Action ofγ-aminobutyric acid and its phenyl derivative on central links of vascular reflexes from aortic-carotid chemo- and mechanoreptors

Experiments on decerebrate cats revealed an inhibitory effect of -aminobutyric acid (GABA; 100–200 g/kg) and its phenyl derivative, phenyl-GABA (20 mg/kg), on depressor responses of the systemic arterial pressure and on inhibition of spontaneous electrical activity in the renal nerve arising in response to excitation of the carotid sinus mechanoreceptors and afferent fibers on the sinus and depressor nerves carrying impulses from mechanoreceptors. Pressor responses of the systemic arterial pressure and electrical activity evoked in the renal nerve by stimulation of the carotid sinus chemoreceptors were intensified after administration of the same doses of GABA and phenyl-GABA. The results are interpreted from the standpoint of the depriming action of GABA and its phenyl derivative on the paramedian reticular nuclei of the medulla.Paper read at the March, 1974 Meeting of the Volgograd Scientific Society of Pharmacologists.Department of Pharmacology, Volgograd Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 4, pp. 71–75, April, 1975.     

Analysis of 5-nitrofuran derivatives in biological objects

Original methods for identification and quantitative photometry of 5-nitrofurane derivatives based on the use of known rhodanine reagents were developed and used in clinical analysis     

Influence of saccadic eye movements on geniculostriate excitability in normal monkeys

Summary Using permanently implanted electrodes in squirrel monkeys and macaques, transmission through the lateral geniculate nucleus (LGN) was assayed from the amplitude of potentials evoked in optic radiation by an electrical pulse applied to optic tract. Averaging of either individually or machine selected potentials, elicited at 0.3, 1.0, 20 or 50 Hz, in all cases showed a decrease in transmission ranging from 5–60 % in the period after saccadic eye movements made ad libitum. The suppression was greater in a patterned visual environment than in diffuse illumination, which in turn was greater than that occurring following saccades in the dark. Demonstration of the effect in darkness always required data averaging and never exceeded 20%. The effect was consistently greater in the magnocellular than parvocellular component. Suppression was often abruptly terminated and replaced by a facilitation of 5–15% about 100 msec after saccade detection. Comparable effects were observed for excitability of striate cortex tested by a stimulus pulse applied to optic radiation. In addition, sharply demarcated potentials inherently arising in LGN and striate cortex were found in association with saccades made even in total darkness. Neglecting a possible but dubious contribution from eye muscle proprioceptors, the experiments establish the existence of a centrally originating modulation of visual processing at both LGN and striate cortex in relation to saccadic eye movement in primates. This modulation may partially underlie the phenomenon of saccadic suppression and hasten the acquisition of a meaningful visual sample immediately following an ocular saccade. It remains uncertain as to how it may relate to similar or greater effects accompanying changes in alertness, or to fluctuations of unknown origin occurring sometimes semirhythmically at 0.05–0.03 Hz (Fig. 7).Supported by Grant NS 03606 and Contract 70-2279 from the National Institutes of Neurological Diseases and Stroke, National Institutes of Health and by Grant GB 7522X from the National Science Foundation. B.B.L. was also aided by a travel grant from the Wellcome Trust (U.K.) and H.S. received a travel grant from the International Brain Research Organization.     

Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat

Summary The role of GABA neurones in the medial preoptic area (MPOA) in regulating the activity of the luteinising hormone-releasing hormone (LHRH) neurones projecting to the median eminence was investigated in the conscious ovariectomised rat. Plasma luteinising hormone (LH) concentrations were measured while (1) endogenous GABA release from the MPOA was monitored with the technique of microdialysis, or (2) activity at the GABA receptor was modulated by local infusions into the MPOA. Microdialysis studies revealed a fluctuating level of GABA release in the MPOA which did not correlate with pulsatile LH secretion. Infusion of 10 M GABA (n=8) or bicuculline methiodide (BMI, n=6) into the MPOA, at a rate of l 1/30 min, significantly inhibited mean LH concentrations (P< 0.05-0.001) and LH pulse frequency (P< 0.05-0.001) compared with controls (n = 8). LH pulse amplitude was not significantly altered by infusion of GABA (P> 0.05) while too few pulses were found after BMI treatment to enable statistical analysis. Infusions of GABA into the ventral half of the MPOA had a more significant inhibitory effect upon LH secretion compared with dorsal infusions (P=0.012). A similar relationship did not exist for BMI infusions. These results show that acute changes in preoptic GABA receptor occupancy result in disruption of pulsatile LH secretion in the ovariectomised rat. This suggests that GABA neurones provide a tonic input important for the functional integrity of the neural network controlling LH secretion. However, as changes in extracellular GABA concentrations in the MPOA do not correlate with pulsatile LH release, the preoptic GABA population, as a whole, is unlikely to be directly responsible for the pulsatile activity of the LHRH neurones in the ovariectomised rat.     

