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A 59-year-old woman was admitted to our clinic with the complaint of left flank pain. Excretory urogram showed left hydronephrosis. Computed tomographic (CT) scan and renal angiography showed a left renal capsular tumor. Histological specimen obtained by a sure cut needle suggested malignant lymphoma. She was treated with a combined treatment of 8 MHz radiofrequency hyperthermia in a total of 10 sessions and 5,440 rads irradiation for 5 weeks. After the treatment, CT scan showed 92% tumor regression. After that, a recurrent tumor in left shoulder muscle became manifest. She received combination chemotherapy with 3 courses of ABEP regimen (aclacinomycin, cytosine arabinoside, etoposide, prednisolone) and 7 courses of ACOPE regimen (adriamycin, cyclophosphamide, vincristine, prednisolone, etoposide) and complete remission was obtained.

By means of sequential ultracentrifugation of plasma from 85 control healthy Japanese subjects and from 15 maternal infant pairs, very low density lipoprotein (VLDL: d less than 1.006 g/ml), low density lipoprotein (LDL: 1.006 less than d less than 1.063 g/ml) and high density lipoprotein (HDL: d greater than 1.063 g/ml) were obtained and analyzed for cholesterol (Ch), triglyceride (TG), phospholipid (PL) and apolipoprotein B (Apo B). These results were compared to values in Western countries reported in the literature. HDL-Ch/LDL-Ch of adult Japanese was much higher than that of subjects in Western countries, especially in males. Umbilical cord (U) plasma-Ch, TG, PL and Apo B were 73.3 +/- 15.9, 51.0 +/- 10.4, 110.0 +/- 21.0 and 47.6 +/- 15.7 (mean +/- S.D.) mg/100 ml, respectively. In cord blood the concentrations of Ch, TG and PL in all lipoprotein density classes were less than one half of those in normal adults. Cord blood has higher levels of HDL-Ch and lower levels of LDL-Ch than normal adults. Therefore, HDL-Ch/LDL-Ch ratio in cord blood (1.58 +/- 0.32 was far higher than the ratio in normal adults (0.50 +/- 0.11). In cord blood, HDL was the predominant Ch, TG and PL carrying lipoprotein. HDL-Ch/LDL-Ch ratios were 1.58 in Japan, 1.14 in USA, 0.89 in Australia and 0.69 in GDR. HDL-Ch/LDL-Ch ratio in Japanese cord blood was the highest among the values reported in the literature. The relationships between maternal and infant lipoproteins were more significant in HDL than in VLDL or LDL. The positive correlation between maternal HDL and infant HDL may suggest the possibility of placental transfer of intact HDL particles.

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)

The action of acetaldehyde on the membrane resistance of the guinea-pig taenia caecum was investigated with a double sucrose-gap method in different ionic environments. Application of acetaldehyde (10--20 mM) produced hyperpolarization, block of spike discharge and reduction of the membrane resistance. The reduction of the membrane resistance by acetaldehyde was potentiated by increasing the external K+ concentration and by replacement of Cl- with NO3-; it was reduced by lowering the external K+ concentration and by replacement of Cl- with benzenesulfonate. Replacement of NaCl with Tris-Cl, sucrose, or LiCl had no appreciable effect on the action of acetaldehyde on the membrane resistance. It therefore seemed likely that acetaldehyde increased the membrane conductance for K+ and Cl- more than for Na+. Although this action of acetaldehyde was similar to the alpha-action of catecholamine, the decrease of the membrane resistance and hyperpolarization induced by acetaldehyde remained unchanged in the presence of phentolamine.

We present 2 patients associated with hypouricemia. Serum uric acid levels were 1.6 and 1.3 mg/100 ml, and the ratios of urate clearance to creatinine clearance were 34.1 and 39.4%, respectively, while glomerular filtration rates (GFR) were normal. In the pyrazinamide (PZA) suppression test these 2 patients showed a different response of urate excretion. In the first patient urate excretion showed only a slight decrease following PZA. The load of benzbromarone did not increase urate excretion significantly. This patient is considered to have a defect of urate reabsorption in the proximal tubule, resulting in renal uricosuria. The second patient, on the contrary, showed nearly complete suppression of urate excretion after PZA. Uricosuric response to benzbromarone was far less than in the normal subjects. The suppression rate of urate excretion following PZA in benzbromarone-induced uricosuria was similar to the value of the normals. These results suggest that the latter had a defect of postsecretory reabsorption of urate in the tubule.

