PubMed Health⌕ Search

Biomedical subjects

W D Lawrence

Publications and source records attributed to W D Lawrence.

At least 19 recordsLinked to original sources
PubMed1992

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol↗
PubMed1992

An ultrastructural study of the developing urogenital tract in early human fetuses.

OBJECTIVES: This study examines the gonoducts during the ambisexual stage of human fetal development to define their ultrastructural characteristics, including the origin and antomic relationship of the mesonephric and paramesonephric ducts during gonoductal development. STUDY DESIGN: The reproductive tracts from five fetuses ranging in gestational age from 35 to 45 days were processed for ultrastructural examination. The developing mesonephric ducts, paramesonephric ducts, and their surrounding mesenchyme were studied with a Phillips 300 transmission electron microscope. RESULTS: The mesonephric ducts and paramesonephric ducts have distinctive cytoplasmic and cell surface ultrastructural characteristics, as well as different morphologic patterns of epithelial-mesenchymal interaction. Cephalad portions of mesonephric ducts and paramesonephric ducts are separated by mesenchyme, but more caudal aspects move progressively closer until they are juxtaposed but separate. CONCLUSIONS: Early mesonephric ducts and paramesonephric ducts may be distinguished because of their distinctive ultrastructural features; epithelial-mesenchymal interaction may be important in their differentiation and maintenance; both gonoducts retain their morphologic identity throughout, supporting their separate origins.

Cell Nucleolus↗
PubMed1991

Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Ascites↗
PubMed1991

Sex-dependent inhibition by retinoic acid of thyroid-hormone action on rabbit reticulocyte Ca2(+)-ATPase activity.

The interaction was examined in vitro of retinoic acid and thyroid hormone with rabbit reticulocyte Ca2(+)-ATPase. L-Thyroxine (T4) (0.1 nM) stimulated female-source Ca2(+)-ATPase activity (+21%; P less than 0.03) and inhibited male-source enzyme (-20%; P less than 0.05). Addition of retinoic acid (10 nM-1 microM) did not influence T4-inhibitable male-source Ca2(+)-ATPase, but caused a 52% loss of T4 effect on the female-source enzyme. Incubation of female-source membranes with testosterone caused the enzyme response to T4 and retinoic acid to become that of male-source membranes, and the male-source enzyme response was converted into the 'female' pattern by exposure to 17 beta-oestradiol. We postulate that a membrane-associated sex-steroid-dependent factor imparts a gender-specific interaction of thyroid hormone and retinoic acid on Ca2(+)-ATPase, and that ultimately the factor is shed during erythrocyte maturation.

Animals↗
PubMed1991

Specific inositol phosphates inhibit basal and calmodulin-stimulated Ca(2+)-ATPase activity in human erythrocyte membranes in vitro and inhibit binding of calmodulin to membranes.

D-Myo-inositol 1,4,5-trisphosphate (Ins[1,4-,5]P3) inhibits rat heart sarcolemmal Ca(2+)-ATPase activity (T. H. Kuo, Biochem. Biophys. Res. Commun. 152: 1111, 1988). We have studied the effect and mechanism of action of Ins(1,4,5)P3 and related inositol phosphates on human red cell membrane Ca(2+)-ATPase (EC 3.6.1.3) activity in vitro. At 10(-6) M, Ins(1,4,5)P3 and D-myo-inositol 4,5-bisphosphate (Ins[4,5]P2) inhibited human erythrocyte membrane Ca(2+)-ATPase activity in vitro by 42 and 31%, respectively. D-Myo-inositol 1,3,4,5-tetrakisphosphate, D-myo-inositol 1,4-bisphosphate, and D-myo-inositol 1-phosphate were not inhibitory. Enzyme inhibition by Ins(1,4,5)P3 was blocked by heparin. Exogenous purified calmodulin also stimulated red cell membrane Ca(2+)-ATPase activity; this stimulation was inhibited by Ins(1,4,5)P3. Ins(4,5)P2 and Ins(1,4,5)P3, but not Ins(1,4)P2, inhibited the binding of [125I]calmodulin to red cell membranes. Thus, specific inositol phosphates reduce plasma membrane Ca(2+)-ATPase activity and enhancement of the latter in vitro by purified calmodulin. The mechanism of these effects may in part relate to inhibition by inositol phosphates of binding of calmodulin to erythrocyte membranes.

Calcium-Transporting ATPases↗
PubMed1990

Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.

Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.

Adult↗
PubMed1990

Endometrial adenocarcinoma with variable-level myometrial involvement limited to adenomyosis: a clinicopathologic study of 23 cases.

