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D B Thomas

Publications and source records attributed to D B Thomas.

At least 181 records · Page 10Linked to original sources
PubMed1985

Rationale and design of cancer chemoprevention studies in Seattle.

Three cancer prevention trials are currently in their early phases at The Fred Hutchinson Cancer Research Center, the University of Washington School of Public Health and Community Medicine, and the Swedish Hospital. All 3 studies are randomized and placebo controlled. One large-scale study involves the daily administration of retinoids to persons with asbestos-related lung disease in an attempt toward reduction of their high risk for bronchogenic carcinomas and mesotheliomas. A second study involves administration of the same agents to long-term heavy smokers; a substantial feasibility and toxicity pilot study will precede a full-scale prevention trial. In the third trial, folic acid administration is evaluated in relation to the progression and regression of cervical dysplasia among women with abnormal Pap smears. We report here the rationale and the design for these 3 studies.

Asbestosis↗
PubMed1984

Do hormones cause breast cancer?

The evidence that various endogenous and exogenous sex hormones play a role in the etiology of breast cancer is reviewed. It is hypothesized that prolonged exposure to normal levels of ovarian estrogens and cyclic progesterone resulting from early menarche and late menopause, and primarily willful nulliparity and late childbearing, act at an early stage in the development of breast cancer by promoting excessive proliferation of normal epithelial stem cells. Excess endogenous or exogenous estrogens can enhance risk by stimulating proliferation of epithelial cells that have undergone partial malignant transformation. The breast, however, is much less responsive to the tumor-promoting effects of estrogens than the endometrium, and estrogens probably play a less important role in the later stages of mammary than endometrial carcinogenesis.

Adolescent↗
PubMed1984

Surface carbohydrate epitopes of Thy-1.1 and Thy-1.2 thymocytes are distinguished by a monoclonal antibody with a specificity common to peanut agglutinin.

NIMF4-31.7 is a monoclonal IgM antibody with affinity for terminal galactose residues of membrane glycoproteins, Sepharose and agarose. It is cytotoxic for a subpopulation of murine thymocytes and peripheral lymphocytes, corresponding to the peanut agglutinin-positive population, but reacts with a majority of cells after neuraminidase treatment. It has revealed a genetic linkage between the Thy-1 locus and quantitative expression of carbohydrate determinants on the thymocyte membrane.

Animals↗
PubMed1984

Flip-flop in the Lyt 2 phenotype of T cells from radiation chimaeras between Thy 1 congenic donor and recipient mice.

We present further evidence that T helper cells change their surface phenotype from Lyt 2- to Lyt 2+, after secondary adoptive transfer. Chimaeras were established with Lyt 2- spleen cells from normal, or carrier-primed A-Thy 1a donors and irradiated, A-Thy 1b recipients. Despite efficient depletion of Lyt 2+ cells from the initial donor, in the fluorescence-activated cell sorter, the majority of chimaeric T cells expressed Lyt 2 and were resistant to monoclonal Thy 1.2 alloantibody and complement treatment. In functional studies, the T helper activity of chimaeras, reconstituted with carrier-primed spleen cells, was present in both Lyt 2+ and Lyt 2- subsets.

Animals↗
PubMed1983

A regulatory role for the memory B cell as suppressor-inducer of feedback control.

A regulatory role is proposed for the antigen-responsive B cell, as suppressor-inducer of feedback control during the secondary response in vivo. In a double adoptive transfer of memory cells primed to a thymus-dependent antigen from one irradiated host to another, antigen-specific suppressors are generated after a critical time in the primary recipient, able to entirely ablate a secondary anti-hapten response. Positive cell selection in the fluorescence-activated cell sorter confirmed that suppression was mediated by an Lyt-2+ T cell; however, positively selected B cells were also inhibitory and able to induce suppressors in a carrier-specific manner: Bhapten induced suppressors in a carrier-primed population, and Bcarrier induced suppressors in a hapten-carrier population. At the peak of the antibody response in the primary host, memory B cells and their progeny were unable to differentiate further to plasma cells due to their intrinsic suppressor-inducer activity, but this autoregulatory circuit could be severed by adoptive transfer to carrier-primed, X-irradiated recipients.

