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Biomedical subjects

A Kingston

Publications and source records attributed to A Kingston.

8 recordsLinked to original sources
PubMed2002

Symptomatic improvement in gastroesophageal reflux disease (GERD) following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The purpose of this study was to determine the effect of laparoscopic Roux-en-Y gastric bypass (LRYGBP) on symptomatic control of gastroesophageal reflux disease (GERD). METHODS: Morbidly obese patients (n = 435) who underwent LRYGBP for morbid obesity were assessed for changes in GERD symptoms, quality of life, and patient satisfaction after surgery. RESULTS: A total of 238 patients (55%) had evidence of chronic GERD, and 152 patients (64%) voluntarily participated in the study. The mean body mass index (BMI) was 48 kg/m2. The mean excess weight loss was 68.8% at 12 months. There was a significant decrease in GERD-related symptoms, including heartburn (from 87% to 22%, p<0.001); water brash (from 18% to 7%, p<0.05); wheezing (from 40% to 5%, p<0.001) laryngitis (from 17% to 7%, p<0.05); and aspiration (from 14% to 2%, p<0.01) following LRYGBP. Postoperatively, the use of medication decreased significantly both for proton pump inhibitors (from 44% to 9%, p<0.001) and for the H2 blockers (from 60% to 10%, p<0.01). SF-36 physical function scores and the mental component summary scores improved after the operation (87 vs 71; p<0.05 and 83 vs 66; p<0.05, respectively). Overall patient satisfaction was 97%. CONCLUSION: LRYGBP results in very good control of GERD in morbidly obese patients with follow-up as late as 3 years. Morbidly obese patients who require surgery for GERD may be better served by LRYGBP than fundoplication because of the additional benefit of significant weight loss.

Anastomosis, Roux-en-Y↗
PubMed1999

Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors.

As part of our ongoing research program aimed at the identification of highly potent, selective, and systemically active agonists for group II metabotropic glutamate (mGlu) receptors, we have prepared novel heterobicyclic amino acids (-)-2-oxa-4-aminobicyclo[3.1. 0]hexane-4,6-dicarboxylate (LY379268, (-)-9) and (-)-2-thia-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY389795, (-)-10). Compounds (-)-9 and (-)-10 are structurally related to our previously described nanomolar potency group II mGlu receptor agonist, (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740 monohydrate, 5), with the C4-methylene unit of 5 being replaced with either an oxygen atom (as in (-)-9) or a sulfur atom (as in (-)-10). Compounds (-)-9 and (-)-10 potently and stereospecifically displaced specific binding of the mGlu2/3 receptor antagonist ([3H]LY341495) in rat cerebral cortical homogenates, displaying IC50 values of 15 +/- 4 and 8.4 +/- 0.8 nM, respectively, while having no effect up to 100 000 nM on radioligand binding to the glutamate recognition site on NMDA, AMPA, or kainate receptors. Compounds (-)-9 and (-)-10 also potently displaced [3H]LY341495 binding from membranes expressing recombinant human group II mGlu receptor subtypes: (-)-9, Ki = 14.1 +/- 1.4 nM at mGlu2 and 5.8 +/- 0.64 nM at mGlu3; (-)-10, Ki = 40.6 +/- 3.7 nM at mGlu2 and 4.7 +/- 1.2 nM at mGlu3. Evaluation of the functional effects of (-)-9 and (-)-10 on second-messenger responses in nonneuronal cells expressing human mGlu receptor subtypes demonstrated each to be a highly potent agonist for group II mGlu receptors: (-)-9, EC50 = 2.69 +/- 0.26 nM at mGlu2 and 4.58 +/- 0.04 nM at mGlu3; (-)-10, EC50 = 3.91 +/- 0.81 nM at mGlu2 and 7.63 +/- 2. 08 nM at mGlu3. In contrast, neither compound (up to 10 000 nM) displayed either agonist or antagonist activity in cells expressing recombinant human mGlu1a, mGlu5a, mGlu4a, or mGlu7a receptors. The agonist effects of (-)-9 and (-)-10 at group II mGlu receptors were not totally specific, however, as mGlu6 agonist activity was observed at high nanomolar concentrations for (-)-9 (EC50 = 401 +/- 46 nM) and at micromolar concentrations (EC50 = 2 430 +/- 600 nM) for (-)-10; furthermore, each activated mGlu8 receptors at micromolar concentrations (EC50 = 1 690 +/- 130 and 7 340 +/- 2 720 nM, respectively). Intraperitoneal administration of either (-)-9 or (-)-10 in the mouse resulted in a dose-related blockade of limbic seizure activity produced by the nonselective group I/group II mGluR agonist (1S,3R)-ACPD ((-)-9 ED50 = 19 mg/kg, (-)-10 ED50 = 14 mg/kg), indicating that these molecules effectively cross the blood-brain barrier following systemic administration and suppress group I mGluR-mediated limbic excitation. Thus, heterobicyclic amino acids (-)-9 and (-)-10 are novel pharmacological tools useful for exploring the functions of mGlu receptors in vitro and in vivo.

