Transport of estrogen-induced oxytocin receptors in the ventromedial hypothalamus.

The modulation of oxytocin (OT) receptors (OTRs) by estrogen was investigated in the ventromedial hypothalamus by in vitro receptor autoradiography. Treatment of ovariectomized and adrenalectomized rats with various doses of estradiol benzoate (EB) increased OTR binding not only in the ventromedial nuclei of the hypothalamus (VMN), but also in the area lateral to the nuclei (IVMN). After a single injection of EB, OTRs first were induced within the ventrolateral parts of the VMN, and only hours later they appeared in the IVMN. This is consistent with the interpretation that OTRs are first induced within the estrogen-sensitive neurons of the ventrolateral VMN and then are transported laterally out of the nuclei. Two additional experiments confirmed this interpretation. First, local infusion of a low dose (10 micrograms) of the neuronal transport inhibitor vinblastine blocked the appearance of OTRs in the IVMN but did not prevent the induction of OTRs by EB within the nuclei. Second, a knife cut placed lateral to the VMN prevented the spread of OTRs out of the nuclei. However, even after treatment with a high dose of EB (2 x 10 micrograms), progesterone (P) was required for a maximal extension of the area covered by OTRs. Thus, the OTR is an estrogen-induced neurotransmitter receptor that is transported to its site of action, the lateral ventromedial hypothalamus, where it is modulated by P and where estrogen-induced OT immunoreactivity is found.     

Estrogen synthesis by osteoblast cell lines.

Estrogens play a central role in modulating bone turnover and in the postmenopausal female are formed almost exclusively by peripheral conversion of sex steroid precursors derived from the adrenals. In this study we have demonstrated that three human osteoblastic cell lines [HOS, U20S (HTB96) and MG63] possess the enzymes necessary for estrogen synthesis and metabolism. Aromatase, estradiol 17 beta-hydroxysteroid dehydrogenase (reductive and oxidative) and estrone sulfatase activities were measured in whole cell monolayers over a 20 h period by isotopic assay techniques. Significant aromatase activity was detected in all three cell lines ranging from 1.8 +/- 0.2 fmol/20 h/10(6) cells (mean +/- S.D., n = 3) for MG63 cells to 51 +/- 1.5 fmol/20 h/10(6) cells for HOS cells. The specific aromatase inhibitor, 4-hydroxyandrostenedione (1 mumol/L) completely inhibited aromatase activity in these cells. Two of the cell lines, HOS and MG63, had significant estradiol 17 beta-hydroxysteroid dehydrogenase activity with oxidative (32.7 +/- 1.9 and 1068.4 +/- 40.2 fmol/20 h/10(6) cells respectively) predominant over reductive activity (1.6 +/- 0.4 and 38.7 +/- 1.8 fmol/20 h/10(6) cells). All three cell lines were able to hydrolyse estrone sulfate to estrone with activities ranging from 13.3 +/- 1.5 fmol/20 h/10(6) cells for U20S cells to 482.2 +/- 3.7 fmol/20 h/10(6) cells for MG63 cells. Since estrogen has been implicated as a critical factor in the modulation of bone resorption and formation, the regulation of skeletal estrogen production, particularly at the time of the menopause, is likely to be an important mechanism by which bone volume is determined in physiological and pathological states.     

Nitric oxide participates in the intestinal pathology associated with murine syngeneic graft-versus-host disease

Syngeneic graft-versus-host disease (SGVHD) develops following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a short course of cyclosporin A (CsA) therapy. The disease is characterized by the development of a T helper cell type 1-like cytokine response [interleukin (IL)-12, interferon-gamma (IFN-gamma), and tumor necrosis factor alpha], and macrophage activation is central to development of the syndrome. It has been shown that nitric oxide (NO) participates significantly in the development of allogeneic GVHD. Studies were initiated to determine if NO participates in the pathology associated with SGVHD. Significant increases in inducible NO synthase (iNOS) mRNA and circulating NO were found in the tissues of SGVHD versus control animals. Treatment of SGVHD animals with the iNOS inhibitor aminoguanidine (AG) reversed the pathology associated with this disease. Furthermore, AG treatment reduced the production of IL-12 and IFN-gamma mRNA in the colons of CsA-treated mice. These studies demonstrate that NO participates in the pathological processes that are associated with the development of murine SGVHD.     

The influence of visual illusions on grasp position

 Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This partial dissociation is discussed in terms of its implications for streams of visual processing. Received: 17 November 1997 / Accepted: 11 September 1998     

Epidemiology of group C rotavirus infection in Western New York women of childbearing age.

Umbilical cord serum samples (380), an average of 10 per month for 3 years (1990 to 1992), were tested by indirect immunofluorescence assay for group C rotavirus immunoglobulin G. Thirty percent were positive, suggesting that approximately one-third of women of childbearing age in western New York have experienced group C rotavirus infection.     

Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center

The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital.