Biomedical subjects

W R Welch

Publications and source records attributed to W R Welch.

At least 73 records · Page 4Linked to original sources

PubMed1986

Lymphocyte dysfunction in autoimmune oophoritis. Resumption of menses with corticosteroids.

In a 32-year-old woman with secondary amenorrhea and biopsy-proven oophoritis, the circulating T lymphocytes were examined utilizing monoclonal antibody L243 to the nonpolymorphic region of the Ia antigen. The percentage of peripheral T cells expressing the Ia "immune-associated' antigen was 5.6 percent (normal 3 percent or less). With corticosteroid therapy, the percentage decreased to 2 percent and menses resumed after secondary amenorrhea of two years' duration. Following cessation of steroid administration, the percentage of Ia-positive T cells rose to 7.0 percent and secondary amenorrhea redeveloped in the patient. After corticosteroid therapy was reinstituted, menses resumed and the percentage of Ia-positive T cells fell to normal. This report represents additional new evidence of immune dysfunction in patients with "autoimmune" oophoritis.

Adult↗

PubMed1985

Pathology of colposcopic findings in 2635 diethylstilbestrol-exposed young women.

An analysis of 6055 colposcopically directed biopsy specimens from 2635 diethylstilbestrol (DES)-exposed women and 445 biopsy specimens from 277 nonexposed women was undertaken to correlate microscopic findings with colposcopic patterns. All examinations were performed using a standardized protocol which required that each participant have colposcopy, cytologic smears, and biopsy of abnormal colposcopic lesions. The findings of colposcopic "columnar epithelium, gland openings, and Nabothian cysts" correlated most often with glandular epithelium in the biopsy specimen. "White epithelium," which includes three related colposcopic patterns, mosaicism, punctation, and white epithelium, was associated most frequently (82-93% of cases) with squamous metaplasia, but occasionally with dysplasia and carcinoma in situ (CIS)(0-6%). The presence of dysplasia or CIS in any individual biopsy specimen occurred most frequently with the observation of higher graded lesions by colposcopy or a prior diagnosis of dysplasia.

Carcinoma in Situ↗

PubMed1984

Atypical vaginal adenosis and cervical ectropion. Association with clear cell adenocarcinoma in diethylstilbestrol-exposed offspring.

Knowledge of the evolution of clear cell adenocarcinomas of the vagina and cervix in diethylstilbestrol-exposed progeny has remained elusive despite the known topographical association of these tumors with the tuboendometrial form of vaginal adenosis and cervical ectropion. Twenty radical hysterectomy or radical hysterectomy and vaginectomy specimens of clear cell adenocarcinoma of the vagina or cervix were serially blocked in toto; tuboendometrial epithelium was found in the vagina in 19 (95%) of the cases, usually in greatest concentration at the margin of the tumor, particularly inferiorly. Foci of atypical tuboendometrial epithelium were identified in 16 (80%) of the cases, almost always immediately adjacent to the tumor. Twenty-five of a second group of 47 specimens in which only substantial portions of the vagina or cervix adjacent to a clear cell adenocarcinoma were available for examination also had foci of atypical tuboendometrial epithelium. The frequency with which atypical tuboendometrial glands in the vagina and cervix were associated with the carcinomas and the proximity of the former to the latter provide strong evidence that atypical vaginal adenosis and atypical cervical ectropion of the tuboendometrial type are precursors of clear cell adenocarcinoma.

Cervix Uteri↗

PubMed1984

Dietary animal fat in relation to ovarian cancer risk.

Food and beverage frequency questionnaires were administered to 215 white women with epithelial ovarian cancer and to 215 control women matched by age, race, and residence. Women with ovarian cancer favored foods higher in animal fats and consumed significantly greater amounts of animal fat and significantly less vegetable fat compared with control subjects. Adjusted for potential confounding due to differences between case and control subjects in weight and parity, there was a significant trend for increasing risk for ovarian cancer with increasing animal fat consumption. No major differences were noted between patients and control subjects in coffee, alcohol, and tobacco use. Dietary factors may partially explain variation in the international incidence of this disease and suggest a new pathway for its etiology.

Alcohol Drinking↗

PubMed1983

Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms.

