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Biomedical subjects

J Bornstein

Publications and source records attributed to J Bornstein.

At least 73 records · Page 4Linked to original sources

Stage III-IV epithelial carcinoma of the ovary: is the second-look operation of any value for the patient?

A second-look operation (SLO) was performed in 18 of 24 patients operated for Stage III-IV epithelial carcinoma of the ovary in order to assess the effect of chemotherapy and to decide if further treatment, such as radiation therapy, was indicated. All patients had postoperative combination chemotherapy: either with PA [Platinol (Bristol, UK) and adriamycin] or with CHAD (cyclophosphamide, hexamethylmelamine, adriamycin and cis-diamminedichloroplatinum). In 7 of 18 (39%) patients who had SLO following chemotherapy, macroscopic tumor was present; in 7 (39%) patients, microscopic residual or recurrent disease was found, as proven by histological examination of the biopsies taken during the operation. Only in four patients (29.7%) was the SLO negative. Of these patients, three had recurrent disease after 3,6 and 7 months postoperatively. These findings indicate that the SLO was noncontributory to the management of the patients. The role of the SLO commonly used in most current treatment protocols of patients with Stage III-IV epithelial carcinoma of the ovary is questionable and requires further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

Activation of phosphoprotein phosphatases by growth hormone sequences with insulin-like activity.

The N-terminal part sequences of pituitary growth hormone, N alpha-acetyl-hGH 7-13 and hGH 6-13, promoted conversion of glycogen synthase b to glycogen synthase a in skeletal muscle and adipose tissue when injected intravenously. The peptides also caused conversion of phosphorylase a to phosphorylase b in liver and adipose tissue, but not in muscle, where the peptides antagonised activation of phosphorylase. Synthase phosphatase activity in muscle and phosphorylase phosphatase activity in liver increased after injection of peptide, with time courses of change similar to those seen for muscle synthase and liver phosphorylase activities. Injection of peptide also decreased both the cyclic AMP dependent and independent synthase kinase activities in muscle. These results show that the insulin-like activities of these peptides on glycogen synthase and phosphorylase involve both increases in protein phosphatase activities and inhibition of protein kinase activities. These results are discussed in relation to the insulin-like activities of growth hormone.

Adipose Tissue↗

Outpatient diagnostic endometrial aspiration curettage with a new aspiration curette.

During a period of 2 years (1981-1982), 226 outpatient endometrial aspiration curettages (EACs) were performed with a new aspiration curette that had been developed by the authors. All patients had risk for general anesthesia. From 17 of them, endometrial polyps were removed by the EAC. Endometrial carcinoma was diagnosed in eight others, adenomatous hyperplasia in four, and cystic hyperplasia in two women. The main advantage of the new curette is the ability to aspirate endometrial polyps through its modified opening.

Adolescent↗

Detection of human papillomavirus DNA in advanced epithelial ovarian carcinoma.

Tissue specimens from 10 out of 12 patients with advanced epithelial ovarian adenocarcinoma contained DNA of human papillomavirus type 6 (HPV-6). HPV DNA was identified by in situ hybridization at high stringency using biotin-labeled DNA probes. Nonneoplastic tissue specimens from other pelvic sites of the same patients were also examined. None showed evidence of HPV DNA. The meaning of these findings in relation to epithelial ovarian carcinoma is discussed.

Adenocarcinoma↗

The "forgotten" intrauterine device.

It is essential to ascertain that women who had an IUD inserted at some time have indeed had the device removed. It is also important to ensure that the whole IUD was removed and that no parts were left in the uterine cavity. This is especially true in cases of infertility and should be ascertained before invasive investigations such as hysterosalpingography or laparoscopy commence. An accurate history and ultrasonography can easily rule out a forgotten or fragmented IUD, thereby preventing considerable unnecessary suffering and expense.

Adult↗

Human papillomavirus associated with vaginal intraepithelial neoplasia in women exposed to diethylstilbestrol in utero.

Five out of 959 young women, exposed to diethylstilbestrol (DES) in utero, developed vaginal intraepithelial neoplasia while they were under follow-up in the Diethylstilbestrol-Adenosis Project at Baylor College of Medicine, Houston, Texas. We suggest that the development of the vaginal intraepithelial neoplasia at a younger age than usual may be caused by a higher susceptibility of the DES-exposed patient to factors associated with the development of intraepithelial neoplasia. A common finding in all five women was the detection of the deoxyribonucleic acid (DNA) of human papillomavirus types 6 or 16 in their lesions, using high-stringency in situ hybridization. The role of human papillomavirus and herpes simplex virus in the etiology of intraepithelial neoplasia is discussed. Close follow-up is recommended for DES-exposed patients, especially those who have risk factors known to be associated with genital neoplasia.

