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Biomedical subjects

W D Lawrence

Publications and source records attributed to W D Lawrence.

At least 73 records · Page 4Linked to original sources
PubMed1987

Action of erythropoietin in vitro on rabbit reticulocyte membrane Ca2+-ATPase activity.

The mechanism of action of erythropoietin is thought to require specific interaction with the target cell surface and involve alteration of cellular calcium metabolism. Using the rabbit reticulocyte membrane as a model of the immature red cell membrane, we investigated the effects of human recombinant erythropoietin on membrane Ca2+-ATPase (calcium pump) activity in vitro. Erythropoietin in a concentration range of 0.025 to 3.0 U/ml progressively decreased membrane Ca2+-ATPase activity by up to 64% (P less than 0.01). These concentrations have been shown by others to stimulate in vitro erythroid growth. The action of erythropoietin on reticulocyte Ca2+-ATPase required an incubation time of 1 h before enzyme assay for maximum effect and was neutralized by antierythropoietin antiserum. Other nonhemopoietic growth factors (epidermal growth factor, insulin) had no effect in this assay. Ca2+-ATPase activity of membranes prepared from rabbit mature red blood cells was not inhibited by erythropoietin. The novel effect of erythropoietin on reticulocyte membrane Ca2+-ATPase activity is a mechanism by which erythropoietin can influence cellular Ca2+ metabolism.

Animals↗
PubMed1986

Structure-activity relationships of sex steroid analogs determined in vitro in a thyroid hormone-responsive membrane Ca2+-ATPase model.

Physiological concentrations of L-T4 were found previously to stimulate Ca2+-ATPase activity in vitro in reticulocyte membranes from female rabbits and to inhibit this enzyme in reticulocyte membranes from males. In these previous studies, preincubation of intact cells or ghosts with testosterone (5 X 10(-11) M) converted female-source reticulocyte membranes to male-type responsiveness to thyroid hormone (inhibition of Ca2+-ATPase activity). Preincubation of reticulocyte membranes with 17 beta-estradiol (5 X 10(-11) M) converted male-source membranes to female-type responsiveness (stimulation by L-T4 of membrane Ca2+-ATPase activity). Using this sex steroid-sensitive thyroid hormone-dependent membrane enzyme system, we investigated the structure-activity relationships of analogs of sex steroids and unrelated steroids. 5 beta-Androstanes were active compared to testosterone in assays using female-source membranes, while 5 alpha-androstanes were less active. Within the 5 beta-androstanes, activity was dependent on at least one hydroxyl group at the C3- or C17-position. Nongonadal steroids tested were less active, establishing specificity of the sex steroid effect in assays using female-source membranes. Assayed in male-source membranes, estrone and 3-hydroxy-1,3,5-(10)7-estratraen-17-one (equilin) were active compared for estrogen effect with 17 beta-estradiol, while estriol was less active. The activities of hydrocortisone and aldosterone were 76% and 71%, respectively, in this system. These structure-activity relationships are distinct from those described for gonadal steroid-cytoplasmic binding proteins or nuclear interactions, and represent a novel sex steroid-thyroid hormone effect on activity of a membrane enzyme.

Animals↗
PubMed1986

A double-blind, controlled comparison of piperacillin and cefoxitin in the prevention of postoperative infection in patients undergoing cesarean section.

Data are presented from a randomized, double-blind multicenter trial (six study sites, involving 346 patients) in which piperacillin was compared with cefoxitin as a prophylactic agent for patients undergoing cesarean section. One hundred and sixty-nine patients received piperacillin and 177 received cefoxitin; in each instance, the total dosage was 6 grams. Strict criteria were used to evaluate safety and efficacy. The courses of all of the patients were evaluable for safety and 183 courses were evaluable for efficacy (136 efficacy-evaluable courses were from patients treated with piperacillin and 147, from those treated with cefoxitin). Postoperative infection was prevented in 89 per cent of the patients treated with piperacillin and in 93 per cent of the those treated with cefoxitin. The difference was not statistically significant. The data from each of the individual study sites, as well as the pooled data, indicated that the short term perioperative administration of piperacillin in patients undergoing a cesarean section was as safe and effective as cefoxitin with regard to prophylactic response, duration of hospitalization and the usage of other systemic antibiotics.

