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W L Gregory

Publications and source records attributed to W L Gregory.

16 recordsLinked to original sources
PubMed1999

Tumour necrosis factor-alpha promoter polymorphisms in primary biliary cirrhosis.

BACKGROUND/AIMS: The incidence of primary biliary cirrhosis (PBC) is increased in the close relatives of patients, suggesting that genetic factors play a role in disease susceptibility. Decreased in vitro production of tumour necrosis factor (TNF)-alpha has been reported in PBC patients, suggesting a potential aetiological role for this cytokine. The aim of this study was to examine two biallelic polymorphisms in the promoter region of the TNF-alpha gene, which may play a role in the control of TNF-alpha secretion, as candidate susceptibility loci in PBC. METHODS: The polymorphisms at positions -238 and -308 in the TNF-alpha promoter region were analysed by polymerase chain reaction in 168 unrelated PBC patients and 145 local unrelated, geographically matched normal individuals. All PBC subjects were also genotyped for HLA DR8, a previously identified susceptibility locus in PBC. RESULTS: The -308 TNF1/TNF1 genotype was seen in a similar proportion of PBC patients (66%) and controls (60%). However, this genotype was found significantly more frequently in the 95 PBC patients with more advanced disease (histological stage III/IV) (77%) than in either controls (p<0.01, OR = 2.2 [1.2-4.0]) or the PBC patients with earlier disease (38/73 (52%), p = 0.001 OR 3.1 [1.6-5.9]). Linkage between TNF -308 and HLA DR8 was not seen. No association was found between PBC and the biallelic -238 TNF-alpha polymorphism, either in the whole PBC population or the histological Stage III/IV subgroup. CONCLUSIONS: Our study provides no evidence for involvement of the TNF-alpha -308 or -238 promoter polymorphisms in genetic predisposition to PBC. However, the significantly increased frequency of the -308 TNF1/TNF1 genotype seen in 95 patients with more advanced disease raises the possibility that this allele may be linked to disease progression rather than susceptibility. The finding of different allele frequencies in PBC patients in different disease subgroups emphasises the importance of clinical phenotype/casemix in the design of disease association studies.

Aged↗
PubMed1995

Heterosexual activity: relationship with ovarian function.

Previous research demonstrated a relationship between the temporal pattern of heterosexual activity and an index of ovarian functioning. In the current study, this relationship was investigated in 147 menstruating heterosexual women (aged 19-53). They kept prospective daily records of menses, basal body temperature, sexual activity, and other behaviors for three consecutive menstrual cycles. In contrast to previous findings, women with intermediate levels of sexual activity displayed more frequent optimal menstrual cycles. Pheromones, semen absorption, and orgasm-related changes were tested as mediators for a causal influence of sexual activity on ovarian functioning; none was supported. Exploratory analyses tested the hypothesis that anovulatory cycles (with presumably lower progesterone) would display more sexual activity than ovulatory cycles. This hypothesis was supported, and the difference in sexual activity was limited to the second half of the cycle, after ovulation would have occurred. Thus, the findings incorporate temporal precedence of ovulation to support the idea that physiological processes influence the level of sexual activity in heterosexual women.

Adult↗
PubMed1994

Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis.

Lipoprotein(a) (Lp(a)) is a unique lipoprotein, elevated serum levels of which are independently associated with an increased risk of coronary heart disease (CHD). Primary biliary cirrhosis (PBC) is often associated with high serum cholesterol, itself a risk factor for CHD. Despite this, patients with PBC are thought to have a lower than expected incidence of CHD. We hypothesised that this may be related to low serum levels of Lp(a) in PBC patients. This was investigated by collecting fasting blood samples from 42 patients with PBC, 39 age- and sex-matched subjects with non-PBC liver disease and 432 community control subjects. Serum was analysed for total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and apolipoproteins A1 and B (apo A1 and apo B). Lp(a) was measured by an enzyme-linked immunosorbent assay (ELISA) technique. There was a significant reduction of Lp(a) concentrations in the PBC group compared with the healthy controls (median value 28.5 mg/l vs. 75.0 mg/l, P < 0.005) and between the non-PBC liver disease group (median value 52.0 mg/l) and control group (P = 0.001). Within both the liver disease and PBC patient groups there were significant negative correlations between Lp(a) levels and bilirubin (R = -0.564, P < 0.001 and R = -0.395, P = 0.010 respectively). This preliminary study has demonstrated reduced Lp(a) levels in PBC patients which may be a contributory factor to explain a possible cardioprotective effect in such patients, despite elevated LDL cholesterol levels.

