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Biomedical subjects

K Tanigawa

Publications and source records attributed to K Tanigawa.

At least 73 records · Page 4Linked to original sources

Unique case of growth hormone (GH) deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

A 43-year-old female was admitted to our hospital for polydipsia and hyperglycemia. She had total blindness and globes were not recognized by inspection, indicating clinical anophthalmia. Physical examination revealed short stature, obesity, prematurely gray hair, shortness of fingers and toes, syndactyly, and multiple dental caries. Laboratory examination showed hyperglycemia, increased glycosilated hemoglobin (HbA1c) and insulin resistance on euglycemic glucose clamp. Blunted growth hormone (GH) secretion was shown in response to insulin-induced hypoglycemia, arginine infusion, and GH-releasing hormone (GHRH) loading test, and in 24 h spontaneous GH profile. Magnetic resonance imaging (MRI) and computed tomography (CT) showed dysostosis of orbit, defect of optic nerve, enlarged suprasellar cistern, and prolonged pituitary stalk. This may be the first report of a unique case with GH deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

Abnormalities, Multiple↗

Role of endogenous hypergastrinemia in regenerating endocrine pancreas after partial pancreatectomy.

We studied the possible role of endogenous gastrin in the regenerating pancreas. Male Wistar rats underwent sham operation or 90% partial pancreatectomy (Px). Lansoprazole (30 mg/kg body wt), a proton pump inhibitor (PPI), was given p.o. for 3 weeks after surgery. Plasma glucose levels were higher in Px rats than in shams. Lansoprazole lowered plasma glucose levels in the Px rats. In addition, integrated insulin secretion during an oral glucose tolerance test (2 g/kg body wt) was significantly (p < 0.01) higher in lansoprazole-treated Px rats than in control Px rats, while lansoprazole did not affect insulin secretion in shams. Fasting serum gastrin levels were higher (p < 0.01) in lansoprazole-treated animals than in controls both in sham rats and in Px rats. Furthermore, lansoprazole increased the pancreas weight per body weight and elevated the insulin content of the pancreas in Px rats. These results suggest that endogenous hypergastrinemia has a trophic effect on endocrine pancreas during regenerating processes and that administration of PPI may be clinically beneficial to the remnant pancreas after pancreatectomy if the whole stomach is preserved.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A novel point mutation in congenital erythropoietic porphyria in two members of Japanese family.

The molecular basis of the uroporphyrinogen III synthase (UROIIIS) deficiency was investigated in two members of a Japanese family. This defect in heme biosynthesis is responsible for a rare autosomal recessive disease: congenital erythropoietic porphyria (CEP) or Gnther's disease. The first patient was homoallelic for a novel missense mutation: a T to C transition of nucleotide 634 that predicted a serine to proline substitution at residue 212 (S212P). The second patient appeared heteroallelic, carrying the same missense mutation and a nonsense mutation: a C to T change at nucleotide 745, resulting in a premature stop at codon 249, instead of a glutamine (Q249X). The corresponding mutated proteins were expressed in Escherichia coli and no residual activity was observed. A family study was also performed to determine the carrier status.

Adult↗

Distribution of nitric oxide synthase-containing nerves in the aganglionic intestine of mutant rats: a histochemical study.

We examined the distribution of nerves containing nitric oxide synthase in the intestine of congenitally aganglionic rats, using a reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemical method for whole-mount and cryostat specimens. A constricted intestinal segment extends from the terminal ileum to the anus in this mutant. No nerve elements with the activity were found in the affected terminal ileum, cecum and proximal colon. Although intrinsic ganglionic neurons were absent along the constricted intestine, nerve fibers with the activity were found in both the submucous and intermuscular layers distal to the proximal colon. These fibers increased in density towards the rectum, forming hypertrophic nerve bundles and unusual fiber networks. However, positive fibers were never seen within the circular and longitudinal musculature of the constricted lesion. Some of these hypertrophic nerve bundles were continuous with ectopic ganglia that were situated in the adventitial connective tissue around the lower rectum and in the submucosa near the anus. The hypertrophic nerve bundles seemed to have an extrinsic origin; some of them may have originated from ectopic ganglia. These results suggest that the defective distribution of nerves containing nitric oxide synthase may be involved in the pathogenesis of congenital colonic aganglionosis.

Animals↗

Expression of hepatocyte growth factor, transforming growth factor alpha, and transforming growth factor beta 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation.

Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) stimulate liver regeneration, whereas transforming growth factor beta 1 (TGF-beta 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF-alpha, and TGF-beta 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF-alpha mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .05). The TGF-beta 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .005). TGF-alpha mRNA expression also correlated with the PCNA LI (r = .92,P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF-alpha produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.

Base Sequence↗

Ontogeny of FAD-linked glycerophosphate dehydrogenase in rat pancreatic islets.

The activities of the mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase were measured in islet and liver homogenates from fetal, neonatal, adult male, adult female, pregnant and lactating rats. Either parallel or dissociated ontogenic changes were observed in islet and liver homogenates. The activity of islet m-GDH was slightly, albeit not significantly, lower in neonates than in adult rats, comparable in male and female adult animals, unaffected by pregnancy, and increased during lactation. It was much higher in fetal or adult islets cultured for 7 days than in freshly isolated islets from adult rats. In cultured islets from adult rats, the increase in m-GDH activity coincided with a dramatic decrease of GPT activity, a situation the mirror image of that found in several animal models of non-insulin-dependent diabetes mellitus. The intrinsic properties of m-GDH, as judged by comparison of measurements made by either a radioisotopic or a colorimetric procedure, were not identical in islet and liver homogenates and differed between fetal and adult islets, suggesting the existence of distinct iso-enzymes. These findings illustrate adaptive changes of islet enzymes, with exclusive or partial mitochondrial location, in ontogenic situations characterized by a remodelling of fuel homeostasis.

Animals↗

Impaired compensatory adaption to B-cell mass reduction in young spontaneously hypertensive rats (SHR).

The aim of this study was to examine the effect of insulin resistance on B-cell function and replication. To this end insulin-resistant spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) as a control were subjected to 90% pancreatectomy (Px) or sham operation at the age of 4 weeks. Islet function and regeneration were examined 4 weeks after surgery. Plasma glucose levels were higher in SHR than in WKY 4 weeks after Px (488 +/- 30 vs. 395 +/- 31 mg/dl; p < 0.01). In sham-operated animals, plasma glucose responses to intravenous injections of glucose (0.5 g/kg body weight) were much higher in WKY than in SHR, while plasma insulin responses were greater in SHR than in WKY. There was no insulin response to glucose in either strain of Px rats. In sham-operated rats, the insulin content of the remnant equivalent pancreas (4.6 +/- 0.8 vs. 3.0 +/- 0.3 micrograms; p < 0.05) and whole pancreas (62.2 +/- 2.8 vs. 53.3 +/- 2.1 micrograms; p < 0.05) were greater in SHR than in WKY. However, the insulin content was lower in SHR than in WKY (1.9 +/- 0.3 vs. 2.5 +/- 0.7 micrograms; p < 0.05) 4 weeks after Px. Fibrotic degeneration of pancreatic islets was greater in Px-SHR than in Px-WKY. These data suggest that the B cells of SHR are more vulnerable to reduction of islet mass than those of WKY. A diminished capacity for islet cell regeneration in SHR may be linked to insulin resistance presented in this animal model of hypertension.

Adaptation, Physiological↗

Ocular complication in congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP), classically known as "Günther disease', is an extremely rare autosomal recessively inherited disorder characterized by mutilating cutaneous photosensitivity and abnormal porphyrin heam biosynthesis in the bone marrow. So far there is no effective therapy for CEP. Because of severe cutaneous photosensitivity, treatment of CEP has mainly been focused upon the avoidance of sunlight and trauma of the skin to minimize skin symptoms. Recently we have encountered ocular complications, especially scleral involvement, in 5 CEP patients. From this point of view, we should pay attention not only to cutaneous symptoms but also to scleral involvement and ophthalmological examination is required to assess the quality of life of CEP patients.

Adult↗

Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion.

