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Biomedical subjects

D A Bell

Publications and source records attributed to D A Bell.

At least 163 records · Page 9Linked to original sources

Development of source testing, analytical, and mutagenicity bioassay procedures for evaluating emissions from municipal and hospital waste combustors.

Incineration is currently being used for disposal of about 10% of the solid waste generated in the United States, and this percentage will likely increase as land disposal declines. Siting new incinerators, however, is often controversial because of concerns related to the possibility of adverse health effects and environmental contamination from long-term exposure to stack emissions. Specific concerns relate to the adequacies of a) stack emission testing protocols, b) existing regulations, and c) compliance monitoring and enforcement of regulations. U.S. Environmental Protection Agency laboratories are cooperatively conducting research aimed at developing new testing equipment and procedures that will allow a more comprehensive assessment of the complex mixture of organics that is present in stack emissions. These efforts are directed specifically toward developing source testing equipment and procedures, analytical procedures, and bioassay procedures. The objectives of this study were to field test two types of high-volume source dilution samplers, collect stack samples for use in developing analytical and mutagenicity bioassay procedures, and determine mutagenicity of organics associated with emission particles from two municipal waste combustors and a hospital waste combustor. Data are presented for particle concentrations and emission rates, extractable organic concentrations and emission rates, and Salmonella (Ames) mutagenic potency and emission rates. The mutagenic emission rates and emission factors are compared to other incinerators and combustion sources.

Air Pollutants↗

Adenocarcinoma in situ of the uterine cervix.

OBJECTIVE: To assess the diagnostic accuracy of cervical conization in women with adenocarcinoma in situ and to determine whether a select group of women could be managed by conization alone without hysterectomy. METHODS: We retrospectively reviewed 40 cases of cervical adenocarcinoma in situ diagnosed on cervical conization. RESULTS: Cervical conization revealed adenocarcinoma in situ alone in 15 women. Twenty-five women had adenocarcinoma in situ coexisting with squamous dysplasia (23) or microinvasive squamous cell carcinoma (two). Twenty-two women underwent hysterectomy after cone biopsy. Adenocarcinoma in situ was detected in the hysterectomy specimen in one of 12 women with uninvolved cone margins, versus seven of ten women with involved margins (P = .006); two of these seven women also had foci of invasive adenocarcinoma in the hysterectomy specimen. Conization was the only treatment for 18 selected women with adenocarcinoma in situ and uninvolved margins; all were relapse-free after a median interval of 3 years (range 1.5-5). CONCLUSIONS: Women with cervical adenocarcinoma in situ diagnosed by conization who have positive margins are at high risk of residual adenocarcinoma in situ and moderate risk of occult invasive adenocarcinoma; expectant management is not warranted. However, a cone biopsy with uninvolved margins can reliably guide subsequent therapy. Selected young women who desire preservation of fertility and have uninvolved margins probably can be managed by conization alone, but further study is required to establish the safety of this approach.

Adenocarcinoma↗

Immunohistochemical characterization of ovarian borderline tumors of intestinal and mullerian types.

A panel of monoclonal antibodies (MAbs) including MOv2, MOv8, anti-CA 19-9, and anti-carcinoembryonic antigen (CEA), and a polyclonal antibody against CEA, was applied to three types of ovarian borderline tumors. The tumors included 19 intestinal-type mucinous borderline tumors (IMBTs), 22 endocervical-like mucinous borderline tumors (EMBTs), and 23 mixed-epithelial borderline tumors (MEBTs); the latter two tumors are of mullerian type. Statistically significant differences in the percentage of positive IMBTs compared to the mullerian tumors were seen for anti-CEA and MOv8; strikingly different staining patterns were also seen. IMBTs were more often and more diffusely CEA-positive than were the mullerian tumors; within the mullerian tumors, only one type of cell, the indifferent eosinophilic cell, was consistently CEA positive. The MAbs MOv2, MOv8, and anti-CA 19-9 showed more extensive positivity in the mullerian tumors than in the IMBTs. This study highlights the differences in cell types between IMBTs and these two types of mullerian borderline tumors.

Antibodies, Monoclonal↗

Perineal exposure to talc and ovarian cancer risk.

