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We report here a case of Sipple's syndrome, and we also analyze the relationship between the type of hypertension and urinary excretion of catecholamines in Sipple's syndrome based on the literature in Japan. One hundred and fourteen cases of Sipple's syndrome have been reported in Japan. The hypertension of patients with Sipple's syndrome shows a ratio of fitfull hypertension to continual hypertension of 6 to 1, whereas the ratio is 1 to 1.5 in patients whose pheochromocytoma is not accompanied by Sipple's syndrome. The patients with Sipple's syndrome, being pheochromocytoma can be classified into the adrenaline (U-AD) dominant type and noradrenaline (U-NA) dominant type based on the catecholamine excretion in the urine. The U-AD predominant (U-AD/U-NA greater than 0.4) patients mostly reveal fitfull hypertension, while patients with continual hypertension hardly show U-AD predominant.

The effect of intraperitoneal administration of heparin to patients on continuous ambulatory peritoneal dialysis (CAPD) remains obscure. We examined 8 patients on CAPD to investigate its effect. When 2.5 U/ml or 5 U/ml of heparin was given intraperitoneally, t1/2 of heparin activity in the dialysate was 0.5 to 2 hrs, and 6 hrs after administration its activity was 0.5 U/ml and 1.4 U/ml respectively. Whole blood clotting time was hardly affected because the transfer of heparin to the plasma was minimal. The plasma antithrombin III (AT -III) levels were comparable to patients on hemodialysis, but the AT-111level in the dialysate was only 1.5% of those in the plasma. We conclude that the intraperitoneal administration of heparin at these doses is effective in preventing fibrin precipitation when intraperitoneal AT -III levels are expected to be relatively increased such as at the start of CAPD or in the presence of peritonitis.

Serum from patients with membranoproliferative glomerulonephritis (MPGN) and acute poststreptococcal glomerulonephritis (APSGN) accelerated the decay of the cell bound C4b2a (C42) and C4b hemolytic activity relative to pooled normal human serum (pNHS) after 5 min incubation at 30 degrees C in EDTA-GVB. The accelerated decay of the C42 hemolytic activity was heat stable (56 degrees C 30 min) and was inhibited by monoclonal antibody against human C4 binding protein (MoAb:C4BP) or C4 binding protein (C4BP) depleted serum. C4 nephritic factor (C4NeF) was employed to stabilize the labile classical pathway C3 convertase C42 complex. Serum from patients with MPGN and APSGN reduced the C4NeF stabilizing activity. Sera from 32 of 46 patients with MPGN and all of 7 patients with APSGN reduced the C42 hemolytic activity relative to 50 normal human serum (NHS) after 5 min incubation at 30 degrees C in EDTA-GVB, and there was no relationship with the serum concentration of C4BP. In vivo, accelerated decay of C42 convertase might interfere with the clearing and processing mechanism of circulating immune complexes (IC) by reducing deposition of C3b on the IC lattice.

A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina. The thrombus was successfully treated with intravenous urokinase and heparin infusions, and there after, coronary angioplasty was performed without any complication.

We studied, prospectively, the predictive value of late potentials to cardiac sudden death and sustained ventricular tachycardias in 385 patients with myocardial infarction surviving over 4 weeks. Signal averaged electrocardiogram was performed over a 4 week period from the onset of acute myocardial infarction in all patients. Late potentials were observed in 118 of 385 patients. During the mean follow up period of 24.3 months, 17 patients had cardiac sudden death and 15 patients had symptomatic sustained ventricular tachycardias. In 16 of 17 patients with cardiac sudden death and 14 of 15 patients with sustained ventricular tachycardias, late potentials were observed. Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy of late potentials to cardiac sudden death in these 385 patients were 94.1%, 72.3%, 13.6%, 99.6% and 73.2% respectively. Also, these predictive values of late potentials to sustained ventricular tachycardias in the group of patients were 93.3%, 71.9%, 11.9%, 99.6% and 72.7%, respectively. We concluded that the clinical usefulness of late potentials in patients with myocardial infarction surviving over 4 weeks in the negative predictive value to cardiac sudden death and sustained ventricular tachycardias is superior to that of positive predictive value. Sensitivity of late potentials to these events is also higher.

