Anionic sites on the glomerular basement membrane (GBM) in human glomerulonephritis were investigated in relation to the permeability of GBM and the morphological change by an electronmicroscope using polyehtyleneimine (PEI) as a cationic probe. Biopsy materials were obtained from the following patients with several glomerulonephritides lipoid nephrosis, membranous nephropathy, IgA nephropathy, purpura nephritis, and SLE. Control materials were obtained from intact parts of the kidney from one patient with clear cell carcinoma and benign recurrent hematuria without proteinuriaR Small tissue blocks were immersed in 0.5% PEI solution to demonstrate the anionic sites. In control materials, PEI stained particles were localized in the lamina rara externa with regular intervals and in lamina rara interna and epithelial cell surface with irregular distribution. These anionic sites disappeared completely in lipoid nephrosis with heavy proteinuria and high selectivity index. After remission by steroid administration, PEI stained particles were appeared again in GBMR In the early stage of membranous nephropathy, PEI stained particles were reduced in number and size and not seen beeath the subepithelial deposits. However in the late stage of membranous nephropathy, anionic sites became apparent around the newly formed lamina densa. In other glomerulon -ephritides with heavy proteinuria and low selectivity index, PEI stained anionicsites were reduced in number and size, or partially disappeared in GBM. These results suggest that alterations of anionic sites on the GBM play an important role in proteinuria and tissue damage in human glomerulonephritides.

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To investigate the relationship of urinary excretion of kallikrein and prostaglandin to plasma vasopressive substances, twenty-four-hour urine in 5 normal subjects were collected under the conditions of normal sodium diet, low sodium diet and low sodium diet plus spironolactone (SP), including every-two-hour urine and peripheral blood both at recumbency and at upright posture. Besides urinary excretion of sodium, kallikrein (UKa1V), prostaglandin E₂ (UPGE₂V) and F (UPGFV), plasma levels of renin activity, aldosterone (PAC), and norepinephrine (PNEC) were also measured. Consequently UKa1V increased under the condition of low sodium diet and decreased by the admistration of SP, while UPGE₂V increased with the enhencement of sodium deficiency, but UPGFV did not show any marked change. UKa1V, UPGE₂V and UPGFV increased under the three-different sodium status at upright posture. From the correlation between these results and the plasma vasopressive substances, it was suggested that UKa1V was related to the effective concentration of PAC and slightly to that of PNEC, while UPGE₂V was related to renin-angiotensin system to some extent but not to PNEC. The production process of PGF seemed to be different from that of PGE₂.

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Hypertension is known to have an adverse effect on the impairment in renal function. In this report, the effects of hypertension on acute renal failure (ARF) were studied. ARF was induced by intramuscular injection of glycerol to spontaneously hypertensive rat (SHR) and Wistar Kyoto rat (WKY). Systemic hemodynamics were measured by the microsphere technique and blood chemistory was analyzed, and the relation between systemic hemodynamics and ARF was examined. As for systemic hemodynamics 10 hours after glycerol injection, blood pressure, cardiac output, renal blood flow and total hepatic blood flow significantly decreased in the SHR group compared to the WKY group. Blood chemistry also indicated that HUN, serum creatinine, GOT and GPT levels gradually increased significantly in the SHR group compared to the WKY group. The above results indicated that in glycerol-induced ARF, the changes in systemic hemodynamics, especially the decreases in renal and hepatic blood flows, correlated with the progress of ARF, and that hypertension was one of the factors that adversely affected ARF.

