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Biomedical subjects

E Nishimura

Publications and source records attributed to E Nishimura.

At least 37 records · Page 2Linked to original sources
PubMed1996

Almost simultaneous measurement of cardiovascular and gas exchange variables during maximal exercise.

We measured gas exchange variables such as oxygen uptake, carbon dioxide output, and lung diffusing capacity using noninvasive techniques almost simultaneous with assessment of cardiovascular variables such as pulmonary blood flow at several levels of treadmill exercise up to and including maximal capacity. We utilized a single breath exhalation technique for measurement of diffusing capacity and cardiac output and breath by breath methodology for evaluating oxygen uptake. The equipment required for these measurements--rapid gas analyzers, oximeters, on-line computation, and pneumatic valves--are well within the capabilities of many exercise laboratories and are not difficult to use with subjects even at the heaviest levels of exercise. The results agreed well with values reported in the literature. From these entirely noninvasive measures, we calculated mixed venous oxygen saturation and maximal tissue oxygen diffusing capacity.

Adult↗
PubMed1996

The Gly40Ser mutation in the human glucagon receptor gene associated with NIDDM results in a receptor with reduced sensitivity to glucagon.

The pancreatic islet hormone, glucagon, stimulates hepatic glucose production and has also been shown to potentiate glucose-induced insulin secretion. Because glucagon is a key regulator of glucose homeostasis, its receptor, which mediates the actions of glucagon, was considered a candidate gene involved in the pathogenesis of NIDDM. We have previously reported that a single heterozygous missense mutation in exon 2 of the glucagon receptor gene, which changes a glycine to a serine (Gly40Ser), is associated with NIDDM in a French population. In the present study, the signaling properties of this mutant receptor were examined in baby hamster kidney cells and rat insulinoma cells (RIN-5AH) stably transfected with either the wild type or Gly40Ser mutant human glucagon receptor cDNAs. Competition assays using (125)I-labeled glucagon were performed, and in both cell types, the Gly40Ser mutant receptor was found to bind glucagon with an approximately threefold lower affinity compared with the wild type receptor. In both cell types, the production of cAMP in response to glucagon was decreased in cells expressing the mutant receptor compared with those expressing the wild type. Finally, glucagon-stimulated insulin secretion by RIN cells expressing the mutant receptor was decreased such that the dose-response curve was shifted to the right in comparison to that obtained with cells expressing the wild type receptor. These results indicate that this single-point mutation located in the extracellular region of the glucagon receptor decreases the sensitivity of target tissues to glucagon.

Amino Acid Sequence↗
PubMed1995

Regulation of glucagon receptor mRNA in cultured primary rat hepatocytes by glucose and cAMP.

Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes. We observed a concentration-dependent increase in glucagon receptor mRNA expression when hepatocytes were cultured in the presence of increasing glucose. A 2-fold induction in glucagon receptor mRNA levels was obtained in hepatocytes cultured for 24 h with 22.5 mM glucose as compared with 5.5 mM glucose. Factors such as 3-isobutyl-1-methylxanthine (IBMX), isoproterenol, and forskolin, which are known to raise intracellular cAMP levels, all caused a reduction in glucagon receptor mRNA expression. IBMX alone, IBMX together with isoproterenol, and forskolin reduced glucagon receptor mRNA expression to approximately 25, 10, and 50%, respectively. Glucagon was found to dose dependently decrease glucagon receptor mRNA expression in the hepatocytes with an approximately 70% reduction in response to 100 nM glucagon. Finally, we observed a marked reduction in the number of glucagon binding sites (35% of control) after hepatocytes were cultured with the combination of IBMX and isoproterenol. These results indicate that hepatic glucagon receptor mRNA levels can be regulated by glucose and intracellular cAMP and that this is also reflected at the protein level. Furthermore, the observed effects of cAMP and glucagon suggest that this may be a means by which glucagon can down-regulate its own receptor expression.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Glucagon receptor mRNA distribution in rat tissues.

In addition to glucagon's role in regulating glucose production from the liver, a number of extrahepatic effects of glucagon have been reported. We have therefore examined various rat tissues for glucagon receptor mRNA expression. In liver, kidney, heart, adipose tissue, spleen, pancreatic islets, ovary, and thymus, glucagon receptor mRNA expression was found to be relatively abundant whereas lower levels were detected in stomach, small intestine, adrenal gland, thyroid, and skeletal muscle. The presence of glucagon receptor mRNA in tissues known to be responsive to glucagon suggests that these effects are mediated by specific glucagon receptors. Furthermore, the finding of glucagon receptor mRNA in the spleen, thymus, thyroid, adrenal gland, ovary, and skeletal muscle, where glucagon is not generally considered to act, indicates that there may be novel actions of glucagon that have yet to be determined.

