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K S McCarty

Publications and source records attributed to K S McCarty.

At least 55 records · Page 3Linked to original sources
PubMed1986

Use of monoclonal antiestrogen receptor antibody to evaluate estrogen receptor content in fine needle aspiration breast biopsies.

A monoclonal antibody prepared against estrogen receptor has been shown to be highly specific and sensitive for the detection and quantification of estrogen receptor in human breast lesions using immunohistochemical methods. A semiquantitative relationship has been shown between the intensity of staining and biochemical receptor analysis. To evaluate the usefulness of this technique in fine needle aspiration biopsies, 41 cases of breast cancer were studied. Nuclear localization of receptor antibody PAP complex was observed. Comparison of the immunocytochemical analysis of the aspiration cytologic specimens to the biochemical analysis of the excised tumor mass revealed a sensitivity and specificity of 80% and 89%, respectively. There was a significant semiquantitative correlation between the methods. These results extend the observation that antireceptor monoclonal antibody in immunohistochemical analysis is an effective tool in the evaluation of estrogen receptor content in human breast lesions and with careful specimen handling and proper controls may be extended to the evaluation of fine needle aspiration biopsies.

Antibodies, Monoclonal↗
PubMed1986

Association between cutaneous occlusive vascular disease, cigarette smoking, and skin slough after rhytidectomy.

This prospective study attempted to determine if nonreversible occlusive vascular changes in the skin contribute to skin slough after rhytidectomy. The dermal microvasculature from 83 consecutive rhytidectomies was evaluated for intimal proliferation and/or hyalin sclerosis. Occlusive vascular disease increased progressively with age in all patients, but smokers and ex-smokers had significantly greater involvement than nonsmokers at any given age (p = 0.03). Severe occlusive vascular disease and skin slough were associated (p = 0.02), and there was a strong trend toward an association between active smoking and skin slough (p = 0.06). Among smokers, there was a significant relationship between skin slough and failure to abstain from smoking postoperatively (p = 0.006). We conclude that with aging, nonreversible occlusive changes develop in the dermal microvasculature. These changes appear to be accelerated by cigarette smoking. Our data, however, show that these nonreversible occlusive vascular changes by themselves do not completely account for the occurrence of skin slough after rhytidectomy.

Adult↗
PubMed1986

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Antibodies, Monoclonal↗
PubMed1986

Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody.

Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. In all cases, H222 localized in the nucleus of target cells. A significant quantitative relationship was shown between histological score (H-Score) and the biochemical analysis of ER content in tissue homogenates (r = 0.65, P = 0.00001). Excellent sensitivity (92%) and specificity (93%) were observed for the comparison of H-Score to the biochemical assay. Significant ER localization was present in stromal and myometrial elements, component H-Score of which correlated weakly with component H-Scores of malignant epithelial elements. Divergent receptor localization in stromal and myometrial versus malignant epithelial elements suggests that biochemical assays of endometrial carcinoma specimens may not reflect cancer-relevant receptor content. The data presented here suggest that the immunoassay of ER using H222 monoclonal antibody provides additional histochemical information to complement conventional analyses of endometrial adenocarcinomas.

Adenocarcinoma↗
PubMed1985

Histologic control of biochemical steroid receptor analysis in endometrial carcinomas.

Histologic review of 422 specimens from endometrial carcinoma submitted for biochemical cytosol estrogen and progesterone receptor analysis revealed that 16 (4.0%) contained no evidence of carcinoma on permanent histologic sections. An additional 11 (2.5%) contained focal carcinomas on permanent sections but had no evidence of malignancy in frozen sections of the tissue submitted for receptor analyses. Despite the paucity or even absence of malignancy, many of these specimens had significant cytoplasmic estrogen and progesterone receptors derived from endometrial and myometrial tissues. Rigorous histologic control of specimens from endometrial carcinomas submitted for biochemical steroid receptor analyses is necessary to establish valid clinical and histologic associations of steroid receptor content.

Cytosol↗
PubMed1985

Influence of cytoplasmic steroid receptor content on prognosis of early stage endometrial carcinoma.

The clinicopathologic associations and effect on prognosis of cytoplasmic steroid receptor content were studied in 168 patients with clinical Stage I and II endometrial carcinoma. Cytoplasmic estrogen receptor status was associated (p less than 0.01) with histologic differentiation, nuclear differentiation, and histologic documentation of extrauterine metastases. Progesterone receptor status was related (p less than 0.05) to histologic differentiation and histologic cell type, and combined estrogen receptor/progesterone receptor status was associated (p less than 0.05) with histologic differentiation, peritoneal cytology, extrauterine metastases, and histologic cell type among the 105 patients who had determination of both estrogen and progesterone receptors. Single-factor analysis revealed significant (p less than 0.05) effects of estrogen receptor status, progesterone receptor status, and estrogen receptor/progesterone receptor status on disease-free survival. All other clinicopathologic features significantly (p less than 0.05) affected prognosis, except for peritoneal cytology. With use of stepwise regression analysis of proportional hazards, estrogen receptor, progesterone receptor, and combined estrogen receptor/progesterone receptor status were significant independent prognostic factors, replacing histologic assessment of glandular or nuclear differentiation in the models. These data suggest that receptor status of primary endometrial carcinomas provides important information relevant to tumor behavior which complements the information provided by conventional clinicopathologic analysis.