Expression of histocompatibility antigens and the intensity of inflammatory cellular infiltrate were evaluated in frozen tissue sections from 70 human ovarian tumors and six normal ovaries using monoclonal antibodies and an avidin-biotin immunoperoxidase technique. In the normal human ovary, surface epithelial cells, mature granulosa cells and lutein cells reacted with anti-HLA-A,B,C (HLA) and beta2-microglobulin antibodies but not with anti-Ia (Ia-like, HLA-DR). Stromal cells and granulosa cells of the primordial follicles did not react with any of the antibodies. Among the neoplasms examined, all benign epithelial tumors, 86% of borderline an 81% of malignant epithelial tumors reacted with anti-HLA and/or beta2-microglobulin antibodies. HLA-negative epithelial tumors were of serous or endometrioid types. Although Ia was not found in normal ovarian surface epithelium, the antigen could be detected in 44% of benign, and 43% of borderline and malignant epithelial ovarian tumors. Mononuclear cellular infiltrate was generally scarce in ovarian tumors and consisted mainly of T cells. Malignant epithelial tumors contained significantly more T cells than did benign tumors. More T cells were observed in HLA-positive ovarian tumors than in HLA-negative neoplasms, but the difference did not achieve statistical significance. No correlation could be found between Ia expression and the intensity of T-cell infiltrate. Significantly more T8 and Leu-3a-positive cells were found in the tumor stroma than amongst neoplastic cells. HNK-I-positive natural killer cells, OK-MI-positive macrophages and BI-positive B lymphocytes were rarely encountered either in the tumor stroma or between adjacent tumor cells.

Antibodies, Monoclonal↗

PubMed1983

Mumps, menarche, menopause, and ovarian cancer.

Clinical history of mumps during childhood, age at menarche, and age at natural menopause were obtained in 119 postmenopausal women with ovarian cancer and 109 postmenopausal control subjects from the general population. Case subjects differed significantly from control subjects in being less certain whether they had had mumps and in being less likely to recall the age at infection. In both groups, a significant inverse correlation was observed between age at menarche and menopause in subjects with a positive clinical history for mumps but not in subjects with a negative clinical history for mumps. The correlation was strongest in case subjects who said they had had mumps, especially those who were nulliparous. We speculate that the mumps virus may be a determinant of reproductive span and, through its potential to cause a depletion of oocytes, increase the risk for ovarian cancer.

Age Factors↗

PubMed1983

Nuclear DNA content of clear cell adenocarcinoma of the vagina and cervix and its relationship to prognosis.

A study was performed to determine if ploidy levels of nuclear DNA content could be used as a prognostic index of the biologic behavior of clear cell adenocarcinoma of the vagina and cervix in young females. Forty tumors were examined. Four patterns of nuclear DNA distribution were identified: (1) peridiploid stem cell lines (2N to 3N); (2) peritetraploid stem cell lines (3N to 5N); (3) hypertetraploid stem cell lines (greater than 5N); and (4) highly aneuploid without detectable stem cell lines. Tumors having peridiploid and peritetraploid stem cell lines (low ploidy group) were most often clinical Stage I or II (87%) and were in general associated with a favorable prognosis. Tumors having hypertetraploid stem cell lines and highly aneuploid distribution (high ploidy group) were usually clinical Stage III or IV (65%). Clinically advanced tumors (Stage III or IV) had poor prognosis irrespective of ploidy level. Among the clinical Stage I and II tumors, the low ploidy group had a slightly better prognosis than the high ploidy group. This difference, however, was not statistically significant.

Adenocarcinoma↗

PubMed1983

Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid, and clear cell types.

