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Biomedical subjects

J Joseph

Publications and source records attributed to J Joseph.

At least 145 records · Page 8Linked to original sources
PubMed1993

Trapping of nitric oxide by nitronyl nitroxides: an electron spin resonance investigation.

Nitric oxide (.NO) exerts a major regulatory physiological role in the cardiovascular and central nervous system. .NO is also metabolically released from nitrovasodilators such as nitroprusside, nitroglycerin, and synonimines whose mechanism of cardioprotection appears to be related to their .NO release. However, techniques to detect and quantitate .NO in solution are limited. In this paper, we report an electron spin resonance (ESR) technique that will continuously monitor the production of .NO in solution. This methodology is based on the reaction between .NO and nitronyl nitroxides (a group of organic compounds with nitronyl and nitroxide functional groups) to produce imino nitroxides. The ESR spectra of nitronyl nitroxides and imino nitroxides are characteristic and distinctly different. Nitronyl nitroxide to imino nitroxide conversion is catalyzed only by .NO, but not by superoxide anion, hydroxyl radical or nitrogen dioxide (.NO2). Nitrite ion (NO2-) was determined to be a major product of this reaction. Using ESR and optical techniques, we have continuously monitored the production of .NO and NO2- during visible irradiation of sodium nitroprusside. We conclude that this ESR approach can be applied to probe mechanisms of .NO and NO2- production from nitrovasodilators. The clinical implications of trapping of .NO by nitronyl nitroxides are also discussed.

Cyclic N-Oxides↗
PubMed1993

Effects of staphylococcal enterotoxin B on T cell receptor V beta utilization and clinical manifestations of experimental allergic encephalomyelitis.

Staphylococcal enterotoxin B (SEB) is a superantigen (SA) that up-regulates and then subsequently down-regulates and deletes T cells expressing V beta 8 T cell receptor (TcR) chains (Marrack and Kappler, 1990; Johnson et al., 1991). We have investigated the effect of SEB on experimental allergic encephalomyelitis (EAE) in PL/J mice, where the predominant encephalitogenic T cells are V beta 8+ (Acha Orbea et al., 1988; Zamvil et al., 1988). SEB did not enhance induction of EAE when administered prior to or after immunization for EAE. PL/J mice pretreated with SEB developed anergy and deletion of V beta 8 bearing cells and concomitant reduction in the incidence of EAE. Following SEB pretreatment, a redistribution in the TcR utilization of MBP-specific lymphocytes occurred. As a result, there was a low frequency of V beta 8 and expansion of other, normally less frequent, myelin basic protein (MBP)-specific clones. These observations indicate that systemic exposure to superantigen can influence organ-specific autoimmune diseases. We observed V beta-specific elimination, rather than activation, of autoimmune clones, a finding of potential therapeutic value. Modification of the TcR repertoire by systemic exposure to this SA indicates plasticity of immune reactivity and demonstrates a mechanism by which an environmental exposure (SEB) can influence a genetically determined, T cell mediated autoimmune disease.

Animals↗
PubMed1993

Interleukin-6 induction in vitro in mouse brain endothelial cells and astrocytes by exposure to mouse hepatitis virus (MHV-4, JHM).

Interleukin-6 (IL-6) induction, as detected by bioassay and Northern analysis, was examined in vitro in endothelial cells or astrocytes derived from BALB/c (susceptible) or SJL (resistant) mice following exposure to mouse hepatitis virus (MHV-4) or UV inactivated MHV-4 (UV-MHV-4). In BALB/c endothelial cells, up to 16-fold more IL-6 (> 640 U/ml) was induced, compared to SJL cells which showed a minimal response (40 U/ml), relative to basal levels (< 20 U/ml). In contrast, both BALB/c and SJL astrocytes showed a substantial IL-6 response to MHV-4 and UV-MHV-4 exposure, although a strain difference persisted. Despite strain and cell specific differences in released IL-6, equivalent levels of IL-6 mRNA were induced in all cell types following exposure to MHV-4 or UV-MHV-4.

Animals↗
PubMed1993

Vasodilatory and toxic effects of spin traps on aerobic cardiac function.