Bilirubin↗
PubMed1994

Defining the immunogenetic susceptibility to primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic cholestatic disease, thought to be immune-mediated with genetic susceptibility encoded in the major histocompatibility complex. In northern Europeans, the best established associations are with HLA-DR8 and the complement allele, C4B2. These associations could be due to a single susceptibility locus on an extended haplotype linking HLA-DR8 and C4B2 or to both HLA-DR8 and C4B2 independently conferring disease susceptibility. C4B2 genotyping was performed on 64 patients with primary biliary cirrhosis and 61 controls matched for ethnic background and frequency of HLA-DR8. C4B2 was associated with HLA-DR8 (p < 0.05) in PBC. No difference in the frequency of C4B2 was detected between control and disease populations, suggesting that HLA-DR8 and C4B2 are in linkage disequilibrium and that C4B2 is not a susceptibility locus for PBC. Taq I polymorphisms were screened in the disease and control populations with the cosmid probe G91, located midway between the HLA-DR and complement loci. One G91 restriction fragment (G91A) was found to be associated with both HLA-DR8 and C4B2, at equal frequency in health and disease, providing evidence of an HLA-DR8-G91A-C4B2 extended haplotype. The frequency of G91A was the same in the disease and control populations, suggesting that G91A does not confer disease susceptibility. These findings establish G91 as the telomeric boundary for disease susceptibility associated with HLA-DR8, encoded on chromosome six. These studies help define the immunogenetic susceptibility locus for primary biliary cirrhosis.

Alleles↗
PubMed1994

Analysis of HLA-class-II-encoded antigen-processing genes TAP1 and TAP2 in primary biliary cirrhosis.

The search for genes involved in the aetiology of primary biliary cirrhosis (PBC) has centred on the major histocompatibility complex (MHC) on chromosome 6. Genotyping studies have confirmed an association with HLA class II allele DR8. We investigated polymorphisms in two newly identified genes (TAP1 and TAP2) situated close to the DR locus and thought to encode membrane transporter molecules involved in endogenous antigen processing. Genomic DNA extracted from PBC patients was compared with local healthy controls. TAP1 was analysed by amplification refractory mutation system (ARMS) PCR, and two alleles (A and B) were identified. In 126 PBC patients and 116 controls, allele frequencies were (A:B) 81:19% and 79:21%, respectively (NS). TAP2 analysis was by PCR followed by Bfal restriction digest, and again two alleles (A and B) were identified. Their frequencies in 109 PBC patients and 96 controls were (A:B) 76:24% and 73:27%, respectively (NS). No TAP1-TAP2 haplotype was associated with PBC. TAP allele frequencies were estimated within the DR8 subgroups (22 PBC, 14 controls). B allele frequency for TAP1 was increased in both DR8-positive PBC patients and controls compared with DR8-negative patients and controls (41% vs. 14% in PBC; 43% vs. 18% in controls), but no disease association was found. However, the increased frequency of TAP1B in DR8-positive subjects (42% DR8-positive vs. 16% DR8-negative, p < 0.001) indicates linkage disequilibrium between these two loci.

Base Sequence↗
PubMed1993

No evidence for menstrual synchrony in lesbian couples.

Menstrual synchrony was investigated in a sample of 29 cohabiting lesbian couples, ranging in age from 22 to 48 years. One or both partners kept prospective daily records of variables including menses onset dates, intimate contact, and sexual activity. All women reported daily intimate interaction with their partners; none reported intimate interaction with men. Despite these potentially optimal conditions for the manifestation of synchrony, the differences between dyad members in menses onset dates were distributed randomly, and there was no evidence of convergence. In fact, most dyads exhibited divergence of onset dates. Reasons for lack of synchrony in this sample are discussed; one conclusion is that there is no solid evidence that menstrual synchrony is a stable attribute of past or contemporary human populations.

Adult↗
PubMed1993

Re-evaluation of the metabolism of carbocisteine in a British white population.

It has been claimed that the amino acid derivative carbocisteine is predominantly metabolized by sulfoxidation and that this pathway exhibits a genetic polymorphism. Moreover, those subjects with a 'poor metabolizer' phenotype have been thought to have a genetic predisposition to developing certain diseases. We have confirmed the observations of others that this marker drug does not undergo significant S-oxidation. Furthermore, a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC) has recently been identified. To determine if a genetic polymorphism for this biotransformation pathway exists, metabolic ratios (% urinary excretion carbocisteine/% urinary excretion CMTC) for 120 healthy volunteers were assessed using high-performance thin-layer chromatography. Urinary excretion of the parent drug ranged from 6% of the dose administered to 56% (mean +/- SD, 23.4 +/- 0.8%). No cysteinyl sulfoxide metabolites were identified in the urine samples. The amount excreted as CMTC exhibited a 12-fold variation but only accounted for mean of 4.4% (1-12%) of the dose given. Two individuals initially had high metabolic ratios (> 30), however, on rechallenge both their MRs were less than 5. Therefore, carbocisteine is not an appropriate probe drug for sulfoxidation. The formation of the novel metabolite CMTC appears to exhibit polymorphism, although the considerable intra-subject variation for its formation does not allow assignment of a phenotype.

Adult↗
PubMed1993

Primary biliary cirrhosis: contribution of HLA class II allele DR8.

