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Biomedical subjects

M Kawaguchi

Publications and source records attributed to M Kawaguchi.

At least 19 recordsLinked to original sources
PubMed1995

Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells.

Although T cells bearing gamma delta T-cell receptors have long been known to be present in the epithelial lining of many organs, their specificity and function remain elusive. In the present study, we examined the intestinal epithelia of T-cell-receptor mutant mice, which were deficient in either gamma delta T cells or alpha beta T cells, and of normal littermates. The absence of gamma delta T cells was associated with a reduction in epithelial cell turnover and a downregulation of the expression of major histocompatibility complex class II molecules. No such effects were observed in alpha beta T-cell-deficient mice. These findings indicate that intraepithelial gamma delta T cells regulate the generation and differentiation of intestinal epithelial cells.

Animals↗
PubMed1995

Beta-cell function and replication in spontaneously hypertensive rats.

We examined beta-cell function and replication in spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Rats were subjected to 90% pancreatectomy (Px) or sham operation at the age of 8 weeks, and islet function and regeneration were examined 4 weeks after surgery. Plasma glucose levels were higher in SHR than in WKY (509 +/- 38 v 325 +/- 109 mg/dL, P < .0001) 1 week after Px and throughout the experimental period. Plasma glucose responses to intravenous injection of glucose (0.5 g/kg body weight) were not different in the sham-operated animals of the two strains, whereas plasma insulin responses were greater in SHR than in WKY. No insulin responses to glucose were observed in either strain of Px rats. The insulin content of the remnant equivalent (6.7 +/- 2.1 v 4.2 +/- 0.4 micrograms, P < .05) and whole pancreas (156.7 +/- 10.7 v 123.8 +/- 23.5 micrograms, P < .01) in sham-operated rats was greater in SHR than in WKY. However, insulin content was lower (P < .05) in Px-SHR (1.0 +/- 0.2 microgram) than in Px-WKY (3.9 +/- 1.7 micrograms). Histological examination showed that fibrotic degeneration of islets was much greater in Px-SHR than in Px-WKY. These data strongly suggest that the beta cells of SHR were more vulnerable to reduction of islet mass than those of WKY. Our data also suggest that hyperinsulinemia and/or insulin resistance in SHR has a deleterious effect on beta-cell replication.

Animals↗
PubMed1995

Coexisting type III hyperlipoproteinemia and familial hypercholesterolemia: a case report.

A 39-year-old man presented with type III hyperlipoproteinemia in association with heterozygous familial hypercholesterolemia (FH). He had extensive tuberous xanthomas over the knees and elbows and xanthomas in the Achilles tendons. He also had palmar xanthomas. He exhibited severe hypercholesterolemia and hypertriglyceridemia. This patient was heterozygous for FH, as evidenced by low low-density lipoprotein (LDL) receptor function on lymphocytes, and had type III hyperlipoproteinemia, as determined by apolipoprotein (apo) E phenotype 2/2 in isoelectric focusing of the E isoproteins and the presence of a broad beta band on electrophoresis. Because therapy consisting of diet restrictions and lipid-lowering agents such as clinofibrate and niceritrol did not decrease serum total cholesterol ([TC] 15.26 mmol/L) and triglyceride ([TG] 10.79 mmol/L) levels effectively, the patient underwent plasmapheresis once every 2 weeks using a dextran sulfate-cellulose column. Repeated plasmapheresis markedly reduced serum TC and TG and induced complete regression of the palmar xanthoma after 6 months. The severity of tuberous xanthomas on the knees and elbows was reduced after 2.5 years. After plasmapheresis, TC decreased to 1.94 mmol/L from 10.40 mmol/L and TG decreased to 0.33 mmol/L from 7.90 mmol/L. Plasmapheresis performed with a dextran sulfate-cellulose column was highly effective in removing the lipoprotein-remnant particles in this patient, leading to generalized improvement in the lipoprotein profile.

Adult↗
PubMed1995

Differential activation through the TCR-CD3 complex affects the requirement for costimulation of human T cells.

