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Biomedical subjects

K Kotani

Publications and source records attributed to K Kotani.

At least 73 records · Page 4Linked to original sources
PubMed1995

Genetic basis of the silent phenotype of serum butyrylcholinesterase in three compound heterozygotes.

Three Japanese patients showed very low butyrylcholinesterase activity in their sera and appeared to be homozygous for silent genes for butyrylcholinesterase. From DNA analysis, all three patients were compound heterozygotes: GGA(Gly) to CGA(Arg) at codon 365 (G365R) and TTC(Phe) to TCC(Ser) at codon 418 (F418S) in patient 1, G365R and CGT(Arg) to TGT(Cys) at codon 515 (R515C) in patient 2 and ACT(Thr) to CCT(Pro) at codon 250 (T250P) and AGA(Arg) to TGA(Stop) at codon 465 (R465X) in patient 3. The K-variant, GCA(Ala) to ACA(Thr) at codon 539, was also found in patients 1 and 2. Simple identification methods for all the mutations were developed and applied to family analysis and control individuals. The mutant alleles (with silent gene and K-variant) were segregated as predicted by theory in pedigrees of patients 1 and 2. Four of the mutations, F418S, R515C, T250P and R465X, were initially discovered in Japan and genetic heterogeneity among the human population for the butyrylcholinesterase gene was suggested.

Alleles↗
PubMed1995

Pathophysiology and pathogenesis of visceral fat obesity.

Based on the analysis of fat distribution by computed tomography (CT) scans, the classification scheme for obesity should include visceral fat obesity in which fat accumulation is predominant in the intra-abdominal cavity. Obese subjects with visceral fat accumulation more frequently demonstrate impairment of glucose and lipid metabolism than those with subcutaneous fat accumulation. We have shown that visceral fat obesity is present in almost 90% of obese patients with ischemic heart disease. Even in non-obese subjects, visceral fat accumulation is correlated with glucose intolerance, hyperlipidemia and hypertension. Forty percent of non-obese subjects with coronary artery disease (CAD) had increased visceral fat. In non-obese subjects, visceral fat area assessed by abdominal CT at the level of the umbilicus correlates with metabolic risk factors, whereas in obese subjects the visceral fat area to subcutaneous fat area ratio provides a more significant correlation. From clinical and basic investigations, aging, sex hormones, excess intake of sucrose and lack of physical exercise have been suggested to be determinants for visceral fat accumulation. Since intra-abdominal fat (mesenteric and omentum fat) has been shown to have high activities of both lipogenesis and lipolysis, its accumulation can induce high levels of free fatty acids, a product of lipolysis, in portal circulation which go into the liver. Excess free fatty acids may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis. Thus we propose a disease entity, visceral fat syndrome, which may increase susceptibility to atherosclerosis due to multiple risk factors induced by visceral fat accumulation.

Adipose Tissue↗
PubMed1995

Visceral fat accumulation and cardiovascular disease.

Classification of Obesity. It has been noted that the incidence of metabolic complications among equally obese subjects differs depending on their physique (11) and there has been more scientific assessment in recent years that complications such as diabetes mellitus or hyperlipidemia are related to adipose tissue distribution (5). In 1983, we reported a method for adipose tissue analysis using computed tomography (CT), which enables the analysis of adipose tissue in the body cavity, e.g., abdominal cavity or thoracic cavity, as well as subcutaneous fat (10). Using this method, we found that the patients with accumulation of fat in the abdominal cavity have a higher incidence of complication (1). Based on this finding, we proposed a classification into visceral fat obesity by visceral fat area (V)/subcutaneous fat area (S) ratios obtained from CT cross sectional pictures of the umbilical region. We divided obese subjects at a V/S ratio of 0.4, classifying those with a ratio of 0.4 or more as a visceral fat obesity group and those with V/S ratio of below 0.4 as a subcutaneous fat obesity group. Disorders of glucose and lipid metabolism were more marked in the visceral fat obesity than subcutaneous fat obesity even when sex and age were matched. We also demonstrated that visceral fat obesity is more frequently accompanied by circulatory disorders such as left ventricular enlargement (8) and hypertension than subcutaneous fat obesity (2).

