Search PubMed⌕ Search

Biomedical subjects

D C Thomas

Publications and source records attributed to D C Thomas.

At least 91 records · Page 5Linked to original sources
PubMed1992

Suprasensitivity to calcitonin gene-related peptide but not vasoactive intestinal peptide in women with chronic pelvic pain.

Chronic pelvic pain in women is associated with radiological evidence of pelvic venous dilatation and reduced flow, termed 'pelvic congestion'. The aim of this study was to elucidate a possible role in this condition for vasoactive intestinal peptide and calcitonin gene-related peptide, both localized in perivascular nerves in the ovaries and uterus. Healthy volunteers and women with chronic pelvic pain and venous congestion received intravenous infusions of vasoactive intestinal peptide (n = 15), calcitonin gene-related peptide (n = 15) or a bland infusate (n = 7). Changes in the uterovaginal and skin blood flow were assessed by continuous measurement of vaginal, axillary, cheek and hand temperature. During calcitonin gene-related peptide infusion median hand temperature changes were +0.97 degrees C in women with pelvic pain and -0.03 degrees C in healthy volunteers (p < 0.05). There were no differences between groups in hand and cheek temperature responses to vasoactive intestinal peptide infusion. Vasoactive intestinal peptide and calcitonin gene-related peptide appeared to dilate the uterovaginal vasculature in healthy subjects but not in those with pelvic pain. Vasoactive intestinal peptide and calcitonin gene-related peptide did not provoke pain in healthy subjects but in those with pelvic pain, symptoms were significantly exacerbated during calcitonin gene-related peptide infusion but not by vasoactive intestinal peptide. Changes in plasma follicle stimulating hormone, luteinizing hormone and oestradiol during either infusion were not significant. These findings indicate greater sensitivity to calcitonin gene-related peptide in women with pelvic pain and suggest a possible underlying neurovascular disorder.

Adult↗
PubMed1992

Measurement of pelvic blood flow changes in response to posture in normal subjects and in women with pelvic pain owing to congestion by using a thermal technique.

1. A method is described for studying pelvic blood flow in women by the indirect method of measuring vaginal temperature changes in response to a posture change. Ten women with chronic pelvic pain and venous congestion and 10 normal subjects were observed during posture changes over a 2 h period. 2. Vaginal temperature minus axillary temperature rose after subjects changed from the supine to the seated position, indicating a fall in the rate of pelvic blood flow. 3. A significantly greater variance in the rate of change in vaginal temperature minus axillary temperature was found in patients with pelvic venous congestion compared with control subjects (P less than 0.005). 4. The findings are consistent with a disorder of blood flow regulation in women with pelvic pain owing to congestion.

Adult↗
PubMed1992

Reproductive outcomes in relation to malathion spraying in the San Francisco Bay Area, 1981-1982.

We studied reproductive outcomes in a cohort of 7,450 pregnancies identified through three Kaiser-Permanente facilities in the San Francisco Bay Area, in relation to exposure to the pesticide malathion, applied aerially to control an infestation by the Mediterranean fruit fly. We included in the cohort all women over age 17 who were registered at these facilities and who were confirmed as pregnant during the spraying period. Residence histories throughout the pregnancy were obtained by mailed questionnaire or telephone interview from 933 women with adverse outcomes and a sample of 1,000 women with normal outcomes, and were converted to geographical coordinates. We linked the coordinates for malathion spraying corridors with the residence coordinates to create individual exposure indices for each week of pregnancy. The statistical analysis compared each of the adverse pregnancy outcome groups against an appropriate control group using logistic regression or survival time regression approaches. After adjustment for various confounders, no important association was found between malathion exposure and spontaneous abortion, intrauterine growth retardation, stillbirth, or most categories of congenital anomalies. Gastrointestinal anomalies were related to second trimester exposure (odds ratio = 2.6), based on 13 cases and not specific to any particular International Classification of Diseases code.

Abnormalities, Drug-Induced↗
PubMed1992

Risk of leukemia caused by diagnostic x-rays.

Using BEIR V risk estimates and age-specific population dose estimates, we estimate that approximately 12% of leukemias may be attributable to diagnostic x-rays. Earlier estimates were markedly lower (< or = 1%) because of their use of earlier risk coefficients, different dose rate effectiveness factors, and, in one case, a methodological error.

Age Factors↗
PubMed1992

Mechanism of interferon action: alpha and gamma interferons differentially affect mRNA levels of the catalytic subunit of protein kinase A and protein Mx in human cells.

