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Biomedical subjects

T Natsume

Publications and source records attributed to T Natsume.

At least 55 records · Page 3Linked to original sources
PubMed1993

Porous collagen sponge for esophageal replacement.

A new artificial esophagus with a bilayered structure made of porous collagen sponge and silicone was studied. The concept of this study was not to replace an esophageal defect permanently with prosthesis but to promote tissue regeneration by collagen. Five centimeters of cervical esophagus were replaced by this artificial esophagus in 19 adult mongrel dogs. Two weeks after implantation, the collagen sponge was replaced by autologous tissue and regeneration of the "neoesophagus" was observed in all animals. The inner surface of the neoesophagus was covered with mature mucosal epithelium similar to the intact esophagus 4-5 weeks after implantation. The replacement site was not complicated by infection, anastomotic leakage, or exuberant granulation tissue development on the luminal surface. In a long-term survival study, animals showed moderate-grade stenosis but could take normal feed orally and with no clinical problems observed.

Animals↗
PubMed1993

Therapeutic advances in the treatment of left ventricular hypertrophy.

As a consequence of persistently raised blood pressure, left ventricular hypertrophy (LVH) develops as a compensatory mechanism for wall stress induced by the increase in afterload. Recent advances in the fields of molecular biology and genetics are now clarifying the mechanisms involved in the development of LVH. It has been reported that messenger RNA of oncogenes, such as c-fos and c-myc, increases by stretching; these oncogenes contribute to the progression of LVH, the messenger RNA expression of myosin and contractile protein synthesis in the cardiomyocytes. Vasoactive hormones and vascular contracting factors are also reported to have a progressive effect on LVH. In contrast, some antihypertensive agents have been shown to have pharmacological effects on regression of LVH in animals and man. The mechanisms responsible for LVH progression have been extensively studied. In contrast, the mechanisms of LVH regression have not been defined and require elucidation. This paper outlines the basic recognition of the mechanisms of LVH progression and discusses the varied pharmacological actions of calcium antagonists and angiotensin converting enzyme inhibitors on the regression of LVH in man and rats. Although the role of antihypertensive therapy in regression of LVH remains controversial, the calcium antagonist nicardipine appears to have an important role to play in the treatment of LVH in hypertension and in congestive heart failure.

Animals↗
PubMed1993

Alterations in cytosolic calcium-binding proteins that increase felodipine fluorescence in spontaneously hypertensive rats.

OBJECTIVE: To clarify the role of calcium-binding proteins (CaBP) in hypertension. DESIGN: CaBP from several organs of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were purified and their characteristics compared between the two strains. The CaBP were purified by applying the soluble cytosolic fractions from mesenteric vessels, heart, kidney and brain of 4- and 10-week-old SHR and WKY rats to a phenyl-Sepharose column. Felodipine binding to the purified CaBP was then measured. RESULTS: The fluorescence intensity of felodipine increased in a calcium-dependent manner when it bound to CaBP. The pK 0.5 Ca2+ values derived from the calcium ion-felodipine fluorescence curves for each CaBP preparation from organs of the two strains were similar, indicating that the calcium sensitivities of the CaBP to the felodipine binding process are similar in SHR and WKY rats. In 10-week-old SHR the mean levels of felodipine-bound CaBP in heart, brain and kidney were significantly altered compared with those in WKY rats. No such alterations were observed in heart, kidney and brain from 4-week-old SHR and WKY rats. Conversely, the mean levels of felodipine-bound CaBP in mesenteric vessels from 4- and 10-week-old SHR were reduced significantly compared with those of age-matched WKY rats. CONCLUSIONS: These results suggest that the levels of cytosolic felodipine-bound CaBP from heart, kidney and brain are altered in response to elevated blood pressure, and that reduced levels of felodipine-bound CaBP in the mesenteric vessels of SHR might be a primary characteristic of this rat strain.

Animals↗
PubMed1993

Becker muscular dystrophy with early manifestation of left heart failure.