Plasma aldosterone concentration (PAC) in patients with chronic renal failure was measured by radioimmunoassay with and without dichloromethane extraction before the assay. Blood samples were obtained from patients with chronic renal failure who were undergoing maintenance hemodialysis, from patients with chronic renal failure who were not undergoing hemodialysis, and from age-matched normal subjects. With the three radioimmunoassay kits tested, the direct assays without extraction in normal subjects gave PAC values comparable to those obtained after the dichloromethane extraction; in contrast, in patients with chronic renal failure, the direct plasma radioimmunoassays yielded consistently higher values than those obtained after the extraction (p less than 0.001). When various plasma steroid metabolite fractions were separated by high-pressure liquid chromatography (HPLC) with a reverse-phase column, and each fraction was assayed for PAC with the three radioimmunoassay kits, high immunoreactivities were found in the polar fractions in the plasma from patients with chronic renal failure but not in normal plasma. The ratios of the immunoreactivities of these polar fractions to that of the aldosterone fraction, determined after HPLC separation, showed a significant positive correlation (r = 0.746, p less than 0.001) with serum creatinine concentrations in plasma from patients with chronic renal failure who were not undergoing hemodialysis. These results indicate that the values for PAC are falsely elevated in chronic renal failure when PAC is measured by radioimmunoassay kits without prior extraction. Furthermore, plasma from patients with chronic renal failure contains a polar substance(s) that cross-reacts with antialdosterone antibodies. This so far-unidentified substance increases with advancing renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

The pressor response to angiotensin II (A II) has been shown to be enhanced, and aldosterone production to be attenuated following administration of indomethacin (Ind), a cyclooxygenase inhibitor, pretreatment. Since PGI2 has been proposed to be a potent vasodepressor prostaglandins, with steroidogenic action, the present study was undertaken to evaluate the regulatory role of PGI2 in the blood pressure and aldosterone responses to A II. Ind was administered to suppress the production of endogenous prostaglandins (30 mg/kg. im. Ind-group) and PGI2 was given after Ind pretreatment (2 ng/kg/min. iv. Ind + PGI2 group) to conscious male rabbits (2.5 approximately 3.5 kg). Baseline blood pressure readings were similar in three groups (control, Ind-, and Ind + PGI2-group). The increment of blood pressure by A II infusion were significantly enhanced in the Ind-group (12.6 +/- 1.3 mmHg) compared with the control-group (8.6 +/- 1.5 mmHg). This enhancement was diminished by PGI2 infusion (7.0 +/- 2.3 mmHg). PGI2 infusion alone does not influence blood pressure in the dose of 0.5 approximately 4.0 ng/kg/min. Aldosterone response to A II was significantly attenuated in the Ind-group (1.5 +/- 1.2 ng/dl) compared with the control-group (7.5 +/- 3.1 ng/dl), but was restored in the Ind + PGI2-group (4.5 +/- 1.3 ng/dl). It is suggested that circulating PGI2 may play a role in the regulation of blood pressure by modulating the pressor response and the aldosterone response to A II.

1) Plasma renin activity (PRA) response to isometric exercise was studied before and after the intravenous administration of 0.2 mg/kg of propranolol in 8 normotensive and 10 normal renin hypertensive patients. 2) Handgrip exercise at the 30% level of maximal voluntary contraction (MVC) for four minutes induced a significant increase in PRA in either normotensive or normal renin hypertensive patients, while the increase in PRA in normal renin hypertensive patients was significantly higher than that in normotensive patients. 3) Pretreatment with the administration of propranolol inhibited an increase in PRA after handgrip exercise in either normotensive or normal renin hypertensive patients. 4) The results suggest that isometric handgrip exercise can induce an augmentation in renin release mainly by stimulation of the sympathetic nervous system in either normotensive or normal renin hypertensive patients. The possible mechanism of the exaggerated response in PRA to handgrip exercise in normal renin hypertensive patients has been discussed.