The IgG fraction of serum from patients with membranoproliferative glomerulonephritis (MPGN) types I and II or partial lipodystrophy (PLD) was found to contain C3 nephritic factor (C3NeF) which reacts with the alternative pathway C3 convertase C3bBb and stabilizes it. Two types of C3NeF were detected, of which one was heat sensitive (56 degrees C for 30 min) and properdin dependent (C3NeF:P) but the other was heat stable and properdin independent (C3NeF:nP). C3NeF:P was found in sera from patients with MPGN types I and II and it displayed the properties of properdin and IgG. C3NeF:P was observed in patients with reduced serum concentrations of C3 and terminal complement components (TCC), and the generation of SC5b-9 complex was increased in mixtures with normal human serum. C3NeF:nP was found in sera from patients with MPGN type II and PLD, whose sera revealed a selective decrease in C3 concentrations.

It is known that membranoproliferative glomerulonephritis (MPGN), hypocomplementaemia and C3 nephritic factor (C3NeF) are closely related to each other, and the presence or absence of C3NeF in the serum is important for evaluating the nature of MPGN. However, some difficulties have been encountered in detecting this factor and therefore a new assay permitting the direct detection of C3NeF without purifying IgG from the patient's serum has been devised. Using this assay method, C3bBb-stabilizing activity was observed even in sera from MPGN patients who were non-hypocomplementaemic. Furthermore, among 98 cases with hypocomplementaemia. C3NeF was found to be absent in 66 cases.

A 29-year-old Japanese male with a 19-year history of subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) was referred to the Nephrology Service of the Nihon University Hospital for evaluation of edema and massive proteinuria. The renal biopsy disclosed minimal glomerular lesions. In this paper a case of nephrotic syndrome associated with eosinophilic lymphoid granuloma is reported.

IZUMI, Y., HONDA, M., HATANO, M. and KAWAHARA, Y. Influence of Food on the Clinical Effect of Angiotensin I Converting Enzyme Inhibitor (SQ 14, 225). Tohoku J. exp. Med., 1983, 139 (3), 279-286 -In order to clarify the influence of food on the clinical effect of angiotensin I converting enzyme inhibitor (SQ 14, 225, captopril), 25mg of the drug was administered to patients with hypertension using in a two-way crossover study design. In the first study (study I), each subject received the drug 30min after breakfast, and changes in blood pressure (BP), blood concentration of captopril (BCC), plasma renin activity (PRA), plasma aldosterone (PA) and plasma angiotensin I converting enzyme activity (ACE-A) were determined for 3 hr. BP was recorded for 6 hr. Four days after study I, the same subjects received the drug 2hr after breakfast, and each parameter was again determined (study II), similarly to study I. No significant difference in the hypotensive responses to captopril was observed between both studies during 6hr of observation. Maximum hypotensive effects were found within 90min of the treatments in study I and study II, and BP returned almost to baseline levels at 6 hr in both studies. Maximum BCC levels were found 60 and 90min after the drug administration in studies I and II, respectively, and these approximated to half of each maximum level at 180min. There were no statistically significant differences in the biological half-life (T1/2), maximum concentration (C max), maximum concentration time (T max), and area under the blood concentration curve [AUC]03 between both studies. The peak in PRA occurred at 60 and 90min after the administration of the drug in studies I and II, respectively. In study I, a slightly greater reduction of PA levels was found, but there was no significant difference in the magnitude of the reduction between both studies. The present results indicate that food did not exert any significant influence on the clinical effect of captopril.

Cell-mediated immunity (CMI) was evaluated in 26 patients with lipoid nephrosis (LN), 50 patients suffering from chronic diffuse proliferative glomerulonephritis (CGN) without renal sufficiency and 24 healthy controls. The following parameters were measured: delayed hypersensitivity skin test responses to purified protein derivative (PPD) and candida, circulating lymphocytes. T lymphocytes and T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) or IgM (Tmu cells). Patients with LN in relapse had less mean induration of skin reactivity and a smaller proportion reacting to both antigens as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in patients with LN in remission and CGN were similar to those of the control subjects. It was also found that the LN patients in relapse had a significant T lymphocytopenia as well as a significant decrease in absolute numbers of Tmu and T gamma cells, whereas the patients with LN in remission and CGN did not differ significantly from the control population. Thus, the majority of patients with LN in relapse demonstrated an impaired response in a CMI assay system. The disturbed CMI may be secondary to hypoproteinemia and other nutritional factors induced by the nephrotic syndrome.

In order to systematically analyze the regulation and metabolism of steroid hormones in a case of primary aldosteronism with multiple lesions, including adenoma and nodular hyperplasia of the left adrenal gland, the amounts of 9 steroids (progesterone (P), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH-B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone (17-OH-P), 11-deoxycortisol (S), cortisol (F) and dehydroepiandrosterone sulfate (DHEAS)) contained in the plasma and in the adrenal tissues were measured. The patient (a 39-year-old female) was admitted to our hospital because of hypokalemia and hypertension. A diagnosis of primary aldosteronism was made on the basis of a complete evaluation, and an adenoma (1.8 x 1.2 cm), a nodular hyperplasia (0.5 x 0.5 cm), a microadenoma and a cortical nodule were found on the left adrenal gland. In vivo studies revealed that the plasma level of Aldo was high, but those of the other steroid hormones were within the normal range. After ACTH infusion, the plasma levels of the 9 steroid hormones increased by 2 to 17 times the base levels. In particular, the responses of DOC and B were markedly high. In vitro studies on P, DOC, B, Aldo and F content in the adenoma (A), the nodular hyperplasia (A'), the adjacent adrenal tissue (C) and the right normal adrenal tissue (D) revealed that, except for F, they were highest in A, followed by A', D and C in that order. In incubation studies with ACTH using A and C, it was found that the levels of 8 steroid hormones with the exception of DHEAS were high in A than in C. In particular, the response of B in A was markedly increased. These findings suggest that aldosteronoma produces 8 steroid hormones under conditions of excess ACTH, while at physiological levels of ACTH, it produces only Aldo in excess.

Forty-eight patients with a variety of primary renal diseases and systemic lupus erythematosus (SLE) were examined for the proportion of circulating T lymphocytes bearing receptors for IgM (T mu cells) or IgG (T gamma cells). Although the control group showed strikingly similar mean values for both T mu and T gamma cells, the whole group of patients with primary renal diseases and SLE showed a wide scatter of values. Sixteen patients with primary renal diseases and SLE had higher proportions of T gamma cells than the control group, whereas seven patients with chronic glomerulonephritis (CGN), membranoproliferative glomerulonephritis (MPGN), lipoid nephrosis (LN), and SLE showed very marked decrease in the proportions of T gamma cells in the peripheral blood. On the other hand, six out of the total group of patients had low proportions of T mu cells in the peripheral blood. However, no consistent relationship between the proportion of T mu and T gamma cells was found in our study. These findings indicate that there exists a heterogeneity of T-lymphocyte subpopulation distribution in some patients with primary renal diseases and SLE. The possible significance of these phenomena in the pathophysiology of renal diseases is discussed.

The effects of somatostatin on plasma renin activity (PRA) and blood pressure were evaluated in patients with essential hypertension (EH) and in normotensive subjects. All subjects examined were hospitalized and placed on a diet containing 7-8 g/day sodium chloride and received an intravenous infusion of somatostatin (500 microgram/20 ml of saline, for 60 min) in the basal condition. During somatostatin infusion, the mean blood pressure (MBP) remained unaffected in all patients with EH and the normotensive subjects, while the PRA decreased slightly in the EH group. When the patients with EH were classified according to their renin levels (low, normal and high), parallel significant decreases in MBP and PRA were found only in the high renin group during the somatostatin infusion. No significant change in MBP and PRA was observed in the other groups including the normotensive subjects. To assess the activity of synthetic somatostatin, the plasma levels of growth hormone (GH) and cyclic AMP were measured. These levels were lowered significantly during the infusion and the GH levels showed a rebound 15 min after cessation of the infusion. The cyclic AMP returned to the basal levels, but no rebound was observed. The above data indicate that the fall in blood pressure in the high renin group in the basal condition was probably due in part to reduced renin release by somatostatin, and the maintenance of high blood pressure especially in high renin EH.

