Human T-lymphocyte subset production of immune (γ) interferon

Human T, T, and T lymphocyte subpopulations have the capacity to respond to phytohemagglutinin (PHA)in vitro with proliferation and the production of a pH 2 and heat-labile interferon. This occurs both when the subsets are isolated by direct rosetting techniques or by negative selection. Macrophages enhance the production of the interferon by each lymphocyte subset and do not themselves produce interferon in response to products of PHA-activated lymphocyte subsets. Thus our studies indicate that subpopulations of T lymphocytes known to differ with regard to morphology, surface receptors, RNA content, response to corticosteroids and X-irradiation, and other functional capabilities do not differ with regard to their capacity to produce interferon.     

Reduced intramembrane charge movement in the dysgenic skeletal muscle cell

Intramembrane charge movement in skeletal muscle cells has been proposed to underlie the process leading to Ca release from the sarcoplasmic reticulum. A number of recent studies suggest that the dihydropyridine receptor located in the transverse-tubular membrane is responsible for the generation of intramembrane charge movement. The skeletal muscle cell of the mutant mouse with Muscular Dysgenesis is characterized by absence of excitation-contraction coupling. Here we investigated the charge movement in freshly dissociated skeletal muscle cells from dysgenic mice. In 9 out of 34 dysgenic mouse cells the charge movement was completely absent, in the remaining cells the charge movement was never more than 30 % of control. The amount of maximum charge movement (Q_max) in mutant muscle cells was less than 30 % of Q_max in normal muscle. Nifedipine, a dihydropyridine derivative, reduced the amount of charge movement in normal muscle cells but it was less effective on charge movement in mutant muscle cells. We conclude that there is an alteration of nifedipine-sensitive charge movement in the skeletal muscle cells from the mutant mice.     

Regulatory T cell-subset imbalance in chronic active hepatitis

Three monoclonal anti-T-cell antibodies, specifically directed against total T cells (OKT3), inducer-helper T cells (OKT4), and suppressor/cytotoxic T cells (OKT8), were used in this study to analyze peripheral T-cell subsets in hepatitis B surface antigen (HBsAg)-positive and -negative chronic active hepatitis (CAH) patients. Results showed that a clear-cut difference exists in the distribution of peripheral T cells of these two groups of subjects. HBsAg-positive CAH patients had a numerical predominance of peripheral T lymphocytes expressing the characteristics of cytotoxic/suppressor T cells. In contrast, patients with autoimmune HBsAg-negative CAH exhibit a predominance of OKT4⁺ T cells, namely, the helper-inducer T-cell subset. In addition, high numbers of circulating doubly labeled cells (expressing both the OKT4 and the OKT8 xenoantigens) were detected in some of the HBsAg-positive and HBsAg-negative CAH patients studied.     

Role of adrenergic structures in functional control over the cerebral circulation

An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with and adrenoblockers showed that the constrictor response of the cerebral vessels is due to excitation of -adrenergic structures and the dilator response to excitation of -adrenergic structures. A possible mechanism of these changes is postulated.Laboratory of Pathophysiology of Respiration, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 9–12, January, 1976.     

Nuclear estradiol receptors in some nontarget organs of rats

Some properties of macromolecules, specifically binding estradiol (E₂), obtained from KCl extracts of nuclei of the uterus, kidneys, liver, testes, and prostate of male and female rats were investigated. These macromolecules from the uterus and liver were shown to be extractable in the largest amounts from chromatin by KCl in a concentration of 0.6 M. The ability of nuclear extracts of the uterus, kidneys, and liver to bind E₂ specifically was completely abolished by treatment with pronase, but not with RNase or DNase, thus indicating the protein nature of these macromolecules. Only estrogens and not testosterone, 5-dihydrotestosterone progesterone, or corticosterone, competed for these E₂-binding sites of the macromolecules from nuclear extracts of all the organs tested.Laboratory of Endocrinology, Biological Faculty, M. V. Lomonosov University, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 68–70, January, 1976.     

Role of adrenergic structures in functional control over the cerebral circulation

An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with and adrenoblockers showed that the constrictor response of the cerebral vessels is due to excitation of-adrenergic structures and the dilator response to excitation of-adrenergic structures. A possible mechanism of these changes is postulated.Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 9–12, January, 1976.     

Human arm stiffness characteristics during the maintenance of posture

Summary When the hand is displaced from an equilibrium position, the muscles generate elastic forces to restore the original posture. In a previous study, Mussa-Ivaldi et al. (1985) have measured and characterized the field of elastic forces associated with hand posture in the horizontal plane. Hand stiffness which describes the relation between force and displacement vectors in the vicinity of equilibrium position was measured and graphically represented by an ellipse, characterized by its size, shape and orientation. The results indicated that the shape and orientation of the stiffness ellipse are strongly dependent on arm configuration. At any given hand position, however, the values of these parameters were found to remain invariant among subjects and over time. In this study we investigate the underlying causes for the observed spatial pattern of variation of the hand stiffness ellipse. Mathematically analyzing the relation between hand and joint stiffness matrices, we found that in order to produce the observed spatial variations of the stiffness ellipse, the shoulder stiffness must covary in the workspace with the stiffness component provided by the two-joint muscles. This condition was found to be satisfied by the measured joint stiffness components. Using anatomical data and considering the effects that muscle cross-sections and changes in muscle moment arms have on the joint stiffness matrix, we found that these anatomical factors are not sufficient to account for the observed pattern of variation of joint stiffness in the workspace. To examine whether the coupling between shoulder and two-joint stiffnesses results from the coactivation of muscles contributing to these stiffnesses, EMG signals were recorded from shoulder, elbow and two-joint muscles. Our results indicated that, while some muscle coactivation may indeed exist, it can be found for only some of the muscles and in only part of the workspace.     

