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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 19 recordsLinked to original sources

Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial.

OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled intervention study. SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age. INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed. CONCLUSIONS: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

Aged

CD28/B7 costimulation regulates autoimmune diabetes induced with multiple low doses of streptozotocin.

Insulin-dependent diabetes mellitus is believed to occur as a result of a T cell-mediated destruction of the islets of Langerhans. The factors that regulate the T cell responses, in particular the costimulatory signals required for the T cell activation, which result in islet cell destruction, are still unclear. CD28/B7 interactions have been shown to be important in the regulation of T cell immune responses. We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus). Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice. The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease. Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice. Expression of only CD86 increased on islet cells in diabetic mice. In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease. We conclude that CD28 signal transduction is required for development of diabetes in multidose STZ-induced diabetes mellitus. CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.

Animals

Seasonality prevalence and incidence of depressive disorder in a general practice sample: identifying differences in timing by caseness.

A total of 2225 consecutive consulting general practice patients attending a North London Health Centre over the course of a year were screened and interviewed for the presence of psychiatric disorder using the GHQ and SADS; 196 patients suffering from RDC depressive disorders were identified and followed up for a further 12 months. A difference in prevalence incidence and recovery time was identified between major and minor depression. Various associations between season of onset and a range of variables were observed. Logistic modelling identified interactions between some of these variables some of which have not been explored in previous studies.

Bipolar Disorder

A comparison of bactericidal/permeability-increasing protein variant versus recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli sepsis in rats .

OBJECTIVE: To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein. DESIGN: Randomized, blinded, controlled study, using a rat model of sepsis. SETTING: Animal research facility. SUBJECTS: Male Wistar rats. INTERVENTIONS: An inoculum of 1.5 x 10(7) to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly. MEASUREMENTS AND MAIN RESULTS: Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs. control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant-treated (p < .001 vs. control) and two (6.5%) of 31 control animals. CONCLUSIONS: Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival. Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability-increasing protein variant in its protective effect at the doses tested. Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.

Animals

Compliance to exercise therapy in older participants with knee osteoarthritis: implications for treating disability.

This investigation examined predictors of compliance with exercise therapy in a clinical trial involving older adults with knee osteoarthritis (OA). The study sample was partitioned into tertiles by level of compliance to determine its effect on several clinical outcome measures in the trial (i.e., knee pain, difficulty with activities of daily living, and performance-related disability). The participants (N = 439) first completed all baseline assessments and were then randomly assigned to one of three treatment conditions: health education control, aerobic exercise, or resistance exercise. The two exercise treatments involved a 3-month center-based phase and a 15-month home-based phase. Variables in five categories (i.e., demographic, fitness, health-related quality of life, performance-related disability, and prior exercise behavior) were entered as predictors of attendance and time spent exercising during each session for three different periods of time across the course of the study. Results of these analyses revealed that it was possible to explain more variance for time spent exercising (approximately 40%) during the first 3 months than for attendance (approximately 10%). Furthermore, once participants completed the first 3 months of their training, prior behavior was the strongest predictor of exercise compliance. In most cases, the regression models accounted anywhere from 26 to 46% of the variance in attendance or time spent exercising (7 of the 8 P values < 0.01). In general, demographic, fitness, psychosocial, and disability-related measures did not predict compliance with any consistency across the various phases of the trial. Analysis of the dose-response data suggest that, in the use of aerobic exercise to deter disability in older people with knee OA, consideration should be given to prescribing frequent bouts of activity (at least 3 times each week) of moderate duration (approximately 35 min).

Activities of Daily Living

Differences in classroom teaching preferences between traditional and adult BSN students.