Alterations in the concentration of plasma dehydroepiandrosterone sulfate (DHEA-S) and cortisol in patients with essential hypertension (EH) were investigated. The subjects were 25 patients with EH: 7 of low plasma renin activity (PRA) group, 10 of normal PRA group and 8 of high PRA group; 7 normal subjects were used as the controls. Plasma DHEA-S and cortisol were measured before and after the following tests: (1) circadian rhythm (6:00, 16:00 and 24:00), (2) furosemide (0.7 mg/kg) test, (3) ACTH (12.5 IU/4 hr) infusion test, (4) dexamethasone (1.0 mg) test, (5) furosemide (0.7 mg/kg) test under dexamethasone (1.0 mg) treatment, (6) metopirone (1.5 g) test, (7) angiotensin II (8 ng/kg/min, 30 min) infusion test and (8) saline (1000 ml/hr) test. The alterations of the endogenous ACTH-adrenal hormone system as well as the renin-angiotensin-aldosterone system induced by these tests did not cause significant changes of plasma levels of DHEA-S in the 3 groups with EH. However, significant enhancement of plasma DHEA-S was observed after both the administration of exogenous ACTH and angiotensin II. It is considered that the responsiveness of DHEA-S to ACTH may increase in the low and normal PRA groups and that the responsiveness of DHEA-S to angiotensin II may increase in the high PRA group. Based on these results, it is suggested that plasma DHEA-S hardly or only partially participates as a causal factor of EH.

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in suppressor cell activity, we studied concanavalin A (Con A)-induced suppressor cell activity (SCA) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The levels of Con A-induced SCA were decreased in patients with LN compared with those in normal controls and those in CGN patients and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the mean responses of Con A-induced SCA in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.

症例は21才男性.減量を目的に6カ月間に約50kg体重を減少させ,全身倦怠感,意識消失発作を来したため入院となった.入院時,心電図上心拍数36回/分の洞性徐脈を認め,心エコーでは心膜液貯留を認めた.また頭部CTスキャンでは脳萎縮を認めた.血液検査では甲状腺機能検査においてlow T3 syndromeを呈し,さらに経過中, GH値の高値,一過性のGOT, GPT値の上昇等を認めた.本症例は著しい体重減少をきたしているものの,入院時,標準体重を示していることから,我国における神経性食欲不振症の診断基準にあてはまらないが,臨床経過等を総括すると,多彩な臨床症状を呈した神経性食欲不振症の男性例と考えられた.

A simplified screening test for differentiating primary aldosteronism (PA) from low renin essential hypertension (LREH) is presented. Nine patients with LREH and 5 patients with PA due to adrenal adenoma were studied. In the patients with LREH, the levels of plasma renin activity (PRA) before and after treatment with furosemide (0.7 mg/kg, i.v.) and a 2-hour ambulation under treatment with dexamethasone (1.0 mg) (dexamethasone + furosemide test) increased briskly, compared to the levels of PRA before and after treatment with furosemide (0.7 mg/kg, i.v.) and a 2-hour ambulation (furosemide test). In patients with PA, there was no significant difference between the mean levels before the furosemide test and before the dexamethasone + furosemide test, or between the mean levels after the furosemide test and after the dexamethasone + furosemide test. These results suggest that the suppression of PRA in patients with LREH may be related to a factor controlled by dexamethasone. It is concluded that the dexamethasone + furosemide test is useful for differentiating PA due to adenoma from LREH.

