PubMed Health⌕ Search

Biomedical subjects

M Sharp

Publications and source records attributed to M Sharp.

At least 19 recordsLinked to original sources
PubMed1995

Age-related differences in cell-mediated immunity to varicella-zoster virus among children and adults immunized with live attenuated varicella vaccine.

Live attenuated varicella vaccine elicits protection against varicella-zoster virus (VZV), but adults require two doses to achieve optimal seroconversion rates. To assess the potential role of cell-mediated immunity (CMI), T cell proliferation to VZV antigen was compared in children and adults. Mean stimulation indices (SI) in two cohorts of 39 children tested 6 weeks after vaccination were 28.6 +/- 6.21 and 22.1 +/- 3.84, whereas 20 adult vaccines had a mean SI of 9.1 +/- 0.99 (P = .04). Vaccinees had significant increases in CMI after a second dose of vaccine. At 1 year, VZV CMI was significantly lower in adults after two doses (10.0 +/- 1.13 vs. 15.6 +/- 1.77; P = .02), even though 82% of children received one dose. Limitations in the adult helper T cell response to VZV antigens may explain the need for booster doses to elicit effective immunity and the more frequent occurrence of varicella when adult vaccines are exposed to wild type virus.

Adolescent↗
PubMed1995

Chronic self-destructiveness and self-defeating personality: similarities and differences.

This study attempts to determine whether the Chronic Self-Destructiveness Scale (CSDS; Kelley, Byrne, et al., 1985) would be better described as a measure of impulsiveness or self-defeating behavior in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., Rev. [DSM-III-R]; American Psychiatric Association, 1987) diagnostic sense. Subjects completed the CSDS, the Self-Defeating Scale (Schill, 1990), and measures of restraint, distress, and psychopathy. Based on the correlations among these scales, we suggest that the CSDS is better described as a measure of impulsiveness, poor judgment, and immediate gratification, rather than a measure of Self-Defeating Personality, which keeps the individual in a victim position.

Adolescent↗
PubMed1995

Self-defeating personality and depression: a closer look.

55 men and 55 women were given Schill's Self-defeating Personality Scale, a measure of Beck's cognitive triad, and a measure of the personality dimensions of sociotropy and autonomy. The more characteristics of self-defeating personality endorsed, the more negative were subjects' cognitions about themselves, the world, and the future. Self-defeating men and women scored higher on sociotropy (social dependence), suggesting threats to relationships may be an important source of depression for them. Self-defeating women also scored higher on the autonomy subscales, suggesting threats to their independence may be a source of depression as well. Implications for treatment were discussed.

Adolescent↗
PubMed1992

Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation.

Bone marrow transplant (BMT) recipients were evaluated for subclinical varicella-zoster virus (VZV) viremia and symptoms of herpes zoster after transplantation. Viremia was demonstrated by testing peripheral blood mononuclear cells using polymerase chain reaction and was documented in 19% of 37 patients. When reactivation was defined as herpes zoster and/or subclinical VZV viremia, 41% of VZV-seropositive BMT recipients experienced VZV reactivation. None of 12 patients tested before VZV reactivation had T lymphocyte proliferation to VZV antigen (mean stimulation index, 1.0 +/- 0.42 [SD] at less than 100 days; 12.0 +/- 6.03 at greater than 100 days [P = .003]). Among patients tested at greater than 100 days, 5 (63%) of 8 with detectable T cell proliferation had subclinical or clinical VZV reactivation compared with none of 6 who lacked VZV T cell responses. Recovery of VZV-specific cytotoxic T lymphocyte function was observed in 50% of BMT patients, but BMT recipients had significantly fewer circulating cytotoxic T lymphocytes that recognized VZV immediate early protein (P = .03) or glycoprotein I (P = .004) than did healthy VZV immune subjects. In vivo reexposure to VZV antigens due to subclinical VZV viremia or symptomatic VZV reactivation may explain the recovery of virus-specific T cell immunity after BMT.

Adolescent↗
PubMed1992

Kinetics and viral protein specificity of the cytotoxic T lymphocyte response in healthy adults immunized with live attenuated varicella vaccine.

