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Biomedical subjects

A Noble

Publications and source records attributed to A Noble.

At least 37 records · Page 2Linked to original sources
PubMed1997

Antigen-specific CD8+ T cells inhibit IgE responses and interleukin-4 production by CD4+ T cells.

There is a growing body of evidence which suggests that CD8+ T cells play an important part in regulating the IgE response to non-replicating antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4+ T cell responses to ovalbumin (OVA) by CD8+ T cell depletion in vivo. Following intraperitoneal immunization with alum-precipitated OVA, OVA-specific T cell responses were detected in the spleen and depletion of CD8+ T cells in vitro significantly enhanced the proliferative response to OVA. Depletion of CD8+ T cells in vivo 7 days after immunization failed to enhance IgE production, while depletion of CD8+ T cells on days 12-18 greatly enhanced the IgE response, which rose to 26 micrograms/ml following a second injection of anti-CD8 on day 35 and remained in excess of 1 microgram/ml over 300 days afterwards. Reconstitution on day 21 of rats CD8-depleted on day 12 with purified CD8+ T cells from animals immunized on day 12 completely inhibited the IgE response. This effect was antigen specific; CD8+ T cells from OVA-primed animals had little effect on the IgE response of bovine serum albumin immunized rats. In vivo, CD8+ T cell depletion decreased interferon (IFN)-gamma production but enhanced interleukin (IL)-4 production by OVA-stimulated splenic CD4+ T cells. Furthermore, CD8+ T cell depletion and addition of anti-IFN-gamma antibody enhanced IgE production in vitro in an IL-4-supplemented mixed lymphocyte reaction. These data clearly show that antigen-specific CD8+ T cells inhibit IgE in the immune response to non-replicating antigens. The data indicate two possible mechanisms: first, CD8+ T cells have direct inhibitory effects on switching to IgE in B cells and second, they inhibit OVA-specific IL-4 production but enhance IFN-gamma production by CD4+ T cells.

Animals↗
PubMed1997

Effects of age on perinatal substance abuse among whites and African Americans.

This descriptive study assessed age effects on perinatal use of alcohol, marijuana, and cocaine among African-American and white women. Data were derived from the California Perinatal Exposure Study, relying on a statistical probability sample n = 29,494) of women who underwent anonymous urine toxicology screening in birthing hospitals. The central hypothesis was that there would be no difference in age effects on drug use among white and African-American women. Marital status and payment source were used as risk factors in order to create detailed age-risk profiles for both racial-ethnic groups. Logistic regression analyses were used and findings indicated that cocaine use peaked in early adulthood for whites and in mid-adulthood for African-Americans who had higher prevalence levels with the same or fewer risk factors as whites. Over one third of African-American women in their mid-thirties who were not married and who had publicly assisted births tested positive for cocaine. In contrast, high risk whites had higher marijuana prevalence levels than African-American women, and prevalence increased with age. Alcohol prevalence increased with age for African-American and white women who were publicly assisted, but decreased with age for all others. Findings for alcohol and marijuana generally followed the same risk-adjusted patterns for African American and white women but with different prevalence levels; however, cocaine use had a unique pattern with higher prevalence among African-American women in mid-adulthood regardless of risk level.

Adolescent↗
PubMed1997

Perinatal drug use among immigrant and native-born Latinas.

Perinatal drug exposures pose a significant health hazard for women and imperil normal fetal and neonatal development. Little is known about patterns of drug exposure among pregnant immigrant and native-born Latinas in the United States. We present multivariate risk factor analyses for alcohol and illicit drug use from the California Perinatal Substance Exposure Study using a statistical probability sample (N = 11,002) of Latinas who were tested anonymously using urine toxicology screening techniques. Alcohol use during pregnancy was pervasive among both immigrant and United States-born Latinas (7%) with little variation on risk factors. Illicit drug use was found primarily in a high risk group of United States-born Latinas between 25 and 34 years of age who received no prenatal care (prevalence 50%, odds ratio of 185). Increased general awareness of perinatal alcohol risk by medical providers and public health practitioners serving this population is needed. The potential isolation of United States-born Latinas who are at risk using illicit drugs during pregnancy requires effective communication and outreach.

Adolescent↗
PubMed1997

The relationship between shoe size and mode of delivery.

This study investigates whether a woman with a small shoe size has a higher chance of being delivered by cesarean section. Data on shoe size and mode of delivery were collected by chart review and telephone survey from clients of a freestanding birth center. Purposive sampling was done to include all women transferred and delivered by cesarean section for CPD or FTP, and an equivalent number of women who had a normal spontaneous vaginal delivery. Data on twenty two first time mothers who were delivered by cesarean section and twenty three who delivered vaginally were compared. This study did not find any relationship between small shoe size and cesarean section delivery.

