Search PubMed⌕ Search

Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 415 records · Page 23Linked to original sources
PubMed1996

Analysis of candidate genes for insulin resistance in essential hypertension.

To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of beta3 adrenergic receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension.

Case-Control Studies↗
PubMed1996

Genetics of insulin-dependent diabetes mellitus.

IDDM is caused by autoimmune destruction of insulin-producing beta cells of the pancreas in genetically susceptible individuals. Although the incidence and prevalence if IDDM in Japan are much lower than those in Caucasian countries, the recurrence risk in siblings of IDDM probands is much higher than the population prevalence, indicating that IDDM is clustered in families even in Japan, where the incidence of the disease is the lowest in the world. The higher concordance rate in monozygotic twins than in dizygotic twins indicates that genetic factors contribute to the familial clustering of IDDM in Japan. Analysis of the HLA region revealed that susceptibility genes (IDDM1) consist of multiple components, those in class II DR and DQ regions and another in the class I region. Analysis in NOD mice, an animal model of IDDM, supports this observation: susceptibility genes (Idd1) are mapped to class II A and E regions, but the incidence of the disease is strongly affected by a gene or genes outside of this segment (Idd16). Studies in both humans and an animal model will clarify the genetic components of IDDM, facilitating prediction of the disease and the development of effective strategies for its prevention.

Animals↗
PubMed1996

[Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women].

To compare the efficacy of estriol (E3) in postmenopausal and senile osteoporosis, we administered orally 1 g/day calcium lactate either alone (control groups) or with 2 mg/day estriol (estrogen groups) for 10 months to 20 postmenopausal women aged 50-65 years and to 29 elderly women aged 70-84 years, and measured their bone mineral density of the lumbar vertebrae by dual energy X-ray absorptiometry. Out of 41 subjects who completed 10 months of treatment, 8 postmenopausal women and 12 elderly women in the estrogen groups had significant (p < 0.05) increases in bone mineral density (5.59 +/- 4.79% of the respective basal values). Ten postmenopausal women and 11 elderly women in the control groups had decreases bone mineral density (-4.02 +/- 7.00% and -3.26 +/- 4.60% of the respective basal values) at the 10th month. Genital bleeding as a side effect of estriol was seen in 6 out 29 elderly subjects at this dose. Moreover, decreases in the levels of calcium, total cholesterol, and triglycerides in serum, and an increase in the level of high-density lipoprotein-cholesterol were seen only in the elderly women receiving estriol. Although a lower dosage of estriol may be recommended for elderly subjects, these observations suggest that hormone replacement therapy with estriol is effective against degenerative osteoporosis, and that low-turnover bones in elderly women are also responsive to estriol.

Aged↗
PubMed1996

[Primary biliary cirrhosis with polymyositis successfully treated with prednisolone and ursodeoxycholic acid].

A 65-year-old woman was given a diagnosis of polymyositis in April 1991. She was treated with prednisolone until December 1993, at which time muscle strength had increased and high blood pressure had developed. In May 1994 she was hospitalized for muscle weakness and mild liver dysfunction. Prednisolone was given and the levels of hepatobiliary enzymes decreased. Immunological examination revealed strongly positive results for anti-mitochondria antibody and M-2 antibody, which lead to the diagnosis of primary biliary cirrhosis. administration of ursodeoxycholic acid in addition to prednisolone was followed by normalization of liver function and a decrease in the production of the autoantibodies. Although polymyositis can be complicated by autoimmune diseases, reports of complication by primary biliary cirrhosis are rare, here we report that treatment with the combination of ursodeoxycholic acid and prednisolone was successful in a patient with liver dysfunction and primary biliary cirrhosis.

Aged↗
PubMed1996

[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan].

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

Aged↗
PubMed1996

Age-related changes of alpha-tocopherol transfer protein expression in rat liver.

Developmental changes in expression of alpha-tocopherol transfer protein (alpha-TTP) after birth were investigated using rats with respect to plasma changes of tocopherols. The expression of alpha-TTP in the neonatal rat liver, which was very low immediately after birth, increased steadily during the two weeks of life before weanling and reached the adult level at four weeks. During the suckling period, the plasma ratio of alpha-tocopherol to gamma-tocopherol linearly increased, because plasma alpha-tocopherol which was low immediately after birth, increased rapidly during the period, while gamma-tocopherol remained unchanged. The increase in the ratio seemed to correlate with the developmental expression of alpha-TTP in the liver during this period. The ratio also reached the adult level after four weeks. The expression of alpha-TTP was investigated using primary cultured rat hepatocytes. The expression of alpha-TTP was found to be extremely low after 20h of culture. The decrease in alpha-TTP expression was exacerbated by adding epidermal growth factor to the culture medium and was inhibited by adding dexamethasone. These observations suggest that expression of alpha-TTP may be affected by the state of hepatic differentiation.