The cytotoxic T lymphocyte (CTL) response was evaluated in adults given live attenuated varicella vaccine, using target cells expressing varicella-zoster virus (VZV) immediate-early protein (IE62) or VZV glycoproteins gpI, gpIV, or gpV to determine viral protein specificity. The frequency of CTL that recognized IE62 was 1:171,000 +/- 46,000 SE in subjects tested 10 days to 8 weeks after the initial vaccine dose; the induction of CTL specific for gpI was equivalent. CTL recognition of VZV proteins was mediated by CD4+ or CD8+ cells. CTL recognition of IE62 and gpIV persisted in vaccinees (tested approximately 4 years later) and was comparable to that in the naturally immune. The mean frequency of CTL specific for gpV was lower (but not significantly) in vaccinees than in naturally immune subjects. Assay of responder cell frequencies showed persistence of equivalent numbers of T lymphocytes that recognized IE62 and gpI in vaccinees and naturally immune subjects. Immunization with this vaccine elicited memory T lymphocyte responses to VZV comparable to those induced by natural infection.

Antibodies, Viral↗
PubMed1991

Equivalent recognition of a varicella-zoster virus immediate early protein (IE62) and glycoprotein I by cytotoxic T lymphocytes of either CD4+ or CD8+ phenotype.

Immunity to varicella-zoster virus (VZV), a member of the alpha-herpes virus family, exemplifies the host response to an ubiquitous human viral pathogen. In this investigation of the cytotoxic T lymphocyte (CTL) response to VZV, the depletion of CD4+ T lymphocytes made it possible to demonstrate CD8(+)-mediated cytotoxic function against autologous VZV-infected lymphoblastoid cells targets. CTL recognition of two major VZV proteins, the immediate early protein (IE62) and gp I, was demonstrated in limiting dilution cultures of T lymphocytes obtained from immune donors, stimulated with inactivated VZV Ag, and tested against lymphoblastoid cells infected with vaccinia recombinants expressing these VZV proteins. Among 11 VZV donors tested at least 20 y after primary infection, the mean precursor frequency for T lymphocytes that recognized the IE62 protein was 1:105,000 +/- 85,000 SD, with a range of 1:13,000 to 1:231,000. The mean frequency of CTL precursors specific for gp I in 11 subjects was equivalent, with a mean of 1:121,000 +/- 86,000 SD (range 1:15,000 to 1:228,000) (p = 0.68). Limiting dilution cultures were also prepared using purified CD4+ or CD8+ T lymphocyte populations recovered from PBMC by sterile fluorescence-activated cell sorting. CTL precursors that recognized the IE62 protein or gp I were derived from each of the major T lymphocyte populations by stimulation with inactivated VZV Ag; CD4+ and CD8+ CTL precursor frequencies for the IE62 protein and gp I were equivalent (p = 0.2). We conclude that antiviral CTL activity against targets expressing VZV proteins was mediated equally well by T lymphocytes of the CD4+ or CD8+ phenotype and that antiviral CTL function could be elicited in each subpopulation by exposure to non-infectious viral Ag.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Human T cells recognize multiple epitopes of an immediate early/tegument protein (IE62) and glycoprotein I of varicella zoster virus.

Infection with varicella zoster virus (VZV) elicits persistent cell-mediated immunity directed against the immediate early (IE62) protein and the glycoprotein I (gp I) in most healthy subjects. In these experiments, synthetic peptides corresponding to residues of the IE62 protein and gp I were used to identify linear amino acid sequences of these immunogenic VZV proteins that were recognized by peripheral blood T lymphocytes from VZV-immune individuals of known major histocompatibility complex (MHC) type. All of 12 VZV-immune donors had T-cell proliferative responses, defined as a stimulation index (SI) greater than or equal to 2.0, to at least two of ten synthetic IE62 peptides; the mean number of IE62 peptides recognized by T cells from VZV-immune donors was seven. Five of the ten IE62 peptides stimulated T cells from 75% to 83% of the VZV-immune donors; the other five IE62 peptides were recognized by T cells from 42% to 67% of the subjects. All VZV-immune donors also had T proliferation responses to at least two of ten synthetic gp I peptides; the mean number of peptides recognized was six. Six of the ten gp I peptides were recognized by T cells from 67% to 92% of the VZV-immune donors; the frequency of donors responding to the other gp I peptides ranged from 42% to 58%. None of five nonimmune donors demonstrated T-cell proliferation to any of the IE62 or gp I peptides. A combination of two IE62 peptides provided epitopes that could be recognized by T cells from all twelve VZV-immune donors, regardless of DR type. Similarly, one gp I peptide in combination with either of two other gp I peptides induced proliferation of T cells from all immune subjects. Memory T cells with specificity for multiple short amino acid sequences of the IE62 protein and gp I were detected in subjects who had had primary VZV infection more than 20 years earlier. These observations indicate that natural VZV infection elicits a diverse cell-mediated immune response to viral proteins that is not restricted to only one or two immunodominant regions. Although the usefulness of peptide vaccines remains to be established, multiple epitopes of the IE62 protein and gp I were identified that could be presented by antigen-presenting cells (APC) and recognized by T cells from most subjects in an "outbred" human population.

