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Liver biopsy samples from 40 chronic alcoholic patients, including 9 with minimal changes of the liver, 6 with mild hepatic fibrosis, 14 with moderate fibrosis, and 11 with severe fibrosis (cirrhosis) were studied by electron microscopy to assess fibrogenesis in the Disse space and the role of fat-storing cells in this process. In the Disse space of normal liver, collagen fibers are few, and while lipid droplets containing fat-storing cells exist, their rough endoplasmic reticulum (RER) is inconspicuous. In the course of progressive hepatic fibrosis, collagen in the Disse space increased. This was significantly associated with gradual development of RER in fat-storing cells, confirmed by morphometric analysis. It is likely, therefore, that the development of RER in the fat-storing cells is a morphological correlative of their activated fibrogenesis and transformation into fibroblasts. To further clarify this, the rate of collagen synthesis was measured by the method of in vitro incorporation of [3H]proline into collagen in 17 liver biopsy samples from alcoholic patients and compared with the degree of morphological changes of RER in fat-storing cells. In liver samples with well-developed RER in fat-storing cells, a significantly higher rate of collagen synthesis was observed. These results suggest that in alcoholic liver injury, fat-storing cells may play an important role in Disse space fibrogenesis.

Amrinone induced similar degrees of relaxation in human mesenteric arteries and veins contracted with KCl, but exerted a more potent vasodilator effect in canine mesenteric veins than in arteries. Dibutyryl cAMP had a stronger effect on KCl-induced contraction in canine mesenteric veins than in arteries. These results suggest that amrinone promotes a different vasodilating action in human and canine mesenteric vessels, possibly via different sensitivity to cAMP in each vascular smooth muscle.

The effect of platelets on the development of immune complex glomerulonephritis (GN) was examined using bovine serum albumin (BSA) GN with platelet depletion. To clarify the role of platelets in the initial stage of BSA GN, thrombocytopenia was induced before BSA infusion. In 18 New Zealand white rabbits, BSA was intravenously injected twice after the presensitization. Eight of these BSA GN rabbits were injected daily with goat anti-rabbit platelet antiserum to induce thrombocytopenia, and platelet counts were maintained below 5 x 10(4)/microliters throughout the experiment. In the thrombocytopenic group, the degree of proteinuria was significantly decreased compared to the control group. Glomerular polymorphonuclear leukocyte infiltration, mononuclear cell proliferation, exudation and glomerular enlargement were significantly suppressed in the thrombocytopenic group. The results suggest that platelets may be quite important in the initiation and development of immune complex GN.

Tuberculosis associated with dialysis was studied at the Renal Unit of the Tokyo Medical and Dental University and Yokosuka Mutual Aid Hospital Kidney Center, in both of which the treatments of chronic renal failure are the same. There were 12 tuberculosis patients out of 367 patients on maintenance hemodialysis from January 1967 to December 1976, an incidence of 3.3%. This was 6–16 times greater than that in the general population of this country according to yearly statistics. The characteristics of dialysis-associated tuberculosis include a high incidence of miliary tuberculosis, especially in aged patients and difficulty in establishing the diagnosis before death. Clinical features which are helpful in the early diagnosis are intermittent high fever of unknown origin, weight loss, anorexia, abnormalities of the central nervous system, erythrocyte sedimentation rate over 100 mm/h, leukocytosis and high value of the C-reactive protein. With the increasing number of dialysis patients, an increase of dialysis-associated tuberculosis is expected and this will be one of the major problems of dialysis patients in future.

飲酒歴毎日3合以上でかつ10年間以上服用している肝障害20例について,各種抗原を添加してLMTを施行した.その結果エタノール単独添加では20例中7例,エタノールと同種肝両者添加では19例中6例,同種肝単独添加では15例中5例,精製HB抗原添加では19例中7例が陽性であった.エタノール単独添加およびエタノールと同種肝両者添加のいずれか,あるいはともにLMTが陽性であった10例では,全例肝機能検査成績は異常値を示し,5例は1日1升以上の多飲者であり,肝組織像では4例は亜小葉性肝硬変であった.HB抗原陽性の大酒家の肝障害5例では,全例HB抗原添加によりLMT陽性を示したが,エタノール添加によりLMT陽性を示したものは2例にすぎなかった.以上の成績より,いわゆるアルコール性肝障害の進展機序に一部の症例ではエタノールおよび精製HB抗原が細胞性免疫の形で関与する可能性があると推測された.

