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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 109 records · Page 6Linked to original sources
PubMed1994

Tissue-specific expression of isoaspartyl protein carboxyl methyltransferase gene in rat brain and testis.

Isoaspartyl protein carboxyl methyltransferase (PIMT) is widely distributed in mammalian tissues. Using a polymerase chain reaction-generated 124-bp DNA fragment from brain cDNA as a probe, four different sizes (approximately 4.0, 2.5, 1.7, and 1.1 kb) of transcripts were detected with northern blot analysis. They were expressed predominantly in rat brain and testis. The major transcripts were 2.5 and 1.7 kb in the brain and 2.5 and 1.1 kb in the testis. One of the major transcripts specific to the testis (1.1 kb) was determined to study the structural difference of major transcripts in the two tissues. This testicular cDNA had neither the 5' (94 nucleotides) nor the 3' (594 nucleotides) end of previously reported brain cDNA corresponding to 1.7 kb. The mRNA levels and enzyme activities of different regions and developmental changes were examined in the brain. The mRNA levels and enzyme activities were concomitantly high in cerebral cortex and hippocampus. Although they increased rapidly approximately 30 days after birth in the testis and decreased in aged rats, they increased gradually after birth and remained high during the aging of the brain. Both structural and developmental studies show that the expression of the PIMT gene in brain and testis is regulated in a tissue-specific manner.

Aging↗
PubMed1994

Frequency of renin gene restriction fragment length polymorphism in hypertensives with a genetic predisposition to hypertension.

The genetic basis of essential hypertension is still uncertain. Because renin is thought to be a candidate gene for essential hypertension, a prospective study was conducted to compare the frequency of renin gene HindIII restriction fragment length polymorphism (RFLP) in normotensive and hypertensive subjects without (HTG-) and with a genetic predisposition to essential hypertension (HTG+). The frequency of the 9.0-kb fragment was significantly (p < 0.05) higher in the HTG+ group than in the normotensive and HTG- groups. An association between renin RFLP and hypertension in man was shown for the first time. It is suggested that a gene for blood pressure regulation has been localized to a part of the genome close to, or identical to, the renin locus.

Adult↗
PubMed1994

Gene expression of 11 beta-hydroxysteroid dehydrogenase in the mesenteric arteries of genetically hypertensive rats.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and plays an important role in controlling blood pressure. We determined 11 beta-HSD activity and mRNA levels in the mesenteric arteries of genetically hypertensive rats, the Dahl salt-sensitive hypertensive rat, and compared them with Dahl salt-resistant and Sprague-Dawley rats. 11 beta-HSD activity was expressed as the percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone. 11 beta-HSD activity was significantly decreased in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats (11.4 +/- 1.4%) compared with Dahl salt-resistant rats (17.4 +/- 1.4%) or Sprague-Dawley rats (18.0 +/- 1.5%) of the same age (P < .05). There were no significant differences in 11 beta-HSD activity between 4-week-old Dahl salt-sensitive hypertensive and Dahl salt-resistant rats of the same age (15.3 +/- 1.3% and 15.1 +/- 1.9%, respectively). The concentration of 11 beta-HSD mRNA in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats was significantly lower than in Dahl salt-resistant or Sprague-Dawley rats of the same age (P < .05). There were no significant differences in the concentration of 11 beta-HSD mRNA in the mesenteric arteries of 4-week-old Dahl salt-sensitive hypertensive rats, Dahl salt-resistant rats, and Sprague-Dawley rats. These results indicate that 11 beta-HSD in the vascular wall may play a role in the pathogenesis of hypertension in this rat model.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol.

Genetic determinants of HDL cholesterol (HDL-C) levels in the general population are poorly understood. We previously described plasma cholesteryl ester transfer protein (CETP) deficiency due to an intron 14 G(+1)-to-A mutation(Int14 A) in several families with very high HDL-C levels in Japan. Subjects with HDL-C > or = 100 mg/dl (n = 130) were screened by PCR single strand conformational polymorphism analysis of the CETP gene. Two other mutations were identified by DNA sequencing or primer-mediated restriction map modification of PCR products: a novel intron 14 splice donor site mutation caused by a T insertion at position +3 from the exon14/intron14 boundary (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G). The Int14 T mutation was only found in one family. However, the D442G and Int14 A mutations were highly prevalent in subjects with HDL-C > or = 60 mg/dl, with combined allele frequencies of 9%, 12%, 21% and 43% for HDL-C 60-79, 80-99, 100-119, and > or = 120 mg/dl, respectively. Furthermore, prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men (n = 236), with heterozygote frequencies of 7% and 2%, respectively. These two mutations accounted for about 10% of the total variance of HDL-C in this population. The phenotype in a genetic compound heterozygote (Int14 T and Int14 A) was similar to that of Int14 A homozygotes (no detectable CETP and markedly increased HDL-C), indicating that the Int14 T produces a null allele. In four D442G homozygotes, mean HDL-C levels (86 +/- 26 mg/dl) were lower than in Int14 A homozygotes (158 +/- 35 mg/dl), reflecting residual CETP activity in plasma. In 47 D442G heterozygotes, mean HDL-C levels were 91 +/- 23 mg/dl, similar to the level in D442G homozygotes, and significantly greater than mean HDL-C levels in Int14 A heterozygotes (69 +/- 15 mg/dl). Thus, the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes, suggesting dominant expression of a partially defective allele. CETP deficiency, reflecting two prevalent mutations (D442G and Int14 A), is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL-C in the general population.