Abdomen↗
PubMed1995

Fasting plasma insulin level is an important risk factor for the development of complications in Japanese obese children--results from a cross-sectional and a longitudinal study.

It is not known what types of factors may contribute to the development of complications in obese children. In the current investigation, we have performed a cross-sectional and a longitudinal study in Japanese obese children to clarify the relationship of the extent of obesity, fat distribution, insulin resistance, and aging to the development of obesity-related complications. In the cross-sectional study of 329 obese boys and 142 obese girls aged 7 to 15 years, the fasting plasma immunoreactive insulin (IRI) level was significantly higher than that of 46 non-obese boys and 48 non-obese girls (boys, 13.4 +/- 6.7 v 4.9 +/- 1.9 microU/mL, P < .001; girls, 14.0 +/- 5.9 v 4.8 +/- 1.8, P < .001). Linear regression analysis demonstrated that fasting plasma IRI correlated positively with fasting plasma glucose (FPG), triglycerides (TG), uric acid (UA), and systolic blood pressure (SBP) in obese boys, and with TG, SBP, and diastolic blood pressure (DBP) in obese girls, and negatively with serum high-density lipoprotein cholesterol (HDL-C) in both obese boys and girls. Multiple regression analysis demonstrated that fasting plasma IRI was independently and positively correlated with FPG, TG, and SBP in obese boys. Fasting plasma IRI in obese girls was positively correlated with TG, SBP, and DBP, and negatively with HDL-C. FPG decreased significantly in non-obese children at the onset of puberty, but it remained unchanged in obese children. Fasting plasma IRI and the IRI to glucose ratio increased with age in obese children, whereas they did not show any significant changes in non-obese children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1995

[Percutaneous placement of intraluminal stent-graft for aortic dissection: experimental study].

Highly porous fabric vascular grafts fabricated of ultrafine polyester fibers (UFPF-graft; porosity, 7,000 ml, 9,000 ml, 11,000 ml at 120 mmHg) were attached between two Gianturco stents connected with two stainless steel struts. UFPF-grafts with two Gianturco stents were placed into the aortas of six adult mongrel dogs without firm contact with the luminal surface. From two days to four months after placement, all the UFPF-grafts were completely sealed with fresh thrombus or neointima. Within two months, complete endothelialization was observed on both surfaces of the neointima. In three dogs, aortic dissections were created experimentally. Then an UFPF-graft (porosity, 9,000 ml) with two Gianturco stents was placed at the site of entry of the dissection, followed by additional Gianturco stents to expand the UFPF-graft. X-ray angiography showed that the entries were closed immediately after placement, and false lumens disappeared within one hour after placement. These results indicated that the method has the possibility of treating aortic dissection with complete sealing of the fabric by the neointima.

Aortic Dissection↗
PubMed1994

Distribution of immunoreactive malondialdehyde-modified low-density lipoprotein in human serum.

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL) in human serum. A monoclonal antibody against MDA-LDL (ML25) used in our method recognized not only MDA-LDL but also other MDA-modified proteins. However, MDA-LDL was able to be detected specifically by using a combination of ML25 and an antibody specific for apolipoprotein B (apo B) (AB16), which was conjugated with beta-galactosidase. Using this method, measurable amounts of MDA-LDL were detected in the sera of 40 healthy individuals. MDA-LDL was observed to be mainly distributed in the human LDL fraction separated by density gradient ultracentrifugation, while in each lipoprotein subfraction the largest amount of MDA-LDL per protein was found at a subfraction between LDL and HDL. The particle size of LDL in this fraction was smaller than that of LDL in the main LDL fraction, as assessed by electrophoresis. In addition, LDL oxidized by Cu2+ was also detectable with this method. We conclude that our method is sensitive and specific for MDA-LDL and might be useful for investigating MDA-LDL in the human circulation.

Antibodies, Monoclonal↗
PubMed1994

1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells.

Insulin stimulation drives the formation of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and 1-phosphatidylinositol 3-kinase (PI 3-kinase; ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase, EC 2.7.1.137), a heterodimer consisting of regulatory 85-kDa (p85) and catalytic 110-kDa (p110) subunits. This interaction takes place via the phosphorylated YMXM motifs of IRS-1 and the Src homology region 2 (SH2) domains of p85. In this study, the stable overexpression in a Chinese hamster ovary (CHO) cell line of a mutant p85 alpha (delta p85) protein, which lacks a binding site for p110, disrupted the complex formation between IRS-1 and the catalytic subunit of PI 3-kinase in intact cells during insulin stimulation. Activation of insulin receptor kinase and the tyrosine phosphorylation of IRS-1 remained unaffected. In this cell line, both insulin-stimulated accumulation of phosphatidylinositol 3,4,5-trisphosphate and the insulin-stimulated glucose uptake due to the translocation of GLUT1 glucose transporters were markedly impaired, whereas neither phorbol 12-myristate 13-acetate-stimulated glucose uptake nor the insulin-stimulated activation of RAS was impaired. These results suggest that PI 3-kinase is required for glucose transport in insulin signaling in CHO cells.

Animals↗
PubMed1994

Involvement of phosphoinositide 3-kinase in insulin- or IGF-1-induced membrane ruffling.

Insulin, IGF-1 or EGF induce membrane ruffling through their respective tyrosine kinase receptors. To elucidate the molecular link between receptor activation and membrane ruffling, we microinjected phosphorylated peptides containing YMXM motifs or a mutant 85 kDa subunit of phosphoinositide (PI) 3-kinase (delta p85) which lacks a binding site for the catalytic 110 kDa subunit of PI 3-kinase into the cytoplasm of human epidermoid carcinoma KB cells. Both inhibited the association of insulin receptor substrate-1 (IRS-1) with PI 3-kinase in a cell-free system and also inhibited insulin- or IGF-1-induced, but not EGF-induced, membrane ruffling in KB cells. Microinjection of nonphosphorylated analogues, phosphorylated peptides containing the EYYE motif or wild-type 85 kDa subunit (Wp85), all of which did not inhibit the association of IRS-1 with PI 3-kinase in a cell-free system, did not inhibit membrane ruffling in KB cells. In addition, wortmannin, an inhibitor of PI 3-kinase activity, inhibited insulin- or IGF-1-induced membrane ruffling. These results suggest that the association of IRS-1 with PI 3-kinase followed by the activation of PI 3-kinase are required for insulin- or IGF-1-induced, but not for EGF-induced, membrane ruffling.

Amino Acid Sequence↗
PubMed1994

Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men.

Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Marked reduction of pancreatic insulin content in male ventromedial hypothalamic-lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats.

The effects of ventromedial hypothalamic (VMH) lesions were examined in male and female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with respect to glucose metabolism and pancreatic insulin content. VMH lesions produced hyperphagia and hyperinsulinemia in both male and female GK rats. In male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 +/- 3.1 mmol/L) were significantly greater than the levels of sham-operated GK rats (10.6 +/- 1.0 mmol/L, P < .001) at 7 weeks after the operation, although there were no differences in these levels between VMH-lesioned and sham-operated groups in Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the pancreatic insulin content of male GK rats (12.0 +/- 2.3 nmol/L/g pancreas) compared with male sham-operated rats (15.8 +/- 1.4 nmol/L/g pancreas, P < .05) 9 weeks postoperatively. In contrast to the results in male rats, female GK rats showed no differences in plasma glucose levels between VMH-lesioned and sham-operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK rats. The insulin content was significantly greater in the VMH-lesioned Wistar group than in the sham-operated Wistar group, regardless of sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Increased plasma cholesteryl ester transfer protein in obese subjects. A possible mechanism for the reduction of serum HDL cholesterol levels in obesity.