The T-colony-forming capacity was examined in 13 normal subjects and 8 patients with biopsy-proven focal glomerular sclerosis (FGS). Fifteen patients with chronic mesangial proliferative glomerulone-phritis (CGN) without renal insufficiency were studied as a disease control. The two main assays used were the counting of T colonies formed by the patients’ lymphocytes, and the measurement of T-colony-forming activity in conditioned medium from cultures of patients’ lymphocytes. The levels of T-colony-forming cells (TCFC) and T-colony-stimulating factor (TCSF) were decreased in patients with FGS compared with those in normal controls and lower in FGS patients with the nephrotic syndrome (NS) than in those without NS. In contrast, these parameters in CGN patients with or without NS did not differ from normal subjects. TCSF activity for TCFC in both normal individuals and FGS patients was removed from media conditioned by phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PHA-LCM) with interleukin-2 (IL-2) receptor bearing cultured T cells. These in vitro findings suggest that IL-2 is the essential factor contained in PHA-LCM. Thus, depressed TCFC in FGS ptients with NS may result in part from impaired generation of TCSF by lymphocytes.

In this study, the effects of angiotensin II (A II, Asn-Arg-Val-Tyr-Val-His-Pro-Phe) and angiotensin III (A III, Arg-Val-Tyr-Ile-His-Pro-Phe) on blood pressure (B.P.), pulse rate, several hormones [plasma renin activity (PRA), plasma aldosterone (PA), ACTH, plasma cortisol (PC), urinary catecholamines and urinary aldosterone] and urinary electrolytes were investigated in 9 male patients with essential hypertension [mean age 36.2 +/- 4.1 (S.E.) years]. A II and A III infusions (8 ng/kg/min, 60 min) were started from 0900 h and blood samples were drawn before, at 15, 30, 45, 60 min after the beginning of the infusions, and at 15 min after their cessation. Urinary samples were collected within 2 hrs before and after the infusions, respectively. A II significantly increased B.P.(p less than 0.01) during the infusions, whereas A III did not increase B.P.. PRA significantly decreased after the infusions of A II and A III (p less than 0.05), but the potency of A II was significantly greater than that of A III (p less than 0.01). PA was increased after both infusions, but in response to A III, a peak was observed at 30 min after the infusion and subsequently, the levels decreased gradually. Significant differences between both responses were found at 45 and 60 min (p less than 0.05) after the infusions. ACTH was unchanged during the infusions, but PC was equipotentially suppressed during the infusions, with the suppression of A II being similar to that of A III. In the responses of urinary catecholamines, noradrenaline and dopamine were equipotentially decreased after the infusions (p less than 0.05). The results of the present study clearly indicate that several differences exist between the biological activities of A II and those of A III. Further systematic experimental studies are needed to resolve the details.

Recently many studies have been done to identify complement pathway activation in renal tissue from patients with renal disease. We examined whether tissues obtained by renal biopsy from such patients would fix guinea pig complement. Nine out of 15 patients with systemic lupus erythematosus (SLE), 4 out of 7 patients with mesangiocapillary glomerulonephritis (MCGN), and 2 out of 7 cases with acute glomerulonephritis (AGN) fixed guinea pig C3. We found that tissues from 5 out of 9 guinea pig C3-positive SLE cases fixed guinea pig C4, while none of the guinea pig C3-positive tissues from patients with MCGN or AGN fixed guinea pig C4. These guinea pig C3-positive renal tissues were further studied for interaction with C4-deficient guinea pig serum, EDTA guinea pig serum, heated guinea pig serum, and EGTA Mg2+ guinea pig serum. The results indicated that activation of both the alternate and classical complement pathways occurred with tissues from patients with SLE, while activation of the alternate pathway occurred with MCGN and AGN. Results for tissues from AGN and MCGN patients indicated the presence of C3 convertase and protease which interacted with guinea pig C3.

The effects of dibutyryladenosine 3', 5'-monophosphate (DBcAMP), a nucleotide analogue, on blood pressure, serum electrolytes and plasma corticoid concentrations were investigated in 10 normotensive healthy subjects who received a constant diet containing 5-8 g sodium chloride in hospital. The systolic blood pressure did not change after infusion of 0.25 or 0.33 mg/kg/min of DBcAMP for 20 min. On the other hand, the diastolic blood pressure was significantly decreased after the infusion of DBcAMP. The levels of serum sodium and potassium were significantly decreased after the infusion of DBcAMP. After infusion of 0.25 mg/kg/min of DBcAMP for 20 min, the changes in plasma levels of 6 corticoids [progesterone, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC), corticosterone, cortisol and dehydroepiandrosterone sulfate (DHEA-S] revealed no significant changes. After infusion of 0.33 mg/kg/min of DBcAMP for 20 min, the plasma levels of cortisol, corticosterone and 18-OH-DOC were significantly increased and the changes in plasma levels of aldosterone showed a tendency to increase but this was not significant. The plasma levels of DOC and DHEA-S were not appreciably changed, while the plasma levels of progesterone were significantly decreased after the infusion of 0.33 mg/kg/min of DBcAMP. It is speculated therefore that DBcAMP may act to enhance the activity of the sodium-potassium pump and to promote steroid biosynthesis dose-dependently in humans.

