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Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cleft palate, mortality and morbidity in infants of substance abusing mothers.

OBJECTIVE: To investigate a high incidence of congenital malformations, morbidity and mortality in infants of drug abusing mothers. METHODOLOGY: In a 10 and a half year period from 1984-95, 497 such babies were reviewed whose mothers had abused a variety of drugs. RESULTS: Thirty babies died or had serious disability. There were five cases of SIDS and 19 babies had major malformations, including seven with cleft lip/palate. Six babies had significant gastrointestinal disorders or feeding difficulties. CONCLUSION: The incidence of clefting was 10 times the normal rate and SIDS five times the expected incidence. In a group of mainly socially disadvantaged women, the abuse of narcotics, amphetamines and other substances, with possible suboptimal nutrition, may have been contributory to this high morbidity and mortality. No specific drug could be implicated.

Abnormalities, Drug-Induced↗
PubMed1995

Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo.

The accumulation of p53 protein following whole body irradiation of adult mice was studied using a new polyclonal antibody to mouse p53. While dramatic accumulation of the protein was apparent in splenocytes, thymocytes and osteocytes no p53 protein accumulation was detected in the hepatocytes of the irradiated mouse. Thus, the upstream initiating signals that control the induction of p53 are controlled in a tissue specific manner. While massive apoptosis accompanies p53 induction in thymocytes and splenocytes it is not seen in the osteocytes. Thus the downstream consequences of p53 induction are also tightly controlled. These results have profound significance for an understanding of the role of the p53 tumour suppression pathway in different tissues.

Animals↗
PubMed1995

Alcohol as a cause of cancer.

This is a review of the epidemiologic literature on alcohol and risks of various cancers. Alcohol has consistently been related to risks of squamous cell carcinomas of the mouth, oral pharynx, larynx, and esophagus in multiple studies of varying design. The joint effects of alcohol and smoking are greater than additive, and are probably multiplicative, suggesting biological synergism. All major types of alcoholic beverages have been casually implicated in the genesis of these diseases. The influence of alcohol on risks of upper aerodigestive tract cancers may be greater in persons with marginal nutritional status than in better-nourished individuals. Alcohol also has been associated with an increased risk of adenocarcinomas of the esophagus, gastro-esophageal junction, and gastric cardia, but the relationship is not as strong as for squamous cell esophageal carcinomas. Alcohol and tobacco account for over 80% of the squamous carcinomas of the mouth, pharynx, larynx, and esophagus in the United States. Risks of cancers of the distal stomach, pancreas, colon, and rectum have not been consistently related to alcohol, although possible relationships between beer drinking and rectal cancer and between heavy use of alcohol and pancreatic cancer warrant further study. Studies of alcohol and liver cancer, in which the confounding influence of hepatitis B was considered, have yielded inconsistent results and should be replicated. An association between heavy alcohol use and breast cancer has been observed in most studies, even after controlling for known risk factors for breast cancer, and additional investigations of this issue are warranted.

Alcohol Drinking↗
PubMed1995

Is the spleen a preferential site of blood cell production in the human fetus?

Information about the status of the spleen as a preferential site of blood cell production in the human fetus is relevant to generalizations about the ontogeny of haematopoietic microenvironments and to speculations about the pathogenesis of myeloid metaplasia. Such information has been accumulated in a comparison of populations of blood cell precursors derived from the blood, the spleens and the livers of human fetuses during the fourth, fifth, sixth and seventh months of gestation. During this period, the spleen does not contain populations of erythroblasts or granulocyte precursors that could not have been derived from the blood. It is inferred that in the human fetus the spleen is not a preferential site of blood cell production between the fourth and seventh months of gestation. Like any other site, the spleen may however accommodate intravascular blood cell precursors, which may proliferate and differentiate in human fetal blood.

Blood Cells↗
PubMed1995

Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma.