Amino Acid Sequence↗
PubMed1990

Clock mutations alter developmental timing in Drosophila.

The developmental time of period mutants in Drosophila melanogaster was monitored under different environmental conditions. We observed that the pers mutants, which have short 19 h circadian cycles, develop faster from eggs to adult than the wild-type: perL mutants, which have long 28 h circadian rhythms, complete development more slowly than the wild-type. These results suggest that endogenous timers may be involved in regulating the development time of D. melanogaster.

Analysis of Variance↗
PubMed1990

Metabolic and cardiorespiratory parameters during three consecutive days of exhaustive running.

The purpose of this study was to examine serum metabolites, cardiorespiratory parameters and creatine kinase during running on 3 consecutive days. Thirteen trained marathon runners exercised to exhaustion on a treadmill at 85 +/- 3% VO2max on each day. Expired gases and blood samples were obtained at rest, after 10 and 30 min of exercise and at exhaustion. There were no significant differences over days for glucose, insulin, lactate, free fatty acids, creatine kinase, oxygen uptake, minute ventilation, heart rate, rating of perceived exertion, respiratory exchange ratio or run times. Serum glycerol was elevated (p less than 0.05) both at rest and during exercise on each successive day. The findings suggested that, except for serum glycerol, acute metabolic and cardiorespiratory responses to exhaustive aerobic exercise are not altered by 3 days daily repetition by endurance trained individuals.

Cardiovascular System↗
PubMed1989

The management and coordination of biotechnology in the U.K. 1980-88.

Government policy towards biotechnology has come a long way since the Spinks Report. Spinks advocated centralized coordination of policy, an approach deliberately rejected in 1981 by the Government in favour of continued pluralism, with each of the scientific research councils and various ministries 'doing their own thing'. This has led to considerable diversity of activity, and during these eight years more has in fact been achieved than is often recognized. But it also created an overlapping of responsibilities with concomitant friction and bad feeling that has wasted time and resources. The paper argues that some degree of friction is inevitable. By their nature new technologies cut across existing disciplines and blur institutional boundaries. The traditional approach has been to muddle through, allowing new institutions to emerge and adapting the old as seems appropriate. Lack of resources, however, argues against too brash a competitive approach. The paper suggests that strategic or precompetitive research should be seen as a complement to, rather than competitive with basic research, and cautions against too radical a restructuring of institutions at the present time.

Biotechnology↗
PubMed1988

Effect of prostaglandin F2 alpha on human parathyroid adenomas: evidence for uncoupling of parathyroid hormone secretion and cAMP accumulation.

Human parathyroid adenomas are aberrantly regulated by extracellular calcium. We tested pertussis toxin, which ADP-ribosylates and inactivates several guanine nucleotide regulatory proteins, to test the role of these proteins in the secretory control of adenomatous parathyroid tissue. Pertussis toxin did not affect basal cAMP accumulation in 12 adenomas and enhanced parathyroid hormone (PTH) release in 6 of 10 adenomas. Prostaglandin F2 alpha (PGF2 alpha) inhibited cAMP in three of six adenomas, and pertussis toxin pretreatment did not affect this result. PTH release in 7 of 10 adenomas was inhibited by PGF2 alpha, and pertussis toxin did not significantly alter PTH release. Pertussis toxin catalyzed ADP-ribosylation of a 40-kDa protein in all adenomas tested (n = 8). We conclude that cAMP accumulation was not affected by pertussis toxin but that in 6 of 10 adenomas, the toxin enhanced PTH release. We suggest that cAMP accumulation and PTH release may be uncoupled from negative control by inhibitory ligands in adenomatous tissue or that the G-proteins involved do not couple to regulatory receptors or to effector.