Aging↗
PubMed1996

Links between hypertension and myocardial infarction.

The mechanisms through which hypertension contributes to the occurrence of myocardial infarction should be discussed from two points of view: (1) common risk factors for the two diseases, such as genetic risk, insulin resistance, sympathetic hyperactivity, and vasoactive substances such as angiotensin K, and (2) linking factors that are induced by hypertension and contribute to the development of atherosclerosis and myocardial infarction, such as atherosclerosis and left ventricular hypertrophy. Mechanical stress on blood vessels because of high blood pressure is an especially important factor in endothelial dysfunction, the progression of atherosclerosis, and plaque rupture. This article concentrates on these factors from the perspective of their relationship with the renin-angiotensin system, because recent multicenter trials have demonstrated that angiotensin-converting enzyme inhibitors are effective for preventing recurrence of myocardial infarction.

Arteriosclerosis↗
PubMed1996

[Clinical characteristics and therapeutic strategy for acute myocardial infarction in the elderly].

Many randomized studies have revealed that reperfusion therapy is an epochmaking treatment for acute myocardial infarction (AMI). However, it is no clear whether it is equally beneficial in the elderly or not. In this study, we elucidated the clinical characteristics and effectiveness of reperfusion therapy and discussed the optimal treatment for AMI in the elderly. The study population comprised 1,891 consecutive patients with AMI. The reinfarction rates and the rates of Killip class III or IV on admission increased with age. The mortality was significantly higher in the older subgroups. In the patients with first AMI within 24 hours of the onset and who underwent emergency catheterization, those accompanied by hypercholesterolemia or with habitual smoking were significantly fewer in the older group. Although the Q-wave MI rate, the peak CPK level and the reperfusion rate were no different, the low cardiac output condition, multi vessel disease and short-term mortality were significantly greater in the older group. The patients over 80-year-old were subdivided into three groups; those treated conventionally (G-C), those treated with intracoronary thrombolysis (G-T) and those treated with direct PTCA (G-A). The overall mortality did not differ among the three groups. However, in patients hospitalized after 1990, the mortality in G-A was significantly lower than in G-C. The prevalence of bleeding complications between G-A and G-T did not differ. The patients in G-A showed greater improvement of the left ventricular wall motion and lower incidence of postinfarctional angina than other groups. Reperfusion therapy by direct PTCA appears to be the optimal strategy for treatment of elder patients with AMI.

Adult↗
PubMed1996

In vivo gene transfer of insulin gene into neonatal rats by the HVJ-liposome method resulted in sustained transgene expression.

In Many areas of disease such as homozygous familial hypercholesterolemia, no known effective therapy exists. The time is ripe for the introduction of gene therapy for the management of incurable disorders. However, for clinical gene therapy it is necessary to establish an efficient and non toxic gene delivery system. Recently, we have developed a gene delivery system mediated by Sendai virus as a potential means of gene therapy. However, this HVJ-liposome method has some disadvantages: (1) transient transgene expression; and (2) no integration. In gene therapy, it is desirable for transgenes to be expressed for as long as possible. To deal with this issue, we hypothesized that gene transfer into newborn animals would result in sustained expression of transgene. Our results demonstrated that transgene expression in liver was subsequently sustained for at least up to 8 weeks, as detected by reverse transcriptase PCR and radioimmunoassay, while our previous studies documented that transgene expression in adult animals disappeared within 2 weeks. Interestingly, we detected the presence of transgene in the host genomic DNA extracted from the nuclei of hepatic cells assessed by PCR. These findings provide new important information for gene therapy, although the mechanisms of sustained transgene expression are not clear.

Aging↗
PubMed1996

[Application of decoy strategy].

Recently, transfection of cis-element double stranded (ds) oligodeoxynucleotides (ODN) (= decoy) as a new powerful tool in a new class of anti-gene strategy for gene therapy and the study of transcriptional regulation has been reported. Transfection of ds ODN corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-element with subsequent modulation of gene expression. Recent studies provide evidence of on in vivo application of this novel molecular approach as a therapeutic strategy against cardiovascular disease, and tool for the study of gene regulation in vivo.

Base Sequence↗
PubMed1996

Fat-soluble vitamins in cord blood and colostrum in the south of China.

