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Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 163 records · Page 9Linked to original sources
PubMed1986

Extensive diversity in the recognition of influenza virus hemagglutinin by murine T helper clones.

A panel of H-2k class II-restricted Th clones were established from individual CBA mice primed by infection with X31 influenza virus. 27 clones, which showed specific recognition of the HA surface glycoprotein, were all H3N2 subtype specific, in contrast to a T cell line which was crossreactive and which may have other specificities. 20 distinct HA-specific clones recognized a tryptic cleavage fragment of X31 consisting of residue 28-328 of HA1 (tops) which includes all the Ab-combining regions of the HA molecule. Seven other HA-specific clones failed to respond to either tops or to aggregate (the remainder of the virus after tryptic cleavage of tops). The specificity of these clones has been mapped, tentatively, to a conformational determinant in the interface antibody-binding region of the HA trimer. Analysis of the fine specificity of the HA-specific clones against a panel of H3N2 natural variant viruses isolated from major virus epidemics from 1968 to 1984 revealed a hitherto unrecognized diversity in T cell recognition of a HA. A total of 12 specificity groupings were evident, and varied from groups of clones that recognized all natural variants to one clone that responded only to isolates from 1968 to 1972. Six out of eight clones from a major specificity group, which failed to recognize variants TX/77, BK/79, or CN/84, responded to two overlapping peptides (48-68 and 53-87), corresponding to a region of HA1 that includes part of two antibody combining sites. An examination of the amino acid sequences of natural variant viruses from this region of HA revealed that residues Asn53 and Asn54 and/or Ile62 were critical for recognition by these clones. We conclude that recognition of HA by Th cells is not restricted to a limited number of epitopes in the conserved regions of the molecule, but is extremely diverse and includes specificities that map to variable antibody-combining regions of the molecule. In addition, the sensitivity of the T cell clones to the amino acid substitutions occurring in HA1 of natural variant viruses suggests that Th may play a role in the immune pressure for antigenic variation in the HA molecule.

Animals↗
PubMed1986

Autoimmunity to Thy-1.

Conditions are described for the induction of autoimmunity to Thy-1 and a large panel of monoclonal CBA and AKR autoantibodies has been characterized. These reveal a hitherto unrecognized complexity at the Thy-1 locus and evidence for intragenic control. Epitopes recognized by the autoantibodies differed in species and tissue distribution from alloantigenic determinants but their specificity was confirmed by transfection studies with the cloned Thy-1b gene. The quantitative and qualitative differences in epitope expression between Thy-1a and Thy-1b alleles were inherited as single Mendelian traits and in the absence of recombinants, suggesting translational control.

Animals↗
PubMed1986

Conformational-dependent recognition of influenza virus hemagglutinin by murine T helper clones.

A panel of H-2k class II-restricted T helper (Th) clones were established from individual CBA mice intranasally infected with A/X31 influenza virus. In a study of their fine specificity, it was revealed that recognition of hemagglutinin (HA) by certain Th clones was dependent on conformational features of the molecule. Five HA-specific Th clones failed to recognize X31 mutant viruses R19 and R20 each with a His to Arg substitution at position 17 of HA1. This amino acid substitution affects the conformational stability of the molecule. Each of the 5 clones responded to purified HA but failed to recognize tryptic fragments of HA consisting of HA1 residues 28-328 (tops) and the remainder of the virus including residues 1-27 of HA1 (aggregate). A further 20 HA-specific clones responded to R19 and R20 mutants and to HA1 tops. The R19 and R20 negative clones also showed diminished proliferative responses to pH 5-treated X31. Low pH treatment results in an irreversIble conformational change which affects the integrity of the globular head region of the HA trimer. In addition, four of the five clones failed to recognize variant virus Eng-72 which has Arg to Gly substitution at position 208 in the interface antibody-binding region. This region is antigenically and structurally altered in tops and pH 5-treated X31. The results suggest that recognition of HA by certain Th clones is dependent on the three-dimensional structure of the molecule and that Th cells may recognize conformational determinants in addition to primary structure.

Animals↗
PubMed1986

Suicide selection of murine T helper clones specific for variable regions of the influenza hemagglutinin molecule.