We encountered a case of dystrophin-verified Becker muscular dystrophy which exhibited left heart failure as an initial symptom but no subjective muscle weakness. Severe cardiac involvement has been thought to rarely occur in the early stage of this disease, however accurate diagnosis was limited until the dystrophin diagnosis became available. This case suggests that some cases of dilated cardiomyopathy might be Becker muscular dystrophy, and that dystrophin tests should be added to the conventional investigation of patients with dilated cardiomyopathy.

Adolescent↗
PubMed1993

[ST-T changes associated with severe hypoxia in a case of obstructive sleep apnea syndrome].

A 59-year-old man with obesity was admitted with nocturnal dyspnea and nocturnal precordial oppression. Catheter data disclosed no cardiac failure. Polysomnography was performed for a total of 3 nights. The diagnosis of obstructive sleep apnea syndrome was made because apnea index was 50 times/hour in average, the max apnea time was about 80 seconds and disappearance of airflow during decrease of endoesophageal pressure was observed. At the max apnea time, ST-T change in leads V2-5 was observed with severe desaturation (arterial oxygen saturation: 49%). It was considered that myocardial hypoxia following sleep apnea might be the cause of nocturnal precordial oppression.

Electrocardiography↗
PubMed1992

Enhanced spontaneous calcium efflux and decrease of calcium-dependent calcium release from the isolated perfused heart of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to clarify the further details of calcium handling in hypertension. DESIGN: By preserving the physiological environment of cell membrane, whole hearts were used for comparison of calcium flux between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. METHODS: Hearts from SHR and WKY rats were perfused with Krebs-Henseleit solution under constant flow and the effluent collected. RESULTS: After labelling of the heart with 45Ca2+ (100 mumol/l), 45Ca2+ binding was found to be saturated, and washing with calcium-free perfusion solution showed two exponential curves for calcium dissociation, indicating a fast (alpha-) and slow (beta-) phase. The half-lives of the beta-phase for both 4- and 8-week-old SHR were significantly shorter than those for age-matched WKY. Also in this phase, infusion of non-radioactive Ca2+ caused a transient dose-dependent release of 45Ca2+. A significant reduction in the amount of 45Ca2+ release induced by 2 mmol/l Ca2+ was observed in both 4- and 8-week-old SHR compared with age-matched WKY rats. Infusion of lanthanum, caffeine, ionomycin (calcium ionophore) and treatment of the hearts with ethyleneglycol-bis-(beta-aminoethylether)-N,N,N,',N'-tetraac etic acid did not alter 45Ca2+ release by non-radioactive Ca2+. From these observations, 45Ca2+ is presumably released from the intracellular calcium pool, and not from extracellular binding sites or sarcoplasmic reticulum. CONCLUSIONS: These findings suggest that an abnormal calcium-handling defect (enhanced calcium efflux and reduction of membrane-bound Ca2+) exists under physiological conditions before and after the onset of hypertension, and that this may be a primary characteristic of SHR.

Aging↗
PubMed1991

Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response.

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.

Animals↗
PubMed1991

Biodegradation and antitumour effect of adriamycin-containing poly(L-lactic acid) microspheres.

Adriamycin-containing poly (L-lactic acid) microspheres were prepared to develop a slow-releasing and long-acting adriamycin delivery system. An almost constant release of adriamycin from the adriamycin-containing poly(L-lactic acid) was achieved in Tris buffer and adriamycin disappeared within 20 d. Adriamycin was not detected in serum for up to 14 d, when the suspension of the adriamycin-containing poly(L-lactic acid) microspheres was injected into lung parenchyma, the femoral muscles of rabbits or the peritoneal cavity of mice. However, adriamycin remained in the rabbit muscles for up to 10 d under formation of scar tissue. When free adriamycin was added to P815 tumour cells in culture, the cell survival rate decreased with the exposure time. The treatment with the adriamycin-containing poly(L-lactic acid) microspheres showed a higher survival rate for mice bearing P815 tumour cells than with free adriamycin. In addition, the systemic side effects were insignificant when the adriamycin-containing poly(L-lactic acid) microspheres were given to mice instead of free adriamycin.

Animals↗
PubMed1991

Reduced calcium sensitivity of dihydropyridine binding to calcium channels in spontaneously hypertensive rats.

