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Biomedical subjects

P Reynolds

Publications and source records attributed to P Reynolds.

At least 19 recordsLinked to original sources
PubMed2005

Intracellular cytokines in blood T cells in lung transplant patients--a more relevant indicator of immunosuppression than drug levels.

Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increase in T-cell pro-inflammatory cytokine expression. Systemic levels of immunosuppressive drugs used to reduce pro-inflammatory cytokine expression are closely monitored to their 'therapeutic range'. However, it is currently unknown if levels of these drugs correlate with pro-inflammatory cytokine expression in peripheral blood T cells. To investigate the immunomodulatory effects of currently used immunosuppressive regimes on peripheral blood T-cell cytokine production, whole blood from stable lung transplant patients and control volunteers were stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry. T-cell IL-2 and TNFalpha production was significantly reduced from lung transplant patients compared to controls. CD4+ T-cell production of IFNgamma was also significantly reduced from lung transplant patients but production of IFNgamma by CD8+ T cells remained unchanged. There was an excellent correlation between the percentage of CD8+ T cells and the percentage of CD8+ T cells producing IFNgamma from transplant patients. T-cell IL-4 and CD8+ T-cell production of TGFbeta was significantly increased from lung transplant patients. We now provide evidence that current immunosuppression protocols have limited effect on peripheral blood IFNgamma production by CD8+ T-cells but do up-regulate T-cell anti-inflammatory cytokines. Drugs that effectively reduce IFNgamma production by CD8+ T cells may improve current protocols for reducing graft rejection in these patients. Intracellular cytokine analysis using flow cytometry may be a more appropriate indicator of immunosuppression than drug levels in these patients. This technique may prove useful in optimizing therapy for individual patients.

Adult↗
PubMed2005

Support students.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed2004

Tinnitus and psychological morbidity: a cross-sectional study to investigate psychological morbidity in tinnitus patients and its relationship with severity of symptoms and illness perceptions.

This study investigates the relationship between tinnitus and psychological morbidity using a cross-sectional survey design from patients of an outpatient audiology department in a typical District General Hospital. The results suggest that a significant number of tinnitus patients suffer from psychological problems both during and more unfortunately after routine treatment for their tinnitus. Anxiety was found to be the main psychological problem. In conclusion, this study suggests that, while further research is needed, many tinnitus patients require psychological treatment and this has implications for the staffing of audiology units in District General Hospitals.

Adult↗
PubMed2003

Application of the headspace CO2 method (ISO 14 593) to the assessment of the ultimate biodegradability of surfactants: results of a calibration exercise.

In the recent review of the control of marketing surfactants used in detergents, the EU decided to increase the severity of the testing procedure by using the criterion of ultimate biodegradability (mineralization) rather than primary biodegradation (removal of the parent molecule) to ensure that possible harmful organic metabolites do not reach the environment. The relatively new ISO headspace CO2 test, considered to be an improvement on the OECD 301B (Sturm CO2) test was chosen. The method was subjected to a ring test by 11 laboratories using one of each of four classes of surfactants plus a poorly degradable reference surfactant; all laboratories satisfactorily applied the method. The necessary addition of silica gel to the medium containing the cationic surfactant, known as a class to be more inhibitory than other classes, was confirmed as a technique for avoiding inhibition of the inoculum. The biodegradability of the surfactants was in general agreement with results reported in the literature and the often reported variable values of % inorganic carbon (IC) produced of the theoretical was found. The anionic and cationic surfactants were readily biodegradable (%IC > 60), the non-ionic surfactant was well below the pass value, while the amphoteric was borderline. The IC production by the blank controls, one of the validity criteria, was about 0.3 mg C/100 ml test medium, equivalent to 3 mg C/l, as recommended in the ISO text. Mild conditions of pre-exposure of the inoculum to the test surfactant did not produce consistent worthwhile effects on either the percentage biodegradation or on its variability.

Biodegradation, Environmental↗
PubMed2003

Role of the transmembrane domain of the VanT serine racemase in resistance to vancomycin in Enterococcus gallinarum BM4174.