A murine monoclonal antibody, OC125, reacts with a surface component of ovarian tumor cells from humans, but fails to react with normal adult ovarian cells. The spectrum of reactivity of OC125 in ovarian tumors from humans was defined by testing cryostat tissue sections from 60 selected ovarian tumors by indirect immunofluorescence. OC125 stained 7/7 benign, and borderline serous ovarian tumors, 19/23 (83%) serous adenocarcinomas, 2/2 mixed serous and endometrioid carcinomas, 2/3 endometrioid carcinomas, 1/4 clear cell carcinomas, and 2/2 undifferentiated carcinomas. No reactivity was found in eight mucinous ovarian tumors or any of the other 11 epithelial sex cord, germ cell, on hematopoietic tumors tested. In neoplastic cysts, papillae, and glands, the staining was most intense on the luminal surface or in subjacent cytoplasm. Cells in solid sheets also showed peripheral staining. Within a reactive tumor, both negative and positive cells could be found, intimately intermixed. There were no differences in these staining patterns between tissues from primary and metastatic sites. The expression of the OC125 antigen was not related to the degree of malignancy as judged by pathologic criteria. Although mucinous tumors lacked reactivity with OC125, seven of eight mucinous adenomas and adenocarcinomas bound a monoclonal antibody against carcinoembryonic antigen (CEA). Thus, OC125 recognizes a common antigen in some but not all ovarian tumors of serous, clear cell, endometrioid, or undifferentiated type. OC125 may prove useful in the pathologic and cytologic identification of certain types of ovarian tumor cells. Its lack of reactivity with mucinous tumors suggests these belong in a distinct subgroup of ovarian epithelial tumors.

Adenocarcinoma↗

PubMed1983

Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125.

OC125, a murine monoclonal antibody, recognizes an antigenic determinant (CA125) that is associated with greater than 80% of epithelial ovarian neoplasms of serous, endometrioid, clear cell, and undifferentiated types. In the present report, a sensitive biotin-avidin immunoperoxidase technique was used to determine reactivity of OC125 with normal adult and fetal tissues, as well as with neoplasms of nonovarian origin. In fetal tissues, the antibody reacted with amnion and with derivatives of the coelomic epithelium, i.e., the müllerian epithelium and the lining cells of the peritoneum, pleura, and pericardium. Among adult tissues, OC125 reacted with the epithelium of fallopian tubes, endometrium, and endocervix. The CA125 determinant was also detected on mesothelial cells in the adult pleura, pericardium, and peritoneum, particularly in areas of inflammation and adhesion. Curiously, the surface epithelium of normal fetal and adult ovaries, thought to be derived from coelomic epithelium, did not express the determinant, except in inclusion cysts, areas of metaplasia, and papillary excrescences. Of neoplastic tissues of nonovarian origin, OC125 reacted consistently only with adenocarcinomas of the endocervix, endometrium, and fallopian tube, and with mesotheliomas. Only seven of 64 nongynecological tumors tested reacted with OC125. Thus, OC125 detects a differentiation antigen shared by fetal coelomic epithelium and its derivatives in the fetus and the adult. Apparently, this antigen disappears early in the course of formation of the ovarian epithelium and is reexpressed in certain reactive and neoplastic lesions, a process that could be termed "molecular metaplasia."

Adenocarcinoma↗

PubMed1983

Determinants of ovarian cancer risk. I. Reproductive experiences and family history.

Reproductive experiences and family history were assessed in 215 white females with epithelial ovarian cancer and in 215 control women matched by age, race, and residence. Pregnancy exerted a strong protective effect against ovarian cancer, which increased with the number of live-born children. After adjustment for parity, an effect of age at first live birth and breast-feeding was not apparent. Menstrual events did not differ significantly between cases and controls, although cases were more likely to have had an earlier menopause and less likely to have had a surgical menopause. Women with ovarian cancer had more frequently used menopausal hormones in cyclic fashion compared to controls. Regarding family history, women with ovarian cancer more frequently reported consanguinity in their ancestry and a highly frequency of primary relatives with cancer of the colon, lung, ovary, and prostate gland.

Consanguinity↗

PubMed1983

Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis.

Entrapment of surface epithelium within the ovarian stroma was proposed as an initial event in the pathogenesis of cystadenocarcinoma of the ovary. Subsequent events, including differentiation, proliferation, and eventual malignant transformation of the entrapped epithelium, may occur as a consequence of stimulation by estrogen or estrogen precursors. These events were more likely when the steroid producing stroma itself had been stimulated by high gonadotropins. Animal experiments suggested that gonadotropin excess and stromal stimulation may result by disturbing normal feedback inhibition between ovary and pituitary or by destroying ovarian follicles. By analogy, in humans, a number of common chemicals and drugs may increase gonadotropins by enhancing estrogen degradation in the liver or by directly stimulating production by the pituitary. Elevated gonadotropins may also result via mechanisms that cause primary ovarian failure including pelvic irradiation, exposure to chemicals or metabolites toxic to follicles, or ovarian infections such as mumps.