BACKGROUND AND PURPOSE: In past studies, cerebral outcome after normothermic cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by resuscitative (postarrest) treatment with either mild hypothermia or hypertension plus hemodilution. We hypothesized that a multifaceted combination treatment would achieve complete cerebral recovery. METHODS: With our established dog outcome model, normothermic ventricular fibrillation of 11 minutes (without blood flow) was followed by controlled reperfusion (with brief normothermic cardiopulmonary bypass simulating low flow and low PaO2 of external cardiopulmonary resuscitation) and defibrillation at < 2 minutes. Controlled ventilation was provided to 20 hours and intensive care to 96 hours. Control group 1 (n = 8) was kept normothermic (37.5 degrees C), normotensive, and hypocapnic throughout. Experimental group 2 (n = 8) received mild resuscitative hypothermia (34 degrees C) from about 10 minutes to 12 hours (by external and peritoneal cooling) plus cerebral blood flow promotion with induced moderate hypertension, mild hemodilution, and normocapnia. RESULTS: All 16 dogs in the protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs achieved overall performance category 1 (normal); 1 dog achieved category 2 (moderate disability), and 1 dog achieved category 3 (P < .001). Final neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were 38 +/- 10% (22% to 45%) in group 1 versus 8 +/- 9% (0% to 27%) in group 2 (P < .001). Total brain histopathologic damage scores were 138 +/- 22 (110 to 176) in group 1 versus 43 +/- 9 (32 to 56) in group 2 (P < .001). Regional scores showed similar group differences. CONCLUSIONS: After normothermic cardiac arrest of 11 minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow promotion can achieve functional recovery with the least histological brain damage yet observed with the same model and comparable insults.

Animals↗

Determination of hemoglobin A1C in normal and diabetic mice: neonatal streptozotocin-induced diabetic mice and KK-Ay mice.

We have determined Hemoglobin A1C (HbA1C) in normal, neonatal streptozotocin-induced diabetic animals (NSZ), a model of lean-type non-insulin-dependent diabetes mellitus (NIDDM) with hypoinsulinaemia, and KK-Ay mice, a model of obese-type NIDDM with hyperinsulinaemia. The HbA1C of NSZ mice was slightly increased from 5 to 20 weeks while the HbA1C of KK-Ay mice was markedly increased from 5 to 10 weeks. Our findings showed a difference between experimentally-induced (NSZ) and genetically (KK-Ay) diabetic animals.

Animals↗

Effect of ginseng radix on GLUT2 protein content in mouse liver in normal and epinephrine-induced hyperglycemic mice.

The oral administration of the water extract of Ginseng Radix (GR) to normal and epinephrine-induced hyperglycemic mice caused a significant decrease in the blood glucose level 4 h after its administration. The hepatic content of facilitative glucose transporter isoform 2, liver type glucose transporter (GLUT2) protein content from mouse liver significantly increased in the orally GR-treated normal and epinephrine-induced hyperglycemic mice compared to that in the controls. These results suggest that the hypoglycemic activity of GR is presumably due, at least in part, to the increment of GLUT2 protein content.

Animals↗

[The postoperative care and treatment in esophageal cancer (4). Postoperative follow up-(recurrence, nutritional management and after-care of IC)].

The points of the postoperative care in radical operation of esophageal cancer are followings. 1) Postoperative nutritional management: In the reconstruction using gastric tube, we make Witzel's gastrostomy in antrum of regardless of the reconstructive routes and transfer to enteral tube-feeding to assist the oral food-taking amount. These management is not only attributing to assist early return to working but also effective to prevent the loss of postoperative physical strength in older patients. 2) Postoperative adjuvant therapy: The esophageal cancer is the diseases that react chemo- and radio-therapy, so most of advanced cases were treated with adjuvant therapy. Nowadays, it is essential for patients to explain the real diagnosis, treatment regimen, then to agree to the informed concent. After informed, the tender mental consult during treatment and outpatient service is required for mental burden. 3) Postoperative follow-up: The recognition of postoperative QOL, early detection of recurrence are mostly emphasized during 2 years after operation. The occurrence of secondary cancer (gastric cancer, cervico-pharyngeal cancer, colorectal cancer etc.) are seen in even 5-10 years after operation. Then the long-term periodical examination and life care are needed.

Chemotherapy, Adjuvant↗

Deleterious effect of formycin A on tumor islet cells.

The adenosine analogue formycin A was recently introduced as a potent insulin secretagogue in normal pancreatic islet cells. In the present study, formycin A was found to inhibit insulin release and to exert a cytotoxic effect in tumor islet cells of the RINm5F line. The latter effect was concentration-related in the 10-100 microM range of formycin A concentrations, not rapidly reversed, and not reproduced by adenosine. This study thus reveals that formycin A may display cytotoxic potential in the same range of concentrations in which it causes a progressive increase of glucose-stimulated insulin secretion in normal pancreatic islets.

Adenoma, Islet Cell↗