Effect of immunization against rabies on γ-aminobutyric metabolism in the animal brain

Subcutaneous injection of fixed rabies virus into albino rats weighing 100–120 g is followed by a decrease in the-aminobytyric acid (GABA) concentration in the animals' brains. An increase in the activity of GABA--ketoglutarate transaminase also is observed in the brain tissue of animals vaccinated against rabies.Laboratory of Immunopathology, D. I. Ivanovskii Institute of Virology. Laboratory of Biochemistry, N. N. Burdenko Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician V. D. Timakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 184–185, February, 1976.     

Cytodifferentiation of human fetal lung tissue following transplantation into "nude" mice

Summary Lung fragments from 10 human fetuses aged 10 to 14 weeks of gestation were implanted into athymic nude mice. Cytodifferentiation of the transplants was studied by both scanning and transmission electron microscopy.Two weeks after implantation mitotic figures of epithelial and stroma cells were observed. In five week old transplants ciliated as well as endocrine cells were found dispersed among undifferentiated bronchial epithelium. During further experimental period epithelial differentiation in the transplants proceeded. Thus, eight week old implants assumed the morphologic appearance of fetal lungs in the canalicular stage displaying prospective type I and II pneumocytes. In addition stroma cells also differentiated forming mature fibroblasts and myofibroblasts.Our study indicates that human fetal lung tissue transplanted into nude mice not only grow but even differentiate. Xenogeneic transplantation of human fetal cells and tissues, therefore, offers additional opportunities to investigate the prenatal development of human tissues.Supported by EMDO and by Hartmann Müller Foundation     

Autogenetic inhibition of γ-motoneurons in the spinal cat uncovered by Dopa injection

Summary The response of identified gastrocnemius -efferents to stretch of the triceps surae muscle was recorded in the acute spinal cat before and after the injection of Dopa. A strong tonic inhibition during static muscle extension was detectable only in those -efferents which had no resting and reflex activity in the spinal cat, but which responded to Dopa injection with an initially high discharge rate. In contrast -motoneurons with background and reflex activity before Dopa, and some previously quiescent units acquiring a low discharge rate after Dopa did not exhibit any signs of a stretch-dependent inhibition. It is concluded that the observed autogenetic inhibition is limited to the static -motoneurons. The responsiveness to stretch-evoked inhibition was found to be correlated with that to antidromic inhibition induced by repetitive stimulation of the ventral root. This could imply that the activation of -motoneurons by muscle stretch leads to a Renshaw inhibition of the -motoneurons. However, this pathway may be only partly responsible for the autogenetic inhibition of -motoneurons in the spinal cat after Dopa, since the inhibitory effects of muscle stretch were more pronounced than those obtained by antidromic activation of motor axons in the ventral root.     

Immediate effects of intravenous IgG administration on peripheral blood B and T cells and polymorphonuclear cells in patients with myasthenia gravis

Five patients with myasthenia gravis, who received treatment with intravenous 7S -globulin were monitored for changes in immunological status. Serum immunoglobulin G increased from an average of 1.4 to 4.7 g/dl during the 5-day course of therapy. Specific antibody to the acetylcholine receptor present in three of five patients did not change. A transient decrease in total peripheral blood leukocytes was observed in five patients due to decreases in the absolute number of polymorphonuclear cells and lymphocytes in the circulation. Lymphocyte surface marker studies revealed that the percentage of surface immunoglobulin positive cells increased in all patients from an average of 13 to 26% by day 5 of therapy; however, the percentage of HLA-Dr- and Leu 12 (CD19)-positive B cells did not change. Lymphoid cells positive for the Leu 11 (CD16) marker doubled from an average of 11 to 24% during the 5-day course of therapy. Surface Ig-positive cells and Leu 11 (CD16)-positive cells returned to pretreatment values by 7 days posttherapy. Helper/suppressor cell ratios slowly decreased in all patients from an average of 2.9 to 2.2 by 1 week posttherapy and remained low for several weeks.     