A case of bilateral cortical necrosis (BCN) was reported because of her abnormal platelet count and aggregability. She was 26 years old primipara.In her past history, at the age of 11, she was operated because of papillary adenocarcinoma of the thyroid gland, when no abnormal bleeding was reported.After cesarean section, atonic hemorrhage occurred and anuria developed. Because BCN was suspected heparin and urokinase therapy were started (later, patchy BCN was verified by renal biopsy). Uremia was controlled by hemodialysis (3/week). Platelet count (Plt.) increased gradually to normal level within a week. After heparin cessation, Plt. continued to increase and exceeded 60×104/mm3. In spite of thrombocytosis, bleeding time (BT) was prolonged to more than 15 min. On 31st hospital day when Plt. was 40×104/mm3and BT more than 15 min., platelet aggregability was investigated by screen filtration pressure (SFP) method (normal range: 264.9±14.3mmHg when induced by 3μM ADP). Her aggregability was no more than 20mmHg. On 34th hospital day, she was attacked by generalized convulsion and tracheotomy was done. Despite 17 units of blood transfusion bleeding was not discontinued. Therfore, 6 units of packed platelet were transfused and bleeding was dramatically stopped within 2 hours. After this episode, BT was normalized while thrombocytosis persisted. On 59th hospital day when Plt. showed 48.1×104/mm3 and BT was 3.5min., platelet aggregability was investigated by SEP method and optical density (O. D.) method. Using SFP method 3μM ADP induced aggregability was 400mmHg. By O. D. method, 10μM ADP induced maximum aggregability (ADP max) was 32.8% (normal 70.2±2.6), 1μg/ml adrenaline induced maximum aggregability (adrenaline max) 90.8% (normal 40.6±4.0), and 1mg/ml collagen induded maximum aggregability (collagen max) 69.6% (normal 74.8±5.6), respectively.She discharged on 14th hospital day, when her creatinine clearance was 17L/day, BUN 31mg/dl, and creatinine 3.3mg/dl, and conservative management was indicated. On 178 th day after BCN, when Plt. revealed 27.6×104/mm3 and was 3min., platelet aggregability was investigated again. Using SFP method, 3μM ADP induced aggregability was 390mmHg, while by O. D. method, ADP max was 63.2%, adrenalin max 98.5%, and collagen max 82.4%, respectively.Throughout her clinical course, fibrin degradation products were 40μg/ml or less, fibrinogen 370-900mg/dl, and euglobulin lysis time 24 hours or more. CB-PC and cephalothin, which were administered when platelet aggregability decreased, were investigated in vitro by O. D. method, with no effect to platelet aggregability being found.

To assess a possible direct tubular action of alpha-human atrial natriuretic peptide (alpha-hANP), we studied the effects of alpha-hANP on volume reabsorption (JV), transepithelial voltage (VT), and p-aminohippuric acid (PAH) secretion in the rabbit proximal straight tubules (PST) by in vitro microperfusion technique. In superficial PST (SFPST), addition of alpha-hANP at various concentrations (10(-7), 10(-9), 10(-11) M) to the bath solution did not alter JV significantly. Bath alpha-hANP (10(-7) M) did not change VT in SFPST, either. In juxtamedullary PST (JMPST), addition of alpha-hANP (10(-7) M) to the bath solution changed neither VT nor JV significantly. The alpha-hANP (10(-7) M) in the luminal fluid caused no changes in either VT or JV in SFPST. Furthermore, alpha-hANP (10(-7) M) in the bath did not change the rate of PAH secretion in SFPST. Thus, we could not obtain any evidence for direct tubular action of alpha-hANP in rabbit PST. Accordingly, alpha-hANP may increase solute excretion without directly affecting solutes transport in PST of the rabbit kidney.

In order to evaluate the usefulness of the peripheral lymphocyte culture method for the diagnosis of drug-induced liver injury, a study was carried out on 21 cases of drug-induced liver injury (Group A). Nine cases in Group A showed a positive lymphocyte stimulation test. Out of 9 cases which showed positive stimulation six cases were cholestatic type of liver injury, and the remaining three were of hepatitic type. The results suggest that peripheral lymphocyte culture method is a useful method for diagnosis of drug-induced liver injury.

Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows: Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rapidly. In contrast, many cases of the adult type were able to be maintained under good control and the renal lesion neither developed nor progressed. Two of the adult type diabetics with poor control showed slowly and slightly progressing renal lesions. The progression of glomerular lesions was significantly related to the control of blood glucose, type of diabetes, age at onset, type of treatment, and degree of obesity, but not to the duration of diabetes or the length of the follow-up period. There was a significant correlation between the type of diabetes and the control of blood glucose over the years. Arteriolar lesions developed concurrently with the progression of the glomerular lesion. Retinopathy also had a tendency to develop in proportion to the progress of glomerular lesions although it was not statistically significant. We have discussed the clinical factors responsible for the progression of diabetic glomerulosclerosis and have suggested that the type of diabetes rather than the degree of control of blood glucose might be more important in determining the development and progression of diabetic glomerulosclerosis. Nevertheless, the possibility remains that successful control of blood glucose may prevent or retard the development of diabetic glomerulosclerosis.