Adult↗
PubMed1994

Synthesis of corticosterone in the vascular wall.

Extra-adrenal steroid 21-hydroxylation and 11 beta-hydroxylation occur in a variety of human tissues. This study was undertaken to determine whether the rat mesenteric artery produces corticosterone and to demonstrate the CYP11B1 mRNA in the vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 h. The perfusate was collected and chromatographed in a reverse-phase HPLC system. The fraction corresponding to synthetic corticosterone was collected and analyzed by mass spectrometry. The concentration of corticosterone in the perfusate from the adrenalectomized rats was measured using radioimmunoassay after separation with the HPLC system. The mass spectra of synthetic corticosterone was identical with corticosterone isolated from the perfusate of the rat mesenteric arteries. The radioactive peak of corticosterone was detected in the perfusate after perfusing the mesenteric artery with Krebs-Ringer solution containing [14C]-pregnenolone. The expression of CYP11B1, 11B2, and 11A mRNA was detected in the mesenteric artery using a RT-PCR. The production of corticosterone in the vascular wall was increased in the adrenalectomized rats compared with that of the controls. This study shows that the rat mesenteric artery produces corticosterone, and the corticosterone synthase is existed in the vasculature.

Animals↗
PubMed1994

Type IV collagen in hypertrophic cardiomyopathy.

Basement membrane of myocytes from patients with hypertrophic cardiomyopathy who died suddenly, seemed to be discontinuous by immunohistochemical methods. With the use of the sandwich immunoassay technique, we determined the frequency of type IV collagen and its influence on functional abnormality in 31 patients with hypertrophic cardiomyopathy and controls. Hypertrophic cardiomyopathy exhibited significantly increased serum type IV collagen compared with controls. A significant correlation was observed between serum type IV collagen and fractional shortening (r = -0.42 p < 0.05), and end-diastolic volume (r = 0.40 p < 0.05), DT (r = -0.50 p < 0.05). These data suggest that serum type IV collagen enhances clusters of cell-surface type IV collagen, including an alteration of the cytoskeleton, which may account for functional abnormalities in hypertrophic cardiomyopathy. Considering the fact that microscopic examination is unable to resolve the structure of the myocardial basement membrane, measurement of serum type IV collagen is thought to be useful in the diagnosis of myocardial basement membrane injury and the progression of hypertrophic cardiomyopathy.

Aged↗
PubMed1994

Detection of anomalous origin of the left coronary artery by transesophageal echocardiography and magnetic resonance imaging.

Anomalous origin of the left coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death, especially during exercise. We present a patient in whom the anomalous origin of the left coronary artery from the posterior aortic (non-coronary) sinus produced ischemic chest pain. The anomaly was identified by transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) as well as by coronary angiography. TEE and MRI are useful for detecting anomalies of the coronary artery both clearly and noninvasively and for evaluating the mechanism of ischemia.

Chest Pain↗
PubMed1994

Angiotensin II up-regulates the expression of type A endothelin receptor in human vascular smooth muscle cells.

Using vascular smooth muscle cells, the effect of angiotensin II on endothelin receptor regulation was examined. Vascular smooth muscle cells cultivated from human pulmonary artery exhibited high affinity receptors for endothelin-1. When the cells were exposed to angiotensin II, the number of receptors was found to be increased without any change in their affinity. The ligand binding was effectively displaced by BQ123, a selective antagonist for type A endothelin receptor, but not by S6c, a selective ligand for type B receptor, in both control and angiotensin II-treated cells. The level of mRNA coding for the type A receptor was elevated in the latter. These results indicate that angiotensin II up-regulates type A endothelin receptors in human vascular smooth muscle cells through an increase in their corresponding mRNA, suggesting a link between the renin-angiotensin and the endothelin systems.

Angiotensin II↗
PubMed1994

[Evaluation of the effective use of the "health notebook"].