γ-Glutamyltranspeptidase-Aktivität im Urin bei Gesunden und Nierenkranken

Zusammenfassung Die -Glutamyltranspeptidase-Aktivität (-GT) in der Niere ist bei chronischen Nephropathien und beim akuten Nierenversagen vermindert. Bei Gesunden wurde im Urin eine -GT-Aktivität von 12,7–37,7 mU/min ermittelt. Serum- und Urinaktivität verhielten sich unabhängig voneinander. Eine erhöhte -GT-Ausscheidung fand sich bei 75% der Nierenkranken mit normaler GFR, aber nur bei 11% mit eingeschränkter GFR.Zwischen -GT-Ausscheidung und Kreatininclearance bestand bei Gesunden (N=68,r=0,67) und Nierenkranken (N=114,r=0,71) eine statistisch hochsignifikante Korrelation. Bei Gesunden wurden deshalb die Toleranzgrenzen für beide Parameter gemeinsam berechnet. Bei Nierenkranken nahm die Enzymausscheidung proportional zur GFR und damit dem funktionsfähig verbleibenden Nierenparenchym ab. Die Relation -GT/C_Kreatinin erlaubt eine pathologisch gesteigerte Enzymabgabe aus den Tubuluszellen bei noch im Normalbereich liegender Gesamtausscheidung zu erkennen.     

Home intravenous immunoglobulin therapy by self-administration

Immunoglobulin replacement therapy is required by patients with certain antibody deficiency syndromes and is finding increasing application in other immune disorders such as immune thrombocytopenia. We describe the long-term home administration of intravenous -globulin by seven patients themselves using a portable infusion pump. Over a period of as long as 2 years, this has proven to be effective, safe, and cost efficient and a good alternative to hospital or physicians' office-based infusions.     

Ontogeny of GABA-immunoreactive cells in the primate cerebellar cortex: comparison with somatostatin-immunoreactivity

The distribution and ontogeny of GABA-immunoreactive cells were studied and compared with that of somatostatin-immunoreactivity in the primate cerebellar cortex. At embryonic day 80, we observed neither GABA-nor somatostatin-immunoreactive cells in the cerebellum. At embryonic day 110, a small number of GABA-immunoreactive cells was detectable in the granular layer only, and these cells seemed to be Golgi cells. At embryonic day 140, although almost all Purkinje cells were somatostatin-immunoreactive, a proportion of these cells was GABA-immunoreactive. At the newborn stage, most of the Purkinje cells were GABA-immunoreactive and almost all of them were also somatostatin-immunoreactive. During the postnatal stages, the number of somatostatin-immunoreactive cells decreased until postnatal day 60. At the adult stage, a large number of Purkinje cell bodies was faintly GABA-immunoreactive and a proportion of Purkinje cell dendrites was GABA-immunoreactive. In the aged animals (28 and 31 years old), a small number of Purkinje cell dendrites was GABA-immunoreactive. These findings suggest that a transition of phenotype from somatostatin to GABA occurred in Purkinje cells during development.Abbreviations Ad Adult - EX embryonic day X - GABA -aminobutyric acid - GAD glutamic acid decarboxylase - ir immunoreactive - Nb newborn (postnatal day 1–3) - NGF nerve growth factor - PX postnatal day X - PXy X years old - P8y < more than 8 years old - PBS phosphate-buffered saline - PL Purkinje cell layer - SOM somatostatin - WM white matter     

Immunomodulation by indoleamines: Serotonin and melatonin action on DNA and interferon-γ synthesis by human peripheral blood mononuclear cells

