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Biomedical subjects

M Dempsey

Publications and source records attributed to M Dempsey.

12 recordsLinked to original sources
PubMed2000

Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies.

Zanamivir is a highly selective neuraminidase (NA) inhibitor with demonstrated clinical efficacy against influenza A and B virus infections. In phase II clinical efficacy trials (NAIB2005 and NAIB2008), virological substudies showed mean reductions in virus shedding after 24 h of treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses compared to a placebo, with no reemergence of virus after the completion of therapy. Paired isolates (n = 41) obtained before and during therapy with zanamivir demonstrated no shifts in susceptibility to zanamivir when measured by NA assays, although for a few isolates NA activity was too low to evaluate. In plaque reduction assays in MDCK cells, the susceptibility of isolates to zanamivir was extremely variable even at baseline and did not correlate with the speed of resolution of virus shedding. Isolates with apparent limited susceptibility to zanamivir by plaque reduction proved highly susceptible in vivo in the ferret model. Further sequence analysis of paired isolates revealed no changes in the hemagglutinin and NA genes in the majority of isolates. The few changes observed were all natural variants. No amino acid changes that had previously been identified in vitro as being involved with reduced susceptibility to zanamivir were observed. These studies highlighted problems associated with monitoring susceptibility to NA inhibitors in the clinic, in that no reliable cell-based assay is available. At present the NA assay is the best available predictor of susceptibility to NA inhibitors in vivo, as measured in the validated ferret model of infection.

Animals↗
PubMed1999

Availability of family support as a moderator of exposure to community violence.

Examined the role of availability of family support in moderating the negative effects of exposure to community violence on internalizing symptoms. Participants were 75 low-income African American children between the ages of 10 and 15. Two measures of availability of family support (mother's presence in the home and family size) were evaluated as moderators of the relations between exposure to community violence and depression and posttraumatic stress disorder (PTSD) symptoms. After controlling for age, sex, and concurrent life stress, mother's presence in the home moderated the relation between exposure to community violence and depressive symptoms but not the relation between exposure to community violence and PTSD symptoms. Children living in mother-absent families were at increased risk of depressive symptoms as exposure to community violence increased. In addition, family size approached significance as a moderator of depressive symptoms but not PTSD symptoms, revealing a trend toward children from smaller families being at increased risk of depressive symptoms as exposure to community violence increased. These findings suggest that although availability of family support is an important moderator for depressive symptoms, this is not the case for PTSD symptoms.

Adolescent↗
PubMed1998

Apoptosis and necrosis: mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line.

BACKGROUND: The mechanisms of cyclosporine (CsA)-induced nephrotoxicity are not fully understood. While hemodynamic changes may be involved in vivo, there is also some evidence for tubular involvement. We previously showed direct toxicity of CsA in the LLC-PK1 renal tubular cell line. In the current study we examined mechanisms (apoptosis or necrosis) of cell death induced by CsA in the LLC-PK1 renal proximal tubular cell line. The possible role of the Fas (APO-1/CD95) antigen-Fas ligand system in the mediation of CsA-induced cell death was also investigated. METHODS: Cells were treated with CsA (0.42 nM to 83 microM) for 24 hours and alterations in DNA and protein synthesis and membrane integrity were examined. Flow cytometry was used to investigate: (i) alterations in the DNA content and cell cycle; (ii) the forward (FSC) and side (SSC) light scattering properties (indicators of cell size and granularity, respectively); (iii) the externalization of phosphatidylserine (PS) as a marker of early apoptosis using FITC-annexin V binding; and (iv) expression of the apoptotic Fas protein. DNA fragmentation in apoptotic cells was also determined by the TUNEL assay. RESULTS: CsA (all doses) caused a block in the G0/G1 phase of the cell cycle as indicated by a decrease in DNA synthesis and supported by an increase in the % of cells in the G0/G1 phase with concurrent decreases of those in the S and G2/M phases. The effect on protein synthesis appeared to be much less. Lower doses of CsA (4.2 nM) caused the appearance of a "sub-G0/G1" peak, indicative of reduced DNA content, on the DNA histogram that was paralleled by a reduction in cell size and an increased cell granularity and an increase in FITC-annexin V binding. DNA fragmentation was evident in these cells as assessed using the TUNEL assay. Higher doses of CsA increased cell size and decreased cell granularity and reduced membrane integrity. Expression of Fas, the cell surface molecule that stimulates apoptosis, was increased following low dose CsA exposure. CONCLUSIONS: These results indicate that CsA is directly toxic to LLC-PK1 cells with reduced DNA synthesis and cell cycle blockade. The mode of cell death, namely apoptosis or necrosis, is dose dependent. Fas may be an important mediator of CsA induced apoptosis in renal proximal tubular cells.