Animals↗
PubMed1983

Bladder cancer and alcoholic beverage consumption.

A population-based case-control study of bladder cancer was conducted in 10 geographic areas in the United States. Risk of bladder cancer was not related to overall alcohol intake, nor to amounts of wine, beer, or spirits consumed. Alcohol also did not interact with known or suspected bladder carcinogens to increase risk, and no evidence was found that indirect mechanisms associated with alcohol ingestion the risk of bladder cancer.

Adult↗
PubMed1983

Factors that promote the development of human breast cancer.

Epidemiologic and endocrinologic studies of breast cancer etiology are reviewed in the context of the Moolgavkar two-stage model for mammary carcinogenesis. Promoters are hypothesized to enhance the growth of stem and intermediate cells, and initiators are assumed to cause stem and intermediate cells to give rise to intermediate and tumor cells, respectively. Although all epidemiologic features of breast cancer can be explained in terms of the cellular events supposed by the model, the specific causes of breast cancer are largely unknown. Aberrations in endogenous steroid sex hormones most probably act as promoters, although their exact nature and etiology are unclear. Ionizing radiation is the only known initiator. The two-stage model implies that others exist and that they are responsible for both the international variation in risk of breast cancer, and its familial aggregation. Results of endocrinologic studies suggest either that aberrations in endogenous sex hormones serve as such initiators or are correlated with them, or that familial and international variations in risk are mediated by promoters.

Adult↗
PubMed1983

Feedback control of the secondary antibody response. I. A suppressor, suppressor-inducer mechanism from the interaction of B-memory cells with Lyt 2- T cells.

The cellular elements of an antigen-specific suppressor system for secondary antibody responses have been identified, using positive cell-selection techniques in the fluorescence-activated cell sorter. In a double-adoptive transfer of memory cells for a thymus-dependent antigen, from one irradiated recipient to another, antigen-specific suppressor T cells are recruited after a critical time in the primary recipient. It is also a source of B cells that are able to induce further suppressors in carrier-primed, but otherwise naive donors. There are two distinct routes, therefore, for the generation of suppressor T cells: primary induction by adoptive transfer with antigen, or secondary induction by B cells recruited in the primary irradiated host. We have shown that both primary and secondary suppressors are recruited from a Lyt 2- memory population, although the Lyt 2 alloantigen is expressed at the effector stage.

Animals↗
PubMed1983

Feedback control of the secondary antibody response. II. Differences in the rate of induction of T-helper and T-suppressor memory.

There is a radical change in the cooperative behaviour of the thymus-dependent B-memory cell after adoptive transfer to irradiated recipients. It acquires the ability to recruit suppressors on further transfer with carrier primed spleen cells. This suppressor inducer activity has provided a probe to study the development of feedback mechanisms after primary immunization. Here, we have shown that helper and suppressor activity exhibit different rates of induction after immunization but both reside in a long-lived memory population.

Animals↗
PubMed1982

T helper cells change their Lyt-1,2 phenotype during an immune response.

Evidence is presented that T helper cells change their Lyt-1,2 phenotype, from Lyt-1+2- to Lyt-1-2+, during a secondary response. In a secondary adoptive transfer the Lyt phenotype of carrier-primed T cells was established before and after secondary challenge using monoclonal antibodies and both positive and negative selection in the fluorescence-activated cell sorter. In a carrier-primed donor, the T helper cells were Lyt-1+2- whereas 3 days after boosting the majority were Lyt-2+, and resistant to treatment with anti-Lyt-1 and complement. Parking experiments in lethally irradiated recipients confirmed that Lyt-2+ T helper cells were generated from Lyt-2- precursors. In a primary response, both Lyt-2- and Lyt-2+ T helper cells were present 4 to 20 days after immunization. Therefore T helper cells do not exhibit invariant expression of the Lyt-1,2 alloantigens.

Animals↗
PubMed1982

Non-contraceptive exogenous estrogens and risk of breast cancer: a review.