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In 52 patients with essential hypertension (18 men and 34 women), lipoperoxides (LPX), total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C) in serum as well as renin activity (PRA) and aldosterone concentration (PAC) in plasma were evaluated in comparison with those in normotensive controls (12 men and 8 women). The mean values (±S. D.) of LPX was significantly higher in hypertensives than in controls as a group (3.93±1.49 vs 3.13±0.60 nmol/ml, p<0, 05), In hypertensives, the LPX levels were significantly higher in those with advanced arteriosclerotic ocular change (Scheie grade III) than in those with the mild change (Scheie grade I) (5.07±0.74 vs 3.43±1.25 nmol/ml, p<0.01). In hypertensives, the LPX was positively correlated with TC (r=0.581, p<0.001) and TG (r=0.518, p<0.001), while the LPX did not correlated with PRA and PAC in both hypertensives and controls. These data suggest that the occurrence and development of arteriosclerosis in essential hypertensives is related to LPX excess, independently of fluctuation of renin-aldosterone system. Hyperlipidemia may play some role in excess production of LPX through increased levels of unsaturated fatty acids presumably derived from TC and TG. It is likely that LPX is practically useful as a risk index for arteriosclerosis in patients with essential hypertension.

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The present study showed the plasma renin substrate concentration (PRS) of various diseases, i, e. essential hypertension, hyperaldosteronism, Cushing's syndrom, isolated ACTH deficiency syndrom, liver cirrhosis and nephrotis. For the next experiment, the effects of various medicine were examined, i. e. furosemide or captopril were administered to the essential hypertensive patients and methylprednisolon was infused to the nephrotic patients with edema. In some of the normotensive subjects, sodium was restiricted and after that sodium was loaded, PRS was measured in before and after these procedures. PRS values were 4144.2±201.5 ng/ml (n=20) in normal subjects and 3720.3±156.6 ng/ml (n=21) in essential hypertensive patients. These values were no significant difference. Primary aldosteronism showed the normal value. On the other hand, PRS levels of Cushing's syndrome were over 5000 ng/ml and these values were decreased after an adrenalectomye The values of liver cirrhosis (2094.6±455.5 ng/ml) were almost half of the normal values. The patients of isolated ACTH deficiency syndrome also showed low level. PRS level of nephrotic syndrome was low but this value was increased with the improvement of an edema. Both acute and chronic administrations of captopril led the PRS level to decline, but these values recovered abruptly after cessation of the medicine. The sodium load caused the PRS level to increase and the plasma renin activity (PRA) to decrease. On the other hand, the increase of sodium excretion due to furosemide responded with the decreased PRS and the increased PRA. By the infusion of methyl-prednisolon 1000 mg for the puls treatment in nephrotic syndrome, the PRS was increased significantly but the PRA was decreased. Although there were no significant differences of the PRS level between normal subjects and hypertensive patients, this value was decreased significantly in the patients of liver cirrhosis. By the administration of a medicine or sodium, the PRS level changed to the opposite direction in the PRA.

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The autonomic function was evaluated in 18 hypotensives (HP), 22 normotensives (NT) and 16 hypertensives (HT) patients on longterm hemodialysis (HD) and compared with 8 with Shy-Drayger syndrome (SDS), etc. The interbeat interval response to Valsalva maneuver (Vm) was significantly lower in HP than NT (p<0 .01) or HT (p<0.001) and was similar to those of SDS (n, s.).Overshoot in arterial pressure after Vm was positive in HP 8.3%, NT 71.4%, HT 100% and SDS 0%. Among HD patients, HP showed the most serious baroreflex arc dysfunction. However, the response to cold pressor test in HD patients was as same as those of SDS and controls . Clonidine test demonstrated depressor response in HP. Although, the decrease of SBP (p<0 .01) and DBP (p<0, 02) during orthostasis was smaller in HP than SDS, no change of heart rate was observed between HP and SDS. Thus, the afferent or efferent limbs and central sympathetic activity appeared to be intact. Although the decrease of pressor response to angiotensin II independent of PRA levels in HP, the response to norepinephrine (NE) was related to plasma NE levels. Furthermore, motor nerve conduction velocity was delayed in HP in comparison with NT and HT Administration of midodrine raised SBP from 91.0±7.6 to 110.0±27.2 mmHg and DBP from 51.613.4 to 61.8±19.6 mmHg. The results suggest the abnormalities in baroreflex arc and vascular wall contractility with peripheral neuropathy. Therefore, we conclude that, although the sites remained to be clarified, HP show the autonomic disorders and that midodrine seems to be effective on such patients.

