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Biomedical subjects

N Sugihara

Publications and source records attributed to N Sugihara.

At least 73 records · Page 4Linked to original sources

Hepatic ATP content and hyperammonemia induced by CCl4 in rats.

An investigation of the mechanism of development of hyperammonemia observed in CCl4-induced hepatic encephalopathy was performed in rats. CCl4 (1.0 ml/kg 3 times per week for over 10 weeks) caused a severe hyperammonemia and depletion of hepatic ATP contents in only those rats with hepatic encephalopathy. However, CCl4 (1.0 ml/kg 3 times per week for 7 weeks) did not cause hepatic encephalopathy and did not change in blood ammonia levels. Administration of 2,4-dinitrophenol (2,4-DNP) in these CCl4-treated rats caused hepatic encephalopathy within 30 min after injection and then the increase of 140 micrograms/dl in blood ammonia levels and the decrease of 80% in hepatic ATP contents were observed. However, the administration of 2,4-DNP in CCl4-untreated rats did not cause hepatic encephalopathy within 30 min after injection although the increase of 70 micrograms/dl in blood ammonia levels and the decrease of 80% in hepatic ATP contents were observed. Hepatic activities of carbamylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), important enzymes of the urea cycle, were significantly inhibited by 85% and 60% respectively, in rats treated with CCl4 plus 2,4-DNP. However, in rats treated with 2,4-DNP and without CCl4, the hepatic activities of CPS and ASS were inhibited only 25% and 0%, respectively. These findings suggest that the severe hyperammonemia, which may be produced by the decrease of hepatic ATP content and the inhibition of CPS and ASS, may play an important role in induction of hepatic encephalopathy.

2,4-Dinitrophenol↗

[Diastolic dysfunction and its relation to myocardial fibrosis in essential hypertension].

This study elucidated diastolic left ventricular dysfunction and whether myocardial interstitial fibrosis correlates with diastolic dysfunction in mild to moderate systemic hypertension (HT). Six normotensive subjects, 18 hypertensive patients without left ventricular hypertrophy (LVH) and 10 hypertensive patients with significant LVH were evaluated. M-mode echocardiography was used to determine fractional shortening (FS), isovolumic relaxation time (IRT), and left ventricular filling volume during rapid and slow filling periods and the atrial contraction period (RFV, SFV, ACV). The quotients of the left ventricular filling volume and the end-diastolic volume and stroke volume were also calculated. Simultaneous biventriculography was used to determine the end-diastolic thickness of the interventricular septum and posterior wall. Right ventricular endomyocardial biopsies were performed to calculate the percentages of fibrosis. The FS was normal in all groups. The percentages of fibrosis in the two HT groups were significantly greater than those in the normals. The IRT of the HT groups was significantly greater, and the RFV, RFV/EDV and RFV/SV were significantly less than those of the normals. Multiple regression analysis showed that the wall thickness and the percentages of fibrosis correlated significantly with IRT, RFV, RFV/EDV and RFV/SV. The standard coefficients of correlation of wall thickness and the percentages of fibrosis were 0.333 and 0.239 in respect to IRT, and -0.304 and -0.473 in respect to RFV. There were significant correlations between the percentages of fibrosis and RFV (r = -0.675), RFV/EDV (r = -0.664) and RFV/SV (r = -0.602) in the normals and in cases of HT without LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

[Serial changes in left ventricular configuration and function in hypertrophic cardiomyopathy].

Fifteen patients, 12 males and three females, with hypertrophic cardiomyopathy (HCM) including three of obstructive type (HOCM) were investigated to observe the long-term course of HCM. Left ventriculography and bi-ventriculography were performed twice serially in all cases. We studied the correlations between the serial ECG changes, especially the negative T wave, and the left ventricular configuration, wall thickness, and left ventricular function. Serial ECG changes included: 1) negativity of the T wave which developed or increased concomitantly with increased voltages of SV1 + RV5 (A-1 group: five cases), 2) the negativity decreased or resolved with decreased voltages of SV1 + RV5 (A-2 group: four cases), and 3) insignificant changes of both T waves and SV1 + RV5 (B group: six cases). In the right oblique views at end-diastole, the configuration of the left ventricle was classified in three forms; (1) spade form (S), (2) round form (R), and (3) intermediate form (SR). The results were as follows: 1. The A-1 group showed increased thickness of the apical and anterior walls, but the thickness of the posterior wall and interventricular septal wall did not change serially. In three cases, the thickness of the interventricular septum showed mild hypertrophy at the initial and final observations. The configuration changed from the R or SR form to the S form. Diastolic dysfunction (peak dV/dt/V, peak dV/dt/EDV) was progressive, but end-diastolic volume and ejection fraction did not change. 2. The A-2 group showed the significantly decreased thickness of the apical and anterior walls. The thicknesses of the posterior wall and interventricular septal wall tended to decrease in all cases. In three cases (75%), the interventricular septal wall was markedly hypertrophied on the initial observation. The configuration changed from the S or SR form to the R form. Left ventricular diastolic function and ejection fraction decreased significantly and end-diastolic volume increased. Two cases showed clinical pictures of dilated cardiomyopathy at the final observation. 3. In the B group, there were no marked changes in wall thickness, left ventricular configuration, or systolic and diastolic functions. In conclusion, serial changes in left ventricular configuration, wall thickness, especially of the anterior and apical walls, and left ventricular function were all compatible with the serial changes of the ECG in hypertrophic cardiomyopathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Coronary angiographic characteristics in Japanese patients with heterozygous familial hypercholesterolemia.