The purpose of the present study was to investigate the effects of various types of treatment such as glibenclamide and insulin on plasma lipids and lipoprotein concentration in diabetics. Treatment of diabetes mellitus was reevaluated from the standpoint of high density lipoprotein (HDL) metabolism. Twenty-one diabetic patients (6 men and 15 women) who have been admitted in the hospital and kept on Japanese standard diet for diabetes mellitus, have been studied. Changes of plasma lipoprotein in diabetic patients were followed up before and after treatment with glibenclamide or insulin. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were decreased and HDL was increased with insulin treatment. However, glibenclamide induced a significant decrease in HDL- cholesterol (Ch). Relationship between triglyceride (TG)-rich lipoproteins and HDL metabolism was studied. A significant negative correlation was found between pretreatment VLDL-TG and changes of VLDL-TG with insulin treatment, indicating an accelerated catabolism of VLDL-TG with possible increase of triglyceride lipases. There was a significant negative correlation between VLDL-TG and HDL-Ch before insulin treatment, but not after treatment. There was no negative correlation between changes of VLDL-TG and changes of HDL-Ch with insulin therapy. These results indicate that an increment of HDL with insulin treatment can not be explained solely by increased HDL formation from TG-rich lipoprotein and that insulin might increase synthesis and secretion of HDL in liver and/or intestine.

The effect of acetaldehyde on the membrane potential and the membrane resistance of the guinea-pig taenia coli has been studied with an intracellular recording technique. Application of acetaldehyde in the concentration of between 5 and 20 mM produces reduction or elimination of the spontaneous spike activity and hyperpolarization of the membrane. The amplitude and the rates of rise and fall of the action potential are reduced by the drug. The duration of the spike is slightly prolonged. Acetaldehyde also reduces the amplitude of the evoked action potential produced by externally applied cathodal stimulation in twice hypertonic solution. Electronic potentials induced by anodal current are reduced both in size and time course by acetaldehyde during the stage of hyperpolarization.

In order to investigate the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (Captopril) in renin-independent essential hypertension (EHT), we studied the effects of the single administration of 100 mg captopril on plasma bradykinin levels by sensitive radioimmunoassay in 21 EHT, who showed agonistic responses to 1Sar, 8Ile-angiotensin II (A IIA). Fourteen of the patients were low renin and 7 were normal renin EHT. There was no correlation between the baseline plasma renin activity (PRA) and the fall in mean blood pressure (MBP) following captopril administration. When the patients were analyzed according to MBP response, the responders (R) showed a significantly greater bradykinin increment (delta BK, +64%) (p less than 0.05), whereas the nonresponders (NR) did not show such an increase. There was a positive correlation between delta BK and the MBP reduction after captopril in the R group (r = 0.623, p less than 0.05). Plasma aldosterone (PA) decreased profoundly in the R group (-36% from baseline, p less than 0.05). Pretreatment ACE activity was significantly higher in the R group than in the NR group (p less than 0.05). Pressor response to A IIA showed a significantly (p less than 0.05) greater response after captopril administration in the R group. There were no significant differences in blood concentration of captopril between the R and NR groups. The present results suggest that bradykinin may be involved in the hypotensive action of captopril in the EHT subgroup, where the renin-angiotensin system appears to play an inert role for the elevation of blood pressure.

The effects of acetaldehyde on monosynaptic reflexes were investigated in the cat spinal cord. Intravenous injection of lower doses of acetaldehyde (0.1-0.5 mg/kg) increased the amplitude of the ventral root monosynaptic reflex potentials elicited by the dorsal root stimulation; the amplitude was decreased at higher doses (1.0-10.0 mg/kg). Acetaldehyde hyperpolarized the motoneuron at lower and depolarized it at higher doses. In some cells, however, acetaldehyde induced an initial, brief depolarization and subsequent hyperpolarization. Depolarization increased with increasing the dose of acetaldehyde. Hyperpolarization was always associated with an increased amplitude of the monosynaptically-induced action potentials. Depolarization was accompanied by a decreased amplitude or block of the action potentials. During aldehyde-induced depolarization, antidromic action potentials were more severely depressed than orthodromic ones. The present results suggest that acetaldehyde acts predominantly on the motoneuron membrane resulting in hyperpolarization at relatively lower doses and in depolarization at higher doses.

