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G Weiss

Publications and source records attributed to G Weiss.

At least 325 records · Page 18Linked to original sources

The effect of in vivo progesterone administration on relaxin-inhibited rat uterine contractions.

Progesterone pretreatment in vitro was previously shown to sensitize myometrium to the inhibiting effect of relaxin. The following experiments were performed to control for possible artifacts of the in vitro system and to place these studies on a more physiologic basis. Immature rats were treated with estrogen and either progesterone or vehicle only. Uterine horn segments were isolated and mounted in a muscle bath. After a baseline contraction pattern was established by means of electrical stimulation, porcine relaxin was added to the bath. At all dose levels of relaxin, greater inhibition of contraction amplitude occurred in uterine segments of progesterone-treated animals. Since both progesterone and relaxin are present in the circulation from the time of the missed menses in human pregnancy, this interaction suggests a physiologic synergism in the maintenance of early human pregnancy.

Animals↗

Phase-I trial of combination therapy with continuous-infusion MMPR and continuous-infusion 5-FU.

Fourty-four evaluable patients were treated with 6-methylmercaptopurine riboside (MMPR) at a dose of 20 mg/m2/day X 5 by continuous IV infusion (days 1-5 and 5-fluorouracil (5-FU) on an escalating dose schedule of 300-1519 mg/m2/day X 5 by continuous IV infusion (days 2-6). Dose-limiting oral mucositis occurred at a 5-FU dose of 1,381 mg/m2/day; other toxicities included nausea, vomiting, diarrhea, skin rash, and occasional myelosuppression. A partial and a complete response were observed in two previously untreated patients with metastatic colon carcinoma given the highest 5-FU doses (1,381 and 1,519 mg/m2/day). Bone marrow phosphoribosyl pyrophosphate (PRPP) levels monitored after 24 h of MMPR treatment indicated increases of 7.8- and 9.2-fold those found prior to therapy.

Adult↗

Lectin target cells in human central nervous system and the pituitary gland.

Peanut lectin (PNL), Concanavalin A (Con A) and Ulex europaeus lectin I (Ulex) were chosen to map their binding sites in different regions of formalin fixed and paraffin embedded human central nervous system tissue and pituitary gland tissues. An extended PaP method was used for PNL and Ulex, whereas a direct peroxidase technique was employed for Con A. In astrocytes, the cytoplasm as well as the delicate processes were stained by PNL and Con A; the most conspicuous binding of PNL was seen in the ependymal cells and on the surface of plexus epithelial cells; in the anterior part of the pituitary gland a selective population was PNL positive. Intracytoplasmic Con A acceptors could be demonstrated in neurons, in ependymal cells, and in plexus epithelial cells. Intracytoplasmic Con A receptors were finely granular in astrocytes, oligodendrocytes, and in some cells in the pituitary gland. Ulex binding was restricted to the vascular endothelial cells and a selective population of cells in the pituitary gland. Our results suggest that lectins may be good tools for the evaluation of their respective target cells in the central nervous system and in the pituitary gland.

Arachis↗

Concanavalin A binding and neuronal differentiation. A light microscopic study on neuronal tumours.

Concanavalin A (Con A) acceptors have been demonstrated in large differentiated neurons in a previous paper. In order to elucidate the correlation between Con A binding in normal and neoplastic neurons and lectin binding dependence upon the differentiation grade, 26 tumours of the neuronal series were examined using formalin fixed and paraffin embedded biopsy specimen. The neoplasms included 3 gangliocytomas, 7 gangliogliomas, 1 central neuroblastoma, 11 medulloblastomas, 2 retinoblastomas, and 2 sympathicoblastomas. Well differentiated neurons in gangliocytomas and gangliogliomas expressed a high intracytoplasmic Con A acceptor density comparable to the feature in large non-neoplastic neurons. Less differentiated neurons and neuroblasts showed a weak perinuclear fine granular binding or an absolute lack of binding molecules, respectively. Our results suggest that in a variety of tumours, Concanavalin A receptor density in neurons depends upon the degree of differentiation of the cell. Well differentiated cells have a higher density than poorly differentiated neoplastic neurons.

Adolescent↗

Concanavalin A target cells in human brain tumours.

