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Biomedical subjects

V Gill

Publications and source records attributed to V Gill.

At least 37 records · Page 2Linked to original sources
PubMed1994

Endogenously generated active oxygen species and cellular glutathione levels in relation to BHK-21 cell proliferation.

In BHK-21 cells (baby hamster kidney fibroblasts) cellularly generated active oxygen species such as hydrogen peroxide and superoxide appear to be important growth regulatory signals as judged from the growth inhibitory effects of catalase, superoxide dismutase and superoxide dismutase mimics. These active oxygen species may contribute a novel redox system of regulatory control superimposed upon established growth signal pathways. This may be achieved by direct oxidative modification of cell regulatory proteins such as transcription factors or protein kinases or indirectly through, for example alterations in levels of glutathione (GSH). This latter possibility is suggested from observations that catalase, or superoxide dismutase treatment of BHK-21 cells brings about increased cellular levels of GSH. However during the normal growth phase cellular levels of GSH actually decline although this effect can be partly reversed by N-acetylcysteine and by mercaptosuccinate which also impair proliferation of these cells.

Acetylcysteine↗
PubMed1993

Cellularly generated active oxygen species and HeLa cell proliferation.

In HeLa cells evidence is provided that active oxygen species such as hydrogen peroxide and superoxide at low levels are important growth regulatory signals. They may constitute a novel regulatory redox system of control superimposed upon the established cell growth signal transduction pathways. Whilst for example hydrogen peroxide can be added exogenously to elicit growth responses in these cells, it is clear that cellularly generated superoxide and hydrogen peroxide are important. Experiments with superoxide dismutase, superoxide dismutase mimics and inhibitors of both superoxide dismutase and xanthine oxidase suggest that superoxide generated intracellularly and superoxide released extracellularly are both relevant to growth control in HeLa cells.

Allopurinol↗
PubMed1993

Reduction of a tetrazolium salt and superoxide generation in human tumor cells (HeLa).

Experiments have been carried out to explore the use of a tetrazolium salt, MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide in the detection of intracellularly generated superoxide in HeLa cells. From the use of a low molecular weight lipophilic mimic of superoxide dismutase, as well as superoxide dismutase, and inhibitors of superoxide dismutase, it is suggested that at least 20-30% of the intracellular reduction of MTT is due to superoxide. Whilst this may arise from mitochondria another possible intracellular source in HeLa cells may be xanthine oxidase. The overall rate of intracellular MTT reduction in HeLa cells is inversely dependent on levels of serum in the culture medium. Serum components with a modulatory role in this context are those with antioxidant function. Reduced MTT is also detectable extracellularly in cultures of HeLa cells and at least 80% of this is due to superoxide. Use of inhibitors suggest that whilst a small proportion (30%) may arise through an NADPH-oxidase type enzyme, other sources of extracellular superoxide in HeLa cells remain a possibility.

Allopurinol↗
PubMed1990

A randomized trial of open lung biopsy versus empiric antimicrobial therapy in cancer patients with diffuse pulmonary infiltrates.

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.

Adult↗
PubMed1990

Oxidative stress and tumour cell proliferation.

The effects of oxidant stress were studied in immortalised hamster (BHK-21) and rat (208F) cell lines before and after transformation to the malignant state with polyoma virus, or activated H-ras, respectively. Whilst intracellular superoxide production was detectable in both transformed and immortalised cells the rate was somewhat higher in the transformed cells which have lower levels of superoxide dismutase. Because growth of transformed cells was particularly depressed in the presence of MTT, a tetrazolium compound reduced by superoxide, the possible role of active oxygen species in the promotion of cell growth was examined. Low levels of hydrogen peroxide were stimulatory towards both immortalised and transformed cells. In the case of H-ras transformed rat cells, paraquat was also stimulatory provided serum was present in the growth medium. In the absence of serum, paraquat was notably inhibitory but inhibition could be alleviated by addition of low concentrations of alpha-tocopherol (10(-8)M) to the serum-depleted medium. Although depletion of serum from the growth medium also leads to lower cell proliferation, subsequent experiments showed that alpha-tocopherol addition to serum-free medium was sufficient to restimulate growth. In the case of transformed cells, yields of cells were even greater than that encountered in the presence of 10% serum. Thus whilst certain active oxygen species (e.g. hydrogen peroxide) may have a role in promoting the growth of transformed and immortalised cells the necessity for antioxidant protection is important.

Animals↗
PubMed1989

Cell proliferation and oxidative stress.

