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Biomedical subjects

J Tashiro

Publications and source records attributed to J Tashiro.

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

Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation.

OBJECTIVES: The purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL). DESIGN AND PATIENTS: A total of 31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26 +/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas were evaluated using a computerized tomographic (CT) method at the level of the umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured using Triton X-100-emulsified triolein and LPL activity was calculated as the activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL enzyme mass was determined by a sandwich enzyme immunoassay. RESULTS: The visceral fat area was found to be negatively correlated with LPL mass (V vs LPL mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12). Subcutaneous fat area, on the other hand, did not show any correlation with LPL activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The visceral fat area was found to be positively correlated with fasting serum insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated with LPL mass or activity in the PHP. Multi-regressional analysis showed that abdominal visceral fat could be correlated with LPL mass in the PHP, independently of fasting serum insulin. The HL activity from PHP of the patients did not show significant correlation with visceral fat area, subcutaneous fat area or body mass index. CONCLUSIONS: Fat distribution affects LPL mass and activity, either directly or via another metabolic abnormality such as insulin resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and very low density lipoproteins (VLDL) in these subjects.

Abdomen↗
PubMed1998

New type of the internalization-defective low-density lipoprotein receptor owing to two-nucleotide deletion (2199delCA or 2201delCA) in Japanese patients with familial hypercholesterolaemia.

BACKGROUND: In mutations of the low-density lipoprotein (LDL) receptor gene, the defect of internalization is caused by a mutation in the cytoplasmic domain of the receptor linked with exons 17 and 18, and the O-linked sugar domain linked with exon 15 has been speculated not to affect the function of the receptor. Here, we describe a novel mutation of the O-linked sugar domain of the LDL receptor gene, designated familial hypercholesterolaemia (FH)-Mishima with Japanese pedigree, which resembles but still differs from classical defective internalization cases. METHODS: LDL metabolism was examined in cultured skin fibroblasts from patients. Immunoprecipitation and immunohistochemical techniques were applied for the detection of the receptor protein size and distribution. Screening of the mutant exon(s) of the LDL receptor gene was performed using the polymerase chain reaction-single-strand conformation polymorphism technique (PCR-SSCP), and sequencing of the mutated alleles was carried out using the dideoxy chain termination method. RESULTS: LDL-binding activity at 4 degrees C in skin fibroblasts from patients was similar to normal, but that at 37 degrees C with the ligand decreased time dependently and was lost at 6 h, resulting in the defect of internalization and degradation of LDL. The receptor protein on the cell surface was detected at 4 degrees C by IgG-C7, an anti-LDL receptor antibody, but was not detected after incubation with LDL at 37 degrees C. The size of the receptor was 112 kD as determined by immunoprecipitation analysis. A deletion of two nucleotides in exon 15 was detected in the DNA sequence of the LDL receptor gene. The deletion results in a shift of the reading frame after Thr-713 of the mutant and makes a stop codon at amino acid 759. CONCLUSION: Deletion of the two nucleotides caused novel amino acid sequences after the O-linked sugar domain, which has the ability of sorting on the cell membrane at 4 degrees C, but not at 37 degrees C in vivo, resulting in the complete cessation of activity of the LDL receptor.

Amino Acid Sequence↗
PubMed1998

Administration of a small amount of lard enhances intimal thickening in the balloon catheter injury model without affecting serum lipids.

Effects of fatty acids on intimal thickening induced by a balloon catheter injury model were investigated by feeding rabbits a small amount of either lard [L] or fish oil [F]. Serum lipids of these groups were not different from those of basal diet-fed rabbits [controls] after 4 weeks of feeding. Serum saturated fatty acids such as 14:0, 16:0, and 18.0 were significantly greater in the L-fed rabbits compared with controls, but those of the aorta were not significantly different. Fatty acid composition of the F-fed rabbits was only different from that of the controls in that n-3 fatty acids slightly increased. The mean and maximum intimal thickening 2 weeks after ballooning, carried out 2 weeks after feeding, were significantly higher in the carotid arteries of the L-fed rabbits than in the controls. The intimal thickening of the F-fed rabbits did not significantly differ from that of the controls. These results suggest that lard promotes the formation of the smooth muscle cell dominant type of arteriosclerosis without affecting serum lipid levels.

Animal Feed↗
PubMed1997

New indices of ischemic heart disease and aging: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease.