Adolescent↗
PubMed1986

A comparison of piperacillin, cephalothin and cefoxitin in the prevention of postoperative infections in patients undergoing vaginal hysterectomy.

A randomized, double-blind, multicenter trial was initiated to compare the safety and efficacy of piperacillin, cephalothin and cefoxitin in the prophylactic treatment of patients undergoing vaginal hysterectomy. The total dose of each antibiotic was 6 grams given in three equally divided doses. A satisfactory prophylactic response was obtained in 143 of 151 (95 per cent) patients treated with piperacillin, in 82 of 87 (94 per cent) patients treated with cephalothin and in 57 of 60 (95 per cent) patients treated with cefoxitin. The pooled data indicated that the piperacillin treatment group did not differ from the combined cephalosporin treatment groups with respect to prophylactic response, presence of febrile morbidity, fever index, duration of postoperative hospitalization and incidence of reported adverse experiences.

Adult↗
PubMed1985

Calmodulin in interferon preparations: effect of interferon on calmodulin bioactivity.

Heat-stable calmodulin immunoreactivity and bioactivity were detected in crude preparations of various types of human, murine and chicken interferons (IFNs). Calmodulin containing HuIFN-alpha was retained on a trifluorophenothiazine-Sepharose column. The two activities were separated by serial elutions with 50 microM Ca2+ (HuIFN-alpha) followed by 2 mM EGTA (calmodulin). While maintaining its full antiviral activity, calmodulin free HuIFN-alpha inhibited enhancement of Ca2+-ATPase activity in vitro by authentic purified eukaryote calmodulin. These results indicate that IFNs are calmodulin-binding proteins and that the secretion of both IFNs and calmodulin occurs from IFN-induced cells.

Animals↗
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↗
PubMed1985

Juvenile granulosa cell tumor of the infantile testis. A report of 14 cases.

Fourteen testicular tumors diagnosed in infants less than 6 months of age had a distinctive appearance resembling that of the juvenile granulosa cell tumor of the ovary. One of them was discovered at autopsy in an infant of 30 weeks' gestational age; seven were diagnosed during the first few days of life, and the remainder between 3 weeks and 4 1/2 months of age. Enlargement of a scrotal testis was the presenting manifestation in 10 cases and abdominal swelling in one case; one tumor was found in a descended testis that had undergone torsion and one was discovered in an inguinal testis at the time of inguinal herniorrhaphy. The tumors ranged from 0.8 to 5.0 cm in diameter and were cystic or partly cystic and partly solid. Microscopic examination disclosed both follicular and solid components. The follicles were of varying sizes and contained eosinophilic or basophilic fluid that stained positively for mucin in some of the cases. The solid foci typically had a nodular arrangement and occasionally were hyalinized or had a basophilic background due to the presence of intercellular mucin. The neoplastic cells contained moderate to large amounts of eosinophilic cytoplasm and round to oval hyperchromatic nuclei, which typically lacked grooves. The mitotic rate varied from less than 1-24/10 high-power fields. Limited follow-up examination revealed no evidence of recurrence. The microscopic features of these neoplasms warrant their designation as "juvenile granulosa cell tumor."

Follow-Up Studies↗
PubMed1985

Juvenile granulosa cell tumor--another neoplasm associated with abnormal chromosomes and ambiguous genitalia. A report of three cases.

Three infants, 3 months of age or younger with abnormal karyotypes and ambiguous genitalia, had gonadal juvenile granulosa cell tumors. Two of the patients had mixed gonadal dysgenesis and the third had an intersexual disorder of undetermined type. Two tumors arose in undescended testes, and the third in an undescended gonad of uncertain nature. The occurrence of this uncommon neoplasm in these infants indicates that it is another type of neoplasm that may develop in the gonad of a patient with an abnormal karyotype and ambiguous genitalia.

Chromosome Aberrations↗
PubMed1984

Increased incidence of cervical and vaginal dysplasia in 3,980 diethylstilbestrol-exposed young women. Experience of the National Collaborative Diethylstilbestrol Adenosis Project.

