Pancreatic B-cell replication in an animal model of insulin-resistant non-insulin-dependent diabetes mellitus.
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Animals↗
Biomedical subjects
M Kawaguchi
Publications and source records attributed to M Kawaguchi.
Preoperative predictors of reduction in arterial blood pressure following dural opening during surgical evacuation of acute subdural hematoma.
To determine preoperative predictors of blood pressure reduction following dural opening during surgical evacuation of hematoma, we retrospectively assessed preoperative variables including clinical profile, hemodynamic parameters, neurological findings, and computed tomography (CT) scan results in 56 patients with traumatic acute subdural hematoma (ASDH). Patients were divided into two groups according to the degree of changes in mean arterial pressure (MAP) in response to dural opening. Group A (n = 18) had a MAP reduction > 20%, and group B (n = 38) had a MAP change within +/- 20% of baseline values (5 min before opening the dura). Significant relationships were found between MAP reductions > 20% and Glasgow coma scale (GCS) scores, abnormalities of the mesencephalic cistern on CT scan, pupillary abnormalities, and degree of midline shift. Low GCS score, absence of the mesencephalic cistern on CT scan, and bilaterally dilated pupils were particularly strong predictors of this amount of blood pressure reduction. The clinical outcomes of patients with MAP reduction > 20% following dural opening during surgery were significantly poorer than those of patients without this amount of blood pressure reduction. Our findings suggest that blood pressure reduction following opening of the dura in patients undergoing surgical evacuation of hematoma for traumatic ASDH may be predicted by careful preoperative assessment of neurological and CT scan findings.
Acute Disease↗
Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain.
The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.
Adrenergic Agents↗
Clinical application of a novel DNA fluorescence intercalator, pyrylium dye, for the quantification of PCR products.
Polymerase chain reaction (PCR) is a powerful tool for clinical diagnosis in the field of oncology, infection, and allergy. However, a simple and sensitive method for quantifying PCR products has not been established. We therefore used a novel fluorescence DNA intercalator, pyrylium iodide (P2) to quantify PCR products. A 838-bp fragment of the human beta-actin gene and a 374-bp fragment of the gene for ornithine decarboxylase (ODC) and ODC primer dimers were generated by PCR and quantified using either P2 or another fluorescence DNA intercalator, YOYO-1. In addition, utilizing RT-PCR and the P2 method, the ODC mRNA expression from 10 colonic cancers was quantified. Serially diluted beta-actin and ODC PCR products could be quantified using P2 without having to separate them from primer dimers and other components of the reaction mixture. However, YOYO-1 could not be used to quantify the PCR products because of high background fluorescence from the primer dimers. In the clinical study, ODC mRNA expression as quantified by P2 was significantly higher in cancerous tissue (113.8 +/- 4.1; mean +/- SEM; plate reader units) than in mucosa of normal appearance (68.4 +/- 4.8). P2 is a promising tool for quantifying PCR products.
Actins↗
[Carcinoid of the gallbladder].
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Carcinoid Tumor↗
[Excellent antiproteinuric effect by LDL apheresis in a case with severe renal dysfunction due to focal segmental glomerulosclerosis].
We report here a 19-year-old man with intractable nephrotic syndrome due to focal glomerulosclerosis (FGS) treated by low-density lipoprotein apheresis (LDL-A). The patient had been receiving several drugs, including steroids, cyclophosphamide, mizoribine and deoxysparguarine, for the past ten years, but the nephrotic syndrome was resistant to these drugs. Although the initial renal biopsy specimen showed minimal change-type lesions, the second biopsy specimen obtained 6 years later revealed typical FGS findings accompanied by lipid deposition (apoB) and macrophage infiltration (CD68) in the involved area. LDL-apheresis was performed ten times per course using a dextran sulfate cellulose column (Liposorba LA-15) as the LDL absorber and polysulfone hollow-fibers (Sulflux) as the plasma separator, processing a total of 3,000 ml of plasma during each apheresis. After treatment the serum levels of LDL and total cholesterol decreased to 50% and 58% of their initial levels, respectively. Immediately after the first course of treatment, the renal dysfunction did not improve, but a decrease in urinary protein was observed (from 43.7 g/day to 8 g/day). Two months later, because urinary protein increased and renal function decreased (Ccr 7 ml/min), a second course of treatment was started. However, his renal dysfunction did not improve and urinary protein did not decrease. In conclusion, in FGS with-progressive renal failure, renal histological findings of positive APO-B, CD68 (macrophage) in sclerotic lesion may be indications of effective LDL-apheresis.