Cell-mediated immunity (CMI) was studied in 28 patients with biopsy-proven lipoid nephrosis (LN). The LN patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by impaired delayed hypersensitivity skin reactivity to purified protein derivative (PPD), depressed local graft-versus-host reaction (GVHR), decreased proportion of T lymphocytes and diminished lymphocyte transformation to phytohemagglutinin (PHA). Concanavalin A (Con A)-induced suppressor cell activity (SCA) was found to be significantly increased in LN patients with NS compared to that in normal individuals. In contrast, the mean levels of CMI and SCA studied in LN patients in remission and in patients with chronic mesangial proliferative glomerulonephritis (CGN) did not differ from normal subjects. Our findings support the notion that at least in some LN patients with the NS, activated suppressor cells are present and possibly account for their decreased CMI.

We investigated the recognition of late potentials in patients with and without organic heart diseases and spontaneous ventricular arrhythmias. None of the normal subjects had late potentials and patients with ventricular arrhythmias but no organic heart diseases, also had no late potentials as well as patients with idiopathic ventricular tachycardias. Late potentials in patients with idiopathic cardiomyopathy were noted more frequently in the dilated type than in the hypertrophic type, especially in those with high grades of ventricular arrhythmias. Patients with old myocardial infarctions had a higher rate of late potentials recognition in cases of sudden death or ventricular tachycardias. On the other hand, we observed lower rates in patients during early stage of acute myocardial infarction in spite of the evidence of a higher rate of ventricular electrical instability. There was no association between ejection fractions, wall motion scores and late potentials. However, a higher recognition of late potentials was found in patients with inferior or posterior myocardial infarction and ventricular aneurysm. We concluded that the late potential must be evaluated in each of the different groups of organic heart diseases in order to estimate the clinical value of ventricular arrhythmias.

The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.

A unique factor causing breakdown of the third component of complement (C3) was detected in a patient with acute glomerulonephritis (AGN). The activity was detected by conversion of C3 in a mixture with normal human serum using crossed immunoelectrophoresis. This factor capable of C3 breakdown was not blocked in the presence of ethylenediaminetetraacetic acid (EDTA), heat-pretreatment (56 degrees C, 30 min) und dialysis against 0.1 M phenylmethylsulfonyl fluoride (PMSF). The factor was isolated and characterized by immunochemical and physicochemical techniques. It had beta-mobility on electrophoresis and was separated at a lighter sedimentation coefficient than 7S by sucrose density gradient ultracentrifugation. The activity was absorbed on a DEAE-cellulose column and was eluted under definite conditions of relative salt concentration. These data appear to suggest that this factor is distinct from C3 nephritic factor (C3NeF), immunoglobulins, immune complexes, and other C3 convertases previously described. Moreover, it is clear that the factor was mainly responsible for the C3 activation observed in the patient with acute glomerulonephritis.

持続性低補体を示し,腎生検にて診断された膜性増殖性糸球体腎炎3例について,長期経過を観察し得,補体活性化の面より検討し,興味ある事実を認めた. 3例の内1例は,尿所見異常は軽度のままで低補体は必ずしも疾患の活動性と一致しないことが考えられた.血清C3値は全例著明な低値を認めているが,他の成分の変動はそれぞれ異なる傾向を示していた. C3分解因子は3例すべてに認められ, C3NeFは1例のみに認められ,他の2例はC3NeFとは異なる補体活性化因子と考えられた. MPGNにおける低補体の原因は一元的にC3NeFによるとは考えられず,多様な機序の存在が示唆された.