Adolescent↗
PubMed1996

Prevalence of markers for hepatitis B virus and HIV-1 among drug injectors in London: injecting careers, positivity and risk behaviour.

Concerns about the risks of HIV infection among drug injectors have eclipsed concerns about the prevalence and transmission of hepatitis, and in particular hepatitis B virus infection. Findings are reported from surveys undertaken with two separate community-recruited samples of drug injectors in London collected in 1992 (n = 505) and in 1993 (n = 507). Anonymized confirmed testing of saliva shows 51.5% of drug injectors in 1992 and 47.9% in 1993 to be antibody positive to the core antigen of hepatitis B virus (anti-HBc). Approximately half of the drug injectors confirmed as anti-HBc positive were unaware that they had been infected with hepatitis. Anti-HIV-1 prevalence was considerably lower at 7.0% in 1992 and 6.9% in 1993. Multivariate analyses showed anti-HBc positivity to be most likely among older injectors with longer injecting careers who had a history of having shared used needles and syringes. HIV-1 positivity was also associated with a history of having shared injecting equipment as well as with recent sharing (i.e. in the last 6 months). Unlike anti-HBc positivity, there were no associations between HIV-1 positivity and age or length of injecting career. Younger injectors with shorter injecting careers were more likely to report recent sharing of used injecting equipment than older injectors with longer injecting careers. We note the potential for continued transmission of HBV and HIV-1, particularly among younger injectors. We recommend an integrated strategy to maximize the health of drug injectors, of which HIV and HBV prevention is a part. There is a need to widen the availability of HBV vaccinations for HBV negative drug injectors and their sexual partners and for clear guidelines to drug injectors about the relative efficacy of bleach to disinfect injecting equipment of HBV and HIV.

Adolescent↗
PubMed1996

Linkage studies of non-syndromic recessive deafness (NSRD) in a family originating from the Mirpur region of Pakistan maps DFNB1 centromeric to D13S175.

Autosomal recessive non-syndromal hearing impairment (NSRD) is genetically heterogeneous. Five loci have been identified to date which map to chromosomes 13 (DFNB1), 11 (DFNB2), 17 (DFNB3), 7 (DFNB4) and 14 (DFBN5). We report definite linkage of NSRD to the locus DFNB1 in a single family of 27 families studied of Pakistani origin. Haplotype analysis of markers in the pericentromeric region of chromosome 13q revealed a recombination event which maps DFNB1 proximal to the marker D13S175 and in the vicinity of D13S143.

Child↗
PubMed1996

Leeds Undergraduate Medical Education Conference, 7-8 July 1995.

The Leeds Undergraduate Medical Education Conference (LUMEC) was held on 7-8 July 1995. This conference, devoted entirely to undergraduate medical education, was unique in that it was organized entirely by four medical students. It attracted a wide and enthusiastic audience and excellent speakers. Professor Charles George (Chairman, Education Committee, General Medical Council) spoke about Tomorrow's Doctors, Dr Mark Bailey (Part-chairman, Medical Students' Committee of the British Medical Association) responded with 'Today's Students on Tomorrow's Doctors', and Dr Fleur Fisher (Ethics, Science and Information Division, British Medical Association) focused on the central place of ethics and communication skills in medicine. Professor Sam Leinster (Director of Medical Studies, Liverpool University) and Professor Tim de Dombal (Director, Clinical Information Science Unit, Leeds University) debated the need for new technology and radical change in the curriculum. Finally, Dr Stella Lowry (International Division, British Medical Association) considered the assessment of staff and Mrs Joy Crosby (Curriculum Facilitator, Dundee Medical School) discussed the assessment of students. Discussions focused on a variety of areas, including the need for change, the control of the money available for teaching and the problems of assessment.

Education, Medical, Undergraduate↗
PubMed1995

IFN-gamma and IL-4 regulate the growth and differentiation of CD8+ T cells into subpopulations with distinct cytokine profiles.