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A quantitative analysis of atherosclerosis was made by measuring the aortic pulse wave velocity (PWV) in 346 chronic hemodialysed patients (male 208, female 106). In addition, the findings of ocular fundus and the degree of roentogenologically observed aortic calcification were assessed to estimate the usefulness of this method. There were fairly good correlation between PWV and findings of ocular fundus, and between the f ormer and the degree of aortic calcification. There was an excellent correlation between PWV and the age of patients, whereas there was no correlation' between PWV and the duration of hemodialysis, From these results, the measurement of PWV was considered to be useful to estimate the degree of atherosclerosis and quantitatively. Furthermore, we supposed that atherosclerosis was not accelerated by the hem dialysis alone. Twenty cases of the 346 (5.8%) died during observation . And 11 deaths out of the 20 (55%) were due to cardio-vascular accidens (mean duration of hemodialysis : 56.9±19.7 months, PWV: 12.0±2.8 m/sec) and 9 (45%) due to other causesr (mean duration of hemodialysis 58.6±20.4 months, PWV: 8.0±2.1 m/sec). There was-a, a significant difference in PWV between the two groups (p<0 .005). From these results, f it was supposed possible to estimate the prognosis of hemodialysed patients by this methods. In conclusion, PWV measurement was considered to be a useful and noninvasive method not only to evaluate but also to follow the degree of atherosclerosis.

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The effect of captopril, i. e. ACI for renal handling of uric acid was studied. How ever, no significant changes were noted in the blood pressure, serum uric acid (S_UA), creatinine, Na and Cl levels when captopril in a single dose of 75 mg was orally administered to 10 healthy male adults. On the other hand, a significant rise was recognized in Ccr, C_UA, U_UAV and U_NaV and UcjV levels after captopril administration. An appreciable rise was also noted in the U_UA/Ccr and C_UA/Ccr levels at their peaks 3-6 hours after administration. Captopril in a daily dose of 37.5 mg was orally administered to 15 patients with essential hypertension and gout for a period of 12 weeks. Captopril alone was given to 8 of these patients (a group given captopril alone) and captopril combined with other antihypertensive drugs were given to 7 (a combined group). As a result, a significant decrease of the blood pressure was noted in both groups in the 4th week of administration, and this therapeutic effect lasted for 12 weeks. Although the S_UA level showed a significant decrease in the 4th week in the group given captopril alone, and this effect lasted for 8 weeks. It tended to increase, on the contrary, in the comobined group for 12 weeks. The Ccr, C_UA and U_UAV levels showed an increase in the group given captopril alone, which tended, however, to decrease in the combined group. Nonetheless, the U_UAV/Ccr and C_UA/Ccr levels increased in both groups while being given the above dose. Particularly, a significant rise was noted in the U_UAV/Ccr level in the group given captopril alone.

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A 43-year old male patient with chronic renal failure was ref ered to our hospital complaining of dyspnea and bloody sputa on He had been receiving hemoR dialysis therapy for seven months. After admission he was diagnosed as having congestive heart failure and treated with the extracorporeal ultrafiltration method and digitalis, but this treatment did not prove effective. We examined the effects of various kinds of vasodilating agents by monitoring the patient's diastolic pulmonary arterial pressure. Sodium nitroprusside reduced diastolic pulmonary arterial pressure and markedly improved the patient's symptoms. Captopril caused a decrease in diastolic pulmonary arterial pressure and markedly improved the patient's symptoms of congestive heart failure, but produced leukopenia (2100/mm³) on the 5th day of administration. Enalapril was also effective in reducing symptoms and signs of congestive heart failure, but induced liver dysfunction. Delapril, however, improved the patient's clinical symptoms, decreased pulmonary arterial pressure and produced no untoward adverse reactions. We found delapril to be a useful agent in treating congestive heart failure in this patients, with no untoward effects.