The incidence rates of dysplasia and carcinoma in situ (CIS) of the cervix and vagina were determined in 3,980 young women exposed prenatally to diethylstilbestrol. Strict criteria were developed to minimize selection bias among the subset of 744 pairs of matched exposed and unexposed (control) cohort participants, all of whom were identified through review of prenatal obstetrical records. A high degree of compliance was achieved throughout the seven-year study period since in each group about 90% of the women remained as active participants, kept 77% of the annual anniversary examinations, and had separate Papanicolaou smears of the cervix and vagina performed in 99% of the anniversary examinations. The incidence rate for dysplasia and CIS was significantly higher in the women exposed to diethylstilbestrol than in those not exposed in the matched cohort (15.7 v 7.9 cases per 1,000 person-years of follow-up). The rates were higher in the exposed women if squamous metaplasia extended to the outer half of the cervix or onto the vagina. In other respects, the matched cohorts were strikingly similar.

Adult↗
PubMed1984

Interaction of thyroid hormone and sex steroids at the rabbit reticulocyte membrane in vitro: control by 17 beta-estradiol and testosterone of thyroid hormone-responsive Ca2+-ATPase activity.

Physiological concentrations (10(-10) M) of L-thyroxine and triiodo-L-thyronine were found in vitro to enhance Ca2+-ATPase activity in reticulocyte-enriched red cell membranes from female rabbits and to inhibit this enzyme in the male reticulocyte. Cross-incubation experiments with reticulocyte-enriched red cells and plasma from the opposite sex demonstrated that this sex-specific membrane response to thyroid hormone was transferable by plasma. Similar experiments with intact reticulocytes exposed to physiological concentrations (10(-11) M) of testosterone and 17 beta-estradiol indicated that the plasma factors were the sex steroids. That is, incubation in vitro with testosterone converted female-source reticulocytes to male-type responsiveness to thyroid hormone (inhibition of Ca2+-ATPase activity); incubation with estradiol converted male-source reticulocyte-enriched red cells to female-type responsiveness (stimulation by iodothyronines of membrane Ca2+-ATPase activity). Similar results were obtained when reticulocyte ghosts were incubated with testosterone and 17 beta-estradiol prior to determination of membrane enzyme activity. Etiocholanolone (5 beta-androstan-3 alpha-ol-17-one) and testosterone were equipotent, but 5 alpha-dihydrotestosterone had little activity in this system. Estrone and estradiol were equipotent, but estriol had no permissive effect on the stimulation by iodothyronine of reticulocyte membrane Ca2+-ATPase activity. Expression of thyroid hormone action in vitro on Ca2+-ATPase activity in the rabbit reticulocyte is determined at the membrane level by testosterone and estrogen. The structure-activity relationships of the sex steroids for this membrane action are different than those reported for nuclear actions of the steroids.

Animals↗
PubMed1984

Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male.

A study was undertaken to determine (1) the effects of endogenous Müllerian inhibiting substance (MIS) on the developing human fetal genital tract; (2) the time in fetal life when MIS is first capable of inhibiting the growth of the embryonic Müllerian ducts; and (3) the reversibility of the effects of MIS on the developing male Müllerian ducts. Human fetal reproductive tracts were transplanted and grown for sustained periods in vivo in athymic nude mice. The genital tracts from 12 male human fetuses, ages 51 to 68 days postovulation, were grafted without their associated gonads into castrated murine hosts and grown for 30 to 70 days. Controls consisted of genital tracts from 8 female human fetuses, ages day 53 to 70 that were grown under identical conditions. Male specimens grew to approximately one-half the size of female specimens and disclosed varying degrees of inhibition of the Müllerian duct system from absence of the Müllerian ducts in older specimens (after Day 63) to poorly segregated segments of stroma as the mildest defect (less than Day 61). It is concluded that (1) MIS secretion by the embryonic testes probably begins before Day 51 of gestation; (2) the effects of MIS are progressive during the so-called critical window; (3) the effects of MIS are permanent; and (4) the mesenchyme is an important target of MIS.

Animals↗
PubMed1984

Immunocytochemical localization of placental lactogen and chorionic gonadotropin in the normal placenta and trophoblastic tumors, with emphasis on intermediate trophoblast and the placental site trophoblastic tumor.