The objective of this study was to compare the effect of several structurally related nitrone and nitroso spin traps on the function of the isolated bicarbonate-buffer perfused rat heart model. Spin traps investigated were alpha-phenyl-tert-butyl N-nitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN), 2-methyl-2-nitroso propane (MNP), 2-hydroxymethyl-2-nitroso propane (MNP/OH), nitrosobenzene (NB), dibromonitrosobenzene-sulfonic acid (DBNBS), and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). During perfusion of hearts with increasing concentrations of spin traps, ventricular pressure, coronary flow rate, and heart rate were continuously recorded. The extent of contractile recovery was subsequently measured upon return to spin-trap free perfusion. The percentage of maximum increase in coronary flow with PBN, POBN, MNP, MNP-OH, NB, DBNBS, and DMPO were 11, 40, 45, 66, 28, 28, and 29%, respectively. Thus, all nitroso and nitrone spin traps studied acted as vasodilators. Over the dose range studied, POBN, MNP, MNP/OH, and DMPO did not exert any chronotropic effect. PBN, NB, and DBNBS exerted a negative chronotropic effect at higher concentrations. All spin traps studied, with the exception of DMPO, exerted a negative inotropic effect at the higher concentrations studied. We conclude that all spin traps examined acted as coronary vasodilators. Their negative chronotropic and inotropic effects were minimal in comparison and only manifest at the higher concentrations studied.

Aerobiosis↗
PubMed1993

Phacoemulsification with poorly dilated pupils.

Tilting the viewing angle of the operating microscope during phacoemulsification provides the surgeon a better view of the cataractous lens. This technique, combined with continuous curvilinear capsulorhexis, divide and conquer nucleofractis, and lens rotation in the capsular bag, allows the surgeon to perform most of the phacoemulsification procedure near a well-visualized 6 o'clock meridian. This procedure can eliminate the need for iris surgery in cases with small pupils. Also discussed is the removal of the upper half of the cortical substance in patients with small pupils.

Cataract Extraction↗
PubMed1993

Early inflammatory response of minocycline and tetracycline on the rabbit pleura.

The histopathologic findings were compared from 20 mg/kg intrapleural tetracycline hydrochloride (TCN) and three doses of intrapleural minocycline hydrochloride (5, 10, and 20 mg/kg) (MCN) in New Zealand white rabbits. Both TCN and MCN produced an early neutrophilic predominant pleural effusion that became mononuclear over 48 h. There was no difference in pleural fluid accumulation, number of adhesions, or histologically measured visceral and parietal pleural thickness between TCN and MCN (all p = ns). The TCN, 20 mg/kg, produced more visceral pleural plaque than MCN, 5 mg/kg (p < 0.05). Increasing MCN doses resulted in greater pleural fluid neutrophil accumulation. With higher dose MCN, greater mesothelial cell desquamation and fibroblast proliferation was evident compared to the 5 mg/kg dose. The MCN and TCN produce similar histopathologic condition in the rabbit pleura which suggests that MCN should cause a similar clinical response in humans.

Analysis of Variance↗
PubMed1993

Monoclonal anti-gamma interferon antibodies enhance experimental allergic encephalomyelitis.

Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-gamma can exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-gamma during the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-gamma did not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-gamma Mab resulted in more sever disease than that induced by MBP stimulated cells or MBP and IFN-gamma co-stimulated cells. However, in vitro proliferation of an MBP specific T cell line was not influenced by IFN-gamma nor anti-IFN-gamma treatment. Mab to IFN-gamma inhibited suppressor function, in a non-specific assay. These in vivo and in vitro results suggest that systemic IFN-gamma serves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-gamma administration contributes to a more severe form of experimental allergic encephalomyelitis.

Animals↗
PubMed1993

Effect of exogenous dexamethasone and corticosterone on weight gain and organ growth in post-hatched white Leghorn chicks.

Induced chronic hypocorticalism by dexamethasone (DXM) and hypercorticalism by corticosterone (CORT) retarded body weight gain as well as the growth of spleen, bursa, liver, kidney and pancreas during the first month of development in male leghorn chicks. Adrenal weight was reduced by DXM and increased by CORT. Correspondingly, there were histological regressive changes in the cortex with a decreased cortico-medullary ratio with DXM treatment, while a reverse trend was there with CORT treatment. However, an increase in weight of testis and better organization of seminiferous cords and interstitium was observed in DXM treated chicks, and there was a decrease in weight and poor histological organization in CORT treated chicks. Both DXM and CORT induced stimulatory changes in thyroid denoted by increased epithelial cell height and decreased colloidal content. These observations indicate that corticosteroids have definite influence on post-hatched growth and maturation of chicks.