It is known that the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of vascular endothelial cells is closely related to the formation of early atherosclerotic lesions. In this study, serum soluble ICAM-1(sICAM-1) and soluble VCAM-1(sVCAM-1) were determined by sandwich ELISA both in normal healthy individuals (n = 114) and in patients with hypercholesterolemia (HC, n = 112) or ischemic heart disease (IHD, n = 38) to clarify the significance of the soluble forms of the adhesion molecules in the development of atherosclerotic diseases. IHD patients, not HC patients, showed significant elevation of sICAM-1, but not of sVCAM-1, compared with controls in age and sex-matched subjects. In addition, multiple linear regression analysis showed that sICAM-1 was correlated only to the presence of IHD but not to age and lipids. Multiple logistic regression analysis revealed that sICAM-1 was the most powerful independent predictor of the presence of IHD. On the other hand, sVCAM-1, not sICAM-1, was positively correlated to age. Multiple linear regression analysis showed that age was the most powerful independent predictor of the level of sVCAM-1. These data suggest that sICAM-1 and sVCAM-1 are useful as indices of clinical manifestations of atherosclerosis and aging, respectively.

Adult↗
PubMed1997

Type III hyperlipidaemia with primary hypothyroidism: a unique clinical course of hyperlipidaemia during replacement therapy of thyroid hormone.

A patient is described with type III hyperlipidaemia and primary hypothyroidism who had a unique clinical course of hyperlipidaemia. The patient was a 65-year-old man with primary hypothyroidism. His plasma total cholesterol, triglyceride and high density lipoprotein-cholesterol concentrations 1 year after starting thyroid hormone replacement therapy were 7.98, 4.04 and 0.72 mmol/l, respectively. His plasma apolipoprotein (apo) E level was 0.29 g/l and its phenotype was E2/2. Remarkably, this patient had no hyperlipidaemia before starting thyroid hormone replacement therapy but it became overt only after the hypothyroidism had been treated. Although we have not confirmed the mechanism for this, we speculate that a decrease in enzyme activities responsible for cholesterol production may have been sufficient to surpass the effect of apolipoprotein E2/2 and the decrease in enzyme activities involved in degrading and excreting plasma cholesterol, resulting in normolipidaemia.

Aged↗
PubMed1995

Treatment of obesity by personality classification-oriented program.

It is apparent that personality is related to the pathogenesis of obesity, and that understanding the personality of the patient may be a key to successful treatment of the disease. Using the Rorschach test and interviews by a psychiatrist, the types of personality were classified into four groups according to the healthiness of personalities. The judgment of healthiness was based mainly on the scores obtained from the Rorschach test. This classification revealed that the occurrence of mental and physical symptoms during therapy with a very low calorie diet (VLCD) and subsequent rebound of bodyweight were more frequently observed in patients with relatively less healthy personalities. We used this classification to adapt our program to treat obese patients. In this program, severe diet restrictions were applied to patients with relatively healthy personalities. These restrictions were applied with modifications to patients with less healthy personality, because severe restrictions would be possibly very stressful for them and would bring about an undesirable reaction. For strengthening the patients' motivation for therapy, the significance of body weight reduction was explained in different ways to patients with different types of personality. The target of bodyweight reduction, reward for patients with successful weight reduction, and the duration of therapy were set up differently for patients with different personalities types. The results showed that bodyweight rebound one or two years after treatment was reduced with the personality-oriented therapy program compared to that observed with the previous conventional therapies. Also, the incidence of psychological problems was remarkably decreased.

Adult↗
PubMed1994

C-type natriuretic peptide inhibits intimal thickening of rabbit carotid artery after balloon catheter injury.

C-type natriuretic peptide (CNP) stimulated cGMP production in rabbit cultured vascular smooth muscle cells, and thymidine uptake was inhibited by CNP. We tested whether CNP inhibits the development of intimal lesions induced by balloon catheter injury in rabbit common carotid artery. CNP (1 microgram/kg/min) infusion through the left jugular vein by DIB balloon catheter pump was started at 30 min before injury and continued until sacrifice. The median of the mean ratio of intima to media in each rabbit after 14 days was 29.5% [14.5-57.8] for control group and 12.0% [2.5-29.8] for CNP group (p < 0.01). Maximum ratio was also significantly low in CNP group. These results suggest that CNP may act as local regulator which suppresses intimal thickening.

