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Biomedical subjects

R S Williams

Publications and source records attributed to R S Williams.

At least 145 records · Page 8Linked to original sources
PubMed1992

Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum.

Transforming growth factor beta (TGF beta) is an extremely potent chemoattractant for macrophages, mononuclear leukocytes, and fibroblasts. It also acts as a potent stimulant for collagen and fibronectin synthesis and inhibits epithelial cell growth. TGF beta plays an important role in healing many types of wounds, but its role in peritoneal adhesion formation is not known. These studies were performed to determine if TGF beta could affect postoperative wound healing in a rat model. In the first experiment, 20 rats were divided into two groups and received either 2 micrograms TGF beta or control diluent IP daily for 5 days after surgical injury to the uterine horns. The severity of the adhesions were graded 2 weeks postoperatively using a score of 0-3. The TGF beta group showed a higher adhesion score at 2 weeks compared to control, 2.9 +/- 0.34 and 1.6 +/- 0.61, respectively (P less than 0.001). On H&E stained sections of the adhesions, there was an increase in the number of both inflammatory cells and fibroblasts in the TGF beta-treated animals. A comparison trial of bone-derived TGF beta (a gift from Collagen Corporation, Palo Alto, CA) versus recombinant TGF beta (a gift from Oncogen, Seattle, WA) versus control using the same protocol as above showed that both sources of TGF beta were more effective in promoting postoperative adhesions when compared to controls, and there was no difference between TGF beta groups, 3.0 +/- 0 for both TGF beta groups, and 2.2 +/- 0.91 for control (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter.

To define transcriptional control elements responsible for muscle-specific expression of the human myoglobin gene, we performed mutational analysis of upstream sequences (nucleotide positions -373 to +7 relative to the transcriptional start site) linked to a firefly luciferase gene. Transient expression assays in avian and mammalian cells indicated that a CCCACCCCC (CCAC box) sequence (-223 to -204) is necessary for muscle-specific transcription directed either by the native myoglobin promoter or by a heterologous minimal promoter linked to the myoglobin upstream enhancer region. A putative MEF2-like site (-160 to -169) was likewise necessary for full transcriptional activity in myotubes. Mutations within either of two CANNTG (E-box) motifs (-176 to -148) had only minimal effects on promoter function. We identified and partially purified from nuclear extracts a 40-kDa protein (CBF40) that binds specifically to oligonucleotides containing the CCAC box sequence. A mutation of the CCAC box that disrupted promoter function in vivo also impaired binding of CBF40 in vitro. These data suggest that cooperative interactions between CBF40 and other factors including MEF-2 are required for expression of the human myoglobin gene in skeletal muscle.

Animals↗
PubMed1992

Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia.

Expression of major stress proteins is induced rapidly in ischemic tissues, a response that may protect cells from ischemic injury. We have shown previously that transcriptional induction of heat-shock protein 70 by hypoxia results from activation of DNA binding of a preexisting, but inactive, pool of heat shock factor (HSF). To determine the intracellular signals generated in hypoxic or ischemic cells that trigger HSF activation, we examined the effects of glucose deprivation and the metabolic inhibitor rotenone on DNA-binding activity of HSF in cultured C2 myogenic cells grown under normoxic conditions. Whole-cell extracts were examined in gel mobility shift assays using a 39-bp synthetic oligonucleotide containing a consensus heat-shock element as probe. ATP pools were determined by high-pressure liquid chromatography and intracellular pH (pHi) was measured using a fluorescent indicator. Glucose deprivation alone reduced the cellular ATP pool to 50% of control levels but failed to activate HSF. However, 2 x 10(-4) M rotenone induced DNA binding of HSF within 30 min, in association with a fall in ATP to 30% of control levels, and a fall in pHi from 7.3 to 6.9. Maneuvers (sodium propionate and amiloride) that lowered pHi to 6.7 without ATP depletion failed to activate HSF. Conversely, in studies that lowered ATP stores at normal pH (high K+/nigericin) we found induction of HSF-DNA binding activity. Our data indicate that the effects of ATP depletion alone are sufficient to induce the DNA binding of HSF when oxidative metabolism is impaired, and are consistent with a model proposed recently for transcriptional regulation of stress protein genes during ischemia.

Acidosis↗
PubMed1992

Immunocytochemical localization of transforming growth factors (TGFs) TGF-alpha and TGF-beta in human ovarian tissues.

