Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 109 records · Page 6Linked to original sources

PubMed1992

Class II (I-Ad) restricted T-cell recognition of the V3 loop region of HIV-1 gp120.

A CD4+ and gp120-specific T-cell line, and subclone, were established from BALB/c mice following immunization with recombinant gp120, using an adjuvant formulation (alum) acceptable for use in the human. The recognition specificity was determined against a panel of synthetic peptides corresponding to the primary sequence of the HXB2 strain of human immunodeficiency virus (HIV). An epitope was identified, corresponding to amino acid residues 322-341, and a further series of truncated peptides established the minimum determinant to be 327-341. Possible reasons for the immunodominance of the V3 loop, and adjacent regions, for both antibody and T-cell recognition are discussed.

Amino Acid Sequence↗

PubMed1992

Do antigenic drift residues in influenza hemagglutinins of the H3 subtype qualify as contact sites for MHC class II interaction?

We have previously reported that a majority of hemagglutinin-specific and class II (Ak or Ad)-restricted T cell clones, elicited by natural infection with X31 virus (H3N2 subtype), focus on regions of the HA1 subunit that have featured in antigenic drift and exhibit extensive diversity in their ability to discriminate between variant viruses with amino acid substitutions in these sites. The structural basis for the loss of recognition of a major antigenic site, HA1 120-139, was investigated by (i) comparing the effects of amino acid substitutions in mutant hemagglutinins (HA1 129 Gly----Glu; 132 Gln----Glu; 135 Gly----Arg) with the corresponding substitutions in synthetic peptides or (ii) by assessing the effects of single amino acid substitutions (to Ala) in the alpha k chain (residues 50-79) on the ability of Ak transfectants to present peptides. Despite the failure to recognise mutant viruses, mutant peptides were recognised as efficiently as wild-type peptides in association with wild-type Ak. However, the mutant Ak transfectants identified a different set of alpha k residues (positions 56, 65, and 72) as being critical for presentation of mutant peptides. Taken together with our previous findings that defects in antigen presentation of mutant hemagglutinin are reversed by single substitutions in the alpha k chain (residues 56 and 62), it would seem that the antigenic drift residues in mutant hemagglutinins alter the profile of contact sites with class II.

Amino Acid Sequence↗

PubMed1992

Persistence of sterile screwworm (Diptera: Calliphoridae) flies at a release site.

Studies to determine the persistence of released, sterile screwworms, Cochliomyia hominivorax (Coquerel), were conducted in Belize, Central America, in 1987-1988. A total of nine releases were made, each consisting of 4,000 females marked with a fluorescent dust. Previous similar studies with baited fly traps indicated that flies died or dispersed from the release site within 3-4 d. For this study, flies were recaptured at sentinel animals. Recapture rates varied greatly between releases, a result that was not correlated with any weather parameter. The pattern of recapture indicated a sharp drop in the released population after 9-10 d, with a few flies persisting in the release area for up to 3 wk. The results suggest that survival of released sterile flies is comparable with estimated survival rate and life span of wild, native flies.

Animals↗

PubMed1992

Kinetic development and decline of antiscrewworm (Diptera: Calliphoridae) antibodies in serum of infested sheep.

Sheep infested with screwworms, Cochliomyia hominivorax (Coquerel), produced specific serum antibodies detectable by ELISA. Significant antibody levels were found beginning at 1 wk after infestation and persisting for 2 mo, with peak levels at 3 wk after infestation. Mean response values and corresponding larval survivorship were similar over a range of 25 to 200 larvae per individual sheep. Anomalous seropositive responses in some noninfested sheep suggested the possibility of cross-reactivity between antigens of screwworm and those of related myiasigenic blowflies.

Animals↗

PubMed1992

A case-control study of occupational risk factors for laryngeal cancer.

To determine whether specific jobs and occupational exposures are associated with laryngeal cancer lifetime occupational histories from a population-based case-control study in western Washington were examined. The study included 235 cases diagnosed between September 1983 and February 1987, and 547 controls identified by random digit dialing. After controlling for alcohol use, cigarette smoking, age and education, significantly increased risks were found for painters in construction (odds ratio (OR)) = 2.8, (95% confidence interval (95% CI) 1.1-6.9), supervisors and miscellaneous mechanics (OR = 2.3, 95% CI 1.1-4.8), construction workers (OR = 3.4, 95% CI 1.4-8.1), metalworking and plastic working machine operators (OR = 2.6, 95% CI 1.3-4.9) and handlers, and equipment cleaners and labourers (OR = 1.5, 95% CI 1.0-2.2). Allowing for a 10 year induction and latent period did not have a consistent effect on the associations. Potential exposures to asbestos, chromium, nickel, formaldehyde, diesel fumes, and cutting oils were assessed by using a job exposure matrix developed for this study. Three measures of exposure were examined--namely, peak, duration, and an intensity weighted exposure score. No significantly raised risks were seen, although increased risk was suggested among those exposed long term to formaldehyde in jobs with the highest exposures.