A 51-year-old woman with primary biliary cirrhosis developed distal renal tubular acidosis and hypouricemia (1.4 mg per 100 ml) in the course of hepatic injury. Her renal clearance of uric acid reached 33.7 ml/min (mean +/- SD in five normal age-matched women: 9.2 +/- 3.1 ml/min). Pyrazinamide, an inhibitor of uric acid secretion, considerably reduced the uric acid clearance, while it was not enhanced by probenecid, a blocker of uric acid reabsorption. Thus, the hypouricemia may have been due to a defect of postsecretory reabsorption of uric acid in the renal tubules. The present case emphasizes the significance of hypouricemia and hyperuricosuria as indicators of renal tubular injury in primary biliary cirrhosis.

Microangiographic evaluation of the effects of heparin on progressive Masugi nephritis. Unilateral progressive Masugi nephritis was produced in rabbits and studied by microangiography as well as light and immunofluorescence microscopy. The following five groups were studied: Group 1. Heparin was started simultaneously with nephrotoxic serum (NTS) and was given for one week. The animals were then sacrificed along with the untreated controls. Group 2. This was the same protocol as in group 1 but with three weeks' heparin. Group 3. Heparin was started one day after NTS and was given for three weeks. Group 4. Heparin was started one to two weeks after NTS and was given for three weeks. Group 5: late effect group. Heparin was started simultaneously with NTS, was given for four weeks, and the animals then were sacrificed 10 to 13 weeks later. Heparin dose was 5,000 U, s.c., per day in all treated groups. The number of glomeruli seen per unit of cortex by microangiography was significantly increased in the first through the third groups, as compared to the controls. Group 1 did not show this increase but there was some decrease of immunofluorescent fibrinogen. The late effect group (group 5) showed no modification by the treatment, suggesting that an initial improvement may have been negated by persistent immunologic insults after heparin withdrawal. Evaluation microangiographique des effets de l'heparine sur la nephrite progressive de Masugi. Une nephrite unilaterale de Masugi a ete produite chez des lapins et etudiee par microangiographie et par microscopie photonique et immunofluorescence. Les cinq groupes suivants ont ete etudies: 1) groupe simultane une semaine, l'heparine est commencee en meme temps que le serum nephrotoxique (NTS) et administree pendant une semaine, 2) groupe simultane trois semaines, semblable a groupe 1, mais l'administration d'heparine dure trois semaines, 3) groupe un jour, l'heparine est commencee un jour apres NTS, et administree pendant trois semaines, 4) groupe une semaine, l'heparine est commencee une a deux semaines apres NTS et administree pendant trois semaines, 5) groupe des effets tardifs, l'heparine est commencee en meme temps que NTS, donnee pendant 4 semaines, les animaux sont sacrifies 10 a 13 semaines plus tard. La dose d'heparine est de 5,000 U, s.c., par jour dans tous les groupes traites. Le nombre de glomerules vus par unite de cortex en microangiographie est significativement augmente dans le premier et le troisieme groupe par comparaison avec les controles. Le groupe une semaine n'a pas une telle augmentation, mais on observe une diminution de la fluorescence du fibrinogene. Le groupe des effets tardifs n'est pas modifie par le traitement, ce qui suggere que l'amelioration initiale peut avoir ete effacee par la persistance du processus immunologique apres l'arret de l'heparine.

Since glucagon and insulin (G/I) have been suggested to be hepatotrophic substances, the effect of G/I infusion on the ability to excrete water and sodium was tested in seven patients with cirrhosis and ascites (decompensated group), and compared with that in seven cirrhotics without ascites (compensated group). A constant infusion of 1 U glucagon and 10 U regular insulin over 2 hours daily for 14 days resulted in a significant improvement of prothrombin time in the decompensated group. Concomitantly, an increase in urine volume (62%, p less than 0.02) and a tendency toward an increase in urinary sodium excretion (68%, 0.05 less than p less than 0.1) were observed only in the decompensated group after the G/I infusion. In addition, these were associated with increases in creatinine clearance and osmotic clearance. These results suggest that glucagon and insulin merit further study in hepatorenal syndrome cases.