Light microscopic immunocytochemical technique was utilized in order to elucidate the presence and cellular distribution of transforming growth factors alpha and beta (TGF-alpha and TGF-beta) in human ovarian tissues in different reproductive states using polyclonal antibodies to TGF-alpha and TGF-beta. The results indicated that the ovarian tissue immunostained for both TGF-alpha and TGF-beta. The immunostaining for TGF-alpha was associated with oocytes in the primary follicles, granulosa and theca cell layers, as well as small and large luteal cells. The granulosa cell layers in the small follicles were immunostained for TGF-alpha, but there was very little staining association to the theca cell layers. However, the immunostaining intensity increased in both granulosa and theca cell layers as the size of the follicles increased. The ovarian stroma cells always showed moderate immunostaining. In luteal tissue, both small and large luteal cells immunostained for TGF-alpha and the intensity was similar in both cell types. The immunostaining intensity was similar in both early and midluteal phases and was less than that seen in the granulosa-theca cell layers of the large follicles, and decreased in the late luteal phase. Both corpora albicans and ectopic pregnancy corpora lutea showed a weak immunostaining. Immunostaining of ovarian tissues for TGF-beta indicated that the oocytes of the small preantral follicles stained faintly in the cytoplasm; however, they stained strongly around the nuclear periphery. In small, medium, and large follicles granulosa and theca cell layers immunostained with similar intensity for TGF-beta and its intensity increased with follicular size. The ovarian stroma cells also immunostained for TGF-beta, but with a moderate to low intensity compared with other regions. In luteal tissue, both small and large luteal cells immunostained for TGF-beta and its intensity was similar in early and midluteal phases and reduced during the late luteal phase. This immunostaining was reduced as compared to the granulosa-theca cell layers of the follicles. Corpora albicans and ectopic pregnancy corpora lutea also immunostained for TGF-beta; however, the immunostaining intensity was lower than that seen in luteal tissues of early, mid, or late luteal phases. There was strong immunostaining of the luteal fibroblasts and, interestingly, in small and medium size arterioles; endothelial and smooth muscle cells also immunostained strongly for TGF-beta, whereas the large arterioles showed very little or no immunostaining.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidermal Growth Factor↗
PubMed1992

Tissue distribution of 125I-labeled fetal thyroid hormone in nude mice xenografted with Ewing sarcoma.

Biodistribution of fetal thyroid hormone (RT3) was studied in nude mice with Ewing's sarcoma xenografts. At 30 min and 1, 2, 4, 8, and 12 hr after injection, blood, tumor and normal organs were measured to determine the amount of radioactivity per gram of tissue. The amount of radioactivity in the blood of tumor-bearing mice decreased sharply from 7.64% of injected dose per gram of tissue (% ID/g) at 30 min after inoculation to 0.45%/ID/g at 12 hr. The % of injected dose per gram for 125I-labeled RT3 in the tumor reached 1.92 at 1 hr after injection and decreased to 0.22 at 12 hr. The radiolocalization indices for tumor to other organs at 12 hr ranged from 1.35 to 4.43. This study suggests increased localization of RT3 in the Ewing's sarcoma as compared to other tissues in the nude mouse.

Animals↗
PubMed1992

Laparoscopic oophoropexy for preservation of ovarian function before pelvic node irradiation.

Pelvic irradiation for the treatment of Hodgkin disease in premenopausal women invariably results in ovarian failure unless the ovaries are shielded. Oophoropexy by laparotomy has been used previously to move the ovaries away from the pelvic nodal areas. We have designed, and used in one patient, a new laparoscopic technique that can be performed as an outpatient procedure and that allows radiation therapy to begin immediately. Oophoropexy was performed laparoscopically with placement of sutures through the utero-ovarian ligaments and posterior uterus. Surgical clips were placed to help identify the position of the ovaries postoperatively.

Adult↗
PubMed1992

Progesterone in diagnosis of ectopic pregnancy.

Previous reports suggest that serum progesterone value may be useful in the diagnosis of ectopic pregnancy. These studies have based discriminatory thresholds on a limited number of patients without using statistical correction for biologic variability in an infinitely large population. This study was designed to determine the ability of a single progesterone value to discriminate between normal, ectopic and blighted pregnancies. Sera were obtained from all positive beta HCG tests at Shands Hospital, University of Florida. All samples were assayed simultaneously with a solid phase RIA for progesterone and the results compared with pregnancy outcome. The mean progesterone for normal pregnancies was 32.8 +/- 4.25 ng/ml (n = 49), for ectopic pregnancies 7.8 +/- 0.79 ng/ml (n = 51), and pregnancies which spontaneously aborted 8.1 +/- 0.91 ng/ml (n = 74). Using individual prediction limits progesterone greater than 24 ng/ml would exclude an ectopic pregnancy in 99% of patients. Thus, this test may be useful in selected patients when the diagnosis is unsure after beta HCG and transvaginal ultrasound have been performed.