A negative selection procedure has been developed to obtain murine T helper clones specific for variable regions of the influenza A hemagglutinin. T cell lines, established from mice primed by intranasal infection with X31 (H3N2) virus, were cross-stimulated with natural variant viruses of known primary sequence (either A/TEXAS/1/77 or A/ENG878/69) and proliferating cells eliminated by treatment with the cell cycle-specific drug 5-bromodeoxyuridine. After two suicide cycles, T cell lines were subtype specific and failed to recognize the natural variants. Clones were established by limiting dilution and their specificity was determined against a panel of viruses. Extensive diversity was evident in the reactivity of clones from individual donors, and two major T cell recognition sites were defined in the globular head region of the hemagglutinin molecule.

Amino Acid Sequence↗
PubMed1986

Efficient selection of controls for multi-centered collaborative studies of rare diseases.

An increasing number of epidemiologic studies of rare diseases are being conducted as collaborative ventures among several institutions in different geographic areas. Geographic area must be accounted for in the analysis, along with age and other potential confounders. This paper shows that it may not be possible to accurately predict the distribution of persons with rare diseases by age and geographic area. Therefore, selecting controls by matching on age group and geographic area is more efficient than selecting controls in all age and geographic area strata based on prior estimates of expected numbers of cases.

Adult↗
PubMed1986

Evidence for a protective effect of lactation on risk of breast cancer in young women. Results from a case-control study.

Female residents of King County, Washington state, aged 25-54 years, in whom breast cancer was diagnosed in 1981 and 1982 were interviewed regarding their reproductive histories. Their responses were compared with the responses of a sample of women from the same population, who were selected by random digit-dialing from the same county, so that their age distribution resembled that of the cases. Premenopausal women who had ever lactated had 0.49 times the risk of developing breast cancer, as compared to premenopausal women who had never lactated (95% confidence interval, 0.30-0.82). Among both premenopausal and postmenopausal women, risk of breast cancer decreased with increasing duration of lifetime lactation experience, although the effect was consistently stronger for premenopausal women. This protective effect persisted after adjustment for age, parity, and age at first full-term pregnancy. Other reproductive factors, and demographic factors such as income and education, did not confound the relationship. This study confirms other recent findings of a protective effect of lactation against the development of breast cancer in young women.

Adult↗
PubMed1986

Hormones and hormone receptors in the etiology of breast cancer.

Many epidemiologic features of breast cancer suggest that endogenous hormones are of importance in the genesis of this disease. Endocrinologic studies based on total levels of various hormones in serum and urine have provided etiologic clues, but have failed to yield a clear understanding of the hormonal aberrations that promote the development of breast cancer. One reason for this is probably that neither urinary hormones, nor total levels of serum hormones accurately reflect biologically active levels to which the cells of origin are exposed. Levels of hormones unbound to serum sex binding globulin may be of more etiologic relevance, and future studies utilizing measurements of such hormone fractions may provide new information of etiologic importance. Some risk factors for breast cancer, especially age at birth of first child, may influence risk by altering the susceptibility of mammary ductal epithelial cells to estrogens or other endogenous hormones by altering the level of hormone receptor proteins in these cells. Additional studies to identify the determinants of hormone receptors in the breast are needed to test this hypothesis.

Adolescent↗
PubMed1986

Risk factors for estrogen receptor-rich and estrogen receptor-poor breast cancers.

A population-based case-control study was conducted in King County, WA, to investigate whether risk factors for estrogen receptor (ER)-rich and ER-poor breast cancers differ. Responses to interviews with 329 women with breast cancer who were between 25 and 54 years of age at the time of diagnosis were compared to responses of 332 women of similar age who were selected from female residents of King County by random digit dialing. Of the 329 interviewed cases, 143 had ER-rich tumors, 97 had ER-poor tumors, and 89 had tumors that were not assayed for receptors. The relative risks of ER-rich and ER-poor breast cancers were similar with respect to late menarche, single marital status, history of extended lactation, menopause before age 40, history of benign breast disease, positive family history of breast cancer, obesity, and history of oral contraceptive and noncontraceptive estrogen use. Late age at first full-term pregnancy was a risk factor for ER-rich breast cancer but not for ER-poor breast cancer. This finding suggests that different causal mechanisms operate for these two types of breast cancer and supports the hypothesis that an early first birth protects against breast cancer by reducing the level of ERs in the mammary epithelial cells from which carcinomas develop.