Using a lectin-peroxidase method, Concanavalin A binding was examined on formalin-fixed paraffin-embedded biopsy specimens (n = 143) of the most frequent central nervous system tumours. The brain tumours included oligodendrogliomas, astrocytomas, glioblastomas, ependymomas, neurinomas, meningiomas, medulloblastomas and plexus papillomas. In oligodendroglioma cells, only a weak granular intracytoplasmic staining was observed. The astrocytomas showed a strong reaction in fibrillary astrocytes and in tumour areas undergoing small cystic degeneration. Staining of protoplasmic astrocytes was weaker; pilocytic astrocytes demonstrated poor perinuclear staining. Intracytoplasmic Con A binding in gemistocytic astrocytes was distinct but inconstant and rather diffuse. In the glioblastomas the lymphocyte-like small astrocytes were negative. Giant multinucleated astrocytes stained strongly. In ependymomas no or at most a weak perinuclear reaction was observed, whereas the acceptor density was as high as in the normal ependymocytes in areas where the tumour was capable of producing organotypical structures. Plexus papillomas showed a strong intracytoplasmic staining comparable to the normal plexus epithelial cell. This feature was preserved in the malignant variants. In general, meningiomas and neurinomas were negative. Xanthomatous-degenerated meningioma cells, however, showed a distinct to strong intracytoplasmic staining. This feature was characteristic for the xanthomatous subtype of meningiomas. Granular cells with strong intracytoplasmic Con A staining often occurred at the border of fibrillary to reticular differentiated areas of neurinomas. Medulloblastomas were completely negative. Our results indicate that Con A binding to human brain tumours is specific and rather cytotypical than histotypical . The Con A acceptor density is probably related to the grade of differentiation. Lectin mapping of tumours leads to cytotypical binding patterns which may contribute to the differential diagnosis of neoplasias.

Astrocytoma↗

Relaxin in human decidua and term placenta.

Using both a homologous porcine RIA and 3 bioassays, we investigated the relaxin content of human decidua from first trimester and term gestations and of placentas at term. Aqueous extracts of these tissues yielded only between 211 and 1090 pg immunoreactive relaxin/g fresh tissue. Neither acetonehexane extraction, octadecylsilica cartridge elution nor molecular sieve chromatography increased these relaxin levels. Compared with term decidua, first trimester decidua contained significantly higher levels of immunoreactive relaxin. In vitro studies did not evidence significant relaxin production by either decidual or placental tissues, even in the presence of decidual prolactin production. These results are in direct contrast to earlier reports of high concentrations of relaxin in decidua and placenta.

Animals↗

Stimulation of human sperm cervical mucus penetration in vitro by relaxin.

The effect of relaxin, a peptide hormone present in seminal plasma, on the penetration of cervical mucus by washed human sperm in vitro was studied. Penetration was analyzed by two methods. The total number of sperm per 100 X field at the 10-mm, 20-mm, and 30-mm points along a mucus-filled capillary tube was counted and the farthest distance 100 sperm and 5 sperm/100 X field penetrated the capillary tube was measured. These measurements were made at 30, 60, and 90 minutes. Treating washed sperm with physiologic concentrations of relaxin resulted in significantly increased sperm penetration as compared with sperm treated with albumin or buffer. Replacing seminal plasma to washed sperm resulted in equivalently increased penetration. The findings strongly suggest that relaxin is necessary for proper penetration of cervical mucus by human sperm.

Albumins↗

The effect of an anti-insulin antiserum on human sperm motility.

Inhibition of sperm motility by anti-relaxin antiserum has been previously reported. This effect may be secondary to a nonspecific effect of immunoglobulins binding to sperm or to a specific inhibition of relaxin activity at the sperm surface. The current investigation demonstrates that an anti-insulin antiserum does not inhibit sperm motility in the same system in which an anti-relaxin antiserum results in inhibition. This supports the hypothesis that the anti-relaxin antiserum effect is specific.

Humans↗

Relaxin.

The past decade has seen major advances in understanding the chemistry of relaxin. Sensitive radioimmunoassays have allowed description of the secretion patterns of relaxin in several species. It is likely that technical advances in the near future will provide significant quantities of human relaxin as well as monoclonal antibodies to various relaxins. These tools should clarify the physiological roles of relaxin, elucidate its mechanisms of action, and enable testing of human relaxin as a potentially useful pharmacological agent.

Animals↗

Effects of semisynthetic diets on xenobiotic metabolizing enzyme activity and morphology of small intestinal mucosa in humans.

