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Biomedical subjects

Y Omori

Publications and source records attributed to Y Omori.

At least 55 records · Page 3Linked to original sources
PubMed1998

Erythrocyte aldose reductase protein: a clue to elucidate risk factors for diabetic neuropathies independent of glycemic control.

Prolonged hyperglycemia has been thought to be the primary cause of diabetic complications, however, some diabetic patients develop severe complications early in duration of diabetes, while some patients have no or mild complications even after prolonged hyperglycemia. To investigate the risk factors for diabetic severe neuropathy independent of glycemic control and duration of diabetes, erythrocyte aldose reductase was determined in 43 non-insulin-dependent diabetic patients by a two-site ELISA using recombinant human aldose reductase. Among 20 patients with severe neuropathy which was developed within 5 years of diagnosis, the level of erythrocyte aldose reductase protein was significantly higher than that of 23 patients with no or mild neuropathy who had more than 8 years duration of diabetes and prolonged hyperglycemia (11.9+/-5.7 vs. 8.3+/-1.3 ng/mgHb, P < 0.0001). There was a significant stability of the erythrocyte aldose reductase (AR) in the 40 diabetic patients during 1-4 years. The logistic regression analysis revealed that the maximum body mass index (BMI) in the past minus present BMI and the level of erythrocyte aldose reductase protein were the independent risk factors for diabetic severe neuropathy. The measurement of erythrocyte AR level may be useful for predicting severe neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients.

Aldehyde Reductase↗
PubMed1998

Role of connexin (gap junction) genes in cell growth control: approach with site-directed mutagenesis and dominant-negative effects.

Evidence is accumulating that connexin (Cx) genes form a family of tumor-suppressor genes. Our long-standing study revealed that, in almost all tumors, some abnormality in gap junction is observed, including loss or reduction of expression, aberrant localization of gap junction. In this study, we have examined the dominant-negative effects of mutant (prepared by site-directed mutagenesis) Cx43 constructs in C6 glioma cells, and of mutant Cx26 constructs in HeLa cells, on tumorigenicity. The mutant Cx43 A253V (Ala 253 to Val) inhibited the tumor-suppressive function exerted by wild-type Cx43 in C6 cells. Similarly, the mutant Cx26 P87L (Pro 87 to Leu) manifested dominant-negative inhibition of connexin-mediated cell growth control in HeLa cells. These results suggest that mutations of connexin genes can affect the tumor-suppressive function of gap junction and that gap junctional intercellular communication can be regulated by not only non-genotoxic but also genotoxic activities of environmental carcinogens.

Animals↗
PubMed1998

Ischemic change on electrocardiogram induced by hypoglycemia in a diabetic patient.

A 34-year-old female patient who presented to our hospital had been treated with insulin for diabetes since she was 25 year old. For the previous year she had experienced chest pain on exertion and during hypoglycemia. During both chest pain and exercise tests, ST depression and flattening of the T wave were recognized in leads II, III, aVF, and V2-V6 on the electrocardiogram, and thus ischemic heart disease was suspected. Cardiac catheterization was performed, but no organic stenosis or spasms were found. Hypoglycemia (41 mg/dl) was induced by intravenous injection of rapid insulin (total 18 U, 0.4 U/kg). However, no coronary change was seen, although she felt chest pain and the same ischemic electrocardiographic changes occurred. We hypothesized the causes of the ischemic change to be both the effects of insulin on the cardiovascular system and the physiologic stress induced by the existence of microvascular abnormality. Special care should therefore be taken with diabetic patients being treated with insulin or hypoglycemic agents.

Adult↗
PubMed1998

[The effect of interviewer distance on eyeblinks and heart rates of interviewee].