Although it is well established that T cells require at least two activation signals, the coordination of primary signaling through the TCR-CD3 complex with costimulatory signals through accessory molecules is incompletely understood. To mimic the signal provided by natural ligand for TCR, we used eight anti-TCR V-region-specific mAbs as well as two anti-TCR-CD3 mAbs, OKT3 and T10B9, to stimulate human peripheral blood T cells in the presence or absence of accessory cells. With accessory cells, only OKT3 in soluble form stimulated T cells, but when mABs were immobilized on plastic, all except the V alpha mAb, F1, induced proliferation. This result suggests that the signaling qualities of TCR V-region-specific mAb may differ from OKT3, which activates through CD3 epsilon. To address this issue, the costimulatory requirements of two V beta-specific mAbs, 1C1 and OT145, were also compared with OKT3 and T10B9 using T cells depleted of accessory cells. The V beta-specific mAb and T10B9 could only be complemented by costimulation through the CD28 molecules, whereas OKT3 was able to synergize with mAb directed not only at CD28, but also CD2 and CD11a. Furthermore, mAb specific for CD80 was able to block activation of T cells in the presence of accessory cells when V beta-specific mAbs were used to activate, whereas anti-CD80 had no effect on activation of T cells by immobilized OKT3. Thus the nature of the signal received through the TCR-CD3 complex, whether TCR alpha beta or CD3 epsilon, may determine the qualitative requirements for costimulation.

Antibodies, Monoclonal↗
PubMed1995

Effect of cholera toxin and pertussis toxin on the growth of A431 cells: kinetics of cyclic AMP and inositol trisphosphate in toxin-treated cells.

Cholera toxin and pertussis toxin were inhibitory to the incorporation of thymidine into A431 cells in serum-free culture. Cholera toxin enhanced the growth inhibitory effect of epidermal growth factor (EGF) on A431 cells, whereas pertussis toxin attenuated the effect. Cholera toxin increased the concentration of intracellular cyclic AMP (cAMP) to three-times the initial concentration at 120 minutes and it increased the concentration of intracellular inositol trisphosphate (IP3) rapidly but transiently. Pertussis toxin reduced the concentration of IP3 both in EGF treated and untreated A431 cells at 10 minutes. cAMP was not involved in pertussis toxin-mediated effects. In conclusion, the intracellular cAMP and IP3 concentrations in CT-treated A431 cells are compatible with previous reports regarding the growth inhibitory effects on A431 cells. The inhibitory effect of PTX on the EGF-induced increase of intracellular IP3 is thought to be compatible with the finding that PTX attenuated the EGF-induced growth inhibition.

Carcinoma, Squamous Cell↗
PubMed1995

Do recently developed techniques for skull base surgery increase the risk of difficult airway management? Assessment of pseudoankylosis of the mandible following surgical manipulation of the temporalis muscle.

We report our experience with anesthetic care for six patients with pseudoankylosis of the mandible following neurosurgical procedures, four of whom required fiberoptically guided intubation for anesthesia. We suggest that the development of operative approaches and reconstruction techniques in skull base surgery may increase the risk of difficult airway due to limitation of mouth opening.

Adult↗
PubMed1995

[Receptive systems for drugs in salivary gland cells].

Investigators have demonstrated many types of receptors or acceptors for endogenous substances in salivary glands. These suggest that salivary glands contain receptive systems for many drugs. These receptors can be classified into three types based on the property of saliva secretion: (1) receptors involved in fluid secretion, (2) receptors involved in exocytosis for the protein secretion, (3) receptors involved in both types of secretion. The receptors involved in fluid secretion include the group of alpha 1B, M3, NK-1 receptors coupled with IP3; the group of beta 2 and VIP receptors coupled with cAMP; and the group of P2Z and P2U receptors coupled with the ATP-gated calcium channel. Whereas alpha 1A, beta 1, VIP, M3, insulin and H2 receptors mediate exocytosis via the cAMP-proteinkinase A pathway. Moreover, the another pathway of diacylglycerol-proteinkinase C has also been demonstrated to be involved in the exocytosis occurring via NK-1 and M3 receptors. Thus, salivary gland cells have many kinds of drug-receptor system. These receptors are all positive to fluid and/or protein exocytosis. Recently our study on the inhibitory regulation of saliva secretion have suggested the existence of GABA and the GABA-synthetic/metabolic pathway, GABA(A) receptors and benzodiazepine (BDZ) receptors of both central and peripheral types, and furthermore, the coupling of GABA(A) and the central type of BDZ receptors. These receptors are involved in decreasing fluid secretion and amylase release elicited by secretagogues. In the future, mechanisms of the intracellular transduction elicited by BDZ or GABA must be clarified.

Animals↗
PubMed1995

Existence of gamma-aminobutyric acid and its biosynthetic and metabolic enzymes in rat salivary glands.

