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Biomedical subjects

W R Williams

Publications and source records attributed to W R Williams.

At least 55 records · Page 3Linked to original sources
PubMed1985

Modulation of lymphocyte adrenergic receptors by hormones and anti-asthmatic drugs.

Viable lymphocytes were used to investigate the binding of physiological concentrations of hormones and therapeutic concentrations of anti-asthmatic drugs to [3H]dihydroalprenolol (DHA, beta antagonist) and [3H]prazosin (alpha antagonist) receptor sites. All studied drugs and hormones inhibited the specific binding of prazosin to receptors identified with 10(-4)M phentolamine. Similar concentrations of drugs and hormones, with the exception of prostaglandin F2 alpha and cimetidine, inhibited the specific binding of DHA to lymphocyte receptors identified with 10(-7)M propranolol. These results confirm current mechanisms of hormone and drug action in asthma.

Asthma↗
PubMed1984

Genetic epidemiology of breast cancer: segregation analysis of 200 Danish pedigrees.

An investigation of the genetic epidemiology of breast cancer involving complex segregation analysis of 200 breast cancer pedigrees of Danish extraction is presented. The observed distribution of breast cancer is compatible with transmission of an autosomal-dominant gene with no evidence for residual family resemblance. The gene frequency of the abnormal allele is 0.00756, and the displacement between the homozygous genotype means is 1.695. The gene frequency accounts for a significant proportion of breast cancer in young women, whereas by an advanced age a majority (87%) of affected women are phenocopies. Genetic modeling of other breast cancer families and results of linkage studies are reviewed.

Adult↗
PubMed1984

The mode of inheritance of psoriasis: evidence for a major gene as well as a multifactorial component and its implication for genetic counselling.

Complex segregation analysis of Lomholt's family data on psoriasis on the Faroe Islands gave evidence for an additive major gene with gene frequency of 0.07 and penetrance 0.12 and 0.44 in the heterozygote and in the homozygote, respectively. In addition, there was a multifactorial component with heritability 0.87. The implications of these findings for genetic counseling are discussed and analytical risk figures are presented for chosen pedigrees.

Age Factors↗
PubMed1984

Modulation of lymphocyte adrenergic receptors and transformation responses by therapeutic drugs.

Lymphocyte transformation responses and adrenergic receptor (adrenoceptor) binding have been studied in the presence of therapeutic drugs. Chloroquine, propranolol and trifluoperazine were the most potent drugs investigated, inhibiting lymphocyte responses and the binding of adrenergic antagonists at 10(-5)M. Drugs such as salicylate and chlorpropamide, with little affinity for adrenoceptors but with a high capacity for binding to albumin, inhibited lymphocyte transformation at 10(-3)M; probably by displacing protein-bound ligands with an affinity for adrenoceptors. Metronidazole and allopurinol had no significant effect on lymphocyte transformation, or on adrenoceptor antagonist binding at 10(-3)M. Adrenoceptor affinity or receptor numbers and lymphocyte responses were increased by non-inhibitory concentrations of most drugs. We conclude that most drugs modify lymphocyte responses by interacting directly or indirectly with adrenoceptors. This modulation of adrenoceptors may have important implications, relating to the induction and control of asthma by drugs.

Binding, Competitive↗
PubMed1983

Complex segregation analysis and computer-assisted genetic risk assessment for Duchenne muscular dystrophy.

Two hundred forty-four Toronto pedigrees of Duchenne muscular dystrophy patients have been partitioned into nuclear families with pointers for complex segregation analysis under a mixed model. The model takes into account the major X-linked locus and a multifactorial transmissible component for creatine kinase activity in females. The incidence in the province of Ontario is estimated to be 292 per million male births. The proportion of sporadic cases is 1/3, demonstrating equal mutation rates in males and females. A multifactorial component (H = 0.379) contributes to family resemblance for creatine kinase measurements. Examples are presented of the application of a computer program, COUNSEL, to derive genetic risks for genetic counseling with consideration of the multifactorial component.

Computers↗
PubMed1983

Cultural and biological inheritance of plasma lipids.