In this study, we have investigated the effects of IL-4 and IFN-gamma on the growth and differentiation of CD8+ T cells in vitro. Rat splenic CD8+ T cells expressed higher levels of IL-4, IL-5, IL-10, and IFN-gamma mRNA, as measured by reverse-transcription PCR, than CD4+ T cells from the same source, whereas CD4+ T cells expressed more IL-2 and IL-6 mRNA. CD8+ T cells were cultured for 6 days with PMA, ionomycin, and IL-2, and their ability to proliferate, to express mRNA for IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma, and to secrete IFN-gamma and IL-2 was determined. IL-4 could act as a growth factor for CD8+ T cells during primary stimulation, but inhibited proliferation of the restimulated 6-day-cultured CD8+ T cells. The highest levels of mRNA for IL-2 and IL-6 were detected in control cultures in which little mRNA for IL-4, IL-5, or IL-10 was detected. Addition of IL-4 to the primary cultures reduced the capacity of the restimulated cells to express mRNA for IL-2, and for IL-6, but enhanced expression of mRNA for IL-4 and IL-5. Addition of IFN-gamma to the cultures, alone or in conjunction with IL-4, or addition of IFN-gamma-specific neutralizing Ab, had little effect. However, in conjunction with IL-4, anti-IFN-gamma enhanced expression of mRNA for IFN-gamma, and for IL-10. These results indicate that IL-4 and IFN-gamma regulate the differentiation of CD8+ T cells and the growth of cytotoxic and other types of CD8+ T cells, and suggest pathways through which CD8+ T cells may interact with other immune cells.

Animals↗
PubMed1995

A limited sampling strategy for the study of pirarubicin pharmacokinetics in humans.

Pirarubicin (4'-O-tetrahydropyranyldoxorubicin, THP-Adriamycin) is a new anthracycline antibiotic that has recently been developed because its reduced cardiac toxicity is associated with an antitumour efficacy similar to that of doxorubicin. Pirarubicin is characterised by strong haematological toxicity, which has been shown to be correlated with pharmacokinetic parameters, especially the area under the time-concentration curve. To obtain routine pharmacokinetic evaluations of pirarubicin for dose monitoring we developed a limited sampling strategy relying on three blood samples taken at the end of the infusion and at 12 and 24 h post-infusion. The characteristics of interindividual variability were assessed on the first courses of treatment performed in 18 patients; the model was then validated on 10 independent first courses of treatment performed in 10 other patients. The main pharmacokinetic parameters (half-lives, total volume of distribution, total plasma clearance) were estimated in the test group by maximum-likelihood estimation using all samples and by Bayesian estimation using three samples. The concordance between the two estimates was correct (the bias and precision for clearance were 2.3% and 12.1%, respectively), which shows that this limited sampling strategy can be used in routine drug monitoring.

Adult↗
PubMed1995

Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics.

The pharmacokinetic monitoring of anthracycline-containing regimens is warranted because of the important toxicity of these drugs and because pharmacokinetic-pharmacodynamic relationships have been clearly established. We studied the pharmacokinetics of the new anthracycline pirarubicin in 80 courses of treatment performed in 27 patients, using a limited sampling protocol we had previously validated. We observed (for 47 of these courses) a significant correlation between the leucocyte cell kill and the pirarubicin area under the time x concentration curve, but the most significant correlation was obtained using the plasma concentration of doxorubicin, a metabolite of pirarubicin, at the end of the infusion. On the basis of this value, it is possible to predict for pirarubicin haematological toxicity in a way that can help the clinician in identifying patients at risk for toxicity.

Adult↗
PubMed1995

Interleukin-4 enhances interferon-gamma synthesis but inhibits development of interferon-gamma-producing cells.

Interleukin-4 (IL-4) is antagonistic for many of the activities of interferon-gamma (IFN-gamma) and, as well as suppressing the development of T-helper type-1 (Th1) cells, has been reported to block directly the synthesis of IFN-gamma in human lymphocytes. However, IL-4 transgenic mice produce increased amounts of IFN-gamma as well as IL-4. We have compared the ability of rat IL-4 to regulate IFN-gamma secretion in short-term cultures of spleen cells with its effect on the differentiation of T lymphocytes into IFN-gamma-producing, or Th1-type, cells. Normal rat spleen cells were stimulated using a variety of mitogens and ovalbumin antigen, with or without IL-4, for 12-24 hr and the levels of IFN-gamma in the supernatants measured by enzyme-linked immunosorbent assay (ELISA). The results show that when normal rat splenocytes were stimulated with phytohaemagglutinin (PHA) or concavalin A (Con A), IL-4 enhanced secretion of IFN-gamma after 12-24 hr. This enhancement was also apparent when splenocytes from animals immunized 10 days previously with alum-precipitated ovalbumin were stimulated with ovalbumin in vitro, and appeared to be mediated primarily via CD+ T cells. In contrast, when spleen cells were maximally stimulated with phorbol myristate acetate (PMA) and ionomycin, addition of IL-4 had no effect on the amount of IFN-gamma secreted. When splenocytes were stimulated with Con A for 4 days in the presence of IL-4, and restimulated with PMA and ionomycin, IFN-gamma secretion was greatly suppressed. Our results indicate that IL-4 exerts differential effects on IFN-gamma secretion and on the development of IFN-gamma-producing lymphocytes.