Animals↗
PubMed1995

Regulation of glucagon and glucagon-like peptide-1 receptor messenger ribonucleic acid expression in cultured rat pancreatic islets by glucose, cyclic adenosine 3',5'-monophosphate, and glucocorticoids.

Glucagon and glucagon-like peptide-1 (GLP-1) are important regulators of glucose homeostasis, and both are involved in regulating pancreatic islet hormone secretion. Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number, we have examined the regulation of glucagon receptor and GLP-1 receptor messenger RNA (mRNA) expression in cultured rat pancreatic islets by various factors, including glucose, cAMP, and glucocorticoids. By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP-1 receptor mRNA in cultured rat islets. We observed a dose-dependent increase in glucagon receptor mRNA expression with increasing glucose concentrations: an approximately 3-fold increase in glucagon receptor mRNA in islets cultured in 22 mM glucose as compared to 3.5 mM glucose. GLP-1 receptor mRNA levels, on the other hand, were not affected by culturing the islets in low glucose concentrations; however, a small, but significant, decrease in GLP-1 receptor mRNA levels was detected when islets were cultured in 20 mM glucose. Forskolin and 3-isobuty-1-methylxanthine, which increase intracellular cAMP levels, caused a 75% reduction in glucagon receptor mRNA expression. Somatostatin 14 and 28, both of which can inhibit intracellular cAMP production, stimulated glucagon receptor mRNA expression by 40% and 75%, respectively. GLP-1 receptor mRNA levels remained unchanged under all conditions that altered intracellular cAMP levels. Finally, in islets cultured in the presence of 10 nM dexamethasone an approximately 50% decrease in both glucagon and GLP-1 receptor mRNA expression was observed. These results indicate that the expression of glucagon and GLP-1 receptor mRNA is differentially regulated in rat pancreatic islets and suggest that regulation of receptor mRNA expression may be an important mechanism for controlling the sensitivity of the islets to glucagon and GLP-1.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Hybridization histochemical localization of activin receptor subtypes in rat brain, pituitary, ovary, and testis.

We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA expression was stronger than that of ActRIIB, and the patterns of expression were similar, although not identical. The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid-hippocampal transition zone; and throughout the cortical mantle, including the primary olfactory cortex (piriform cortex and olfactory tubercle); other regions of the cortex showing lesser degrees of hybridization included the cingulate cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nuclei. Moreover, activin receptors were also expressed in regions with inputs to the hypothalamus, both in the forebrain (bed nucleus of the stria terminalis and medial preoptic area) and within the brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, and mesencephalic raphé system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed throughout all three pituitary divisions. In both male and female gonads, activin receptor message was clearly present in germ cells, and ActRII was the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and granulosa cells during diestrous day 1. In the testis, there was a strong ActRII signal in rounded spermatids, and a moderate signal in pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammalian tissues. Although consistent with some previously suggested functional associations of activin-containing pathways in the brain, this pattern of expression suggests a greater role for activin than was previously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.

Activin Receptors↗
PubMed1991

Production and characterization of murine monoclonal antibodies against staphylococcal enterotoxins A and E.

Six murine monoclonal antibodies (MAbs) against staphylococcal enterotoxin A (SEA) and enterotoxin E (SEE) were prepared by fusion of myeloma cells with mouse spleen cells immunized with SEA and SEE. Of five MAbs to SEA tested, two MAbs were reactive with only SEA, whereas three were specific for both SEA and SEE. On the other hand, one MAb to SEE was found to be specific for only SEE. To study specificities of the combining sites of these MAbs, competitive binding assays with either SEA or SEE and horseradish peroxidase conjugated MAbs were performed using unconjugated MAbs as inhibitors. The results obtained in the assays suggest that different epitopes may be located on SEA and that some of them may be cross-reacting epitopes between SEA and SEE.

Animals↗
PubMed1991

Photodynamic therapy using rhodamine-123 as a new laser dye: biodistribution, metabolism and histology in New Zealand rabbits.

Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.