Antioxidants such as mannitol, butylated hydroxytoluene and alpha-tocopherol enhance the growth of polyoma virus transformed and non-transformed BHK-21 cells. In the case of mannitol this is observed even in the absence of added calf serum. In part these effects may operate to protect cellular growth control mechanisms. On the other hand oxidants such as H2O2 and t-butyl hydroperoxide can inhibit growth and overall cellular protein synthesis, through mechanisms that are likely to involve radicals. In the case of H2O2 the inhibitory effects can nevertheless be reduced by 'prestressing' the cells with mild heat or with H2O2 itself. Paradoxically very low concentrations (10(-8) M) of H2O2 or t-butyl hydroperoxide can actually stimulate cell growth, even in the absence of serum. These stimulatory effects however do not appear to involve radicals as they are enhanced by inclusion of mannitol or DMSO in the medium.

Amino Acids↗
PubMed1986

Prospective evaluation of a monoclonal antibody in diagnosis of Pneumocystis carinii pneumonia.

To evaluate the ability of a mouse monoclonal antibody, 2G2, directed against human Pneumocystis carinii, to detect the organism in clinical specimens, a prospective study of the antibody in an indirect immunofluorescent assay was undertaken. P carinii was rapidly detected in thirteen of fourteen bronchoalveolar lavage specimens positive by toluidine-blue-O stain, none of eleven lavage specimens negative by toluidine-blue-O, neither of two impression smears of histologically negative open-lung biopsy specimens, and both of two impression smears of histologically positive necropsy specimens. Immunofluorescence with monoclonal antibody 2G2 is a rapid, simple, and specific technique for detection of P carinii in clinical specimens.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Emergence of Clostridium tertium as a pathogen in neutropenic patients.

Although usually considered a non-pathogen, Clostridium tertium was isolated from 10 immunosuppressed patients including seven patients with bacteremia. This organism can grow aerobically and can be easily disregarded as a contaminant. It also has a somewhat unusual susceptibility pattern, with significant resistance to the penicillins, cephalosporins, and clindamycin, possibly explaining its emergence in immunocompromised patients already receiving multiple antibiotics.

Adult↗
PubMed1985

Erysipelothrix rhusiopathiae bacteremia presenting as septic shock.

Erysipelothrix rhusiopathiae rarely causes bacteremia, and it has never been reported to cause septic shock. A 58-year-old man with fulminant hyperdynamic shock associated with E. rhusiopathiae bacteremia is described. Erysipelothrix must be considered when a patient with an appropriate history presents with septic shock.

Animals↗
PubMed1984

Immunocytochemical localization of urotensin I neurons in the caudal neurosecretory system of the white sucker (Catostomus commersoni).

The localization of urotensin I has been investigated in the caudal neurosecretory system of the white sucker (Catostomus commersoni). The peptide is present in all the cells of the system both large and small, in the large axons passing to the urophysis, and in fine beaded fibres not only within the urophysis but also in a fine plexus lateral to the large cells in the spinal cord proper. The possibility that the caudal neurosecretory system is not a functionally uniform system but rather a collection of dissimilar cells of different synaptic inputs with a common entity, urotensin I, is discussed. Moreover, the feasibility of a urotensin-I feedback loop is described.

Animals↗
PubMed1984

Hyperthermia, Na+K+ATPase and lactic acid production in some human tumour cells.

When HeLa cells are exposed to brief heat shock at 45 degrees C there is a reduction in the cellular level of Na+K+ATPase. Return of the cells to the normal growth temperature of 37 degrees C leads to a partial restoration of enzyme activity. The pattern of this recovery of activity suggests that it may be associated with the induction of heat shock proteins. Indeed other means of heat shock protein induction such as continuous heat treatment at 42 degrees C, or treatment of cells at 37 degrees C with sodium arsenite, leads to elevated levels of Na+K+ATPase activity and alterations in the kinetic properties of the enzyme. Continuous hyperthermia at 42 degrees C led to increased lactate production which could be blocked with ouabain suggesting that effects on Na+K+ATPase activity could partly influence glycolysis. A number of other human and hamster cells also showed increased lactate production at 42 degrees C and also an inhibition of lactate production by ouabain. Whilst incubation of HeLa cells with cyanide had little effect on glycolysis at 37 degrees C elevation of the temperature to 42 degrees C (or 45 degrees C), in the presence of cyanide, impaired glycolysis. The possible role in this phenomenon, of an unusual oxygen-sensitive isoenzyme of lactate dehydrogenase, expressed in human cancers, is discussed.

Animals↗
PubMed1984

The diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome using subsegmental bronchoalveolar lavage.