Animals↗
PubMed1979

Scanning electron microscope studies of some normal and diseased conditions of mammalian skin as revealed in leather manufacture.

Sheep, goat and bovine skins, as leather, were examined. The surface contours of dermal response to sunburn, facial eczema, rape scald, and demodicosis are illustrated. In sunburn, demodicosis and rape scald, finger-like and ridge pattern projections had developed. In the photo-sensitive condition of rape scald and facial eczema distension was apparent, and in addition in rape scald reactions of contrasting nature involving hair follicles indicated a considerable disorientation of the skin. The transition from str. basale to str. corneum in bovine epidermis has been examined in leather from which the epidermis had unintentionally been incompletely removed in the course of manufacture, during attack on the keratinous tissue by hydrosulphide ions at high hydroxyl ion concentration. A "pore" presumably related to the position of the nucleus was observed in the outer surface of each of the cells in each layer exposed by the attack. The walls of the basal and adjacent cells appeared remarkably sturdy. As judged from the basal cells the intercellular cement (cell coating) disappeared before the cell wall degraded, but intercellular bridges remained clearly visible in the prickle cell layer, while towards the exterior, adjacent cell walls appeared more closely knit and the str. corneum (residues of which were observed around the follicles) appeared to lie in sheets. Discrete and fibrous cell components were exposed. At the latest degree of degradation observed in the basal cells the wall had reduced to a fibrous network.

Animals↗
PubMed1976

Treatement of excessive weight gain in patients taking lithium.

Six female primary affective disorder patients who had gained an average of 9.5 kg while taking lithium lost an average of 2.9 kg on a 10-day 900 calorie a day hospital diet containing 100 mEq of sodium per day. No evidence of lithium toxicity was observed on this regimen. There was no evidence that fluid retention played a major role in the weight gain.

Bipolar Disorder↗
PubMed1976

Plasma high-density lipoprotein cholesterol concentrations determined after removal of other lipoproteins by heparin/manganese precipitation or by ultracentrifugation.

The widely used heparin/MnCl2 precipitation procedure for determination of plasma high-density lipoprotein cholesterol has been re-examined in light of recent reports that isolated preparations of the lipoprotein are only partly precipitated under the test conditions. In the present study, the procedure as applied to plasma tolerated rather wide variations in heparin and MnCl2 concentrations without significant effects on the assayed values in several plasma pools tested. The procedure was further tested on 129 individual samples by comparison with an ultracentrifugal method in which high-density lipoprotein-cholesterol is assumed to be represented by the cholesterol content of the plasma fraction of relative (to water) density greater than 1.063. Our results indicate that high-density lipoprotein is not precipitated under the test conditions when applied to unfractionated plasma.

Cholesterol↗
PubMed1976

A study of "atypical schizophrenia". Comparison with schizophrenia and affective disorder by sex, age of admission, precipitant, outcome, and family history.

Eighty-five cases of atypical schizophrenia were compared with 200 of schizophrenia, 100 of bipolar (mania), and 225 of unipolar (depression) affective disorder. Comparisons were made on the basis of sex, age at admission, precipitating factors, outcome, and a family history of schizophrenia or of affective disorder. The atypical schizophrenia differed remarkably from the schizophrenia and most closely resembled the bipolar affective disorder when allowance was made for a younger age at onset and a higher frequency of precipitants. An analysis of symptoms verified the predominance of schizophrenic features in the atypical schizophrenia, but also showed a high percentage (80%) of patients who had one or more manic symptoms at index admission. It is concluded that great care should be taken in diagnosing schizophrenia in a patient who also has manic symptoms.

Adult↗