Coronary angiographic findings were analyzed in 51 consecutive patients (36 males and 15 females) with heterozygous familial hypercholesterolemia (FH) and 279 consecutive patients (216 males and 63 females) without FH (non-FH). The coronary stenosis index and over 75% stenosis vessel subset were almost three times as high in the FH group. The incidence of myocardial infarction was almost twice as high in the FH group. Levels of total cholesterol and its lipoprotein fractions, except HDL-cholesterol, were almost twice as high in the FH group. In the FH group aged under 50 years, the two parameters of coronary angiogram and the incidence of myocardial infarction were significantly higher in males than in females. However, in the group aged over 50 years, all three parameters were not significantly different between those in males and females. The level of HDL-cholesterol was significantly lower in males than in females. A significantly higher incidence (18%) of coronary ectasia was observed in the FH group compared with the incidence (2%) in non-FH. All patients with coronary ectasia were males, except one female with FH. On comparison of the males among the FH patients with those among the non-FH patients matched for total cholesterol, age and other risk factors, the FH patients were associated with a significantly higher degree of coronary atherosclerosis and lower level of HDL-cholesterol. Seven FH patients with a normal coronary angiogram were observed. However, any factors as regards age, total cholesterol, HDL-cholesterol and Achilles tendon thickness failed to distinguish between the FH patients with a normal coronary angiogram and those without.(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon↗

Blood ammonia levels and hepatic encephalopathy induced by CCl4 in rats.

An investigation of the mechanism of development of hepatic encephalopathy induced by CCl4 was performed in rats. CCl4 (1.0 ml/kg three times per week for over 10 weeks) caused hepatic encephalopathy in 80% of the treated rats. Accompanying the hepatic encephalopathy were hematemesis, abdominal dropsy, and hyperammonemia, conditions observed in hepatic coma patients. The blood ammonia levels were tremendously increased in only those rats with hepatic encephalopathy. Hepatic activities of carbamylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), important enzymes of the urea cycle, were significantly inhibited by CCl4. However, the causality between the inhibition of CPS or ASS activity and the increase in blood ammonia levels was not observed. On the other hand, the content of ATP, which is a substrate of CPS and ASS, was decreased by 60% in liver of rats with hepatic encephalopathy. The activity of Mg2+-ATPase which can decompose hepatic ATP was increased by 60 and 300% in mitochondria and microsomes, respectively, of livers of rats with CCl4-induced encephalopathy. There was a good correlation between the decreased hepatic ATP content and the increased mitochondrial Mg2+-ATPase activity. Furthermore, there was also a good correlation between the increase in blood ammonia levels and the increase in Mg2+-ATPase activity in microsomes. These findings suggest that hyperammonemia, which was produced by the decrease in hepatic content and by the inhibition of CPS and ASS, may play an important role in induction of hepatic encephalopathy.

Adenosine Triphosphate↗

[Electrocardiographic and angiographic follow-up of patients with hypertrophic cardiomyopathy].