Primary biliary cirrhosis is a chronic cholestatic disease of unknown aetiology which predominantly affects middle-aged women. It is thought to be autoimmune in nature, but unlike many autoimmune diseases no clear HLA association has been described. Several studies have suggested conflicting associations with HLA class II, although a DR8 association is most frequently described. To test the hypothesis that primary biliary cirrhosis is associated with a certain HLA class II locus we genotyped 130 patients with the disease from the north-east region of England and 363 local healthy controls. HLA-DRB1 and confirmatory DQA and DQB genotypes were determined by TaqI restriction fragment DNA length polymorphism analysis. In addition, a polymerase chain reaction technique (double ARMS) was used to investigate the DRB3 locus (DR52) in 98 primary biliary cirrhosis patients and 107 local controls. We found an increased frequency of HLA-DR8 (18.5% vs 9.2%, p < 0.005, relative risk of 2.0 [1.3-3.1]) in the primary biliary cirrhosis group. HLA-DR8-positive primary biliary cirrhosis patients had a higher serum bilirubin level (p = 0.03) than DR8-negative patients. There was no difference in the DR52 frequencies and no association with markers of disease severity. These results support earlier serological findings, although the association between primary biliary cirrhosis and DR8 is weaker than previously described. In addition, DR8-positivity may identify a clinical subgroup with a worse prognosis.

Adult↗
PubMed1991

Heterosexual activity and cycle length variability: effect of gynecological maturity.

Previous studies linking heterosexual activity to women's menstrual cycle variability have failed to take into account the effects of gynecological maturity. One hundred thirty-two women, all at least seven years postmenarche and not using birth control pills, completed daily records of their cycles and their heterosexual behavior. Data from women classified as sexually celibate or as regularly sexually active (having sex at least once per week in every nonmenstruating week) replicated previous findings while controlling for gynecological maturity: Women classified as celibate had more variable cycles than women who engaged regularly in heterosexual activity. An interaction between gynecological maturity and sexual status was also found, precluding a comparison involving women who were sexually active on an irregular basis. The interaction revealed that increased gynecological maturity is associated with less variable cycles in the sexually sporadic women, but is not associated with cycle variability in either celibate or sexually regular women. Possible biological mechanisms for these findings and their implications are discussed.

Adult↗
PubMed1990

Maladjustment in statistical minorities within ethnically unbalanced classrooms.

Ascertained if being a member of a statistical minority influences children's adjustment in school, as measured by the AML, a teacher-administered adjustment rating scale. Teachers from a southwest school district evaluated elementary students on aggressive, acting-out behaviors, moody-internalized behaviors, and learning difficulties. Analyses conducted on 376 students revealed significant effects of statistical minority status on certain dimensions of adjustment ratings for both Hispanic and Anglo students. Hispanic students in the statistical minority received poorer ratings on the moodiness dimension of the AML than nonminority Hispanic students. Anglo students in the statistical minority received poorer ratings on the aggression dimension of the AML than nonminority Anglo students. These results were interpreted in terms of cultural differences in coping with statistical minority status. Traits commonly exhibited within a culture may intensify and be perceived as maladaptive when stress resulting from being a minority occurs. Implications of the finding that statistical minority status within the school environment influences adjustment are discussed.

Adaptation, Psychological↗
PubMed1982

Community perceptions of natural disasters and post-disaster mental health services.

This research was designed to examine the cognitive and affective responses of residential dwellers in the aftermath of a natural disaster (a flood). In a 2 X 3 factorial design, the effects of fear (High, Medium, and Low) and sex on perceptions of the disaster were assessed. The results indicated that respondents who were highly fearful of the disaster were more likely than moderate or low fear respondents to believe that: a) additional flooding would occur in their vicinity, and b) that they resided closer to the flood zone than they actually did. The policy implications of the results suggested that post-disaster mental health services might have to be extended to include residents of geographical areas not directly affected by natural or man-made disasters.

Arizona↗
PubMed1979

Learned helplessness and learned effectiveness: effects of explicit response cues on individuals differing in personal control expectancies.

Female undergraduates (n = 62) who scored as extreme internals or externals on the Mirels Personal Fate Control Scale participated in a partial replication of Hiroto's learned helplessness experiment. Lights were added to the treatment apparatus, which made explicit to subjects the contingency or noncontingency between their responses and the termination of an aversive tone. As predicted, the performance of internals was significantly impaired by uncontrollability (learned helplessness), while that of externals was facilitated by controllability (learned effectiveness). Externals performed as well as internals in the "escapable" condition, but their performance was inferior to that of internals in the control condition. Following "inescapable" treatment, internals performed worse than externals. These results are supportive of Lefcourt's theory of cue explication. Implications for locus of control and learned helplessness research are discussed.

Acoustic Stimulation↗
PubMedDate not supplied

The use of bromocriptine for the treatment of attention deficit disorder in two chemically dependent patients.

The dually diagnosed patient with attention deficit disorder, residual type (ADD-RT) may be especially prone to cocaine abuse, because ADD includes dopamine deficiencies and cocaine is a dopamine agonist. It is hypothesized that bromocriptine, a dopamine agonist, will reduce a patient's craving for cocaine and simultaneously address the patient's ADD-RT symptoms. A single-organism, double-blind research design is used to evaluate the efficacy of bromocriptine, as measured by scale 9 of the MMPI, the digit span and digit symbol tests of the Wechsler Intelligence Scale-Revised, and the signaling to numbers test. Statistical analysis of the results revealed an equivocal response to bromocriptine.

Adolescent↗