Generation of pH gradient across the rabbit collecting duct segments perfused in vitro . Ability of pH gradient generation was examined in three segments of rabbit collecting duct, cortical collecting duct (CCD), outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD). These segments were perfused in vitro, and the steady–state luminal pH in stop–flow condition (pH s ) and the electrochemical potential difference of H + (E H ) were determined using double-barreled liquid membrane pH microelectrode punctured into the lumen. In CCD, pH s was 7.71 ± 0.08 in normal rabbits, 7.72 ± 0.08 in DOCA-treated rabbits and 7.27 ± 0.05 in starved rabbits, while peritubular fluid was kept at pH 7.5. E H (positive value means H + accumulation in the lumen above electrochemical equilibrium) was -15.3 ± 5.2, -31.3 ± 3.7 and 10.3 ± 3.1 mV, respectively. Peritubular acidification (peritubular pH 6.8) by reducing HC0 3 - concentration decreased pH s , but increased its negativity of E H in all groups. In OMCD pH s was 6.57 ± 0.08 in normal, 6.58 ± 0.11 in DOCA-treated and 6.47 ± 0.12 in starved animals. E H was 54.5 ± 4.6, 57.7 ± 6.8 and 64.2 ± 6.9 mV, respectively. Peritubular acidification lowered pH s further, 5.51 ± 0.07, 5.67 ± 0.16 and 5.41 ± 0.19, respectively. E H was enhanced in all groups. In IMCD pH s was 7.36 ± 0.04 with E H being 6.8 ± 2.9 mV, and peritubular acidification did not generate pH gradient. These data suggest that the generation of a steep acid pH gradient is mainly due to OMCD. Luminal alkalinization predominated in CCD except in starved rabbits. IMCD did not generate appreciable pH gradient. The acid pH gradient in OMCD was enhanced by acute bath pH reduction, but not affected by chronic metabolic acidosis or mineralocorticoid pretreatment. Thus rabbit collecting ducts have distinct axial heterogeneity in the formation of pH gradient.

Clinical and experimental studies were carried out in order to evaluate the role of myocardial dysfunction in the genesis of circulatory congestion associated with renal failure. Among the patients with chronic renal failure, those with circulatory congestion had greater blood volume and higher venous pressure while lower cardiac index and stroke work index than those without circulatory congestion. After peritoneal dialysis, although blood volume and venous pressure decreased in both groups, cardiac index increased in the former while it decreased in the latter group. In 15 dogs, acute renal failure was produced by ligating both ureters. As uremia developed, blood volume and left ventricular end-diastolic pressure increased with or without an increase in cardiac index. The depression of ventricular function curve was evident in all the dogs. The peritoneal dialysis performed at this stage resulted in a prompt recovery of left ventricular end-diastolic pressure with minimum change in cardiac index. The measurement of dp/dt/IIT also indicated a depression of myocardial contractility at uremic stage and its recovery after dialysis. We conclude that impairment of myocardial function is implicated in the development of circulatory congestion in renal failure.

A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.

Susceptibility of unipolar AAI pacemakers to myopotential inhibition (MPI) was assessed in 10 patients by provocative maneuvers and 24-hour Holter monitoring, and compared to that of unipolar VVI pacemakers in 12 patients. Five maneuvers were performed for each of four different sensitivity levels, and an MPI score of from 0-4 points was given according to the lowest sensitivity level at which MPI was provoked. The MPI score in patients with AAI pacemakers was significantly lower than that in patients with VVI pacemakers, 1.60 +/- 1.26 vs 2.83 +/- 1.03 (p less than 0.05). On Holter monitoring, no MPI was detected in any of the patients with AAI pacemakers, whereas myopotential inhibition was detected in 5/12 patients (42%) with VVI pacemakers. Intracardiac electrograms were of lower amplitudes for AAI pacing than for VVI pacing, 3.13 +/- 1.83 mV vs 11.20 +/- 5.95 mV (p less than 0.01). Although the amplitude of atrial signals was lower than that of ventricular signals, the AAI pacemakers were less susceptible to MPI than were the VVI pacemakers. However, when MPI occurs in AAI pacing, it may be more difficult to correct without undersensing because of the lower amplitude of the intracardiac signals.