Adolescent↗

Triiodothyronine (T3) regulation of thyrotropin subunit gene transcription is proportional to T3 nuclear receptor occupancy.

We have investigated the relationship between T3 nuclear receptor occupancy and the T3-mediated responses of TSH subunit gene expression. Hypothyroid mice bearing TtT 97 thyrotropic tumors were injected daily for 12 days with 0-10 micrograms T3/100 g BW, ip. T3 levels were measured in plasma and in tumor nuclei, and the maximal T3-binding capacity of tumor nuclei and the fractional occupancy of T3 nuclear receptors at each dose were calculated. T3-mediated decreases in TSH secretion were half-maximal at a dose of 0.2-0.3 micrograms/100 g BW, which resulted in plasma T3 levels of 0.98-1.2 ng/ml. Responses at the TSH subunit gene levels followed a similar pattern. Transcription of TSH beta and alpha-subunit genes was decreased maximally from 384 to 26 ppm for TSH beta and from 424 to 112 ppm for alpha-subunit. Inhibition of transcription was half-maximal at plasma T3 concentrations of 0.8 and 1.0 ng/ml for TSH beta and alpha-subunit, respectively. The half-maximal effective doses of T3 for decreases in TSH gene transcription were in good agreement with the amount of T3 necessary to saturate 50% of nuclear T3 receptors in the tumor, calculated at 1.07 ng/ml T3. A plot of fractional decrease in TSH subunit gene transcription vs. fractional T3 nuclear receptor occupancy demonstrated a straight line relationship for both TSH beta and alpha-subunit. Thus, the response of both TSH subunit genes to T3, a decrease in TSH beta and alpha-subunit gene transcription, is directly proportional to nuclear T3 receptor occupancy.

Animals↗

Substance P enteric neurons mediate non-cholinergic transmission to the circular muscle of the guinea-pig intestine.

The sites of action and possible roles of substance P in contracting the circular muscle of the guinea-pig ileum were studied using two analogues of substance P that act as antagonists of some of its actions. These are D-Arg1, D-Pro2, D-Trp7,9, Leu11-substance P and D-Pro2, D-Trp7,9-substance P, referred to by the single letter amino acid codes for the substituting amino acids as (RPWWL)-SP and (PWW)-SP, respectively. Records of circular muscle activity were taken from strips of intestine free of mucosa and submucosa and from rings with all layers of intestine intact. Substance P was equally effective in contracting the circular muscle strips as it was in contracting the longitudinal muscle. The contractions of strips were not blocked by hyoscine (2 X 10(-6) M) or tetrodotoxin (6 X 10(-7) M), but were substantially reduced by (RPWWL)-SP (6.7 X 10(-6) M) or (PWW)-SP (2 X 10(-5) M). In contrast, contractions of the circular muscle of whole rings of intestine elicited by low concentrations of substance P (4 X 10(-7) M) were blocked by hyoscine or tetrodotoxin but not reduced by the substance P antagonists in the concentrations referred to above. These observations indicate that the antagonists are effective at receptors for substance P on the muscle, but not at substance P receptors on enteric cholinergic nerves. Transmural stimulation of strips of circular muscle or of intestinal rings in the presence of hyoscine evoked contractions that were blocked by tetrodotoxin. These hyoscine-resistant, nerve-mediated contractions could be elicited by single pulses in the strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assay of insulin mediator activity with soluble pyruvate dehydrogenase phosphatase.

The putative mediator of intracellular insulin action has been assayed quantitatively by its ability to increase the activity of solubilized pyruvate dehydrogenase (PDH) phosphatase. Conversion of soluble beef heart PDH b to PDH a by PDH phosphatase increased when incubation was carried out in the presence of a crude insulin mediator fraction generated from insulin-treated adipose tissue or liver plasma membranes. Increased PDH phosphatase activity was proportional to the concentration of added insulin mediator. Mediator generation was rapid, with a half-time of approximately 45 sec and was insulin dose dependent. Half-maximal mediator activity was produced at 0.3 nM added insulin, with maximal activity being generated at approximately 3 nM insulin. Mediator activity was significantly decreased at 7 nM insulin, but was increased 4-fold after ethanol extraction. Mediator behaved as an activator of PDH phosphatase, apparently by abolishing the inhibitory effects of ATP on phosphatase activity, but had no effect on PDH kinase activity. The assay of insulin mediator activity described here can be carried out under standardized conditions, in contrast to previously described methods using particulate mitochondrial preparations.

Adenosine Triphosphate↗

Continuous extraovular prostaglandin F2 alpha instillation for second-trimester pregnancy termination.

