Alterations in lung macrophage antimicrobial activity associated with viral pneumonia.

Secondary bacterial infections are a common sequelae of viral pneumonias. To study 2 functions of the phagocytic defenses of the lung, macrophages were obtained by lung lavage from parainfluenza 1 virus-infected and noninfected mice. The phagocytic capacities (binding, ingestion, and killing) of these cells were assessed in vitro against viable Candida krusei. Viral pneumonia resulted in a progressive suppression (through day 7 of the infection) of the ability of macrophages to bind candida to their surfaces by nonimmunological or complement receptors; ingestion and intracellular killing of candida were also decreased. After day 7, all these functions returned and, in fact, cells with enhanced activities were present on day 17. After introduction of virus into the lungs, the lung macrophage population increased significantly between days 3 and 7 of infection. This resulted in an increase in the phagocytic potential of the lung, despite the virus-associated suppression of the phagocytic activity in a portion of the macrophages. However, the ability of the macrophages to kill ingested microorganisms was also reduced, resulting in an overall deficiency in the lung macrophage defenses. It was concluded that viral pneumonia was associated with at least two suppressive effects on the lung macrophage-decreased receptor activity and microbicidal activity-resulting in a deficiency in the lung phagocytic defenses represented by these cells. These effects were maximal 1 week after infection and could account for the increased susceptibility of these lungs to secondary bacterial pneumonias. In contrast, during the period of convalescence, the lung macrophage antimicrobial activities were increased and reflected in enhanced resistance of the lungs to infections.


Pathogenesis of Marek's disease; effect of immunization with inactivated viral and tumor-associated antigens.

Inactivated Marek's disease virus-infected chicken kidney cells and inactivated MSB-1 lymphoblastoid Marek's disease tumor cells were used to immunize chickens as virus- and tumor-associated antigens, respectively. Immune and nonimmune birds were then challenged by exposure to live virulent Marek's disease virus. Both vaccines protected significant numbers of chickens (P less than 0.05) against subsequent tumor development, although viral antigen appeared superior to tumor antigen. After challenge, the early appearance of viral antigen, infected lymphocytes, and degenerative changes in lymphoid organs was inhibited only by the viral antigen vaccine, whereas the early appearance of cells bearing tumor antigen was prevented by both vaccines. These results support the hypothesis that effective immunity in Marek's disease could be directed against either virus replication and spread or events associated with transformation and proliferation of lymphoid cells.


Neuraminidase-dependent hamagglutination of human erythrocytes by human strains of Actinomyces viscosus and Actinomyces naeslundii.

Human A, B, and O erythrocytes (RBC) were agglutinated by many human strains of Actinomyces viscosus and A. naeslundii. At 37 degrees C, these bacterium-mediated hemagglutination reactions required the action of bacterial neuraminidase upon the RBC; however, at 4 degrees C, the requirement for neuraminidase was not as striking. Bacterial cell suspensions which caused hemagglutination at 37 degrees C contained both soluble extracellular and cell-associated neuraminidase activities as shown by enzyme assays using a soluble substrate (i.e., alpha 1-acid glycoprotein). Bacterium-mediated hemagglutination occurred only in the presence of soluble neuraminidase activity, and the rate of hemagglutination could be inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a competitive inhibitor of purified soluble neuraminidase from A. viscosus T14V. Suspensions of bacteria which contained only cell-associated neuraminidase activity were unable to initiate hemagglutination, but they caused immediate hemagglutination when mixed with neuraminidase-treated RBC. All hemagglutination reactions were reversible in the presence of 0.02 M lactose and were abolished by heating (85 degrees C for 30 min) the actinomycete cells but not the RBC. The proposed mechanism of hemagglutination involves two sequential steps: (i) the action of neuraminidase to unmask galactose-containing receptors on the RBC and (ii) the multivalent binding of these receptors by many low-affinity lection sites on the bacterial surface.


Resistance of C58 mice to primary systemic herpes simplex virus infection: macrophage dependence and T-cell independence.

The relative contribution of thymus-derived lymphocytes (T-cells) and of macrophages to resistance to primary infection with herpes simplex virus type 1 (HSV-1) was studied in C58 mice. Resistance was dependent on macrophage competence, but was relatively independent of T-lymphocyte competence. Although aging mice became progressively more deficient in functional T-cells, as demonstrated by a decreasing resistance to transplanted line Ib leukemia and by declining responses to T-cell nitogens (concanavalin A and phytohemagglutinin), their resistance to HSV-1 increased with increasing age. Moreover, in mice that were made selectively deficient in T-cells by the combination of adult thymectomy and treatment with anti-thymocyte serum, resistance to HSV-1 did not correlate spleen and mesenteric lymph nodes. However, selective reduction of macrophages by intraperitoneal injection of silica resulted in enhanced susceptibility to HSV-1. Furthermore, in vitro suppression of HSV-1 plaque formation in mouse embryo fibroblast cells was obtained by cocultivation of infected fibroblast monolayers with peritoneal macrophages, but not with splenic lymphocytes, from adult mice. Macrophages from weanling mice failed to suppress the development of plaques, indicating that the increase in resistance to HSV-1 with age is a result of increased macrophage competence.


Infection of cultured human type II pneumonocytes with certain respiratory viruses.

Human type II alveolar pneumonocytes were grown either as monolayers derived from a clone or as organotypic cultures of fetal lung. The type II cells in these cultures retained in their cytoplasm multilamellar bodies which were morphologically identical to similar organelles present in type II cells of intact human fetal and adult lung. A number of respiratory viruses infected the cells and produced a cytopathic effect in the cultures. Viral components were also detected in some of the infected cells. Adenovirus type 3, human coronavirus 229E, and rhinovirus types 2 and 9 produced new infectious virus, but influenza A and parainfluenza 3 virus apparently did not.


Comparison of methods for immunocytochemical detection of rotavirus infections.

Rotavirus infections in intestinal tissues of animals or in tissue culture cells were detected by the immunocytochemical unlabeled soluble enzyme peroxidase antiperoxidase method. Comparison of the immunofluorescence and peroxidase antiperoxidase immunological staining techniques revealed that the two methods are equally sensitive for detection of rotavirus-infected cells. The peroxidase antiperoxidase technique offers the advantages of negligible nonspecific staining reactions, the use of a standard light microscope, the production of permanent slides, and the conservation of immunological reagents. The ability to detect antigens in paraffin-embedded tissues enhances the usefulness of the peroxidase antiperoxidase test for both prospective and retrospective studies.


Appearance of immunoglobulin G Fc receptor in cultured human cells infected with varicella-zoster virus.

After infection with varicella-zoster virus, HeLa and human embryo lung cells developed a receptor for the Fc portion of human and rabbit immunoglobulin G. The receptor was detected by both hemadsorption and immunofluorescence, using antibody-coated erythrocytes and heat-aggregated immunoglobulin G. However, sheep erythrocytes sensitized with F(ab')2 of anti-sheep erythrocyte antibody did not adsorb to the receptor. When cell-free varicella-zoster virus was inoculated into the HeLa cell monolayer, the Fc receptor appeared at first 6 h after infection; varicella-zoster virus antigen in the cytoplasm and detectable cytopathic effects appeared later.


Studies on antibody to hepatitis A virus in children and adults in London.

366 specimens of serum from children and adults without liver disease were screened for antibody to hepatitis A virus (anti-HAV) by means of radioimmunoassay. 56% were born in London, 26% came to London from various parts of the United Kingdom and the remainder (18%) from various parts of the world. The prevalence of antibody was related to increasing age, ranging from 7% in children under ten years of age to 77% in adults aged 50 years or more. The prevalence of anti-HAV was significantly higher in females, in the lower socio-economic class and in those not indigenous to London. In comparison to other urban populations such as those of the United States and Western Europe, the prevalence of anti-HAV was similar in terms of the overall prevalence and age distribution. By contrast, these findings were entirely different from the countries of Eastern Europe and the Middle East where the overall prevalence was higher but the anti-HAV was equal in all ages. Thus, the findings presented indicate that hepatitis A virus infection is common in London and also shows a clear relationship to advancing age, lower socioeconomic class and the country of origin.


A comparative trial of pivmecillinam and ampicillin in bacteriuria of pregnancy.

A comparative trial of pivmecillinam and ampicillin was performed on 100 women with bacteriuria of pregnancy. They received either 400 mg pivmecillinam four times daily or 500 mg ampicillin four times daily for seven days. Cure rates at two weeks were 88% in the pivmecillinam group and 85% in the ampicillin group. At six weeks the respective rates were 76% and 64%. Failure of therapy was not associated with the appearance of bacterial resistance in either treatment group. Side-effects, particularly vomiting and premature cessation of therapy, were significantly more frequent in the pivmecillinam group. No significant effects on liver function were found. In subsequent patients treated in a non-comparative manner with 200 mg pivmecillinam three times daily, the incidence of side effects was markedly reduced with no loss of efficacy.


Propagation of human hepatitis A virus in a hepatoma cell line.

Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage.


A spin-label study of the effect of gamma radiation on erythrocyte membrane. Influence of lipid peroxidation on membrane structure.

Gamma-irradiation of bovine erythrocyte membranes (0.1-4 Mrad) resulted in a decrease in the degree of order of membrane lipids, as measured by spin-labelled fatty acid esters, at the depth of C12 but not at the depth of C5. Dose dependence of this phenomenon corresponded to dose dependence of malondialdehyde formation in the membranes. On this basis a mechanism for the effect of lipid peroxidation on the membrance structure is proposed. Membrane proteins underwent radiation-induced conformational transitions revealed by maleimide spin label which could be also connected with lipid peroxidation.


Stability-indicating assay for mecillinam using high-pressure liquid chromatography.

A high-pressure liquid chromatographic method has been developed for use as a stability-indicating assay for mecillinam. Seven related compounds and at least one unknown degradation product are well separated and easily determined. The accuracy of the method is in good agreement with the published UV assay and the precision of a series of seven replicate determinations is +/- 1.0% R.S.D.


Urine analysis of platinum species derived from cis-dichlorodiammineplatinum(II) by high-performance liquid chromatography following derivatization with sodium diethyldithiocarbamate.