Adenocarcinoma↗
PubMed1985

Malignant melanoma and pregnancy.

Confusion exists concerning the influence of pregnancy on survival in patients with malignant melanoma. To evaluate this problem a retrospective computer-aided study was performed of women in the child-bearing years treated for Stage I cutaneous melanoma at the Duke University Comprehensive Cancer Center. Fifty-eight women were identified who had melanoma arise during pregnancy (Group 1) and 43 patients were noted who became pregnant within 5 years of diagnosis of their melanoma (Group 2). Appropriate control groups matched for the clinical variables of age, primary site, and stage of disease and the pathologic variables of Clark's Level, tumor thickness, ulceration, and histologic type were selected from the cohort of 2938 melanoma patients seen at Duke. Actuarial survivals for Group 1 and 2 patients did not differ from their respective controls, although the small number of deaths in each group resulted in wide confidence intervals. When actuarial disease-free intervals were plotted, there was a significant difference between women who had melanoma develop during pregnancy when compared to their controls (P = 0.04). In a multivariate regression analysis, after adjustment for the influence of the more significant prognostic factors for Stage 1 melanoma, including Clark's Level, ulceration and tumor thickness, the effect of pregnancy on disease-free interval became more apparent (P = 0.02). No difference in actuarial disease-free interval was noted in the melanoma patients who elected to become pregnant within 5 years of diagnosis (P = 0.31). A multivariate regression analysis confirmed this finding. These data indicate that although an intercurrent melanoma during pregnancy has a worse prognosis than the control groups, once a woman has been diagnosed as having a cutaneous melanoma, a subsequent pregnancy has no effect on recurrence rate or survival.

Actuarial Analysis↗
PubMed1985

Electrophoretic characterization of purified bovine, porcine, murine, rat, and human uterine estrogen receptors.

The calf uterine estrogen receptor (E2R) in the presence of sodium molybdate has been purified, 7,000-fold by a single passage over an estradiol affinity column. A dominant 70,000-dalton band and two minor bands at 50,000 and 30,000 daltons were observed by electrophoretic analysis. These bands had been eluted using estradiol, sodium sulfocyanate, CHAPS, and HEPES (pH 7.4) with insulin as a carrier protein. The identities of the protein bands were initially confirmed by their failure to bind the affinity column when saturated with estradiol. This single step purification procedure was reproducible and rapid, with yields of 10-20%, providing 25% purity. Diffusion blot analysis, with specific 35S- and 125I-labeled monoclonal antibodies to E2R, confirmed that the 70,000-dalton band represented the estrogen receptor. Specificity was demonstrated by inhibition of binding of purified E2R by both estradiol and diethylstilbestrol but not testosterone, progesterone, corticosterone, aldosterone, or hydrocortisone. The relative binding affinity of the purified receptor was: ethynyl estradiol greater than 17 beta estradiol greater than estriol greater than or equal to estrone greater than or equal to 17 alpha-estradiol greater than mestranol. Pig, human, mouse, and rat uterine estrogen receptors were similarly purified with the affinity column. As with the calf uterine preparations, a dominant 70,000-dalton band with minor bands at 50,000 and 30,000 daltons was identified by diffusion blot analysis in all the species examined.

Animals↗
PubMed1985

Lack of adverse effect of silicone implant on sarcoidosis of the breast.

Involvement of the breast by sarcoidosis is extremely rare, with only 11 case reports in the literature. The potential adverse interaction between silicone prostheses and this disease process poses an unusual clinical dilemma. However, two patients with sarcoidosis of the breast had silicone breast implants placed without exacerbation of their disease nor unusual periprosthetic complications. We conclude that sarcoidosis of the breast does not appear to be a contraindication to placement of silicone implants.

Adult↗
PubMed1985

Long-term clinical outcome of immediate reconstruction after mastectomy.