Adult↗

PubMed1992

Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate.

The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered.

Animals↗

PubMed1992

Oxidant-evoked release of acetylcholine from enteric neurons of the rat colon.

In the presence of halides, granulocytes generate hypochlorous acid and, subsequently, chlorinated amines (chloramines). These lipophilic, potent reactive oxygen metabolites may contribute to the mucosal pathophysiology associated with inflammatory bowel disease. A common symptom of inflammatory bowel disease is mucosal secretion of fluid and electrolytes, leading to diarrhea. Because acetylcholine (Ach) can stimulate colonic fluid secretion, we determined the effect of monochloramine (NH2Cl) on Ach release by mucosal/submucosal nerves. Mucosa from the rat colon was separated from outer muscle layers and minced before incubation with [14C]choline to label stores of Ach in cholinergic neurons. Release of [14C]Ach was evoked with NH2Cl in the absence and presence of 5-aminosalicylic acid, glutathione, nordihydroguaiarectic acid or the cyclooxygenase inhibitor piroxicam. NH2Cl produced concentration-related increases in [14C] Ach release into the medium; greater than 100% over base line was observed at 0.5 mM. Glutathione inhibited the NH2Cl-evoked release in a concentration-dependent fashion. Release induced by 0.1 mM NH2Cl was abolished by 5-aminosalicylic acid and significantly inhibited by nordihydroguaiarectic acid. Piroxicam also prevented the effect of NH2Cl on release of [14C] Ach. None of these agents alone had any effect on base line [14C]Ach release. Tetrodotoxin (5 microM) did not significantly inhibit the NH2Cl-evoked transmitter release. We conclude that NH2Cl, at concentrations believed to exist in inflamed tissue, causes the release of Ach from mucosal/submucosal nerves primarily through nonspecific neural membrane injury. Endogenous prostaglandins, possibly liberated as a consequence of the injury, may be involved in the Ach release process.

Acetylcholine↗

PubMed1991

Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer.

OBJECTIVE: To identify time trends and factors associated with breast-conserving surgery (BCS) and delivery of postoperative radiation therapy among women with stage I or II breast cancer. DESIGN: Survey. SETTING: Population-based cancer registry in the Seattle-Puget Sound (Wash) region. PARTICIPANTS: The study included 8095 women diagnosed with stage I or II breast cancer (American Joint Committee on Cancer staging criteria) from 1983 through 1989. MAIN OUTCOME MEASURES: Breast-conserving surgery with or without radiation therapy vs mastectomy, and, among women with BCS, a comparison of radiation therapy vs no therapy. RESULTS: In 1985 when results from a US randomized clinical trial of BCS were published, the frequency of BCS peaked (46.3% of stage I; 30.1% of stage II) followed by a return to levels before 1985 for women with stage II breast cancer and a more moderate decline for stage I breast cancer. The likelihood of BCS decreased with increasing age (P less than .001), with stage II disease, and with residence outside the region's major urban center, and it increased with education (P less than .001) or median income (P less than .001) by census tract. The proportion of women who received radiation therapy after BCS decreased with age (P less than .001), was lower for women with stage II than stage I disease, and was lowest in counties without radiation therapy facilities. CONCLUSIONS: Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer as recommended by the National Institutes of Health, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health.

Aged↗

PubMed1991

Hormonal content of combined oral contraceptives in relation to the reduced risk of endometrial carcinoma. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between the strength of the estrogenic and progestational components of combined oral contraceptives and risk of endometrial carcinoma was examined in a multinational hospital-based case-control study comparing 220 cases from 7 countries with 1,537 age- and hospital-matched controls. Oral contraceptives were classified according to their relative content of estrogen and progestin. The risk was not altered in women who used preparations containing high-dose estrogen/low-dose progestin compounds [odds ratio (OR) = 1.10, 95% CI = 0.13-9.96]. In contrast, the risk among users of low-dose estrogen/high-dose progestin oral contraceptives was greatly decreased (OR = 0, 95% CI = 0-1.08). Risks observed for users of high-dose estrogen/high-dose progestin (OR = 0.15, 95% CI = 0.045-0.50) and low-dose estrogen/low-dose progesterone (OR = 0.59, 95% CI = 0.26-1.30) preparations were intermediate between those for users of the 2 other types of preparation. A significantly lower risk was observed for high-dose progestin users than for low-dose users [ratio of odds ratios (ROR) = 0.21, 95% CI = 0.05-0.84]. Although the numbers are small, findings from this study suggest that combined oral contraceptives with varying strengths of estrogen and progestin have different effects on the risk of endometrial carcinoma.