Adenocarcinomas of the esophagus and gastric cardia were once rare. However, for unknown reasons, their incidence has been increasing rapidly over the past 15 years in the United States and parts of Western Europe. In contrast, the incidence of esophageal squamous cell carcinomas has remained relatively constant. To investigate possible reasons for these diverging incidence rates we analyzed data from two population-based case-control studies of cancers of the esophagus and gastric cardia that were conducted among male and female residents of western Washington between 1983 and 1990. Information on body mass index, cigarette use, alcohol intake, and other possible risk factors was collected via personal interviews with 404 cases or their next of kin (including 298 adenocarcinomas and 106 squamous cell carcinomas) and 724 controls identified by random digit dialing. Use of alcohol and cigarettes were significant risk factors for both histological types. The increase in risk for current smokers of 80 or more pack-years compared to nonsmokers was substantially higher for squamous cell cancer [odds ratio (OR) = 16.9; 95% confidence interval (CI) = 4.1-69.1] than for adenocarcinoma (OR = 3.4; 95% CI = 1.4-8.0), as was the increase for persons who typically drank 21 or more drinks/week compared to those who drank <7/week (OR = 9.5; 95% CI = 4.1-22.3 versus OR = 1.8; 95% CI = 1.1-3.1). For squamous cell carcinoma, body mass index was inversely associated with risk, whereas for adenocarcinoma, the highest risk was observed among persons who were in the highest decile of body mass index (OR = 1.9; 95% CI = 1.1-3.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Comparison of control subjects recruited by random digit dialing and area survey.

Although random digit dialing (RDD) is an accepted and commonly used method of sampling populations for controls in case-control studies, there have been surprisingly few attempts to compare the accuracy of RDD with that of the best traditional alternative, i.e., household area surveys. The aim of the present study was to compare a variety of characteristics of control subjects selected by RDD and area survey methods. All data were gathered through in-person interviews of both types of control subjects. The area survey identified a population-based sample of 20- to 79-year-old residents of two Washington State counties in 1978 and 1979. Control groups for three case-control studies of bladder cancer, gynecologic cancers, and multiple myeloma were drawn from this area sample, for a total of 240 control subjects. Controls aged 21-64 years from the same counties were identified for the National Bladder Cancer Study using RDD telephone sampling during the same time period. There were 134 respondents in the RDD control group. Overall, the two control groups selected by these two different methods yielded similar estimated frequencies of various population characteristics. The small differences observed in some age/sex subgroups and the statistical significance of the overall measure of association for occupational exposure to organic substances may be attributed to multiple comparisons.

Adult↗
PubMed1994

Modulation of immunodominant sites in influenza hemagglutinin compromise antigenic variation and select receptor-binding variant viruses.

The regions of antigenic variation in influenza hemagglutinin (HA) are located on surface-accessible regions in the three-dimensional structure of the HA1 monomer. The aim of this study was to establish whether a novel variant virus, IMUT4, in which we had mutated specific amino acid residues (HA1 63, 144, 158, and 193) in these regions, previously shown to be immunodominant for CBA/Ca mice, would either (a) establish holes in the antibody (ab) repertoire or (b) preclude further antigenic variation in IMUT4. CBA/Ca mice were able to mount a neutralizing ab response to IMUT4 infection and molecular recognition sites were established by sequencing of the HA genes of monoclonal antibody (mAb)-selected laboratory variants of wild-type X31 virus (HA1 131, 145, 155, and 196). However, each of these mAbs failed to select further antigenic variants of IMUT4, in ovo, but rather a receptor binding mutant (HA1 190 Glu-->Asp; 226 Leu-->Gln) that was still recognized by the selecting mAb, specific for HA1 155 of X31 virus. The facility for antigenic variation in influenza would appear to be compromised, therefore, by targeted mutation of immunodominant sites, as initially proposed by S. Fazekas de St. Groth (Fazekas de St. Groth, S. 1977. Antigenic, adaptive and adsorptive variants of the influenza haemagglutinin. In Topics in Infectious Diseases. Vol. 3. R.G. Laver, H. Bachmayer, and R. Weil, editors. Springer-Verlag, Vienna. 25-48.). It is interesting to note that recent isolates of the H3 subtype, (e.g., A/Beijing/92) obtained between 1991 and 1993, contain the same substitutions at HA1 190 and 226, which may indicate similar constraints to immune evasion and the relevance of our findings to antigenic variation in the human population.

Animals↗
PubMed1994

Alcoholism and cancer of the larynx: a case-control study in western Washington (United States).

