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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 127 records · Page 7Linked to original sources
PubMed1993

Induction of renal pelvic carcinoma by phenacetin in hydronephrosis-bearing rats of the SD/cShi strain.

Carcinogenicity of phenacetin (PH) to the urinary tract was tested with the use of spontaneously hydronephrosis-bearing rats. In Experiment 1, 55 SD/cShi male rats were fed with 2% PH-containing diet for 85 weeks, and 32 SD/cShi male rats fed basal diet for 85 weeks served as controls. Forty-three of 53 rats fed with PH had renal pelvic carcinoma with lung metastases in three. The mean induction time was 78 weeks. Ureteral carcinoma and urinary bladder carcinoma were observed in 2 and 6 of 53 rats given PH, respectively. No urinary tract carcinoma was found in control animals. In Experiment 2, early lesions of the kidney affected by PH were also evaluated with the use of SD/cShi and Sprague-Dawley (SD) rats. Two groups of animals containing 6 SD/cShi or 6 SD male rats per group were fed 2% PH-containing diet for 8 weeks. Control animals containing 6 SD/cShi rats or 6 SD rats were fed basal diet for 8 weeks. Simple hyperplasia was found in 5 of 6 SD/cShi rats given PH and 2 of 6 SD/cShi control rats. Papillary necrosis was seen in 4 of 6 SD/cShi and 2 of 6 SD rats given PH. SD/cShi rats, especially those treated with PH, showed higher but not significant 5-bromo-2'-deoxyuridine labeling indices in the covering epithelium of the renal pelvis and papillae. In this short term experiment PH and its metabolites, N-hydroxyphenacetin and N-acetyl-p-aminophenol, were measured in urine and plasma by using high performance liquid chromatography. Significantly higher PH and slightly higher metabolites were detected in urine and plasma of SD/cShi rats compared to SD rats. These results indicated that the renal pelvis of SD/cShi rats had more sensitivity to PH carcinogenicity. This paper provides experimental proof of PH carcinogenicity toward the renal pelvis in an animal model.

Animals↗
PubMed1993

Cyclosporine A induces endothelin-1 release from cultured rat vascular smooth muscle cells.

Since vascular smooth muscle cells in culture are capable of secreting endothelin-1 (ET-1), we investigated the effect of cyclosporine A on ET-1 release from rat vascular smooth muscle cells. Cyclosporine A 10 microM significantly (P < 0.05) enhanced the secretion of ET-1 at 2, 8, 24 and 48 h (6.5 +/- 0.5, 11 +/- 0.7, 19 +/- 0.5, 37 +/- 1.6 fmol/10(6) cells, respectively) compared with vehicle (4.7 +/- 0.3, 8.1 +/- 0.6, 15 +/- 0.4, 27 +/- 2.0 fmol/10(6) cells, respectively). The cyclosporine-induced synthesis of ET-1 by vascular smooth muscle cell may participate in the pathogenesis of cyclosporine-induced vasoconstriction and vasculopathy via an autocrine regulatory mechanism.

Animals↗
PubMed1993

[The effect of alacepril on insulin sensitivity in patients with essential hypertension].

The aim of this study was to determine the effect of angiotensin-converting-enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT). Ten patients (5 men and 5 women) with EHT (3 with mild diabetes and 2 with borderline glucose tolerance) participated. We measured insulin sensitivity using the two-hour euglycemic-hyperinsulinemic clamp technique and plasma glucose and insulin responses to a 75 g oral glucose tolerance test (75 g OGTT) before and after 6-8 weeks of treatment with alacepril (dose, 50 mg/day). Glucose infusion rate (GIR) during the last 30 min of the clamp study increased from 5.83 +/- 0.70 to 6.59 +/- 0.65 mg per kilogram of body weight per minute (P < 0.05) after treatment with alacepril. The insulin-sensitivity index, which was calculated by dividing the GIR by the mean insulin concentration during the same period of the clamp, also increased from 5.91 +/- 0.66 to 7.20 +/- 0.90 (P < 0.05) after treatment with alacepril. Plasma glucose responses to a 75 g OGTT were changed from diabetic pattern to borderline pattern in two patients and from borderline pattern to normal pattern in one patient after treatment with alacepril. Body weight did not significantly change throughout the study in any of the patients studied. Our study demonstrated that alacepril significantly improves insulin sensitivity in patients with EHT.

Adult↗
PubMed1993

Mechanisms underlying post-inspiratory depolarization in post-inspiratory neurons of the cat.

The mechanism of the post-inspiratory depolarization in bulbar post-inspiratory neurons was investigated in decerebrate cats with a coaxial multibarrelled microelectrode technique. Iontophoresed tetrodotoxin eliminated a dominant part of the post-inspiratory depolarization and left a small depolarization to occur. This residual potential was increased with depolarization. When depolarization exceeded a potential of average -63 mV, there appeared a large bell-shaped depolarization that was suppressed by iontophoresed cadmium. These results suggest that the post-inspiratory depolarization in this neuron is formed by the cooperation between excitatory synaptic potentials and voltage-dependent Ca2+ currents.

Action Potentials↗
PubMed1993

Variations in membrane potential trajectory of post-inspiratory neurons in the ventrolateral medulla of the cat.

In decerebrate cats, intracellular recordings were made in 124 expiratory neurons displaying either a plateau-phase of depolarization during post-inspiration or a steadily decrementing depolarization throughout expiration. Both groups consisted of vagal motoneurons and non-antidromically activated neurons. Five neurons were antidromically activated by both vagal and spinal cord stimuli. The pattern in membrane potential was changed from one type to another either spontaneously or experimentally. The present results suggest that the variable appearance of the membrane potential trajectory does not represent the different functional category of bulbar post-inspiratory neurons.

Anesthesia↗
PubMed1993

Asymmetrical septal hypertrophy in patients with hypertension: a type of hypertensive left ventricular hypertrophy or hypertrophic cardiomyopathy combined with hypertension?

To determine whether asymmetrical septal hypertrophy (ASH) in patients with essential hypertension (HT) is a type of hypertensive left ventricular (LV) hypertrophy or hypertrophic cardiomyopathy (HCM) combined with HT, we investigated a group of 7 hypertensive patients with ASH compared with 12 HCM patients and 10 healthy controls using radionuclide angiography and right ventricular endomyocardial biopsy. The LV time-volume curve and its first and second derivative curves were constructed from cardiac output and time-activity curves constructed by combined forward and reverse-gating from the R wave. The LV wall thickness and ejection fraction were significantly greater in both the HT and HCM groups than in the control group, whereas there were no differences in these indices between the HT and HCM groups. Rapid filling volume index and rapid filling fraction showed significantly lower values in the HCM group than in the control group (p < 0.005). In contrast to the HCM group, these indices in the HT group did not differ from those in the control group. The time to peak filling rate was prolonged in the control, hypertension, and HCM groups in increasing order. Histopathological study revealed a higher incidence of myocardial cell disarray in the HCM than in the HT group. The above results suggest that ASH in hypertensive patients is a type of hypertensive LV hypertrophy.

Analysis of Variance↗
PubMed1993

Rapid detection and prevalence of cholesteryl ester transfer protein deficiency caused by an intron 14 splicing defect in hyperalphalipoproteinemia.

A deficiency of plasma cholesteryl ester transfer protein (CETP) is one of the genetic causes of increased serum high density lipoprotein (HDL)-cholesterol levels (hyperalphalipoproteinemia). A splicing defect (G-->A mutation) at the +1 position of intron 14 of the human CETP gene is a common mutation in the Japanese CETP deficiency. A rapid screening method for the splicing defect by means of primer-specified restriction map modification was described. The frequency of the mutation in hyperalphalipoproteinemia was determined, and its frequency in the general population was estimated. During polymerase chain reaction (PCR) with a modified primer, a novel NdeI restriction endonuclease site was created from the mutated allele in the PCR products, which could be visualized after electrophoresis of the digested products. As a result, 21 of 121 unrelated hyperalphalipoproteinemic subjects with HDL-cholesterol > or = 60 mg/dl (1.55 mmol/l), were found to have the G-->A mutation. Of the 21 individuals, 8 were found to be homozygous for the mutation. Allele frequency of the mutation was 1.5% (1/68), 2.8% (2/72), 7.1% (4/56), and 47.8% (22/46) in the groups with HDL-cholesterol levels of 60-79 mg/dl, 80-99 mg/dl, 100-119 mg/dl, and > or = 120 mg/dl, respectively. Based on the percentage of the area under the computed normal distribution curve of serum HDL-cholesterol, the frequency of the mutated allele in the general population was estimated to be 0.81% from the present results. This rapid detection method facilitates large-scale screening of CETP deficiency caused by the splicing defect. The mutation was frequent in Japanese subjects with hyperalphalipoproteinemia, especially in the group with HDL-cholesterol > or = 120 mg/dl.