Treatment of human HeLa and amnion U cells with gamma interferon (IFN-gamma), either alone or in combination with alpha interferon (IFN-alpha), reduced the steady-state level of mRNA encoding the catalytic (C) subunit of protein kinase A (PKA) as measured by Northern gel-blot (RNA) analysis. In addition, IFN-gamma treatment increased the ratio of C alpha to C alpha 2 (the two splice-site variants of PKA C alpha subunit mRNA produced in HeLa cells) as measured by a polymerase chain reaction assay. IFN-gamma greatly reduced the amount of a novel splice-site variant of PKA, C alpha 2, which retains introns G and H, relative to the amount of C alpha, which lacks introns G and H. IFN-alpha treatment in combination with IFN-gamma did not further reduce the level of PKA C alpha transcripts beyond that of IFN-gamma alone, as measured by Northern blots; however, IFN-alpha in combination with IFN-gamma did cause a synergistic increase in the level of human Mx transcripts.

Base Sequence↗
PubMed1992

A Gibbs sampling approach to linkage analysis.

We present a Monte Carlo approach to estimation of the recombination fraction theta and the profile likelihood for a dichotomous trait and a single marker gene with 2 alleles. The method is an application of a technique known as 'Gibbs sampling', in which random samples of each of the unknowns (here genotypes, theta and nuisance parameters, including the allele frequencies and the penetrances) are drawn from their posterior distributions, given the data and the current values of all the other unknowns. Upon convergence, the resulting samples derive from the marginal distribution of all the unknowns, given only the data, so that the uncertainty in the specification of the nuisance parameters is reflected in the variance of the posterior distribution of theta. Prior knowledge about the distribution of theta and the nuisance parameters can be incorporated using a Bayesian approach, but adoption of a flat prior for theta and point priors for the nuisance parameters would correspond to the standard likelihood approach. The method is easy to program, runs quickly on a microcomputer, and could be generalized to multiple alleles, multipoint linkage, continuous phenotypes and more complex models of disease etiology. The basic approach is illustrated by application to data on cholesterol levels and an a low-density lipoprotein receptor gene in a single large pedigree.

Animals↗
PubMed1992

Use of external rates in nested case-control studies with application to the international radiation study of cervical cancer patients.

A method is proposed for analysis of nested case-control studies that combines the matched comparison of covariate values between cases and controls and a comparison of the observed numbers of cases in the nesting cohort with expected numbers based on external rates and average relative risks estimated from the controls. The former comparison is based on the conditional likelihood for matched case-control studies and the latter on the unconditional likelihood for Poisson regression. It is shown that the two likelihoods are orthogonal and that their product is an estimator of the full survival likelihood that would have been obtained on the total cohort, had complete covariate data been available. Parameter estimation and significance tests follow in the usual way by maximizing this product likelihood. The method is illustrated using data on leukemia following irradiation for cervical cancer. In this study, the original cohort study showed a clear excess of leukemia in the first 15 years after exposure, but it was not feasible to obtain dose estimates on the entire cohort. However, the subsequent nested case-control study failed to demonstrate significant differences between alternative dose-response relations and effects of time-related modifiers. The combined analysis allows much clearer discrimination between alternative dose-time-response models.

Case-Control Studies↗
PubMed1991

Fidelity of mammalian DNA replication and replicative DNA polymerases.

Current models suggest that two or more DNA polymerases may be required for high-fidelity semiconservative DNA replication in eukaryotic cells. In the present study, we directly compare the fidelity of SV40 origin-dependent DNA replication in human cell extracts to the fidelity of mammalian DNA polymerases alpha, delta, and epsilon using lacZ alpha of M13mp2 as a reporter gene. Their fidelity, in decreasing order, is replication greater than or equal to pol epsilon greater than pol delta greater than pol alpha. DNA sequence analysis of mutants derived from extract reactions suggests that replication is accurate when considering single-base substitutions, single-base frameshifts, and larger deletions. The exonuclease-containing calf thymus DNA polymerase epsilon is also highly accurate. When high concentrations of deoxynucleoside triphosphates and deoxyguanosine monophosphate are included in the pol epsilon reaction, both base substitution and frameshift error rates increase. This response suggests that exonucleolytic proofreading contributes to the high base substitution and frameshift fidelity. Exonuclease-containing calf thymus DNA polymerase delta, which requires proliferating cell nuclear antigen for efficient synthesis, is significantly less accurate than pol epsilon. In contrast to pol epsilon, pol delta generates errors during synthesis at a relatively modest concentration of deoxynucleoside triphosphates (100 microM), and the error rate did not increase upon addition of adenosine monophosphate. Thus, we are as yet unable to demonstrate that exonucleolytic proofreading contributes to accuracy during synthesis by DNA polymerase delta. The four-subunit DNA polymerase alpha-primase complex from both HeLa cells and calf thymus is the least accurate replicative polymerase. Fidelity is similar whether the enzyme is assayed immediately after purification or after being stored frozen.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1991

Exposure to residential electric and magnetic fields and risk of childhood leukemia.

