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Biomedical subjects

J Joseph

Publications and source records attributed to J Joseph.

At least 19 recordsLinked to original sources

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

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

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

Alterations in carbohydrate metabolism by exogenous dexamethasone and corticosterone in post-hatched White Leghorn chicks.

1. Alterations in carbohydrate metabolism in terms of tissue glycogen contents, phosphorylase (EC 2.4.1.1) activity, hepatic glucose-6-phosphatase (6-6-Pase: EC 3.1.3.9) activity and blood glucose have been evaluated in 30-d-old White Leghorn chicks under induced chronic hypocorticalism (by dexamethasone: DXM) and hypercorticalism (by corticosterone: CORT). 2. DXM treatment showed increased tissue glycogen contents and hypoglycaemia with decreased phosphorylase activity while CORT treatment produced a reverse set of changes. 3. Both steroid treatments increased hepatic G-6-Pase activity. These observations have been taken to indicate a definite role for glucocorticoids in regulating carbohydrate metabolism in neonatal chicks. 4. It is suggested that hypo- or hyper-corticalism could influence carbohydrate metabolism by affecting the secretory/activity ratio of pancreatic hormones.

Animals

A dual-isotope method for studying protein kinetics in pleural effusions in humans.

A method is described for studying protein kinetics in pleural effusions in humans. In 15 patients with pleural effusions from a variety of causes, protein inflow was monitored by measuring the rate of appearance in the effusion of the plasma protein transferrin, radiolabelled in vivo by intravenous injection of 113InmCl3. Protein outflow was measured from the rate of appearance in the blood of intrapleurally administered 125I-albumin. Compartmental analysis has been used to determine rate constants k(in) and kout for the movement of labelled proteins into and out of the effusion, respectively. The mean value of k(in) for 15 patients was 9.4 x 10(-4) h-1 (range 2.2-21.4). The mean value of kout in the same patients was 28 x 10(-4) h-1 (range 6-68). Using appropriate assumptions where necessary, the absolute transfer rates of albumin and transferrin were also estimated. For albumin, the mean rate of outflow was 66 mg h-1 (range 27-158), compared to mean estimated inflow of 133 mg h-1 (range 36-381). Protein inflow was highest in a case of metastatic ovarian carcinoma with pleural and peritoneal seedlings, indicating high vascular permeability. Protein outflow was very low in a case of mesothelioma, suggesting severely impaired lymphatic drainage. The technique may prove to be a useful tool for studying mechanisms resulting in the formation of malignant and nonmalignant pleural effusions, and may also be useful for studying the effects of putative therapeutic intervention.

Aged

A prospective study of amylase-rich pleural effusions with special reference to amylase isoenzyme analysis.

By analysis of pleural effusions from 200 patients, 25 cases of amylase-rich effusions were identified, for an overall incidence of 13 percent. Four of the 25 patients (16 percent) had evidence of pancreatitis. These patients had higher mean ratios of pleural fluid to serum amylase levels (18 +/- 6.3 [SEM] vs 4.8 +/- 1.3) compared to patients with nonpancreatic diseases (p = 0.003); all four exhibited a predominant pancreatic isoenzyme profile. Of the 21 patients with nonpancreatic amylase-rich effusions, lung cancer was the most commonly associated condition (8 patients). In 14 of the 21 patients in whom an isoenzyme profile was obtained, salivary-type amylase was predominant. Amylase-rich pleural effusions occur frequently, and pleural fluid isoamylase determination is specific for pancreatitis-associated effusions. The finding of a pleural effusion rich in salivary isoamylase should prompt an evaluation for carcinoma (particularly of lung primary), but may also be seen in other pleural inflammatory conditions.

Amylases

Potentials associated with the initiation and inhibition of visually triggered finger movement in humans: the "no-go potential" in the go/no-go paradigm.