The primary purposes of this study were to identify the best teaching practices for adult baccalaureate (BSN) nursing students and to examine if adult students' teaching preferences differed from those of traditional BSN students. The sample consisted of 206 adult and traditional students in four BSN programs. The adult nursing student sample was further subdivided into two groups: adults with no prior nursing education (adult non-nurses) and adults with prior nursing education (RN's). Using a two-part, self-administered questionnaire, respondents were asked to rate the frequency with which 41 teaching strategies were used in their best and in their worst classroom learning experiences in nursing. In most cases, adult non-nurses' teaching preferences did not vary significantly from the preferences of traditional students. However, adults with no prior nursing education did show a preference for knowledgeable and organized instructors. In contrast RNs' preferred classroom situations wer where time on task was emphasized, cooperative learning was encouraged, and expectations for learning were high. Results indicate that classroom teaching preferences vary as a function of prior experience with the subject matter and are not attributable to age itself. Findings suggest that prior experience with course content is a more important consideration in planning programs than generalized adult experience.

Adolescent

The Seasonal Pattern Assessment Questionnaire for identifying seasonal affective disorders.

The SPAQ is a widely used tool for identifying possible cases of recurrent major depressive disorders with a seasonal pattern. However, its test-retest reliability, sensitivity, specificity, positive predictive value, negative predictive value, efficiency and predictive validity have not previously been formally assessed. Forty-seven subjects who fulfilled the DSMIIIR criteria for a major depressive disorder with a seasonal pattern were traced and re-interviewed after five to eight years. The SPAQ was found to have a positive predictive value of 48% and an efficiency of 57% in identifying cases of SAD confirmed by follow-up. The test-retest reliability was low. There was a mean difference in seasonality score between the first and second test of 3.17 +/- 4.7 (mean +/- 1 S.D.). Although the SPAQ is a rapid method of collecting information about recent seasonal variation, it has low test-retest reliability and on its own is unable to predict the seasonality of the future course of illness.

Depressive Disorder

Parallel synthesis and screening of a solid phase carbohydrate library.

A solid phase carbohydrate library was synthesized and screened against Bauhinia purpurea lectin. The library, which contains approximately 1300 di- and trisaccharides, was synthesized with chemical encoding on TentaGel resin so that each bead contained a single carbohydrate. Two ligands that bind more tightly to the lectin than Gal-beta-1,3-GalNAc (the known ligand) have been identified. The strategy outlined can be used to identify carbohydrate-based ligands for any receptor; however, because the derivatized beads mimic the polyvalent presentation of cell surface carbohydrates, the screen may prove especially valuable for discovering new compounds that bind to proteins participating in cell adhesion.

Acylation

Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.

BACKGROUND: In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction. METHODS: In a multicenter study, blood specimens from 1404 symptomatic patients were analyzed for cardiac troponin I, a serum marker not detected in the blood of healthy persons. The relation between mortality at 42 days and the level of cardiac troponin I in the specimen obtained on enrollment was determined both before and after adjustment for baseline characteristics. RESULTS: The mortality rate at 42 days was significantly higher in the 573 patients with cardiac troponin I levels of at least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0 percent; P < 0.001). There were statistically significant increases in mortality with increasing levels of cardiac troponin I (P < 0.001). Each increase of 1 ng per milliliter in the cardiac troponin I level was associated with a significant increase (P = 0.03) in the risk ratio for death after adjustment for the base-line characteristics that were independently predictive of mortality (ST-segment depression and age > or = 65 years). CONCLUSIONS: In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.

Acute Disease

Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas-mediated apoptosis.

CD40--CD40L interactions between resting B cells and activated T cells are essential for germinal center formation. It has been shown that CD40L can induce both Fas expression and susceptibility to Fas-mediated killing in B cells, while anti-Ig can partially rescue B cells from Fas-mediated killing. However, the intracellular mechanism for this phenomenon is not known. We examined the expression of Fas and bcl-2 family gene products, such as Bcl-2, Bcl-x, Bax, and Mcl-1, in human tonsillar B cells. The activation of naive B cells by CD40L induced transient expression of Bcl-xL. As the Bcl-xL level decreased in CD40-activated B cells, the cells became susceptible to apoptosis by anti-Fas antibodies. Though anti-Ig did not change the Fas expression, it protected CD40-activated B cells from Fas-mediated killing by up-regulating Bcl-xL expression. The addition of anti-Ig did not significantly change Bcl-2, Bax, and Mcl-1 levels compared to those of B cells activated by CD40L alone.