The relation between exposure to electric and magnetic fields in the home, as assessed by measurements, wiring configuration, and self-reported appliance use, and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California. Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random digit dialing. Interviews were obtained from 232 cases and 232 controls. Available for analysis were measurements of the magnetic field in the child's bedroom over 24 hours or longer (164 cases and 144 controls), spot measurements of magnetic and electric fields (140 cases and 109 controls), and wiring configuration (219 cases and 207 controls). No clear associations between leukemia risk and measured magnetic or electric fields were seen. An association between the Denver Wertheimer-Leeper wiring configuration and childhood leukemia risk was observed (odds ratio for very high relative to very low current and underground configuration combined = 2.15, 95% confidence interval 1.08-4.28; p for trend = 0.008) and was not substantially altered by adjustment for potential confounding factors. Cases were more likely than controls to report use of several appliances that produce high electric and magnetic fields. Our results support an association between childhood leukemia risk and wiring configuration, but not direct measurements of electric and magnetic fields.

Adult↗
PubMed1991

Exonucleolytic proofreading of leading and lagging strand DNA replication errors.

We have asked whether exonucleolytic proofreading occurs during simian virus 40 origin-dependent, bidirectional DNA replication in extracts of human HeLa cells. In addition, we have compared the fidelity of leading and lagging strand DNA synthesis. In a fidelity assay that scores single-base substitution errors that revert a TGA codon in the lacZ alpha gene in an M13mp vector, providing an excess of a single dNTP substrate over the other three dNTP substrates in a replication reaction generates defined, strand-specific errors. Fidelity measurements with two vectors having the origin of replication on opposite sides of the opal codon demonstrate that error rates for two different A.dCTP and T.dGTP mispairs increase when deoxyguanosine monophosphate is added to replication reaction mixtures or when the concentration of deoxynucleoside triphosphates is increased. The data suggest that exonucleolytic proofreading occurs on both strands during bidirectional replication. Measurements using the two simian virus 40 origin-containing vectors suggest that base substitution error rates are similar for replication of the leading and lagging strands.

Antigens, Polyomavirus Transforming↗
PubMed1991

Heteroduplex repair in extracts of human HeLa cells.

A general repair process for DNA heteroduplexes has been detected in HeLa cell extracts. Using a variety of M13mp2 DNA substrates containing single-base mismatches and extra nucleotides, extensive repair is observed after incubation with HeLa cell cytoplasmic extracts and subsequent transfection of bacterial cells with the treated DNA. Most, but not all, mispairs as well as two frameshift heteroduplexes are repaired efficiently. Parallel measurements of repair in HeLa extracts and in Escherichia coli suggest that repair specificities are similar for the two systems. The presence of a nick in the molecule is required for efficient repair in HeLa cell extracts, and the strand containing the nick is the predominantly repaired strand. Mismatch-dependent DNA synthesis is observed when radiolabeled restriction fragments, produced by reaction of the extract with heteroduplex and homoduplex molecules, are compared. Specific labeling of fragments, representing a region of approximately 1,000 base pairs and containing the nick and the mismatch, is detected for the heteroduplex substrate but not the homoduplex. The repair reaction is complete after 20 min and requires added Mg2+, ATP, and an ATP-regenerating system, but not dNTPs, which are present at sufficient levels in the extract. An inhibitor of DNA polymerase beta, dideoxythimidine 5'-triphosphate, does not inhibit mismatch-specific DNA synthesis. Aphidicolin, an inhibitor of DNA polymerases alpha, delta, and epsilom, inhibits both semiconservative replication and repair synthesis in the extract. Butylphenyl-dGTP also inhibits both replicative and repair synthesis but at a concentration known to inhibit DNA polymerase alpha preferentially rather than delta or epsilon. This suggests that DNA polymerase alpha may function in mismatch repair.

Adenosine Triphosphate↗
PubMed1991

Sequence effect on incision by (A)BC excinuclease of 4NQO adducts and UV photoproducts.