Animals↗
PubMed1994

Diabetic control and progression of retinopathy in elderly patients: five-year follow-up study.

OBJECTIVE: To assess whether control of diabetes mellitus is as important in the elderly as in young and middle-aged diabetic patients in terms of progression of retinopathy. DESIGN: A 5-year longitudinal cohort study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred fourteen non-insulin-dependent diabetic patients (30 males, 84 females) > or = 60 years of age. MEASUREMENTS: Retinopathy was checked at the beginning and end of the follow-up period. During the 5-year follow-up period, demographic variables, body mass index, HbA1c, blood pressure, and plasma lipids were monitored. Retinopathy was classified as follows: grade 0, no lesion; grade 1, non-proliferative retinopathy; grade 2, pre-proliferative retinopathy; grade 3, proliferative retinopathy. Progression of retinopathy during the 5-year follow-up was defined as an increase in its grade. RESULTS: At the start of the study, 13% of the patients already had retinopathy, all of grade 1. The 5-year follow-up study showed that progression of retinopathy was 23.6% in all cases, 22.2% in those with grade 0 initially, and 33.3% in those with grade 1 initially. The progression rates of retinopathy as a function of the mean HbA1c during the follow-up were as follows: lower than 7%, 2%; 7-8%, 20%; 8-9%, 40%; more than 9%, 61%. Multiple logistic regression analysis showed that, of the parameters examined, only HbA1c was a significant risk factor for progression of retinopathy. CONCLUSIONS: Control of diabetes mellitus is the most important factor associated with prevention of progression of retinopathy in elderly patients.

Aged↗
PubMed1994

Lipoprotein(a) is a risk factor for diabetic retinopathy in the elderly.

OBJECTIVE: To assess whether serum lipoprotein(a) is a risk factor for diabetic retinopathy in the elderly. DESIGN: A cross-sectional study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred four noninsulin-dependent diabetic patients (35 males, 69 females). Twenty-three were less than 60 years of age (middle-aged), and 81 were 60 years or older (elderly). MEASUREMENT: Levels of lipoprotein(a) (Lp(a)) and lipids were measured in fasting serum. HbA1c was also measured as an indicator of diabetic control. Other indicators possibly related to retinopathy were also checked. Retinopathy was estimated by photographs of fundi. RESULTS: Significantly higher indicators in the group with retinopathy than in the group without were: HbA1c, Lp(a), duration of diabetes, and systolic blood pressure (BP) in the total cases; HbA1c, duration of diabetes, and Lp(a) in the middle-aged; HbA1c, systolic BP, and Lp(a) in the elderly. Multiple logistic regression analysis showed that only HbA1c and Lp(a) were independent risk factors for retinopathy in all cases and in the elderly. The incidence of retinopathy was positively correlated to serum Lp(a) levels. CONCLUSION: Lp(a) is an independent risk factor for diabetic retinopathy.

Aged↗
PubMed1994

Effects of treatment with bezafibrate on lipoprotein lipase activity and mass in patients with hypertriglyceridemia.

The activity and mass of lipoprotein lipase (LPL) in postheparin plasma (PHP) from patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance, hyperinsulinemia were investigated in order to clarify the cause of hypertriglyceridemia and the effects of bezafibrate (CAS 41859-67-0), a novel lipid lowering agent. Eight weeks of treatment with bezafibrate (200 mg/d) lowered plasma total cholesterol and triglyceride by 7 and 39%, respectively, and increased plasma high density lipoprotein (HDL) cholesterol by 23% in the patients (n = 15). The LPL activity and mass of PHP in the patients were found to be lower than in the normal controls. The LPL activity and mass of PHP in the patients before treatment with bezafibrate (n = 15) were 2.05 +/- 1.06 mumol/ml/h and 147 +/- 45 ng/ml, respectively, whereas after treatment with 200 mg/d of bezafibrate for 8 weeks, these values were 3.62 +/- 1.30 mumol/ml/h (p < 0.01) and 226 +/- 57 ng/ml (p < 0.05), respectively. The increases of LPL mass were positively correlated with the decrease of triglyceride levels during the same period. These results suggest that the expression of LPL enzyme protein is impaired in patients with hypertriglyceridemia coupled with hypertension, impaired glucose tolerance and hyperinsulinemia, and the impaired expression of LPL recovers during treatment with bezafibrate, resulting in improvement of hypertriglyceridemia.