Electrocardiographic follow-up was conducted for 17 patients with hypertrophic cardiomyopathy including six cases who received left ventriculographic follow-up. 1. Serial ECG changes were as follows: 1) In seven patients negativity of the T wave appeared or increased concomitantly with increased voltage of SV1 + RV5 (A-1 group). 2) In four patients, negativity of the T wave decreased or disappeared with the decreased voltage of SV1 + RV5 (A-2 group). 3) In six patients, there were insignificant changes of both T wave and SV1 + RV5 (B group). 2. Results of serial left ventriculography and biventriculography were as follows: 1) Two patients (A-1 group) showed an increased voltage of SV1 + RV5 (25 mm----48 mm, 42 mm----54 mm), and increased thickness of the apical wall (10 mm----12 mm, 8 mm----11 mm) and the anterior wall (13 mm----16 mm, 10 mm----16 mm). However, the thickness of the posterior and interventricular septal walls did not change. The configuration of the end-diastolic left ventriculogram (RAO 30 degrees) changed from a round configuration to the so-called "beak" configuration. 2) Two patients (A-2 group) showed a decreased voltage of SV1 + RV5 (81 mm----26 mm, 73 mm----53 mm), decreased thickness of the apical wall (18 mm----10 mm, 21 mm----15 mm) and the anterior wall (12 mm----9 mm, 17 mm----12 mm). The end-diastolic left ventriculogram changed from a spade-like configuration to a round configuration. In the analysis of diastolic function measured by digitized cineangiograms using a picture-analyzer, diastolic dysfunction was already present at the initial observation. The diastolic and systolic dysfunction progressed during serial observations. These patients showed the clinical pictures of dilated cardiomyopathy at the final observation. 3) Two patients with no remarkable changes of the T wave (B group) showed insignificant changes in configuration of the left ventriculogram and wall thickness. In conclusion, serial changes in configuration of the left ventricle and wall thickness, especially of the anterior and apical walls, are compatible with the serial changes of the ECG in hypertrophic cardiomyopathy. The patients whose negative T waves decreased or disappeared had diastolic dysfunction at the initial observation, and deterioration of both diastolic and systolic dysfunctions during serial observations.

Adult↗

Clinical studies on diabetic myocardial disease using exercise testing with myocardial scintigraphy and endomyocardial biopsy.

Nine diabetics without significant coronary stenosis participated in an exercise testing protocol with thallium-201 myocardial scintigraphy. Endomyocardial biopsy of right ventricle was also obtained. There were 4 patients with abnormal perfusion (positive group) and 5 patients with normal perfusion (negative group). All cases of the positive group were familial diabetics and there was only one case of dietary treatment, whereas in the negative group, there were only 2 cases of familial diabetics and 3 cases receiving dietary treatment. No statistical differences between the positive and negative groups were observed for the data of exercise performance and hemodynamic parameters in cardiac catheterization at rest. However, the mean ejection fraction in the positive group (62 +/- 13%) was significantly lower than in the negative group (77 +/- 4%). In both groups, the mean diameter of myocardial cells and the mean percent fibrosis of biopsy specimens showed significant increases compared with the control group. The mean percent fibrosis in the positive group (24.1 +/- 8.5%) compared with that in the negative group (16.5 +/- 5.9%) showed a tendency to increase. It is suggested that the abnormal perfusion of thallium-201 in the positive group indicates subclinically a pathological change of microcirculation caused by diabetes mellitus.

Adult↗

Urinary alpha 1-microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure.

An epidemiologic investigation was carried out to clarify the significance of the urinary excretion of alpha 1-microglobulin (alpha 1-MG) in people aged 50 years and over living in a Cd-polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of alpha 1-MG to creatinine clearance were compared with various parameters (age, urinary beta 2-microglobulin (beta 2-MG), total protein, Cd, Cu and Zn, serum beta 2-MG, creatinine and blood urea nitrogen and relative clearances of alpha 1-MG, beta 2-MG, inorganic phosphate and uric acid). It was found that the urinary excretion of alpha 1-MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary alpha 1-MG level markedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfunction caused by environmental Cd exposure.

Age Factors↗

Enhanced small intestinal absorption of beta-lactam antibiotics in rats in the presence of monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi).

Monodesmoside, saponin A, B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) have been shown to promote absorption of poorly absorbed beta-lactam antibiotics by the small intestine using an in situ loop method. Monodesmosides were solubilized with ginseng crude saponin extract, a mixture of bisdesmosides, saponin X, Y1 and Y2 which were isolated also from Sapindus mukurossi. These solubilizing agents were demonstrated not to influence the absorption promoting effect of monodesmosides. Among the monodesmosides, saponin B showed the greatest effect. No influence of osmolarity of the administered solution on the absorption promoting action was observed. The promoting functions of the three monodesmosides for the small intestinal absorption of antibiotics were suppressed by Ca2+ ion coexisting in the administered solution.

Animals↗

[Washout rate in hypertrophic cardiomyopathy assessed by exercise myocardial scintigraphy].