Apoptosis

Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia.

OBJECTIVE: To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. DESIGN: An open, randomized immunogenicity study. SETTING: A busy urban health center in The Gambia. STUDY PARTICIPANTS: A total of 451 pregnant women enrolled during the third trimester of pregnancy. INTERVENTION: Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age. In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. MAIN OUTCOME MEASURES: Anti-PRP antibody measurements of maternal cord, and infant blood. RESULTS: Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer 9.0 micrograms/mL), which was greatest in women in their first or second pregnancy. Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations. In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35 and 2.84 micrograms/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 micrograms/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 micrograms/mL). CONCLUSIONS: In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization.

Antibodies, Bacterial

Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain.

Nucleotide excision repair (NER) is an ordered process in nonmalignant cells, in both human and nonhuman systems. We previously reported that in human brain there is discordant mRNA expression of excision repair cross-complementing (ERCC) 1 and ERCC2 in malignant tissues, concurrent with excellent concordance of these genes in nonmalignant tissues from the same patients. Here we have extended these studies to compare low-grade tumors to high-grade tumors and to include ERCC3 (which links DNA repair with DNA transcription) and ERCC6 (which is essential for gene-specific repair). Glial tumor and adjacent normal brain specimens from 19 individuals were studied. Paired malignant and nonmalignant tissues were obtained from 12 of these patients. For ERCC3, there was excellent concordance of mRNA expression between malignant and nonmalignant tissues from the same individuals (P = 0.003). For ERCC6, no concordance was observed (P = 0.314). Tumor tissue from patients with high-grade gliomas exhibited marked discordance of mRNA expression patterns in situations in which good concordance was observed in tumor tissue from low-grade gliomas. We previously established that malignant brain tumors show increased disorder of genes in the NER process, as compared with nonmalignant tissues. These data suggest that increasing disorder in the NER process may occur as cells move from low-grade to high-grade malignancy.

Astrocytoma

The validation of a 7-locus multiplex STR test for use in forensic casework. (I). Mixtures, ageing, degradation and species studies.

We have evaluated a multiplex STR system for routine forensic use, which co-amplifies six short tandem repeat (STR) loci; HUMTH01, D21S11, D18S51, D8S1179, HUMVWF31/A and HUMFIBRA (FGA), in conjunction with the X-Y homologous gene Amelogenin. Analysis of PCR products employs denaturing polyacrylamide gels coupled with fluorescent labelled primers and detection is undertaken on ABD 373A automated sequencers. The technique was shown to be robust and reproducible when samples were analysed under conditions consistent with those encountered in a forensic environment. The system was demonstrated to be human specific and is suitable for use with both aged and degraded material. Somatic stability was proven with a wide range of tissue types and we were able to detect mixtures at ratios between 1:10 and 10:1. During this study no incidence of sample mis-typing due to allelic or locus drop-out was observed. Furthermore, although additional artefact bands were occasionally encountered these did not interfere with the interpretation of results. The performance of the system with poor quality samples demonstrated its suitability as a powerful tool in forensic investigation.

Adult

Readability of printed sources of diet and health information.

This study surveyed nutrition education materials which are low in cost, brief and the type most used in patient education to determine which might be useful with low literacy clients. Readability of 209 pamphlets from professional health organizations, commercial organizations, government agencies, and educational institutions was assessed using three different tests. Using the Flesch and Raygor tests, materials from educational institutions had significantly lower reading levels than materials from professional organizations and government agencies. No significant differences were seen among the sources using the Fry test. Sixty-eight percent (142) of the publications were written at ninth grade level or higher. Eleven percent (24) scored at sixth grade or below on either the Fry or Raygor scale. Only two publications were written at the third grade level. Many of the publications reviewed can be read and understood by many Americans, but there were few for the millions that have limited literacy skills.

Educational Status

Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic beta cell line, INS-1.

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. We have examined the mode of cell death caused by streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.

Animals