Animals↗
PubMed1990

Interstitial laser phototherapy assisted by magnetic resonance imaging: a new technique for monitoring laser-tissue interaction.

The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.

Animals↗
PubMed1989

Ectopic growth of mouse whiskers from implanted lengths of plucked vibrissa follicles.

A method for transplanting whole or partial whisker follicles from adult mice to a site beneath the kidney capsule of syngeneic mice is described. Follicles were removed from the upper lip and the growing whiskers plucked. The follicles were either left intact or divided into two parts by transection and implanted under the kidney capsule. The intact whole follicles remained viable and regenerated whiskers which were later shed. The lower one-half or one-third follicle implants reorganized their base and produced a short, curled whisker. On the other hand, none of the upper one-half or two-thirds implants regenerated a dermal papilla, and no whisker production was observed. However, when a single dermal papilla which had been dissected out from another follicle was introduced into each upper follicle cavity in contact with the cut edge, a bulbar region emerged, and subsequently, a long, thick, medullated whisker developed from the implants. This technique should be useful in studying the induction and regeneration of adult mouse whiskers.

Animals↗
PubMed1987

Identification and characterization of a pituitary corticotropin-releasing factor binding protein by chemical cross-linking.

A corticotropin-releasing factor (CRF) binding protein has been identified based on the chemical cross-linking of ovine [Nle21,m-125I-Tyr32]CRF (125I-oCRF) to bovine anterior pituitary membranes using disuccinimidyl suberate (DSS). The apparent molecular weight of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 75,000 and was slightly decreased in its nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the molecular weight of 125I-oCRF, the binding protein appeared to have a molecular weight of approximately 70,000. The cross-linking was specific since an excess (1 microM) of an unrelated peptide (insulin) did not affect the appearance of the Mr 75,000 band. The concentration of CRF required to inhibit cross-linking by 50% was found to be similar to that determined for bovine pituitary CRF receptors by radioreceptor assay. The nonhydrolyzable GTP analogue 5'-guanylylimidodiphosphate dose dependently inhibited the cross-linking of 125I-oCRF to the Mr 70,000 protein. 50 nM of the inactive CRF analogue, [Ala14]oCRF, had no effect on the cross-linking, an observation which is consistent with this compound's low potencies in bioassays and radioreceptor assays. These results strongly suggest that this Mr 70,000 protein is the biological bovine anterior pituitary CRF receptor.

Adrenocorticotropic Hormone↗
PubMed1986

Release of [Leu5]enkephalin immunoreactivity from the isolated perfused rat stomach.

The release of [Leu5]enkephalin immunoreactivity ([Leu5]enk-IR) from the isolated perfused rat stomach was demonstrated under basal conditions in the presence of peptidase inhibitors (0.1 microM thiorphan, 1 microM captopril and 2 microM bestatin). Depolarization with 50 mM KCl resulted in a four-fold increase in both [Leu5]enk-IR and gastrin (IR-gastrin) levels. Administration of the nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (10 microM) stimulated the release of [Leu5]enk-IR in a calcium-dependent manner. The muscarinic acetylcholine receptor agonist methacholine (10 microM) had no effect on [Leu5]enk-IR release.

Animals↗
PubMed1986

Autoradiographic localization of mu- and delta-type opioid receptors in the gastrointestinal tract of the rat and guinea pig.

The distribution of delta- and mu-type opioid binding sites in the gastrointestinal tract of the rat and guinea pig was studied by autoradiography after in vitro incubation of tissue slices with 3H-D-Ala2,D-Leu5-enkephalin, and 3H-naloxone or 3H-dihydromorphine to locate delta- and mu-type opioid receptors, respectively. In the gastric fundus, both mu- and delta-type binding sites were found to occur associated with the circular muscle, muscularis mucosae, and submucosal plexus, whereas in the corpus and antrum, binding was located primarily in the submucosal plexus, deep muscular plexus, and mucosa. Some mu-type opioid receptor sites were present in the myenteric plexus. A dense distribution of both mu- and delta-type binding sites was observed throughout the mucosa of the duodenum and ileum of the rat. In guinea pig ileal tissue, however, only mu-type binding could be demonstrated, occurring in the submucosal plexus and diffusely over the muscle layers. Endogenous opioid peptides, acting at these receptors sites, might be involved in the control of gastrointestinal motility, endocrine and exocrine secretions, as well as intestinal fluid and electrolyte transport.