OBJECTIVE: We sought to determine whether the use of talc in genital hygiene increases the risk for epithelial ovarian cancer. METHODS: We interviewed 235 white women diagnosed with epithelial ovarian cancer between 1984-1987 at ten Boston metropolitan area hospitals and 239 population-based controls of similar race, age, and residence. RESULTS: Overall, 49% of cases and 39% of controls reported exposure to talc, via direct application to the perineum or to undergarments, sanitary napkins, or diaphragms, which yielded a 1.5 odds ratio (OR) for ovarian cancer (95% confidence interval [CI] 1.0-2.1). Among women with perineal exposure to talc, the risk was significantly elevated in the subgroups of women who applied it: 1) directly as a body powder (OR 1.7, 95% CI 1.1-2.7), 2) on a daily basis (OR 1.8, 95% CI 1.1-3.0), and 3) for more than 10 years (OR 1.6, 95% CI 1.0-2.7). The greatest ovarian cancer risk associated with perineal talc use was observed in the subgroup of women estimated to have made more than 10,000 applications during years when they were ovulating and had an intact genital tract (OR 2.8, 95% CI 1.4-5.4); however, this exposure was found in only 14% of the women with ovarian cancer. CONCLUSIONS: These data support the concept that a life-time pattern of perineal talc use may increase the risk for epithelial ovarian cancer but is unlikely to be the etiology for the majority of epithelial ovarian cancers.

Adult↗

Endocervical glandular atypia in Papanicolaou smears.

The importance of endocervical glandular atypia in a cervicovaginal Papanicolaou smear has not been fully investigated. Between July 1988 and June 1989, 21,930 cervicovaginal smears were reviewed by the Massachusetts General Hospital Cytopathology Laboratory. One hundred smears with endocervical atypia were identified, an incidence of 0.46%. Follow-up was available on 63 cases: Seven had negative follow-up smears for at least 2 years, 15 had negative biopsies, seven had endocervical polyps, two had endometrial hyperplasia, eight had mild dysplasia, five had moderate dysplasia, six had severe dysplasia, six had squamous carcinoma in situ, five had adenocarcinoma in situ, and two had invasive adenocarcinoma. Twelve women's smears showed endocervical atypia with features suggestive of reactive atypia; three of these had dysplasia. Twenty-six (41%) of the Papanicolaou smears with endocervical atypia had coexisting squamous atypia or dysplasia. We conclude that endocervical atypia may be associated with substantial cervical disease in as many as half of cases.

Adult↗

The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk.

The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years.

Adult↗

General occurrence of binding to acetylcholinesterase-substrate complex in noncompetitive inhibition and in inhibition by substrate.

To assess the relative importance of binding to enzyme-substrate complex (E.S) and to acetylenzyme (EA), noncompetitive inhibition has been studied in hydrolysis by acetylcholinesterase (AcChE) of cationic and uncharged substrates - acetylcholine (AcCh), 3,3-dimethylbutyl acetate, n-butyl acetate, 2-(methylammonio)ethyl acetate, 2- (N,N-diethyl-N-n-butylammonio)ethyl acetate (DEBAAc) and 2-(methylsulfonyl)ethyl acetate. For the N-trimethyl quaternary ions related to AcCh, tetramethylammonium ion, choline and choline ethyl ether, noncompetitive inhibition (Ki(nonc) is more favorable with the slower substrates than with AcCh, i.e., when E.S greater than EA, and is attributed to formation of enzyme-substrate-inhibitor complexes, E.S.I'. Noncompetitive inhibition by tetraethyl-, tert-butyl- and isopropylammonium ions, and acetamidocholine and its lower dimethyl analogue, is also attributed to E.S.I' complexes. Peripheral binding of these inhibitors decreases acylation more than deacylation. Some tertiary dimethylamonio ions have more favorable Ki(nonc) values with AcCh, decreasing deacylation more than acylation. The substrate DEBAAc is a more effective noncompetitive than competitive inhibitor in hydrolysis of AcCh, indicating that it binds more strongly in a peripheral site than in the active site of the free enzyme. In its hydrolysis by AcChE, it acts as its own noncompetitive inhibitor, by this non-productive binding. Formation of E.S.I' complexes is a general characteristic of hydrolysis by AcChE and decrease in rates at high concentrations of AcCh and related substrates is attributed to peripheral regulatory site binding, formation of E.S.S' complexes, rather than to binding to the acetylenzyme.