The present study clarified the pathogenesis of disproportional hypertrophy in terms of disturbed coronary microcirculation. Twenty-eight patients with hypertrophic cardiomyopathy (HCM) who had normal coronary angiograms were categorized in four groups according to distributions of disproportional hypertrophy on left ventriculography and biventriculography: (1) Interventricular septal hypertrophy, (2) septal and apico-anterior wall hypertrophy, (3) apico-anterior hypertrophy, and (4) nonspecific hypertrophy of the entire wall. All 28 HCM patients and 10 normal volunteers were tested using exercise myocardial scintigraphy, and the circumferential profiles were processed by computer to relate the washout rate and disproportional hypertrophy. Comparison of the mean curves and mean segmental values of the circumferential profiles of the HCM groups with those of the control group showed that the mean initial uptake values of the HCM groups were to be relatively low in the apical segment and in the lower portion of the anteroseptal segment representing disproportional hypertrophy of these segments. The mean values were significantly elevated in the upper portion of the anteroseptal segment which was projected as the largest amount of the myocardium three-dimensionally. The mean washout rates in the HCM groups were significantly decreased in all segments, especially in those segments which reflected disproportional hypertrophy. This trend was also observed in the segments with increased initial uptakes. On comparing the segmental values of all groups, the segments with initial uptakes and/or washout rates with having the mean value minus 2SD of the control group were observed in the profiles of 12 of the 28 HCM patients. These all had decreased washout rates. In 25 of the total segments of the HCM patients, the initial uptakes and/or washout rates were below the normal limit; 21 of these segments had only decreased washout rates, and 16 of these 21 segments belonged to disproportionally hypertrophic wall. These results indicate that the decreased washout rate in the disproportionally hypertrophic wall is characteristic of HCM. It is suggested that the decreased washout rate with the decreased initial uptake is caused by disturbance of the coronary microcirculation. In addition, the decreased washout rate without a decreased initial uptake is caused not only by disturbance of coronary microcirculation, but by a metabolic disturbance of the myocardial cells as well. Furthermore, both disturbances are closely related to the pathogenesis of disproportional hypertrophy.

Adult↗

[Left ventriculography and serial ECG changes in hypertrophic cardiomyopathy with special reference to the negative T wave].

To clarify the correlation between the configuration of the left ventriculogram and serial ECG changes, 16 patients with hypertrophic cardiomyopathy (HCM) associated with asymmetrical septal hypertrophy were examined. In the right oblique view at end-diastole, the configurations were classified by form as round (R, n = 7), round with inferior concavity (R-i, n = 2), spade (S, n = 4) and spade with inferior concavity (S-i, n = 3). These patients were divided into two groups according to serial T wave changes; nine with marked changes (A group) and seven without (B group). Furthermore, group A was separated into two subgroups; seven with increasing negativity or appearance of the negative T wave (A-1 group) and two with decreasing negativity or disappearance of the negative T wave (A-2 group). The results were as follows: Five (71%) of the seven cases with the S and S-i form belonged to the A group. Their apical walls showed marked hypertrophy and their ECGs showed deep negative T waves. The other two cases (29%) belonged to the B group, and did not show marked apical hypertrophy. Four (44%) of the nine cases with the R and R-i form belonged to the A group. They showed mild apical hypertrophy, and initially did not show deep negative T waves. A deep negative T wave appeared in three during observation. The initial depth of the maximum negativity of T wave correlated significantly with apical wall thickness, SV1 + RV5, and the total depth of the negative T wave in precordial leads. During the observation, the A-1 group showed a marked increase of SV1 + RV5. The A-2 group showed a decrease of SV1 + RV5. In conclusion, HCM with deep negative T waves has a tendency to present wide changes in the T wave during serial ECG observation and to show apical hypertrophy on left ventriculography. Cases of increasing negativity of the T wave showed marked increase in voltage of SV1 + RV5. However, cases of decreasing negativity of the T wave showed decreasing SV1 + RV5. These ECG changes, especially the negative T wave changes are reputed to be related to apical wall thickness.

Cardiomyopathy, Hypertrophic↗

Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus.