Animals↗
PubMed1986

Characterization of opioid peptides in the rat stomach.

A combination of several chromatographic and assay systems was used to characterize the opioid peptides in rat stomach extracts. Partial purification of opioid material in acetic acid extracts of the corpus plus antrum regions of the rat stomach was carried out by gel filtration chromatography on Sephadex G-50, followed by adsorption onto Amberlite XAD-2 resin. A single peak in opioid activity was determined by both radioreceptor assay (RRA) and bioassay. By high performance liquid chromatography, this peak was resolved into five distinct components, characterized by RRA and (or) radioimmunoassay, with retention times corresponding to methionine enkephalin (met-enk), leucine enkephalin, met-enk-arg6-gly7-leu8, met-enk-arg6-phe7, and dynorphin 1-13. Closer examination of the dynorphin component revealed the presence of dynorphins 1-17, 1-13, and 1-8. Trypsin digestion of the partially purified (Sephadex G-50 and Amberlite XAD-2 chromatographed) extract resulted in an overall increase in opioid activity, suggesting the presence of larger, possibly precursor forms.

Animals↗
PubMed1986

[General pharmacological action of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride). Influence on respiratory and cardiovascular systems, renal function, autonomic nervous system, isolated smooth muscle and digestive organs].

MCI-2016 at 3 mg/kg, i.v., caused slight changes in systemic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and ECG but at 10 mg/kg, i.v., it caused a significant increase in RR, decrease in SBP, increase or decrease in HR and a moderate change in ECG. Biphasic changes in SBP, HR and blood flow were sometimes observed after high doses. MCI-2016 also decreased SBP at 30 mg/kg, i.p., in SHR. MCI-2016 (50 mg/kg, p.o./day) showed little influence on SBP, HR and ECG in conscious beagle dogs. In isolated hearts, MCI-2016 decreased HR and contractility at the concentrations above 10(-5) g/ml, and 30 micrograms, i.a. MCI-2016 prolonged the AVCT at 10 mg/kg, i.v. MCI-2016 (i.v. or i.a.) moderately increased cerebral and femoral artery blood flows. MCI-2016 did not change CMRO2, but decreased MVO2. Coronary and renal artery flows were moderately increased by 10 mg/kg, i.v., of MCI-2016. Renal function was suppressed after 10 mg/kg, i.v., or 300 mg/kg, p.o., of MCI-2016. MCI-2016 potentiated the action of NE (increase in SBP, contractions of nictitating membrane and vas deferens), but showed little anti-cholinergic action. In contrast, MCI-2016 moderately increased gastrointestinal motility and salivatory response. As for the influence on isolated smooth muscles, MCI-2016 antagonized the contraction of blood vessels by high K+ at 10(-6) g/ml, or more, and it depressed the contractions by ACh, 5-HT, histamine and BaCl2 and also depressed spontaneous movements of uterus and ileum at 10(-5) M or more, in a nonspecific manner. MCI-2016 had no influence on liver damage and bile secretion, but inhibited stress ulcer and gastric acid secretion on the one hand, and caused gastric damage (125 mg/kg p.o., or more) on the other hand.

Animals↗
PubMed1985

Autoradiographic localization of binding sites for atrial natriuretic factor.

The distribution of atrial natriuretic factor (ANF) binding sites in Wistar rat tissues, as well as tissues from other species was studied. Using autoradiography of slide mounted tissue sections incubated with 125I-labelled ANF, high densities of binding sites were found in the renal glomeruli and papilla, aortic smooth muscle, iliac vein, choroid plexus, anterior pituitary, lung, and adrenal zona glomerulosa. Results from renal, aortic, adrenal, and lung tissues from spontaneously hypertensive rats did not differ from those of Wistar rats. Binding sites were also observed in guinea pig glomeruli, renal medulla, and aorta as well as in the rabbit aorta.

Adrenal Cortex↗
PubMed1984

Autoradiographic localization of opioid receptors in the rat stomach.

The distribution of opioid receptors in the stomach has been studied using autoradiography of slide-mounted tissue sections incubated with [3H]D-Ala2,D-Leu5-enkephalin. The major sites of binding were the mucosa and the submucosal and deep muscular plexi. Other regions did not exhibit significant binding. These locations suggest that endogenous delta-opioid receptors may regulate mucosal ion transport and smooth muscle motility in the stomach.

Animals↗