Acetates↗

Detection of DNA sequence polymorphisms in carcinogen metabolism genes by polymerase chain reaction.

The glutathione transferase mu gene (GST1) and the debrisoquine hydroxylase gene (CYP2D6) are known to be polymorphic in the human population and have been associated with increased susceptibility to cancer. Smokers with low lymphocyte GST mu activity are at higher risk for lung cancer, while low debrisoquine hydroxylase activity has been correlated with lower risk for lung and bladder cancer. Phenotypic characterization of these polymorphisms by lymphocyte enzyme activity (GST) and urine metabolite ratios (debrisoquine) is cumbersome for population studies. Recent cloning and sequencing of the mutant alleles of these genes has allowed genotyping via the polymerase chain reaction (PCR). Advantages of PCR approaches are speed, technical simplicity, and minimal sample requirements. This article reviews the PCR-based methods for detection of genetic polymorphisms in human cancer susceptibility genes.

Chromosome Deletion↗

The spontaneous apoptotic cell death of normal human lymphocytes in vitro: the release of, and immunoproliferative response to, nucleosomes in vitro.

Nucleosomes released spontaneously in short-term culture from murine spleen cells have a significant immunoproliferative effect in vitro, including the stimulation of anti-DNA antibody responses. The present studies show that during short-term cultures, tonsil lymphoid cells also undergo spontaneous apoptosis revealed morphologically (electron microscopy) by the appearance of changes in nuclear chromatin, typical of apoptosis and similar to morphologic changes of apoptosis in cultured normal splenic lymphocytes. This process is followed by the release, in the greater than 30-kDa cell free supernatant fraction, of core histones (H2A, H2B, H3, H4) and low molecular weight DNA (approx 160 bp) constituents of nucleosomes. The greater than 30-kDa tonsil lymphocyte cell-free supernatant material containing the constituents of core nucleosomes, as well as the greater than 30-kDa supernatant fractions of tonsil cell lysates harvested at the same time, had a significant immunoproliferative effect on human or murine lymphocytes, increasing both DNA and immunoglobulin synthesis (protein A plaque-forming cells). Thus the release of immunoproliferative nucleosomes form dying human lymphoid cells provides an autocrine lymphocyte stimulatory network which may be important in immunoproliferative disorders and in normal cell turnover. Apoptosis in vivo may also provide a potential source for the circulating nucleosomal DNA identified in plasma in some systemic lupus erythematosus patients as well as contributing to increased polyclonal B lymphocyte stimulation and autoantibody responses in this disorder.

Cell Survival↗

DNA sequence analysis of revertants of the hisD3052 allele of Salmonella typhimurium TA98 using the polymerase chain reaction and direct sequencing: application to 1-nitropyrene-induced revertants.

We have used the polymerase chain reaction (PCR) to speed the DNA sequence analysis of revertants of Salmonella typhimurium TA98. Briefly, a crude DNA extract from a single colony was prepared and used in an asymmetric PCR to amplify a 328-bp fragment containing the hisD3052 mutation approximately in the center. Following ultrafiltration, the ssDNA was sequenced using an end-labeled probe and dideoxy sequencing. The most frequent mutation among the revertants was a -2 deletion of GC or CG within the sequence CGCGCGCG, which is upstream of the hisD3052 mutation. This deletion occurred in 38% (6/16) of the spontaneous (-S9) revertants and in 94% (15/16) of a set of 1-nitropyrene-induced revertants. Other mutations, mostly deletions but also some complex mutations (i.e., single mutational events involving a combination of insertions, deletions, and substitutions), occurred within quasipalindromic regions of DNA. Possible mutational mechanisms are discussed, and the results with 1-NP are compared to those obtained in other systems.

Base Sequence↗

Mucinous adenofibromas of the ovary. A report of 10 cases.

