obtained after treatment by pepsin appeared to be directed against the viral capsid antigen of Epstein-Barr virus.


[Induction of glucocorticoid hormone receptors in continuous human T-lymphocyte cultures (proceedings)]. The presence is documented of high levels of specific glucocorticoid hormone receptors in human cultured T cells (CTC) maintained with a conditioned medium. When conditioned medium was removed from CTC for 24 h, receptor levels reverted to those of fresh, unstimulated lymphocytes. When conditioned medium, or phytohemagglutinin, was then added at various times before testing for glucocorticoid receptors, these stimuli were shown gradually to induce more receptor activity, beginning at about 10 h of stimulation and increasing to 10-fold through 24 h.


Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus). Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.


Vitamin D3-induced calcium binding protein in bone tissue. As detected by radioimmunoassay with antiserums against chick intestinal calcium binding protein (CaBP), administration of vitamin D3 to rachitic chicks causes a 25- to 100-fold increase in immunoreactive CaBP in chick bone. The bone CaBP has a higher molecular weight (approximately 34,000 daltons) than intestinal CaBP (28,000 daltons), is concentrated principally in the spongiosa and cartilage plate regions of tibia, and responds adaptively to reflect the level of dietary calcium.


beta-Endorphin is not detectable in plasma from normal human subjects. beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects.


Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. Capillary endothelial cells isolated from rat brain exhibit Na+-dependent uptake of the neutral amino acid analog alpha-(methylamino)isobutyric acid. Since studies in vivo demonstrate that this transport system is not present on the blood side of brain capillaries we conclude that Na+-dependent neutral amino acid transport is located on the brain side. Therefore, the luminal plasma membrane and the antiluminal plasma membrane appear to be functionally distinct. This polarity should permit brain capillary endothelial cells to actively regulate the internal milieu of the brain.


Alkaline phosphatase in Epstein-Barr viral nuclear antigen--positive cell lines. The production and nature of alkaline phosphatase were studied in Epstein-Barr viral nuclear antigen-positive, surface membrane immunoglobulin negative-cell lines established from two patients, one with acute myeloid leukemia and one with acute lymphoblastic leukemia. The acute myeloid leukemia-derived cells contained myeloid alkaline phosphatase, while the acute lymphoblastic leukemia-derived cells contained lymphoid alkaline phosphatase. The presence of the myeloid-specific enzyme in a surface membrane immunoglobin--negative cell line suggests that the line is composed of myeloid precursor cells and that such cells may be susceptible to infection with Epstein-Barr virus.


Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment. After 3 weeks of twice-daily administration of desipramine to rats, the frequency-response curve for field stimulation of adrenergic neurons in isolated left atrial strips was shifted markedly to the left and the efflux of [3H]norepinephrine was enhanced greatly. After 1 day of treatment, only slight shifts in the frequency-response curve and small increases in [3H]norepinephrine efflux occurred although inhibition of [3H]norepinephrine uptake was already maximal, and phenoxybenzamine caused a further shift to the left in the frequency-response curve similar to that which occurred after 3 weeks of desipramine treatment alone. A gradual decrease in the sensitivity of the presynaptic alpha receptor would explain the delay in the onset of the linical effect of the tricyclic antidepressants.


[Anti hepatitis A antibodies in the French population and in polyvalent plasma immunoglobulins at a transfusion center (Gamma TS)]. A search for antibodies directed specifically against hepatitis virus A was carried out in 600 blood donors in the Paris region (354 men and 246 women) by a radio-immunological technic in solid phase. 75.3% had a positive test, no difference was found as regards sex on country of origin (57 were not French). An increase in the frequency of carriers of anti-HAV carriers was observed in relation to age, for 48.4% were aged between 18 and 24 years and 85.9% had antibodies after age 40 years. An estimation of anti-HAV antibodies was made on 19 lots of immunoglobulins from French transfusion centers by the same technic. High and homogenous levels were observed (average 1/4 270). These data were discussed and compared with those in the literature. A better prophylaxis of hepatitis A and the determination of specific activity of polyvalent immunoglobulins with regard to this virus is then considered.