Adult↗
[Anesthetic management for a patient with pheochromocytoma using magnesium sulfate and epidural block].
A 54-year-old woman with pheochromocytoma was anesthetized using magnesium sulfate infusion. Anesthesia was induced with thiopental and fentanyl, and maintained with 0.5% sevoflurane in nitrous oxide/oxygen and 60 mg.hr-1 of epidurally infused lidocaine. Muscle relaxation was achieved with intermittent administration of vecuronium under neuromuscular monitoring. Magnesium 2 g was infused prior to the tracheal intubation and followed by continuous infusion of 2 g.hr-1. These anesthetic techniques made hemodynamic state stable, and no additional vasoactive agents were needed. However, the infusion rate of magnesium was reduced to a half because of PQ interval prolongation. Magnesium is believed to be useful for anesthetic management for patients with pheochromocytoma, but the proper dose and the way of administration should be further investigated for their safe clinical use.
Adrenal Gland Neoplasms↗
Association of Helicobacter pylori and diffuse type gastric cancer.
The major purpose of this study was to evaluate the association of Helicobacter pylori and diffuse type gastric cancer (DGC) clinicopathologically (study 1). The second aim was to investigate genetic differences of H. pylori in patients with DGC and intestinal type cancer (IGC) (study 2). The prevalence of H. pylori and the types of histopathological changes were evaluated in resected early gastric cancer (DGC; 25 patients, IGC; 25 patients). Genetic differences of H. pylori in DGC patients (n = 19) and IGC patients (n = 22) were analyzed by polymerase chain reaction (PCR) methods in terms of restriction fragment length polymorphism patterns of the ureB gene and cagA gene positive rates. All patients had evidence of H. pylori infection in the resected stomach, but the positive rate for H. pylori in the area surrounding cancer was 52% (in DGC; 56%, IGC; 48%). But in 40.0% of DGC cases (10/25), mucosal atrophy and intestinal metaplasia were rarely seen in the area surrounding cancer and the positive rate of H. pylori was 80.0% (8/10), in contrast, in 60.0% of IGC cases (15/25), atrophy and metaplasia were progressed and positive rate of H. pylori was 26.7% (4/15) in the area. UreB gene products from 89.5% of DGC cases (17/19) were unable to be digested by Spe I. 31.8% of products from IGC cases (7/22) were also unable to be digested by Spe I, but the positive rate of cagA gene in this group was higher than other groups. The high prevalence of H. pylori infection in DGC patients suggests that H. pylori plays a role in the pathogenesis of DGC, but in the stomach with DGC, it is considered atrophy and intestinal metaplasia are not so implicated in H. pylori, compared with IGC. A genetic specificity of H. pylori in DGC and IGC was indicated by the results, suggesting that H. pylori may play different roles in the pathogenesis of DGC and IGC.
Base Sequence↗
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↗
Influence of anti-LDL receptor antibody on the transfer of cholesterol from LDL to isolated lymphocytes in normal subjects.
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Antibodies↗
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↗
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↗
Intraoperative electrophysiologic monitoring of cranial motor nerves in skull base surgery.
BACKGROUND: Intraoperative cranial nerve monitoring has been applied for the preservation of nerve function during skull base surgery. However, its usefulness is controversial because clinical results reported are limited. METHODS: We evaluated the usefulness of intraoperative electrophysiologic monitoring of the third to seventh cranial motor nerves in 15 patients undergoing skull base surgery. Intracranial bipolar electrical stimulation of each nerve was performed, and compound muscle action potentials (CMAP) were recorded from the innervated muscles. RESULTS: CMAPs were successfully recorded from 23 of the innervated muscles. The loss of the CMAP response during the manipulation of lesions or high stimulus intensity at the end of manipulation seem to be related to the postoperative deficits of nerve function. CONCLUSIONS: The results suggest that intraoperative electrophysiologic monitoring of cranial motor nerves is useful for prediction of postoperative nerve function.