Animals↗
PubMed1994

Immune regulation: a new role for the CD8+ T cell.

During an immune response, peripheral T cells develop into functionally distinct subpopulations that effect cell-mediated immunity and regulate humoral immune responses through the secretion of specific cytokines. Recent data suggest that CD8+ T cells, which have long been regarded simply as cytotoxic cells, play a more active role in the regulation of the immune response. In this article, Mike Kemeny and colleagues suggest that there are functionally distinct subsets of CD8+ T cells that produce different combinations of cytokines and appear to play an important part in determining the pattern of cytokines produced by CD4+ T cells and the isotype of immunoglobulins expressed by B cells.

Animals↗
PubMed1994

A double-blind, randomised, crossover comparison of granisetron and ondansetron in 5-day fractionated chemotherapy: assessment of efficacy, safety and patient preference. The Granisetron Study Group.

We report the first double-blind, randomised, crossover study comparing granisetron and ondansetron as antiemetics in cancer chemotherapy. Patients receiving two cycles of identical chemotherapy fractionated over 5 days were given either granisetron (3 mg/day) or ondansetron (24 mg/day) on each day of chemotherapy, using a double-dummy technique to preserve study blindness. Patients then crossed over to the other therapy. 309 patients (237 male) completed the crossover: 260 received cisplatin (mean dose 19.2 mg/m2/day) and 49 received ifosfamide (mean dose 1415 mg/m2/day). Primary efficacy variables were prospectively defined as complete response (no vomiting and mild or absent nausea) over 5 days, and patient preference. Both agents achieved good control of emetic symptoms with 5-day complete response rates of 44.0% on granisetron and 39.8% on ondansetron [95% confidence interval (CI) for odds ratio 0.8, 1.9]. Complete response rates were very similar in patients receiving either cisplatin (40.8% granisetron, 37.6% ondansetron) or ifosfamide (61.2% granisetron, 51.0% ondansetron). There was a statistically significant difference in patient preference in favour of granisetron, 105 patients preferred granisetron, 79 preferred ondansetron, 121 had no preference (P = 0.048: 95% CI for odds ratio 1.00, 1.84). Single daily doses of granisetron (3 mg/day) appeared similarly effective and well tolerated to three daily doses of ondansetron (8 mg three times daily) in prevention of emesis induced by 5-day fractionated chemotherapy, however, significantly more patients preferred granisetron.

Adolescent↗
PubMed1993

Prevalence and magnitude of perinatal substance exposures in California.

BACKGROUND: Perinatal substance exposure has been linked to many neonatal and obstetrical complications. There have been few population-based epidemiologic studies to identify the prevalence and demographic profiles associated with drugs, alcohol, and smoking during pregnancy. METHODS: We studied a fully probabilistic stratified-cluster sample to estimate the prevalence of perinatal substance exposures in California in 1992. Urine samples from 29,494 women presenting for delivery in 202 hospitals were coded and screened for toxins; the results of toxicology screening were later linked by code number to the subjects' demographic variables and their reported use of tobacco and prescribed drugs. Urinary toxicologic tests provide conservative estimates because they can detect only very recent substance use. RESULTS: The weighted prevalence for perinatal substance exposure was 5.16 percent for the use of one or more drugs, 6.72 percent for alcohol (analyzed independently), and 8.82 percent for self-reported smoking. The percentage of women testing positive for any drug, including alcohol, was 11.35 percent. Estimates for racial and ethnic groups varied widely. Black women had the highest prevalence of total drug use (14.22 percent), alcohol use (11.58 percent), cocaine use (7.79 percent), and tobacco use (20.12 percent). Most drug exposures occurred among white non-Hispanic and Hispanic women. White non-Hispanic women had the second highest prevalence rate for the use of one or more drugs (6.79 percent) and self-reported tobacco use (14.82 percent). Hispanic women had the second highest prevalence rate for alcohol (6.87 percent). CONCLUSIONS: In California in 1992, there were 67,361 estimated perinatal exposures to one or more drugs, including alcohol, and 52,346 self-reported exposures to tobacco. These findings have clinical and public health implications.

Alcohol Drinking↗