Immediate reconstruction of a breast removed for treatment of carcinoma can be accomplished without altering the cancer-ablative surgical procedure. The theoretical possibility that reconstruction might compromise the cure rate has tempered enthusiasm for this approach. To test this issue, the relapse-free survival of 101 patients who underwent breast reconstruction in the immediate postmastectomy period was compared with that of 377 patients with breast cancer who underwent mastectomy without immediate reconstruction. This comparison was accomplished using multivariable statistical techniques to correct for baseline inequalities between the patient groups. After adjustment for the relevant prognostic factors, no significant difference remained between the two groups. We conclude that immediate reconstruction has no discernible adverse influence on the natural history of surgically treated breast carcinoma.

Adult↗
PubMed1985

Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.

Attempts at histochemical localization of estrogen receptor with anti-steroid antibody or some fluoresceinated estrogens have given unacceptable sensitivities and specificities when compared with biochemical methods or clinical response. In the present study a monoclonal antibody against estrogen receptor (H222 Sp gamma) was used on cryostat sections of freshly frozen breast tumors with a peroxidase-antiperoxidase immunoperoxidase technique. Biochemical receptor analyses were by dextran-coated charcoal analyses. Tumors from three separate cohorts of patients were studied as follows: population A, 62 primary breast cancers from 1983; population B, 72 primary lesions stored from 1976 to 1983; and population C, 23 patients with metastases, treated with hormonal therapy. Distinct staining was seen in the cell nucleus. A semiquantitative relationship was seen between histochemical score assessment of staining and biochemical assay in each cohort. The sensitivity and specificity using a threshold of 75 for the histochemical score and more than 20 femtomoles/mg of protein for dextran-coated charcoal analyses were as follows: population A, specificity, 89%, and sensitivity, 95%; population B, specificity, 94%, and sensitivity 88%; and for population C, the comparison was with objective clinical response yielding specificity, 89%, and sensitivity, 93%.

Antibodies, Monoclonal↗
PubMed1984

Cytoplasmic estrogen and progesterone receptor content of uterine sarcomas.

Analyses of cytoplasmic estrogen receptor and progesterone receptor were performed on tumor specimens from 32 patients with uterine sarcomas. While the median and maximal quantitative levels of binding were lower than those observed in endometrial carcinomas, examples of estrogen receptor- and progesterone receptor-positive as well as estrogen receptor- and progesterone receptor-negative tumors were observed in all histologic categories of sarcomas. The presence of significant levels of estrogen receptor binding correlated (p less than 0.05) with the presence of progesterone receptor. The receptor binding status did not correlate with the histologic type of sarcoma, clinical stage, primary or metastatic tumor, presence of extrauterine metastases, age, previous exogenous estrogen therapy, mitotic count, or overall differentiation or nuclear differentiation of the sarcoma. The overall and nuclear differentiation of the carcinomatous elements of homologous mixed müllerian tumors did not correlate with receptor status. The presence of significant levels of estrogen receptor did demonstrate a trend (p less than 0.10) favoring enhanced survival through short-term follow-up, but this trend was not demonstrated with survival beyond 36 months. Steroid receptor status did not otherwise affect prognosis or disease-free survival. No correlation between receptor content and response to hormonal therapy or chemotherapy was observed.

Cytoplasm↗
PubMed1984

Porcine liver nuclear histone acetyltransferase. Partial purification and basic properties.

The major histone acetyltransferase activity from porcine liver nuclei has been isolated and partially purified by a simple, rapid, and reproducible method. Extraction of nuclei in buffered 30% saturated ammonium sulfate and subsequent ammonium sulfate fractionation, chromatography on DEAE-Sephacel and hydroxylapatite, and ultracentrifugation on linear 15-30% glycerol gradients provides an 8650-fold purification (over nuclei) in 42% yield. The molecular weight of the enzyme is approximately 94,000 as determined by glycerol gradient ultracentrifugation and gel filtration on Sephacryl S-200. The optimum pH for the reaction is 7.5 and the activity is inhibited by monovalent and divalent salts and by sulfhydryl blocking reagents. The enzyme activity is substantially protected from thermal denaturation at 37 degrees C by the addition of glycerol to the incubation medium. In the presence of the core histones, the enzyme catalyzes the acetylation reaction in the order H3 greater than H4 greater than H2B greater than H2A; the order for histones bound in nucleosome core particles is H4 greater than H2B greater than H3 greater than H2A. The high mobility group proteins 14 and 17 serve as substrates for the enzyme in vitro, suggesting a possible role for enzymatic high mobility group acetylation in chromatin function.

Acetyltransferases↗
PubMed1984

Hormonal stimulation of avian embryonic cartilage growth in vitro: histologic and ultrastructural features.