It is well known that obesity is frequently associated with low levels of serum high-density lipoprotein (HDL) cholesterol. However, the mechanism for this reduction has not been fully clarified. Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins and plays an important role in regulating the concentration and composition of HDL. To elucidate the mechanism for the reduction of serum HDL cholesterol in obesity, we analyzed serum lipoproteins, CETP, and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in 30 obese subjects (17 women and 13 men, age 44 +/- 14 years, mean +/- SD). We also investigated the relationship between these variables, total adiposity, and indices of body fat distribution. The average body mass index of the obese subjects was 33.1 +/- 4.8 kg/m2 (range, 26.4 to 43.8 kg/m2). The obese subjects showed significantly lower serum HDL cholesterol levels than control subjects (1.04 +/- 0.28 versus 1.50 +/- 0.34 mmol/L, P < .01). In the obese subjects, both activities and protein mass of CETP and postheparin HTGL activities were significantly increased, whereas postheparin LPL activities were significantly decreased. CETP activities, independent of postheparin HTGL and LPL activities, were correlated negatively with HDL cholesterol (r = -.39, P < .05) and the cholesteryl ester to triglyceride ratio of HDL2 and HDL3 (r = -.36, P < .05; r = -.46, P < .05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Sexual dimorphism of age-related changes in whole-body fat distribution in the obese.

We performed a cross-sectional study using whole-body computerized tomographic (CT) scans in order to clarify age-related changes in whole-body fat distribution in both genders. The subjects were 66 men and 96 women, whose body mass index (BMI) was over 25 kg/m2. CT scans were performed at seven levels (head, fore-arms, upper arms, chest, abdomen, thighs and calves), and the fat volumes of the segments were calculated from the cross-sectional areas of the fat tissues. After calibrating to the total fat volumes, the relationship between age and the relative segmental fat volumes was analysed. In both genders, the relative intra-abdominal visceral fat volume increased and that of the legs decreased with age. The relative abdominal subcutaneous fat volume decreased with age only in male subjects. The increase in the relative visceral fat volume with age was about 2.6 times larger in males than in pre-menopausal females, while post-menopausal females showed the same increase as male subjects. These data suggest that there is a definite gender difference in the age-related changes in whole-body fat distribution, especially in the abdominal fat tissues. In addition, the accumulation of visceral fat is markedly accelerated by menopause in women.

Abdomen↗
PubMed1994

[Reestimation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio based on JSCC consensus method--changes of criteria for a differential diagnosis of hepatic disorders following the alteration from Karmen method to JSCC method].

We estimated clinical criteria of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio that is measured by the consensus method of JSCC (Japan Society of Clinical Chemistry) for serum AST and ALT. The JSCC consensus method is closely correlated with both IFCC (International Federation of Clinical Chemistry) recommended method without pyridoxal phosphate and Karmen method recommended by the expert panel of liver function tests in Japanese Society of Gastroenterology. The slopes of the regression line is estimated to be 1.00 and 0.87 respectively. We propose that the decision making value of AST/ALT ratio to differentiate several types of liver diseases should be set to 0.87 measured by JSCC consensus method, instead of 1.0 measured by Karmen method.

Alanine Transaminase↗
PubMed1993

[A study of transsplenic CO2 gas enhanced portal angioechography].

Transsplenic CO2 gas enhanced portal angioechography was examined. The spleen of three dogs was punctured by 23 gauge needle with two side holes. From 5 ml to 20 ml of CO2 gas was injected into the splenic vein via the splenic parenchyma, and elevation of echo level of the liver was observed. Hematoma was not seen at the site of puncture. Good image was obtained in the case of 5 ml CO2 injection. In one dog with pseudotumor in the liver, the hyperechoic tumor changed into negative enhanced nodule after CO2 gas enhancement. Transsplenic CO2 gas enhanced portal angioechography is thought to be useful to evaluate hepatic tumors.