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To elucidate the characteristics of cardiac function of the hemodialysis (HD) patients, M, mode echocardiography was performed in 32 HD patients (Group A; consisting of 21 males and 11 females, aged 47±9) within 13-24 hours after HD undertaken for 3-4 hours a day and 3 times a week Eighteen normals (Group B; 14 males and 4 females, aged 42±11) were served as control, Fractional shortening of LV internal dimension (%δD) and mean LV circumferential fiber shortening (mVcf) were employed as LV systolic function, while peak filling rate (PFR) obtained from the derivative of LV dimension curve and the time from endsystole to PFR (TPFR) were used as LV diastolic function. LV wall thickness (WT), LV volume and LV mass were also calculated. Furthermore, the HD patients were subdivided into two groups according to PFR; Group AA (followed by abnormal diastolic function, consisting of 11 males and 5 females, aged 49±5) and Group AB (followed by the normal one, 10 males and 6 females, aged 45±10). There were no significant differences of age, heart rate, blood pressure or LV volume between Group A and Group Be No significant difference was also observed in LV systolic function (%δD and mVcf) between the two groups, while significant differences were demonstrated in LV diastolic function, PFR was significantly decreased (p<0.001) and TPFR was contrarily prolonged significantly (p<0.01) in Group A. PFR was correlated significantly with WT (γ=-0.64, p<O.01) and LV mass (γ=-0.72, p<0.01), respectively. In the HD patients, blood pressure was tended to raise, WT and LV mass were significantly increased to 24±5 mm and 312±95g, respectively, in Group AA as compared with those of 20±3 mm and 249±65 g, respectively, in Group AB, although there were no differences in HD history or laboratory data before HD between the two groups. In conclusion, LV diastolic function was initially deteriorated simplier than LV systolic function together with the increase of WT, LV mass and blood pressure in the HD patients. It is, therefore, conceivable that echocardiography is useful for earlier detection of LV impairement in the HD patients.

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Twenty patients with tuberculosis were identified over a 11 year period in a group of 409 patients undergoing maintenance hemodialysis. Eight were definite cases and the other were indefinite cases. The incidence of tuberculosis was 4.9% in our study. In definite cases, four of 8 cases had extrapulmonary lesions. This data revealed remarkably high frequency of extrapulmonary tuberculosis in patients undergoing mainten ance hemodialysis. The most common symptom was fever, and many patients presented with general symptoms such as fatigue and anorexia. Many cases presented leukocytosis with shift to left, accelerated erythrocyte sedi mentation rate and positive C reactive protein test, which suggested acute bacterial infection. Most patients responded well to antituberculous chemotherapy using isoniazid, rifampicin, streptomycin and ethambutol, and the outcome was favorable them. The diagnosis of tuberm culosis in dialysis patients was difficult because the symptoms were nonspecific, there were more frequent extrapulmonary involvements and tubercle bacilli were rarely isolated from dialysis patients. But, if the diagnosis of tuberculosis is highly suggestive, even without bacteriologic confirmation, a therapeutic trial of antituberculosis drugs should be given.

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In order to clarify the substantial differences between premalignant and malignant hypertension, we investigated the histories of hypertension and renal function in 23 patients with essential hypertension of grade III hypertensive retinopathy (K-W criteria) and 16 patients of grade IV retinopathy. Between the groups, there were no differences in the age (33 vs. 34 years) and blood pressure (BP) (190/117 vs. 186/107 mmHg) when hypertension was first noticed. The duration of hypertension (11 vs. 12 years), the age (47 vs. 44 years) and renal function (serum creatinine 4.7 vs. 5.1 mg/dl) at the onset of (pre) malignant hypertension were also not significantly different. The number of patients who had been under antihypertensive drug treatments was significantly greater in group III (8/23, 35%) than in group IV (1/16, 6%). Systolic BP (229 vs. 246 mmHg, P<0.05) and diastolic BP (141 vs. 150 mmHg, P<0.1) at the onset of (pre) malignant hypertension tended to be higher in group IV than in group III. Systolic and diastolic BP and renal function at the discharge of the hospital were not different between the two groups. It is concluded that BP at admission was more elevated in group IV (malignant hypertension) but the renal function had been already decreased in group III to the same extent as in group IV.