Role of the adenylate cyclase system in inductive acetylcholinesterase synthesis in the brain

The increase in acetylcholinesterase (ACE) activity in the rat brain after intraventricular injection of adrenalin and the dibutyryl analog of cyclic AMP was shown to be the result of inductive synthesis of the enzyme. Induction of ACE is manifested to a greater degree in the white matter of the subcortex than in the cortex. Blocking -adrenergic receptors inhibits the stimulating action of adrenalin on ACE activity but does not alter the effect of cyclic AMP. Blocking of the -adrenergic receptors, on the other hand, potentiates induction of synthesis of the enzyme. The effects of adrenalin and of dibutyryl-cyclic AMP are similar in direction and are mediated through -adrenergic receptors. The increase in ACE activity after blocking of receptors can be explained by the elimination of their inhibitory effect on -adrenergic receptors.Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 545–548, May, 1977.     

Changes in antigenic characteristics of erythrocytes and number metaphase chromosome in bone marrow cells after experimental and clinical bone marrow transplantation

Transplantation of allogenic bone marrow from HLA-identical sibs to patients with acute and chronic leukemia receiving immunosuppressive therapy is associated with the appearance of erythrocytes simultaneously carrying donor and recipient antigenic markers: AB0 system, rhesus factor and its subtypes, M and N antigens. Integration of genes responsible for each antigen is realized independently presumably at the level of stem cell, which ensures long-term (>3 years) repopulation of these erythrocytes. Experiments on inbred mice showed that transplantation of allogenic bone marrow is associated with an increase of chromosome number in 39% bone marrow cells 4 days after transplantation, which indicate the possibility of integration of whole chromosomes.     

In vitro contractility of the hypertrophied right ventricle of rats with pulmonary hypertension due to confinement in “hypoxic cages”

Summary Four weeks' confinement of rats in individual airtight cages with walls of defined permeability for respiratory gases induced hypoxic pulmonary hypertension and right ventricular hypertrophy.Parameters of isometric contractility of strips of hypertrophied right myocardium did not show significant changes when compared with the parameters of the inotropic state of slices of normal right ventricle.     

Therapeutic effects of intraarterial phentolamine in “Raynaud's syndrome”

Summary Five patients suffering from Raynaud's syndrome were studied as regards the effects of increasing doses of intraarterially administered phentolamine on the blood flow to the digital arteries. Upon angiography they had shown multiple occlusions of their digital arteries. Venous occlusive plethysmography of the forearm, volume pulse amplitude of a finger tip of treated and untreated extremity, respectively, intraarterial pressure in the brachial artery and ECG lead II have been monitored continuously. The blockade of the alpha-adrenoceptors by phentolamine resulted in a favourable effect upon the accompanying functional component: The volume pulse amplitude of and the blood flow to the treated extremity increased considerably, without significant changes in the other hemodynamic parameters upon administration of doses up to 0.5 mg of phentolamine. A dose of 0.5 to 1.0 mg of phentolamine seems to be the optimum, higher doses yielding no better results. The effective blockade of the alpha-adrenoceptors could be demonstrated by the influence on the arterial blood pressure during a Valsalva maneuvre, on the venous reflex response, and the diminished effectiveness of noradrenaline in the treated extremity.     

Angiogenesis from mononuclear cells in thrombi

Summary In organizing thrombi angiogenesis is not dependent on invasion of vasa vasora from the vascular wall. Mononuclear cells of the monohistiocytic system are always present within the clotted blood and are capable of differentiation into various types of mesenchymal cells, including endothelial cells. At first autolytic slits and clefts appear in the fibrinous superficial areas of the thrombus. They are gradually lined by spindle-shaped pre-endothelial cells that already possess immunohistological properties of endothelial cells but still resemble primitive mesenchymal cells ultrastructurally. Later these cells gain connection with each other by pseudopodia, overlapping and interdigitation until the channels in the fibrinous matrix are covered by an uninterrupted layer of cells. These cells are now characterized ultrastructurally by the appearance of specific endothelial organelles (Weibel-Palade bodies). Circulation within these channels begins from the blood stream. In addition, angiogenesis by sprouting of vasa vasora from the vascular wall occurs in those areas of the thrombus in contact with the vessel wall. In blood vessels with on unimpaired intimal layer, angiogenesis by invasion of capillaries occurs at an earlier date than capillary formation by mononuclear cells.     

Role of level of serotonin activity in the “shock lung” syndrome

Experiments on rats showed that the level of serotonin activity influences the formation of the shock lung syndrome. In hypoactivity tachyhypopnea is observed and the lung shows a pathomorphological picture characterized by numerous atelectases; in hyperactivity there is a corresponding tachyhyperpnea and a very small number of atelectases.Kazan' Research Institute of Traumatology and Orthopedics. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1181–1183, October, 1976.     

Flow Cytometric Analysis of In Vitro Proinflammatory Cytokine Secretion in Peripheral Blood from Multiple Sclerosis Patients

The cytokines, interferon- (IFN-), tumor necrosis factor- (TNF-rpar;, and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-, IL-2, and TNF- from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-, IL-2, and TNF- secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF- secreting CDS cell percentage is correlated with the IFN- and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF- secreting CD3 cell percentage is correlated with IFN-. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.