Oxidant stress stimulates Na/K pump activity in bovine pulmonary arterial endothelial cells.
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Animals↗
Biomedical subjects
A Charles
Publications and source records attributed to A Charles.
[Endometrial evaluation prior to tamoxifen: preliminary results of a prospective study].
The objective of this study was to try to identify, by pretreatment screening, a group of patients at higher risk of developing endometrial carcinoma on tamoxifen. Between January 1993 and January 1997, 360 postmenopausal patients with breast cancer were enrolled in this prospective study. Basal screening included gynaecologic examination with a Papanicolaou smear and endovaginal sonography. In the case of an abnormal ultrasound (endometrial thickness greater than 4 mm), an outpatient hysteroscopy with an endometrial biopsy was carried out. These examinations were repeated annually. By means of this preliminary evaluation, two groups of patients were identified: patients without initial lesions (group I) and patients with initial endometrial lesions (group II). These two groups of patients were followed up separately exactly in the same way. Endometrial lesions taken into account were: adenocarcinomas (in situ and invasive), polyps with or without atypia, myomas and adenomyotic lesions with irregular mucosa. After 3 years and after 4 years of follow-up, the percentage of atypical lesions was significantly higher in the group with initial lesions than in the group without initial lesions. This study suggests that a group of high risk patients more sensitive to the carcinogenic effect of tamoxifen can be identified by pretreatment evaluation.
Adenoma↗
Lipid transport genes and their relation to the syndrome of insulin resistance.
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Adult↗
Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect.
Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes have a decreased ability to express IL-12 mRNA subunits and to produce IL-12 p40 and bioactive p70 proteins in response to Staphylococcus aureus strain cowan I (SAC). We showed that in human monocyte cultures, HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after SAC-activation. Similar data were obtained with human macrophages. These results suggest that, during HIV infection, gp120 induces in uninfected monocytes and macrophages IL-10/IL-12 disregulation, which can alter immune response.
HIV Envelope Protein gp120↗
Studies on the mechanism of short-term regulation of pulmonary artery endothelial cell Na/K pump activity.
The Na/K pump is critically important in maintenance of cell homeostasis in the face of injury. Little is known about the regulation of endothelial cell Na/K-pump activity. We previously reported that short-term (30-minute) oxidant-induced endothelial cell perturbation increased Na/K-pump activity in intact monolayers of bovine pulmonary artery endothelial cells (BPAECs). In this study we investigated the mechanism of oxidant-induced increases in endothelial Na/K-pump activity, focusing on short-term modulation of alpha1-pump subunit. By using immunofluorescence microscopy and confocal scanning laser microscopy, we found alpha1 subunit on both apical and basal aspects of BPAECs without polarized distribution. Short-term (30-minute) incubation of PAEC monolayers with H2O2 (1 mmol/L) did not change the relative amounts of alpha1 subunit in membrane fractions, as assessed by immunoblotting. Phosphorylation of the alpha1 subunit also was not affected by H2O2 treatment. Because protein kinases have been reported to alter Na/K-pump activity in several tissues and because H2O2 has been reported to increase PKC activity of endothelial cells, we determined the effects of inhibition and activation of protein kinase C (PKC) on Na/K-pump activity quantitated as ouabain-inhibitable uptake of 86Rb. We also determined the effects of PKC activation and inhibition on H2O2-induced increases in Na/K-pump activity. Inhibitors of PKC increased Na/K-pump activity over a 30-minute period in intact monolayers. Inhibition or depletion of PKC did not prevent H2O2-induced increases in pump activity. These results indicate that PKC is an endogenous regulator of pulmonary artery endothelial cell Na/K-pump activity but that the effects of H2O2 are not mediated by activation of PKC or by changes in the expression or phosphorylation of alpha1 subunit.
Animals↗
Mutations at the lipoprotein lipase gene locus in subjects with diabetes mellitus, obesity and lipaemia.
1. The common association of obesity, diabetes mellitus and hyperlipidaemia may have a primary aetiological basis. Insulin resistance has been postulated as a possible cause, but defects in the plasma transport of triacylglycerol or fatty acids could also be primary determinants. 2. We have therefore studied 18 patients with diabetes mellitus, obesity and severe hypertriglyceridaemia for defects of a key protein involved in the clearance of plasma triacylglycerols, lipoprotein lipase. 3. DNA was prepared from leucocytes of 18 patients with the above syndrome, and exons encoding lipoprotein lipase were amplified by PCR. The products were sequenced using the dideoxy chain-termination method. 4. Eight of the subjects were found to possess genetic variants at the lipoprotein lipase gene locus. These were: (a) G579-->A, V108V; (b) G818-->A, G188E; (c) C829-->T, R192; (d) A1127-->G, N291S; (e) C1308-->G, F351L; (f) C1338-->A, T361T; and (g) C1595-->G, S447. Three of these, (c), (e) and (f), have not hitherto been described. Variant (f), appears to be a population polymorphism whose allele frequency in normolipidaemic diabetics was found to be 0.12 (162 chromosomes studied). The others are all rare at frequencies of < 0.01 and may contribute to the phenotype by impairing clearance of plasma triacylglycerols. 5. We conclude that genetic variants at the lipoprotein lipase locus occur commonly in subjects with this syndrome (four out of 18 subjects with probably functional mutants) and may affect the individual's response to obesity and diabetes mellitus for the development of lipaemia.
