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Biomedical subjects

B Shopsin

Publications and source records attributed to B Shopsin.

At least 19 recordsLinked to original sources

Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains.

Three hundred and twenty isolates of Staphylococcus aureus were typed by DNA sequence analysis of the X region of the protein A gene (spa). spa typing was compared to both phenotypic and molecular techniques for the ability to differentiate and categorize S. aureus strains into groups that correlate with epidemiological information. Two previously characterized study populations were examined. A collection of 59 isolates (F. C. Tenover, R. Arbeit, G. Archer, J. Biddle, S. Byrne, R. Goering, G. Hancock, G. A. Hébert, B. Hill, R. Hollis, W. R. Jarvis, B. Kreiswirth, W. Eisner, J. Maslow, L. K. McDougal, J. M. Miller, M. Mulligan, and M. A. Pfaller, J. Clin. Microbiol. 32:407-415, 1994) from the Centers for Disease Control and Prevention (CDC) was used to test for the ability to discriminate outbreak from epidemiologically unrelated strains. A separate collection of 261 isolates form a multicenter study (R. B. Roberts, A. de Lencastre, W. Eisner, E. P. Severina, B. Shopsin, B. N. Kreiswirth, and A. Tomasz, J. Infect. Dis. 178:164-171, 1998) of methicillin-resistant S. aureus in New York City (NYC) was used to compare the ability of spa typing to group strains along clonal lines to that of the combination of pulsed-field gel electrophoresis and Southern hybridization. In the 320 isolates studied, spa typing identified 24 distinct repeat types and 33 different strain types. spa typing distinguished 27 of 29 related strains and did not provide a unique fingerprint for 4 unrelated strains from the four outbreaks of the CDC collection. In the NYC collection, spa typing provided a clonal assignment for 185 of 195 strains within the five major groups previously described. spa sequencing appears to be a highly effective rapid typing tool for S. aureus that, despite some expense of specificity, has significant advantages in terms of speed, ease of use, ease of interpretation, and standardization among laboratories.

Amino Acid Sequence

Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York hospitals. MRSA Collaborative Study Group.

Consecutive single-patient methicillin-resistant Staphylococcus aureus (MRSA) isolates (270) from 12 hospitals (8217 beds) in metropolitan New York City were collected during May 1996. In 11 of 12 hospitals, MRSA was most frequent in the general medical services. DNA typing ("fingerprinting") revealed that mecA:Tn554:PFGE (pulsed-field gel electrophoresis) type I:A:A accounted for 113 (42%) of 270 isolates, was detected in all hospitals, and was the predominant clone in 9. Thirteen of 15 I:E:F isolates were from 1 hospital, and the remaining 2 were from another hospital of the same health system. Type V:NH:E was isolated from 22 (79%) of the 28 patients with AIDS, including 8 of 9 patients from an additional hospital. Subtype V:NH:E2 was recovered from 11 patients, 9 of whom had AIDS, including all 5 AIDS patients from one floor of a nursing home affiliated with a third hospital. By using both mecA:Tn554 probes and PFGE, MRSA clusters and outbreaks may be detected and provide a rationale for appropriate infection control intervention.

Adolescent

The in vitro generation of post-Golgi vesicles carrying viral envelope glycoproteins requires an ARF-like GTP-binding protein and a protein kinase C associated with the Golgi apparatus.

We have developed a system that recreates in vitro the generation of post-Golgi vesicles from an isolated Golgi fraction prepared from vesicular stomatitis virus- or influenza virus-infected Madin-Darby canine kidney or HepG2 cells. In this system, vesicle generation is temperature- and ATP-dependent and requires a supply of cytosolic proteins, including an N-ethylmaleimide-sensitive factor distinct from NSF. Cytosolic proteins obtained from yeast were as effective as mammalian cytosolic proteins in supporting vesicle formation and had the same requirements. The vesicles produced (50-80 nm in diameter) are depleted of the trans Golgi marker sialyltransferase, contain the viral glycoprotein molecules with their cytoplasmic tails exposed, and do not show an easily recognizable protein coat. Vesicle generation was inhibited by brefeldin A, which indicates that it requires the activation of an Arf-like GTP-binding protein that promotes assembly of a vesicle coat. Vesicles formed in the presence of the nonhydrolyzable GTP analogue guanosine 5'-3-O-(thio)triphosphate retained a nonclathrin protein coat resembling that of COP-coated vesicles, and sedimented more rapidly in a sucrose gradient than the uncoated ones generated in its absence. This indicates that GTP hydrolysis is not required for vesicle generation but that it is for vesicle uncoating. The activity of a Golgi-associated protein kinase C (PKC) was found to be necessary for the release of post-Golgi vesicles, as indicated by the capacity of a variety of inhibitors and antibodies to PKC to suppress it, as well as by the stimulatory effect of the PKC activator 12-O-tetradecanoylphorbol-13-acetate.

ADP-Ribosylation Factors

The effect of lithium on renal haemodynamic function.