Animals↗
PubMed1992

Direct modification of low density lipoprotein by the spin trap 3,5-dibromo-4-nitrosobenzenesulfonic acid.

We have previously reported that the spin trap alpha-phenyl-tert-butyl nitrone (PBN) inhibited the oxidative modification of low density lipoprotein (LDL) (Kalyanaraman, B., Antholine, W.E. and Parthasarathy, S. (1990) Biochim. Biophys. Acta 1035, 286-292). In the present study, we report that 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS), a water-soluble spin trap, also inhibited the oxidation of LDL as measured by the formation of thiobarbituric acid reactive substances (TBARS). However, when compared with LDL incubated without DBNBS, the DBNBS-incubated LDL showed increased negative charge on agarose gel electrophoresis and was avidly degraded by mouse peritoneal macrophages. Despite the suggestion of biological modification, there was no decrease in lysine-amino groups in DBNBS-incubated LDL. Furthermore, reductively methylated LDL in which more than 85% of the amino group of lysines was blocked, was also modified by DBNBS. A sulfonic acid analog of PBN failed to modify LDL in a similar manner, suggesting that the presence of sulfonic acid alone does not ensure modification. When LDL was incubated with DBNBS, radical adducts associated with both lipid and protein were detected by electron paramagnetic resonance (EPR) technique. It is suggested that DBNBS may bind to the apoprotein B100 and lipids of LDL by a lysine-independent mechanism resulting in increased recognition and degradation by macrophages. The present work offers a novel approach for rapid modification of LDL.

Benzenesulfonates↗
PubMed1992

Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of low density lipoprotein.

Chain-breaking antioxidants such as butylated hydroxytoluene, alpha-tocopherol, and probucol have been shown to decrease markedly the oxidative modification of low density lipoprotein (LDL). Their mechanism of action appears to involve scavenging of LDL-lipid peroxyl radicals. The purpose of this study was to investigate the occurrence of radical reactions produced during oxidation of LDL and LDL-containing probucol initiated by lipoxygenase or copper. In addition, we have investigated the possibility of a synergistic interaction between ascorbate and probucol in inhibiting the oxidation of LDL. Incubation of LDL-containing probucol and lipoxygenase produced a composite electron spin resonance (ESR) spectrum due to the endogenous alpha-tocopheroxyl radical and probucol-derived phenoxyl radical. The spectral assignment was further verified by chemical oxidation of alpha-tocopherol and probucol. In the presence of ascorbic acid, these radicals in the LDL particle were reduced to their parent compounds with concomitant formation of the ascorbate radical. In both the peroxidation of linoleic acid and the copper-initiated peroxidation of LDL, the antioxidant activity of probucol was significantly increased by low (3-6 microM) concentrations of ascorbate. The probucol-dependent inhibition of LDL oxidation was enhanced in the presence of ascorbic acid. We conclude that the reaction between the phenoxyl radical of probucol and ascorbate results in a synergistic enhancement of the antioxidant capacity of these two compounds and speculate that such reactions could play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo.

Analysis of Variance↗
PubMed1992

Autoimmune inflammation of astrocyte transplants.

Astrocytes have been shown to be capable of serving as antigen-presenting cells and as targets for encephalitogenic cytotoxic T lymphocytes. The role of astrocytes in central nervous system (CNS) autoimmune inflammation is unclear. To study this further, we transplanted astrocyte aggregates into the anterior eye chamber of the mouse. The astrocytic nature of these transplants was confirmed by immunohistochemical detection of glial fibrillary acidic protein and the inability to detect oligodendrocyte or microglial markers. When mice bearing transplants were induced to develop experimental allergic encephalomyelitis by either passive or active protocols, the astrocyte transplants developed a perivascular inflammatory response similar to that seen in the host CNS during the course of the encephalomyelitis. The data suggest that astrocytes could serve as targets for the autoimmune attack of experimental allergic encephalomyelitis and support the possibility that the pathogenesis of this disease may involve an autoimmune reaction against a site other than the myelin sheath.

Animals↗