Since 1983, with the institution of the "Health Service Law for the Aged", the "health notebook" has been issued to people aged 40 years and over in order to aid in management of their health. Few people actually fill their health data in notebook by themselves. In order to develop effective use of the health notebook by residents and health professionals, the uses of the health notebooks by residents aged 40 years and over, public health nurses, and physicians were investigated. Three hundred and fifty four residents aged 40 and over, 41 public health nurses, and 18 physicians were studied in 1990, in Yamagata city. A majority of residents took their health notebooks with them to health consultations, and public health nurses used the notebooks to provide advice to them. Public health nurses effectively issued the health notebooks to residents using occasions where residents gathered. Some physicians reported that health notebooks were useful for motivating the people to maintain their health, while others preferred using a health card media. When comparing the health notebooks to the maternity passbooks, health notebooks need to be more easily utilized by users for recording information, and their value should be effectively explained to them. Furthermore, in order to promote self-care behaviors, greater use of health notebooks by all health professionals in indicated.

Adult↗
PubMed1994

Effect of glycyrrhizin on cortisol metabolism in humans.

Urinary cortisol and cortisone excretion were measured after glycyrrhizin administration (225 mg/day, per os) for seven consecutive days in five healthy volunteers. The ratio of plasma cortisol and cortisone during hydrocortisone (0.6 mg/kg i.v.) infusion was also examined. After glycyrrhizin administration, the urinary cortisone to cortisol ratio was significantly decreased, but the ratio of plasma cortisol to cortisone was not significantly altered. Glycyrrhizin inhibited 11 beta-hydroxysteroid dehydrogenase in the kidney and so inhibited the conversion of cortisol to cortisone. The increased cortisol in the kidney could be the cause of the apparent mineralocorticoid excess syndrome induced by glycyrrhizin.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

[Analysis of synthetic corticoids by high performance liquid chromatography].

High performance liquid chromatography (HPLC) has been developed to analyze the synthetic corticoids (SCS) in human biological fluids. First, steroid moiety was extracted with a chemical solvent and/or an octadecylsilan (or diatomaceous earth) column, then the extracts were separated on the ordinary or reversed phase HPLC column with ultraviolet detection, at 254 nm. The total automatic system for the HPLC method has improved the accuracy and precision of SCS measurement for clinical use. Protein binding and free steroids, assayed by HPLC in plasma and saliva of the subjects treated with SCS may relate to steroid sensitivity. On the other hand, the simultaneous analysis of the metabolites of SCS in urine and other fluids reveals the clinical activity of the given SCS. HPLC analysis can therefore be utilized for evaluation of SCS pharmacodynamics.

Chromatography, High Pressure Liquid↗
PubMed1994

Assessment of postischemic reperfusion and diamox activation test in stroke using 99mTc-ECD SPECT.

To evaluate the cerebral distribution of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated postischemic reperfusion and acetazolamide (Diamox) activation test in stroke patients. The postischemic reperfusion was studied in 10 patients who showed a postischemic hyperperfusion area on other single photon emission computed tomography (SPECT) studies using N-isopropyl-rho-[123I]iodoamphetamine ([123I]IMP), 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO), or 133Xe. 99mTc-ECD SPECT demonstrated a hyperactive area in one case, an isoactive area in four, and a hypoactive area in five. Correlations with CT findings revealed hyperactive areas without any abnormality, isoactive areas with perifocal rim, perifocal edema, or diffuse cerebral edema, and hypoactive areas with an infarct core. The Diamox activation test was studied in eight other patients with atherothrombotic stroke, and a limitation in vasodilative capacity was classified into three grades: Gr. 0 (none to minimal), Gr. I (mild), and Gr. II (moderate). [123I]IMP SPECT showed Gr. II and limitation in all eight cases. However, 99mTc-ECD showed Gr. II in three cases and Gr. I in five, and 99mTc-HMPAO revealed Gr. II in two cases, Gr. I in three, and Gr. 0 in three. We suggest that a lack of retention of 99mTc-ECD in a postischemic reperfusion area indicates the severity of the initial brain damage. Although the limitation in vasodilative capacity under Diamox-activated conditions was underestimated using 99mTc-labeled CBF tracers as compared with [123I]IMP, a retention of 99mTc-ECD in the unaffected area with an increased CBF under Diamox activation could be relatively superior to 99mTc-HMPAO.

Acetazolamide↗
PubMed1993

[Production of mineralocorticoid and enzyme expression for steroidogenesis in blood vessels as components of the vascular auto-/paracrine system].