To explore the role of calcium channels in hypertension, dihydropyridine ([3H]PN200-110) binding to heart, brain, and skeletal muscle microsomes of 4-, 8- and 15-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was measured. At a constant Ca2+ ion concentration (pCa 3.0), maximal binding (Bmax) of dihydropyridine binding to heart and brain microsomes was significantly enhanced in 8- and 15-week-old SHR compared with WKY rats (p less than 0.01), whereas this phenomenon was not observed in 4-week-old SHR and WKY rats. Bmax and dissociation constant (Kd) values for skeletal muscle microsomes from SHR showed no difference compared with WKY rats irrespective of age. Dihydropyridine binding to heart microsomes, brain microsomes, and solubilized skeletal muscle microsomes exhibited strong calcium dependence. The Ca2(+)-dependent dihydropyridine binding curves for heart showed a Hill slope, and pK 0.5 values for 15-week-old SHR and WKY rats were 0.70 +/- 0.12 and 4.66 +/- 0.12 versus 0.72 +/- 0.12 and 5.66 +/- 0.08 (n = 4, mean +/- SD), respectively, indicating that 15-week-old SHR require 10-fold higher calcium concentration than WKY rats to promote dihydropyridine binding. The pK 0.5 values of calcium for brain and solubilized skeletal muscle calcium channels in 15-week-old SHR were also significantly lower than in WKY rats. This difference first became apparent in SHR and WKY rats as early as 4 and 8 weeks after birth. These results suggest that enhancement of calcium channel density might occur in the heart and brain of SHR in response to elevated blood pressure and that reduced calcium sensitivity of dihydropyridine binding to calcium channels might be a primary characteristic of this rat strain.

Animals↗
PubMed1991

Assessment of hypertensive heart by 2-dimensional echocardiography in mass screening.

Two-dimensional echocardiography (2DE) was used in the mass screening of 3,017 participants (1,195 males, 1,822 females, mean age 59) living in 13 areas in Japan. The 2DE findings of left ventricular hypertrophy (LVH) and LV function were compared with the presence and severity of hypertension (Ht). Out of 1,100 patients who had an evident history of Ht above 160/95 mmHg (Ht group), 298 patients (27.4%) were complicated by LVH. In contrast, LVH was also recognized in 60 (11.2%) of 535 borderline Ht cases and in 87 (6.3%) of 1,382 normotension cases. LVH cases in the Ht group were divided into 3 groups: mild (220: 73.8%), moderate (63: 21.2) and severe (15: 5.0). Asymmetric septal hypertrophy (ASH) was recognized in 111 patients (37.2%) of the 298 LVH cases. The prevalence of ASH in these LVH patients was higher according to the severity of the LVH: mild LVH = 31%, moderate LVH = 51% and severe LVH = 67%. The prevalence of LVH was higher in males than in females. This was especially apparent in the moderate to severe LVH groups and also noted to be higher according to the increase of mean blood pressure. The prevalence of mild to moderate LVH was significantly higher in the poorly-controlled group than in the well-controlled group. In contrast, no significant difference in prevalence of severe LVH was noted between the well-controlled and poorly-controlled groups. The prevalence of LV dysfunction was significantly greater in moderate or severe LVH groups than in non or mild LVH groups. It tended to be higher in the poorly-controlled group compared with the well-controlled group. The regression of LVH was frequently detected in the well-controlled group by the follow-up study. We conclude that 2DE observation of LV performance in mass screening will be extremely valuable in the long term follow-up of Ht patients.

Adult↗
PubMed1990

The relevance of psychosocial factors in acute ischemic heart disease. A case-control study of a Japanese population.

We investigated, by case-control study, the relevance of psychosocial factors on the prevalence of acute ischemic heart disease (IHD) in middle aged Japanese men. We questioned 109 acute IHD patients and 80 individuals in an age-adjusted sampled control group. Multiple logistic regression analysis showed the following statistically significant factors: hypertension (odds ratio 4.01, p less than 0.001), Type A behavior pattern (2.25, p less than 0.05) and high job demand (2.23, p less than 0.02). No direct influence of family function or social support to the prevalence of acute IHD was apparent. These results suggest that, among men in Japan, Type A behavior pattern and high job demand represent psychosocial risk factors of IHD. Due to the case-control protocol, causal relationships cannot be decided. The limitation of the study design is discussed within that context.