Surface event-related potentials associated with visually triggered movements (Go) and the inhibition of planned movements (No-Go) of the right index finger were examined in seven normal healthy subjects. Subjects' response priming was manipulated by presenting two sessions which either emphasized the Go condition (50 go trials vs. 30 no-go trials) or the No-Go condition (30 go trials vs. 50 no-go trials). Stimulus-locked waveforms showed enhanced components (P1-N1, N2, N1-P300) for the No-Go trials particularly in the response priming which emphasized the Go condition. It is suggested that the inhibition of planned movements is associated with surface negativity which trails the sensory P1-N1 potential yet may partially overlap it and therefore influence its amplitude. This "no-go" potential is dependent on the response priming of the subject and is most apparent when fast responses are planned and then arrested.

Adult

The link between sexually transmitted disease clinics and HIV counseling and testing centers: who is not getting referred?

A total of 236 clients attending human immunodeficiency virus (HIV) counseling and testing (C&T) centers and sexually transmitted disease (STD) clinics were interviewed to evaluate who is being reached by C&T services and if STD clients are being referred to HIV C&T centers. Respondents receiving HIV C&T reported significantly more sexual risk based on characteristics of their partners, whereas STD clinics respondents more frequently reported previous STD diagnoses and sex with prostitutes. Over 50% of the high-risk individuals attending STD clinics were not referred to HIV C&T centers. The differences in perceived risk of current and future infection between STD and HIV C&T centers and the low referral rates of high-risk individuals for HIV C&T indicate a need for increased education efforts, more effective risk-assessment policies in STD clinics, and a tightening of the link between STD clinics and HIV C&T centers.

Adolescent

Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant and malignant disease.

TAG-72 is a tumor-associated antigen identified by the monoclonal antibody B72.3. Serum levels of TAG-72 were measured in patients with non-malignant and malignant disease. TAG-72 is not a specific marker of cancer and slightly elevated levels of this antigen can also be detected in the serum of healthy subjects. However, our results show that specificity (92%) and positive predictive value (86%) of this marker are very high. TAG-72 levels above the cut-off limit of 6 U/mL were found in patients with tumors of various organs, including gastrointestinal, ovarian, lung and breast cancer. TAG-72 assay sensitivity is related to tumor stage with values being highest with advanced disease, especially in patients with gastric cancer and lung adenocarcinoma.

Antigens, Neoplasm

Mouse hepatitis virus (MHV-4, JHM) blocks gamma-interferon-induced major histocompatibility complex class II antigen expression on murine cerebral endothelial cells.

The regulation of gamma-interferon-induced major histocompatibility complex (MHC) class II antigen expression on mouse cerebral endothelial cells by the neurotropic mouse hepatitis virus (MHV-4, JHM) was studied in vitro. The results presented demonstrate that MHV-4 can selectively block gamma-interferon-induced class II antigen expression on cerebral endothelial cells. The blocking effect of class II expression occurs in a strain-dependent manner, and is limited to virus-susceptible mouse strains. Virus replication is not required to obtain the blocking effect since UV-inactivated MHV-4 produces the same result. MHV-4 blocking of gamma-interferon-induced class II antigen expression is observed at both the cell surface (flow cytometry) and transcriptional level (Northern analysis).

Animals

Stressful life events and symptom onset in HIV infection.

OBJECTIVE: The authors' goal is to provide basic epidemiologic data on the issue of reactivity to stress and HIV symptom onset by studying the relationship between a broad set of naturally occurring stressor events and HIV natural history in a large longitudinal community sample of HIV-seropositive homosexual men. METHOD: Subjects were recruited from a cohort of 1,011 homosexual men enrolled in the Chicago site of the Multicenter AIDS Cohort Study who also participated in the Coping and Change Study. The men were given self-administered questionnaires assessing behavioral, psychological, and psychosocial variables. Relationships between reports of stressful life events and longitudinal biomedical data measuring illness progression were examined. Life events were assessed by reports on the numbers of lovers, friends, and acquaintances who were diagnosed with AIDS or had died of AIDS and by scores on a checklist of 24 more general serious stressor events. The variables indicating progression of illness among initially asymptomatic men were a drop in T-helper lymphocyte percent (CD4%) between pairs of examinations of at least 25% and onset between examinations of thrush and/or fever lasting a minimum of 2 weeks. RESULTS: The authors found no evidence that serious stressor events have any meaningful effect on symptom onset indicated by either a drop in CD4% or onset of fever or thrush. CONCLUSIONS: There is no need for asymptomatic people with HIV infection to restrict their lives in order to avoid exposure to stressful life experiences or to develop special skills for coping with stress to forestall the progression of HIV illness.