With the recent advance in immunohistochemical and molecular-genetic techniques, all of the components of the renin-angiotensin system (RAS) have been shown to exist in the vascular tissue of various animal species as well as in humans. The author's group previously reported that angiotensin II (AII) was generated in the mesenteric arteries of several experimental rat models. Vascular AII generation appears to be regulated independently of circulating renin levels, as suggested by the expression of tissue-specific angiotensinogen mRNA. In the light of recent reports that aldosterone may be synthesized in the cultured endothelial cells from bovine aorta, and that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) plays a key role in determining the specificity in mineralocorticoid activity in various mineralocorticoid-responsive tissues, the author wishes to review the studies carried out by colleagues on the production of aldosterone with its precursor steroids and enzyme expression for aldosterone synthesis in the blood vessels as the components of the vascular auto-/paracrine system. The first part of the present paper is summarized as follows: 1) With Northern blotting and RT-PCR of the RNA which was prepared from rat arterial tissue or cultured human arterial smooth muscle cells (SMC), the expression of mineralo- and glucocorticoid receptors was confirmed. 2) The vascular production of aldosterone and corticosterone from the rat mesenteric artery was demonstrated in analyzing the arterial perfusates using a HPLC and GC/MS. Moreover, in this ex vivo experiment, the production of aldosterone in the vasculature was found to be partially controlled by angiotensin II generated locally. 3) It was clearly demonstrated using an RT-PCR method for the first time that aldosterone synthase, cytochrome P450aldo (c 18 or c mo); CYP 11B2 messenger RNA is expressed in the cultured endothelial cells (EC) from human pulmonary artery. From these data, the author would like to propose the concept of a vascular renin-angiotensin-aldosterone system under which paracrinaly produced mineralocorticoid in the vascular EC may easily reach the vascular SMC and in turn act to increase the vascular tone through binding to the receptor there. The second part can be summarized as follows: 1) The expression of 11 beta-HSD in the vasculature was confirmed by bioassay using ex vivo experiment of the isolated rat mesenteric artery perfusion system, immunocytochemical staining methods, in situ hybridization and also by Northern blot analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Left ventricular functional reserve in patients with syndrome X: evaluation by continuous ventricular function monitoring.

OBJECTIVES: The objective of this study was to evaluate cardiac functional reserve in patients with syndrome X. BACKGROUND: Syndrome X is characterized by stress-induced anginal pain and ST segment depression, normal findings on coronary angiography and normal left ventricular function at rest. Reduced coronary vasodilative reserve and abnormal myocardial lactate metabolism have been described in such patients. METHODS: To assess left ventricular functional reserve in patients with syndrome X, continuous radionuclide monitoring of left ventricular end-diastolic volume, end-systolic volume and ejection fraction was performed in 12 patients and 13 normal control subjects during supine bicycle ergometer exercise. RESULTS: In control subjects, end-diastolic volume increased at peak exercise from 100% to 106.5% (p < 0.01), end-systolic volume decreased from 39.1% to 22.6% (p < 0.01) and ejection fraction increased from 60.9% to 78.6% (p < 0.01). In patients with syndrome X, end-diastolic volume increased at peak exercise from 100% to 106% (p < 0.01), and end-systolic volume decreased at ST segment depression < or = 0.5 mm (the ST point) from 37% to 28.8% (p < 0.01) but increased at peak exercise to 44.7% (p < 0.01 vs. the ST point). Thus, ejection fraction increased at the ST point from 63% to 72.7% (p < 0.01) but decreased at peak exercise to 57.7% (p < 0.01 vs. the ST point and control subjects) in proportion to the degree of ST segment depression. In nine patients (75%), ejection fraction at peak exercise was lower than baseline values. All patients and control subjects showed a rapid ejection fraction increase just after exercise during the recovery period. The degree of ejection fraction "overshoot" in patients was similar to that in control subjects, but the interval from the end of exercise to the overshoot in patients was significantly longer than that in control subjects (118 vs. 65 s, p < 0.01). CONCLUSIONS: In patients with syndrome X subjected to exercise stress, left ventricular function remained normal before the onset of ST segment depression. Once ST segment depression appeared, left ventricular function deteriorated in proportion to the degree of depression, and reduced left ventricular function persisted into the recovery period. Continuous ventricular function monitoring is thus a useful predictor of reduced left ventricular functional reserve in patients with syndrome X.

Adult↗
PubMed1993

Microiontophoresis of baclofen on membrane potential and input resistance in bulbar respiratory neurons in the cat.

Iontophoresis of baclofen produced hyperpolarization and a decrease in input resistance in 32 neurons and no effect in 24 neurons of the ventral respiratory group in cats. Iontophoresed phaclofen antagonized the effect of baclofen, but had negligible effects on periodic fluctuations in membrane potential and spike activity in these neurons. The hyperpolarizing effect of baclofen persisted after iontophoresis of tetrodotoxin, suggesting that baclofen acted directly at the postsynaptic gamma-aminobutyric acid (GABA)B receptors.

Action Potentials↗