Different concentrations of indoleamines, serotonin and melatonin, inhibited phytohemagglutinin stimulated DNA synthesis. Thus, 10^–3 to 10^–4 M of either indoleamine acted at the optimal phytohemagglutinin concentration, while 10^–3 to 10^–7 M acted at suboptimal phytohemagglutinin levels. The serotonin effect was reversed by the serotonergic S₁-S₂ receptor antagonist methysergide but not by the S₂ antagonist ketanserin. This indicates that only the S₁ receptor is involved in the inhibitory effect. Inhibition of lymphoproliferation by indoleamines was also exerted on pokeweed mitogen and protein A fromStaphylococcus aureus stimulations. Serotonin and melatonin also inhibited phytohemagglutinin and protein A from Staphylococcus aureus induction of interferon- synthesis. The initial uptake of Ca²⁺ was not affected by indoleamines, suggesting that it is not the mechanism of their inhibitory effects. As interferon- induced tryptophan uptake by T lymphocyte- and macrophage-depleted populations, and tryptophan is the metabolic precursor of serotonin and melatonin, a new immunoregulatory circuit is postulated.     

Enhancement of interleukin-2 and γ-interferon productionin vitro on cord blood lymphocytes andin vivo on primary cellular immunodeficiency patients with thymic extract (Thymostimulin)

Cord blood mononuclear cells (MNC) were isolated from 20 normal full-term newborns. These MNC were preincubated with either 50, 100, or 200 µg/ml Thymostimulin or without Thymostimulin. The interleukin-2 (IL-2) and -interferon (-IFN) production, cytotoxicity, and lymphoproliferation and IL-2 receptor (Tac) expression were all significantly increased after Thymostimulin treatment. For evaluation of thein vivo effect, two combined-imimunodeficiency patients defective on the thymic level, one with progressive BCG infection, and one with DiGeorge syndrome were used. Before Thymostimulin treatment, the patient's MNC did not produce sufficient amounts of IL-2 and -IFN. The cytotoxicity and lymphoproliferation were also low. After Thymostimulin treatment, the IL-2 and -IFN production, cytotoxicity, and lymphoproliferative response were enhanced. These results suggest that Thymostimulin may be beneficial in the clinical treatment of primary cellular immunodeficiency. The improved immune reactivity including cytotoxicity and enhanced IL-2 and -IFN production in the Thymostimulin treatment also indicates that there may be a beneficial effect on the combination of chemotherapy and Thymostimulin.     

Interferon-γ for treatment of severe atopic eczema in two children

Two 4- and 5-year-old children suffering from refractory atopic dermatitis were treated with recombinant interferon- (rIFN-). rIFN- was injected at 50 g subcutaneously three times a week in the first child for 3 weeks, followed by three times 25 g in week 4. In the other child two treatment courses of 4 weeks were given after a break of 2 weeks. Therapy was well tolerated. In child one reductions in eczematous body surface and severity of lesions were observed, while no beneficial effect was seen in the other. Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. While marked immunological changes were noted during IFN- treatment, clinical benefits were not encouraging. Diminished IFN- production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN- can be recommended for therapy of pediatric atopic eczema.Abbreviations IFN- interferon- - IL interleukin     

Formation of Supramolecular Aggregations of γ-Globulin as a Metal-Dependent Process

The presence of copper cations in the solution of human serum -globulin induced the formation of supramolecular forms of the protein. The intensity of this reaction increased with increasing copper concentration. The mechanisms of -globulin aggregate formation under normal conditions and the possible role of bivalent metal cations in the regulation of protein effector functions are discussed.__________Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 139, No. 2, pp. 185–187, February, 2005     

Effect of whole-body γ-ray irradiation on the rate of steroid hormone hydroxylation by rat liver microsomes

The rate of hydroxylation of androgens was shown to be significantly reduced by -ray irradiation in doses of over 600 R. The rate of hydroxylation of estrogens showed little change. During irradiation under these conditions the content of cytochrome P-450 in the rat liver microsomes fell. The decrease in the rate of hydroxylation of steroid hormones by rat liver microsomes under the influence of whole-body -ray irradiation evidently depends on quantitative changes in cytochrome P-450.Department of Molecular Pharmacology and Radiobiology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute.(Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Pokrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 668–670, June, 1976.