[Hypercalcemia and biologically active parathyroid hormone]. Hypercalcaemia always results in serious clinical sequalae and, if not treated, carries a most unfavourable prognosis. The clinician will gain major diagnostic help from an evaluation of the calcitonin and parathyroid hormone blood levels. With regard to parathyroid hormone we have developed, for the first time, a radioimmunoassay which is specific for the estimation of biologically active hormone in the circulation. We are dealing here with an unusual radioimmunological situation as the immunochemical sites are generally quite distinct from those associated with hormonal activity. We are presenting in this first paper the normal values and also the variations that occur in different types of hypercalcaemia. The comparison of these results with those obtained by the usual methods of estimation for parathyroid hormone assay lacking in biological activity shows the value of this new technique.


[Routine biopsy of the liver during tuberculosis in the African adult. 129 cases at Dakar]. The routine use of needle biopsy of the liver in 129 African patients, aged over 15 years and suffering from various varieties of tuberculosis, gave the following results : specific lesions, above all during miliary tuberculosis, 25,6%, non-specific lesions alone, 37,2% ; normal parenchyma : 37,2%. These result were comparable with those obtained in Europe, in two similar studies, carried only by Coury and al. on pulmonary tuberculosis patients only, an by Morère et al. concerning all forms of tubercuosis. Steatosis without any alcoholic explanation, was observed in 24% of cases. Bacteriological research, even on a culture of liver tissue, was usually disapponting; only one positive result for 34 cultures. This possible spread of tuberculous infection at all stages of its course is still difficult to explain. It leads one to distinguish secondary liver infestations which suggest another localisation of the disease, from liver tuberculosis observed in clinically primary forms.


[The interaction between drugs and oral anticoagulants of the coumarin group]. The problem of drug interactions during prolonged use of coumarin anticoagulants is important for most patients receiving anticoagulants take several other drugs. Frequent interaction causes either potentialisation of the anticoagulant effect with risk of hemorrhage or inhibition of the anticoagulant effect with risk of thrombosis. The various mechanisms which may explain most interactions are reviewed and the authors propose a list of drugs which should not be administered with coumarin.


[Opportunistic microbial infections and their importance in general pathology]. Opportunist germs are commensal bacteria or fungi of the skin and mucosae or saprophytes of the external media, which become virulent when general or local resistance of the organism is lowered. Under the influence of favouring factors, mainly certain drugs, infections due to opportunist germs are becoming more and more frequent, mainly in hospitals, constant or occasional contact of man with these bacteria make diagnosis and prophylaxis of their infections difficult.


[Therapeutic use of tiapride in movement disorders]. Tiapridal was given to twenty-four patients suffering from dyskinesias. Therapeutic efficacity seems to the etiology. Not any fonctitonal improvement was observed in parkinsonism with dyskinesia consecutive to Dopa therapy. On the other hand a good efficacity was found in the treatment of choreas with a quite good tolerance; the functional result will depend of the evolutive state of the disease.


[Paget's disease, ankylosing vertebral hyperostosis and hyperostosis frontalis interna]. Ankylosing vertebral hyperostosis and internal frontal hyperostosis have a frequency of 5% and 8% respectively. In Paget's disease, these two disorders are found with a frequency of 40% and 19.1% respectively. This frequency is not due to chance. There exists a link between the 3 diseases. Ankylosing vertebral hyperostosis is thusa new pathological association in Paget's disease. It is even the most frequent of these associations. It seems Paget's disease induces hyperostosis and not the contrary. The authors suggest the theory that cortical and periostal hypervascularisation in pagetoid bone favour the development of these hyperostoses.


[Treatment of acute peptic ulcer. Present concept]. Cimetidine, a powerful inhibitor of acid secretion has produced profound changes in the treatment of acute peptic ulcer. The authors propose a therapeutic attitude takeing into consideration modern knowledge concerning the ulcer patient and his ulcer. After a simplified diagram of the inhibitory mechanisms of acid secretion illustrating the role of the histamine receptors, the various pathogenic routes of treatment are considered with their indications (cimetidine, sulpiride, vagolytics, carbenoxolone). The association of an antacid is useful, except for cimetidine. A choice is necessary in all cases which takes into consideration the patient's interests and the cost of treatment and permits one to avoid pleonasms and illogical treatment. Finally, classical treatment and even milk diet may remain of interest depending on the context of the case.