A path analytic model for the analysis of nuclear family data is described and used to analyze the results of two major studies of cholesterol (CH) and triglyceride (TG), the Honolulu Heart Study (HHS) of Japanese-Americans and the Cincinnati Lipid Research Clinic (LRC) study of Caucasians. The studies were first analyzed separately to assess evidence for genetic and cultural transmission, marital resemblance, and maternal environmental effects for the two plasma lipids, and then simultaneously to identify the nature and sources of any between-study-heterogeneity. There were significant sources of heterogeneity between the two studies for CH (only marital environmental resemblance and non-transmitted sibling environmental resemblance) and for TG (only non-transmitted sibling environmental resemblance). The two studies were homogeneous with respect to the magnitude of genetic and cultural effects; for CH genetic heritability was estimated as h2 = .594 +/- .041 while cultural heritability was estimated as c2 = .035 +/- .008, and for TG the two heritabilities were estimated as h2 = .259 +/- .034 and c2 = .108 +/- .014. An additional bivariate analysis of the association between the two lipids revealed that all phenotypic resemblance could be explained in terms of an association of non-transmitted residual environments with little evidence for a genetic association. The relevance of these results for an understanding of the genetic epidemiology of plasma lipids is discussed.

Asian People↗
PubMed1983

Effects of therapeutic drugs on lymphocyte transformation.

1 Over 40 non-steroidal drugs, routinely given on a long term therapeutic basis, were tested in lymphocyte transformation cultures at high therapeutic concentrations, or in serum cultures after short term oral drug administration. Lymphocyte transformation was assessed by measuring thymidine and 2-deoxyuridine incorporation into DNA. 2 When added in vitro, salicylate significantly inhibited thymidine (48%, n = 35) and deoxyuridine incorporation (20%, n = 12). Thymidine incorporation was specifically inhibited by phenylbutazone (39%, n = 6) and chlorpropamide (48%, n = 5). Specific inhibition of deoxyuridine incorporation, indicative of impaired lymphocyte folate metabolism, was obtained following the addition of pyrimethamine (51%, n = 3) and to some extent by carbimazole (30%, n = 2). In serum cultures, pyrimethamine inhibited deoxyuridine incorporation (30%, n = 3) and chloroquine inhibited the incorporation of both thymidine (37%, n = 3) and deoxyuridine (46%, n = 3). 3 Most classes of drugs used long term are unlikely to cause any significant clinical effect, by impairing lymphocyte function. Caution may be warranted when high doses of salicylate, phenylbutazone, chloroquine, pyrimethamine, chloropropamide or combinations of these drugs are prescribed.

Deoxyuridine↗
PubMed1983

Family resemblance for fasting blood glucose in a population of Japanese Americans.

The pattern of inheritance of fasting blood glucose was examined in a Japanese cohort of 500 nuclear families living in Hawaii. A principal component of glucose was defined to improve the ranking of diabetics and individuals receiving treatment (medication and/or diet) for hyperglycemia, thereby allowing as well as possible for inability to determine untreated levels in patients. Results from path and segregation analysis show that family resemblance for glucose is low in this population. The additive variation can be explained by a cultural model of inheritance without introducing intergenerational differences, a maternal-paternal effect, or even genetic parameters. Heritability is approximately 0.125. Complex segregation analysis provides no convincing evidence for a major gene, with preliminary support based upon leptokurtic outliers in five families disappearing on further analysis by partial truncation. A claim by other workers of a major recessive gene for hyperglycemia may be due to their failure to allow for treatment, skewness, and multifactorial heritability. In future, the search for major loci acting on liability to hyperglycemia should use multiple determinations of fasting glucose or be addressed to more primary and repeatable variables than fasting blood glucose.

Adult↗
PubMed1983

Comparison between fenoprofen and ibuprofen in the treatment of soft-tissue rheumatism.

Fenoprofen calcium 600 mg, four times daily, and ibuprofen 400 mg, four times daily, were compared in a double-blind crossover study involving the treatment of soft-tissue rheumatism in fifty patients. After 7 days there was no significant difference between the efficacy of the two drugs with respect to 'pain at rest', 'pain on movement', 'tenderness' or 'sleep disturbance' but fenoprofen was significantly better when considering 'limitation of movement' and 'The physician's assessment of the severity of the condition'. Combining data from Weeks 1 and 2 of treatment, 14 days fenoprofen treatment brought about significant improvements in all of the above parameters. Ibuprofen did not significantly improve 'pain at rest' but did improve the other parameters.

Adult↗
PubMed1983

An immunological study on patients with chronic cadmium disease.