To obtain more insight into the physiological role of gamma-aminobutyric acid (GABA) in rat salivary glands, we measured the concentration of GABA and the activities of its biosynthetic and metabolic enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T). The GABA concentrations in rat parotid and submandibular glands were 10.0 and 14.3 nmol/g weight, respectively, which were 0.6-0.8% of the levels in the brain (cerebellum and medulla oblongata), whereas glutamic acid (Glu) was abundant in the two glands. These GABA levels in the two glands were significantly decreased by administration of semicarbazide (200 mg/kg, i.p.), a GAD inhibitor, and increased by gabaculine (50 mg/kg, i.p.), a GABA-T inhibitor. The activities of both GAD and GABA-T were also detected in homogenates of the two salivary glands, but they were lower than those in the brain. However, kinetic analysis showed that the values of Michaelis constants for Glu and GABA in both enzyme reactions in these two glands were similar to those in the brain. These results indicate that GABA and its biosynthetic and metabolic enzymes are present in rat salivary glands as well as the brain.

4-Aminobutyrate Transaminase↗
PubMed1995

[Usefulness of 123I-BMIPP myocardial imaging in patients with stable effort angina and unstable angina].

We evaluated the clinical significance of myocardial imaging using 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy in patients with stable effort angina pectoris (SAP) and unstable angina pectoris (UAP). Thirty-three patients with SAP were studied using rest BMIPP and stress 201TlCl (Tl) myocardial scintigraphy, and 13 patients with worsening effort type of UAP were also examined using both rest BMIPP and Tl scintigraphy. We compared those BMIPP findings with myocardial perfusion images obtained with Tl and the regional wall motion determined by left ventriculography. In 45% of 282 segments of myocardial ischemia of SAP, the degree of myocardial uptake of BMIPP was concordant with that of stress Tl and the defect score of Tl was higher than that of BMIPP. On the other hand, in 32% of 62 segments of ischemia of UAP, the degree of myocardial BMIPP and Tl uptake was concordant and BMIPP defect score was higher than Tl score. In SAP, the decrease in regional wall motion agreed better with the decrease in myocardial uptake of BMIPP than that of Tl. These results suggest that myocardial ischemic regions decreased BMIPP uptake show the disturbance of fatty acid metabolism and lead to abnormal wall motions. Such ischemic regions may be clinically severe state in patients with angina pectoris.

Aged↗
PubMed1994

Immunocytochemical characterization and identification of SGE1, a rat glomerular epithelial cell line.

Glomerular epithelial cells (GEC) in culture facilitate the study of glomerular physiology and pathology. However, characterization and identification of GECs in culture have been difficult due to the absence of markers specific to them. We compared the immunocytochemical characteristics of a rat normal GEC line (SGE1) and glomerular cells from rat kidney sections using a lectin and commercially available and newly raised monoclonal and polyclonal antibodies. Antivimentin, anti-dipeptidyl-peptidase-IV (gp 108) and monoclonal antibody 5-1-6 antibodies and Limax flavus lectin bound to visceral GECs, anticytokeratin antibody and antibody against common acute lymphocytic leukemia antigen bound to parietal GECs, and anti-SGE1 cell membrane and monoclonal antibody PHM 5 antibodies bound to both visceral GECs and parietal GECs in normal rat kidney sections, and all of these antibodies and L. flavus lectin consistently bound to SGE1 cells in culture. The pattern of antigenic expression on SGE1 cells indicates that SGE1 cells possess phenotypic characteristics of visceral GECs and parietal GECs, and it further suggests that SGE1 cells may be stem cells or cells undergoing differentiation.

Animals↗
PubMed1994

Nonadrenergic noncholinergic nerves regulate basal coronary flow via release of capsaicin-sensitive neuropeptides in the rat heart.