[Prolonged fever revealing acquired toxoplasmosis in an adult]. Two cases of acquired toxoplasmosis are reported in 16 and 44 year old patients; prolonged fever was the dominating sign in both cases. It follows from these observations that toxoplasmosis has to be systematically considered as a possible etiology of prolonged fever of undetermined origin.


[Comparative crossover study of tiapride and meprobamate used in agitated states]. A comparative cross over study of the action of tiapride and meprobamate in behaviour problems with motor and verbal agitation was conducted on 42 hospitalized patients. Tiapride was shown to be statistically superior as far as its efficacy on agitation and its tolerance as it did not modified the patient's vigilance.


[Alpha heavy chain disease].

[Alpha heavy chain disease]. Alpha chain disease is a fairly rare disease (less than 80 cases have been diagnosed to date) the diagnosis of which should be considered as a routine in France when a young arab or oriental jew presents with digestive symptoms such as chronic diarrhoea, abdominal pain of abdominal tumour. The diagnosis of the disease requires two examinations 1) serum immunoelectrophoresis with monospecific anti-IgA antiserum, which alone isolates in 100% of cases the paraprotein. 2) Exploratory laparatomy seems advisable in all cases, for it alone permits multiple lymph node and intestinal biopsies whict are necessary to determine the stage of the disease, the prognosis and treatment. 3) Generally speaking, heavy chain disease seems to represent like Burkitt's lymphoma, a model for experimental carcinoma.


[Duality of dopaminergic receptors. Pharmacologic and clinical perspectives]. A univocal disorder of dopaminergic activity in the nerve structures responsible for extra-pyramidal motility does not take into account the total phenomena seen in psychomotor neurological studies. The hypothesis of two categories of dopaminergic receptors-respectively excitatory (DA) and inhibitory (DAi)--in the striatal and mesolimbic structures concerned, was derived from experimental and clinical anatomical cytological, and pharmacological data. This duality of the receptors could establish a relationship between dopaminergic mediating, mechanism and adrenergic mediation for with the existence of a least two types of distinct receptors, alpha and beta, has been demonstrated. The author discusses the physiopathology of neuromotor disorders wuch as Parkinson's disease, chorea, and various types of dyskinesias, in relation to this dual mediation. By separation of dopamine antagonists and agonists in this new context, it should be possible to have a more selective approach, which would be better adapted, therefore, for the treatment of these affections. The study of the effects of a new medication, tiapride, on dyskinesias provoked by levodopa in parkinsonian patients, is a step forwards in this new method exploration in neurology.


[Mononucleosis syndrome and thrombocytopenic purpura in Q fever (Rickettsia burneti)]. Case of a patient with a mononucleosis syndrome and thrombocytopenic purpura during Q Fever. This etiology could lead to a systematic search for a rickettsial cause for such a symptomatology with a negative Paul-Bunnell-Davidson reaction.


[Prescribing tiapridal for headache and other painful conditions]. Tiapridal a new molecule of the benzamide family, raises the pain-threshold level in the mesolimbic system. It has been shown to be effective in 66% of cases of headaches and pain resistant to therapy, and 75% of patients with nausea and vomiting associated with headaches. The average dosage is between 150 and 300 mg or day (1/2 to 1 tablet, 3 times a day). The product is extremely well-tolerated. Somnolence, the most frequent side-effect was noted in 17% of cases. Because of its excellent tolerance it can be prescribed in debilitated patients, alcoholics, and the elderly.


[Acute renal failure and consumption coagulopathy in the puerperium]. Disseminated intravascular coagulation accompanied 18% of cases of acute renal failure during puerperal disorders. We studied in particular 31 cases of disseminated intravascular coagulation with renal failure due to obstetric disorders : 12 post-abortion infections, 3 retentions of a dead foetus, 5 infections, 6 cases of toxemia, 2 retroplacental hemorrhages, two hemorrhages during the third stage, one uremohemolytic syndrome. For diagnosis one relies on the clinical data (bleeding, purpura, shock, hemolysis, visceral involvement) and laboratory data, (coagulation should be supervised throughout the course). The renal lesions are either cortical necrosis, or interstitial nephritis. The analogies with experimental phenomena suggest a human equivalent of the Schwartzmann-Sanarelli syndrome.