Case-Control Studies↗

PubMed1991

Occupational exposure to electromagnetic fields and breast cancer in men.

Data from a population-based case-control study of breast cancer in men were used to examine the hypothesis that occupational exposure to electromagnetic fields increases the risk of breast cancer. Incident cases (n = 227) diagnosed between 1983 and 1987 were obtained from 10 population-based cancer registries of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Controls (n = 300) were selected by random digit dialing and from Medicare eligibility lists. Exposure status, defined as ever having been employed in a job which has been classified as involving potential exposure to electromagnetic fields, was assigned without knowledge of case/control status. An elevated risk was found for any job with exposure (odds ratio (OR) = 1.8, 95 percent confidence interval (CI) 1.0-3.7), and risk was highest among electricians, telephone linemen, and electric power workers (OR = 6.0, 95 percent CI 1.7-21) and radio and communications workers (OR = 2.9, 95 percent CI 0.8-10). Risk did not vary with duration of exposed employment. The risk was highest among subjects who were first employed in jobs with exposure before the age of 30 years and who were initially exposed at least 30 years prior to diagnosis. These results lend support to the theory that electromagnetic fields may be related to breast cancer in men. The hypothesis warrants evaluation in women.

Adult↗

PubMed1991

Breast cancer in men: aspects of familial aggregation.

Familial aggregation of breast cancer in males was investigated in a population-based case-control study. Cases were ascertained from 10 Surveillance, Epidemiology, and End Results Program registries in the United States between 1983 and 1986. Controls were identified by random-digit dialing and from lists of Medicare recipients. The relative odds of developing breast cancer were similar in men with affected paternal and maternal relatives and in men with affected mothers and sisters. The risk increased with the number of affected relatives. The relative odds of developing breast cancer were greater in men with first-degree relatives who developed their mammary neoplasm before the age of 45 than in men with older first-degree affected relatives; the enhancement of risk in men with an affected sister was greater in those under age 60 than in older men. These results are similar to those observed by others in studies of breast cancer in women.

Breast Neoplasms↗

PubMed1991

A case-control study of oral cancer and pre-diagnostic concentrations of selenium and zinc in nail tissue.

A case-control study of oral cancer was conducted in western Washington state between 1983 and 1987. Cases (n = 379) were identified through a population-based registry, and controls (n = 514) were selected by telephone using random digit dialing. Subjects participated in a personal interview, completed a food-frequency questionnaire, and submitted clippings from the nails of each great toe for the determination of selenium and zinc concentrations. The odds ratio (OR) for low selenium levels in nail tissue (lowest 25% of the distribution compared to the upper 75%) was 1.4 (95% confidence interval (CI) 1.0-2.2). Likewise, the odds ratio for low zinc levels in nails was 1.6 (95% CI 1.0-2.3), but for low dietary zinc was 1.0 (95% CI 0.7-1.7). Men with oral cancer had lower nail selenium levels than did the controls (OR = 1.9), but women with oral cancer did not (OR = 0.6). Individuals 20 to 39 years of age with oral cancer, in particular, were more likely to have lower selenium levels in nail tissue than controls (OR = 16.4). There was a significant interaction between selenium and ascorbic acid levels which could not be explained by cigarette use. Subjects at greatest risk had low levels of both nutrients (OR = 3.8 for smokers and OR = 5.7 for non-smokers). However, since the elements were deposited in the nail matrix close to the date of diagnosis, the differences in the element concentrations between cases and controls may have been a result of the disease. Further etiologic studies of selenium, vitamin intake and oral carcinoma are warranted.

Adult↗

PubMed1991

Structural assignment of novel and immunodominant antigenic sites in the neutralizing antibody response of CBA/Ca mice to influenza hemagglutinin.