Coronary Disease↗
PubMed1990

Hyponatremia and hyperreninemic hypoaldosteronism in a critically ill patient: combination of insensitivity to angiotensin II and tubular unresponsiveness to mineralocorticoid.

A 62-year-old man with pneumonia and left flank pain had a clinical syndrome of hyponatremia, hypotension, dehydration, and high urinary sodium excretion in the presence of a normal glomerular filtration rate. The plasma level of antidiuretic hormone was relatively high despite decreased serum osmolality. Thyroid function and excretion of glucocorticoid and sex steroids were normal. The serum aldosterone level was very low despite elevated plasma renin activity. Angiotensin II failed to stimulate any secretion of aldosterone, despite the occurrence of a progressive rise in blood pressure. On the other hand, rapid ACTH administration increased both serum aldosterone and cortisol. The patient showed no effective response to increased salt intake, but large doses of mineralocorticoid resulted in a normal serum sodium level without dehydration. Subsequently, he suffered cardiac arrest secondary to ventricular tachycardia. Postmortem examination showed well differentiated adenocarcinoma in the left pleura and an intact, histologically normal adrenal zona glomerulosa and kidney. This is the first reported case of a critically ill patient with hyponatremia caused by hyperreninemic hypoaldosteronism possibly due to angiotensin II insensitivity and tubular unresponsiveness to mineralocorticoid.

Adrenal Glands↗
PubMed1989

Ventricular performance in spontaneously hypertensive rats (SHR) with reduced cardiac mass.

This study was designed to investigate the effect of 4 weeks of captopril treatment on cardiac mass and performance in spontaneously hypertensive rats (SHR). Left (LV) and right (RV) ventricular mass of SHR and normotensive WKY rats was reduced (p less than 0.01). Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) in the treated SHR and WKY were reduced; cardiac (CI) and stroke (SI) indices remained unaltered in SHR but increased in WKY. Ventricular performance (i.e., cardiac pumping ability), assessed by rapid blood infusion, did not differ between untreated SHR and WKY, and between treated and untreated WKY rats. However, the ventricular performance curves for the treated SHR shifted down and to the right from the untreated SHR (p less than 0.01). Moreover, when MAP of treated SHR (with regressed LV mass) was elevated to their pretreatment levels, cardiac performance curves shifted further rightward and downward. In contrast, the performance curves of treated WKY whose MAP was also elevated to the level of untreated WKY were no different from those of untreated WKY. These data demonstrate that captopril treatment (at doses used in this study) reduced MAP in SHR through decreased TPRI while decreasing biventricular mass. Furthermore, the cardiac-pumping ability of previously hypertrophied SHR hearts was reduced, suggesting that certain antihypertensive agents that diminish cardiac mass could produce impaired cardiac function when called upon to increase performance (e.g., when MAP is suddenly raised).

Animals↗
PubMed1989

The development and reversal of tolerance to antianginal effect of isosorbide dinitrate in patients with effort angina.

The development and reversal of tolerance to the hemodynamic and anti-anginal effects of isosorbide dinitrate in a sustained release form (ISDN-SR) were investigated in 11 male patients (mean age 58.9 y.o.) with stable effort angina. Treadmill exercise test, evaluation of hemodynamic parameters and measurement of plasma ISDN concentrations were performed during the control period, on the 1st, 7th and 14th days of therapy with 40 mg of ISDN-SR orally every 8 h and, subsequently, on the day when ISDN-SR was re-administered after a 72 h placebo period (17th day). Initially, exercise tolerance time (ETT) was prolonged significantly (p less than 0.001) by ISDN-SR from 257 +/- 50 sec in the control period to 434 +/- 55 sec on day 1. This prolongation was significantly reduced with sustained therapy and ETT was shortened to 332 +/- 69 sec on the 7th day (p less than 0.01 vs day 1) and 326 +/- 73 sec on the 14th day (p less than 0.01 vs day 1). The effects of ISDN-SR initially observed were restored after a 72 h placebo period and ETT was prolonged to 432 +/- 57 sec on the 17th day. The resting heart rate was increased significantly (p less than 0.01 vs control) and systolic blood pressure was decreased (p less than 0.001 vs control) by ISDN-SR on day 1. These changes were also diminished significantly (p less than 0.01 vs day 1) with sustained therapy and were restored after a 72 h nitrate-free interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Mechanical adaptation of heart rate change for coronary circulation in patients with and without ventricular hypertrophy.

