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T Sanke

Publications and source records attributed to T Sanke.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with deterioration during pregnancy.

We report a 31-year-old woman who developed myopathy and neuropathy during pregnancy. She was diagnosed as having mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). A T-to-C transition mutation at nucleotide position 3271 was detected in the mitochondrial gene. Her symptoms subsided spontaneously and she delivered a male infant at 38 weeks of gestation. Prior reports on mitochondrial diseases with pregnancy are very rare, probably because of the early onset of the disease. The metabolic changes during pregnancy increase the stress on the mitochondrial function, particularly in patients with impaired mitochondrial function. Therefore pregnancy can aggravate mitochondrial diseases.

Adult↗
PubMed1998

[Acute abdomina pain as a presenting symptom of varicella-zoster virus infection in an allogeneic bone marrow transplant].

A 26-year old man was admitted because of acute abdominal pain. He had received an allogeneic bone marrow transplant (BMT) for aplastic anemia 6 months before. All physical, laboratory, roentgenographic, and ultrasonographic studies were performed but nondiagnostic. On the fourth hospital day the patient developed visual disturbance and on the following day skin eruption appeared. Laboratory findings revealed severe liver dysfunction. We diagnosed this case as varicella-zoster virus (VZV) infection with visceral dissemination. Antiviral therapy with acyclovir was initiated and abdominal pain markedly reduced and visual acuity was recovered after 4 days. In case of VZV infection, acute abdominal pain prior to skin eruptions is rare. However in such cases the patients are highly fatal due to visceral dissemination. Antiviral therapy begun before visceral dissemination of VZV is highly effective in preventing serious disease, whereas it is less effective after dissemination. We consider that early diagnosis and treatment of VZV infection is necessary for BMT recipients who are undergoing immunosuppressive therapy.

Abdominal Pain↗
PubMed1997

The absence of synergism between the effects of an aldose reductase inhibitor, epalrestat, and a vasodilator, cilostazol, on the nerve conduction slowing and the myelinated fiber atrophy in streptozotocin-induced diabetic rats.

The preventive effects of combined or separate treatment for 10 weeks with an aldose reductase inhibitor, epalrestat (50 mg/kg/day), and a vasodilator, cilostazol (30 mg/kg/day), on nerve conduction deficits and morphometric alterations were examined in streptozotocin-induced diabetic rats. The average motor nerve conduction velocities (MNCV) in the tail nerve of the untreated diabetic (DM) group, the group treated with epalrestat (ES), the group treated with cilostazol (CZ), the group with both agents together (ES&CZ), and the normal control group were 34.7, 37.7, 39.3, 39.0 and 42.1 m/s, respectively. All treatments partially but significantly prevented a reduction in MNCV. The MNCV in the ES&CZ group was almost the same as in the CZ group. In a morphometric study of the sural nerve, the DM group showed a reduction in the average diameter of myelinated fiber and in occupancy (percentage of the fascicular area occupied by myelinated fibers), and a shift in the diameter-frequency histogram to smaller diameters. Only the CZ group showed evidence of a partial but significant preventive effect on the decrease in occupancy. In the CS and ES&CZ groups, there was a significant tendency away from the shift of histograms to smaller diameters. The ES&CZ group did not show any fewer morphometric changes than the CZ group. Thus, there was no synergism between the effects of epalrestat and cilostazol on the development of experimental diabetic neuropathy. This finding may provide a useful clue to the mechanisms of action of ES and CZ in diabetic neuropathy.

Aldehyde Reductase↗
PubMed1997

A missense mutation of the muscle glycogen synthase gene (M416V) is associated with insulin resistance in the Japanese population.