For the purpose of studying the clinicopathology of the biopsied myocardium in patients with diabetes mellitus, the diameter of right ventricular myocardial cells and diffuse perimysial fibrosis of biopsied myocardium were measured quantitatively. Seven healthy controls and nine diabetic patients without hypertension or coronary arterial disease were subjected to this study. The degree of diabetic complications was mild to moderate. The diameter of myocardial cells was measured and the degree of diffuse perimysial fibrosis was assessed by the point-counting method using a square grid, in which the distance between the points was 10 micron. Over 2000 points which lay on the longitudinally cut myocardial cells and on the interstitial fibrosis stained by the Mallory-Azan method were measured. Percentage fibrosis was calculated according to the formula: percentage fibrosis = (points lying on the interstitial fibrosis)/[(points lying on the myocardial cell) + (points lying on the interstitial fibrosis)] X 100. The results were as follows. The mean diameter of right ventricular myocardial cells in patients with diabetes mellitus was significantly larger than that of controls (P less than 0.01). The percentage fibrosis of diabetic patients was significantly higher than that of controls (P less than 0.01). There was no significant correlation between the histopathological measurements and clinical features. It is concluded that hypertrophy of myocardial cells and interstitial fibrosis of the myocardium exist even in mild diabetes mellitus.

Adult↗

Enhanced rectal absorption of beta-lactam antibiotics in rat by monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi).

Monodesmosides, saponin A,B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) were shown to promote the rectal absorption of beta-lactam antibiotics in rat, using an in situ loop method and an in vivo method. In the in situ loop method, monodesmosides were solubilized with a mixture of bisdesmosides, mukurozi-saponin X, Y1 and Y2, each of which was isolated from pericarps of Sapindus mukurossi. The promoting functions of the three monodesmosides for the rectal absorption of antibiotics were comparable and also suppressed by Ca2+ ion coexisting in the administered solution. Unlike the case of N-acylcollagenpeptides, which were also previously reported as absorption promoters, no influence of osmolarity of the administered solution on the absorption promoting action was observed. Absorption of beta-lactam antibiotics from suppositories was enhanced with the aid of either of monodesmosides without solubilizing agent.

Animals↗

Reversible hyperkalemia induced by flufenamic acid in asymptomatic hyporeninemic patient.

Reversible hyperkalemia induced by flufenamic acid in an asymptomatic hyporeninemic patient with IgA nephropathy is reported. Flufenamic acid, 600 mg daily, was given for four months to a 64-year-old woman with biopsy proven IgA-nephropathy. This produced hyperkalemia, hypertension and congestive heart failure with slowly progressive renal impairment. We conclude that a further suppression of the renin angiotensin system causing selective hypoaldosteronism together with the nephrotoxic effects of this drug may have been responsible for hyperkalemia in this patient.

Female↗

[Biventriculographic and clinicopathologic evaluation of apical hypertrophy: with reference to asymmetrical septal hypertrophy with hypertension].

To clarify the pathogenesis of apical hypertrophy with asymmetrical septal hypertrophy (ASH), left ventriculography in the right anterior oblique projection (LVG), biventriculography (BVG), and endomyocardial biopsy of the right ventricle were performed for patients with ASH. The patients were categorized in four groups according to ECG, LVG and BVG. Patients with hypertrophic cardiomyopathy (HCM) were divided into two subsets; (A) Apical hypertrophy group (AH: nine patients), with ECG showing left ventricular hypertrophy (LVH) and giant negative T waves (GNT), and with LV configurations showing the S or SR form at end-diastole on LVG. (B) Non-apical hypertrophy group (non-AH: 12 patients), with ECG showing LVH without GNT and LV configuration showing R form at end-diastole on LVG (cf: Fig. 1). Patients with ASH and hypertension (ASH-HT) were also divided into two subsets; (A) AH: seven patients. (B) non-AH: nine patients. Analysis of LVG and BVG: In HCM, the septal configuration showed the TS X S form in both two subset groups. The septal configuration in ASH-HT was divided into the NH form, which was clearly distinguishable from the septal configuration in HCM, and the TS X S form as in cases with HCM. In both HCM and ASH-HT, the diastolic thickness of the anterior apical wall was significantly thicker in all patients with AH than that in non AH. In HCM, the diastolic thickness of the septum and the percent systolic thickening did not significantly differ between AH and non-AH groups. In ASH-HT, the NH form showed similar diastolic thickness of the septum and % systolic thickening in AH and non-AH groups. On the other hand, the TS X S form in non-AH group showed greater thickness and lower % systolic thickening similar to those of HCM. Histological analysis of endomyocardial biopsy; In HCM, the transverse diameters of the myocytes and the biopsy scores did not differ significantly between AH and non-AH groups. In ASH-HT, the TS X S form in non-AH group had longer diameters and higher biopsy scores similar to those of HCM compared to the NH form in AH group. In conclusion, both HCM and ASH-HT may have apical hypertrophy manifested by giant negative T waves in the EKG and spade like form of left ventriculogram. In addition, apical hypertrophy in ASH-HT with the NH form of septal configuration seemed to be caused by hypertension.

Adult↗