Information on the antigenic structure of influenza hemagglutinin (HA) has been deduced previously from sequence analyses of laboratory mutant viruses selected, in vitro, with neutralizing monoclonal antibody (mAb) established exclusively from BALB/c (H-2d) mice; and there has been no attempt to investigate the influence of host genetic background, or natural route of infection, on the protective antibody repertoire. CBA/Ca mice are extremely sensitive to X31 virus infection, and in the present study a structural analysis was made of the antibody repertoire, by direct sequencing of the HA genes of laboratory mutant viruses selected, in ovo with mAb from CBA/Ca mice primed by natural infection with X31 virus at two different infectious doses. Single nucleotide substitutions in the HA genes of mutant viruses identified both novel and immunodominant antigenic sites on the HA1 subunit: a majority of mAbs, from different donors, were of the IgG2a isotype and were specific for HA1 158 Gly. In addition, novel laboratory mutants were obtained containing substitutions in the HA1 subunit that had not been reported previously for H3 subtype viruses, either natural variants or laboratory mutants, at residues: HA1 62 Ile----Arg; HA1 165 Asn----Ser (resulting in the loss of a N-glycosylation site); and HA1 273 Pro----Leu. Our findings suggest that host genetic background and/or a natural route of infection may be significant factors in the selection of different and distinct neutralizing antibody responses to influenza HA and therefore be of some relevance in our further understanding of the immune pressure for antigenic drift, and the immunogenic features of a protective antigen.

Amino Acid Sequence↗

PubMed1991

Risk of breast cancer in relation to use of combined oral contraceptives near the age of menopause. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Data from a multinational, hospital-based, case-control study were analyzed to determine whether use of combined oral contraceptives (OC) around the time of menopause preferentially increases risk of breast cancer. Results show that the relative risk (RR) of breast cancer was increased in women of all ages who had used oral contraceptives within the past year, but not to a greater extent in women near the age of menopause than in younger women. RRs did not increase with duration of OC use after age 45 in either pre- or postmenopausal women. RRs also were not found to be higher in women who were using OCs near the time of either a natural or artificial menopause than in women who used them at other times. This study thus provides no support for the hypothesis that OCs enhance risk of breast cancer by a greater amount when taken around the time of menopause than when taken at other times.

Adult↗

PubMed1991

Oral contraceptives and breast cancer: review of the epidemiologic literature.

Oral contraceptives have caused little or no overall increase in risk of breast cancer in women in developed countries, even in long-term users or after more than two decades since initial exposure. Limited evidence suggests a possible small increase in risk in users of oral contraceptives in developing countries, and further studies of breast cancer and oral contraceptives in low risk populations are warranted. Oral contraceptives may enhance risk of breast cancer in young women with a history of benign breast disease, and this possibility should also be investigated further. Multiple investigations have fairly consistently shown risk of breast cancer in women under age 45 years to be increased slightly in long-term users of oral contraceptives. Further studies should be conducted to elucidate the mechanism of this apparent phenomenon.

Breast Neoplasms↗

PubMed1991

The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.

A hospital-based case-control study was conducted in eight developing and three developed countries to determine whether use of combined oral contraceptives alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of oral contraceptives, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing than developed countries. Both causal and non-causal interpretations of this finding have been offered. No associations were found between oral contraceptives and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas; but the power of this study to detect alterations in risks of these neoplasms in long-term users was low.

Breast Neoplasms↗

PubMed1991

Combined oral contraceptives containing chlormadinone acetate and breast cancer: results of a case-control study.

The main subject of this hospital-based case-control study was the possible relationship between use of combined oral contraceptives (OCs) containing chlormadinone acetate and breast cancer. Analyses were based on data from 490 cases with newly diagnosed breast cancer and 1,223 controls and were separately performed for combined OCs with and without chlormadinone. For either of the combined OCs, risk was not elevated in ever users, did not increase with duration of use and did not change with time since initial exposure or with time since most recent use. However, the relative risk was increased in current users: RR = 1.72 (0.88, 3.36) for combined OCs with chlormadinone and RR = 1.42 (1.01, 2.00) for combined OCs without chlormadinone, which is, however, explained as a screening effect. These results show that chlormadinone as a constituent of combined OCs does not influence breast cancer risk.

Adult↗

PubMed1991

Time-activity budget of adult screwworm behavior (Diptera: Calliphoridae).

A time-activity budget of adult screwworm behavior was determined in an outdoor screened enclosure. Screwworms spent most (75.7%) of their time in the passive behaviors of resting and grooming. The adults spent 9.5% of daytime activity feeding, mainly on flowers or nectaries, but also on animal wound fluids and feces. Adults moving in vegetation preferred walking over flying in both frequency and duration. Flying was a frequent activity, but flights were of short (13.7 s) duration. Courtship, mating, and oviposition constituted less than 1% of a fly's total activity. The unusual behavior characterized as "bubbling" was interpreted as either thermoregulation or a nectar concentration.

Animals↗