Cell Differentiation↗

PubMed1982

Factors affecting the association of oral contraceptives and ovarian cancer.

We investigated the relation between epithelial ovarian cancer and the use of oral contraceptives in a case-control study of 144 white women under the age of 60 who had ovarian cancer and 139 white women under 60 who were selected from the general population. We observed a decreased risk for ovarian cancer associated with the use of oral contraceptives in subjects 40 through 59 years of age at the time of the study. The relative risk, adjusted for parity, was 0.11, with 95 per cent confidence limits of 0.04 to 0.33. In contrast to the findings in older women, a decreased risk for ovarian cancer associated with oral-contraceptive use was not found in women under 40. In this group, the adjusted relative risk associated with any use of oral contraceptives was 1.98, with 95 per cent confidence limits of 0.74 to 5.27. The lowest risk for ovarian cancer associated with the use of oral contraceptives was observed in older parous subjects and in women who had discontinued use more than 10 years previously.

Adult↗

PubMed1982

Ovarian sex cord tumor with annular tubules: review of 74 cases including 27 with Peutz-Jeghers syndrome and four with adenoma malignum of the cervix.

The sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian neoplasm the predominant component of which has morphologic features intermediate between those of the granulosa cell tumor and those of the Sertoli cell tumor; focal differentiation into either granulosa cell or Sertoli cell tumor may occur. Of the 74 cases that form the basis of this investigation 27 were associated with the Peutz-Jeghers syndrome; these tumors were all benign and were typically multifocal, bilateral, very small or even microscopical in size and calcified. Twelve of the 27 patients had symptoms suggestive of hyperestrinism attributable to the SCTAT; menstrual irregularity had occurred in eleven cases and postmenopausal bleeding in one. Four of the 27 patients had "adenoma malignum" of the cervix and two of them died of it. The 47 tumors from patients without evidence of the Peutz-Jeghers syndrome were unilateral and usually large. Twenty-five of them were accompanied by symptoms suggestive of hyperestrinism, such as menstrual irregularity, postmenopausal bleeding or sexual precocity; seven were malignant and four of these were fatal.

Adenocarcinoma↗

PubMed1982

Ovarian cancer and talc: a case-control study.

Opportunities for genital exposure to talc were assessed in 215 white females with epithelial ovarian cancers and in 215 control women from the general population matched by age, race, and residence. Ninety-two (42.8%) cases regularly used talc either as a dusting powder on the perineum or on sanitary napkins compared with 61 (28.4%) controls. Adjusted for parity and menopausal status, this difference yielded a relative risk of 1.92 (P less than 0.003) for ovarian cancer associated with these practices. Women who had regularly engaged in both practices had an adjusted relative risk of 3.28 (P less than 0.001) compared to women with neither exposure. This provides some support for an association between talc and ovarian cancer hypothesized because of the similarity of ovarian cancer to mesotheliomas and the chemical relation of talc to asbestos, a known cause of mesotheliomas. The authors also investigated opportunities for potential talc exposure from rubber products such as condoms or diaphragms or from pelvic surgery. No significant differences were noted between cases and controls in these exposures, although the intensity of talc exposure from these sources was likely affected by variables not assessed in this study.

Adolescent↗

PubMed1982

Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: perspective derived from a clinicopathologic analysis of twenty-one cases.