Adult↗
Effect of chronic vanadate administration in partially depancreatized rats.
The effects of vanadate on B-cell function and replication in rats after 90% partial pancreatectomy (Px) were compared with insulin therapy. At the age of 4 weeks, male Wistar rats were subjected to sham operation or Px. Vanadate (0.2 mg/ml) was given in drinking water for 3 weeks starting at 2 weeks after surgery. Regular insulin (2.4 units/day) was administered as a continuous subcutaneous infusion through an osmotic pump. Plasma glucose levels were significantly higher in the Px rats than in the sham rats from 1 week after surgery. Vanadate lowered plasma glucose levels to near normal values in the Px rats as early as 2 days. The effect was sustained throughout the experiment. The hypoglycemic effect of insulin was less than that of vanadate. During an i.p. glucose tolerance test, plasma glucose levels were decreased in the Px rats treated with vanadate or insulin, while plasma insulin levels were not affected. The insulin content in the Px rats treated with vanadate was significantly (P < 0.01) greater than in the insulin-treated Px rats. Histological examination showed fibrotic degeneration in the enlarged islets of Px rats, whereas the normal structure was retained in most islets of the Px rats treated with vanadate and insulin. In addition, B-cell areas within the islet were restored to normal levels not only in the insulin-treated Px rats but in the vanadate-treated Px rats. However, both vanadate and insulin failed to stimulate proliferative activity of the B-cells. These data suggest that vanadate is a new therapeutic option to ameliorate the diabetic state after Px.
Analysis of Variance↗
Lack of effect of CS-045, a new antidiabetic agent, on insulin secretion in the remnant pancreas after 90% pancreatectomy in rats.
We assessed the effect of CS-045, a new hypoglycemic agent, on B-cell function in partially pancreatectomized rats. At the age of 4 weeks, male Wistar rats were subjected to 90% pancreatectomy (Px). For 2 weeks starting at 6 weeks after surgery the Px rats were treated with CS-045 (CS rats) mixed with chow pellets in a proportion of 0.2% (w/w). To compare the efficacy of CS-045 with that of insulin therapy, an osmotic pump was implanted to release insulin (1.2 units/day) into the intraperitoneal cavity of the Px rats (Is rats). Plasma glucose levels in the CS and Is rats were significantly lower than in the control Px rats; however, no marked improvement in plasma glucose or insulin levels was observed in glucose tolerance test (2 g/kg, i.p.) in the CS rats. Insulin secretion by the isolated perfused pancreas in response to 16.7 mM glucose showed a biphasic pattern, but was slightly reduced in the Px and CS rats compared with the Is rats. Insulin secretion induced by 19 mM arginine was unaffected by the treatment. The insulin content of the CS rats was significantly greater than in the Px and Is rats. Histological observations suggested regranulation of the pancreatic islets of the CS rats. B-cell areas within the islet were restored to normal levels in the Cs and Is rats. These findings indicate that the hypoglycemic effect of CS-045, which is not mediated by insulin secretion from the residual pancreas, prevents destruction of the islet.
Animals↗
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↗
Pathogenicity of bacteria using a simulated root canal system.
The purpose of this study was to investigate the reliability of an implantation test using Teflon-simulated root canals for evaluating the pathogenicity of root canal bacteria. Models including suspensions of lyophilized strains (Actinomyces israelii, Streptococcus faecalis, and Porphyromonas asaccharolyticus) were implanted in rat subcutaneous tissue for 1 wk, and histological changes were observed. Severe inflammation occurred around the models. Among them, P. asaccharolyticus induced the severest inflammatory response. Further study using P. asaccharolyticus was conducted to compare the implantation test's ability to evaluate pathogenicity with that of an injection test at 1, 2, or 4 wk. Tissue injected with a bacterial suspension showed no clear response through the experimental periods, whereas tissue around implantation sites showed a severe response at 1 wk. However, the inflammatory response subsided at later stages. Consequently, further improvement is needed to investigate pathogenicity for long periods.
Actinomyces↗
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↗