We studied the effects of semisynthetic (elemental) diets on the function and morphology of the human small intestine. The enzymatic capacity of the intestinal mucosa to metabolize lipophilic xenobiotics was investigated using jejunal biopsy specimens from 15 normal subjects who were on an isocaloric, nutritionally balanced semisynthetic diet for 7 days and thereafter on a normal home diet. Each subject underwent biopsy twice: on day 7 of semisynthetic diet and again on home diet 2-6 wk later. The jejunal mucosal tissue was examined by histologic morphometry and stereomicroscopy. Moreover, 25-50 mg of the biopsy material was homogenized and the following enzyme activities were determined in 20,000 g supernatant: for cytochrome P450-dependent monooxygenase activity with 7-ethoxycoumarin O-deethylase (EOD) and with nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and for conjugation activity with 1-naphthol glucuronyltransferase (NGT). The NGT and reductase activities were unchanged by the dietary alterations. However, the EOD activity was significantly depressed on semisynthetic diet and rose to control range on home diet (from 5.3 +/- 2.5 to 12.4 +/- 8.6 pmol/min X 10 mg wet wt). Male subjects had significantly higher EOD activities than female subjects on semisynthetic diet (6.6 +/- 2.3 vs. 3.2 +/- 0.9) as well as on home diet (16.3 +/- 9.0 vs. 6.4 +/- 3.0). Semisynthetic diet also reduced the jejunal villous height significantly when compared with home diet (408 +/- 49 vs. 373 +/- 44 micron). Therefore, on semisynthetic diet the toxicity of dietary xenobiotics that are inactivated by the intestinal mucosa may be increased.

7-Alkoxycoumarin O-Dealkylase↗

Effect of prolactin and relaxin on in vitro rat uterine contractions and prolactin interaction with relaxin.

The balance between relaxin and prolactin has been suggested to be significant in the control of uterine activity during pregnancy. The current study was designed to determine the effect of rat prolactin on rat uterine horn segment contractility and its interaction with relaxin. Rat uterine segments mounted on a smooth muscle transducer were treated sequentially with prolactin and relaxin, and stimulated electrically. No stimulatory effect of prolactin was noted. Relaxin-inhibited uterine horn segment activity was not altered by prolactin. The reported stimulatory effect of prolactin may have been a pharmacologic effect of human prolactin on rat uterine horn segments, or may have resulted from contaminants in the preparations used.

Animals↗

[Relaxin].

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Humans↗

The effect of relaxin and progesterone on rat uterine contractions.

The effect of porcine relaxin on electrically stimulated in vitro contractions of isolated uterine horn segments from estrogen-pretreated immature rats was studied. Relaxin decreased the amplitude of contractions. A mean of 8.3 ng/ml of relaxin produced a 90% decrease in contraction amplitude. There was a minimal effect of 1.0 microgram/ml of progesterone on contraction amplitude. In vitro pretreatment of the isolated uterine segment with this dose of progesterone for 15 minutes did not significantly affect the dose of relaxin needed to decrease the amplitude of contractions. In contrast, pretreatment with progesterone for 45 minutes significantly decreased the concentration of relaxin needed to decrease contraction amplitude. Only 4.7 ng/ml of relaxin was needed to produce a 90% decrease in amplitude after progesterone pretreatment for 45 minutes (p less than 0.005). Relaxin and progesterone synergize in decreasing the amplitude of uterine contractions in vitro. A similar effect may occur in vivo.

Animals↗

Long-term outcome of hyperactive children.

A review of outcome studies of hyperactive children suggests that they experience significant academic, social, and conduct difficulties during adolescence, and that social, emotional, and impulse problems persist into young adulthood for the majority. While some hyperactive children were found to be functioning normally as adults, a troublesome minority were experiencing severe psychiatric or antisocial problems.

Achievement↗

Stimulatory effect of luteinizing hormone upon relaxin secretion by cultured porcine preovulatory granulosa cells.

Relaxin, a peptide hormone capable of causing connective tissue alterations, is produced by the corpus luteum and traditionally considered a hormone of pregnancy. We have cultured granulosa cells from preovulatory porcine follicles and have found that these non-pregnancy associated cells secrete relaxin, and that luteinizing hormone, which stimulates ovulation, enhances relaxin secretion by cells from large preovulatory follicles. These results suggest that relaxin secreted prior to ovulation may have a local ovarian effect, perhaps facilitating ovulation.

Animals↗

Effect of anti-relaxin antiserum on sperm motility in vitro.

Rabbit anti-relaxin antisera, but not normal rabbit sera, causes a rapid decline of motility of washed human sperm. Preincubation of the antisera with relaxin eliminates this effect. This sperm immobilization effect can serve as a basis of a rapid screening test for anti-relaxin antisera and as a novel adjuvant to barrier contraceptive methods.

Antigen-Antibody Complex↗