Adult↗
PubMed1993

Assessment of autonomic nervous activity by heart rate spectral analysis in patients with variant angina.

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Adult↗
PubMed1993

Formation of 18-deoxy-19-noraldosterone by a human aldosterone-producing adenoma.

The recently synthesized 18-deoxy-19-noraldosterone is a potent aldosterone antagonist. In the present study we demonstrate the in vitro formation of 18-deoxy-19-noraldosterone from 19-noraldosterone in a human aldosterone-producing adenoma and normal adrenal tissue. The metabolite was isopolar, cochromatographed with the authentic standard on high-performance liquid chromatography, and the identity was further analyzed by mass spectrometry. The possible role of 18-deoxy-19-noraldosterone in primary aldosteronism is also discussed.

Adenoma↗
PubMed1993

Increased concentration of endothelin messenger RNA in the mesenteric arteries of cyclosporine-induced hypertensive rats.

The aim of this study was to investigate the expression of endothelin-1 (ET-1) in the mesenteric arteries of cyclosporine-induced hypertensive rats. The concentration of plasma ET-1 and of mesenteric artery ET-1 messenger RNA was measured in cyclosporine-induced hypertensive and control rats. The concentration of ET-1 messenger RNA in the mesenteric arteries of cyclosporine-treated rats (25 mg/kg/day for 6 weeks) was significantly greater than in control rats (P < .05). We propose that cyclosporine-induced hypertension may be due to an increased synthesis of ET-1 in the resistant vessels.

Animals↗
PubMed1993

Stimulation of endothelin mRNA and secretion in human endothelial cells by FK 506.

FK 506 is a powerful new immunosuppressant that is more effective in preventing and treating allograft rejection than cyclosporine (CyA). This study was undertaken to examine the effect of FK 506 on stimulation of endothelin-1 (ET-1) mRNA and secretion of ET-1 in human endothelial cells (EC) compared with the effects of CyA. The dose of 0.1 microM of CyA used in clinical practice induced expression of ET-1 mRNA and increased secretion of ET-1 in EC. The same dose of FK 506 had the same effect. A clinical dose of 0.01 microM of FK 506 did not induce expression of ET-1 mRNA and did not increase the secretion of ET-1 in EC. These findings suggest that the lower incidence of complications seen with FK 506 is due in part to its use at a lower clinical dose compared with that of CyA.

Cells, Cultured↗
PubMed1993

11 beta-Hydroxysteroid dehydrogenase activity in mesenteric arteries of spontaneously hypertensive rats.

1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%, respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively; P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Increased left atrial chamber stiffness in hypertrophic cardiomyopathy.

OBJECTIVE: To investigate left atrial chamber stiffness and its influence on left atrial and left ventricular functions in hypertrophic cardiomyopathy. DESIGN: Prospective study. SETTING: Department of internal medicine in a university teaching hospital. PATIENTS: Five control subjects, six patients with essential hypertension, and 11 patients with hypertrophic cardiomyopathy. INTERVENTIONS: Measurement of left atrial pressure by a tip micromanometer and of real-time left atrial volume from left atrial cineangiograms. MAIN OUTCOME MEASURE: Left atrial stiffness constant determined by fitting the ascending limb of the v loop of the left atrial pressure-volume relation to an exponential curve. RESULTS: The mean (SD) left atrial chamber stiffness constant was significantly larger in patients with hypertrophic cardiomyopathy than in controls (0.063 (0.018) v 0.041 (0.006), p < 0.05) and was correlated with left ventricular wall thickness (r = 0.560, p < 0.01). Left atrial reservoir volume (left atrial emptying volume before atrial contraction) was significantly smaller in patients with hypertrophic cardiomyopathy than in the controls (7.3 (2.1) v 12.5 (4.4) ml/m2, p < 0.01) and was inversely correlated with the left atrial chamber stiffness constant (r = -0.598, p < 0.01). The cardiac index was inversely correlated with the left atrial chamber stiffness constant (r = -0.542, p < 0.01). CONCLUSIONS: Left atrial chamber stiffness was increased in patients with hypertrophic cardiomyopathy and this affected the left atrial reservoir function. This may in turn have affected cardiac output.