Adult↗
Extracellular calcium sensing by glial cells: low extracellular calcium induces intracellular calcium release and intercellular signaling.
Glial cells in primary mixed cultures or purified astrocyte cultures from mouse cortex respond to reduced extracellular calcium concentration ([Ca2+]e) with increases in intracellular calcium concentration ([Ca2+]i) that include single-cell Ca2+ oscillations and propagated intercellular Ca2+ waves. The rate and pattern of propagation of low [Ca2+]e-induced intercellular Ca2+ waves are altered by rapid perfusion of the extracellular medium, suggesting the involvement of an extracellular messenger in Ca2+ wave propagation. The low [Ca2+]e-induced Ca2+ response is abolished by thapsigargin and by the phospholipase antagonist U73122. The low [Ca2+]e-induced response is also blocked by replacement of extracellular Ca2+ with Ba2+, Zn2+, or Ni2+, and by 100 microM La3+. Glial cells in lowered [Ca2+]e (0.1-0.5 mM) show an increased [Ca2+]i response to bath application of ATP, whereas glial cells in increased [Ca2+]e (10-15 mM) show a decreased [Ca2+]i response to ATP. These results show that glial cells possess a mechanism for coupling between [Ca2+]e and the release of Ca2+ from intracellular stores. This mechanism may be involved in glial responses to the extracellular environment and may be important in pathological conditions associated with low extracellular Ca2+ such as seizures or ischemia.
Adenosine Triphosphate↗
Fatal pulmonary embolism in hospitalised medical patients.
This study aimed to determine the frequency of fatal pulmonary emboli in hospitalised medical patients by a retrospective necropsy review and prospective non-interventional patient follow up study. The main outcome measure, necropsy proven fatal pulmonary embolism, was determined from 400 consecutive necropsy records and 200 consecutive medical inpatient episodes. Fatal pulmonary embolism was recorded in 29 of 400 necropsies; 17 were medical patients. Thirty one of 200 consecutive medical patients died. Fourteen necropsies were performed and revealed pulmonary embolism as the cause of death in five patients. The incidence of necropsy proven fatal pulmonary embolism was therefore 2.5% (95% confidence intervals 0.8% to 5.7%). Therefore, one in 40 medical patients had pulmonary embolism recorded as the cause of death at necropsy. As the necropsy rate was only 45% the incidence of fatal pulmonary embolism may be greater. There is, therefore, a need to perform more large prospective studies to confirm the incidence of fatal pulmonary embolism in medical patients and to identify risk factors and effective antithrombotic prophylaxis.
Aged↗
Microcirculation of the islets of Langerhans. Long Beach Veterans Administration Regional Medical Education Center Symposium.
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Animals↗
Early morphological evidence of autosomal recessive polycystic kidney disease.
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Female↗
Multi-motor unit action potential analysis (MMA)
We have developed an algorithm, called multi-motor unit action potential analysis (MMA), to aid quantification in routine needle EMG examination. In only 5-8 min, it was possible to extract, analyze, and validate 20 motor unit action potentials (MUAPs). In the biceps muscle of normal subjects, the MUAP measurements are compared with measurements using manual, triggered averaging, automatic decomposition, and other MMA algorithms described in the literature. The mean values of MUAP features by MMA fell between the extreme limits obtained from the amplitude-triggered method and the manual method described in the literature. In patients, the results are consistent with routine EMG and similar to those results described in the literature. Fast acquisition and analysis of MUAPs as well as interference pattern (IP) analysis make this technique useful to document EMG abnormalities in routine needle examination.
Action Potentials↗
Carbohydrate and peptide antigens in macrophage populations derived from human bone marrow and milk: an immunomorphological and immunochemical analysis.