Enterococcus gallinarum BM4175 (a vancomycin-susceptible derivative of BM4174 obtained by insertional inactivation of vanC-1) was transformed with plasmid constructs pCA10 (containing the genes necessary for resistance, vanC-1-XYc-T), pJP1 (with a fragment lacking the DNA encoding the transmembrane region of VanT, -vanC-1-XYc-T((Delta))(2-322)-) and with plasmids containing fragments encoding either the transmembrane (mvanT(1-322)) or racemase (svanT(323-698)) domains of VanT under the control of a constitutive promoter. Accumulated peptidoglycan precursors were measured in all strains in the presence of L-Ser, D-Ser (50 mM) or in the absence of any growth supplement. Uptake of 0.1 mM L-[(14)C]serine was also determined in BM4174, BM4175 and BM4175/pCA10. Vancomycin resistance was restored in BM4175 transformed with pCA10(C-1-XYc-T), and the profile of peptidoglycan precursors was similar to wild-type E. gallinarum BM4174. Transformation of E. gallinarum BM4175 with plasmid pJP1(vanC-1-XYc-T((Delta))(2-322)) resulted in: (i) vancomycin MICs remaining within susceptible levels (< or =4 mg/L) in the absence of any growth supplement, but increasing to 8 mg/L when either L-Ser or D-Ser was added to the medium; and (ii) the relative amounts of accumulated UDP-MurNAc-pentapeptide[D-Ser] and tetrapeptide precursors decreasing substantially compared with BM4175/pCA10 and BM4174. The effect on the appearance of tetrapeptide appeared to be host dependent, since a substantial amount was present when the same plasmid construct pJP1(vanC-1-XYc-T((Delta))(2-322)) was electroporated into Enterococcus faecalis JH2-2. The uptake of L-[(14)C]Ser at 240 s was decreased by approximately 40% in BM4175 compared with BM4174. Plasmid pCA10(C-1-XY(C)-T) restored uptake of L-[(14)C]Ser at 180 and 240 s in BM4175. The results suggest that the transmembrane domain of VanT is likely to be involved in the transport of L-Ser, and that in its absence the resistance phenotype is compromised.

Bacterial Proteins↗
PubMed2002

Daycare attendance and risk of childhood acute lymphoblastic leukaemia.

The relationship between daycare/preschool ("daycare") attendance and the risk of acute lymphoblastic leukaemia was evaluated in the Northern California Childhood Leukaemia Study. Incident cases (age 1-14 years) were rapidly ascertained during 1995-1999. Population-based controls were randomly selected from the California birth registry, individually matched on date of birth, gender, race, Hispanicity, and residence, resulting in a total of 140 case-controls pairs. Fewer cases (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more total child-hours had a significantly reduced risk of ALL. The odds ratio associated with each thousand child-hours was 0.991 (95% confidence interval (CI): 0.984-0.999), which means that a child with 50 thousand child-hours (who may have, for example, attended a daycare with 15 other children, 25 h per week, for a total duration of 30.65 months) would have an odds ratio of (0.991)(50)=0.64 (95% CI: 0.45, 0.95), compared to children who never attended daycare. Besides, controls started daycare at a younger age, attended daycare for longer duration, remained in daycare for more hours, and were exposed to more children at each daycare. These findings support the hypothesis that delayed exposure to common infections plays an important role in the aetiology of childhood acute lymphoblastic leukaemia, and suggest that extensive contact with other children in a daycare setting is associated with a reduced risk of acute lymphoblastic leukaemia.

Adolescent↗
PubMed2002

Correlates of vitamin supplement use in the United States: data from the California Teachers Study cohort.

OBJECTIVE: To describe factors associated with vitamin supplement use in a large cohort of adult women. METHODS: California teachers and administrators (n = 133,479) completed a questionnaire on lifestyle factors and medical history. Specific supplement users regularly used at least one specific vitamin supplement in the past year; multivitamin users regularly used a multivitamin; and multivitamin and specific supplement users took a multivitamin and one or more specific supplements. Associations between supplement use and other variables were quantified using means, cross-tabulations, and age-adjusted prevalence odds ratios. RESULTS: Multivitamin and specific supplement users tended to be older and Caucasian. Compared to non-users, they were also leaner (odds ratio [OR] for BMI > or = 30 kg/m2 = 0.6 for specific supplement users with or without multivitamins, and OR = 0.7 for multivitamin only users), and were less likely to be current smokers (OR for current smoking = 0.8 for multivitamin plus specific supplement users, OR = 0.9 for specific supplement only users, and OR = 0.7 for multivitamin only users). Specific supplement users (with or without multivitamins) were more likely to use cancer screening tests, eat fruits and vegetables, and exercise than were multivitamin only users or non-users. CONCLUSIONS: A variety of demographic, dietary, and health-related factors were associated with different categories of supplement use.

