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J Simms

Publications and source records attributed to J Simms.

10 recordsLinked to original sources

The pharmacology of CGRP-responsive receptors in cultured and transfected cells.

Historically, CGRP receptors have been classified as CGRP(1) or CGRP(2) subtypes, chiefly depending on their affinity for the antagonist CGRP(8-37). It has been shown that the complex between calcitonin receptor-like receptor (CRLR or CL) and receptor activity modifying protein (RAMP) 1 provides a molecular correlate for the CGRP(1) receptor; however, this does not explain the range of affinities seen for CGRP(8-37) in isolated tissues. It is suggested that these may largely be explained by a combination of methodological factors and CGRP-responsive receptors generated by CL and RAMP2 or RAMP3 and complexes of RAMPs with the calcitonin receptor.

Animals↗

Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin.

RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, allowing the generation of six distinct receptors with preferences for CGRP (CT gene-related peptide), adrenomedullin, amylin and CT. There are three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of receptor pharmacology, whereas the transmembrane domain contributes to association of the RAMP with the GPCR. The N-terminus of all members of the RAMP family probably contains two disulphide bonds; a potential third disulphide is found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the ligand and plays a key role in its binding, either directly or indirectly. BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very high selectivity for the human CGRP(1) receptor.

Adrenomedullin↗

Agonist binding to peptide hormone receptors.

A fundamental issue in molecular pharmacology is to define how agonist-receptor interaction differs from that of antagonist-receptor interaction. The V(1a) vasopressin receptor (V(1a)R) is a member of a family of related G-protein-coupled receptors (GPCRs) that are activated by vasopressin, oxytocin (OT) and related peptides. A segment of the N-terminus that was required for agonist binding, but not antagonist binding, was identified by characterizing truncated V(1a)R constructs. Site-directed mutagenesis revealed that a single residue (Arg(46)) was critical for agonist binding and receptor activation. The N-terminus of the related OT receptor (OTR) could recover agonist binding in a chimaeric OTR(N)-V(1a)R construct. Furthermore, Arg(34) of the human OTR, which corresponds to Arg(46) of the rat V(1a)R, provided agonist-specific binding epitopes in the OTR, indicating a conserved function of this locus throughout this GPCR subfamily. Mutation of Arg(46) revealed that high-affinity agonist binding had an absolute requirement for arginine at this position.

Animals↗

The potential for biofilm growth in water distribution systems.

Biofilms on pipe walls in water distribution systems are composed of bacteria in a polymeric matrix, which can lead to chlorine demand, coliform growth, pipe corrosion and water taste and odour problems. The majority of previous studies have been laboratory or pilot plant based and few results are available for field conditions. In this study, field observations of biofilm were made using biofilm potential monitors. The monitor results were compared with pipe samples taken from the distribution system and with laboratory pipe reactors. An empirical equation quantified the inhibitory effects of free chlorine and decrease of temperature on biofilm growth. With water having total organic carbon concentrations in the range 1.5-3.9mg/1 a free chlorine residual of 0.2 mg/l was needed to reduce biofilm concentration to below 50 pg ATP cm2. Pipe material influenced biofilm activity far less than chlorine with mean biofilm activity being ranked in the order glass (136 pg ATP/cm2) < cement (212 pg ATP/cm2) < MDPE (302 pg ATP/ cm2) < PVC (509 pg ATP/cm2).

Biofilms↗

Nursing week 1998

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Journal Article↗

Latex allergy alert.

Reports of children and adults having allergic reactions after latex exposure are appearing in the literature in increasing numbers. The reactions have ranged from rashes, hives and swelling to respiratory distress and even death. Unfortunately, although latex is a common component in many hospital and household products, many health care workers remain unaware of the potential implications of latex allergy on their work and on the health and safety of their patients.

Adult↗

Identification of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced pelvic adhesions in the rat and intraperitoneal adhesions in the human.

OBJECTIVE: Our purpose was to determine the presence and cellular distribution of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced pelvic fibrous adhesions in rat uterine horns subjected to burn, crush, and debridement injury and intraperitoneal fibrous adhesions formed to various organs in the human. STUDY DESIGN: A total of 15 injured and five uninjured rats were used in this study, and fibrous adhesions and intact peritoneum were removed for processing 2 weeks after surgery. Fibrous adhesions formed to uterine, ovarian, and oviductal tissues and the peritoneal wall from eight patients who had gynecologic surgery were also collected. The tissues were processed for immunohistochemical localization of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor with specific antibodies to human and rat epidermal growth factor and transforming growth factor-alpha and the extracellular binding domain of the epidermal growth factor receptor. RESULTS: All the cell types in the rat fibrous adhesion immunostained for epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor. The highest immunostaining intensity for epidermal growth factor was associated with inflammatory cells infiltrated into the fibrous adhesion, followed by arteriole endothelial and smooth muscle cells, fascial striated muscle, and fibroblasts of the fibrous adhesion. In the uterine tissue at the site of injuries myometrial smooth muscle cells, in addition to inflammatory cells that migrated among stromal cells, also immunostained for epidermal growth factor. Fibrous adhesions also immunostained for transforming growth factor-alpha with three separate polyclonal antibodies to the amino and carboxy termini of transforming growth factor-alpha precursor and the mature transforming growth factor-alpha, with no substantial differences in their intensity and pattern compared with epidermal growth factor. The pattern and cellular distribution of epidermal growth factor receptor was similar to that seen for epidermal growth factor and transforming growth factor-alpha. Fibrous adhesions from patients with intraperitoneal adhesions immunostained for epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor with a pattern and intensity similar to that observed in fibrous adhesions in the rats. CONCLUSIONS: The data suggest that epidermal growth factor and transforming growth factor-alpha may play a key role both in normal mechanism of peritoneal repair after injury and formation and maintenance of fibrous adhesions.

Animals↗

Viral hepatitis in pregnancy.

Hepatitis A is usually a benign, self-limited infection. A chronic carrier state does not exist, and perinatal transmission does not occur. Hepatitis B may cause chronic infection, and infants delivered to infected mothers are at considerable risk of developing neonatal hepatitis. Passive and active immunization with HBIG and HBV is highly effective in preventing perinatal transmission. Hepatitis D typically occurs as a coinfection or superinfection with hepatitis B. Patients infected with both viruses are at high risk for chronic liver disease. Perinatal transmission of hepatitis D can be prevented by the immunoprophylaxis used for hepatitis B. Non-A, non-B hepatitis occurs in two distinct forms: parenterally transmitted hepatitis C and enterically transmitted hepatitis E. Perinatal transmission of hepatitis C can occur, particularly in women who are concurrently infected with the human immunodeficiency virus. Neonatal immunoprophylaxis is not yet available. Hepatitis E may be associated with high maternal mortality rates in developing nations. However, a chronic carrier state does not exist, and perinatal transmission does not occur. Table 2 summarizes the most important features of each form of viral hepatitis.

Female↗