An immunomorphological and immunochemical study was performed to elucidate the pattern of carbohydrate antigens and their relationships to the cluster differentiation (CD) 68 epitopes on macrophages derived from human bone marrow and milk. Core and backbone antigens recognized by lectins from Bauhinia purpurea (BPA), Helix pomatia (HPA), Arachis hypogaea (PNA), Glycine max. (SBA), Griffonia simplicifolia (GSA-I-B4), Lycopersicon esculentum (LEA) and Erythrina cristagalli (ECA) were expressed by both macrophage populations. Additionally, they exhibited various peripheral type 1 and type 2 carbohydrate antigens. In bone marrow trephine biopsies, the number of macrophages stained by the CD68-specific monoclonal antibody PG-M1 exceeded significantly (range 30-40%) the subpopulation expressing SBA, GSA-I-B4, and ECA binding sites as well as the Lewisa antigen. This result is very interesting since, from in vitro studies GSA-I-B4 and SBA are known to react especially with activated macrophages. Western blotting experiments on milk macrophage lysates revealed that ECA, GSA-I-B4, BPA, PNA and MAA visualize a 110 kDa band isographic with the CD68 antigen detected by PG-M1, KP1 and Ki-M1P monoclonal antibodies. These antibodies recognize peptide epitopes as shown by enzyme-linked immunosorbent assays after biochemical modification of milk macrophage lysates. This result is in keeping with the assumption that the CD68 antigen consists of a highly glycosylated mucin-type glycoprotein comprising various differentiation-dependent epitopes.
Antibodies, Monoclonal↗
Carbohydrate antigens of human megakaryocytes and platelet glycoproteins: a comparative study.
Until now, carbohydrate antigens of human megakaryocytes have not been studied very extensively. For this reason, we investigated the staining pattern of 25 lectins and carbohydrate-specific monoclonal antibodies on paraffin-embedded trephine biopsies and acetone-fixed smears from patients with reactive and neoplastic bone marrow lesions. A biotin-streptavidin-alkaline phosphatase assay was used to visualize the binding of lectins or antibodies. Ulex europaeus agglutinin I (UEA-I) stained megakaryocytes in all cases tested. Monoclonal antibodies detecting fucosylated Lewis type 2 chain antigens (19-OLE, 12-4LE and LeuM1) were also reactive. Several lectins detecting backbone and core oligosaccharides [Helix pomatia agglutinin (HPA), peanut agglutinin (PNA), Erythrina cristagalli agglutinin (ECA), soybean agglutinin (SBA)] bound to megakaryocytes only after neuraminidase digestion. Moreover, we investigated human platelet lysates to gain some information about the carbohydrate residues of platelet glycoproteins which are synthesized by megakaryocytes. The carbohydrate expression of platelets showed striking similarities to that of megakaryocytes. Immunoblotting experiments revealed a strong binding of UEA-I, 19-OLE and 12-4LE to a band isographic to glycoprotein (gp) Ib. After desialylation of glycoproteins transblotted to nitrocellulose, ECA and PNA also reacted with a band of this molecular weight. Gp Ib is known to contain a mucin-like peptide core with a great number of potential O-glycosylation sites. Therefore, it is tempting to speculate that carbohydrate residues characterized in this study are involved in the complex biological interactions of gp Ib.
Antibodies, Monoclonal↗
Hydrogen peroxide stimulates sodium-potassium pump activity in cultured pulmonary arterial endothelial cells.
Oxidant injury to pulmonary vascular endothelium is an important factor in the pathogenesis of acute lung injury. Oxidant injury to other cell types has been reported to alter the function of Na-K-adenosinetriphophatase (ATPase) an enzyme important in maintenance of cellular ionic homeostasis and in transport of ions across biological membranes. We investigated the effect of H2O2 (0.001-10 mM) or xanthine (X) (15.2 micrograms/ml) plus xanthine oxidase (XO) (0.0153 U/ml) on the Na-K pump activity of cultured bovine pulmonary arterial endothelial cells (PAECs). We used a functional assay, using 86RbCl as a tracer for K+ and expressing Na-K pump activity as ouabain-inhibitable K+ uptake. Our results demonstrate that H2O2 and X/XO stimulate Na-K pump activity of bovine PAECs, an effect prevented by catalase. In addition, we assessed the affinity, number, and turnover of [3H]ouabain binding sites on intact endothelial monolayers and found that H2O2 increased affinity to [3H]ouabain, decreased the number of binding sites, and increased the rate of pump turnover. Influx of 22Na increased in response to a nonlytic concentration of H2O2. Cell injury, as assessed by 51Cr release, adherent cell number, and phase-microscopic morphology, was not observed after 30-min incubations with the lowest dose (1 mM) of H2O2 effective in stimulating Na-K pump activity, or after incubation with X/XO. Na-K pump inhibition by ouabain significantly increased the 51Cr release caused by H2O2 or by X/XO, suggesting that the increase in Na-K pump activity may be a compensatory response to the cellular alterations produced by H2O2. Incubation with H2O2 decreased cell ATP content, an effect which was not prevented by coincubation with ouabain. In summary, these results show that H2O2 increases Na-K pump activity of PAECs, an effect mediated, at least in part, by increased intracellular [Na] and by an increased rate of pump turnover. It is possible that the increased pump activity may be an early marker of endothelial cell perturbation.