Adult↗
PubMed1985

A new thymocyte membrane differentiation antigen for mouse and rat.

A new thymocyte membrane-brain antigenic system is defined for the mouse and rat. Monoclonal antibody NIM-M129 recognizes a membrane antigen that has a similar size to Thy-1 (20-23 kd) but entirely different tissue distribution. It is absent from cortisone-resistant thymocytes, murine peripheral T cells, T-cell blasts, and T-cell lymphomas, or rat bone marrow. However, the determinant exhibits a quantitative difference in expression on thymocytes of Thy-1a (low) and Thy-1b (high) mice, with intermediate values for their F1 progeny. Backcross and F2 segregation tests between CBA and CBA-Thy-1a congenic lines established firm genetic linkage between Thy-1 and the level of epitope expression on the thymocyte cell surface.

Animals↗
PubMed1985

Two MMPI approaches for identifying alcoholics: evaluation and implications for further research.

Though contrasting MMPI approaches yield opposing conclusions regarding personalities of alcoholics, the relative efficacy of the approaches has not been evaluated. In this study of 309 domiciliary patients, the alcoholism scale and cluster analytic approaches were compared with respect to the identification of alcoholics and excessive-drinking subjects. The MacAndrew Alcoholism Scale significantly identified alcoholics; however, there was no identification with the profiles of the clinical scales generated by the cluster analytic technique. The conclusions suggest the greater efficacy of the alcoholism scale approach and suggest that the clustering strategy might be more fruitfully applied to alcoholism scales.

Alcohol Drinking↗
PubMed1985

Invasive cervical cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Preliminary results of a study of the possible relationship of depot-medroxy-progesterone acetate (DMPA) to invasive cervical cancer are presented. The findings are based on data from three participating centres in Thailand and one in Mexico. A relative risk for cervical cancer of 1.2 was observed in women who had ever used DMPA; this was not statistically significant. No consistent increase in risk with duration of use was observed, although a relative risk of 2 was found in women who had used DMPA for more than 5 years. This observed increase in risk was confined to women who were aged under 46 years or who had first been exposed to DMPA before 30 years of age. These findings are based on small numbers of subjects, and may not represent a causal relationship.

Contraceptive Agents, Female↗
PubMed1985

Breast cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The preliminary results of a study of the incidence of breast cancer in relation to use of depot-medroxyprogesterone acetate (DMPA) are presented. The findings are based on data from three participating centres in Thailand, and one each in Kenya and Mexico. A relative risk for breast cancer of 0.7 was observed in women who had ever used DMPA; this was not statistically significant. Although no consistent decrease in risk with duration of use was observed, the lowest relative risk (0.5) was observed in women who had used DMPA for three or more years. These findings are based on small numbers and must be considered preliminary. However, they provide no evidence that DMPA increases the risk of breast cancer, and suggest that it may exert a protective effect, particularly in long-term users.

Breast Neoplasms↗
PubMed1985

Cancer incidence in Caucasians living in the Pacific Basin.

Variations in cancer incidence among whites in 1973-77 in 8 geographic areas of the Pacific Basin were compared. Substantial differences were found for the occurrences of lung cancer, cancer of the corpus uteri, and malignant melanoma. White women living in New Zealand and Australia had the lowest risk of developing lung cancer, whereas white men living in the western United States had the highest risk. Cancer of the corpus uteri occurred more commonly in the western United States than elsewhere in the Pacific Basin. Geographic areas located closest to the equator experienced the highest incidence of malignant melanoma. In all areas, the incidence rates of cancers of the lung and corpus uteri and malignant melanoma increased significantly between 1960-66 and 1973-77; after the mid-1970s, rates of cancer of the corpus uteri declined. The incidence of stomach cancer decreased in all areas. Although cervical cancer decreased in incidence over time for most women, it increased noticeably in young women. The incidence of breast cancer also rose during the 17-year period. In at least 1 geographic area, the observed increases in breast cancer incidence were confined to women under age 40.

Adult↗