Abortion, Spontaneous↗
PubMed1991

Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles.

Foreign genes were expressed in liver and skin cells of live mice by using a new apparatus to accelerate DNA-coated microprojectiles into tissues. After introduction of a plasmid in which the firefly luciferase gene was controlled by the human beta-actin promoter, luciferase activity was detectable for up to 14 days in mouse tissues (skin and liver). In situ hybridization histochemistry revealed that microprojectiles penetrated through multiple cell layers without evidence of tissue injury and that 10-20% of the cells in the bombarded area expressed the foreign gene. An advantage of the new design is that internal organs, such as liver, can be transfected without subjecting the tissue to a vacuum. This procedure potentially is applicable to a wide variety of tissues and cell types for studies of transcriptional control elements and for expression of foreign proteins in intact animals.

Actins↗
PubMed1991

Endometriosis associated with massive ascites and absence of pelvic peritoneum.

Although massive ascites associated with endometriosis has been reported in rare cases, this patient was also noted to have massive destruction of the pelvic peritoneum. Failure of medical suppression necessitated total abdominal hysterectomy and bilateral salpingo-oophorectomy. Several months after surgery ascites resolved, possibly with reestablishment of the pelvic peritoneum.

Adult↗
PubMed1991

Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation.

Tonic contractile activity induces mitochondrial biogenesis in mammalian skeletal muscles, necessitating regulation of both nuclear and mitochondrial genes encoding mitochondrial proteins. In this study we compared the time course of induction of citrate synthase (CS) mRNA, a nuclear gene product, to that of genes encoded by mitochondrial DNA during the adaptive response to indirect nerve stimulation in tibialis anterior muscles of adult rabbits. A CS cDNA probe was prepared from a rabbit heart cDNA library by the polymerase chain reaction using synthetic oligonucleotide primers based on the published sequence of the porcine gene. This cDNA probe hybridized to a single band on Northern blots of total or polyadenylated RNA from adult rabbit tissues. Nerve stimulation for 3 days increased the abundance of CS mRNA relative to total cellular RNA by 2.3 +/- 0.2-fold (mean +/- SE, n = 8; P less than 0.01). In contrast, CS enzyme activity and mitochondrial RNA transcripts were not significantly increased at this time point. However, when nerve stimulation was continued for 21 days, the increases in CS mRNA and mitochondrial RNAs were similar. These results support the hypothesis that genetic signaling mechanisms triggered by neural input are sensed initially within the nucleus and that expression of mitochondrial genes is regulated as a secondary event.

Animals↗
PubMed1991

Morphometric analysis of the prefrontal cortex in Huntington's disease.

We performed a morphometric analysis of cresyl violet-stained sections from the dorsolateral prefrontal cortex of 81 patients with Huntington's disease (HD) (grades 2, 3, and 4) and 23 age-matched normal controls. We counted large pyramidal neurons, small neurons, astrocytes, oligodendroglia, and microglia under the guidance of a specifically predefined set of morphologic criteria for each cell type and recorded the thickness of each cortical layer. Our results demonstrate a selective and progressive loss of a subset of the large pyramidal neurons in cortical layers III, V, and VI of HD patients, and a decrease in the thickness of the respective cortical laminae. A genetically determined, cell-autonomous degeneration of cortical neurons could constitute the primary pathologic process. However, the loss of only a fraction of pyramidal cells suggest a parallel, or an alternative, possibility of a retrograde degeneration of cortical neurons that project solely, or principally, to the site of primary degeneration in caudate nuclei.

Adult↗
PubMed1991

Evaluation and treatment of sexual dysfunction in men with diabetes mellitus.

Sexual dysfunction is common among men with Type I and Type II diabetes. Tests of nocturnal penile tumescence (NPT) combined with waking tumescence and questionnaires can more accurately differentiate between primary organic and primary psychogenic impotence. This ability to differentiate the etiology of erectile dysfunction avoids the inappropriate use of penile injections and costly surgical procedures which are unnecessary in treatment of diabetic patients with primary psychogenic impotence. In patients with primary organic impotence, several new treatments are available which result in high patient satisfaction.

Diabetes Complications↗
PubMed1991

Stress proteins and cardiovascular disease.