目的: 再使用ダイアライザーによる透析中の白血球・補体系の経時的変化を観察し, 初回使用時との比較を通じて, 白血球減少への補体系の関与と, それに対する膜表面の血液成分による被覆の効果を検討した.対象と方法: 6名の透析患者を対象とし, セルロース膜を用いたダイアライザーによる連続する2回の透析において, 初回を新しいダイアライザー, 次回を再使用として, この連続する2回の透析を1クールとし, 計7クールを行なった. 再使用の手技は初回透析後4u/mlヘパリン化生理食塩液2000mlにて洗浄, 冷蔵保存とし, 次回透析に使用した. 各透析ごとにヘマトクリット, 白血球数, CH 50, C 3, C 4を測定した.結果: 白血球減少は初回では最初の15分で65.9±8.9 (M±SD)%と高度の低下をみたが, 再使用時は47.7±16.6%の低下にとどまり, 減少率の差はクリアランス変化を用いた面積補正を行なっても有意であった. 補体系は, 初回では, 最初の15分にCH 50, C 3に有意の低下を認めたが, 再使用では有意の低下はみられなかった. 白血球減少率と補体各成分の減少率の間には, 初回および再使用を通じ, 有意の相関は認められなかった.考察とまとめ: ダイアライザーの再使用により, 白血球減少と補体活性化の程度を軽減させることが可能であった. 血液成分による膜面の被覆が, 血液・透析膜間の相互作用に変化を与えたものと考えられた. セルロース膜を人工臓器材料として用いる場合の生体適合性の示標と考えられているこれら2つの反応は, 適切な膜面処理により防止しうるものと考えられた. また, 補体活性化は白血球減少の一部であることを示唆する.

B型劇症肝炎(感染源不明)の回復期に,黄疸を伴うSGPTの再上昇がみとめられ,非A・非B型急性肝炎が併発したと考えられた21歳女性例を報告した.B型劇症肝炎の極期(昏睡IV度の時期)には,血中免疫複合体と血中HBs抗原・抗体免疫複合体(ともにRaji細胞法)の出現をみとめたが,SGPTの再上昇の際には前者しか検出されず,また,HBs抗原のcpm値の再上昇もみとめられなかった.肝組織像では,B型劇症肝炎による昏睡出現後8日目の肝生検では,肝細胞の壊死はみとめられず,広汎性の肝細胞の水腫様腫大をみとめたのに比し,SGPTの再上昇時の肝生検では,亜小葉性の肝実質の脱落と肝実質内に著明な炎症細胞浸潤をみとめた.SGPTの再上昇の原因は,劇症肝炎の際に施行した輸血による非A・非B型急性肝炎と考えられた.

The mechanism of lowered renin-aldosterone system was investigated in 17 patients with diabetic nephropathy (serum Cr less than 3 mg/100 ml) with concomitant control of the blood sugar level. The response of plasma renin activity (PRA) to upright stimulation was lower in the low renin group (group I) than in the normal to high renin group (group II) and in the control group. The PRA response to theophylline was delayed in group I. The percentage of the luminal area of the arteriole in the biopsy specimens was larger in group I and the control group than in group II. Plasma aldosterone concentration (PAC) was not increased by angiotensin II in group I. Low PRA in diabetic nephropathy with slightly to moderately impaired renal function may not be due to hyaline destruction of the arteriolar walls, but to other factors such as sympathetic nervous dysfunction. The adrenal responses of PAC to angiotensin II may also be impaired.

17 adult-onset nephrotic patients with minimal-change glomerular lesions experienced 39 relapses in all. The relationship between the remission period t (expressed in months) preceding each relapse and the rate of relapse (relapse rate) F (t) was proven to correspond closely to Weibull's distribution function as follows (chi 2 = 1.72, 0.5 less than p less than 0.75): In In (formula - see text) From the equation, the time when 99% of relapsing patients have relapsed is 39.3 months. This means that adult-relapsing nephrotic patients with minimal-change lesions will experience a relapse within 39.3 months of remission. They should be free from relapse and considered cured with a 99% reliability when remission has continued longer than 39.3 months, i.e. beyond the 'period of freedom from relapse'.

It has been reported that agents which block the prostaglandin system inhibit the development of glomerulonephritis. However, the mechanisms of these effects are not clear. We studied the effect of a selective thromboxane A2 (TXA2) synthetase inhibitor, 1-benzylimidazole (BIm), on the immune complex glomerulonephritis produced by bovine serum albumin (BSA) in New Zealand white rabbits. As the BSA nephritis developed, there was no change of creatinine (Cr), serum urea nitrogen (SUN), or creatinine clearance (Ccr), but urinary protein excretion increased almost 3-fold. Coagulation and fibrinolytic studies suggested a hypercoagulable state and increased fibrinolytic activity. Platelet aggregation showed the reduction of maximum aggregation induced by ADP and collagen. Histological examination by light microscopy, immunofiuorescence, and electron microscopy revealed glomerular polymorphonuclear leukocyte (PMN) infiltration, mononuclear cell (MON) proliferation, and fibrin deposition. In 70% of the rabbits, IgG and C3 deposits were seen by immunofluorescene mainly in mesangial areas. The administration of BIm to BSA nephritis had no effects on Cr, SUN or Ccr, but it significantly lessened the proteinuria. The study of coagulation and fibrinolytic activity suggested a less hypercoagulable state, and more efficient fibrinolysis occurred than in the group without BIm. BIm tended to normalize platelet aggregation. It also lessened the histological PMN infiltration (p 2 may play an important pathogenetic role in the development and progression of glomerulonephritis.