To assess the sensitivity of bronchoalveolar lavage in patients with the acquired immunodeficiency syndrome (AIDS) in diagnosing Pneumocystis carinii pneumonia (PCP), we prospectively performed 27 bronchoalveolar lavages (BAL) in 16 patients either because there was an initially high index of suspicion of PCP or in order to assess therapeutic response to anti-Pneumocystis medication in those patients who had had PCP documented. Pneumocystis organisms were demonstrated on BAL specimens in 16 of 18 procedures in patients with histologic evidence of PCP on simultaneously obtained pulmonary tissue. The diagnosis was established rapidly by BAL and there was no substantial morbidity attributable to the procedure. Subsegmental BAL may be an important and sensitive tool for early diagnosis of PCP in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The correlation of changes in systolic blood pressure with regional anatomical regression of hypertensive left ventricular hypertrophy in patients on chronic antihypertensive therapy (greater than 1 year): alpha-methyldopa compared to propranolol.

Twenty patients with mild to moderate hypertension and evidence of left ventricular hypertrophy (relative wall thickness greater than or equal to 0.45), who previously had not received either alpha-methyldopa or propranolol, were allocated at random to treatment with one or other of these drugs as monotherapy after a 2-week baseline period on no medication. Dosage was titrated until normotension was attained and patients were then maintained on this treatment for a year. Analysis of blood pressure measurements and echocardiograms taken before and during maintenance therapy showed that there were significantly correlated changes in systolic blood pressure and heart rate with left ventricular cavity and regional wall changes during chronic drug administration. In the alpha-methyldopa group there were significant correlations between changes in erect and supine systolic blood pressure and the posterior wall index, and in erect systolic blood pressure and left ventricular mass. In the propranolol group, there were significant correlations between changes in supine systolic blood pressure and interventricular septal thickness, and in erect heart rate and supine systolic blood pressure with the percentage change in internal diameter of the left ventricle. It is suggested that these observations may have important therapeutic implications for hypertensive patients with documented left ventricular hypertrophy.

Adult↗
PubMed1983

Unresponsiveness of Legionella bozemanii pneumonia to erythromycin administration despite in vitro sensitivity.

We report a case of Legionella bozemanii pneumonia that failed to respond clinically and microbiologically to erythromycin administration. The organism was recovered from bronchial brushings and washings and was demonstrated to be sensitive in vitro to erythromycin as well as to rifampin and sulfamethoxazole-trimethoprim. The patient received a 9-day course of erythromycin before she died. Nonetheless, postmortem lung tissue yielded Legionella bozemanii. In treating Legionella pneumonia unresponsive to erythromycin, addition of another antibiotic, based on sensitivity testing, should be considered.

Erythromycin↗
PubMed1983

Bacteremia due to Mycobacterium avium-intracellulare in the acquired immunodeficiency syndrome.

The presence of Mycobacterium avium-intracellulare has frequently been demonstrated in tissue specimens from patients with the acquired immunodeficiency syndrome. The importance of this mycobacterium as a cause of constitutional symptoms and organ dysfunction has been unclear, however, because of the sparse inflammatory response evoked and the frequent concurrence of other pathogenic organisms. We detected M. avium-intracellulare in blood samples from eight patients with the acquired immunodeficiency syndrome, seven of whom had a previously recognized M. avium-intracellulare infection. Blood cultures were positive on 1 to 14 occasions over 135 days using the Dupont isolator system or the Bactec 12B medium system. Cultures were positive within 14 to 51 or 7 to 14 days with the respective techniques. The ability to rapidly isolate M. avium-intracellulare from blood may provide a useful diagnostic technique for detecting disseminated mycobacterial disease in patients with the acquired immunodeficiency syndrome as well as in other patient populations. This technique may also be useful for assessing the efficacy of drug therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Potassium conservation with amiloride/hydrochlorothiazide ("Moduret') in thiazide-induced hypokalaemia in hypertension.

A double-blind study was carried out in 24 hypertensive patients with thiazide-induced hypokalaemia (serum potassium less than 3.2 mmol/l) to compare the effects of treatment with an amiloride/hydrochlorothiazide combination or hydrochlorothiazide alone. The study was divided into three phases: (i) potassium repletion (Weeks 0 to 4) with oral potassium chloride (40 mmol/day), (ii) stabilization (Weeks 4 to 6) of normokalaemia, and (iii) active drug treatment (Weeks 6 to 14), patients being allocated at random to receive one or other of the two treatments. Dosage was 2 tablets per day of the 5 mg amiloride plus 50 mg hydrochlorothiazide combination or of 50 mg hydrochlorothiazide alone. The results showed that blood pressure control was comparable in both treatment groups but hydrochlorothiazide alone caused a statistically significant reduction in serum potassium levels compared to the drug combination. Apart from 1 patient who developed hypokalaemia on hydrochlorothiazide alone, no other side-effects of treatment were reported.

Amiloride↗