Muscle glycogen synthase (GYS1) is a key enzyme of non-oxidative pathway of glucose metabolism that has been reported to be related to insulin resistance in non-insulin-dependent diabetic (NIDDM) patients. We scanned the GYS1 gene for mutation by single strand conformational polymorphism in 244 non-obese Japanese NIDDM patients and 181 non-diabetic control subjects, and found two missense mutations; Met to Val at position 416 in the exon 10 (M416V) and Pro to Ala at position 442 in the exon 11 (P442A). The P442A mutation was found in only one NIDDM patient treated with sulfonylureas. On the other hand, the M416V mutation was widely found in the Japanese population. The mutant allele frequency in the NIDDM patients (13.7%) was slightly higher but not statistically significant compared with that in non-diabetic subjects (9.7%). However, the insulin sensitivity index [SI: x 10(-4) x min(-1) x (microU/ml)(-1)] estimated by Minimal Model analysis in the NIDDM patients carrying the M416V mutation was significantly lower than that in those without the mutation (1.18 +/- 0.27, n = 21 vs 2.20 +/- 0.20, n = 60, mean +/- SEM, p < 0.01). Glucose effectiveness, age, body mass index, and levels of glycated haemoglobin and serum lipids were not significantly different between the two groups. The same trend could be seen in non-diabetic subjects (SI: 3.70 +/- 0.46, 9 subjects with the mutation vs 5.94 +/- 0.66, 19 subjects without the mutation, p < 0.05). These findings indicate that the M416V mutation of the GYS1 gene is one of the factors contributing to the insulin resistance in the Japanese population and may play some role in the pathogenesis of NIDDM.

Adult↗
PubMed1997

Cloning of mouse islet amyloid polypeptide gene and characterization of its promoter.

Islet amyloid polypeptide (IAPP) was isolated from islet amyloid deposits in patients with insulinoma and pancreatic islets of non-insulin-dependent diabetes mellitus (NIDDM) and several reports suggested that it may contribute to the development of NIDDM. IAPP is mainly expressed and synthesized in pancreatic B cells and cosecreted with insulin, so analysis of the transcriptional regulation of the IAPP gene would be helpful for the elucidation of pancreatic B cell specific gene expression. The mouse IAPP gene spans about 5.8 kb and, like the human and rat genes, it consists of three exons, and analysis of the promoter/enhancer activity of mouse IAPP gene reveals the region from -171 to -87 bp to be essential. Within this region, an E-box like sequence, CACCTG (-122 to -117 bp), and a TAAT-box like sequence, TTAATG (-139 to -134 bp), are thought to be important. The disruption of each sequence resulted in a severe decrease in promoter activity, although the decrease was less in the disruption of the E-box than that of TAAT-box like sequence, suggesting the latter is more important for IAPP gene transcription. Like the rat IAPP gene, the CCAAT-box, which does not exist in the human gene, was identified in the mouse gene, indicating the possibility of species difference in the IAPP gene transcriptional mechanism. An enhancer-like activity was also identified within intron 1, although further elucidation is necessary.

Amino Acid Sequence↗
PubMed1997

[Insulin gene].

Explore the source record for details and available documents.

Adolescent↗
PubMed1996

Beta-thalassemia (beta 90 GAG-->TAG): genetic diagnosis by allele-specific polymerase chain reaction and estimation of mutant mRNA expression by reverse transcription polymerase chain reaction.

Genetic diagnosis of a family of beta-thalassemia (beta 90 GAG-->TAG) was carried out by allele-specific polymerase chain reaction (AS-PCR). The proband, her daughter and granddaughter were proved to be heterozygotes of normal and mutant alleles. As some nonsense mutations express a decreased amount of MrNAs, we determined the expression level of the mutant mRNA of beta-thalassemia (beta 90 GAG-->TAG), by application of a combination method of reverse transcription PCR (RT-PCR) and dot-blot hybridization with allele-specific oligonucleotides. The mutant mRNA was not markedly reduced. In conclusion, 1) individuals with the mutant beta-globin gene were diagnosed successfully by AS-PCR, and 2) a significant amount of the mutant beta-globin mRNA was synthesized.

Alleles↗
PubMed1996

Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM.

Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3). PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide. Thus, PC3 plays a key role in regulating insulin biosynthesis. Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing. NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder. To examine this hypothesis, we have isolated and characterized the human PC3 gene and screened it for mutations in a group of Japanese subjects with NIDDM. The PC3 gene consists of 14 exons spanning more than 35 kb. The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family. Single-strand conformational analysis and nucleotide sequencing of the entire coding region of the PC3 gene in 102 Japanese subjects with NIDDM revealed missense mutations in exons 2 (Arg/Gln53) and 14 (Gln/Glu638), neither of which was associated with NIDDM in this population. These data suggest that genetic variation in the PC3 gene is unlikely to be a major contributor to NIDDM susceptibility in Japanese.

Animals↗
PubMed1996

Missense mutation of amylin gene (S20G) in Japanese NIDDM patients.