Amino Acids↗
PubMed1999

Neuroprotective activity of the potent and selective mGlu1a metabotropic glutamate receptor antagonist, (+)-2-methyl-4 carboxyphenylglycine (LY367385): comparison with LY357366, a broader spectrum antagonist with equal affinity for mGlu1a and mGlu5 receptors.

(+)-2-Methyl-4-carboxyphenylglycine (LY367385), a potent and selective antagonist of mGlu1a metabotropic glutamate receptors, was neuroprotective in the following in vitro and in vivo models of excitotoxic death: (i) mixed cultures of murine cortical cells transiently exposed to N-methyl-D-aspartate (NMDA); (ii) rats monolaterally infused with NMDA into the caudate nucleus; and (iii) gerbils subjected to transient global ischemia. We have compared the activity of LY367385 with that of the novel compound (+/-)-alpha-thioxantylmethyl-4-carboxyphenylglycine (LY367366), which antagonizes both mGlu1a and -5 receptors at low micromolar concentrations, but also recruits other subtypes at higher concentrations. Although LY367366 was neuroprotective, it was in general less efficacious than LY357385, suggesting that inhibition of mGlu1 receptors is sufficient to confer significant neuroprotection. We conclude that endogenous activation of mGlu1a receptors (or perhaps other mGlu1 receptor splice variants) contributes to the development of neuronal degeneration of excitotoxic origin.

Animals↗
PubMed1992

Rat Schwann cells can be induced to express major histocompatibility complex class II molecules in vivo.

Previous studies, showing that cultured rat Schwann cells could be induced to express MHC class II molecules, raised the possibility that Schwann cells in living nerves might, under some conditions, express MHC class II molecules and take part in activation of T lymphocytes. In the present work, the ability of myelin- and non-myelin-forming Schwann cells in vivo to express MHC class II molecules was investigated. Lymphokines or bacterial antigens were injected into the living sciatic nerve of adult rats. Examination of the nerves three days after injection of interferon-gamma or six days after injection of either tumour necrosis factor, antigens from mycobacterium leprae or whole mycobacteria leprae, revealed strong MHC class II immunostaining on some myelin-forming Schwann cells in the vicinity of the injection site. Very few non-myelin-forming cells expressed MHC class II molecules. MHC class II positive mononuclear cells were present in the injected nerves and endothelial cells of capillaries expressed high levels of MHC class II antigens. Crushing the sciatic nerve without injection of factors also induced MHC class II molecules on a few Schwann cells. Thus rat Schwann cells can be induced to express MHC class II molecules in vivo as in vitro. This strengthens the possibility that in living nerves Schwann cells are able to function as accessory cells in the initiation or augmentation of T cell-mediated immune responses.

Animals↗
PubMed1991

Rat Schwann cells produce interleukin-1.

There is increasing evidence that Schwann cells of peripheral nerves may be able to function as accessory cells, interacting with the immune system in T cell-mediated immune responses, by expression of the major histocompatibility complex (MHC) class II molecules. In addition to MHC class II-associated presentation of antigen to T lymphocytes, the release of a co-stimulatory factor, interleukin-1 (IL-1), is an essential function of accessory cells for T cell activation. In this study, we investigated if Schwann cells were able to produce IL-1. Purified cultures of neonatal and adult rat Schwann cells were incubated with various stimulatory agents. Supernatants and cell lysates were collected from these cultures and IL-1 activity was assayed. Both neonatal and adult rat Schwann cells produced IL-1 activity in response to bacterial antigens and the IL-1 activity was often higher in the cell lysate than in the supernatant. When stimulated neonatal or adult rat Schwann cells were examined with antibody against IL-1, strong immunolabelling was seen intracellularly, but no IL-1 was detected on the cell surface. Since IL-1 plays an important role in the initiation of immune responses, these observations support the view that Schwann cells may function as antigen-presenting cells, thereby taking part in neuroimmunological responses within peripheral nerves.

Aging↗