Alcohol consumption is a well-known risk factor for laryngeal cancer. To determine whether alcoholism, as measured by responses to the Michigan alcoholism screening test (MAST), is a risk factor for laryngeal cancer independent of alcohol consumption, we analyzed data from a population-based case-control study. Personal interviews were conducted with 235 patients (81 percent response rate) with laryngeal cancer diagnosed from September 1983 through February 1987, who were residents of the Seattle metropolitan area. A total of 547 controls frequency-matched by age and gender, selected by random-digit dialing, were interviewed (75 percent response rate). When considered in a multivariate model, independent risk factors for laryngeal cancer included: alcohol consumption (42 or more drinks/wk compared with seven or less drinks/wk: odds ratio [OR] = 3.1, 95 percent confidence interval [CI] = 1.2-7.9); cigarette use (40 or more cigarettes/day compared with never-smoked: OR = 23.1, CI = 9.4-52.6); and weighted positive responses to the MAST (score of five or more compared with score of zero: OR = 1.9, CI = 1.1-3.4). Possible explanations for the association between alcoholism and laryngeal cancer are that a measure of alcoholism improves the accuracy of assessment of alcohol consumption, that alcoholism is associated with a pattern of alcohol consumption that increases the risk of laryngeal cancer, or that alcoholism may be a marker for host susceptibility to the carcinogenic effects of alcohol.

Adult↗
PubMed1994

Ionizing radiation and breast cancer in men (United States).

The purposes of this study were to determine whether exposure of the vestigial male breast to ionizing radiation is associated with an increase in risk of breast cancer and, if so, to determine whether the apparent effects on risk in men are similar to those reported for women. A population-based case-control study of breast cancer in men was conducted in 10 geographic areas of the United States. Information on possible prior exposure to ionizing radiation, and on other potential risk factors for breast cancer, was obtained from personal interviews of 227 cases and 300 controls who were recruited from October 1983 to September 1986. Evidence from this study that ionizing radiation can cause breast cancer in men includes: a modest trend of increasing risk with frequency of chest X-rays; an increase in risk in men with three or more radiographic examinations, especially if received prior to 1963; and an increase in risk in men who received X-ray treatments to the chest and adjacent body areas. Risk was increased only from 20 to 35 years after initial exposure from either radiographic examinations or X-ray treatments, and declined after three to four decades since last exposure, suggesting a wave of increased risk of finite duration following exposure. The doses of radiation received could not be estimated precisely, but those from diagnostic procedures were likely similar to those received by prepubertal females in prior studies, and the results of those and the present investigation are compatible. The carcinogenic effects of ionizing radiation may be similar in the male and prepubertal female breast.

Breast Neoplasms↗
PubMed1994

Risk factors for invasive cervical cancer in Kenyan women.

BACKGROUND: Few epidemiological investigations of invasive cervical cancer have been conducted in Sub-Saharan African populations. METHODS: Using information collected as part of the hospital-based World Health Organization (WHO) Collaborative Study of Neoplasia and Steroid Contraceptives, we examined potential risk factors for invasive cervical cancer among Kenyan women. In all 112 women with histologically confirmed invasive cervical cancer diagnosed at the Kenyatta National Hospital, Nairobi, Kenya, between June 1981 and September 1988 and 749 control subjects were included in the present analyses. All women were interviewed regarding their medical and reproductive history, methods of birth control, and history of sexual relationships and sexually transmitted infections. Multiple logistic regression procedures were used to derive maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjusting for age, several factors were found to be associated with invasive cervical cancer. These include multiple sexual partners, early age at first sexual intercourse (OR = 1.9 and 2.6 for women reporting first intercourse at age 16-17 years and < 15 years, respectively, compared to women with first intercourse > or = 18 years), history of abnormal vaginal discharge (OR = 13.8, 95% CI: 8.3-23.0), and history of gonorrhoeal infection (OR = 3.2, 95% CI: 1.6-6.2). Low educational attainment and multiparity were also associated with the risk of invasive cervical cancer. Although the Papanicolaou smear has been extensively used as a screening method for cervical cancer in many countries, only three cases and four controls reported ever having a Papanicolaou smear (2.6% cases and 0.5% of controls). CONCLUSIONS: As has been observed in other parts of the world, cervical neoplasia in Kenya appears to be a late consequence of venereally transmitted carcinogenic agents.