Adenoma↗
PubMed1988

Day-care center exclusion of sick children: comparison of opinions of day-care staff, working mothers, and pediatricians.

Day-care center staff are often faced with the decision of whether to send sick children home. Some pediatricians may question the criteria used by day-care centers to exclude children who have mild infectious illnesses. To determine whether there is a consensus on illness policy, we asked day-care center staff, mothers, and pediatricians which sick children in day care should be excluded. Randomly selected day-care center staff, mothers, and pediatricians in three North Carolina counties completed self-administered questionnaires. We asked how combinations of temperature and symptoms that occur with common childhood infections should affect the staff's decisions to "call the parent for immediate pickup." Response rates were 302 of 347 staff (87%), 134 of 200 mothers (67%), and 69 of 80 pediatricians (86%). A temperature of 37.2 degrees to 37.7 degrees C (99 degrees to 99.9 degrees F) was considered a fever by 35% of staff, 24% of mothers, and 6% of pediatricians (P less than .01). At every level of elevated temperature from 37.2 degrees to 38.9 degrees C (99 degrees to 102 degrees F), day-care center staff were more likely to request immediate pickup than mothers or pediatricians (P less than .01). For each of eight symptoms and for all three groups of respondents, the addition of a temperature of 37.8 degrees C (100 degrees F) increased the proportion of children sent home (P less than .01). Day-care center staff, mothers, and pediatricians differ in their reported exclusionary practices for ill day-care children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Day Care Centers↗
PubMed1983

Protein subunit vaccines of parainfluenza type 3 virus: immunogenic effect in lambs and mice.

Protein subunit vaccines were prepared from a mixture of the haemagglutinin (HN) and fusion (F) glycoproteins of parainfluenza type 3 virus (PI-3). The glycoproteins were isolated in three different forms and characterized by their sedimentation coefficients: 30S protein micelles (a complex of several HN and F glycoproteins devoid of detergent and lipid), 18S protein-TX complexes (a complex of several glycoproteins containing the detergent Triton X-100), and 4S protein-TX complexes (probably monomers of the glycoproteins complexed to Triton X-100). These preparations were tested as vaccines in mice and lambs. The immune response in the mice was assayed both in the serum and in extracts from the lungs using an ELISA technique. Both of the multimeric complexes were highly immunogenic. The 30S protein micelles induced a high antibody response after two injections with either 10 or 1 microgram protein. The serum IgG titres reached levels of about 90 micrograms/ml and 40 micrograms/ml respectively. Similar titres were reached with the 18S protein-TX complexes. After two injections of either the 30S or the 18S complexes IgA antibody responses were detected in the lung extracts. The 4S protein-TX complexes were poor immunogens and induced low antibody responses in mice. The lambs were vaccinated with the 30S protein micelles, and the immune response was evaluated serologically and in challenge experiments. The 30S protein micelles in an oil adjuvant induced detectable serum antibody titres as well as protective immunity against the pneumonia caused by the PI-3 virus.

Animals↗
PubMed1980

Cell-mediated immune responses to chlamydial antigens in guinea pigs injected with inactivated chlamydiae.

Cell-mediated immunity (CMI) to chlamydial antigens was readily induced in guinea pigs by a single injection of Betaprone-inactivated chlamydiae in complete Freund adjuvant. The CMI was measured in vivo by delayed hypersensitivity skin tests, and in vitro by inhibition of migration of peritoneal exudate cells and by proliferation of lymph node lymphocytes. There was an overall correlation between in vivo and in vitro responses. Of the in vitro assays, migration inhibition reflected the state of sensitization, as judged by skin tests, more uniformly than lymphocyte stimulation. Extensive inter- and intra-species cross-reactivity was noted between LB-1, a strain of C. trachomatis, and three strains of C. psittaci, 6BC, GPIC, and 562F. Cross-reactivity between LB-1 and 6BC was one-way only, by all three parameters: LB-1 elicited strong cross-reactions in 6BC-immunized animals but not vice versa. Antichlamydial antibodies could not be demonstrated in any of the animals by microimmunofluorescence.

Animals↗