Nonadrenergic noncholinergic nerve fibers supposedly modulate basal coronary flow by releasing capsaicin-sensitive neuropeptides, but the physiological effects of this intrinsic action have not been clarified. We investigated the intrinsic function of nonadrenergic noncholinergic innervation in modulating basal coronary flow in rats. We administered capsaicin to 44 rats to deplete neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P and administered inert vehicle to 60 control rats. Four days later, we measured the coronary pressure-flow relation in the basal state and during maximal coronary vasodilation induced by intracoronary adenosine administration using Langendorff's method. Changes in basal coronary flow prompted by intracoronary infusion of CGRP or substance P and their antagonists were measured in 54 and 30 rats, respectively. Capsaicin-treated rats showed a 31.5 +/- 0.9% (mean +/- SEM) reduction (P < .01) of basal coronary flow in the range of perfusion pressures between 60 and 140 mm Hg compared with untreated control rats, but the maximal coronary flow after adenosine was similar between the two groups. Although basal coronary flow was reduced in capsaicin-treated hearts, left ventricular contractile force and myocardial oxygen consumption did not fall significantly. CGRP increased the coronary flow, but substance P did not. CGRP(8-37), a CGRP receptor antagonist, reduced basal coronary flow by 24.5 +/- 2.1% (P < .01), but FK888, a substance P antagonist, had little effect on it. Thus, capsaicin-sensitive neuropeptides in the rat heart modulate basal coronary flow, providing approximately 30% of it.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Pituitary adenoma invading the skull base--a strategy for skull base surgery.

A strategy for surgical management, including the approach and preoperative evaluation, of pituitary adenoma invading the skull base is described. Preoperative evaluation requires a balloon occlusion test of the internal carotid artery (ICA) to determine tolerance to occlusion. Failure to tolerate occlusion indicates administration of brain protective agents and/or a bypass procedure before tumor removal. The transsphenoidal, pterional, orbitofrontomalar, and infratemporal fossa approaches are all suitable for various tumor locations. A combined orbitofrontomalar and extended frontal approach allows removal of tumor with extensive invasion and is suitable for bypass procedures. Preoperative evaluation of ICA occlusion can prevent development of hemodynamic stroke. We treated five patients with pituitary adenoma invading the skull base, including two primary and three recurrent cases. All symptoms improved, but temporary oculomotor nerve disturbance occurred in three patients and anosmia in one. Reoperations for recurrent pituitary adenomas were effective in reversing the symptoms. No hemodynamic stroke was seen postoperatively. These tumors, except for drug-responsive cases, are indicated for skull base surgery.

Adenoma↗
PubMed1994

Differential insulin secretory activity in rat pancreatic islets and HIT cells.

We compared insulin secretory activity from rat pancreatic islets with that from a hamster beta-cell line (HIT-T). Insulin release from HIT cells was maximally stimulated with glucose at a concentration of 11.1 mM, and rather inhibited by higher concentrations of glucose. Blunted insulin release induced by glucose was shown in the isolated rat islets exposed to either streptozotocin (2.2 mM) for 30 min or alloxan (2 mM) for 5 min, whereas glucose-induced insulin release from HIT cells was not affected by pre-treatment with such beta-cell toxin. When pancreatic islets and HIT cells were cultured for 7 days with 10 mM nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, glucose-induced insulin release from the islets was inhibited, whereas insulin release from HIT cells was rather enhanced. Insulin release induced by either arginine or leucine was also enhanced in HIT cells cultured with nicotinamide. These findings indicate that the multiple components of insulin stimulus-secretion coupling in HIT cells are considerably different from those in rat pancreatic islets.

Alloxan↗
PubMed1992

Roles of active oxygen species in glomerular epithelial cell injury in vitro caused by puromycin aminonucleoside.

The mechanism of puromycin aminonucleoside (PAN)-induced nephrosis has not yet been well defined. In the present study, we examined the protective effect of active oxygen scavengers on the PAN-induced injury of cultured rat glomerular epithelial cells (GECs) and the generation of active oxygen species in PAN-treated GECs. When exposed to PAN (greater than or equal to 25 micrograms/ml), cellular damage occurred in a time- and dose-dependent manner as evaluated by both the LDH release and MTT colorimetric assays. Concomitant addition of either the hydrogen peroxide (H2O2) scavenger, catalase, or the iron chelating agent, deferoxamine, to the culture medium caused a striking reduction of cellular injury. This suggested a role for H2O2 and for hydroxyl radicals (OH.) generated via the iron-catalyzed breakdown of H2O2 in PAN nephrosis. Using the scopoletin fluorescence assay, the release of H2O2 into the culture medium by GECs exposed to PAN (greater than or equal to 50 micrograms/ml) was shown to increase dose-dependently (greater than or equal to 57 +/- 11 pmol/4.4 x 10(6) cells per h, P less than 0.01) as compared with control cells (14 +/- 2 pmol/4.4 x 10(6) cells per h). These results strongly suggested that active oxygen species, especially H2O2 and OH., might play an important role in PAN-induced GEC injury in vitro as well as in vivo.

Animals↗