Mucinous epithelium is the most uncommon type identified in ovarian adenofibromas. Because of the rarity of mucinous adenofibromas and the presence of cytologic atypia in some, these neoplasms may be mistaken for low-grade metastatic adenocarcinoma. The clinicopathologic features of 10 mucinous adenofibromas are reviewed. They occurred in women 24 to 76 (mean, 51) years of age, were unilateral, and ranged in diameter from 1 to 25 cm. Seven tumors were classified as benign, containing glands lined by a single layer of mucin-containing columnar cells. Three tumors that contained crowded glands lined by mucin-containing cells with mild to moderate nuclear atypia, nuclear stratification of up to three cells in thickness, and focal tufting were classified as benign with epithelial atypia. Most women had a hysterectomy and bilateral salpingo-oophorectomy. Follow-up information was available on six women, who were alive and well from 6 to 126 (mean 41) months after diagnosis. The identification of mucinous glands in typical fibromatous stroma should allow the distinction of these benign neoplasms from metastatic carcinomas.

Adenofibroma↗

Application of DNA flow cytometry from paraffin-embedded tissue to the diagnosis of mycosis fungoides.

The distinction of mycosis fungoides from benign inflammatory lesions is sometimes difficult by conventional histological techniques. Aneuploidy, a feature often associated with malignant tumors, can be assessed even in tissue routinely processed in paraffin using the flow cytometric technique of Hedley and associates. In many tumor systems, there are significant diploid clones. We have evaluated the flow cytometric DNA ploidy of paraffin-embedded tissue in the diagnosis and prognosis of mycosis fungoides (MF). We studied 22 cases of MF and 10 control cases of inflammatory skin lesions with epidermal involvement. Aneuploidy was found in 27% of the MF cases, but in none of the controls (ED). Aneuploid features were seen in 23% of tissues from early stage disease. Aneuploidy did not correlate with atypia, epidermotropism, or number of mitoses. There was a trend towards showing adverse outcome in those patients with aneuploid lesions. The detection of aneuploidy might be helpful for early diagnosis of MF.

Aneuploidy↗

Cerebral ischemic events associated with endocarditis, retinal vascular disease, and lupus anticoagulant.

PURPOSE: A group of young patients presenting with cerebral ischemic events, endocardial lesions, and lupus anticoagulant is described in order to highlight the common clinical laboratory features. PATIENTS AND METHODS: Fourteen consecutive patients (10 females, age range 17 to 53 years [mean 38 years]) at onset of symptoms of cerebral ischemia who had evidence of the lupus anticoagulant syndrome and were being followed prospectively are reviewed. All patients had abnormal phospholipid-dependent coagulation test results, and most had anticardiolipin antibody at the time of presentation. Three of 14 had four or more American Rheumatism Association criteria for definite systemic lupus erythematosus and the remaining patients were considered to have primary lupus anticoagulant syndrome. RESULTS: The common features among these patients included at least one cerebral ischemic event at presentation (stroke or transient ischemic attack), or recurrent episodes suggesting cerebral ischemia (amaurosis fugax, recurrent severe migraine headaches), livedo reticularis, endocardial valvular lesions noted on echocardiography (11 mitral, two aortic valve) that were often associated with discrete vegetations, retinal vascular lesions, and computed tomographic/magnetic resonance imaging scanning or angiographic evidence of multiple cerebral infarction. Venous thromboembolic events were uncommon (three of 14). Common laboratory studies included thrombocytopenia (10 of 14), positive direct Coombs' test result (11 of 14), and hypocomplementemia (11 of 14). Follow-up after initial treatment with either salicylates or anticoagulant therapy (warfarin) for up to 10 years indicated that while many patients had recurrent symptoms suggesting cerebral ischemia, major stroke syndromes did not recur nor new episodes emerge. CONCLUSION: The combination of multiple cerebral ischemic lesions and endocardial lesions, including valvular vegetations, suggests that these cerebral ischemic events represent cerebral emboli, and that these cerebral embolic events originate from vegetative lesions on the mitral or, less commonly, aortic valve, in association with lupus anticoagulant.

Adolescent↗

Aneuploidy in pancreatic insulinomas does not predict malignancy.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas.

Adolescent↗

Pathology of gynecologic malignancies.

This review encompasses advances in the pathology of female genital tract tumors that have been deemed to have clinical significance. A number of newly described neoplasms are discussed as are the results of analyses of large series of cases of previously described tumors. Recent revision in terminology and the application of newer techniques for evaluating neoplasms, such as flow cytometry, are also briefly reviewed.

Female↗