1日3合以上,10年以上の常習飲酒者37名(非肝疾患群13例,アルコール性肝障害群7例,アルコール性肝硬変群17例)を対象として,免疫遺伝学的見地からアルコール性肝障害の発生しやすい個体が存在するか否かを検討し,次の結論を得た.1) アルコール摂取量が30g/kg体重/日×年未満のアルコール性肝硬変少量飲酒群ではHLA-B12の表現型を示す頻度が高い傾向がみられた.2) HLA-B12表現型陽性のアルコール性肝硬変では,陰性群に比し,RA因子の出現率が高い傾向がみられた.3) アルコール性肝硬変少量飲酒群では,比較的大量飲酒群に比べ,RA因子の出現率が有意に高頻度にみられた.4) しかしながら,症例数が少ないため,アルコール性肝硬変が比較的少量の飲酒によって生じた群でも,肝硬変の発生にHLAで表現される遺伝学的素因が関与したとは明確にこしえなかった.

急性肝炎の予後不良例とくに早期死亡例の早期鑑別を目的として,rapid turnover serum proteinを明らかな肝性昏睡や消化管出血のみられる前に測定した.その結果血中半減期が1ないし2日間ときわめて短いprealbumin値は亜急性肝炎の死亡例,生存例ともに著減し差はみられなかった.しかし半減期4ないし5日間のα2-HS-glycoprotein値は死亡例と生存例で有意の差がみられ,かつ重なりもほとんどみられなかった.以上よりα2-HS-glycoproteinの測定は早期死亡例の鑑別に有用であると考えられた.

飲酒歴のみられない慢性肝障害36例(A群),大酒家の肝障害19例(B群)について,エタノールおよび精製HBsAg添加して白血球遊走阻止試験を行なった.エタノール添加によりLMT陽性を示したものは,36例中16例であり,とくにHBsAg陽性の慢性肝炎活動型,小葉改築傾向を伴う慢性肝炎活動型,非代償性肝硬変では陽性率は高値を示した.B群では19例中11例がLMT陽性を示し,亜小葉性肝硬変では4例全例がLMT陽性であった.大酒家の肝障害では,HBsAg陽性群の方が,陰性群より,精製HBsAg添加によりLMT陽性を示す症例が多くみられたが,肝病変の進展度にしたがって高値をとるとはいえなかった.以上の成績より,飲酒歴の著明でない活動性の強い慢性肝障害および大酒家の肝障害の一部の症例では,エタノール,精製HBsAgに対する細胞性免疫異常状態が成立しているものと推測されたが,病因論的については,今後の検討が必要である.

症例は32才,女性.昭和54年1月より出現した筋肉痛・筋力低下と,手の典型的なGottron徴候を主訴として入院した.血清の筋原性酵素活性の軽度の上昇と,皮膚・筋生検の所見より皮膚筋炎と診断し, prednisoloneの投与を開始した.しかし入院第12病日より胸部X線像でびまん性の浸潤影を呈したのをきつかけに筋肉痛が増強し,筋原性酵素が著明に増加した.第15病日より急性腎不全とDICを合併し,第23病日に肺出血のため発病より全経過2カ月余りで死亡した.剖検の組織学的検索では,著明な筋線維の変性と壊死が認められた.また腎では軽度の尿細管の変性と顆粒状円柱の尿細管内への沈着を認め,イエウサギの特異抗体を用いた直接および間接法蛍光染色にて,ミオグロビンの尿細管上皮への沈着と尿細管内の円柱への沈着を認めた.従来皮膚筋炎は慢性の経過をとる症例が大部分で,急性の経過をとる症例はきわめて少ない.実際本症例のように,筋原性酵素の著明な上昇と筋の急激な変性と壊死が認められるような激症型の皮膚筋炎は,内外の文献上でも数例の報告があるのみである.また本症例の急性腎不全に関与したと考えられるミオグロビンが,腎組織中で証明された症例は本邦では極めて希である.従つて本症例は皮膚筋炎が激症の経過をとつたこと,および急性腎不全の成因にミオグロビンが関与したことの2点について,貴重な症例と考えられる.