Certain diseases have been associated with micronutrient deficiencies in China, and nutritional assessments have become important means of preventing such diseases. In the present study, fat-soluble vitamins including vitamins A, D, E, K, and beta-carotene in the cord blood and colostrum of Chinese subjects in Guilin, China, were assayed and compared with those of Japanese subjects in Osaka, Japan. These vitamins were analyzed by high-performance liquid chromatography. Vitamin A and E levels in the cord blood and colostrum of the Chinese group showed almost the same values as those of the Japanese group. There was also no significant difference in vitamin D level in cord blood between the two groups, while significantly lower levels of beta-carotene and cryptoxanthin, and a higher level of PIVKA-II (protein induced in vitamin K absence) in cord blood were observed in the Chinese group. These findings pointed to a restricted intake of green-yellow vegetables in the Chinese group and an increased risk of hemorrhagic disease in newborn of that group is suggested.

China↗
PubMed1996

[Bartter syndrome].

The characteristic clinical features of Bartter syndrome consist of hypokalemia, hypochloremic metabolic alkalosis, and normal blood pressure despite hyperreninemia and hyperaldosteronism. Some are constantly present, such as juxtaglomelular hyperplasia, decrease of the pressor response for angiotensin II infusion, impairment of concentrating ability, and elevated prostaglandin E2 and I2, while others such as hypomagnesemia are observed in some cases. The primary cause remains unknown, but the most likely candidate is reduced sodium chloride reabsorption in the thick ascending limb of Henle's loop. Exclusion of pseudo-Bartter syndrome, mainly of surreptitious vomiting and diuretic abuse, is necessary to diagnose the syndrome. The current therapy focuses on multiple agents to reduce massive potassium loss and to inhibit the syntheses of prostaglandin.

Bartter Syndrome↗
PubMed1996

In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid.

One of the tools to test an in vitro hypothesis in vivo is transgenic/gene targeting technology. Transgenic technology provides many advantages such as: (1) the study of specific gene function as systemic and developmental effects; and (2) testing of specific gene function chronically. nevertheless, one disadvantage of this technology is the difficulty in tissue-specific targeting of the transgenic expression. Another useful tool is the in vivo gene transfer approach. Therefore, we tested a potential novel model for the study of transgene expression and knock-out using antisense technology. Here, we have demonstrated that incubation of hemagglutinating virus of Japan (HVJ)-liposome complex containing FITC-labeled oligonucleotides in the amniotic fluid of fetal rats resulted in the nuclear localization of fluorescence in the skin (epidermis and dermis). Similarly, transfection of beta-galactosidase gene resulted in positive staining in several surface layers of the skin. Thus, local gene or antisense oligonucleotide transfer approach into the skin may be useful for studying the role of autocrine/paracrine mediators and treating diseases.

Amniotic Fluid↗
PubMed1996

The clinical efficacy and tolerability of the angiotensin II-receptor antagonist losartan in Japanese patients with hypertension.

The clinical efficacy and tolerability of losartan were studied in clinical trials in Japanese patients with essential hypertension. In a short-term trial, losartan (25 to 100 mg once daily) provided good control of blood pressure for 24 h without affecting the patient's own diurnal blood pressure profile. In a double-blind study, the efficacy and tolerability of losartan (25 to 50 mg once daily) were compared to enalapril (5 to 10 mg) in Japanese patients with mild to moderate essential hypertension. Losartan, 25 to 50 mg given once daily, produced an antihypertensive effect comparable to enalapril, 5 to 10 mg, in these patients. The incidence of adverse reactions in the losartan group was 9.0% (13/144), which was lower than that observed in the enalapril group, 20.3% (29/143). The incidence of cough in the losartan group (0.7%) was lower than that of the enalapril group (13.3%). No discontinuation due to cough was observed in the losartan group: however, seven patients were discontinued from the enalapril group. Losartan exhibited antihypertensive efficacy comparable to enalapril and a tolerability profile superior to enalapril in this study. The efficacy and tolerability of losartan were also investigated in 29 hypertensive patients with renal impairment. When losartan (25 to 100 mg) once daily was used, blood pressure was controlled in 62.1% (18/29) of patients. The rate of cases assessed as "useful" was 58.3% when the pretreatment serum creatinine level was less than 3.0 mg/dL. No cases, however, were assessed as "useful" in patients in which the level was 3.0 mg/dL or higher. In a trial with hypertensive diabetic patients, losartan did not adversely affect glucose tolerance and lipid metabolism. Losartan was associated with a decreased total cholesterol (p < 0.01) and LDL cholesterol (p < 0.01) without significantly changing HDL cholesterol in patients with total serum cholesterol of > 220 mg/dL. In summary, losartan, the first angiotensin II antagonist, is an effective antihypertensive agent with an excellent tolerability profile.

Adult↗
PubMed1996

[Linkage mapping].

Explore the source record for details and available documents.

Chromosome Mapping↗