A clinically useful method is described for the quantitative analysis of platinum species derived from cis-dichlorodiammineplatinum(II) in urine. The drug and its biodegradation products are derivatized directly in urine by reaction with sodium diethyldithiocarbamate (DDTC) to form a common product, a 2:1 DDTC-platinum adduct. This complex is stable and can be quantitatively extracted into 0.1 volumes of chloroform. An aliquot of the chloroform layer is then subjected to high-performance liquid chromatography on a muBondapak CN column and the eluent monitored spectrophotometrically at 254 nm. At this wavelength the DDTC-platinum adduct has a molar absorptivity of 43,000, and platinum levels of 25 ng/ml or urine can be detected with a precision of +/- 2.5% and an accuracy of +/- 4%.


Combined high-performance liquid chromatography and radioimmunoassay method for the analysis of delta 9-tetrahydrocannabinol metabolites in human urine.

A high-performance liquid chromatography-radioimmunoassay method for the measurement of cannabinoids in urine is described. The method involves chromatographing a hydrolysed urine sample with high-performance liquid chromatography and quantifying the eluting cross-reacting cannabinoids with radioimmunoassay. It has been applied to the analysis of cannabinoids in human urine obtained from subjects who had smoked delta 9-tetrahydrocannabinol and the identities of some of the cross-reacting cannabinoids have been established by gas chromatography-mass spectrometry. The method is suitable for use as a routine procedure for cannabinoid analysis in urine.


[Variability of the relay neurons in the corpus geniculatum laterale, pars dorsalis in the albino rat].

38 Golgi-impregnated relay cells from the Wistar rat's dLGN were investigated considering their possible differentiation into 2 types using camera lucida drawings with a magnification of 800. The following criteria were taken into account: 1. size of neurons (perikarya, size of dendritic domains) 2. structure of dendrites (number of dendrites, branching points, distribution of dendritic density in relation to the perikaryon, surface structures of dendrites). It was tried to correlate the investigated parameters quantitatively and qualitatively. The results showed that inspite of a missing clear subdivision into 2 types there exists a trend towards developing a second type of relay cells.


[Nuclear spheroids in neurons of the human hypothalamus].

Morphological structure, distribution and frequency of the so-called "nuclear spheroids" have been studied in the human hypothalamus. The following results were obtained: 1. By light microscopy, the nuclear spheroids turned out to be small or large spheroid bodies inside the nucleus. They are almost homogeneous, rarely granular, vacuolar or reticular and occasionally they are multiple. They are best stained with the cresyl-violet technique. They do not exhibit any histochemical pecularities. Aside from typical nuclear spheroids, irregularly shaped nuclei were frequently seen, associated with increased nuclear folds, transitional stages between nuclear folds and nuclear spheroids were also present. Certain microscopic features suggest invagination and displacement of nuclear membrane and cytoplasm into the karyoplasma. 2. By electron microscopy, the nuclear spheroids consist of nuclear membranes and cytoplasmic constituents. They, therefore, actually represent cytoplasm protruding into the cell nucleus. 3. The nuclear spheroids occur almost regularly and most frequently in the ventromedial field of the tuber cinereum, foremost in the infundibular (= arcuate) nucleus. They numerically increase during life. They are rarely found in the ventromedial nucleus but do occur in most of the adults. In the paraventricular nucleus, the supraoptic nucleus, the lateral nuclei tuberis, and in lateral hypothalamic nucleus, they are found by far less often. They scarcely develop in the preoptic area, in the dorsal field, in the tubero-mamillar complex, in the parafornical nuclear groups, in the premamillary nucleus and in the mamillary nuclei. 4. Within the infundibular (= arcuate) nucleus, the nuclear spheroids are particularly numerous in the basal and basolateral regions, whose neurons, under certain functional conditions--such as the Sheedan syndrome, in the menopause and in association with pituitary neoplasms-, appear hypertrophic. Within the hypertrophic neurons of this region, which we designate the subventricular part of the infundibular nucleus, nuclear spheroids are definitely more frequent, and they are of the large type. 5. A separation of the subventricular part based on the distributional pattern of the nuclear spheroids indicates a pathological karyoarchitectonics which supplements the normal karyoarchitectonics (Bachmann, 1948). 6. The nuclear spheroids seem to be associated with increased neuronal activities, for their frequently strongly correlates with the neuronal hypertrophy which expresses enhanced neuroendocrinological activity.


Biological standards for energy dispersive x-ray analysis.

Biological standards containing known concentrations of crystalline silica were prepared for x-ray energy spectrometry (XES) using homogenized tissue and gelatin. Sections of 7 micrometer thickness were cut, air dried, carbon coated, and analyzed by XES. All sections containing crystalline silica generated x-ray counts on a linear relationship with increasing concentrations of silica in the standards. However, tissue sections containing identical concentrations of silica generated x-ray counts approximately 50 percent lower than gelatin sections. Gelatin sections showed considerable shrinkage during drying which may have influenced x-ray generation. The combined effects of elements present in the biological system and high density of tissues also may have contributed to the lower XES counts. These results stress the importance of using standards identical to specimens undergoing XES analysis.


Effects of pesticides on 3H-dihydrotestosterone binding to cytosol proteins from various tissues of the mouse.

These in vitro studies, utilizing cytosols prepared from various tissues (viz. anterior prostate gland, seminal vesicle, kidney and liver) taken from mice 3 days post-castration, were undertaken in order to determine whether or not certain pesticides could alter the binding of 3H-DHT to cytosolic androgen binding components. Estrone, cyproterone acetate, and unlabeled DHT were employed to confirm the presence of specific 3H-DHT binding components in the cytosols. The effects of various pesticides on 3H-DHT binding in these tissue cytosols were then assessed. Parathion (10(-8)--10(-5) M) was found to be an effective inhibitor of total 3H-DHT binding in the prostate, seminal veiscle, kidney and liver. This organophosphate was unable to compete with 3H-DHT for cytosol binding sites in the intestine. Similar in vitro binding studies using dieldrin, DDT, or carbaryl failed to reveal any interference with 3H-DHT binding in any of the tissue studied. The mechanism of parathion's interference with 3H-DHT binding is unclear.


Clinical aspects of gut enzymology.

Enzymological alterations in functional disturbances and in diseases of the intestine are reviewed. Examples are given for diagnostic significance (e.g. in Hirschsprung's and Crohn's diseases), for pathogenetic considerations (e.g. in hypolactasia and in celiac disease), and for secondary involvement of the liver (e.g. in intestinal tumors and after bypass surgery) and are discussed in more detail.


Modulation of transmission at a glutamate synapse.

The amino acid L-aspartate markedly potentiates the responses elicited by L-glutamate at excitatory neuromuscular synapses in lobster walking limbs. Results are consistent with the idea that aspartate increases the affinity between glutamate and its binding sites in the postsynaptic receptor. Although complications due to release from other amino acid sources are a serious qualification, studies of neurally induced release of glutamate and aspartate suggest that both amino acids are released from excitatory nerve terminals. Experiments comparing the potentiating action of a variety of amino acids with their ability to inhibit glutamate uptake are not supportive of the notion that inhibition of agonist removal is the primary mode of action in the potentiation process. However, this idea, as well as the suggestion that aspartate may induce release of glutamate from extrajunctional entrapment sites, are not ruled out. Indeed, it is likely that the modulatory process embodies a multiplicity of reactions with given ones dominating from preparation to preparation.


Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system.

At least two different types of excitatory amino acid receptors have been identified in the mammalian and amphibian central nervous systems. One type ('NMDA receptors') appears to be important in amino acid-mediated synaptic excitation, NMDA being the most potent and specific exogenous agonist for this type of receptor. Many antagonists have selective blocking actions at these NMDA receptors, and such substances are also selective antagonists of synaptic excitation in the vertebrate spinal cord. It is proposed that these receptors are transmitter receptors activated by an excitatory amino acid. In addition, extrasynaptic receptors, activated by domoate, kainate, quisqualate and L-glutamate, but not by NMDA, and only weakly by L-aspartate, have been identified on dorsal root fibres of the immature rat.


High-affinity binding processes for GABA, glycine, and beta-alanine in synaptosome-enriched fractions of rats CNS.

A bicuculline-sensitive component of the binding of GABA and strychnine-sensitive components of the binding of glycine and beta alanine to synaptosome-enriched fractions of rat CNS have been demonstrated in the presence of physiological concentrations of Na+ and other inorganic ions. These processes might be related to synaptic receptors for these inhibitory amino-acids.


The depolarizing responses to GABA in rat sensory ganglia in vivo and in vitro. A study of the role of glial uptake.

Intracellular recordings of neurones in dorsal root ganglia (DRG) have demonstrated that GABA transport into DRG satellite cell does not affect neuronal responses to this amino acid. The experiments were performed with transport-resistant GABA analogues and with inhibition of GABA uptake. GABA response characteristics can thus be considered exclusively neuronal in origin.


Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system.

1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed.


[The monoamines in molluscs. II. Dopamine and neurotransmission. Cardiac dopaminergic innervation in Helix pomatia (author's transl)].

In the molluscs, dopamine is very probably a chemical transmitter at the level of both the central nervous system and certain peripheral structures. The heart of Helix pomatia does not have any intrinsic innervation, but it receives extrinsic innervation from fibres coming from the visceral nerve. Formaldehyde fluorescence histochemistry localizes the cardiac catecholamines in some of these fibres and in their endings. However, dopamine, which dominates, does not seem to be a transmitter involved in cardioregulation in the same way as 5-hydroxytryptamine. The quantities of active dopamine (stimulants) cannot be compared with those required for a neurotransmitter. This is also true for noradrenaline. Dopamine more certainly plays a role at the metabolic and tropic level by acting within a more or less short period as a regulator of cellular activity and contractility. The Helix heart is a suitable model for future research in this field.


[Protein metabolism and sensitivity to tetrodotoxin of cardiomyoblasts cultured in vitro. Influence of insulin (author's transl)].

1. Insulin prevents the decrease in sensitivity to tetrodotoxin in populations of embryonic cardiomyoblasts cultured in vitro. This effect of insulin remains when the hormone is added to the culture medium up to 16 hours after the beginning of the culture. 2. Amino-acid deprivation results in an acceleration of the loss of sensitivity to tetrodotoxin in cultured cardiomyoblasts. Addition of cycloheximide, an inhibitor of protein synthesis, has the same effect. These results suggest that the sensitivity to tetrodotoxin of the cardiac cells depends on aspects of protein metabolism which can be controlled by insulin. 3. Return of the cell population to a culture medium containing amino acids and serum or insulin after 7 hours of culture in an amino acid free medium induces a striking increase in the percentage of cardiac cells sensitive to tetrodotoxin. This sensitivity to the inhibitor of the fast sodium carrying mechanism appears to be an element of the pleiotypic response of the cells in culture to serum or to insulin.