Endometrial adenocarcinoma (EA) with myometrial involvement limited to foci of adenomyosis has been associated with a better 5-year survival than EA with myometrial invasion at the corresponding depth. We identified 23 cases of stage I EA diagnosed between 1975 and 1981 in which myometrial involvement was confined entirely to adenomyotic foci. Histopathological criteria used to determine adenomyotic involvement by EA included presence of endometrial stroma; presence of adjacent benign "marker" glands to indicate partial replacement of adenomyosis; either bulging expansion of the endomyometrial junction by EA or a smooth rounded contour of entirely intramyometrial tumor nests; and absence of peritumoral desmoplasia or stromal loosening around such foci. In any one case no single criterion was sufficient to differentiate adenomyotic involvement from true invasion; however, none of the cases showed the last phenomenon. Adenomyotic involvement extended to the inner third of the myometrium in 15 cases, the middle third in 6 cases, and the outer third in 2 cases. Twenty-one cases were pure adenocarcinoma, with one adenocarcinoma with squamous differentiation (adenoacanthoma) and one adenosquamous carcinoma; 18 cases were FIGO grade 1 and 5 were FIGO grade 2. Adenomyosis containing atypical hyperplasia was seen in 13 cases, suggesting that EA may arise de novo in adenomyosis at variable levels in the myometrium. Current follow-up data were available for all patients, with 19 presently alive and free of disease. Four died of unrelated causes, three of whom had inner third involvement and one, middle third involvement. Twelve patients were treated with preoperative or postoperative radiation. This study supports previous smaller series suggesting that cases of EA in which myometrial involvement is limited to adenomyosis have a better prognosis than those with true myometrial invasion at an equivalent level and that adenocarcinoma may arise de novo in adenomyosis.

Adenocarcinoma↗
PubMed1990

The immunohistochemical profile of malignant mixed müllerian tumor. Overlap with endometrial adenocarcinoma.

The distinction between malignant mixed müllerian tumor (MMMT) of the female genital tract and poorly differentiated endometrial adenocarcinoma (EA) is sometimes difficult and arbitrary. Although several studies have described the immunohistochemical profile of MMMT and EA, the results have varied, and controversy regarding the histogenetic relationship between them remains. The authors examined the histologic characteristics and immunohistochemistry of 31 formalin-fixed paraffin-embedded MMMTs from a variety of female genital tract sites with a panel of monoclonal and polyclonal antibodies using the avidin-biotin-peroxidase complex (ABC) method. Eighteen neoplasms were homologous and 13 were heterologous; the average patient age was 67 years. In all cases the epithelial component stained for keratin (K), whereas the stromal component stained in 48%; vimentin (V) was detected in the epithelial component in 35% and the stromal component in 81%. Myoglobin (M) detected rhabdomyoblasts in three of five cases tested; desmin (D) was found in five of six and actin (A) in all six cases with skeletal muscle. Overall, A stained the stromal components in 45% of cases, whereas none of the epithelial components stained. The coexpression of K and V in the epithelial component of 35% of cases and in the stromal component of 48% of cases led the authors to conclude that the immunoprofile of MMMT broadly overlaps with that of EA and, independent of morphologic findings, it is often not reliable or useful in distinguishing between the two. Furthermore, the variable immunoprofile suggests that MMMT may be a histogenetically heterogeneous group of neoplasms, including both carcinomas (metaplastic, sarcomatoid) as well as true carcinosarcomas. Although A detected rhabdomyoblasts in all cases, it also stained neoplastic mesenchymal elements in eight more cases, suggesting the presence of smooth muscle or myofibroblasts in the stroma of some MMMTs.

Adenocarcinoma↗
PubMed1989

Stimulation in vitro of rabbit erythrocyte cytosol phospholipid-dependent protein kinase activity. A novel action of thyroid hormone.

L-Thyroxine (T4) and 3,3',5-L-triiodothyronine (T3) at 10(-10) M stimulated phospholipid- and Ca2+-dependent protein kinase activity in rabbit red cell cytosol in vitro by 151 and 176%, respectively. Kinase of 30-fold greater specific activity, developed with 0.4 mM NaCl from cytosol applied to DEAE-cellulose, was also stimulated up to 2-fold by thyroid hormone. Hormone enhancement of kinase activity occurred after 60 min of incubation at 37 degrees C prior to enzyme assay. Thyroid hormone analogues triiodothyroacetic acid, 3,5-dimethyl-3'-isopropyl-L-thyronine, D-T3, D-T4, and 3,3',5'-L-triiodothyronine (reverse T3) were inactive. These results support a role for thyroid hormone endogenously in regulation of phospholipid-dependent protein kinase activity.

Animals↗
PubMed1989

Retroorbital metastases in ovarian cancer.

We report a patient with unilateral metastasis to the posterior orbit from poorly differentiated ovarian carcinoma with neuroendocrine features. Ocular metastases from pelvic neoplasms have been reported infrequently; however, we report the first case of an ovarian cancer with orbital metastasis as the initial presenting symptom.

Aged↗
PubMed1989

Reliability of frozen section examination in identifying poor prognostic indicators in stage I endometrial adenocarcinoma.