Serum lipid levels of 10,977 normal Japanese subjects in 1980 were determined by a joint study of 14 institutions, specializing in lipid research, located in 9 districts of Japan. The data obtained were compared with those in 1960 and 1970. Total cholesterol (TC) levels in 1980 increased with age except for the 1st decade and reached maximum (205 mg/dl) at the 7th decade. The mean value in any age was higher than that of 20 years ago by 10-15 mg/dl. Triglyceride (TG) levels also increased with age and reached maximum (130 mg/dl) at the 7th decade. The mean values of subjects over the 5th decade were higher than those of 10 years ago by 10-20 mg/dl. In contrast with TC and TG, HDL-cholesterol levels were highest at the 1st decade and declined gradually with age. TC and TG levels of younger age (1st to 3rd decade) were equal to or even higher than those of Americans in 1972-76. It was concluded that serum lipid levels of Japanese have increased in the past 20 years and approached to the levels of Europeans and Americans.

To evaluate myocardial involvement in diabetes mellitus, we studied 39 patients with negative double-Master's test and without hypertension by exercise thallium-201 (T1-201) myocardial scintigraphy using a bicycle ergometer. Among the 39 patients, 12 (30.8%) showed filling defects in the scintigrams (positive cases), including eight with stress-induced defects and four with fixed defects. The positive cases had higher scores of diabetic complications (3.6 +/- 2.4 vs 2.1 +/- 1.8; p less than 0.05) and longer durations of diabetes as compared with those of the negative cases. The frequency of insulin therapy was also greater in the positive cases. Eleven patients (5 positive and 6 negative cases) who underwent cardiac catheterization had no significant stenotic lesions of their coronary arteries. However, all of the positive cases showed abnormal wall motion, mainly hypokinesis, by left ventriculography (LVG). The abnormalities of the LVG corresponded to the findings of the scintigrams (i.e. filling defects and decrease in washout ratios by circumferential profile analysis). These results suggest that in some diabetics myocardial involvement exists in the early stage without overt cardiac disease and exercise T1-201 scintigraphy is useful in detecting pre-clinical cardiomyopathy. Cardiomyopathy in diabetics seems to be due to disturbances of the myocardial microcirculation.

To clarify clinically the pathogenesis of septal hypertrophy in terms of its morphology and wall dynamics, simultaneous biventricular cineangiography (BVG) and endomyocardial biopsy of the left ventricle were performed for patients with left ventricular hypertrophy. The patients were categorized in four groups according to their clinical and BVG findings; 1) 24 normal control subjects (C), 2) 39 patients with hypertension and symmetrical septal hypertrophy (SH-HT), 3) 17 patients with hypertension and asymmetrical septal hypertrophy characterized by the ratio (IVS/PW) greater than or equal to 1.3 by BVG, and 4) 25 patients with hypertrophic cardiomyopathy (HCM). The BVG's configuration of the septum in SH-HT showed a normal form of septal hypertrophy (NH form) essentially similar to that of the control subjects (N form), except for septal thickness increases of more than 10 mm. In HCM, a triangle or shell (TS) form or spindle (S) form of the septum was demonstrated by BVG. The TS form was characterized by straight or convex thickening of the septum from its center to its base toward the left ventricle. The S form was characterized by convex thickening localized to the central part and a relatively thin base. However, the configuration in ASH-HT was either the NH form (7 cases) or the TS or S form (10 cases). The configuration in ASH-HT with the NH form was not distinguishable from that of SH-HT, nor was the configuration in ASH-HT with the TS or S form distinguishable from that of HCM. Systolic thickening (%) of the septum and systolic shortening (%) of the septal length decreased significantly in this order: C, SH-HT, ASH-HT with the NH form, and ASH-HT with the TS or S form. Those of HCM were similar to those of ASH-HT with the TS or S form. In the cases of the N or NH form, there was a negative correlation between systolic thickening (%) and thickness of the septum in diastole. In cases with the TS or S form, systolic thickening (%) was not affected by the thickness of the septum in diastole, and a lower value was observed in all cases. Histological studies of endomyocardial biopsies revealed a positive correlation between the transverse diameters of the myocytes and the total systemic peripheral resistance (TSPR) in 25 patients with SH-HT. In 12 patients with HCM, there was no correlation, and severe hypertrophy of the myocytes was observed despite a lower TSPR.(ABSTRACT TRUNCATED AT 400 WORDS)