[Comparison of the effects of analgesia-producing peripheral and central stimulations in cats. Effect of nalorphine (author's transl)].

The effects of weak intensity percutaneous peripheral stimulations (SPPc) on the transmission of nociceptive messages induced by stimulation of the dental pulp have been studied on anaesthetized cats. 1. The jaw opening reflex (ROG) and the evoked potentials in the thalamic center median (CM), by stimulation of the dental pulp, disappear after a mean of 30 min after the start of SPPc. 2. These effects are analogous to those obtained by stimulation of the periaqueductal gray matter (St.GC) or by I.V. morphine injection. 3. The I.V. injection of the morphine antagonist (Nalorphine) blocks both the effects of the SPPc and those of the St.GC. 4. The authors put forth the hypothesis of a common mechanism of action of the SPPc and the St.GC which, through the liberation of endogenous morphinomimetic substances, would activate descending inhibitor impulses.


Effects of cortisone on mechanical activity and membrane ionic currents in frog auricular fibres.

The influence of cortisone on the mechanical and electrical activity of frog auricular fibres was investigated under voltage clamp conditions. 1. Cortisone exerted in vitro an inotropic action depending on concentration; a maximal positive inotropic effect was observed with 2 x 10(-4) g/ml of cortisone. 2. The positive inotropic effect of cortisone might be either an indirect sympathomimetic effect or an adrenaline-like effect. 3. The positive inotropic action of cortisone was correlated with modifications of the cardiac action potential: the amplitude of the action potential was enhanced while the resting membrane potential was unchanged; the amplitude and duration of the plateau were increased and the duration of the action potential was lengthened. 4. The electrical changes were related to an increase in the slow calcium current intensity resulting from an increase in the slow calcium conductance.


[Collagenase inhibition: an experiment in the treatment of scleromalacia perforans (author's transl)].

Report on local application of Cystin eye drops in a case of scleromalacia perforans. This medication brought the necrotizing disease process to a standstill. There was even discrete neoformation of scleral tissue, which we attribute to the collagenase inhibiting action of this drug.


[Corneal deposits in children on dialysis and treatment with vitamin D3 and 1,25 DHCC (author's transl)].

The corneas of 15 children on intermittent long-term dialysis for renal failure were studied, first during a period of treatment with high doses of vitamin D3 and subsequently during a study with the vitamin D metabolite 1,25 DHCC. Metastatic calcification of the limbus or increased limbic deposits only occurred during the second treatment phase, with vitamin 1,25 DHCC. In 5 of these children phases with plasma calcium levels were recorded which were closely related to the times when corneal changes occurred. In 3 children phosphate values were also increased. Only one child presented with normal calcium values and merely an increase in phosphate concentration. Regression of corneal deposits following normalization of calcium metabolism seems possible in the light of observations so far.


Role of the microfibrillar system in knob action of transformed cells.

Transformed cells often display knobs (or blebs) distributed over their surface throughout most of interphase. Scanning electron microscopy (SEM) and time-lapse cinematography on CHO-K1 cells reveal roughly spherical knobs of 0.5-4 micron in diameter distributed densely around the cell periphery but sparsely over the central, nuclear hillock and oscillating in and out of the membrane with a period of 15-60 sec. Cyclic AMP derivatives cause the phenomenon of reverse transformation, in which the cell is converted to a fibroblastic morphology with disappearance of the knobs. A model was proposed attributing knob formation to the disorganization of the jointly operating microtubular and microfilamentous structure of the normal fibroblast. Evidence for this model includes the following: 1) Either colcemid or cytochalasin B (CB) prevents the knob disappearance normally produced by cAMP, and can elicit similar knobs from smooth-surfaced cells; 2) knob removal by cAMP is specific, with little effect on microvilli and lamellipodia; 3) immunofluorescence with antiactin sera reveals condensed, amorphous masses directly beneath the membrane of CB-treated cells instead of smooth, parallel fibrous patterns of reverse-transformed cells or normal fibroblasts; 4) transmission electron microscopy (TEM) of sections show dense, elongated microfilament bundles and microtubules parallel to the long axis of the reverse-transformed CHO cell, but sparse, random microtubules throughout the transformed cell and an apparent disordered network of 6-nm microfilaments beneath the knobs; 5) cell membranes at the end of telophase, when the spindle disappears and cleavage is complete, display typical knob activity as expected by this picture.


Alteration of human breast tumor cell membrane functions by chromosome-mediated gene transfer.

BOT-2 cells (human breast tumor origin) have an impaired ability to utilize exogenous thymidine. Previous studies revealed this deficiency to be the permeation event rather than phosphorylation, since the cells have active thymidine kinase. Chromosome-mediated gene transfer was used to transfer genetic information in the form of metaphase chromosomes, from HeLa-65 cells to the BOT-2 cells, correcting the permease deficiency. Poly-L-ornithine or lipochromes were used for facilitation of chromosome uptake. After selection on HAT medium, transferant clones were isolated at a frequency of 4 x 10(-5) and 1 x 10(-5), respectively. Transferants MGP-1 and MGL-1 are stable after 18 months and have been characterized on the bases of purine and pyrimidine nucleoside uptake, relative thymidine kinase activities, alkaline phosphatase activities, and hydrocortisone-induced alkaline phosphatase activity. MGP-1 demonstrates positive thymidine uptake and incorporates radiolabeled thymidine into DNA. MGL-1 remains thymidine transport-deficient and surveys on HAT by increasing endogenous dihydrofolate reductase activity. Alkaline phosphatase activity in MGL-1 is similar to HeLa-65, 2% of that in BOT-2, and in addition, is inducible 25-30-fold by 3 micro M hydrocortisone. We have separated, genetically, a thymidine permease function from phosphorylation in cells of human origin and have transferred genetic information for the regulation of alkaline phosphatase.


[Urinary excretion of cAMP after PTH injection in patients with hypohyperparathyroidism (author's transl)].

The urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphate in response to an intravenous injection of 200 U.I. PTH in two women with hypohyperparathyroidism was studied. PTH activity was previously verified. Both patients were under treatment with vitamin D and their plasma calcium and phosphate levels were normal at the time of the study. Basal values for urinary excretion of cAMP were 2.25 nmol/min in one patient and 4.2 nmol/min in the other. Maximum excretion after PTH injection were 6.4 nmol/min and 5.5 nmol/min respectively. Basal values for urinary excretion of phosphate were 0.32 mg/min in the first patient and 0.18 mg/min in the second. After PTH injection the peak values were 0.73 mg/min and 0.35 mg/min respectively. These results pointed out the existence of a renal resistance to PTH which, unlike what happens in other similar patients, cannot be corrected with the administration of vitamin D.


[The usefulness of the quantitative evaluation of the plasma levels of the carcinoembryonic antigen (CEA) in patients with respiratory neoplasms (author's transl)].

Plasma concentration of the carcinoembryonic antigen (CEA) was determined by radioimmunoassay in 80 patients affected with different neoplasms of the respiratory system, among which the most predominant was bronchial carcinoma. For this type of tumor the results showed a percentage of positivity of 69 percent, with a greater value in the disseminated neoplasias (81 percent) in comparison with those which were localized (48 percent). The concentrations of the antigen were greater in the metastatic tumors; in 55 percent of the cases levels above 40 ng/ml were observed. On the other hand this figure was reached only by 4 percent of the localized tumors. Values of the antigen higher than 40 ng/ml should lead to the suspicion of the existence of neoplastic widespread. Among the rest of the series the negativity noticed in all the cases of pleural mesothelioma stands out, and indicates that this type of tumors does not produce CEA.


[Bulk vegetable material in human nutrition (author's transl)].

Intake of bulk vegetable material has diminished in the western countries considerably since the beginning of industrialisation. Lack of bulk substances is being held responsible lately for the increase of diseases of the gastrointestinal tract. It has been shown, that bulk materials increased stool weight and decreased gastrointestinal passage time; it is assumed, that they do have beneficial effects in the treatment of diverticulosis of the colon. It is still controversial, how bulk materials influence mineral metabolism, especially intestinal resorption of iron, calcium and other bivalent cations. Hypocholesterinemic effects of lignin and pectin, which form part of vegetable bulk food, are as yet not well defined. The question is still open, if bulk foods do have prophylactic effects in regard to carcinoma of the colon.


Malignant pheochromocytoma in childhood: report of a case with familial neurofibromatosis.

A 14-year-old male with familial neurofibromatosis and widely disseminated malignant pheochromocytoma is described. Current criteria for the diagnosis and management of this rare malignancy are discussed.


Serum phosphodiesterase I activity in breast cancer patients.

Serum phosphodiesterase I (PDE I) activity was determined in 13 control and 51 breast-cancer patients with various stages of disease. Patients with both localized and metastatic breast cancer had significantly elevated serum PDE I activity. The highest activity was seen in patients with liver metastases. A decline in serum PDE I activity was seen after surgical resection of all known disease.


[(Gynecomastia as precancerous lesion: aspiration biopsy cytology and its histology)].

In 19 of 39 patients suffering from gynecomastia, between 1967 and 1979 aspiration biopsy cytology and surgery was performed by the author. Atypia and precancerous lesions accompanied by an advanced stage of epithelial proliferation were found in two cases, in two other ones, in addition to the above mentioned lesions, breast cancer was discovered. The myoepithelial elements observed cytologically and histologically are important pathognomonic signs in theses patients. In spite of the few cases, the precancerous nature of gynecomastia, primarily in its proliferative forms, manifests itself.


[Effect of DNA supercoiling on transcription performed by normal and mutant Escherichia coli RNA-polymerases].

A specific DNA-gyrase, inhibitor, coumermycin A1, causes differential changes in the spectrum of proteins synthesized in E. coli wild types cells, while protein spectrum in the mutant cells with coumermycin-resistant DNA-gyrase is left unaffected. The mutation of RNA-polymerase RpoB265 lowers the sensitivity of bacteria to coumermycin A1, whereas the RpoC3 enhances it. The differences between the normal and mutant RpoB265 RNA polymerases on interaction in vitro with ColE1 DNA plasmid depend on its supercoiling. No dependences of this kind were detected when comparing the normal and RpoC3-RNA polymerase. The obtained data indicate that the template supercoiling may significantly affect the transcription in vivo and that the properties of RNA polymerase may in some cases define this influence.


