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Biomedical subjects

J J Osborne

Publications and source records attributed to J J Osborne.

6 recordsLinked to original sources
PubMed1999

Threonine phosphorylations induced by RX-871024 and insulin secretagogues in betaTC6-F7 cells.

Treatment of the pancreatic beta-cell line betaTC6-F7 with an imidazoline compound, RX-871024, KCl, or tolbutamide resulted in increased threonine phosphorylation of a 220-kDa protein (p220) concurrent with enhanced insulin secretion, which can be partially antagonized by diazoxide, an ATP-sensitive potassium (K(ATP)) channel activator. Although phosphorylation of p220 was regulated by cytoplasmic free calcium concentration ([Ca(2+)](i)), membrane depolarization alone was not sufficient to induce phosphorylation. Phosphorylation of p220 also was not directly mediated by protein kinase A, protein kinase C, or insulin exocytosis. Analysis of subcellular fractions indicated that p220 is a hydrophilic protein localized exclusively in the cytosol. Subsequently, p220 was purified to homogeneity, sequenced, and identified as nonmuscle myosin heavy chain-A (MHC-A). Stimulation of threonine phosphorylation of nonmuscle MHC-A by KCl treatment also resulted in increased phosphorylation of a 40-kDa protein, which was coimmunoprecipitated by antibody to MHC-A. Our results suggest that both nonmuscle MHC-A and the 40-kDa protein may play roles in regulating signal transduction, leading to insulin secretion.

Amino Acid Sequence↗
PubMed1997

Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity.

Raloxifene (LY139481 HCl) is a selective estrogen receptor modulator (SERM) which blocks the effects of estrogen on some tissues, such as the breast and uterus, while mimicking estrogen in other tissues, such as bone. To study the origins of this unique pharmacology, we have prepared the major metabolites of raloxifene as chemical probes for examining the estrogen receptor function in vitro and in vivo. In human breast cancer cell (MCF-7) related assays, these glucuronide conjugates show little affinity for the estrogen receptor and are more than two orders of magnitude less potent at inhibiting cell proliferation than raloxifene. In non-traditional estrogen target tissue, such as bone, these metabolites are less effective than the parent at inhibiting cytokine-stimulated bone resorbing activity in rat osteoclasts or producing transforming growth factor beta-3 (TGF-beta3). In animal models, tissue distribution studies with radiolabelled metabolite indicate that conversion to raloxifene occurs readily in a variety of tissues including the liver, lung, spleen, kidney, bone and uterus. Differential conversion of metabolite in target organs, such as bone and the uterus, is not observed indicating that the origin of raloxifene's pharmacology does not result from tissue-selective deconjugation of metabolite to parent.

Adenocarcinoma↗
PubMed1989

A physical therapy protocol for orthognathic surgery.

Physical therapy has become standard procedure for treatment of many aspects of temporomandibular joint dysfunction. In the area of orthognathic surgery, there appears to be a significant gap in the use of physical therapy. This article offers a suggested protocol of treatment to improve the overall outcome and provide for consistency of treatment.

Humans↗
PubMed1986

Opioid agonist activity of ICI 174864 and its carboxypeptidase degradation product, LY281217.

The opioid peptide antagonist, ICI 174864 ([allyl]2-Tyr-alpha-amino-isobutyric acid (Aib)-Aib-Phe-Leu-OH), can produce analgesic effects in mice. The present study explored the possibility that ICI 174864 1) may have affinity and agonist efficacy at mu receptors and/or 2) may form a carboxypeptidase degradation product in vivo that possesses mu agonist activity. In vitro, ICI 174864 (10(-7) to 10(-4) M) inhibited the twitch in the electrically stimulated mouse vas deferens (ED50 = 90 microM) and guinea pig ileum (ED50 greater than 10(-4) M). The in vitro partial agonist activity of ICI 174864 was due to interaction with delta and not mu receptors because the apparent dissociation constant for naloxone using ICI 174864 as the agonist was similar to the apparent dissociation constant for the interaction of naloxone with delta and not mu receptors. Thus, ICI 174864 is a weak partial agonist at delta receptors with little affinity or efficacy at mu receptors. The incubation of ICI 174864 with carboxypeptidase A generated a peptide, LY281217 [(allyl)2-Tyr-Aib-Aib-Phe-OH], which was a more potent agonist in the mouse vas deferens and guinea pig ileum than ICI 174864. The agonist activity of LY281217 was due to interaction with mu and not delta receptors because LY281217 was approximately 100-fold more potent than ICI 174864 as an agonist in the guinea pig ileum, the apparent dissociation constant for naloxone using LY281217 as the agonist was similar to the apparent dissociation constant for the interaction of naloxone with mu receptors and the delta selective antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics, Opioid↗
PubMedDate not supplied

Improving treatment adherence in drug abusers who are HIV-positive.

This article discusses the complex dual diagnosis of HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome) and substance abuse, which affects a growing number of individuals worldwide. A brief review of HIV/AIDS is provided and the connection between HIV/AIDS and substance abuse is described. Substance abuse complicates both HIV/AIDS and its management because of the effects that illicit drugs have on various body systems and because of the behavioral disturbances that accompany substance use. For a variety of reasons adherence to treatment is poor in this population and several factors that negatively impact adherence are outlined. Treatment of drug abusers who are HIV-positive requires more flexibility than treating drug abuse and HIV separately. Because medication regimens can be complicated and demanding and nonadherence to treatment can cause mutation of the virus resulting in drug-resistant strains, it is essential to get the patient committed to treatment The goals of treatment are abstinence from illicit drugs, adherence to a treatment regimen, suppression of viral load, improved CD4 count, and improved quality of life. The role of the case manager is critical to improving treatment adherence. Essential attributes include knowledge of disease processes, critical thinking, and the ability to navigate the healthcare system. Case management interventions to improve treatment adherence should be directed at the patient, the regimen, the client-patient relationship, and the healthcare system. Because HIV/AIDS is now classified as a chronic disease and is no longer viewed as a death sentence, people who are HIV-positive have hope for longevity and a cure. It is this hope for a longer life and possible cure that can be used to motivate substance abusers who are HIV-infected to improve their treatment adherence and quality of life.

Antiretroviral Therapy, Highly Active↗