Animals↗
Production of neutrophil-specific lipid chemoattractant activity by cultured endothelial cells: heterogeneity dependent on species, ligand, or endothelial cell site of origin.
Previous studies have demonstrated that the interaction of cultured bovine aortic and pulmonary arterial endothelial cells and the proinflammatory vasoactive amines histamine, serotonin, and angiotensin II, causes production of three novel lipid neutrophil-specific chemoattractants that are distinct from other phospholipid or lipid neutrophil chemoattractants. In this study, we investigated the species and site specificity of this inflammatory response by incubating human aortic and pulmonary arterial endothelial cells with histamine, serotonin, and angiotensin II and assaying the supernatants for their effect on neutrophil migration. Each of these vasoactive amines caused production of neutrophil chemoattractant activity in a concentration dependent manner in both cell types. For each amine, production was blocked by a specific antagonist: cimetidine for histamine, methiothepin for serotonin-stimulated aortas, ketanserin for serotonin-stimulated pulmonary arteries, and saralasin for angiotensin II. In each case, all chemoattractant activity partitioned into the organic phase and resolution by HPLC yielded two chemotactic lipids. As with the lipid chemoattractants produced by bovine endothelial cells, these lipids did not coelute with PAF, LTB4, 5-HETE, or 15-HETE, nor did they increase lymphocyte or monocyte migration. The pattern of chemotactic activity following resolution by HPLC was similar in both human aortic and pulmonary arterial endothelial cells, but was different from that of bovine aortic and pulmonary arterial endothelial cells in that only two chemoattractant lipids appeared; the third chemotactic lipid was never produced. These studies demonstrate that human endothelial cells may actively participate in neutrophil enriched local inflammatory responses by production of neutrophil-specific chemotactic factors. They also suggest this response may be dissimilar depending on the site and species from which the endothelial cells originate.
Animals↗
Low-dose, low-volume chemonucleolysis. A biochemical study.
Thirty patients with persistent sciatica due to a single disc protrusion were injected with 0.5 ml (2.0 mg) or 2.0 ml (8.0 mg) of chymopapain. Serial 24-hour urine samples were collected 1 day preinjection and for 5 days postinjection for glycosaminoglycan analysis. There was a significant increase in urinary glycosaminoglycan in both groups following chemonucleolysis, but no significant difference was found between the two groups in the total excretion of glycosaminoglycan during the 5-day period. Low-dose, low-volume chemonucleolysis may be as effective as standard doses in releasing glycosaminoglycan from intervertebral discs.
Adult↗
Pneumococcal bacteremia with pneumonia. Mortality in acquired immunodeficiency syndrome.
OBJECTIVE: To compare mortality due to bacteremic pneumococcal pneumonia in patients with acquired immunodeficiency syndrome (AIDS) vs (control) patients without human immunodeficiency virus (HIV) infection. Non-AIDS patients with HIV infection were incidentally tabulated as a separate group. DESIGN: A two-year retrospective study. SETTING: Inpatients of St. Clare's Hospital, a community hospital in New York City. PATIENTS: Forty-nine patients had 50 separate episodes with at least one positive blood culture for Streptococcus pneumoniae (all were penicillin-sensitive) and pneumonia on chest roentgenogram. Twenty-four patients had no HIV infection, 14 patients had AIDS, and 11 patients with 12 bacteremic episodes were HIV-positive without AIDS. INTERVENTIONS: Treatment for pneumonia was determined by the patient's individual physician. MEASUREMENTS AND MAIN RESULTS: AIDS patients with pneumonia had a mortality of 57.1 percent (8/14), which was significantly higher than the 25 percent (6/24) seen in patients without HIV infection (p less than 0.025, two-sample test for independent proportions). Septic shock, usually occurring within the first five days of hospitalization, was the primary cause of death, occurring in six of eight AIDS patients and six of six patients without HIV infection. If the mortality in the first five days of hospitalization was excluded, the mortality would drop to 33.3 percent in the AIDS population and 5.3 percent in patients without HIV infection. Eleven HIV-infected patients without AIDS survived 12 episodes of bacteremic pneumococcal pneumonia. CONCLUSIONS: Bacteremic pneumococcal pneumonia in the setting of AIDS has a survival rate of less than 50 percent with septic shock as the usual mode of death. This is the highest pneumococcal pneumonia mortality rate ever reported in a large subgroup of patients in the antibiotic era. On the other hand, HIV-infected patients without progression to AIDS have an excellent chance for survival. This may be related in part to young age, absence of many underlying diseases, and a better humoral immune system.
Acquired Immunodeficiency Syndrome↗