[Analysis of vaccinia virus genome with restriction endonucleases EcoRI, BamHI, KpnI and HindIII].

Restriction endonucleases EcoRI, BamHI, Hind III and KpnI were used for analysis of acccinia virus DNA. The number and size of restriction endonuclease fragments were determined by gel electrophoresis and the analysis of 3H-labeled vaccinia virus DNA. It was shown that many EcoRI and BamHI fragments had the same and similar sizes. The exact number of EcoRI and BamHI fragments were estimated only after analysis of [3H]-labeled vaccinia DNA. The vaccinia genome sizes calculated from HindIII, KpnI and EcoRI are very close to the actual genome weight. But the sum of BamHI fragments is much lower than those determined by electron microscope method.


[Isolation of DNA fraction bound to the axial structure of metaphase chromosomes and studies of renaturation].

Mitotic chromosomes of L cells (metaphase plates) were dehistonized by centrifugation through a layer of 2 M NaCl and then treated with restriction endonuclease EcoRI and HindIII. Alternatively, they were pretreated with EcoRI endonuclease. The DNA remaining attached to the axial structure of the chromosomes was isolated and investigated in renaturation experiments. It was found to be enriched in reiterated base sequences belonging to the satellite and to abundant intermediate repeats.


Median neuropathy affecting the first dorsal interosseous muscle.

This case report documents the clinical entity of median nerve supply to the first dorsal interosseous muscle, which occurs in 3% of individuals. This must be remembered in evaluation of neuropathy involving the hand muscles.


Cirrhosis of the liver: a reversible disease?

This paper is a speculative review of the irreversibility of cirrhosis of the liver. Experimental studies dealing with the specific issue of irreversibility of the process are summarized, and the following three general propositions are derived: 1. All experimental models of cirrhosis are reversible, provided the inciting agent is removed and sufficient time is allowed for the return to normal liver structure. 2. Experimental cirrhosis of the liver goes through two successive stages, differing (among many other features) in the time and completeness of their reversibility. 3. Increased reticulum fibers are more easily and completely resorbed than thick collagenous bundles. Human cases of cirrhosis of the liver in which the fact of regression appears to be sufficiently documented are also summarized. Most of them seem to fulfil the three conditions derived from the analysis of experimental data, namely, withdrawal of the etiologic agent at an early stage in their development (with a predominance of reticulum over collagen fibers) and allowance of sufficient time to document the disappearance of the disease. Experimental studies on the mechanisms of collagen degradation in general, and in the liver of mammals in particular, are also reviewed. It is concluded that much remains to be done but that the outcome is by no means hopeless.


Myosin changes in experimental 2,4-dichlorophenoxyacetate myopathy.

Young rats treated with 10 to 14 daily injections of 2,4-dichlorophenoxyacetate (2,4-D) developed a myopathy mainly involving fast muscles. Myosin isolated from the gastrocnemius muscles of treated and normal control animals differed in several respects. The Ca2+- and Mg2+-mediated ATPases were higher in myopathic muscle myosin than in normals. Alkylation of thiols by N-ethylmaleimide (NEM) induced an increase of Ca2+-activated ATPase that was higher in normal than in myopathic myosin. Trinitrophenylation of reactive amino groups by 2,4,6-trinitrobenzene sulfonate (TBS) induced on increase in Mg2+-mediated ATPase in both preparations, but the increase was higher in normals. Although the heavy- and light-chain pattern was identical in normal and myopathic myosin, during storage at 0 degrees C the relative amount of myopathic L2 light chain decreased. Myosins fragmented either by limited proteolysis with trypsin and chymotrypsin or by specific cleavage at tryptophanyl and cysteinyl peptide bonds showed differences on sodium dodecylsulfate (SDS)-polyacrylamide-gel electrophoresis. The results indicate that there is a change in the heavy chains of myosin isolated from the gastrocnemius muscle in 2,4-D-induced rat myopathy.


Latent infection by herpes simplex virus.

The experimental evidence contributing to the understanding of herpes simplex virus latent infection has been reviewed. The site of residence of the virus during silent periods of the disease appears to be, in the majority of instances, the sensory ganglion innervating the territory of prime infection. Little is known about the factors that bring about latent infection, maintain it, and regulate the production of infectious particles that cause recurrences.


An endonucleolytic activity of nuclease TT1 specific for superhelical DNA.

Highly purified nuclease TT1 from T. thermophilus HB8 acts on a linear single- and double-stranded DNA as an exonuclease and produces 5'-mononucleotides either from the 5'- or 3'-terminus. It was found that the enzyme also possesses an endonuclease activity specific for superhelical (form I) and single-stranded circular DNA. Form I of various kinds of DNA (phi X174, PM2, Co1E1 and RF 1010 etc.) is nicked to yield first relaxed circles (form II) and then nicked at the opposite site to yield unit length linear DNA (form III), which is subsequently hydrolyzed from the 5'- or 3'-terminus. A single cleavage of the form I of phi X174 DNA seemed to occur at a limited number of unique sites. Both endonuclease and the known exonuclease activities co-migrate on polyacrylmide gels, show the same pH and temperature optima, are stimulated by Mg2+ and are inactivated by EDTA similarly.


DNA glycosylases of human lymphoblastoid cells.

Lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from xeroderma pigmentosum (XP) patients and normal donors. These lines expressed B-lymphocyte characteristics. Typical characteristics related to XP of these cell lines were not altered by transformation. Extracts of these cells catalyzed release of uracil (Ura) and 3-methyladenine (3MeAde) from Ura-containing DNA (Ura-DNA) and methylated DNA (Me-DNA), respectively. These two activities, Ura-DNA glycosylase and 3MeAde-DNA glycosylase, differed in heat stability. Extracts released Ura more rapidly and 3MeAde more slowly from a single-stranded DNA than from a double-stranded DNA. On incubation with reconstituted chromatins prepared from Ura-DNA and Me-DNA, respectively, with calf thymus chromosomal protein, cell extracts released all the Ura but about half the 3MeAde residues. The activity levels of these two enzymes of XP cells were similar to those of normal cells.


The specific, diverse effects of purine and pyrimidine nucleoside-5'-di(tri)-3'-diphosphates on the eucaryote translation system in vitro.

All the eight 5'-di(tri)-3'-diphosphates of four common ribonucleosides were prepared by the enzymic pyrophosphoryl transfer catalysed by Streptomyces adephospholyticus ATP:nucleotide pyrophosphokinase (E.C.2.7.6.4) form dATP to the respective 5'-phosphates, and their effects on the translation of mRNAs by a wheat germ system in vitro were studied. (p) ppPupp decreased the total 14C-leucine incorporation directed by a rat liver mRNA whereas (p) ppPypp did not. With a silkworm pupa ovary mRNA, distinctly reverase results were obtained. Gel electrophoretic profiles of the translation products disclosed the mRNA species-specific stimulatory or inhibitory effects for each of the polyphosphates tested.


The primary sequence of the late region of polyoma virus DNA II. The expression of the late genes and comparison with DNA sequences of SV40 and BKV.

The nucleotide sequence of the late region of the polyoma virus genome has been deduced, which codes for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. The amino acid sequence of VP1 predicted from the nucleotide sequence is in good agreement with the partial N-terminal sequence 1 and amino acid composition of VP1 2,3. When both nucleotide and amono acid sequences are compared with their counterparts in the related viruses, SV40 4,5 and BKV (R. Young, personal communication), extensive homologies are found along the entire regions of the viral genes. Maximum homologies appear to occur in the regions which code for the C-terminal of VP1, on the contrary of the result of heteroduplex analysis 6 with 6 with SV40 and polyoma virus DNAs.


Photobinding of 8-methoxypsoralen and changes in nuclease digestability of replicating SV40 chromatin.

To analyze the structure of the replicating regions of simian virus 40 nucleoprotein complex (SV40 chromatin), photochemical binding of 8-methoxypsoralen (8-MOP) and changes in digestability with micrococcal nuclease were studied. 8-MOP bound preferentially to the linker DNA of nucleosomes and strongly inhibited nuclease digestion. Nuclease digestability of newly synthesized DNA in the replicating chromatin was markedly increased, but it was inhibited in the early time of nuclease reaction by photobinding of 8-MOP. The data suggest that the replicating regions of chromatin are more exposed than the bulk of mature chromatin.


Uterine prostaglandin levels following stimulation of the decidual cell reaction: effects of indomethacin and tranylcypromine.

Prostaglandin E (PGE) and F (PGF) levels were measured in mouse uteri at various times after either trauma (hemostat crusing) or oil stimulation of the decidual cell reaction (DCR). The oil induced DCR led to an early increase (within 5 min) in both PGE and PGF levels. Both returned to baseline by 1 h after stimulation. A second peak in PGF levels was observed at 120 min after oil stimulation. This study demonstrates a distinct difference between the pattern of PGE and PGF changes in the uterus following oil stimulation of the DCR. Indomethacin pretreatment completely blocked the oil stimulated DCR as well as all prostaglandin increases following either stimulus. The trauma stimulated DCR was not completely blocked by indomethacin pretreatment. Pretreatment with tranylcypromine, an inhibitor of prostacyclin biosynthesis, did not block the prostaglandin E and F increases, but did block the oil stimulated DCR. These findings suggest that prostacyclin may be an early mediator of the DCR.


Effect of modulators of cytoskeletal function on desensitization and recovery of PGE2-responsive ovarian adenylate cyclase.

Exposure of cultured Graafian follicles to PGE2 for 20 h resulted in a loss of the cyclic AMP response to fresh hormone. This desensitization was prevented by addition to the medium of D2O (25--50%) or Li+ (0.6--6 mM), agents believed to stabilize microtubules, as well as by phalloidin (1.0--10 microM), believed to stabilize the polymerized state of actin, in a dose-dependent manner. The spontaneous recovery of responsiveness to PGE2 upon incubation of refractory follicles for 6 h in hormone-free medium was prevented by addition to the medium of cytochalasin B (CB; 3 microgram/ml) or of the actin-binding myosin subfragment HMM S-1 (80 microgram/ml) or of anti-actin serum; viz. by agents likely to interfere with microfilament function. D2O (50%) caused morphological damage to the inner layer of the membrana granulosa and severe depression of protein synthesis. The other drugs used (phalloidin, LiCl and cytochalasin B) had no such effects. Resensitization of refractory follicles was also prevented by cycloheximide (10 micrograms/ml) and by actinomycin D (10 micrograms/ml). It is speculated that the recovery process may involve the insertion of a newly synthesized protein, such as PG-receptor, into the membrane by a mechanism dependent on microfilament action. These findings provide suggestive evidence for the hypothesis that cytoskeletal elements associated with the cell membrane take part in the modulation of the adenylate cyclase response to hormones.