Acquired Immunodeficiency Syndrome

Endobronchial radiation therapy (EBRT) in the management of lung cancer.

Between October 1987 and November 1988, 19 endobronchial Iridium-192 line source placements were attempted in 17 patients with advanced incurable lung cancer. Approximately 30 Gy was delivered to the endobronchus using a low dose rate (LDR) afterloading technique delivering a mean dose of 70 cGy/hr at 5 mm. Improvement in subjective symptoms was noted in 67% of evaluable patients whereas objective responses defined by chest X ray and bronchoscopy were noted in 26% and 60%, respectively. No significant morbidity was observed. The radiation exposure to health care workers was low ranging from 10 to 40 mRem per treatment course with most of the staff receiving less than 10 mRem per treatment course (minimal detectable level 10 mRem). The results of this series are compared with selected series using low dose rate as well as intermediate dose rate (IDR) and high dose rate (HDR) endobronchial radiation therapy (EBRT). Based on bronchoscopic responses from the selected series reviewed, both HDR low total dose per treatment (range 7.5-10 Gy) and LDR high total dose per treatment (range 30-50 Gy) are effective in palliating the vast majority of patients with endobronchial lesions. Intermediate dose rate is also effective using fractions similar to high dose rate but total dose similar to low dose rate. The efficacy of endobronchial radiation therapy in the palliative setting suggest a possible role for endobronchial radiation therapy combined with external beam irradiation with or without chemotherapy in the initial management of localized lung cancer. Defining the optimal total dose, dose rate, and the exact role of endobronchial radiation therapy in the management of lung cancer will require large cooperative trials with standardization of techniques and definitions.

Airway Obstruction

Adrenal demedullation and peripheral 6-OHDA administration in the rabbit: effects on body weight, general activity and cardiovascular responsivity.

Two experiments were undertaken to determine the effects of systemic 6-hydroxydopamine (6-OHDA) administration and adrenal enucleation on body weight, brain and heart norepinephrine, general activity, and cardiovascular responsivity in the rabbit. 6-Hydroxydopamine produced long lasting, dose related decreases in baseline blood pressure (BP) and in pressor responses following electric shock. Partial reversal of the BP changes was observed in nonenucleated animals tested 20 days after 6-OHDA administration but not in enucleated animals tested 5, 10 or 20 days post-injection or in control animals tested 5, 10 or 15 days after vehicle injection. Although 6-OHDA administration produced transient weight loss and activity decrements, no long term weight or activity changes were observed.

Adrenal Medulla

Movements at the hip joint.

Movements at the hip joint are first discussed in terms of free movement of the lower limb on the trunk. The biomechanics of standing on one lower limb limited to the situation in the coronal plane are presented. The role of the hip muscles in the upright posture and in the movements at the hip joint during walking on the flat and upstairs and downstairs is described.

Female

Synthesis of the spin-labeled derivative of an ether-linked phospholipid possessing high antineoplastic activity.

We report here the complete synthesis of the spin-labeled derivative of an antitumor ether phospholipid, 1-O-octadecyl-2-O-(4'-doxylpentyl)-rac-glycerol-3-phosphocholine. This also represents the first time that the synthesis of a nitroxide spin-labeled diether phospholipid is described. In vitro experiments showed that at micromolar concentrations, this new analog is readily incorporated into the plasma membranes of human HL60 and mouse E8/AK.D1 leukemic cells, and subsequently kills the cells. The availability of this new probe should permit the electron spin resonance spectroscopic approach to investigate ways by which anti-tumor ether phospholipids selectively destroy the tumor cells.

Animals