Suppressor cell activity (SCA) was analyzed in 8 patients with focal glomerular sclerosis (FGS) and 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the FGS patients with nephrotic syndrome (NS) had significantly increased levels of suppression index when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from FGS patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of FGS patients with NS demonstrated an alteration in Con A-induced SCA. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

A case report of a 32-year-old male with renovascular hypertension, suspected to be pheochromocytoma as a result of a tentative diagnosis, is given. The suspicion was based on the observation of high levels of urinary noradrenaline on several occasions with the sign of hyperreninemia. Reduction of the urinary noradrenaline levels by the administration of angiotensin converting enzyme inhibitor (SQ-14225) suggested that the high urinary noradrenaline probably resulted from hyperreninemia which reflected high plasma levels of angiotensin II. Radioisotope renography and intravenous urography strongly suggested a reduction of the right renal blood flow, and the final diagnosis of renovascular hypertension was obtained on the basis of renal arteriography. On the other hand, the possibility of a catecholamine releasing tumor was carefully excluded by angiography before undertaking surgical treatment. The affected kidney was transplanted autogenously into the abdominal cavity. The successful operation led to a decrease in plasma renin activity, blood pressure and urinary noradrenaline excretion. In the present case, we were thus unable to define at first whether the primary genesis of hypertension was related to the hyperactivity of the reninangiotensin system caused by renovascular stenosis or a noradrenaline releasing tumor.

In order to investigate the role of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in essential hypertension (EH), the responses of plasma 17-OH-DOC to 7 stimulation tests (furosemide test, adrenal suppression test, angiotensin II infusion test, adrenal stimulation test, metopirone test, saline infusion test and potassium chloride infusion test) and the circadian rhythm were investigated in 18 patients with essential hypertension (low renin group: 8, and normal renin group: 10). From the present study, it micht be thought that plasma 18-OH-DOC does not play an important role in the suppression of PRA in patients with low PRA.

Cell-mediated immunity (CMI) was evaluated in 11 patients with idiopathic membranous nephropathy (MN), 50 patients suffering from chronic proliferative glomerulonephritis (CGN) without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative (PPD), circulating lymphocytes, lymphocyte cell-surface markers (En and EAC rosettes) and functional markers (mitogenic responses to Con A and PHA). The MN patients with nephrotic syndrome (NS) had less mean induration of skin reactivity and a smaller proportion reacting to the PPD antigen as compared with the control subjects. In contrast, the intensity of skin reactivity and the frequency of negative reactions in MN patients in remission and CGN were similar to those of the control subjects. During the nephrotic stage of MN the proportion of T lymphocytes decreased with simultaneous increase of the proportion of B lymphocytes. It was also found that the MN patients with NS showed impaired lymphocyte reactivity with lower Con A and PHA responses compared to the normal controls. Conversely, the mean mitogenic responses to the antigens in patients with MN in remission and CGN were similar to those of the control subjects. Thus, the majority of MN patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Various doses (5 mg, 12.5 mg and 25 mg) of angiotensin I converting enzyme inhibitor (SQ 14,255, captopril) were administered to 8 patients with essential hypertension on a three-crossover study design, and the time course of mean blood pressure (MBP), plasma renin activity (PRA), plasma angiotensin converting enzyme activity (ACE-A), plasma cortisol (PC) and plasma aldosterone (PA) were determined following administration of the drug. MBP fell in a dose dependent manner, and PRA showed a minor but significant increases in cases receiving 5 and 12.5 mg of the drug. A large and significant increase in PRA was observed following 25 mg of captopril. ACE-A was also reduced in a dose dependent manner. There was no difference between changes in PC at any of the three dose levels. The serum potassium concentration was determined before and 3 hr after 25 mg of captopril treatment and no significant change was observed. In spite of the dose dependent and theoretical changes in the above parameters, lowered responses of PA to each dose of the drug were shown in reverse order against an increasing dose. That is to say, the grade of fall in PA following 25 of captopril was smaller than that following the other doses of the drug, and 5 mg induced a greater decrease in PA than 12.5 mg. Based on these findings, the relatively high dose of captopril in the present study was apparently more effective in increasing some factors which suppressed reduction of PA by a fall in angiotensin II than a low dose of the drug.