Prostacyclin stimulation of dog arterial cyclic AMP levels.

Prostacyclin (PGI2) dose-dependently increases the adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels in canine femoral, carotid, and canine and bovine coronary arteries. The prostacyclin-stimulation is enhanced by phosphodiesterase inhibitors, and is readily measurable after 60 sec incubation. The prostaglandin endoperoxide PGH2, but not PGH1, also elevates cAMP levels in femoral arteries. Inhibition of arterial prostacyclin synthetase with 28 microM 9,11-azoprosta-5,13-dienoic acid (azo analog I) blocks the PGH2-stimulation of cAMP accumulation. Azo analog I does not attenuate a direct PGI2 stimulation, indicating that the PGH2 dependent elevation of cAMP is due to conversion of PGH2 to PGI2 by the artery. PGI2 and PGE1 increase cyclic AMP levels and relax dog femoral and bovine coronary arteries, while PGE2, which actually contracts bovine coronary arteries, has no effect on arterial cyclic AMP levels. The significance of the PGI2-stimulation of arterial cyclic AMP is not known, but it is probably related to relaxation of arterial strips.


The determination of bone age in the elbow as compared to the hand. A study in 390 children.

In a prospective study, bone age (BA) from both hand and elbow was assessed in 390 children, aged 6-15 years, in order to determine: (a) whether or not BA assessment from the hand and from the elbow give comparable results, and (b) whether the accuracy of predicting skeletal age from the hand may be improved by the additional BA determination in the elbow. BA assessment in the hand was performed according to the method of Greulich and Pyle while the standards of Schinz and Baensch were used for the elbow. Statistical analysis of data was carried out according to age groups as well as according to groups of clinical diagnoses. With only one exception in the group of so-called "healthy individuals", there was no difference between "hand age" and "elbow age". Thus, except in a very small group of subjects, both methods of BA assessment were found to be equivalent in predicting skeletal age in children between 6-15 years. Equivocal results were obtained regarding the question of whether the accuracy of BA assessment in the hand may be improved by the simultaneous BA determination from the elbow. Until further studies on larger statistical material provide more conclusive information in this matter, we feel that the combined determination of BA in the hand and elbow is not warranted for clinical purposes.


The effect of baclofen on the hind limb flexor reflex of the spinal rat.

The effect of baclofen on the hind limb flexor reflex of the spinal rat was studied. Baclofen inhibited the flexor reflex, this effect not being antagonized by picrotoxin and bicuculline. Baclofen reduced the stimulating action of quipazine and LSD, had no effect on the clonidine-induced reflex stimulation, but inhibited the flexor reflex stimulation induced by amphetamine and fenfluramine. The results obtained bring forth some doubts as to the GABA-mimetic action of baclofen. The action of baclofen on the spinal cord seems to be directed mainly to the presynaptic part of the noradrenergic and serotonergic systems.


[Breast cancer in men].

Carcinoma of the breast is relatively uncommon in men. Represents somewhere between 0.9 to 1.5 of all tumors of the breast. Most patients are within the 7th to 8th decade of life. The most common symptoms at the time of presentation are a tumor mass in either breast, ulceration of the nipple or nipple retraction or fixation of the skin. Extension to the axiliar nodes takes place early in the course of the disease. The presence of nipple discharge should be considered expression of carcinoma of the breast unless otherwise proven. The final diagnosis is established by biopsy. The most common form of carcinoma of the breast is the ductal carcinoma. The surgical management takes basically that followed in carcinoma of the breast in the female patient. Also orquiectomy has been used which is equivalent to ovariectomy in woman. In the presence of metastasis both estrogens and androgens have been used. Hypophysectomy and post-op radiation therapy has been used. Most recently chemotherapy has been widely used in those cases with widespread metastasis. However, in spite of all these efforts carcinoma of the breast in the male still carries a very serious prognosis. We present our experience in 16 cases.


[Cancer of the alpha cells of the pancreas].

Endocrine tumors of the pancreas are rare. One of them is the so called alpha cell carcinoma also called glucagonoma usually associated with diabetes and skin lesions somewhat typical. A case of a male patient fifty-three years of age with clinical diabetes mellitus and generalized dermatitis is presented. The pancreatic scan showed some enlargement of the head of the pancreas as well as the body which was confirmed by ultrasound. Angiography showed that this change was due to pancreatic tumor with intrahepatic metastasis. The patient was taken to surgery where a glucagonoma of the pancreas was found. This case is reported because only 32 other cases have been reported in the literature.


[Longitudinal study of 5 patients with "primary empty sella" (author's transl)].

The clinical symptoms and the radiographic findings of five female patients with "primary empty sella" were studied. The patients were treated with corticosteroid therapy and the clinical syndrome, with the exception of optic subatrophy of the left eye in one patient and of both eyes in another patients, improved in all of them. In subsequent controls, the radiographic findings did not show any evolution suggesting that the cause of the empty sella syndrome is a potentially regressive element (endocranial hypertension?). The small number of our cases does not prove with any certainty that corticosteroid treatment, was beneficial but as improvement occurred and in all the subjects this therapy should be tried in other patients with "empty sella" syndrome. The possible improvement of the empty sella syndrome has to be taken into account before deciding on surgical intervention.


[Red cell indices in the aged. 1 726 patients over the age of 70 (author's transl)].

Statistical analysis of red cell constants in 1 726 patients over the age of 70 shows that red cell counts, hemoglobin and hematocrits are slightly lower than those in young adults. However, the quality of the red cells is normal, because the MCV (mean cell volume) and MCHC (mean cell hemoglobin concentration) are normal.


[Frequency and etiology of anemia in patients over the age of 70 (author's transl)].

The study of 1 726 patients living in homes for the aged, or hospitalized shows that 20% of them have anemia. There is no increase in prevalence of the disease in females. A wide variety of mechanisms may cause anemia. However, chronic bleeding of essentially digestive origin is the most common. Several anemia-causing factors are particularly frequent in the aged: bleeding, inflammation, nutritional deficiencies, bone marrow failure. Diagnosis is complicated and may require examinations which are not always easily accepted by the aged.


["Non-secreting" plasma cell myeloma preceded by refractory sideroblastic anemia (author's transl)].

The authors report the association of a refractory sideroblastic anemia and a "non-excreting" plasma cell myeloma. The anemia was observed 8 years before the onset of the myeloma, which had typical hematological characteristics. Both kappa and gamma light chains were found in the cytoplasm and on the surface of the plasma cells. Pathologic characteristics of this type of myeloma are briefly recalled, as well as the relationships between sideroblastic anemia and kahler's disease, an example of disorders of two lines of hematopoiesis (erythrocytes and leucocytes).


[Crohn's disease (acute regional colitis) (author's transl)].

This article reports the observation of acute form of Crohn's disease, limited to colonic involvement, in a 40-year old female. Diagnosis was based upon pathologic examination of biopsy. The patient died after four months of acute disease. Clinical and paraclinical justification of the diagnosis of Crohn's disease (colonic), as well as description of treatment are given.


[Primary hydatic cyst of the lung. Diagnostic problems (author's transl)].

Diagnosis of primary cystic disease of the lung is often difficult, and because of this, in non-endemic regions, patients are often referred to the surgeon with an erroneous diagnosis. Clinical signs are completely non-specific. The most common one is hemoptysis; X-rays often fail to confirm hydatic cyst because of the volume, topography, or rupture of the cyst. Biological tests are often of little help. Serological reactions are negative in over one-half of the cases. The advantage of other complementary examinations (bronchiography, bronchoscopy, angiography, echotomography, scintigraphy) including transparietal punctions of the cyst, are discussed in light of the literature.


[Lactic acidosis and intensive care. 16 cases (author's transl)].

Sixteen cases of lactic acidosis are reported: 7 phenformin treated diabetes, 5 cardiovascular diseases (2 myocardial infractions, 2 pulmonary embolisms, 1 heart failure). In 2 patients no etiology was found. Concomittant renal failure or liver diseases were found in respectively 9 and 4 cases. Patients presented the usual criteria of lactic acidosis: clinical, polypnea, severe hypotension (9/16), peripheral symptoms of shock (12/16), hypothermia (9/16), abdominal pain (9/16): biologically, acidosis (pH = 6,99 +/- 0,01, HCO3- = 5,9 +/- 1,5 mmol), hyperlactatemia (14,1 +/- 3,6 mmol/l) with hig lactate/pyruvate ratio (105 +/- 73), and anion gap (24,3 +/- 4,2 mmol/l). Sodium bicarbonate infusion was performed in all cases (2,5 to 42 mmol/kg). Few cases required volhemic expansion or furosemid induced diuresis. One patient was treated with extrarenal dialysis. 13 patients were alkalinised with less than 185% of estimated deficit measured from alkalin reserve: 12 died. 3 patients received 185% more than this deficit, associated with furosemid (1,8 to 12,5 mg/kg): only one patient died ten days after by casual disease, with lactatemia of 3,2 mmol/l. In spite of the small number of patients, these findings suggest that an early and massive alkalinisation, with large doses of furosemid, can improve the severe lactic acidosis prognosis.


[Plasma androgens in boys from birth to adolescence (author's transl)].

Plasma testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by radioimmunoassay in 222 normal boys aged 1 hour to 18 years and 40 normal men aged 20 to 40 years. Three periods of high testosterone levels were observed in boys during extra-uterine life: first day (mean level 12 nmol/l), from the 12th to the 119th day (9 nmol/l) and from 13 years onwards in pubertal boys; the highest values were  reached between 20 and 40 years (18 nmol/l). Androstenedione curve exhibited three coincident high concentrations phases: mean level at birth 8.7 nmol/l, and from 12th to 119th day 2.6 nmol/l. The lowest values were observed between 2 and 4 years; then a progressive increase occured up to adult age levels: 3.5 nmol/l. Dehydroepiandrosterone mean level was high at birth (20 nmol/l) then decreased slowly, either regularly or with a rebound during the 2nd month, a minimum being reached between 2 and 4 years (0.28 nmol/l). It increased thereafter exponentially up to adult levels reached after the age of 16 years (14 nmol/l). Dehydroepiandrosterone-sulfate mean level decreased regularly from birth to the second year, then its curve paralleled the dehydroepiandrosterone curve.