Body Weight↗
PubMed2001

A case-control pilot study of traffic exposures and early childhood leukemia using a geographic information system.

The scientific debate on risk relationships between proximity to electric and magnetic fields and the development of childhood leukemia has recently focused on the role of other factors that may be strongly correlated with power lines. Proximity to high traffic density, as defined by major roadways or automobile counts, and associated socioeconomic neighborhood characteristics have been suggested as potentially important confounders. For traffic or socioeconomic status (SES) to confound any EMF effect these factors would need to have their own independent impact on leukemia risk. This study was designed to use geographic information system (GIS) technology to empirically examine the relationship between traffic density and socioeconomic indicators to early childhood leukemia in an urban area of California. Ninety cases of childhood leukemia diagnosed under the age of five between 1988 and 1994 among children born in San Diego County were matched by gender and birth date to a total of 349 children also born in the county and not known to have developed any cancer. Case-control differences were assessed via conditional logistic regression. No significant differences were observed for the neighborhood median family income of the birth residences. When comparing neighborhoods with median annual income > or = $56,000 to those with incomes < or = $18,000 the odds ratio was 0.86 (95% confidence interval 0.31, 2.38). Traffic density was measured using a variety of methods, including information on average daily traffic counts and road characteristics. None of the measures of traffic were associated with case status. Neither SES or traffic density near the birth address as assessed with GIS methods are strong enough risk factors for leukemia to be confounders which could totally explain the effect of another variable (such as wire code). Associations with the diagnosis address or with more direct exposure measures may differ from those reported here.

California↗
PubMed2001

Agricultural pesticide use in California: pesticide prioritization, use densities, and population distributions for a childhood cancer study.

Several studies have suggested an association between childhood cancer and pesticide exposure. California leads the nation in agricultural pesticide use. A mandatory reporting system for all agricultural pesticide use in the state provides information on the active ingredient, amount used, and location. We calculated pesticide use density to quantify agricultural pesticide use in California block groups for a childhood cancer study. Pesticides with similar toxicologic properties (probable carcinogens, possible carcinogens, genotoxic compounds, and developmental or reproductive toxicants) were grouped together for this analysis. To prioritize pesticides, we weighted pesticide use by the carcinogenic and exposure potential of each compound. The top-ranking individual pesticides were propargite, methyl bromide, and trifluralin. We used a geographic information system to calculate pesticide use density in pounds per square mile of total land area for all United States census-block groups in the state. Most block groups (77%) averaged less than 1 pound per square mile of use for 1991-1994 for pesticides classified as probable human carcinogens. However, at the high end of use density (> 90th percentile), there were 493 block groups with more than 569 pounds per square mile. Approximately 170,000 children under 15 years of age were living in these block groups in 1990. The distribution of agricultural pesticide use and number of potentially exposed children suggests that pesticide use density would be of value for a study of childhood cancer.

Adolescent↗
PubMed2000

Use of coping strategies and breast cancer survival: results from the Black/White Cancer Survival Study.

This analysis was designed to evaluate the association between coping strategies and breast cancer survival among Black and White women in a large population-based study. A total of 442 Black and 405 White US women diagnosed with invasive breast cancer during 1985-1986 and actively followed for survival through 1994 were administered a modified Folkman and Lazarus Ways of Coping questionnaire. Coping strategies were characterized via factor analyses of the responses. Hazard ratios associated with coping strategies were estimated using Cox proportional hazards models, with adjustment for age, race, tumor stage, study location, tumor hormone responsiveness, comorbidity, health insurance status, smoking, relative body weight, and alcohol consumption. Emotion-focused coping strategies were significantly associated with survival. Expression of emotion was associated with better survival (hazard ratio = 0.6; 95% confidence interval: 0.4, 0.9). When it was considered jointly with the presence or absence of perceived emotional support, women reporting low levels of both emotional expression and perceived emotional support experienced poorer survival than women reporting high levels of both (hazard ratio = 2.5; 95% confidence interval: 1.7, 3.7). Similar risk relations were evident for Blacks and Whites and for patients with early and late stage disease. These results suggest that the opportunity for emotional expression may help improve survival among patients with invasive breast cancer.