Cell-mediated immunity (CMI) was evaluated in 8 patients with focal glomerular sclerosis (FGS), 50 patients suffering from chronic mesangial proliferative glomerulonephritis without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative, circulating lymphocytes, lymphocyte cell-surface markers (neuraminidase-treated sheep erythrocyte and erythrocyte-antibody-complement rosettes) and functional markers (mitogenic responses to concanavalin A and phytohemagglutinin). The FGS patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by decreased responses of the lymphocytes to both concanavalin A and phytohemagglutinin, impaired delayed hypersensitivity to purified protein derivative and a decreased proportion of T lymphocytes as compared with normal subjects. In contrast, the levels of all CMI parameters studied in FGS patients in remission and in patients with chronic glomerulonephritis with or without NS did not differ from normal subjects. Thus, the majority of FGS patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Cell-mediated immunity (CMI) was evaluated in 76 patients with renal disease by summation of delayed cutaneous hypersensitivity (DHS) responses to 4 test antigens, purified protein derivative (PPD), Candida, mumps and keyhole limpet hemocyanin (KLH). Patients with lipoid nephrosis (LN) in the nephrotic stage had less mean induration of skin reactivity and a smaller proportion reacting to the former 3 antigens as compared with normal controls or LN patients without the nephrotic syndrome (NS). In contrast, the intensity of skin reactivity and the frequency of negative reactions in LN patients in remission and chronic mesangial proliferative glomerulonephritis (CGN) were similar to those of the control subjects. Immune response to KLH was also impaired in LN patients with the NS as measured by skin testing. The data indicate an impaired DHS in LN and suggest that the impairment relates to the clinical stage of disease.

The time courses of mean blood pressure (MBP), plasma renin activity (PRA), plasma aldosterone (PA), serum prostaglandin E (PGE), serum angiotensin I converting enzyme (ACE), and blood levels of angiotensin I converting enzyme inhibitor (SQ 14,225) (captopril) were studied in 6 patients with essential hypertension (5 men and 1 woman, aged 44 +/- 5.6 (mean +/- S.E.) years) before and 30, 60, 120 and 180 min after administration of 25 mg captopril. MBP and ACE began to fall within 30 min and reached a significant minimum between 60 and 180 min after captopril administration. PRA was significantly increased 60 min after captopril administration and continued for 180 min. On the other hand, PA had begun to fall significantly 180 min after captopril administration. The blood levels of captopril were significantly increased 30 min after captopril administration, with a peak at 120 min. The levels at 180 min were half the peak. The levels of PGE were not significantly changed within 180 min after captopril administration. These results suggest a discrepancy between the changes in MBP and the blood levels of captopril. The blood pressure lowering effect may be due to inhibition of angiotensin II (Ang. II) during the short-acting effect, and due to decrease of PA, metabolites of captopril, increase of kinin in the blood, inhibition of the slow pressor effect of Ang. II, increases of other depressor hormones such as prostacyclin and other depressor mechanisms during the long-acting effect.

Leukocyte adherence inhibition (LAI) test was examined in 35 patients with renal diseases and 14 normal controls, using collagenase-treated glomerular basement membrane, glycosidase-treated glomerular basement membrane and renal tubular epithelium as antigens. Although the control group showed strikingly similar mean LAI indices for all antigens tested, the whole group of patients with renal diseases showed a wide scatter of values. Two categories of patients had significantly increased LAI indices (p less than 0.01) when their mean values were compared with those of normal controls: (1) rapidly progressive glomerulonephritis (RPGN) and (2) lupus nephritis (SLE). In the serial studies of the RPGN and SLE cases, there were no significant changes in the pattern of LAI and they continued to give positive and very comparable results when re-examined at intervals of 1-6 months. Out of the 30 patients who were able to be evaluated with the three antigens, 15 cases exhibited positive LAI response to two or more antigens simultaneously. These in vitro findings suggest that there is an abnormal cellular response to certain antigen or widespread LAI reactivity to a variety of renal antigens in certain forms of human glomerulonephritis.