In liver cirrhosis, an associated defect in urinary acidification is well known but its pathophysiologic nature is not well defined. Recent studies suggest that the urine Pco2 during maximal alkalinization of the urine is an adequate index of distal hydrogen ion secretion. To evaluate the nature of distal renal tubular acidosis (distal RTA) in cirrhosis, the urine minus blood Pco2 gradient [(U – B)Pco2] in alkaline urine was determined in four patients with cirrhosis and distal RTA, and compared with that in four patients without distal RTA (control subjects), as well as with that in one patient with Sjogren's syndrome and distal RTA (subject with impaired distal acidification). As expected, the (U – B)Pco2 after sodium bicarbonate loading was low (10.6 mmHg) in the subjects with impaired distal acidification and normal (32.5 mmHg, s.e.m. = 4.8) in control subjects. By contrast, all four patients with cirrhosis and distal RTA were able to achieve a normal (U – B)Pco2 gradient (33.8 mmHg, s.e.m. = 4.0) after sodium bicarbonate loading, even in the presence of the defect in urinary acidification under acid loading. These results suggest that the pathophysiology of the urinary acidification defect in liver cirrhosis is distinct from that in ordinary distal RTA; the latter signifies a defect in H+ secretion (secretory or voltage-dependent RTA), whereas, in cirrhosis, an increased permeability for H+ may cause the inability to acidify the urine.

Abnormal lactation (galactorrhea) was observed in 5 female patients with renal failure. This appeared in association with amenorrhea in the terminal stage of renal failure. Lactation gradually decreas

ヘモグロビンの酸素親和性は組織への酸素供給の重要な因子である. 慢性腎不全患者では, 貧血に対する適応現象としてヘモグロビンの酸素親和性が減少し, 血液の酸素運搬能が上昇していることが知られている. 酢酸透析はアシドーシスを改善させ, Bohr効果により酸素親和性を増大させるとされているが, 重炭酸透析が酸素親和性にいかなる影響を及ぼすかは十分に検討されていない。そこで, 著者らはヘモグロビンの酸素親和性に及ぼす影響について, 酢酸透析と重炭酸透析との間で比較検討した. 対象は明らかな心・肺疾患を有しない血液透析患者8例である. 同一症例に対して, 酢酸透析と重炭酸透析を施行し各透析前後で, 動脈血ガス分析, ヘモグロビン濃度 (Hb), 血清無機リン (S-iP), 赤血球2, 3-diphosphoglycerate (2, 3-DPG), 酸素解離曲線について検討した.その結果, 動脈血ガスでは両透析でpHの上昇, Po2の低下がみられたが, 透析後のPco2が重炭酸透析で有意に高値である以外, 両透析間には差が認められなかった. Hbは両透析で不変, S-Pは両透析で減少,, 3-DPGは両透析で不変であり, いずれも両透析間に差が認められなかった. P50 (in vivo) は酢酸透析において透析前28.5±0.6 (平均値±SE) mmHgより透析後25.7±0.6mmHgへと有意に減少し, 重炭酸透析においても前28.6±1.0mmHgから後26.7±0.8mmHgへと有意ではないが, 減少傾向を示した. なお, 前値, 後値, 変化量には両透析間で差が認められなかった.以上より, ヘモグロビンの酸素親和性に及ぼす影響には, 酢酸透析と重炭酸透析との間で差がないと考えられた.

The mechanism of kaliuresis induced by massive antibiotic administration was studied using alpha-sulfobenzyl penicillin (SBPC). In experimental group (n = 8), urinary electrolytes excretion were compared between following the infusion of 10 g SBPC in 200 ml water at a constant rate and following the infusion of 48 mmol of NaCl (equal to that contained in 10 g SBPC) in 200 ml water. For the control group, 96 mmol NaCl in 400 ml water was infused (n = 5). In the experimental group, urinary Na (UNaV) and urinary K excretion (UKV) increased relative to the control period. In the control group, UKV was not increased although UNaV was increased (p less than 0.05). UKV following SBPC infusion was correlated with UNaV (p less than 0.05) and urinary SBPC excretion (p less than 0.05). The ratio of urinary anion gap to urinary cation [1-(urinary Cl concentration/(urinary Na concentration + urinary K concentration))] was significantly increased following SBPC infusion (p less than 0.005) but not in the control group. This increase in anion gap is possibly due to urinary SBPC, which will be ionized over 90% as nonreabsorbable anion in maximally acidic urine. We conclude that the kaliuresis induced by massive SBPC administration in man is probably caused by the nonreabsorbable anion effect of SBPC itself.

Hemodynamic effects of 2 mg of sublingual molsidomine were evaluated in 11 patients with ischemic heart disease using a weight-sustaining isometric exercise (WSIE) that we developed. Left ventricular end diastolic pressure (LVEDP), mean pulmonary pressure, mean systemic arterial pressure (mAP), cardiac index and stroke work index increased significantly during WSIE before and after molsidomine. Although WSIE resulted in a similar rise of mAP before and after molsidomine, the increment value of LVEDP during WSIE was significantly lower after molsidomine. The recovery time to the resting state of all parameters was shorter and the left ventricular function curves showed a leftward deviation with molsidomine.In conclusion, the results suggest that molsidomine will produce a preload reduction and improve the left ventricular function during WSIE in patients with ischemic heart disease.