Adaptation, Psychological↗
PubMed2000

Glycopeptide-resistant Enterococcus faecium BM4416 is a VanD-type strain with an impaired D-Alanine:D-Alanine ligase.

VanD-type Enterococcus faecium BM4416 was constitutively resistant to vancomycin and to teicoplanin by synthesis of peptidoglycan precursors ending in D-alanyl-D-lactate. Like E. faecium BM4339, the only VanD-type strain described so far, BM4416 produced an impaired D-alanine:D-alanine ligase. Unlike for BM4339, which had a 5-bp insertion in ddl, inactivation of the gene in BM4416 was due to insertion of IS19.

Amino Acid Sequence↗
PubMed1999

Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B).

We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa25-44 MAP compared with mice immunized with the 25-44 monomer. Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25-44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa287-301 determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa287-301 peptide. However, immunization with the multivalent mLa287-301 peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa287-301 peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence.

Amino Acid Sequence↗
PubMed1999

Cancer in California school employees, 1988-1992.

BACKGROUND: Periodic concerns about excesses of cancer among teachers in California schools prompted our examination of cancer incidence in California school employees. METHODS: Records of school employees between 1987-1992 were linked to the California Cancer Registry of incident cases diagnosed 1988-1992. Sex-, race-, and age-adjusted standardized incidence ratios were calculated for specific cancer sites. Analyses stratified by sex, race/ethnicity, and job assignment were also performed. RESULTS: Melanoma of the skin, thyroid cancer, prostate cancer, and female cancers of the breast, uterus, and ovary all occurred more frequently than expected in these school employees. In contrast, cancers of the respiratory system, oral cavity, digestive system, urinary system, and uterine cervix occurred less frequently. CONCLUSIONS: The incidence of cancers thought to be related to hormones and/or higher socioeconomic status appeared elevated while cancers often linked to smoking and/or alcohol intake occurred less frequently in this large cohort of professional school employees.

Adult↗
PubMed1999

Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector.

Adenoviral vectors are attractive gene delivery vehicles, but their in vivo utility is reduced by lack of cell-specific infection. Tropism modification of the virion by genetic manipulation of capsid proteins is an attractive strategy to achieve targeted transduction. However, no genetic targeting strategies have yet been shown to modify the distribution of transgene expression following systemic administration of vector. This is an essential requirement if such approaches are to form a basis for further vector develop- ment. In this report we present data showing that insertion of a RGD motif into the HI loop of the adenoviral fiber knob results in a significant change in transgene expression profile following intravenous administration. The key finding that a motif in the HI loop is available for cellular interaction when administered systemically means that such modifications can be rationally considered as a foundation upon which further genetic modifications can be superimposed for targeted systemic gene therapy.

Adenoviridae↗
PubMed1999

Moderate-level resistance to glycopeptide LY333328 mediated by genes of the vanA and vanB clusters in enterococci.

Three of five natural plasmids carrying a wild-type vanA gene cluster did not confer LY333328 glycopeptide resistance on Enterococcus faecalis JH2-2 (MIC = 2 microg/ml). The two remaining plasmids conferred resistance to the drug (MIC, 8 microg/ml). The vanB gene cluster did not confer resistance to LY333328, since this antibiotic was not an inducer. Mutations in the vanS(B) sensor gene that allowed induction by teicoplanin or constitutive expression of the vanB cluster led to LY333328 resistance (MIC, 8 to 16 microg/ml). Overproduction of the VanH, VanA, and VanX proteins for D-alanyl-D-lactate (D-Ala-D-Lac) synthesis and D-Ala-D-Ala hydrolysis was sufficient for resistance to LY333328 (MIC, 16 microg/ml). Mutations in the host D-Ala:D-Ala ligase contributed to LY333328 resistance in certain VanA- and VanB-type strains, but the MICs of the antibiotic did not exceed 16 microg/ml. Addition of D-2-hydroxybutyrate in the culture medium of mutants that did not produce the VanH D-lactate dehydrogenase led to incorporation of this D-2-hydroxy acid at the C-terminal ends of the peptidoglycan precursors and to LY333328 resistance (MIC, 64 microg/ml). The vanZ gene of the vanA cluster conferred resistance to LY333328 (MIC, 8 microg/ml) by an unknown mechanism. These data indicate that VanA- and VanB-type enterococci may acquire moderate-level resistance to LY333328 (MIC </= 16 microg/ml) in a single step by various mechanisms.

Anti-Bacterial Agents↗