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Biomedical subjects

S Varga

Publications and source records attributed to S Varga.

At least 55 records · Page 3Linked to original sources

Pressure effects on sarcoplasmic reticulum.

The irreversible effects of pressure (1-2000 atm) upon the enzymatic activity and structure of the Ca2+-ATPase of sarcoplasmic reticulum were investigated. Sarcoplasmic reticulum vesicles suspended in a medium of 0.1 M KCl, 10 mM imidazole, pH 7.0, 5 mM MgCl2, and 0.5 mM EGTA irreversibly lose their Ca2+ transport and Ca2+-stimulated ATPase activities on exposure to pressures of 800-2000 atmospheres. The pressure-induced inactivation of Ca2+-ATPase is accompanied by inhibition of the formation of phosphorylated enzyme intermediate, an increase in the passive Ca2+ permeability of the membrane, and structural changes in the Ca2+-ATPase as shown by disruption of Ca2+-ATPase membrane crystals, increased susceptibility to tryptic digestion, unmasking of SH groups, and loss of the conformational responses to Ca2+ and vanadate. The sensitivity to pressure is influenced by enzyme conformation. Ca2+ or vanadate + EGTA protect the Ca2+-ATPase against pressure-induced inactivation, implying a greater stability of the enzyme in the E1 and E2 states than in the conformational equilibrium that prevails at low [Ca2+] in the absence of vanadate. Protection against pressure inactivation was also observed in the presence of sucrose, glycerol, ethylene glycol and 1 M KCl, suggesting that water density modifying groups significantly affect the stability of Ca2+-ATPase under pressure.

4-Nitrophenylphosphatase↗

Competition between decavanadate and fluorescein isothiocyanate on the Ca2+-ATPase of sarcoplasmic reticulum.

The binding of vanadate and fluorescein isothiocyanate to the Ca2+-transport ATPase of sarcoplasmic reticulum (EC 3.6.1.3) was analyzed. Monovanadate binds to the Ca2+-transport ATPase at a single high affinity site (site 1), that is presumably related to the binding site for inorganic orthophosphate, and to one of the two sites for decavanadate. Binding of vanadate to this site stabilizes the enzyme in the E2 conformation, with inhibition of ATPase activity and the formation of crystalline arrays of Ca2+-ATPase. Decavanadate also binds with high affinity to a second site on the Ca2+-ATPase (site 2), that is blocked by fluorescein isothiocyanate and may be part of the binding site for ATP. Crystallization of Ca2+-ATPase in sarcoplasmic reticulum, labeled with fluorescein isothiocyanate, by either monovanadate or decavanadate implies that occupation of site 1, but not of site 2, by vanadate is required for the conformational change of Ca2+-ATPase leading to the formation of crystalline arrays.

Animals↗

The binding of vanadium (V) oligoanions to sarcoplasmic reticulum.

The binding of monovanadate and decavanadate anions to sarcoplasmic reticulum vesicles was measured by equilibrium sedimentation. The affinity of vanadate binding and the molar amount of vanadium (V) bound at equilibrium is much greater with decavanadate than with monovanadate. The binding data can be rationalized in terms of one binding site per ATPase molecule for monovanadate and two sites per ATPase for decavanadate. The Ca-ATPase crystals formed with monovanadate and with decavanadate are similar in appearance, but decavanadate is particularly effective in promoting the crystallization of Ca2+-ATPase at low V concentration (10-100 microM) in a Ca2+-free medium.

Animals↗

The detection of circulating immune complexes containing C1q and IgG using a new rapid serum ELISA test system.

An ELISA sandwich assay for detecting circulating immune complexes (CIC) was evaluated. Heat-aggregated IgG (HAG) containing Clq (HAG:Clq) is used to generate standard curves for quantitation of CIC. Sera from 488 normal donors had an means of 3.8 +/- 15.3 micrograms/ml HAG eq and 97.1% had concentrations less than 35 micrograms/ml HAG eq (2 SD greater than means) and were considered negative. Sera from rheumatoid arthritis (RA) patients in active disease tested 86% positive for CIC (means = 104.5 +/- 63.4 micrograms/ml HAG eq) while 100% with inactive disease were negative (means = 11.4 +/- 3.7 micrograms/ml HAG eq). Similarly, in systemic lupus erythematosus (SLE) patients with active disease, 100% were positive (means = 133.1 +/- 50.6 micrograms/ml HAG eq) while 80% with inactive disease were negative (means = 20.4 +/- 21.4 micrograms/ml HAG eq). In AIDS (AIDS related), 88.5% of AIDS sera and 77.1% of lymphadenopathy syndrome (LAS) sera had elevated CIC. Sera from asymptomatic homosexual controls showed 85% positive for CIC. The serum ELISA test for CIC compared favorably with the 125I-staphylococcus binding assay but was more sensitive than the 125I-C1qBA. The OKT4/OKT8 ratios were also significantly reduced in AIDS and LAS.

Acquired Immunodeficiency Syndrome↗

Activity and characteristics of inflammatory effector cells in newborns.