[Treatment of hypertension with Sotalol (author's transl)].

Sotalol is a new beta-adrenoceptor blocking drug without membrane stabilizing activity, without intrinsic sympathomimetic activity and with a low cardio-depressive effect. This beta-blocking agent has an half-life much longer than the other beta-blockers (T 1/2 from 10 to 13 hours). The antihypertensive effect and tolerance of 160 mg tablets of sotalol were studied in 35 hypertensive patients aged 18 to 60 years. The drug was administred once daily in the morning. Sotalol prescribed as the only antihypertensive drug lowered the blood pressure to normal values in 21 cases with a single daily of 1 to 3 tablets. In 8 patients a partial response was obtained (25 % reduction of the initial systolic and diatolic pressure). Six patients did not respond. The clinical and biological tolerances were good; Sotalol was only discontinued in three cases. Sotalol appears to be an effective and well tolerated antihypertensive agent, specially for the treatment of moderate and recent essential hypertension in young patients.


[Histological and immunofluorescence study of forty two cases of Dühring-Brocq disease (author's transl)].

Fourty-two cases of Dühring-Brocq disease were analysed clinically, histologically and with direct and indirect immunofluorescence. One could only discriminate between bullous pemphigoid and dermatitis herpetiformis when all those criteriors were studied together. 17 cases were clinically composite ; histological and immunofluorescent analyses differentiated between 16 cases of bullous pemphigoid and 1 case of dermatitis herpetiformis.


[Acute pancreatitis and cholelithiasis. A study of thirty cases (author's transl)].

The authors report a series of 30 cases of acute pancreatitis associated with cholelithiasis. There were 9 cases of necrotizing pancreatitis and the latter group included the 4 deaths observed in this series. Clinical, radiological and laboratory data were in favor of this association in 24 out of the 30 cases. Cholelithiasis appeared to be directly responsible for initiating the pancreatitis in 1/3 of cases. In another 1/3 of cases the mecanism was thought to be related to scarring of the sphincter of Oddi. In the remaining 1/3 of cases no direct relationship could be found. On the basis of these findings, the authors recommend that emergency surgery be reserved for these cases in which cholelithiasis appears to be the etiology. (The biliary syndrome overshadowing the pancreatic syndrome) and to postpone treatment of pancreatic lesions. In all other cases, the authors suggest to keep elective surgery, for after a period of initial conservative treatment with the hope of then treating together biliary and pancreatic lesions.


Isolation and toxicological study of tetrahydrocannabivarol, an homolog of tetrahydrocannabinol (delta 1--THC).

Selection and culture in a Phytotron of plants of Cannabis sativa L. with high content of propyl-THC are obtained. Then it was possible to isolate a large quantity of propyl-THC by column chromatography. Spectroscopic analysis is done. Pharmacological tests are being run; first results revealed the allergenicity of this substance by comparison with the properties of tetrahydrocannabinol, the active principle of Cannabis.


Electroretinographic study during acute Aramite intoxication of the white mouse.

Aramite was injected to white mice and the electroretinograms recorded in response to electronic flashes. The following phenomena were remarked: a more and more important flattening of a-waves; a simultaneous collapse of b-waves; a more and more delayed return of a-waves to the isoelectric line; vanishing c-waves. Those actions were explained by an intoxication of the photoreceptors by Aramite and by a resulting difficulty of the photoreceptors to stimulate bipolar cells.


[Acute thrombocytopenic purpura associated with fenoprofene (author's transl)].

A 73-year-old woman, taking daily 3 to 4 tablets (900 to 1200 mg) of fenoprofene for 2 weeks, had a purpura related to an acute peripheric thrombocytopenia (platelet count of 24 000/mm3) with fast regression when we have stopped therapy. It is the second case of literature. This drug is also capable of causing acute agranulocytosis.


[Stenosis of the left coronary artery: a report on 50 cases (author's transl)].

Stenosis of the left coronary artery differs from other atheromatous lesions by the severity of the affection. It is not a rare condition as it occured in 50 out of 750 patients. Clinical and electrocardiographic signs are not truly specific and coronarography is essential for diagnosis even though this procedure carries a certain risk of accidents (2%). At a time when medical and surgical treatment of coronary insufficiency is being compared, stenosis of the left coronary insufficiency is being compared, stenosis of the left coronary artery definitely required operative intervention which improves both functional prognosis and mortality.


[Biological age in children with clefts].

The skeletal and the dental maturity in a group of 189 children with cleft lip and/or cleft palate were determined by means of X-rays of the wrist joint and orthopantomogrammes. In 60 children, anthropometric determinations were also performed. 486 normal children involved in the Nijmegen growth study served as control subjects. The ages ranged from 4 to 14 years. A retardation in dental development was evidenced in boys with clefts. There was no remarkable difference in dental development between girls with clefts and girls without clefts. The progression in skeletal maturity was greater in girls with clefts than in girls without clefts. There was no remarkable difference in skeletal maturity between boys with clefts and normal boys. The determination of 10 anthropometric values revealed only a few remarkable differences between children with clefts and normal children.


[Thyroid dysembryoma. Report of a case in an adult (author's transl)].

One case of dysembryoma of the thyroid gland is reported. 115 cases of that rare disease have been published; the tumor is particularly rare in adult (14 cases). Salient features are reviewed, mostly complications and malignant degeneration. Surgical removal is the only treatment and also the only mean to have histological diagnosis.


[Quantitative study of hepatic fibrosis in Hodgkin's disease (author's transl)].

The construction of a prototype apparatus adapted to the constraints of tissue structures has permitted not only the quantification of fibrosis within the liver but also analysis of its distribution. The cumulative histograms thus achieved permit the characterization of the liver in Hodgkin's disease.


[Angina and "normal coronarography" results: diagnostic approach and future perspectives (author's transl)].

Patients with angina but with "normal coronarography" results, are not a rare finding during angiographic investigations, more especially in the case of women. The authors review the clinical, electrical, hemodynamic and metabolic characteristics of these cases, and discuss the principal known etiologies, and limits of "normality" with respect to coronary artery angiography results.


[Multilocular Paget's disease--a case report (author's transl)].

The simultaneous occurrence of Paget's disease in five different regions in a 76-year old woman is reported. Only one lesion exhibited the typical clinical appearance of this condition, whereas the others were diagnosed histologically. After radical surgical treatment of all lesions the patient has remained free from recurrence for more than three years.


REM sleep and the prevention of endogenous depression.

The possibility of preventing endogenous depression may depend upon our understanding the brain mechanisms involved in the improvement of depression. Recent work in our laboratory has shed some light on these mechanisms. I will first describe this work and then suggest its possible preventive implications. Throughout this paper, the term depression means endogenous depression unless stated otherwise.


REM sleep dependent release of vasotocin into cerebrospinal fluid of narcoleptics.

The lumbar cerebrospinal fluid (CSF) collected from 6 narcoleptic patients (three males and three females) aged between 31 and 47 years, as well as from 2 patients having Pickwickian syndromes with hypersomnia attacks (two males), aged 43-51 years, contained relatively high amounts of arginine vasotocin (AVT) only if the CSF was removed after a REM sleep period. The release was not induced by darkness since the same release of AVT occurred when the CSF was removed after a REM sleep period during daylight hours. No detectable AVT levels have been found in the CSF samples of four narcoleptics collected after a NREM period of sleep, either during night or daylight hours. The present results suggest a possible alteration of the rhythmical release of AVT both in narcolepsy and in narcoleptic syndromes.


[Histological study of the teleost liver. III. The system of biliary pathways].

In the liver of Haplochromis burtoni four divisions of the intrahepatic biliary pathways can be distinguished: canaliculus, canaliculus ductulus transition, ductulus biliferus, ductus biliferus. There are no transitional stages between the hepatocytes and biliary epithelial cells. The results of the investigation suggest that the ductules open into the ducts in two ways, directly and by graded transition of structure. The first part of the ductulus has a very narrow lumen and therefore is similar to the "Schaltstück" of salivary glands. Terminal ductulus cells can protrude into the canaliculus (= lumen of the liver tubulus), giving the appearance of centrotubular cells in cross-section. In the liver of most of the teleosts investigated here the canaliculi are intercellular. Tangentially cut diverticuli of the canaliculi appear to be unicellular ("intracellular") canaliculi, but are, however, merely unicellular ("intracellular") protrusions of the intercellular canaliculi. On the other hand the three cyprinid species (Barbus tetrazona, Idus idus, Carassius auratus) possess true unicellular ("intracellular") canaliculi. These can definitely be distinguished from the diverticuli of intercellular canaliculi by several criteria. Phylogenetically the unicellular ("intracellular") canaliculus must be regarded as derivative, and the intercellular canaliculus as the original form. The morphology of the wall of the gall-bladder of Haplochromis burtoni indicates that transfer of substances is increased together with transportation and drainage of fluids and variations in volume. The ultrastructure of the epithelial cells reveals a zonal arrangement.


[Gartner's duct carcinoma of vagina in pregnancy - case report (author's transl)].

Reported in this paper is a mesonephroid carcinoma in the vagina of a primigravida, 27 years of age, in the 27th or 28th week of pregnancy. The carcionoma originated from Gartner's duct and is characterised by typical papillary structures. Such carcionoma quite often cannot be morphologically differentiated from metamesonephroid carcionomas which originate from Mueller's epithelium to occur on the same site. Both tumour forms are rather often be considered an entity in relevant literature. The development of that carcinoma during gravidity is considered accidental. - Included in the therapeutic approach were Caesarean section, radical hysterectomy, including radical adnexectomy and removal of a 5-cm vaginal collar, removal of the Douglas peritoneum because of visible intraperitoneal metastasation, and extensive lymphonodectomy, all in one session. - Biaxial telecobalt pendulum irradiation followed postsurgically, the focal dose being 7,000 rd. No sign of recurrence has been recordable from follow-up checks and clinical examinations, one year from surgery.


Pineal vasotocin: REM sleep dependent release into cerebrospinal fluid of man.