The clinical and pathologic aspects of 21 cases of mixed gonadal dysgenesis (MGD) were studied. The gonads in 15 patients consisted of a macroscopic testis and a streak gonad; six patients had variants, including two with bilateral testes and four with bilateral streak gonads or tumors. Functionally, the gonads were incompetent. Testes 1) failed to completely inhibit müllerian development, 2) failed to support full differentiation of mesonephric duct structures, 3) failed to adequately masculinize development of the external genitalia, or 4) often failed to mediate their own descent, resulting in asymmetry of the internal and external genitalia. None of the streak gonads mediated normal female adolescent development or fertility. Microscopic examination revealed that every gonad, regardless of its gross appearance, was morphologically abnormal. Although gonads with seminiferous tubules usually developed to a moderately advanced state, macroscopically resembling testes, the hilar zone remained architecturally disorganized; the cortex invariably lacked more than a rudimentary tunica albuginea or exhibited partial ovarian differentiation, sometimes even with a rare primordial follicle. Over time, the seminiferous tubules atrophied and hyalinized. Gonads that grossly resembled streak gonads were observed microscopically to be composed of a stroma resembling that of normal ovarian cortex. In patients more than several years of age, the entire complement of germ cells in streak gonads disappeared. It is suggested that patients with MGD be raised as females. Early removal of gonads will prevent the development of gonadoblastoma and dysgerminoma. If the uterus is retained and the patient is subsequently given exogenous estrogen, care should be taken to detect early any signs of the development of endometrial carcinoma or its precursor, to which these patients may be prone.

Adolescent↗

PubMed1982

Topographic relation of cervical ectropion and vaginal adenosis to clear cell adenocarcinoma.

Twenty specimens of uterus and vagina removed because of clear cell adenocarcinoma of the cervix or vagina in women exposed prenatally to diethylstilbestrol were serially blocked and sectioned to study the topographic relation between the carcinoma and the cervical ectropion and vaginal adenosis. Three tumors were cervical; 17 were vaginal. Iodine staining performed on 8 specimens indicated that the carcinoma developed consistently just above the distal limit of the cervical or vaginal surface that failed to stain with iodine, a location that usually corresponds to the distal limit of abnormality visible by colposcopic examination. Microscopic examination disclosed the presence of both cervical ectropion and vaginal adenosis in all the specimens. Mucinous glands were abundant above the tumor. In 18 of the 20 cases, tuboendometrial glands were intimately related to the carcinoma, either surrounding it or abutting its inferior border. These data, in addition to other evidence, suggest that tuboendometrial epithelium, whether in the ectocervix or vagina, provides the bed from which clear cell adenocarcinoma develops.

Adenocarcinoma↗

PubMed1981

Trends in the incidence of endometrioid and clear cell cancers of the ovary in the United States.

An increase in reported incidence of endometrioid and clear cell cancers of the ovary occurred in the United States during the 1970s, while no change occurred in the overall incidence of ovarian cancer. The authors can not rule out that this was due to a shift in the criteria for histologic classification or improved coding, although these seem unlikely to account entirely for the change. In the four areas where the trend for endometrioid and clear cell cancers of the ovary was examined, the per cent increases in their occurrence were correlated with the per cent increases in the occurrence of carcinoma of the uterine corpus. The concomitant trends and the biologic similarities between these histologic types of ovarian cancer and the uterine cancers suggest that common etiologic factors may be involved. The role of postmenopausal estrogen use in the etiology of ovarian cancer must be clarified by further epidemiologic studies, but such studies should take tumor histology into consideration.

Adenocarcinoma↗

PubMed1980

Ultrastructure of 16 cases of clear cell adenocarcinoma of the vagina and cervix in young women.

Sixteen cases of clear cell adenocarcinoma of the cervix and vagina in young women were studied by electron microscopy and the observations were compared with the light microscopic appearance. Ultrastructurally, the neoplastic cells were found to be of the same basic type, regardless of whether light microscopy disclosed a solid or tubulocystic tumor pattern, and whether the cells were clear, hobnail, flat or of a nonspecific müllerian appearance. Cytoplasmic glycogen and short, blunt, surface villi were the outstanding features. Less consistent findings included prominent Golgi apparatuses and numerous mitochondria. The fine structural characteristics were similar to those reported for clear cell adenocarcinoma of the endometrium and ovary in older women. This study disclosed no difference between 14 tumors that arose in patients with confirmed histories of prenatal exposure to diethylstilbestrol (DES) or dienestrol, and reported cases of clear cell carcinoma in which there were no histories of such exposure. No specific ultrastructural features could be identified as prognostic indices for the neoplasms.

Adenocarcinoma↗