To investigate the aspecific activity of inflammatory effector cells (mononuclear and polymorphonuclear leukocytes) of newborn babies, a comparative study was performed of chemotactic and random filter motility, phagocytic activity, and bactericidal capacity of these cells, of the electron microscopic counterparts of these activities, the serum factors influencing motility and of the content and ratio of cyclic nucleotides present in the cells of subjects of different ages. It was found that chemotaxis of the mononuclear and polymorphonuclear leukocytes is a gradually maturing function; its deficiency observed during the neonatal period is not caused by a depressed excitability by chemical agents, by the presence of inactivators of chemotactic factors or of chemotaxis inhibitors. It is the low serum levels of total complement, C 3, IgG, IgM and properdin that explain the reduced chemotactic mobility. In addition to these factors reduced leukocyte flexibility, condition and activity of the flexibility, condition and activity of the microtubular and microfilamentary system depending on calcium ion and cyclic nucleotide concentrations, and an eventual immaturity or exhaustion of certain intracellular enzymes also play a part. In respect to orientation towards chemical stimuli, the leukocytes of the newborn largely differ from those of children or adults. Similarly, a difference in uptake and elimination of bacteria and in ultrastructural changes accompanying these processes can be demonstrated between newborn and adult cells. The aspecific cellular functions, the reduction of which plays an important part in the weak resistance of the newborn, also depend on certain properties of the infective agents.

Adult↗

Experimental calcipenic osteopathy.

Calcipenic osteopathy was used as a model, in order to reveal the diagnostic value and capacity of the noninvasive radiological methods (microradioscopy, densitometry, and Roentgen-morphometry), in comparison with the results of histological, histomorphometrical, and atomic absorption methods. The study proved that calcipenic diet causes an osteoporosis in the experimental animals. The alterations observed meet both the histological and radiological criteria.

Animals↗

Alterations of the connective tissue in nude mice.

The epiphyseal cartilage of nude mice was studied by light and electron microscopy. The resting and maturation zones become narrow and mineralization of the ground substance starts already in the zone of proliferation. Electron microscopy reveals signs of degeneration in the chondrocytes of this latter zone. An increased osteoclast activity can be observed in the metaphysis. The alterations may be due to a decrease in T-cell-mediated immunoreactivity of nude mice, as well as to an increased production of the osteoclast-activating factor, which might be attributed, among other things, to the B lymphocytes or macrophages.

Animals↗

The effect of experimental hypothyrosis on the fine structure of the epiphyseal cartilage of young rats.

Authors studied the effect of hypothyrosis induced by thyro-parathyroidectomy and mercaptoimidazole treatment on the fine structure of the proximal epiphyseal cartilage of tibia in growing male rats. It has been established that the cell density of the epiphyseal cartilage decreases in the experimental hypothyrosis, about 30 to 50% of the chondrocytes display degenerative signs, whereas the Golgisystem seems to be well developed. The most characteristic alteration appear in the zones of proliferation and maturation of the epiphyseal cartilage. The endoplasmic reticulum (ER) and mitochondria show a considerable regression also in the chondrocytes displaying minimal or even no signs of degeneration. Elements indicating calcification were encountered more frequently in the cartilaginous matrix of the zones of maturation and calcification under the effect of mercaptoimidazole treatment as compared to the controls, whereas the matrix of the animals operated was poorer in minerals than the corresponding zones of the controls. This difference is attributed by the authors to the different levels of thyrocalcitonin in the two kinds of experiments.

Animals↗

[Leukocyte function in colostrum (author's transl)].

Breast milk, especially colostrum was analysed quantitatively and qualitatively as well as the function of various cell types in it. The phagocyte activity of the mass of leukocytes consisting predominantly of macro- and microphages approaches the phagocyte index of leukocytes of the newborn infant, however, neither of them reaches the level of adults.--The lymphocytes traceable in a minor proportion produce secretory IgA as well as IgG.--On the basis of literary data the authors discuss the literature and their own results regarding the immunobiological significance of breast milk.

Colostrum↗

Ultrastructural changes of the rat renal glomeruli in the early phase of renovascular hypertension.

Electron microscopic studies were carried out on rat kidneys during the early phase of "two-kidney" Goldblatt hypertension. Pathologic ultrastructural changes (confluence of foot processes of the podocytes, formation of intercellular juctions between them, etc.) and an enhanced permeability to ferritin were found in the glomeruli of both the ischaemic and the contralateral kidneys. Signs of activation and exhaustion of the lysosomal system appeared in the glomerular epithelial cells of the untouched kidneys. These signs were absent in the kidneys with constricted arteries. The possible significance and pathogenesis of the alteration are discussed in comparison with other pathological conditions showing a similar ultrastructural picture.

Animals↗

Studies on cartilage formation XIX. Oxygen and glucose supply of the regenerating articular surface.

Complete removal of the articular cartilage in dogs is followed by regeneration of the articular surface. At the site of the bone wound, granulation tissue develops, which later differentiates into cartilage. The O2 and glucose supply of the regenerating articular surface is ensured by the synovial fluid, by the large exposed surface of the medullary cavity, and by the capillary network of the granulation tissue. Oxygen and glucose supply of the articular surface in different stages of differentiation has been statistically analyzed. It is suggested that in the early stage of regeneration O2 supply comes predominantly from the capillaries of the granulation tissue. Later on, as capillarization regresses, the oxygen supply, originating from the synovia and medullary cavity, assumes a more important role. In the stage of cartilage regeneration an oxygen-deficient state can be supposed in the entire articular surface, but areas differing in oxygen supply may be formed owing to local differences (due mainly to the extent of vascularization and degree of generation of the subchondral bone layer). At the site of chondrogenesis, conditions allowing aerobic metabolism of cells with reduced O2 requirements seem to be ensured. Glucose supply deriving from the above-mentioned sources satisfies the highest glucose requirements of the cells in the regenerating articular surface.

Animals↗