To clarify the mechanical adaptation and interference of coronary vessels, we studied hemodynamics of coronary circulation in control and 4 different pacing rates (80, 100, 120, 150/min) in 5 patients with angina pectoris (AP) and in 5 patients with hypertrophic cardiomyopathy (HCM). Coronary sinus flow (CSF) was measured by a Webster's thermodilution catheter, and we applied ascorbic acid-platinum reaction for the mean transit time measurement in left coronary flow (t0-t2). Coronary vascular bed (CVB) was obtained by multiplying CSF and t0-t2. CSF in AP gradually increased from 104 +/- 21 ml/min at 72/min to 148 +/- 42 ml/min at 120/min, while CSF in HCM changed slightly from 91 +/- 25 ml/min at 64/min to 94 ml/min at 120/min. Average t0-t2 in HCM was 6.0 +/- 1.6 sec in control which was significantly lower than that in AP (7.8 +/- 0.7 sec). Calculated CVB in AP increased at any given heart rate up to 120/min (13.5 +/- 2.4, 15.8 +/- 1.7, 15.0 +/- 4.7, 15.1 +/- 4.3 ml), but CVB in HCM decreased from 9.1 +/- 2.3 ml at 64/min to 8.1 +/- 1.7 ml at 120/min. These data suggest that myocardial compression and suction at different heart rates and with different cardiac muscle structures play an important role for beat to beat adjustment of coronary circulation in cardiac cycle.

Adaptation, Physiological↗
PubMed1988

Measurement of left atrial systolic time intervals in hypertensive patients using Doppler echocardiography: relation to fourth heart sound and left ventricular wall thickness.

The concept of left atrial systolic time intervals and Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardiographic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejection period (the atrial pre-ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave). Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre-ejection period (81 +/- 10 versus 89 +/- 14 ms p less than 0.05) and a corrected atrial pre-ejection period (66 +/- 17 versus 83 +/- 18 ms, p less than 0.01), as well as a longer atrial ejection time (147 +/- 15 versus 126 +/- 13 ms, p less than 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 +/- 0.08 versus 0.71 +/- 0.11, p less than 0.001; 0.46 +/- 0.16 ms-1 versus 0.67 +/- 0.17 ms-1, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Protein kinase C activation aggravates hypoxic myocardial injury by stimulating Na+/H+ exchange.

The physiological and pathophysiological roles of protein kinase C activation were investigated in cultured mouse myocardial cells. First, effects of 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C, on the intracellular pH (pHi) and cytosolic free Ca2+ level [( Ca2+]i) were studied, using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and quin-2, respectively. In the presence of the Ca ionophore A23187, TPA induced a rise in pHi by activating amiloride-sensitive Na+/H+ exchange and also produced a rise in [Ca2+]i above that seen with A23187 alone. These effects were totally inhibited by amiloride. Second, the effect of TPA on hypoxia-induced myocardial cell injury was evaluated. The addition of TPA to the culture medium enhanced creatine kinase release from hypoxic myocardial cells (95% N2 + 5% CO2). This effect was markedly suppressed by the addition of amiloride. These data suggests that protein kinase C activation aggravates hypoxic myocardial injury, presumably by inducing Ca2+ overload. This event is secondary to activation of Na+/Ca2+ exchange through accelerated influx of Na+ into the cells as a result of Na+/H+ exchange stimulation by protein kinase C.

Animals↗