Animals↗
PubMed1993

Syntheses of modified 2-chloro-4-nitrophenyl beta-maltopentaosides as useful substrates for assay of human alpha amylase.

Twenty-three novel 2-chloro-4-nitrophenyl beta-D-maltopentaosides modified at the 6(5) and/or 4(5) position were synthesized as substrates for human alpha amylase. Two human alpha amylases hydrolyzed 6(5)-deoxy-6(5)-, 6(5)-O-, and 4(5),6(5)-di-O-substituted derivatives at essentially a single D-glucosidic linkage, but 4(5),6(5)-O-bridged and 4(5)-O-substituted derivatives were hydrolyzed at two or more linkages. The amylases displayed smaller Km values for the compounds having hydrophobic modifications. In these derivatives, 2-chloro-4-nitrophenyl O-(6-bromo-6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha-D- glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (10), 2-chloro-4-nitrophenyl O-(6-azido-6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (19), and 2-chloro-4-nitrophenyl O-[6-O-(N-isopropyl)carbamoyl-alpha-D-glucopyranosyl]-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (30), which were rapidly hydrolyzed by the two amylases at a limited position at an approximately equal rate, were shown to be very useful blocked-type substrates for assay of human alpha amylase.

Carbohydrate Sequence↗
PubMed1993

Syntheses of subtractively modified 2-chloro-4-nitrophenyl beta-maltopentaosides and their application to the differential assay of human alpha-amylases.

Three novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-xylo-hex-5-enopyranosyl)-(1-->4)-tris[O-alpha-D - glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (3), 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (10), and 2-chloro-4-nitrophenyl O-(3,6-anhydro-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha-D-glucopyran osyl- (1-->4)]-beta-D-glucopyranoside (26) were synthesized by chemical and enzymatic reactions. Two human alpha-amylases, salivary alpha-amylase (HSA) and pancreatic alpha-amylase (HPA), hydrolyzed 3 and 10 with the same specificity, almost entirely at a single D-glucosidic linkage, but had no hydrolytic activity for 26. Compound 3 was hydrolyzed by each of these amylases at an approximately equal rate, while 10 was hydrolyzed by HSA 4-fold faster than by HPA. Taking advantage of the difference in the hydrolytic rate of 10, we developed a new method for the differential assay of these two human alpha-amylases.

Carbohydrate Sequence↗
PubMed1993

Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility.

Evidence is accumulating that rho p21, a ras p21-related small GTP-binding protein (G protein), regulates the actomyosin system. The actomyosin system is known to be essential for cell motility. In the present study, we examined the action of rho p21, its inhibitory GDP/GTP exchange protein (named rho GDI), its stimulatory GDP/GTP exchange protein (named smg GDS), and Clostridium botulinum ADP-ribosyltransferase C3, known to selectively ADP-ribosylate rho p21 and to impair its function, in cell motility (chemokinesis) of Swiss 3T3 cells. We quantitated the capacity of cell motility by measuring cell tracks by phagokinesis. Microinjection of the GTP gamma S-bound active form of rhoA p21 or smg GDS into Swiss 3T3 cells did not affect cell motility, but microinjection of rho GDI into the cells did inhibit cell motility. This rho GDI action was prevented by comicroinjection of rho GDI with the GTP gamma S-bound form of rhoA p21 but not with the same form of rhoA p21 lacking the C-terminal three amino acids which was not posttranslationally modified with lipids. The rho GDI action was not prevented by Ki-rasVal-12 p21 or any of the GTP gamma S-bound form of other small GTP-binding proteins including rac1 p21, G25K, and smg p21B. Among these small G proteins, rhoA p21, rac1 p21, and G25K are known to be substrates for rho GDI. The rho GDI action was not prevented by comicroinjection of rho GDI with smg GDS. Microinjection of C3 into Swiss 3T3 cells also inhibited cell motility. These results indicate that the rho GDI-rho p21 system regulates cell motility, presumably through the actomyosin system.

3T3 Cells↗