Lumbar cerebrospinal fluid (CSF) of seven healthy male volunteers contains detectable levels of arginine vasotocin (AVT) when CSF was removed after awakening from rapid eye movement (REM) sleep. No detectable levels of AVT were found in the CSF of the same subjects when CSF WAS removed after awakening from non rapid eye movement (NREM) sleep. The amount of AVT detected in CSF after REM sleep was significantly higher if the subjects experienced vivid and emotive dreams. The present results provide the first evidence for a REM sleep dependent release of AVT into CSF of man.


Influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission.

The influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission was studied in the isolated saphenous vein of the dog. Pancuronium increased the response of vascular smooth muscle to adrenergic nerve stimulation and to exogenous norepinephrine; gallamine, d-tubocurarine and succinylcholine had no effect. The relaxation caused by small doses of acetylcholine added during sympathetic nerve stimulation (prejunctional effect), was inhibited by pancuronium and by gallamine. In vein strips, charged with (3H) norepinephrine, acetylcholine inhibits the catecholamine-efflux evoked by sympathetic nerve stimulation. That inhibition was abolished by gallamine. This confirms that gallamine inhibits the prejunctional effect of acetylcholine on adrenergic neurotransmission. When extrapolated to the intact organism, this means that gallamine and pancuronium will augment the release of norepinephrine by acting as muscarinic antagonists also at prejunctional receptor sites in tissues exposed to combined sympathetic and vagal nerve activity. This mechanism would explain in part the cardiovascular effects of these muscle relaxants.


Determination of enzyme activity by chromatography and videodensitometry. II. Urea cycle enzymes in tissue homogenates.

Methods are described for the determination of the activity of urea cycle enzymes in human and rat tissues by chromatography and videodensitometry(CV-technique). With specific substrates carbamoyl-phosphate synthetase and ornithine carbamoyltransferase activities were determined as the amounts of citrulline formed. Argininosuccinate synthetase, argininosuccinate lyase and arginase activities were measured from the changes in ornithine concentration. For measuring the activity of five enzymes 5 to 10 mg wet weight of tissue was sufficient. The CV-technique could be conveniently applied for the investigation of enzyme content in samples from human biopsy.


Myofibrillar proteins, enzyme activity and fibre types in human skeletal muscle.

The myofibrillar proteins and relative LC-3 content of myofibrils prepared from five different, left and right muscles of the human forearm were studied by electrophoresis in 10% SDS-polyacrylamide gels followed by densitometry. The specific K-activated ATPase activity of the myofibrillar myosin of the myofibrils was determined and the distribution of the fibre types was analyzed by histochemical methods. The qualitative pattern of the myofibrillar proteins was found to be identical in the different muscles; in the other parameters, however, a variation in a narrow range was observed. The relative LC-3 content, the ATPase activity and the type II fibre content of the right side muscles were always higher than those of the corresponding left side muscles.


The study of nitroxide radical active esters as spin labels on muscle protein actin.

Nitroxide radical active esters were used to label the muscle protein actin and to study the orientation dependence of the EPR spectra of the labelled protein. It is concluded that the labels are located at least at two different sites of the protein with strong polar environment and different mobilities. The EPR spectrum of the strongly immobilized labels exhibits orientation dependence, the N--O bond axis of the spin labels is nearly perpendicular to the long axis of the F-actin threads, and the labels undergo a rapid rotational motion about an axis directed perpendicular to the filament axis. The application of the nitroxide radical active esters may be useful in the study of ordered systems as muscle or muscle protein systems.


Central mediation of hormonal influences on instrumental avoidance conditioning.

Two behaviorally active hormones of the pituitary-adrenal system are adrenocorticotropic hormones (ACTH) and corticosterone, and their behavioral effects are facilitation and inhibition of performance of previously learned avoidance responses, respectively. Their uptake, distribution and effects on central nervous system are reviewed. Hypothalamic neurotransmitter control of corticotropin releasing hormone (CRH) is described together with hypothalamic and extra-hypothalamic (hippocampal) regulation of pituitary-adrenal activity. Extra-hypothalamic mediation of the behavioral effects of ACTH is evaluated. Recent isotopic mappings of the efferents of the hippocampal formation have identified pathways from hippocampal subiculum to hypothalamus and posterior lateral and anterior thalamic nuclei. The evidence reviewed suggests a complex circuit involving hippocampal subiculum, thalamus and hypothalamus may be involved both in regulating pituitary-adrenal responses to stress and in mediating the effects of ACTH on avoidance behavior.


Relationships between phenomena of paradoxical sleep and their counterparts in wakefulness.

Our studies suggest that paradoxical sleep is a state in which the brainstem is in a functional mode normally associated with presentations of novel stimuli. Furthermore, the combination of atonia and an internal state of activation indicates sustained activity of a brainstem mechanism designed to dampen responses to sudden, novel stimuli in wakefulness lest the animal over react and run blindly into danger prior to stimulus analysis. This conclusion stems from two sets of data. Studies of large-amplitude waves, which characteristically occur spontaneously just prior to and during paradoxical sleep, have demonstrated that the waves are signs of alerting. These waves, termed ponto-geniculooccipital (PGO) spikes, can be induced during both slow wave and paradoxical sleep by external stimuli at a threshold below actual arousal. Whenever cats are confronted with novel stimuli during wakefulness, eye movement potentials, which are recorded from the same sites as PGO spikes but differ from them in several characteristics, assume all the characteristics of PGO spikes. These observations indicate that the central nervous system during paradoxical sleep is in a "peculiar" state of activation which is not behaviorally expressed. Other experiments have focused on the muscle atonia of paradoxical sleep. Small, bilateral dorsolateral pontine tegmental lesions create the dramatic phenomenon of paradoxical sleep without atonia which is characterized as follows: After slow wave sleep, when paradoxical sleep with muscle atonia would normally appear, cats raise their heads, make body righting movements, exhibit alternating movements of the limbs, and even attempt to stand. Throughout an episode, which shows all other aspects of paradoxical sleep, including unresponsiveness to visual stimuli, cats act as if they are being startled, searching and sometimes attacking an object. In wakefulness they show minor cerebellar signs. Presumably the lesions disrupt both the pontine excitation of the medullary inhibitory area and the inhibition of a brainstem system for mobilizing activity normally in force during paradoxical sleep. Studies of the same cats during wakefulness have shown that there in an increase in exploratory locomotor activity of 23 to 127 percent as measured in an open-field test. The existence of parallel effects on motor control in wakefulness and paradoxical sleep produced by pontine lesions suggests that the atonia of paradoxical sleep is a reflection of excessive activity of a brainstem response dampening mechanism which operates more subtly during wakefulness to produce appropriately modulated responses to various unexpected stimuli.


Modulation of T cells and macrophages by cholera toxin treatment in vivo and in vitro.

Cholera Toxin influences the antibody response to SRBC. Enhanced responses occur in vivo and in vitro when CT is added together with antigen. However, CT depresses antibody formation when given in vivo before antigen but enhances in vitro responses under the same conditions. Modulation of antibody formation appeared due to effects of T lymphocytes as well as macrophages. Co-cultivation of immunologically impaired spleen cells from CT pretreated animals with macrophage-rich peritoneal cells or educated T cells increased the antibody response.


Tobacco smoke and the pulmonary alveolar macrophage.

Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis.


[Hereditary abnormalities of galactose metabolism: diagnosis and biochemical supervision (author's transl)].

The authors define the main stages of the biochemical study of hereditary abnormalities of galactose metabolism. They review laboratory examinations for detection, enzyme examinations which provide the diagnostic proof, further examinations which permit one to follow the course and efficacy of a galactose-free diet, the demonstration of genetic variants, the technics of antenatal diagnosis and routine neonatal detection.


[Cell-mediated cytotoxicity against Rous sarcoma in the hamster (author's transl)].

The cytotoxic response of lymphoid cells from hamsters immunized against RS 2/3 cells, transformed by Rous sarcoma virus, was investigated. The highest cytotoxic response was obtained after the third inoculation of RS 2/3 cells. Both the non-tumor-bearing hamsters immunized with physically or chemically treated RS 2/3 cells and the tumor-bearing hamsters, grafted with live RS 2/3 cells provided splenic cytotoxic lymphoid cells. On the contrary, lymphoid cells obtained from lymph nodes were only slightly cytotoxic. The results did not permit to establish a relationship between the cytotoxic activity of the lymphoid cells obtained from the spleen and from the lymph nodes. The cytotoxic response of lymphoid cells in vitro was not correlated with tumor rejection, in vivo.


Effect of dexamethasone and ACTH on the secretion pattern of fractionated 17-ketosteroids in hirsutism.

Urinary steroid fractionations of 17-ketosteroids were carried out in 3 normally-ovulating young women and in 2 women with hirsutism. Dehydroepiandrosterone, aetiocholanolone, androsterone, 11 beta-hydroxyaetiocholanolone, 11 beta-hydroxyandrosterone, 11-oxoaetiocholanolone and 11-oxondrosterone were determined quantitatively by paper chromatography. Both patients had decreased levels of 11-deoxy and 11-oxy-17-ketosteroids compared with the normals. The ready suppression of 11-oxy-17-ketosteroids and the poor suppression of 11-deoxy-17-ketosteroids by dexamethasone in both patients suggests an ovarian origin of 11-deoxy-17-ketosteroids. Supporting evidence for an ovarian origin in Case 1 was furnished by the poor suppression of testosterone by dexamethasone and lack of response to ACTH stimulation of the adrenal glands. The presented data emphasize that the precursor of 11-deoxy-17-ketosteroids of ovarian origin, possibly testosterone, may well be the cause of hirsutism in both patients.


[Twin pregnancy following bromocriptine in an acromegalic patient staying sterile after removal of a pituitary adenoma. Immunocytochemical study of the tumor (author's transl)].

A pituitary adenoma was removed from a young woman who had acromegaly with galactorrhea-amenorrhea. Postoperatively, the dysmorphic acromegalic syndrome and galactorrhea decreased but amenorrhea, elevated serum GH and PRL concentrations remained. After Bromocriptine administration (5 mg daily) GH and PRL levels became normal, vaginal bleeding ensued within 3 months and a twin pregnancy was induced. An immunocytochemical study of the pituitary adenoma revealed the presence of two well defined, distinct cell types, each secreting one hormone with large preponderance of GH cells.


[Adrenocortical function in hyperprolactinemia. The study of glucocorticoids, mineralocorticoids and androgens in chronic and acute hyperprolactinemias (author's transl)].