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Parapelvic renal cyst is almost asymptomatic, so clinical case is rare. But recently the incidence of this disease is increasing, because computerized tomography has come into wide use. We reported 6 cases of parapelvic renal cyst. None of them had symptoms originated from this disease, All cases were discovered by chance at the auxilliary examination of renal stone, hematuria or other disease. In all cases DIP showed SOL at the renal hilus with or without hydronephrosis, being finally diagnosed by computerized tomography. For treatment, in one case unroofing of the cyst wall and in 5 cases ultrasound-guided aspiration and 95% ethanol instillation therapy were performed. Postoperative DIP no longer showed SOL at the renal hilus and no recurrence was observed. Ultrasound-guided aspiration and 95% ethanol instillation therapy is useful for parapelvic renal cyst as in the case of simple renal cyst.

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The 24-hr urinary excretions of adrenaline, noradrenaline and dopamine in free, conjugated and total forms were measured and the relationship among each variables were examined in patients with essential hypertension who had mild blood pressure elevation. There was a positive correlation between a given pair of the urinary excretions of the 3 catecholamines in a free, conjugated or total form. Especially, the urinary excretions of the 3 free catecholamines were well correlated with each other. Furthermore, the urinary excretion of each catecholamine in a total form was significantly correlated with that of the respective free catecholamine and highly correlated with that of the respective bound form, while the urinary excretion of each free catecholamine was inversely correlated with its conjugation ratio. These results suggest that the urinary excretions of 3 catecholamines are intimately correlated with each other, and that the amount of each catechom famine in a bound form, which is excreted into urine, changes in parallel closely to that of the catecholamine releases However, further studies are needed to clarify whether a mechanism other than nonspecific conjugation is involved in the conversion of urinary catecholamines from a free to a bound form.

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The in vivo effect of PTH on 24, 25-dihydroxyvitamin D₃ [24, 25(OH)₂D₃] production was examined in vitamin D-deficient thyroparathyroidectomized (TPTX) rats by an in vivo assay measuring the accumulation of metabolites in plasma 5 hours after injection of tritiated 25-hydroxyvitamin D₃[25(OH) [³H]D₃]. Infusion for 20 hours of either human PTH-(1-34) or cAMP (except at 250 nmol/h) did not significantly change the plasma levels of calcium and phospholus compared with those in TPTX rats given 125 ng 1α, 25-diydroxyvitamin D₃[1α, 25 (OH)₂D₃] to stimulate the 24, 25(OH)D₃ production, On the other hand, human PTHm (1-34) markedly inhibited the 24, 25 (OH)₂D₃ production and stimulated the 1α, 25(OH)₂D₃ production. The effective concentration of human PTH-(1-34) was much lower for inhibiting the 24, 25 (OH)₂D₃ production than that for stimulating the 1α, 25 (OH)₂D₃ production, Infusion of less than 100 nmol/h cAMP similarly inhibited the 24, 25(OH)₂D₃ production without enhancing the 1α, 25(OH)₂D₃ production. Either theophylline (1μmol/h) or a submaximal dose (25 pmol/h) of human PTH- (1-34) alone inhibited the 24, 25(OH)₂D₃ production only slightly, but the concomitant infusion of both chemicals markedly inhibited the 24, 25(OH)₂D₃ production without stimulat or ing the 1α, 25(OH)₂D₃ production, The present study clearly indicates that besides its well known action in stimulating the 1α, 25(OH)₂D₃ production, PTH inhibits the 24, 25(OH)₂D₃ production by a mechanism involving cAMP into in vivo study with mammalian.

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