Atrial Function, Left↗
PubMed1993

Collagen remodelling in myocardia of patients with diabetes.

AIMS: To investigate collagen remodelling in the interstitium of the heart in patients with diabetes. METHODS: Immunohistochemical study of the biopsied myocardium using type specific anticollagen antibodies (I, III, IV, V, VI) was performed in 12 patients with non-insulin dependent diabetes mellitus and six non-diabetic patients. There was no history of hypertension or coronary artery stenosis in any of the patients. RESULTS: Noticeable accumulations of collagen types I, III, and VI in the myocardial interstitium were recognised in both groups, but little accumulation of types IV or V was found. Types I and III mainly stained in the perimysium and perivascular region, while type VI predominantly stained in the endomysium. There was no disease specific accumulation of collagen in diabetes mellitus. The percentage of total interstitial fibrosis in the myocardium was significantly higher in the diabetic group than in the control group (p < 0.05). Although the percentages of collagen types I and VI did not differ between the two groups, the percentage type of III was significantly higher in the diabetic group than in the controls (p < 0.01). CONCLUSIONS: Collagen remodelling mainly as a result of an increase in collagen type III in the perimysium and perivascular region, occurs in the hearts of patients with diabetes.

Adult↗
PubMed1993

Abdominal aortic aneurysms in familial hypercholesterolemia--case reports.

Familial hypercholesterolemia (FH) is a genetic disease characterized by high serum cholesterol levels and premature coronary atherosclerosis. Hypercholesterolemia is one of the factors promoting the arteriosclerotic process and is a major cause of aortic aneurysm. Few data are available, however, about abdominal aortic aneurysms (AAAs) in patients with FH. In this study, the clinical and angiographic characteristics of AAAs found in patients with FH were investigated. Thirty-one cases (23 men, 8 women, aged fifty +/- fourteen years) were examined by coronary angiography, thoracic and abdominal aortography, and clinical data. Abdominal aortography detected abdominal aneurysms in 8 cases (26%), all of whom were men, including 4 cases (50%) that were complicated by diabetes mellitus. The abdominal aneurysm patients manifested severe coronary atherosclerosis, severe abdominal aortic irregularity, and higher blood pressure than the nonaneurysm FH patients. These findings suggest that AAAs are an important and prevalent feature in FH, especially in men with diabetes mellitus and high blood pressure.

Adult↗
PubMed1993

Increased plasma endothelin levels in Kawasaki disease: a possible marker for Kawasaki disease.

Plasma immunoreactive endothelin (iET) levels were investigated in patients with Kawasaki disease (KD). The iET level was 2.49 +/- 0.13 pg/mL in KD patients and 1.32 +/- 0.06 in age-matched control subjects, showing a significant increase with KD. The iET level was not increased in patients with febrile inflammatory diseases of bacterial origin without KD (non-KD group). Parameters indicating an inflammatory reaction, such as C-reactive protein, platelet count, white blood cell count, and interleukin-6 level, were increased in the KD patients. However, they were similarly increased in the patients with febrile diseases of bacterial origin and showed no significant differences between the two groups. This study is the first to report that plasma iET levels are elevated in a disease mainly involving vasculitis. These results suggest that blood iET levels are increased in KD patients as a result of the associated vascular endothelial damage and that iET can be a useful marker for the diagnosis of KD.

Biomarkers↗
PubMed1993

Preload dependency of left atrial pump function in hypertrophic cardiomyopathy.

In our previous study, we reported that the left atrial contribution to left ventricular filling was decreased to a greater extent in patients with hypertrophic cardiomyopathy than in those with myocardial infarction or normal subjects during lower body negative pressure (LBNP)-induced preload reduction. To clarify the factors responsible for this difference in response, we examined changes in left atrial hemodynamic and M-mode echocardiographic indices during LBNP in patients with hypertrophic cardiomyopathy and myocardial infarction. The same degree of decrease in left atrial preload and afterload was found in both groups. Moreover, we detected no change in the left atrial fractional shortening during left atrial systole (%LAFS) in patients with hypertrophic cardiomyopathy, in contrast to a significant increase found in patients with myocardial infarction. These results showed that the greater decrease in the left atrial contribution in hypertrophic cardiomyopathy during LBNP could not result from differences in changes in left atrial preload or afterload, suggesting that it may be closely related to limitations in the compensatory augmentation of left atrial contractility.

Atrial Function, Left↗