This report presents preliminary observations on the immunocytochemical localization of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) in placental site trophoblastic tumors, hydatidiform moles, and choriocarcinomas and compares the findings with those of a similar immunocytochemical analysis of the placenta at various stages of development. In addition to cytotrophoblast (CT) and syncytiotrophoblast (ST), a third form of trophoblast designated "intermediate trophoblast" (IT) is present during normal pregnancy and in trophoblastic disease. Intermediate trophoblastic cells are mononucleate, larger than CT, and contain more abundant eosinophilic cytoplasm, resulting in a partial resemblance to ST. Intermediate trophoblast has distinctive immunocytochemical features that distinguish it from CT and ST. The localization of hPL and hCG in both IT and ST varies with the age of the placenta, with the type of trophoblastic neoplasm, and from one specimen to another within each category of tumor. Syncytiotrophoblast may contain both hormones in large amounts, whereas IT contains hPL predominantly and hCG focally. Cytotrophoblast is devoid of hCG and hPL except in choriocarcinoma, which may show focal weak staining for hCG. Immunocytochemical identification of hCG and hPL has proved helpful in clarifying the histogenesis of trophoblastic neoplasms and may also be of value in establishing their diagnosis and in determining their prognosis.

Adult↗
PubMed1983

Histologic, nuclear DNA, and human papillomavirus studies of cervical condylomas.

Fifty-four cervical condylomatous lesions, with and without nuclear atypia, from 42 women, were studied with the Feulgen microspectrophotometric technique for nuclear DNA quantitation and an immunoperoxidase technique for human papillomavirus (HPV) antigen. All ordinary cervical condylomas (without atypia/dysplasia) had a diploid or polyploid nuclear DNA distribution; 61% had detectable HPV antigen. Among the cervical condylomas with atypia/dysplasia, 55% (17/31) had diploid or polyploid nuclear DNA pattern, and, of these, 59% (10/17) had demonstrable papillomavirus antigen. Fourteen (45%) were aneuploid lesions, 2 of which had a small number of cells with papillomavirus antigen (14%). These findings suggest that the majority of cervical condylomas are related to papillomavirus infection. That lesions with dysplasia, including high degrees of dysplasia, may also exhibit coexistence of papillomavirus infection suggests the possibility of an infectious etiology in the genesis of cervical squamous neoplasia.

Adolescent↗
PubMed1983

Endodermal sinus tumor of the vulva in an infant.

An endodermal sinus tumor arising in the vulva of a 22-month-old infant is reported and the features of 3 previously recorded endodermal sinus tumors of the vulva are reviewed. Despite radical surgery, radiation therapy, and chemotherapy the tumor was fatal within 6 months. Only one of the 3 previously described patients with this type of vulvar tumor has survived more than 2 years. That tumor was the smallest reported, being the only one under 2 cm in diameter.

Biopsy↗
PubMed1981

Attachment of particle-bound IgG and complement to human neutrophils.

The attachment of particle-bound IgG in a nonphagocytic system stimulates formation of a microfilament-rich, organelle-poor zone in the subjacent cytoplasm of human neutrophils. The attachment site is characterized by ruffling and invagination of the neutrophil membrane. Both IgG attachment and formation of the organelle-poor zone are inhibited by the microfilament inhibitor cytochalasin-B, but not by inhibitors of microtubules, such as colchicine or vinca alkaloids. In contrast, attachment of particle-bound complement is not inhibited by cytochalasin-B in doses known to disrupt actin filaments. There is no discernable change in the subjacent cytoplasm of the neutrophil in response to complement and the membrane attachment site is smooth, without ruffling or invagination. These studies disclose that both IgG-mediated attachment to neutrophils and its sequel, peripheral cytoplasmic reorganization, are mediated by cytochalasin-sensitive structures, possibly actin. Complement-mediated attachment to neutrophils is insensitive to high doses of cytochalasin, suggesting that actin integrity is not required.

Animals↗
PubMed1980

Early physiologic squamous metaplasia of the cervix: light and electron microscopic observations.

A light and electron microscopic study was undertaken of the early phases of cervical squamous metaplasia. A study of areas of columnar epithelium with one row of subcolumnar cells revealed a spectrum of squamous differentiation ranging from cytologically undifferentiation to more characteristically basal type squamous cells. With increasing differentiation, squamous characteristics, such as tonofibrils and desmosomes, became qualitatively and quantitatively more evident in the cells. Ultrastructural examination also revealed cells in the subepithelial stroma with prominent basal lamina and hemidesmosome-like structures along the periphery. From a light and electron microscopic viewpoint, the most likely origin for the subcolumnar progenitor cells appears to be the subepithelial stromal cells. The resemblance of these subepithelial stromal cells to the subcolumnar cells in very early stages of metaplasia is often striking.

Adult↗