One hundred midtrimester pregnancy terminations were successfully induced with continuous extraovular infusion of prostaglandin F2 alpha (PGF2 alpha). The solution was infused into the extraovular space with a newly developed double-balloon catheter. The mean instillation abortion time was 12.9 h. Abortion was completed in 48% of the patients within 12 h, in 80% within 18 h, and in 96% within 24 h. The mean total dose of PGF2 alpha instilled was 12.4 mg/patient. Only four patients aborted after 24 h from the insertion of the catheter and instillation of the PGF2 alpha. Side effects were few. Thirteen patients (13%) had nausea and vomiting, and 14 (14%) had transient pyrexia (above 38 C). No major complications occurred. It appears that this method has a high success rate, good patient tolerance, and an acceptable safety factor with few minor side effects.

Abortifacient Agents↗

Ambulatory removal of cervical polyps under colposcopy.

Hospitalization, polypectomy, and D&C under general anesthesia, are the usual way to treat a cervical polyp. This article describes a simple, ambulatory way of performing polypectomy under colposcopic vision, with no need for hospitalization and general anesthesia. The paper summarizes our experience with this method in 96 patients. Our conclusion is that this simple procedure spares the patient general anesthesia, D&C, and unnecessary hospitalization with attendant expense.

Adult↗

Regulation of glycogen synthase activity in muscle by a C-terminal part sequence of human growth hormone.

The synthetic peptide hGH 177-191, corresponding to the last 15 residues at the carboxyl terminus of human pituitary growth hormone, promotes the conversion of glycogen synthase a to glycogen synthase b in muscle. When injected, the peptide was found to produce inactivation of glycogen synthase phosphatase activity in rat skeletal muscle. The time course of phosphatase inactivation was closely correlated with that for glycogen synthase. The peptide had no effect either on muscle 3',5'-cyclic AMP levels or on synthase kinase activity. These results can be explained in terms of a dynamic cycle of interconversion of synthase between active and inactive forms, by the simultaneous action of synthase kinases and synthase phosphatases. A decrease in the ratio of phosphatase to kinase activity would result in a decrease in the steady-state level of synthase a activity.

Animals↗

Modulation of hepatic insulin receptors by a human growth hormone fragment (hGH 6-13).

A synthetic amino-terminal fragment of human growth hormone (hGH) containing the sequence H2N-Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala-COOH (hGH 6-13) was shown to increase [125I]iodoinsulin binding to rat hepatic receptors in vivo. Analysis of the binding data indicated an increase in the capacity of the insulin receptors or the number of available receptors. In vitro experiments with isolated hepatocytes and hepatic plasma membranes revealed no direct interaction between the hGH 6-13 and the hepatic insulin receptors. When the isolated hepatocytes were preincubated with the synthetic hGH fragment (10 micrograms/ml) at 37 degrees C for 30 min prior to tests for insulin binding, the binding of [125I]iodoinsulin to the hepatic receptors was significantly enhanced. The variance between the in vivo and in vitro findings was considered in terms of the mechanism of hormonal actions mediated through a secondary cellular mediator.

Animals↗

Parallel insulin-like actions of human growth hormone and its part sequence hGH 7-13.

The insulin-like effects of human growth hormone and the synthetic part sequence, N alpha-acetyl-hGH 7-13, on glycogen synthase and phosphorylase have been compared in an in vivo system using 16--18-day-old rats. Both the hormone and its part sequences had similar effects, increasing muscle glycogen synthase a activity and decreasing liver phosphorylase a activity, without affecting phosphorylase activity in muscle or synthase activity in liver. Insulin had similar effects, but also increased liver synthase a activity. The effects of all three substances could be abolished by prior treatment of the animals with anti-insulin serum, showing that the effects of growth hormone and its part sequences were insulin-dependent. Both growth hormone and the synthetic peptide increased the binding of insulin to liver plasma membrane. It is concluded that the insulin-like activity of human growth hormone is associated with a region containing residues 7 to 13 of the hormone molecule, and that this activity is insulin-dependent. It is suggested that both growth hormone and the synthetic peptide produce insulin-like activity by enhancing the binding of circulating insulin to its receptor.

Animals↗

Metabolic actions of pituitary growth hormone. I. Inhibition of acetyl CoA carboxylase by human growth hormone and a carboxyl terminal part sequence acting through a second messenger.

Evidence is presented showing that human growth hormone (hGH) and its part sequence hGH 172-191 inhibit acetyl CoA carboxylase and hence fatty acid synthesis by interacting with adipocyte and hepatocyte plasma membranes, resulting in the release of a relatively non-polar second 'messenger'. This second 'messenger' inhibits the enzyme in a soluble fraction by increasing its phosphorylation. It appears that growth hormone requires some modification prior to demonstrating this activity, as it is active in intact cells and unfractionated homogenates but has no activity in 'messenger release' from purified membrane fractions. The relations of these actions to the in vivo effects of hGH are discussed.

Acetyl-CoA Carboxylase↗