Renal concentrating capacity following 18 hours of fluid deprivation was measured in 75 patients receiving prophylactic lithium therapy, and in 30 affectively ill subjects receiving other drugs. The lithium-treated patients had significantly lower urine osmolality and higher serum osmolality than the control subjects. Older subjects, patients maintained at higher serum lithium levels and those with a history of previous neurotoxicity showed the most impairment. Ten patients with urine osmolalities of less than 700 mOsm/1 following this test were investigated further. Inulin and para-amino hippurate (PAH) clearance rates were determined and the effect of a subpressor challenge of dopamine on these measures was observed. Half of the patients showed some reduction in inulin and PAH clearance, which was greatest in those patients who had been taking lithium for over 10 years. However, all of the patients tested showed the expected increase in renal blood flow and sodium and water excretion in response to dopamine. Six additional patients had clearance estimations made before starting lithium treatment which were repeated after a period of 3-6 months on the drug. No consistent changes in haemodynamics were observed. Lithium clearly reduces renal concentrating capacity, but other measures of renal tubular function were well preserved in patients receiving long-term therapy. Glomerular function may be slightly reduced in patients taking lithium for long periods. The results show that prophylactic lithium treatment does not affect renal cortical function adversely in the majority of patients, but impaired renal concentrating ability is a common accompaniment.

Adult

Bupropion's prophylactic efficacy in bipolar affective illness.

Three bipolar manic-depressive patients are described who, after responding to bupropion treatment for an acute depressive relapse, were maintained on the drug alone for a 1-year period, without recurrences of mania or depression. Discontinuation of medication was followed within 8 weeks by a manic or depressive recurrence in all three cases. Data are presented to suggest that bupropion probably exerted a prophylactic effect in preventing acute affective recurrences in these cases. This drug merits investigational attention as an alternative approach to current maintenance chemotherapy of recurrent affective disorder.

Acute Disease

Adjuvant effects of lithium chloride on human mononuclear cells in suppressor-enriched and suppressor-depleted systems.

Lithium enhances several in vitro indices of immune function, including thymidine uptake by mitogen-stimulated human mononuclear cells. To further characterize the mechanism of action of lithium and to determine whether it acts by abrogating suppressor cell activity or by enhancing helper cell function, we have compared the effects of lithium on the mitogenic response of normal, suppressor-depleted and suppressor-enriched mononuclear cell preparations. In normal cultures, lithium enhanced thymidine uptake in response to concanavalin A (Con A) and phytohemagglutinin (PHA). In the suppressor-depleted cultures, thymidine uptake after Con A stimulation was significantly higher than in normal cultures, and was further enhanced by lithium. In the suppressor-enriched system, response to PHA was significantly lower than in normal cultures, and addition of lithium reversed the observed suppression. These results indicate that lithium may be enhancing thymidine uptake in response to mitogen at least in part by abrogating suppressor cell activity. The observed increase in thymidine incorporation in the suppressor-depleted cultures suggests that lithium may also have a direct stimulatory effect on helper cell activity.

Adjuvants, Immunologic

Estimation of lithium dose requirement by lithium clearance, serum lithium and saliva lithium following a loading dose of lithium carbonate.

Renal lithium clearance and the serum lithium levels following a single oral loading dose of lithium were used as measures to predict lithium dose requirement during long-term maintenance at 3 different psychiatric centers in North America. Saliva lithium values were also investigated at one of the centers. The correlation between lithium clearance and the 17-hour serum lithium level, and subsequent dosage was high; the mean correlation co-efficient from the 3 centers being 0.84 for renal lithium clearance and 0.75 for both the 17-hour and 10-hour serum lithium levels. These tests can therefore be recommended as a guide to estimate lithium dose requirement in patients starting lithium maintenance treatment although absolute reliance should not be placed on the prediction formulae obtained. The correlation between saliva lithium and eventual dosage was poor and of little predictive value.

Adult

An immunodeficient child with inflammatory bowel disease: involvement of cyclic nucleotides and effects of lithium.

A 3-year-old male with inflammatory bowel disease and hypogammaglobulinemia was found to have decreased T lymphocyte function. His serum was shown to depress normal T cell proliferative responses to phytohemagglutinin. Incorporation of lithium chloride to in vitro cultures enhanced autologous lymphocyte responses to phytohemagglutinin. Since lithium acts by inhibiting cAMP production, the child's lymphocytes were postulated to have increased levels of cAMP. Both lymphocytes and serum were shown to contain elevated levels of cAMP. In vivo therapy with lithium citrate was initiated and enhanced T cell numbers and function were observed concomitantly. Serum cAMP was also reduced to normal levels. The patient showed initially marked clinical improvement as assessed by mood, weight gain, and diminution of diarrhea. This clinical improvement was unfortunately not sustained despite the continued improvement in immune parameters and cAMP levels.

Agammaglobulinemia

Lithium as an immunologic adjuvant.

Lithium, an adenylate cyclase inhibitor, stimulates a variety of in vitro indices of immune function, including proliferation of lymphocytes in response to mitogens, rosette formation by T-cells and phagocytosis by macrophages. Lithium enhances these immunologic responses at concentrations comparable to those achieved in patients receiving lithium for treatment of manic-depressive disorders. Lithium may prove to have important therapeutic applications as an immune adjuvant, particularly in immune deficiency states associated with excessive C-AMP production.

Adjuvants, Immunologic