Adolescent↗
PubMed1994

Productive re-arrangement at both alleles of the T-cell receptor beta-chain locus in CD4 T-cell clones specific for influenza haemagglutinin.

T-cell receptor (TcR) beta-chain usage, and VDJ junctional region sequences thereof in a panel of CD4+ T-cell clones Ad-, or Ak- or Ek-restricted for major antigenic sites of influenza haemagglutinin (H3 subtype), were investigated. Direct sequencing of cDNA, obtained by polymerase chain reaction, revealed that the majority of T-cell clones contained both productive and non-productive rearranged transcripts. Moreover, T-cell clones specific for p206-227 (Ad) or p245-265 (AK) contained double-productive re-arranged transcripts (V beta 6 J beta 2.6, V beta 4, J beta 1.2) and (V beta 6 J beta 1.3, V beta 8.2, J beta 1.5) respectively. However, FACS analysis with V beta-specific monoclonal antibodies established that, for each of these T-cell clones, only a single beta-chain was expressed at the cell surface, thereby indicating post-transcriptional editing.

Alleles↗
PubMed1994

Immunodominance correlates with T-cell receptor (alpha beta) gene usage in the class II-restricted response to influenza haemagglutinin.

Class II-restricted T-cell clones elicited by natural infection with influenza A virus (H3N2 subtype) exhibit extensive diversity in their recognition specificity for the envelope glycoprotein, haemagglutinin, and focus on hypervariable regions of the HA1 subunit that feature in antigenic drift. However, T-cell clones established from the same individual focus on a single antigenic site with differing fine specificity for mutant viruses. We wished to determine whether such diversity of the haplotype and contrasting immunodominance of the individual's repertoire was mirrored in T-cell receptor (TcR) gene usage. A structural analysis was undertaken of the alpha and beta chains of TcR from a panel of CD4+ T-cell memory clones established in vitro after natural infection with X31 virus and specific for eight distinct antigenic sites of the HA1 subunit: p48-67 (Ak), p58-73 (Ad), p120-139 (Ak), p177-199 (Ad), p186-200 (Ad), p226-245 (Ek), p246-265 (Ek) and p269-288 (Ak). Direct sequencing of the alpha and beta chains, using the polymerase chain reaction, revealed that T-cell clones derived from the same donor used identical V beta D beta J beta and V alpha J alpha elements. Moreover there was extensive diversity in usage of V beta (V beta 1 or V beta 4 or V beta 8) genes between individual mice, in association with diverse J beta and V alpha J alpha elements for the recognition of a common antigenic peptide. We conclude that the CD4+ T-cell memory repertoire of the individual, following primary exposure to infectious virus, is oligoclonal and recruited from a limited number of precursor cells.

Amino Acid Sequence↗
PubMed1993

Comparison of recalled and validated oral contraceptive histories.

From a case-control study of the relation between oral contraceptives and breast cancer carried out in East Germany during 1982-1986, the authors obtained information on oral contraceptive use through interviews of study subjects and from the records of prescribing gynecologists. The degree of agreement regarding information from these two sources was assessed for 234 breast cancer cases and 524 controls who had ever used oral contraceptives. Agreement between information obtained from medical records and that from interviews on total duration of use, number of episodes of use, and time since first and last use was reasonably good, and levels of agreement did not differ appreciably between cases and controls. Lower levels of agreement were observed for individual brand names and the duration of use of specific brands. Attempts should be made to obtain information on specific brands from medical records when investigating the effects of individual preparations.

Adult↗
PubMed1993

Age distribution of histologic types of breast carcinoma.

The large number of cases in the Surveillance, Epidemiology and End Results (SEER) program of the US National Cancer Institute allowed a detailed analysis of the age distribution of the histologic types of invasive breast carcinoma. Between ages 50 and 85 years in females, the age-specific incidence rate shows little change for medullary, inflammatory and apocrine carcinomas; is about doubled for Paget's disease and for ductal, lobular, tubular and metaplastic carcinomas; and increases to 4 to 8 times the menopausal level for mucinous, papillary and signet-ring-cell carcinomas. The peri-menopausal break on the age-incidence curve is most marked for carcinomas of predominantly lobular origin and virtually absent for carcinomas of predominantly ductal origin. In males, the age distribution of papillary carcinoma is similar to that of all types combined, whereas that of mucinous carcinoma is skewed towards older ages, as in females.