Management of Stage I adenocarcinoma of the uterus includes hysterectomy, bilateral salpingo-oophorectomy, and selective paraaortic and pelvic lymphadenectomy. Postoperative radiation therapy (RT) is selectively employed in patients with histologically defined poor prognostic indicators. We attempted to identify these poor prognostic indicators by frozen section (FS) at primary surgery in 55 patients with Stage I endometrial adenocarcinoma; we found an excellent correlation between the results obtained on gross examination of the uterus with selected FS and the results after extensive sampling and microscopic examination of permanent section (PS). The depth of myometrial invasion was accurately predicted in 96.5%, and histologic grade in 94.5% of these patients. Sixty-six percent of patients with occult invasion of the cervix on PS were identified on FS. Using the above criteria, we identified by FS all patients (15/55) who required adjuvant RT obviating the need for pelvic lymph node dissection. On the basis of our preliminary data, we recommend the use of careful gross examination and selective FS to identify patients requiring selective pelvic and paraaortic lymphadenectomy and adjuvant therapy, thereby eliminating the need for staging lymph node dissection with its associated morbidity and complications.

Adenocarcinoma↗
PubMed1989

Thyroid hormone regulation of membrane Ca2(+)-ATPase activity.

The Ca2(+)-ATPase of plasma membranes from a variety of tissues is subject to stimulation in vitro, and apparently in vivo, by physiological concentrations of iodothyronines regarded as biologically active in other bioassay systems. This calmodulin-dependent action of thyroid hormone is nongenomic, that is, directly on the cell membrane and independent of the cell nucleus. In the case of human erythrocyte Ca2(+)-ATPase, this assay of thyroid hormone bioactivity is attractive as an in vitro, readily-studied model of hormone action in a human cell. Enzyme activity is paralleled, as expected, by changes in calcium pump activity. Thyroid hormone action in this system is subject to modulation by glucose and by a variety of compounds which, like iodothyronines, are hydrophobic. The mechanism of thyroid hormone action on membrane Ca2(+)-ATPase involves, at least in part, membrane lipids, including components of the phosphatidylinositol cycle. The physiologic role of thyroid hormone action on cell membrane Ca2(+)-ATPase is speculative. In plasma membranes of nonexcitable and excitable tissues, ambient thyroid hormone may set basal activity of Ca2(+)-ATPase or magnitude of the enzymatic response to calmodulin Ca2+.

Animals↗
PubMed1988

"Placental polyp": light microscopic and immunohistochemical observations.

A case of the chronic type of placental polyp, occurring in a 37-year-old woman approximately 9 years after abortion of her last known pregnancy, is reported. The placental polyp was predominantly composed of necrotic and hyalinized chorionic villi without identifiable lining trophoblast; however, some villi showed a thin rim of apparently viable syncytiotrophoblast that exhibited focal strong positivity for human chorionic gonadotropin by immunohistochemical studies. Intermediate trophoblast, especially abundant within the intervillous fibrin, appeared most viable and showed strong positivity for human placental lactogen (hPL); syncytiotrophoblast also showed focal positivity for hPL. The basal aspect of the polyp was composed of abundant decidua that contained dilated and ectatic blood vessels. This study demonstrates the presence of cytoplasmic markers for pregnancy in a chronic type of placental polyp, apparently of 9 years' duration, and draws attention to an entity that may be encountered more frequently due to the current prevalence of induced abortions.

Adult↗
PubMed1988

Absence of teratogenic effects of progesterone on the developing genital tract of the human female fetus.

It has been questioned whether prenatal exposure to progesterone, like exposure to diethylstilbestrol (DES), results in teratogenic abnormalities of the upper and lower genital tract in human females. Through the use of a recently described model in which human fetal reproductive tracts can be transplanted and grown in vivo for extended periods in athymic nude mice, genital tracts from human female fetuses, ages 7 to 18 weeks postovulation, were grafted into castrated murine hosts and grown for 4 to 10 weeks in the presence or absence of continuous exposure to progesterone. Substantial growth was observed. For all specimens, the morphogenetic process proceeded normally, resulting in the harmonious organization of a complete, well differentiated genital tract composed of fallopian tubes, uterine corpus, and cervix and vagina. The fallopian tubes were highly convoluted and disclosed fimbria. The uterine corpus was lined by a simple columnar epithelium; two layers of stroma in the wall were distinctly separated from each other. In the older specimens, the outer layer of stroma had assumed microscopic properties diagnostic of smooth muscle (myometrium). In the majority of specimens the region of the cervix/vagina disclosed the development of a fornix-like evagination at which point or slightly cranially there was a gradual but defined transition from columnar epithelium to squamous epithelium. The inner layer of endometrial stroma tapered and disappeared at or close to the squamocolumnar junction. The vaginal stroma was a single homogeneous layer and was continuous with the myometrium of the uterine corpus. In the context of this model system, prenatal exposure of the developing human female genital tract of progesterone was not associated with any obvious teratogenic effects.

Animals↗