[Heat stroke and disseminated intravascular coagulation. Apropos of 2 cases]. Two cases of fatal heat stroke, concerning a 20 year-old soldier and a 44 year-old psychiatric patient, treated with neuroleptics, are reported. The clinical picture, starting suddenly with coma and hyperthermia, was quite identical for both. Secondarily, while hyperthermia decreases  and the conscience improved partially, an hemorrhagic syndrome similar to a consumption coagulopathy, acute renal insufficiency and acute hepatic failure appear. Death occurred after aggravated neurological disorders and respiratory distress. The anatomical lesions spread on all the viscera include tubular nephritis, and hepatic centro-lobular necrosis and an interstitial and alveolar oedema with hemorrhages and hyaline membranes in the lungs.


[Therapeutic trial of tiapride in ENT].

[Therapeutic trial of tiapride in ENT]. Tiapride was studied in 60 patients with ENT affections. The dosage was 1 to 2 ampoules IM a day for 7 to 10 days, followed by a half a tablet 3 to 4 times a day for 2 weeks to 2 months. Results were excellent or good for 16 out of 20 cases of essential headache, 6 out of 6 cases of Barré Liéou's syndrome, 7 out 8 cases of sinus pain, 6 out of 8 cases of Méniè's disease, and 6 out of 6 cases of facial paralysis "a frigore". In 7 cases of post-concussion syndrome, excellent results were observed in all the patients, on headache. Vertigo was reduced in intensity. The effects was moderate or nil on tinnitus and deafness due to Ménières syndrome, as well as in 2 casls of facial neuralgia. Tolorance was excellent as, in these 60 patients, only 2 cases of dry mouth and 1 case of vomiting in a diabetic were reported.


[Postoperative medical icterus].

[Postoperative medical icterus]. The onset of jaundice following a surgical operation sometimes raises difficult problems. It is rarely due to hemolysis, infective hepatitis or decomposated cirrhosis of the liver. One should seek as a routine hepatitis due to halotane. However the most frequent cause is "benign postoperative cholestasis". This variety of jaundice presents in the form of an icterus due to conjugated bilirubine with often a large increase in alkaline phosphatase levels. The ocurse is variable. Almost always due to severe surgical or septic trauma, accompanied by shock and/or anoxia, it raises difficult diagnostic problems. The clinical and physiopathological aspects of benign postoperative cholestasis are recalled. One should remember, above all, that this is not an autonomous clinical entity but the sign of local or general complications which should be sought carefully.


[Study of 13 cases of ostensibly idiopathic male infertility treated successfully by HMG/HCG combination]. Amoung 95 cases of infertility due to oligo-asthenospermia with normal or low FHS, treated by the association HMG/HCG, 13 cases could be considered a success. From this particularly favourable slries, the author attempts to codify the indications of gonadotrophines in male sterilities. He suggests that such an indication, obvious in case of hypogonadotrophic hypogonadism could be expanded to some normoor hypogonadotrophic hypofertilities.


[Obesity, hypertension and their relationship in children and adolescents. An epidemiological study in schools (author's transl)]. In a school population of 532 boys between 10 and 18 years and 287 girls between 10 and 15 years, were drawn up the normal weight height ratios and blood pressures. The frequency of obesity was 6% in both sexes. Girls were more obese than boys. The disease started before the age of 5--6 years. They are frequently familial. A narrow correlation exists between the weight height ratios and blood pressure. The obese patients had in 8 cases a high systolic blood pressure and in 4 cases a high diastolic blood pressure. Half the hypertensive patients were over weight. A strong link between obesity and high blood pressure was also found in the family history. These facts should lead us to treat obesity in children by slimming diets or at least prevent the disease by an appropriate diet. Half the cases of high blood pressure in children and adolescents improved on losing weight.