Results from epidemiologic and related studies of non-contraceptive estrogens and breast cancer are reviewed. Exogenous estrogens in high doses can enhance the risk of breast cancer. Moderate use of estrogens for menopausal symptoms probably has little effect on risk, but long-term users, and women who take high-strength preparations, appear to be at slightly increased risk. Exogenous estrogens probably reduce the protective effect of premenopausal oophorectomy, and may preferentially enhance the risk of breast cancer in women with some types of benign breast disease, although data from some studies do not support these conclusions. There is no evidence that the influence on risk of breast cancer is different for synthetic and conjugated estrogens. Needs for reanalysis of data from existing studies, and for additional investigations, are summarized.

Breast Neoplasms↗
PubMed1982

Cancer incidence in relation to asbestos in drinking water in the Puget Sound region.

Population-based and proportional odds ratios for various cancers, based on incidence data from 1974-1977 and mortality data from 1965-1975 for western Washington State, were calculated in relation to three measures of exposure to asbestos in community water supplies. Six odds ratios were calculated for each neoplasm that occurred in sufficient numbers in each sex. About half of the 332 odds ratios calculated were above unity and half were below unity, and no more of them differed significantly from unity at the 5% level than would be expected by chance. Odds ratios for tumors of the small intestine were consistently elevated in both sexes, as were those for neoplasms of the thyroid, eye, testis, and prostate in males; however, odds ratios for brain tumors and leukemia were consistently less than one in both sexes. Chance is the most likely explanation for these findings. Results of this study and prior studies of cancer in relation to waterborne asbestos are inconsistent, and provide little evidence that asbestos in community water supplies has altered the risk of any cancer. However, all investigations conducted to date are correlational studies which have an inherently higher probability of failing to detect actual increased risks associated with imbibed asbestos, and additional studies of individual exposures are warranted. Neoplasms of the pancreas and small intestine should be included in such studies.

Adult↗
PubMed1982

Evidence for two T-helper populations with distinct specificity in the humoral response to influenza A viruses.

Virus specificity of T-helper cells for the humoral antibody response to influenza A viruses was studied with a hapten-carrier secondary adoptive transfer system, using whole virus, or viral components inserted into liposomes as carrier with B cells primed to DNP human gamma globulin. Evidence was obtained for two distinct T-helper cell populations from mice primed by influenza infection: a T-helper cell cross-reactive for all type A influenza viruses and a second T-helper population specific for the variant haemagglutinin. In vivo the virus cross-reactive T helpers recognized whole virus, but did not recognize isolated surface glycoproteins or internal virus proteins.

Animals↗
PubMed1982

Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases.

A group of 1,439 white women who were initially treated for biopsy-proved benign breast diseases from 1942 to 1975 in a single private surgery practice were followed through 1976 for development of breast cancer. Information on age, parity, and use of noncontraceptive estrogens was collected on all women at the time of their initial benign lesions. At follow-up, ages at menarche, menopause, and birth of first child were obtained, as was information on use of estrogens after the initial lesion. Slides from the initial lesion were reinterpreted and classified by a panel of pathologists. The influence of gross and microscopic features of the initial benign conditions on subsequent risk of breast cancer was ascertained and reported previously. This paper presents results of additional analyses based largely on Cox's proportional hazards model. Risk of breast cancer was related to nulliparity and ages at menarche and birth of first child and to a lesser extent to age at artificial menopause. Exogenous estrogen taken prior to the initial benign lesion did not alter risk of breast cancer. Subsequent use, primarily of conjugated estrogens, eliminated the protective effect of an artificial menopause and appeared to act synergistically with epithelial hyperplasia or papillomatosis in the initial lesion and calcification of that lesion to increase the risk of breast cancer. A marked increase in risk of breast cancer in succeeding birth cohorts was unexpectedly found that could not be explained by temporal changes in any of the other risk factors considered.

Adult↗
PubMed1982

Use of hair dyes and risk of bladder cancer.

The relation between use of hair dyes and risk of bladder cancer was assessed using data from a case-control study of bladder cancer. Incident cases (2982) and general population controls (5782) were interviewed. The overall estimate of relative risk of bladder cancer for users of hair dyes was 1.0 (95%) confidence interval, 0.9 to 1.2) compared to nonusers. No consistent pattern of association was detected between bladder cancer risk and various indices of timing or intensity of exposure to hair dyes. Various explanations of the lack of association are discussed.

Female↗