Many studies suggest that amylin, which is cosecreted with insulin from islet beta-cells, is a biologically active peptide and modulates plasma glucose levels. We therefore scanned the amylin gene for mutations in 294 Japanese NIDDM patients by single-strand conformational polymorphism, and we found a single heterozygous missense mutation (Ser-->Gly at position 20: S20G mutation) in 12 NIDDM patients (frequency 4.1%). None of the 187 nondiabetic subjects or 59 IDDM patients had the mutation. Of 12 patients carrying the mutation, 8 were diagnosed as having NIDDM at a relatively early age (< or = 35 years), and they had severe diabetes and strong family histories of late-onset NIDDM. On the other hand, the remaining four patients were diagnosed as having NIDDM after age 51, and they had mild diabetes without family histories of diabetes. In high-performance liquid chromatography analysis, a small amount (16%) of amylin immunoreactivity appeared in the position corresponding to normal amylin and a much larger amount (84%) appeared in the position corresponding to mutant amylin. These findings suggest that the S20G mutation of the amylin gene may play a partial role in the pathogenesis of early-onset NIDDM in the Japanese population and may also provide an important model to investigate the true physiological action of amylin.

Adult↗
PubMed1995

Effects of cilostazol on development of experimental diabetic neuropathy: functional and structural studies, and Na+ -K+ -ATPase acidity in peripheral nerve in rats with streptozotocin-induced diabetes.

We studied the ability of cilostazol (CL), an antithrombotic and vasodilating agent, to prevent functional, structural and biochemical abnormalities including delayed motor nerve conduction velocity (MNCV), morphological changes in myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the tail nerve, and morphometric analysis of the sural nerves revealed that this dose of cilostazol had a significant effect on reduction of average size of myelinated fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase activity of peripheral nerve were each significantly less than in normal control rats. Cilostazol (30 mg/kg/day) prevented reduction of Na(+)-K(+)-ATPase activity. Decrease in cyclic AMP content was completely prevented with both doses of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may have beneficial effects in the treatment of diabetic neuropathy, possibly via improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content. Cilostazol may thus be a potent drug for the clinical treatment of diabetic neuropathy.

Animals↗
PubMed1995

Association of the prohormone convertase 2 gene (PCSK2) on chromosome 20 with NIDDM in Japanese subjects.

Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3. PC2 is a type II proinsulin-processing enzyme, and it cleaves the proinsulin molecule on the COOH-terminal side of dibasic peptide, Lys64-Arg65, which joins the C-peptide and the A-chain domains. We have previously cloned and characterized the exon-intron organization of the human PC2 gene (gene symbol PCSK2), localized this gene to human chromosome 20 band p11.2 by fluorescence in situ hybridization, and identified a simple tandem-repeat DNA polymorphism (STRP) in intron 2 of the form (CA)n, suitable for genetic studies. Since non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased secretion of proinsulin and proinsulin-like molecules, we conducted a case-control study to determine whether a genetic variation in PCSK2 might contribute to the development of NIDDM. The study population consisted of 152 Japanese NIDDM subjects and 102 normal healthy nondiabetic control subjects matched for age and body mass index. The subjects were genotyped at the STRP in intron 2, and the results indicated a significant difference (P = 0.004) in the overall allele frequency distribution between the two groups. The A1 allele was found more frequently in NIDDM than in nondiabetic subjects (11 vs. 4%, P = 0.0068). The NIDDM patients were divided into two subgroups according to the presence or absence of the A1 allele.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Simple tandem repeat DNA polymorphism in the human glycogen synthase gene is associated with NIDDM in Japanese subjects.

We investigated the possible association between alleles of a simple tandem repeat DNA polymorphism in the human glycogen synthase gene and non-obese non-insulin-dependent diabetes (NIDDM) in Japanese subjects. Nine alleles (-4G, -3G, -2G, -1G, 0G, 1G, 2G, 3G, and 4G) were identified in the study group of 164 patients with NIDDM and 115 non-diabetic subjects. The overall frequency distribution of the glycogen synthase gene alleles was significantly different between the two groups (p = 0.0316). The 2G allele was found more frequently in patients with NIDDM than in non-diabetic subjects (17.7% vs 8.7%, p = 0.0016). These results suggest that the 2G allele could be a genetic marker of NIDDM in Japanese subjects.

Adult↗