The purpose of the present study was to investigate the effect of interviewer distance on interviewee eyeblinks and heart rates. The interviewer was a 22 year-old woman, and 21 undergraduates, eight men and 13 women, participated in the study as interviewees. Interviews were conducted under three distance conditions: close (0.8 m), middle (2.0 m), and distant (4.0 m). A polygraph recorded the interviewee's eyeblinks and heart rates during the interview. After the interview, the interviewee rated his/her own psychological state during the interview, and reported impressions of the interviewer. Results showed that interviewees blinked more frequently in the close condition than the other conditions. No significant effect was found on heart rate. Interviewees rated their psychological state as more negative in the close condition, but impression to the interviewer remained the same across the conditions. These results indicated that eyeblink is a useful physiological index of effects that interpersonal situations have.

Adult↗
PubMed1997

Cloning and characterization of a novel member of the human Mad gene family (MADH6).

MAD (mothers against decapentaplegic)-related proteins (MADRs) are intracellular components that play critical roles in signal-transduction pathways involving the transforming growth factor beta (TGFbeta) superfamily. Some Mad genes are candidates for tumor-suppressor functions. From a human fetal brain cDNA library we have isolated a novel Mad-related gene. Two alternatively transcribed mRNAs encode deduced 430- and 467-amino-acid peptides that showed high levels of similarity to MADR1/Smad1/hMAD1 (about 80% identity at the amino acid level). This gene, which we designated MADH6, resides on 13q12-q14 between BRCA2 and RB, a region that frequently displays loss of heterozygosity in breast, liver, and prostate cancers.

Amino Acid Sequence↗
PubMed1997

Insulin gene region contributes to genetic susceptibility to, but may not to low incidence of, insulin-dependent diabetes mellitus in Japanese.

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms in INS region. We found a significant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest that IDDM2 is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDDM2 locus is not responsible for the low incidence of IDDM in Japanese.

DNA, Satellite↗
PubMed1997

Isolation of a novel human cDNA (rhoHP1) homologous to rho genes.

A novel full-length cDNA showing homology with rho genes was isolated from a human placenta cDNA library. Sequencing of a total of 1086 nucleotides of this clone revealed an open reading frame of 630 nucleotides (210 amino acids). In view of its degree of homology to members of the Rho family of molecules (50-54% identical amino acids, 60-63% identical nucleotides within the coding region), the predicted product was designated RhoHP1(Rho-related protein HP1). Northern analysis indicated that a message about 1.2-kb long is expressed in human heart, placenta, liver, skeletal muscle, and pancreas and, with weaker intensity, in several other tissues.

Amino Acid Sequence↗
PubMed1997

Connexin 37 mutations in rat hepatic angiosarcomas induced by vinyl chloride.

Connexin genes have been shown to restore normal cell growth when transfected into certain tumorigenic cells and thus are considered to form a family of tumor suppressor genes. In this study, we have analyzed mutations of the connexin 37 (Cx37) gene in rat hepatic angiosarcomas induced by vinyl chloride. A total of 25 rat liver tumors (22 hepatic angiosarcomas and 3 hepatocellular carcinomas) were analyzed by PCR-single-strand conformation polymorphism analysis and DNA sequencing. Four mutations were detected in three tumors: (a) one GGG(Gly) to GAG(Glu) mutation at codon 168; and (b) three silent mutations, CGA(Arg) to CGC(Arg), at codon 166. In addition, we found that codon 88 is polymorphic (GAG(Glu) to GAA(Glu)). Cx37 proteins are detectable in endothelial cells of normal liver by immunohistochemical analysis, but none of the angiosarcomas showed Cx37-positive spots. These results suggest that Cx37-mediated gap junctional intercellular communication may be disturbed in most of these angiosarcomas, but mutation of the Cx37 gene is rare.

Animals↗
PubMed1997

Predictors of the progression of diabetic nephropathy and the beneficial effect of angiotensin-converting enzyme inhibitors in NIDDM patients.