Understanding the molecular basis by which cells of the heart and blood vessels adapt to physiological stress conditions is an important goal for cardiovascular investigators. The ubiquitous heat shock response provides a model for cellular adaptations to metabolic stresses that are encountered in cardiac disease. Stress-induced synthesis of a family of highly conserved proteins serves to protect cells from injury. In addition, members of this family have essential roles in protein processing and assembly of macromolecular complexes, and in regulation of gene expression, even in unstressed cells. Research concerning the regulation and function of stress proteins potentially is pertinent to the pathophysiology of myocardial hypertrophy, remodeling, and failure, to age-related changes in the cardiovascular system, as well as to ischemic heart disease.

Animals↗
PubMed1991

Identification of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced endometriosis in rats.

The present immunohistochemical studies used polyclonal antibodies specific to epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and monoclonal antibodies to the extracellular binding domain of EGF receptor to elucidate their presence and cellular distribution in surgically induced endometriosis in the rat. Uterine segments were implanted in the mesenteric region adjacent to a blood vessel for a period of 4-6 weeks. During operative reexploration, the implanted tissues were intact, morphologically similar to the controls, and consisted of a cyst containing clear fluid and associated adhesion formation. All the uterine cell types immunostained with antibody to EGF. The highest immunostaining intensity was associated with inflammatory cells infiltrated among endometrial stromal cells, followed by luminal and glandular epithelial and stromal cells. The cysts consisted of an inner simple columnar epithelium, surrounded by several layers of smooth muscle and connective tissue. The cyst epithelial layer immunostained weakly, while the supporting wall stained moderately. The inflammatory cells found within the cyst cavity immunostained very intensely, comparable to those in the endometrium. The patterns of immunostaining for TGF-alpha and EGF receptor were similar to that observed for EGF. Myometrial smooth-muscle cells and endothelial and smooth-muscle cells of arterioles were also immunostained for EGF, TGF-alpha, and EGF receptor, but with lower intensity than that of the endometrium. These observations suggest that, like normal uterine tissue, endometrial implants produce EGF and TGF-alpha locally and contain receptors for EGF. These results imply a possible paracrine or autocrine role for growth factors in the establishment and/or maintenance of endometriotic tissue.

Animals↗
PubMed1990

Increased plasma tumor necrosis factor in severe alcoholic hepatitis.

STUDY OBJECTIVE: To determine whether elevated tumor necrosis factor levels contribute to the clinical manifestations and complications of severe acute alcoholic hepatitis and to evaluate the relation between tumor necrosis factor and plasma levels of endotoxin and interleukin-1 beta. DESIGN: Prospective, controlled study. SETTING: The liver unit of a university teaching hospital. PATIENTS: We studied 21 patients with acute severe alcoholic hepatitis. There were four control groups: patients with inactive alcoholic cirrhosis, alcoholic persons without liver disease, patients with impaired renal function, and normal subjects. MEASUREMENTS AND MAIN RESULTS: With one exception, patients with alcoholic hepatitis had higher tumor necrosis factor levels (mean, 26.3 ng/L; 95% CI, 21.7 to 30.9) than normal subjects (6.4 ng/L; CI, 5.4 to 7.4). Patients who subsequently died had a higher tumor necrosis factor level (34.7 ng/L; CI, 27.8 to 41.6) than survivors (16.6 ng/L; CI, 14.0 to 19.2). In patients with alcoholic hepatitis, tumor necrosis factor levels correlated positively with serum bilirubin (r = 0.74; P = 0.0009) and serum creatinine (r = 0.81; P = 0.0003). Patients with alcoholic hepatitis had higher tumor necrosis factor levels than patients with inactive alcoholic cirrhosis (11.1 ng/L; CI, 8.9 to 13.3) and severely alcoholic persons without liver disease (6.4 ng/L; CI, 5.0 to 7.8). Patients with abnormal renal function had lower tumor necrosis factor levels (14.1 ng/L; CI, 5.4 to 22.8) than patients with alcoholic hepatitis. Serial samples obtained during a 1-week period from patients with alcoholic hepatitis showed no significant change in tumor necrosis factor when patients who died were compared with survivors. No correlation was found between tumor necrosis factor and plasma endotoxin. Levels of interleukin-1 beta did not exceed 20 ng/L. CONCLUSIONS: Elevations in tumor necrosis factor in alcoholic hepatitis are most marked in severe cases, suggesting that tumor necrosis factor plays a role in the pathogenesis.

Alcoholism↗