[The lower urinary tract and pseudo-neoplastic sigmoiditis]. A report is given on the results of 12 radiological explorations of the bladder in 12 patients with pseudo-neoplastic sigmoiditis. In all cases the bladder had an abnormal aspect, in two cases there was a pseudotumor, in two an inflammatory aspect, in four conical attraction of the bladder by the sigmoid. In all 12 cases morphological anomalies of the filled bladder were seen. The ureters were either normal or dilated but without true stenoses. These various aspects may contribute to the differential diagnosis between sigmoiditis and cancer. The differential diagnosis of such vesical lesions is discussed.


[An approach to the psychiatric manifestations of alcoholism]. The authors of this article, confronted with the frequent and common emergencies associated with the "alcoholic's" behavioral changes-whether he be a symptomatic drinker, an episodic excessive drinker, or a chronic alcoholic-tested an original molecule belonging to the group of alkylsulfone-0-anisamides (triaprid) on twenty patients hospitalized in a general medical service. The results were very encouraging, showing an improvement of numerous symptoms,in patrticular, tremors, diverse pain, and aggressiveness. The authors note that daily doses of 300 to 400 mg of the modification were well tolerated.


[Quantitative study of bacterial flora in operating room air]. A comparative study of two air-bacteria counting machines, MK II (Casella, London) and R.B. (Joubert, Lyon) was carried out. Pre-operation air samples from operating rooms were drawn by the two machines working simultaneously. The results from the two machines are similar, however the RB machine is more sensitive of the two machines. Moreover, an old operating room without filtrated air had a significantly higher air bacteria contamination (m = 199 +/- 173 bacteria/m3) than a new one with filtrated air (m = 40 +/- 36 bacteria/m3). Samples from laminar air flow (m = 1,3 +/- 1,5 bacteria/m3) were examined as test studies. Working methods and results of air bacteria counts are studied.


[Note concerning the absence of action of tiapride on ocular pressure]. The effect of tiapride on ocular pressure was evaluated on 24 in-patients divided in to two groups, 12 out of them were suffering from glaucoma, and the other 12 had normal ocular pressure. The dosage was 400 mg daily for 8 days. The ocular pressure was measured two times per day before and during treatment. No significant change in ocular pressure has been observed.


[Familial carpal tunnel syndrome].

[Familial carpal tunnel syndrome]. As the incidence of the carpal tunnel syndrome among family members of patients is not precisely defined in the literature, we described here two new cases. Few authors reporting on patients with the carpal tunnel syndrome refer to the familial occurrence of the disorder. Median nerves were constricted under thickened carpal ligaments. In one case, we looked for amyloidosis in the transverse carpal ligament under electron microscope but we could not find any.


[A case of staphylococcal spondylodiscitis after spinal injury. Post-traumatic spondylodiscitis?]. The authors report the case of a patient who had a D9-D10 staphylococcic spondylodiscitis three month after a fracture of the first lumbar vertebra, which they consider to be posttraumatic despite the fact that it is localised in a different area. They insist on the insufficiency of the literature existing on such cases and on the various pathogenic hypotheses to be applied by the practitionner.


[Cecum perforation, complication of an acute idiopathic dilatation of the colon, or Ogilvie's syndrome. Practical interest of various pathogenic data. Apropos of one case]. The authors report a new case of caecal perforation complicating acute dilatation of the colon without organic obstruction (Ogilvie's syndrome). They recall the two characteristics of this syndrome : abdominal distension due to colonic ileus, without any organic cause, and the constant coexistence of an associated pathological condition (traumatic, post-operative, infective, cardio-vascular, respiratory or neurological). The major complication is caecal perforation, announced by a clinical and radiological preperforative syndrome. The pathogenesis of Ogilvie's syndrome remains mysterious. Two facts are worth attention : the role of the sympathetic nerve in intestinal paralysis and the direct intervention of an extra-intestinal pathological factor in the onset of this syndrome. Hence two therapeutic consequences : the favourable effect of splanchnic infiltrations on intestinal motility, and the parallel course of acute colonic dilatation and the extra-intestinal disease.