A progressive decline in glomerular function occurs in diabetic nephropathy. The predictive effects of progression promoters were examined in 182 non-insulin-dependent diabetic patients from a baseline serum creatinine concentration of 133 mumol/l. During a total of 605 person-years follow-up, 107 patients developed end-stage renal failure requiring dialysis. The rate of decline of renal function was highly variable. Urinary protein excretion was the strongest predictor correlated to the rate of decline, followed by diastolic and systolic blood pressure, total cholesterol and platelet count, while the protective effects were seen in serum albumin and haematocrit. Adjustment for urinary protein excretion revealed that diastolic blood pressure, familial predisposition to hypertension, serum albumin, and smoking were independent significant predictors. Angiotensin converting enzyme inhibitors (ACE-I) significantly retarded the development of end-stage renal failure compared to antihypertensives other than ACE-I (mostly nifedipine), and the effect was evident particularly in patients with proteinuria below the median (2.5 g/24 h) (presumably those who responded to ACE-I). A complex effect of proteinuria in association with blood pressure elevation, familial predisposition to hypertension, hypoalbuminaemia, and smoking may play an important role in the progression of nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Urinary albumin excretion rate is related to insulin resistance in normotensive subjects with impaired glucose tolerance.

Microalbuminuria has been reported to precede the development of NIDDM and to be a risk marker for cardiovascular disease. Therefore, the present study investigated the relationship between urinary albumin excretion rate (UAER) and the degree of insulin resistance in Japanese subjects with impaired glucose tolerance (IGT). Thirty-three normotensive IGT subjects were divided into three groups and twenty hypertensive IGT subjects were divided into two groups according to the degree of insulin resistance (GIR value) estimated by the euglycemic hyperinsulinemic clamp method. UAER was significantly higher in the lower GIR group in normotensive subjects (highest GIR group, 6.6 +/- 0.9 mg/24 h; intermediate group, 10.5 +/- 3.0 mg/24 h; lowest group, 21.3 +/- 3.8 mg/24 h; P<0.01 between highest and both of the other groups), but not in hypertensive subjects. The lowest GIR was associated with higher fasting plasma insulin, increased insulin response to glucose, higher plasma triglyceride and uric acid, and lower high-density-lipoprotein cholesterol, but not with increased creatinine clearance rate in normotensive subjects. A similar tendency was also found in hypertensive subjects. It is concluded that UAER is related to insulin resistance in normotensive subjects with IGT through a mechanism other than glomerular hyperfiltration.

Adult↗
PubMed1997

The level of erythrocyte aldose reductase: a risk factor for diabetic neuropathy?

The level of erythrocyte aldose reductase protein (AR-p) was determined in diabetic patients as well as in 76 healthy controls by a two-site enzyme-linked immunosorbent assay. No significant difference in the mean AR-p level was demonstrated between the healthy and diabetic individuals. Based on the results of seven nerve function tests, 95 non-insulin-dependent diabetes mellitus (NIDDM) patients were classified into two groups: Group I, without demonstrable neuropathy ( < or = 1 abnormal test results); Group II, overt neuropathy ( > or = 2 abnormal results). The AR-p level was significantly higher in Group II than that in Group I. Multivariate logistic regression analysis identified two independent risk factors for overt neuropathy: longer duration of diabetes after clinical diagnosis (odds ratio, 1.15 per year; 95% confidence interval, 1.05-1.25) and a higher level of AR-p (odds ratio, 1.92 per 1 ng mgHb(-1); 95% confidence interval, 1.39-2.65). On 31 patients the AR-p level was re-assessed after a 12-month follow-up period. Irrespective of improved or stable HbA(1c) levels during the follow-up period, no apparent alteration in the level of AR-p was demonstrated. These results suggest that erythrocyte AR-p level may affect the susceptibility or development of diabetic neuropathy in NIDDM patients.

Adult↗
PubMed1997

The well-balanced nucleoside-nucleotide mixture "OG-VI" for special medical purposes.