Adult↗
PubMed1993

Mammographic calcifications and risk of subsequent breast cancer.

BACKGROUND: Women with proliferative benign breast lesions are at increased risk of breast cancer, and some studies have provided evidence that microscopic calcifications in such lesions enhance the risk. PURPOSE: This study was performed to determine whether calcifications on mammograms are predictive of subsequent breast cancer. METHODS: Data for this study were collected on women enrolled at four of the clinics that participated in the Breast Cancer Detection and Demonstration Project (BCDDP). The presence, morphology, and distribution of calcifications visualized on baseline mammograms for 686 women who developed breast cancer over a 7- to 10-year period of follow-up were compared with those for 1357 controls who remained cancer free. We also compared presence and types of calcifications in breasts in which cancer subsequently developed with those in the contralateral breast. RESULTS: Calcifications were evident at baseline in at least one breast in 381 (55.5%) of 686 cases and in 606 (44.7%) of 1357 controls. The estimated relative risk (RR) of breast cancer was 1.68 in women with calcifications, compared with those having none. There was a statistically significant trend of increasing risk with number of breasts with calcifications; RR increased from 1.28 to 2.14 in women with calcifications in one and both breasts, respectively. In women with unilateral calcifications, RR was greater for the breast in which the calcification occurred (1.48) than for the opposite breast (1.08). The elevated risk persisted for more than 6 years from identification of the calcification, suggesting that these lesions were not indicative of existing carcinomas detected later. Risk was greatest in women with clustered calcifications of any morphology or linearly distributed punctate calcifications (RR = 3.64), and the cancer in women with such calcifications was 4.65 times more likely to occur in the involved breast than in the contralateral breast. Multiple and scattered punctate calcifications, and those of any number or distribution that were ring-shaped or linear, were also associated with subsequent risk of breast cancer (RR = 2.09 and 1.76, respectively) but were not strongly predictive of the side on which the breast cancer occurred. Risk was not altered in women with single punctate or large conglomerate calcifications, although the cancers that subsequently occurred in women with the latter lesions were over three times more likely to develop in the breast with the calcification than in the opposite breast. CONCLUSIONS: These findings are consistent with previously reported relationships between breast cancer and specific histologic types of noninvasive breast lesions. Some types of mammographic calcifications appear to be independent risk factors for breast cancer. IMPLICATIONS: If these results are confirmed by other investigators, mammographic calcifications could serve as an additional indicator of women at high risk for breast cancer who may benefit from intensified follow-up.

Breast Diseases↗
PubMed1993

The infusion of human fetal liver cells.

Only transient engraftment of infused fetal liver cells has been demonstrated in a small proportion of patients with hypoplastic bone marrow or patients undergoing treatment for acute leukemia. This presumably reflects the ability of the recipient to reject the infused cells, the infusion of too few viable stem cells or the availability of too few accessory cells; it is clear from the successful engraftment of infused fetal liver cells in a high proportion of infants and fetuses with severe immunodeficiency diseases that, under favorable circumstances, cells derived from human fetal liver are capable of establishing effective grafts and making a substantial contribution to hematopoiesis comparable to that of transplanted cells derived from the liver of the fetal mouse, rat, rabbit or dog. Significant clinical and hematological improvements have been described following infusions of fetal liver cells without evidence of engraftment. These improvements have been attributed to the ability of the infused cells to promote regeneration of autologous hematopoiesis and to inhibit the growth of tumor cells. These possibilities are worthy of evaluation in relation to the production of putative regulators of cellular proliferation in the liver. Meanwhile a suppressor of tumor growth is being used to purge bone marrow prior to autologous transplantation. The generation in vitro of cells which possess the properties of hematopoietic stem cells generated in the liver--from cells which can be maintained as permanent cell lines--would transform hematopoietic cell replacement therapy, and the possibility may not be too unrealistic to contemplate.

Animals↗
PubMed1993

Consistent lack of association between breast cancer and oral contraceptives using either hospital or neighborhood controls.

BACKGROUND: Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls. METHODS: To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years. RESULTS: Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol. CONCLUSIONS: Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years.

Adolescent↗