Glucocorticoids, mineralocorticoids, and adrenal androgens were studied in 3 groups of patients: control subjects (group I), hyperprolactinemic subjects (group II) and miscellaneous patients including chromophobe adenomas and normalized hyperprolactinemic subjects treated with Bromocriptine (group III). All the patients were studied in the basal state and under various conditions: Metyrapone, ACTH, TRH for glucocorticoids, ACTH, TRH, saline perfusion for mineralocorticoids, ACTH and TRH for androgens. It is concluded that: the adrenal secretion of glucocorticoids, mineralocorticoids and androgens is not altered under basal conditions in chronic hyperprolactinemia nor during dynamic tests in chronic hyperprolactinemia (prolactin adenoma) nor in acute hyperprolactinemia (induced by TRH).


[Immunocytochemical similarities between basophilic and chromophobe pituitary adenomas. Light and electron microscopic study of 13 cases (author's transl)].

ACTH, beta MSH, beta LPH, beta endorpSin, leucine and methionine enkephalin activities were tested in four Cushing pituitary basophilic adenomas and nine "chromophobe" adenomas with immunoperoxidase methods. The antisera gave various positive reactions in both of these groups. ACTH, alpha MSH and enkephalins were predominant. The reason why these hormones are clinically silent in "chromophobe" or, even, basophilic adenomas is still to be elucidated.


[Pituitary adenomas with cells containing bêta MSH, alpha and bêta endorphins and without ACTH (author's transl)].

By using immunohistoenzymatic techniques, cells of 4 pituitary adenomas are revealed with beta MSH, alpha and beta endorphins antisera but do not react with 1--24 and 17--39 ACTH antisera. These data suggest that adenomatous cells are able to synthesize and LPH-like molecule without ACTH. The levels of plasmatic LPH and beta MSH, studied by RIA, stay normal. These results are discussed.


[A feminizing adrenal carcinoma in man: in vivo and in vitro study (author's transl)].

A 31 years old man with an adrenocortical carcinoma was studied. Clinically he had a bilateral and recidiving gynecomastia and showed high urinary oestrogens, 17 cetosteroids, tetra-hydro-desoxy-cortisol and pregnandiol excretion with normal cortisol production. A partial increase on ACTH, no suppression on dexamethasone and no variation on HCG administration were observed. The surgical resection of the tumor normalized this urinary excretion. The serum dehydro-epiandrosterone (DHEA) and sulfate (DHEAS), oestrone, oestradiol, androstenedione (A) levels were greatly elevated. No variations of the cortisol, A, DHEA and DHEAS was noted after ACTH injection. In vitro the lack of ACTH's action was related to an anomaly of ACTH receptor with normal protein kinase activity.


[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 4. Epizootiology].

Necrotising enteritis had been the cause of death of 4.9 per cent in 5,177 nursed piglets, which was established by pathological examination. The number of piglets, in that context, which had come from industrialised sow breeding units was equivalent to 92 per cent. The nursed piglet held the third position, next to smaller ruminants (19.4 per cent) and fowl (6.0 per cent), with regard to the occurrence of Clostridium perfringens enterotoxemia or necrotising enteritis in 112,218 animals which were pathologically examined after death. Necrotising enteritis so far has been rare in the GDR. No regional accumulation has been observed. Several outbreaks on industrialised sow breeding units actually remained stationary. The occurrence of the disease may be favoured by a number of factors which are conducive to accumulation of Clostridium perfringens Type C in a given stock. Group keeping of pregnant sows, simultaneous farrowing of larger groups of sows, group treatment of nursed piglets, using neomycin, chloramphenicol, oxytetracycline, and other antibiotics to which Clostridium perfringens is primarily resistant or has acquired resistance in the course of time are some of those contributive factors. Transmission of Clostridium perfringens Type C through feedstuff is possible, though it would lead to a real outbreak only by high intensity of the contamination, and it played a minor role in proliferation of the disease. 3479 Clostridium perfringens strains were isolated from 9,481 animals, both clinically intact and after death, with 30 species being included. Type classification revealed 2454 strains of Type A (70 per cent), 204 of Type D (5.88 per cent), 164 of Type C (four per cent), and 48 of Type B (1.34 per cent). There were 688 atoxic strains (17 per cent). Swine is the major carrier of Clostridium perfringens Type C, with 87 per cent of all Clostridium perfringens Type C strains having been isolated from swine. Swine was followed by fowl (four per cent), sheep (four per cent), cattle, rabbit, and dog (1.27 per cent each). Clostridium perfringens Type C was obtained from the faeces of clinically intact sows in seven instances, including two cases with sows (0.46 per cent) from farms with no previous record of necrotising enteritis.


[Studies of necrotizing enteritis of suckling piglets (Clostridium perfringens type C enterotoxemia) in industrialized sow breeding units. 5. Control of the disease].

Recent methods used and experience obtained in the control of necrotising enteritis are reported in this paper, with reference being made to both the pathogenesis and epizootiology of the disease. Two inoculations of the sows, using "Enterotoxämievakzine Dessau bivalent" five and three weeks before parturition, have worked well for prophylaxis. Oral treatment was applied to nursed piglets, using 40,000 I.U. of "Aviapen" and "V-Tablopen" penicillin per animal and day over periods between two and four days, helped to minimise piglet loss, particularly in the period between a fresh outbreak and full effectiveness of immunoprophylactic action. Such treatment was conducted metaphylactically and therapeutically. The first metaphylactic treatment was given within 24 hours from parturition. Combination of mother animal vaccination with the above therapeutic use of those two penicillin preparations worked extremely well in enzootically contaminated stocks and proved to be the most effective approach, for the time being, to controlling necrotising enteritis of nursed piglets. Yet, all those control measures failed to bring about full stock sanitation on industrialised units. Sow trading was not permitted until at least four weeks had elapsed from full effectiveness of mother animal vaccination, with the view to reducing the proliferation of Clostridium perfringens Type C via sales of breeding animals. All sows were given two "Enterotoxämievakzine Dessau bivalent" vaccinations, prior to sale. The animals were sold only to smaller farms (less than 500 sows for breeding) with concentional keeping patterns which were kept under constant diagnostic supervision. Neomycin, oxytetracycline, chloramphenicol, and other antibiotics against which Clostridium perfringens was resistant or in a position to assume resistance were used on endangered stocks only in conjunction with penicillin or not at all. This programme of control has proved to be efficient through a period of more than three years.


[Studies of the regulation potential of glucose metabolism in the calf following infusion of fructose solution and using various hormones (ACTH, prednisolone, adrenaline and noradrenaline)].

Infusion of fructose solution (25 g in 100 ml) in sugar rations of 0.5 g or 1.0 g per kilogram of body weight usually induced in calf temporary drop of glucose in the blood plasma. This was attributable to rise in insulin secretion and glucose conversion or insufficiently fast effectiveness of insulin antagonists (adrenaline, glucagon, glucocorticosteroids). Such glucose drop could not be prevented by administration of 50 mg of prednisolone four hours before fructose infusion and 25 IU of ACTH five hours before infusion. Glucose as well as free fatty acids in the blood plasma went up in response to injection of 2.5 microgram/kg body weight during hypoglycaemia. The action of adrenaline was found to depend on the insulin dose given before in cases of insulin-induced hypoglycaemia. Doses of 0.5 g fructose per kilogram of body weight were administered in nine experimental infusions. Average half-life recorded from the blood plasma was 21.3 +/- 3.4 minutes.


Purification and characterization of bovine leukemia virus DNA polymerase.

An RNA-directed DNA polymerase was purified from bovine leukemia virus (BLV) by successive glycerol gradient centrifugation, column chromatography on phosphocellulose and gel filtration on Sephadex G-200. The purified DNA polymerase transcribes heteropolymeric regions of 30--40 S RNA isolated from avian myeloblastosis virus. The enzyme differs from other known DNA polymerases of mammalian type-C RNA tumor viruses by the following properties: 1. Its apparent molecular weight as estimated by velocity sedimentation data is 58,000 at 0.12 M KCl and 43,000 in the presence of 0.50 M KCl. 2. It has a Mg2+ optimum of 10 mM, and a Mn2+ optimum of 0.25 mM with (rA)n-(dT)10 as template. 3. At 50 mM KCl it is inhibited more than 70%, but it is not inhibited by phosphate ions at 2 mM. These properties confirm the peculiar position of BLV within the family Retraviridae.


Metabolism of cyclic nucleotides in allergic rhinitis: studies on lymphocytes, granulocytes, and plasma level.

The effect of isoproterenol on the cyclic nucleotide level in peripheral lymphocytes and granulocytes with allergic rhinitis patients and normal subjects has been studied. Responsiveness to 10(-5) M isoproterenol of lymphocytes decreased in the case of allergic rhinitis patients. When asthma was complicated to perennial rhinitis, a more significant depression was noted. In granulocytes the same tendency as with lymphocytes was noted although the difference was not significant. Basal level and responsiveness to 5 X 10(-3) M theophylline of both lymphocytes and granulocytes were similar in allergic rhinitis patients to normal subjects. The ratio of plasma cAMP to cGMP concentration was lower in the allergic rhinitis patients although the difference was not significant.


[Behavior of serum 25-hydroxycholecalciferol in humans after administration of vitamin D and 25-OHD3].

Serum levels of 25 hydroxycholecalciferol were evaluated following i.m. and p.o. vit. D2 and D3 and p.o. 25OHD3 administration. While no increment in 25OHD3 serum levels were observed after i. m. administration of non-hydroxylated calciferols, a marked increment of the metabolite was found following the oral administration. However the peak values were largely impredictable. Acute and chronic p.o. administration of 25OHD3 determines a rapid and dose-dependent increase of the serum levels of the metabolite. In addition considering that a lower dosage is required of 25OHD3 compared to vit. D, this metabolite is preferable in the therapeutic use.


Interference of MHV3 virus on ascites tumor growth.

In this experimental study the Authors have evaluated the interference of MHV3 hepatitis virus on Ascites Tumor's growth, using 4 groups of mice, the first one considered as control, the others inoculated with the virus 48 hours before, at the same time and 48 hours after tumor's inoculation. In each group labeling index, mitotic index and ascites volume were assessed a week after tumor's inoculation. The results seem to reveal an inhibition of tumor's growth in the second group. For this reason on the base of these encouraging observation, the Authors will continue researches to further confirm these preliminary results.