Nucleotides and nucleosides are essential components in all cells. However, nucleotides have not been supplied in parenteral nutrition regimens. We developed a well-balanced nucleoside-nucleotide mixture "OG-VI" and examined its effect in animals under some stressed conditions. OG-VI was composed of 30 mmol/l of inosine, 30 mmol/l of guanosine monophosphate, 30 mmol/l of cytidine, 22.5 mmol/l of uridine and 7.4 mmol/l of thymidine. The whole body protein turnover increased significantly in rats receiving total parenteral nutrition (TPN) with OG-VI solution after 70% hepatectomy, compared with rats receiving normal TPN without OG-VI (122.1 +/- 20.9 mgN.kg-1.h-1 vs. 97.4 +/- 10.1 mgN.kg-1.h-1, P < 0.01, n = 10). OG-VI significantly enhanced protein synthesis while it did not decrease protein breakdown. The effect of OG-VI on myocardium after hypoxic challenge was also examined in rats. The creatine phosphate (PCr)/inorganic phosphate (Pi) was decreased in normal rat myocardium after hypoxic challenge. However, in the rats administered OG-VI, PCr/Pi was maintained at baseline level and did not decrease after hypoxia. There was no significant change in the level of adenosine triphosphate (ATP) between before and after hypoxic challenge in myocardium of the rats administered OG-VI. In the rats receiving normal saline, instead of OG-VI, the ATP level decreased significantly after hypoxic challenge (4132 +/- 276 nmol/g tissue, n = 3, vs. 3439 +/- 465 nmol/g tissue, n = 5, P < 0.05). These data suggested that the well-balanced nucleoside-nucleotide mixture, OG-VI improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗
PubMed1997

A simple method for purification of adult pig pancreatic endocrine cells.

Adult pig pancreatic endocrine cells were harvested by autodigestion without added enzymes. The isolated, crude cells were purified by mono-poly resolving medium (MPRM). The purity of the harvested cells was determined by dithizone staining and the number of pancreatic endocrine cells was counted. A large number of the cells were stained red with dithizone and showed a high viability and a good insulin secretory response to glucose stimulation. The average number of cells purified by MPRM was 3.40 +/- 1.32 x 10(5) cells/g pancreas and the number of dithizone-stained cells was 2.81 +/- 1.09 x 10(5) cells/g pancreas. The insulin secretion from the pancreatic endocrine cells was maintained throughout a 40-day observation period and high glucose stimulation induced an increase in insulin secretion from the cultured cells. In the cells purified by MPRM, light and electron microscopic studies showed the cells to be typical pancreatic endocrine cells. The present purification method using MPRM allowed us quickly to obtain a large amount of adult pig pancreatic endocrine cells from the unpurified preparations. It is thought to be useful for transplantation and biochemical or biological studies of adult pig pancreatic endocrine cells.

Animals↗
PubMed1997

Cloning, expression and mapping of a novel human zinc-finger gene TCF17 homologous to rodent Kid1.

We isolated a novel human zinc-finger gene TCF17 homologous to rat Kid1, a zinc-finger gene of the Krüppel type expressed predominantly in kidney. In the rat this gene seems to be a transcription factor expressed in response to renal injury and ischemia. The 2435-bp human cDNA contained an open reading frame encoding 605 amino acids. The deduced amino acid sequence showed 86.0% and 87.2% identity (91.6% and 92.8% similarity) with the rat Kid1 and mouse Tcf17 respectively. In contrast with rat Kid1, human TCF17 was expressed in all human tissues examined, including kidney. This gene was mapped by FISH to chromosome 5q35.3, where cytogenetic and molecular abnormalities have been reported often in renal cell carcinomas.

Animals↗
PubMed1997

Assessment of insulin resistance in acromegaly associated with diabetes mellitus before and after transsphenoidal adenomectomy.

With a euglycemic hyperinsulinemic clamp method, whole-body insulin resistance was assessed in 6 cases with acromegaly associated with diabetes mellitus before and after transsphenoidal adenomectomy. The glucose infusion rate (GIR) correlated well with the plasma IGF-I level but poorly with that of GH. Further improvement in insulin sensitivity occurred 3-4 months after operation without substantial changes in plasma levels of both GH and IGF-I or glycemic control. These results indicate that GH excess can induce insulin resistance in association with plasma IGF-I and also through undefined secondary effect.

Acromegaly↗
PubMed1997

Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan.

We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4 kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[-1]) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from 5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/-1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36 pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho 0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.

Administration, Oral↗