Nucleotide excision repair in Escherichia coli is initiated by (A)BC excinuclease, an enzyme which incises DNA on both sides of bulky adducts and removes the damaged nucleotide as a 12-13 base long oligomer. The incision pattern of the enzyme was examined using DNA modified by 4-nitroquinoline 1-oxide (4NQO) and UV light. Similar to the cleavage pattern of UV photoproducts and other bulky adducts, the enzyme incises the 8th phosphodiester bond 5' and 5th phosphodiester bond 3' to the 4NQO-modifed base, primarily guanine. The extent of DNA damage by these agents was determined using techniques which quantitatively cleave the DNA or stop at the site of the adduct. By comparison of the intensity of gel bands created by (A)BC excinuclease and the specific cleavage at the damaged site, the efficiency of (A)BC excinuclease incision at 13 different 4NQO-induced adducts and 13 different photoproducts was determined by densitometric scanning. In general, incisions made at 4NQO-induced adducts are proportional to the extent of damage, though the efficiency of cutting throughout the sequence tested varies from 25 to 75%. Incisions made at pyrimidine dimers are less efficient than at 4NQO-adducts, ranging from 13 to 65% incision relative to modification, though most are around 50%. The two (6-4) photoproducts within the region tested are incised more efficiently than any pyrimidine dimer.

4-Nitroquinoline-1-oxide↗
PubMed1991

A comparative trial of two walking systems for paralysed people.

A trial has been performed to compare two designs of reciprocal walking orthosis for paralysed people--the hip guidance orthosis (HGO) from Oswestry, England, and the reciprocating gait orthosis (RGO) from New Orleans, USA. Eighteen male and 4 female paraplegic subjects used each orthosis for 4 months, in a crossover study. All aspects of the provision and use of the devices were monitored, and a variety of assessments were made. Fifteen subjects were able to use both orthoses, 5 were unable to use either and 2 succeeded with the HGO but not the RGO. At the end of the trial 12 subjects chose to keep the RGO, 4 the HGO, and 6 kept neither. Those choosing the RGO liked its appearance; those choosing the HGO liked the speed of donning and doffing. The RGO was about 50% more expensive to supply than the HGO.

Adaptation, Psychological↗
PubMed1991

Local blood volume changes in women with pelvic congestion measured by applied potential tomography.

1. Applied potential tomography is a new, non-invasive technology for observing changes in blood volume. We have used it to study 12 women with lower abdominal pain caused by pelvic congestion, and 15 control subjects. 2. A significant increase in blood volume of 1.8% was observed in the pelvis of women with congestion when changing from the supine to the erect position, and of 2.7% in the control subjects (P less than 0.0002). The difference between the groups was not significant. 3. The distribution of the area over which blood volume changes took place was significantly different between the two groups (P less than 0.002). More of the posterolateral part of the pelvis was involved in women with pelvic congestion than in the control subjects. 4. Applied potential tomography distinguishes between normal women and those having pelvic congestion with a specificity of 87% and a sensitivity of 75%.

Blood Volume↗
PubMed1991

Efficiency of cohort sampling designs: some surprising results.

Cohort sampling designs are proposed which one would intuitively expect to be more efficient than nested case-control sampling. Two of these designs start with a nested case-control sample and distribute controls to sampled risk sets other than those for which they were picked. The third design has the goal of maximizing the number of distinct persons in a nested case-control sample. Simulation results show surprisingly little gain, and more often a loss in efficiency of these new designs relative to nested case-control sampling. This is due to the sampling-induced covariance between score terms. We conclude that the often stated intuition that nested case-control sampling does not make good use of sampled individuals' covariate histories is false.

Analysis of Variance↗
PubMed1990

Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study.

Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.

Acute Disease↗
PubMed1990

Bivariate survival models for analysis of genetic and environmental effects in twins.

Classic methods in genetics for the analysis of binary attributes, based on an assumption of a "threshold" on a normally distributed latent variable called "liability," estimate the strength of genetic and environmental effects from differences in correlations between relatives of differing genetic relatedness. Two problems that are not easily addressed by these methods are the need to take the age of onset into account (particularly in chronic diseases in which incidence rates vary considerably with age and the lengths of time at risk can vary between individuals) and the desirability of incorporating measured covariates (genetic or environmental). The standard methods of cohort analysis used in epidemiology allow for both of these features, but until recently have been restricted to independent individuals. Recent developments in survival analysis have extended the widely used "proportional hazards" model of Cox by the addition of latent variable, epsilon, reflecting the shared susceptibility of related subjects because of their shared genes or shared environment. We show how this approach can be combined with more traditional models of gene-environment interaction to allow the main effects of measured genetic markers and environmental variables to be estimated, as well as the residual variance of genetic and environment and their interactions. The approaches are applied to a cohort of female twin births in Sweden from 1886 to 1958, linked with the Swedish cancer registry from 1961 to 1982.

Adult↗