Adult↗
PubMed1993

Lipoprotein lipase mass and activity in severe hypertriglyceridemia.

To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LPL mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was 2,960 +/- 1,057 nmol/ml/h. The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were 25 +/- 5 ng/ml and 224 +/- 60 ng/ml, respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 mumol FFA released/h/microgram LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than -2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than -2 S.D. despite the fact that LPL masses were not less than -2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.

Adult↗
PubMed1993

A missense mutation (Ala334-->Thr) in exon 7 of the lipoprotein lipase gene in a case with type I hyperlipidemia.

The patient is a 34-year-old female. Her fasting plasma triglyceride and cholesterol levels were 7523 mg/dl and 818 mg/dl, respectively, at 35 weeks' gestation. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the proband were 0.02 (normal range: 5.51 +/- 1.12 mu mol/ml/h) and 168 ng/ml (normal range: 220 +/- 42 ng/ml), respectively, indicating that the LPL of the patient would be functionally defective LPL. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a G--> A transition at nucleotide position of 1255 resulting in an amino acid substitution of Thr for Ala 334. This is the first natural missense mutation identified in exon 7 of the LPL gene.

Adult↗
PubMed1993

The 'midband' lipoprotein is a coronary risk factor in Japanese patients with familial hypercholesterolaemia.

The relationship between coronary stenosis and 'midband' lipoprotein, which was observed between low density lipoproteins and very low density lipoproteins by 3% polyacrylamide gel electrophoresis, was studied in patients with heterozygous familial hypercholesterolaemia (FH). The subjects were 46 patients with FH, who were evaluated by coronary angiography. The groups with and without coronary artery disease (CAD) were compared. Age, sex ratio, total cholesterol, triglyceride, HDL-cholesterol and lipoprotein(a) levels were matched in these two groups. In addition, Achilles tendon thickness and the incidence of risk factors such as diabetes mellitus, hypertension and smoking between these two groups were matched. Under these conditions, the frequency of midband was higher in the patients with CAD (20/26) than that in patients without (4/20). The results suggest that the presence of a midband among Japanese is an independent risk factor for coronary stenosis even in cases of FH who have severe hypercholesterolaemia.

Adult↗
PubMed1992

Effects of substitutions of glycine and asparagine for serine132 on activity and binding of human lipoprotein lipase to very low density lipoproteins.

For studying the role of Ser132 in the putative catalytic site of human lipoprotein lipase (LPL), mutant LPL cDNAs expressing LPLs with amino acid substitutions of Gly or Asn for Ser132 were obtained by site-directed mutagenesis, and were expressed in COS-1 cells. Considerable amounts of LPL enzyme protein mass were detected in the culture medium of COS-1 cells transfected with wild-type LPL, LPL-Gly132, or LPL-Asn132. LPL-Gly132 hydrolyzed Triton X-100-triolein and tributyrin as effectively as wild-type LPL, whereas LPL-Asn132 showed no activity. LPL-Asn132 bound to very low density lipoproteins as effectively as wild-type LPL.

Amino Acid Sequence↗
PubMed1992

Trypsin treatment may impair the interfacial activation action of lipoprotein lipase.

Lipoprotein lipase was expressed in Chinese hamster ovary (CHO) cells transfected with human lipoprotein lipase cDNA. The lipoprotein lipase retained tributyrin, water-soluble substrate, hydrolyzing activity (esterase activity). The catalytic action of this enzyme was studied by monitoring the esterase activity. The esterase activity was enhanced 4.5-fold by the addition of triolein emulsified with Triton X-100. This process was named interfacial activation. Treatment of LPL with trypsin (100 micrograms/ml, 37 degrees C for 10 min) caused the loss of the triolein hydrolyzing activity without that of the esterase activity. The esterase activity of trypsin-treated LPL was not enhanced by the addition of the triolein emulsion. The trypsin-treated LPL retained the ability to bind to very low density lipoproteins (VLDL). These results are consistent with the idea that LPL has a catalytic site and a lipid interface recognition site, and that the enzyme undergoes interfacial activation, in which the concealed catalytic site is revealed after the enzyme binds to the surface. Based on this hypothesis, the results obtained suggest that trypsin nicking may impair the interfacial activation process and cause the loss of the lipase activity.

Animals↗
PubMed1992

Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats.

The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level.

Adipose Tissue↗