Parameters of humoral and cellular immunity were investigated in patients with chronic cadmium (Cd) disease and compared to values in an age matched control group. In the patient group, there was a slight reduction in WBC although T and B lymphocyte ratios were normal. RBC counts were significantly reduced (P less than 0.05). No significant differences in serum immunoglobulin (Ig) concentrations were found. Blood Cd was significantly raised (P less than 0.001) and urine Cd was elevated. In lymphocyte transformation tests, responses to Staphylococcus aureus, PHA and PPD were not impaired and no evidence of Cd hypersensitivity was found. Responses in PHA and ADCC cytotoxicity tests were normal and nitro-blue tetrazolium (NBT) reduction was only slightly decreased in the patient group. beta 2-Microglobulin (beta 2M) was significantly raised in serum (P less than 0.001) and urine (P less than 0.001) of patients. Patient 3 day lymphocyte cultures produced significantly more beta 2M than cultures from the control group (P less than 0.01). beta 2M was increased in lymphocyte cultures, from patient and control groups, containing PHA (P less than 0.01), low Cd concentrations (P less than 0.01) or PPD. The results indicate that chronic Cd disease is not associated with significant alterations in immunological parameters in vitro. The high beta 2M levels associated with this disease may not result entirely from kidney damage but may in part be due to an increase in the release of beta 2M from cells, induced by Cd.

Aged↗
PubMed1983

Platelet binding in mononuclear cell preparations from peripheral blood.

We have investigated the relative binding affinity of white blood cells for platelets, during the centrifugation and washing procedures used for separating mononuclear cells from peripheral blood. In wet cell preparations the majority of monocytes (greater than 90%) showed platelet binding, compared to 14% of lymphocytes and 38% of polymorphs. Monocytes also had greater numbers of attached platelets per cell and demonstrated considerable variation in their affinity for platelets. The phenomenon was affected by the calcium concentration of the medium. Our observations are of value for identifying monocytes in wet cell preparations. The technique may also be useful for studying platelet adhesion in vascular disease.

Calcium↗
PubMed1982

The influence of culture conditions on the suppression of lymphocyte transformation by salicylate.

Therapeutic concentrations of salicylate enhanced or inhibited human lymphocyte PHA transformation, depending on the conditions of culture. Response to salicylate were influenced by serum and cell concentration, PHA mitogenic activity and concentration. In particular, pre-incubation of the mononuclear cell population, in salicylate-free medium, made lymphocyte transformation more susceptible to inhibition. The results suggest that the inhibitory effect of salicylate on lymphocyte transformation may be mitigated by a factor released form adherent mononuclear cells. The extent to which culture conditions influence the results of this test emphasise its limitations for assessing the effects of drugs on lymphocyte function in vivo.

Blood↗
PubMed1982

Comparison of lymphocyte transformation and macrophage migration inhibition tests in the detection of beryllium hypersensitivity.

In seven patients with chronic beryllium disease (Be) the Be lymphocyte transformation test was positive in 100%, independent of steroid therapy, and was reproducible. The Be macrophage migration inhibition test was only positive in four of seven patients (57%) not on steroids, and was not reproducible. In 72 potentially exposed healthy beryllium workers the lymphocyte transformation test was negative in all subjects. The macrophage test was positive in four of 78 and again the results were not reproducible. The workers with positive results showed no differences in age, type or duration of employment from those with negative results and showed no evidence of disease. In addition, the macrophage test was positive in two of 45 non-exposed control subjects. We also confirmed the above advantages of the lymphocyte transformation technique by using tuberculin antigen (PPD). The PPD lymphocyte transformation test gave positive results in approximately 60% of healthy beryllium workers, but the PPD macrophage test was only positive in 7%. We conclude that the Be lymphocyte transformation test is the most sensitive and reproducible and advocate its use in the diagnosis of disease and in monitoring the health of potentially exposed workers.

Adult↗
PubMed1982

Development of beryllium lymphocyte transformation tests in chronic beryllium disease.

We found that optimal conditions for the beryllium transformation test required the use of purified lymphocyte suspensions in 20% human serum, with beryllium sulphate at concentrations of 10(-6) to 10(-7) M. Using these conditions, all 15 chronic beryllium patients tested gave a stimulation index of more than 2. Despite the above, 10(-5) and 10(-6)M, BeSO4 inhibited spontaneous thymidine incorporation and lymphocyte transformation to PHA and PPD in normal subjects. Alternative methods, using whole blood, venous and thumb-prick samples, gave fewer and less reproducible positive results.

Berylliosis↗