We studied the histologic and ultrastructural features of embryonic chick cartilage after the cartilage had been incubated in serum-free medium that contained hormones and growth factors known to stimulate in vitro cartilage growth. Pelvic cartilages from 9 d chick embryos were incubated in BGJb ( Fitton -Jackson modification) medium alone (control) or medium containing one of the following: N6 monobutyryl cyclic AMP 0.5 mM, forskolin 100 microM, triiodothyronine (T3) 10 nM, insulin 45 nM, or somatomedin C 0.67 nM. At the end of 3 d of incubation the cartilages were fixed in buffered formalin. Significant growth (increases in size, wet and dry weight) was seen with each treatment group. N6-Monobutyryl cAMP treated cartilage had an increased number of flattened immature chondrocytes with large nuclei and prominent nucleoli. The histologic and ultrastructural features of forskolin treated cartilage were indistinguishable from N6-monobutyryl cAMP treatment. The T3 treated cartilage contained large hypertrophic chondrocytes with prominent lacunar typical of mature cartilage. T3 treated cartilage had considerable vacuole formation and dilated endoplasmic reticulum. Insulin and somatomedin treated cartilage had histologic appearance similar to control cartilage. Thus, the effects of various hormones on embryonic cartilage growth in vitro can be separated as to whether growth is the result of chondrocytic hyperplasia (cyclic AMP mediated), chondrocytic hypertrophy with maturation (T3), or a combination of both hyperplasia and hypertrophy (insulin and somatomedin-C).

Animals↗
PubMed1984

Hormonal and personal effects on estrogen receptors in breast cancer.

Since high estrogen receptor protein in breast cancer tissue has a favorable effect on patient prognosis, factors influencing estrogen receptor levels are the focus of this research. From April 1977 to December 1978, 246 histologically confirmed primary breast cancer patients from three North Carolina hospitals were interviewed and provided with photographic displays of hormonal products. Their tumor tissue was analyzed for estrogen receptor protein by the sucrose density gradient assay. Data were analyzed by multiple regression and logistic regression techniques. No statistically significant relationship was found between gonadal hormone usage and estrogen receptor levels, although recent users of either oral contraceptives or replacement estrogens had lower receptor levels. Users of progestogen-predominant and -intermediate types of oral contraceptives also had lower estrogen receptor protein. An effect of menopausal status, independent of age, was not evident. Statistically significant associations involved age and race among postmenopausal patients. With black breast cancer patients aged less than 70 years as the reference group, the relative odds of having high estrogen receptor protein (greater than 10 fmol/mg of cytosol protein) were 2.4 times greater among whites aged less than 70, 1.6 times greater in blacks aged greater than or equal to 70, and 12.8 times greater in whites greater than or equal to 70 years. These differences in estrogen receptor protein may contribute to the black-white differential in breast cancer survival.

Adult↗
PubMed1984

Granular cell tumors of the breast. Steroid receptor analysis and localization of carcinoembryonic antigen, myoglobin, and S100 protein.

Granular cell tumors occur in a variety of sites, including the breast (6%). Origins from histiocytic, myogenic, fibroblastic, and neurogenic elements have been proposed. Female predominance suggests that estrogenic hormones are involved. Four granular cell tumors of the breast and one in an axillary lymph node were studied for sex steroid receptor content, myoglobin, carcinoembryonic antigen, and S100 protein localization. Antimyoglobin antibody did not localize in these tumors. Carcinoembryonic antigen and S100 protein localized in the cytoplasm of these tumors. Neither estrogen nor progesterone receptor protein were present in these tumors in detectable amounts. Ultrastructural features of these granular cell tumors in the breast are similar to those described for extramammary granular cell tumors. These studies agree with previous data that suggest a neurogenic origin for granular cell tumors.

Breast Neoplasms↗
PubMed1984

Galactorrhea-amenorrhea and hyperprolactinemia associated with pituitary tumors of growth-hormone- and adrenocorticotropic-hormone-secreting cells. A report of two cases.

In women with galactorrhea, amenorrhea/oligomenorrhea, hyperprolactinemia and radiographic evidence of a pituitary tumor, the presumed etiology is usually a primary prolactin-secreting tumor. We treated two patients whose presenting symptoms (galactorrhea and oligomenorrhea) and initial investigation (which showed radiographic enlargement of the sella and hyperprolactinemia) suggested a prolactin-secreting pituitary tumor. However, after further endocrinologic investigation, transsphenoidal exploration and ultrastructural-immunohistologic evaluation of the excised pituitary tumors, the tumors were found to be composed of cells characteristic of growth-hormone and adrenocorticotropic-hormone production. These data are consistent with the hypothesis that any factor or factors increasing intrasellar pressure, including pituitary tumors originating in cells other than galactotrophs, can elevate serum prolactin and present clinically as galactorrhea-amenorrhea. They suggest further that a diligent search be done for elevations of other pituitary trophic hormones when a pituitary tumor is suspected in order not to overlook other kinds of serious endocrinopathy.

Adenoma↗