An immunological process is suggested to play some role in the pathogenesis of alcoholic hepatitis; however, its nature has not been clarified. In the present study, we examined, in 30 patients with alcoholic liver disease, an in vitro effect of prednisolone on suppressor T cell activity to see whether an altered cellular immunoregulatory mechanism is affected by corticosteroid. Suppressor T cell activity, which was induced by concanavalin A (Con A), was assessed by inhibition of phytohemagglutinin-stimulated blast transformation of autologous lymphocytes, and prednisolone (10 micrograms/ml) was added when suppressor T cells were induced. Low suppressor T cell activity was found in alcoholic patients with hepatic fibrosis, alcoholic hepatitis, and cirrhosis with hepatitis; these reductions recovered to a normal range when lymphocytes were incubated in vitro with prednisolone, suggesting an improvement in the altered immunoregulation by prednisolone. Although immunotherapy is shown to be of no benefit in the treatment of alcoholic hepatitis, we propose a need to elucidate further the therapeutic modalities for correction of the immunoregulatory abnormalities in such patients.

To study the acute effects of ISDN, nifedipine, propranolol and placebo on cardiac function in patients with myocardial ischemia and to characterize their hemodynamic effects by PANOVA, we repetitively performed exercise radionuclide angiography (RNA) following random assignment of each drug in 20 patients with effort angina pectoris. We obtained exercise response curves of hemodynamic parameters determined by RNA. ANOVA was performed to analyze the sizes (average height) of those response curves, and PANOVA (principal component analysis, PCA, combined with ANOVA) to analyze differences in the profiles (patterns) of the curves. By conventional analysis of variance followed by a Scheffe type multiple comparison, end-diastolic volume after ISDN, which was significantly smaller than those after the other drugs at rest (p less than 0.01), was similar to those after nifedipine and propranolol during exercise (96.4 +/- 4.6 ml/m2 vs. 94.8 +/- 5.1 ml/m2 and 97.1 +/- 4.9 ml/m2, respectively). Systemic vascular resistance after nifedipine, which was also significantly lower than those after the other drugs at rest (p less than 0.05), was not different from that after placebo during exercise (16.9 +/- 1.1 units vs. 18.7 +/- 1.3 units). Thus, this analysis was considered insufficient to fully differentiate the characteristics of each drug. By PANOVA, the profiles of LVEF with these three antianginal drugs were similar, and significantly differentiated from that of placebo (p less than 0.05). This indicated that the antianginal effect could be represented by the profiles of the response curves of LVEF, using PANOVA. Evaluating the underlying hemodynamic mechanisms of these drugs by PANOVA, ISDN was significantly differentiated from nifedipine and propranolol by the profile of end-diastolic volume (p less than 0.05). The characteristics of nifedipine were clearly demonstrated by the size and profile of systemic vascular resistance, and those of propranolol were also differentiated by the size and profile of the double product and P-V index. Hence, it is concluded that with the aid of PANOVA, the changes in hemodynamic parameters during ischemia can be evaluated in a manner that is highly effective in differentiating the characteristics of the effects of antianginal drugs in patients with angina pectoris.

To investigate the immunological mechanisms underlying corticosteroid therapy in chronic active hepatitis (CAH), in vitro effects of prednisolone on suppressor T-cell and interleukin 2 (IL-2) activities were examined in six corticosteroid therapy-effective and six therapy-ineffective patients with CAH prior to the therapy. Whereas low suppressor T-cell activity and decreased response to IL-2 in T cells were found in the corticosteroid therapy-effective group, these reductions recovered to the normal range when the activity or response was tested in the presence of prednisolone (1 and 10 micrograms/ml). Corresponding with these recoveries, suppressor T-cell activity arrived at normal values after corticosteroid therapy for 8 weeks. By contrast, in the corticosteroid-ineffective group, no apparent effects of prednisolone on suppressor T-cell activity and the response to IL-2 were observed. The relationship between the clinical effect of corticosteroid therapy and in vitro improvement in suppressor T-cell activity or in the response to IL-2 by prednisolone suggests that, in CAH, the corticosteroid effect is likely to be due to an immunomodulation in T-cell function.

慢性活動性肝炎23例および,正常者139人のHLA typingを行ない,慢性活動性肝炎とHLAとの間に相関(association)があるか否かを検討した.さらに肝炎群をHBs陽性群(7例)と陰性群(16例)に分けて検討した.その結果,HB感染の有無にかかわらず,肝炎群では正常者との間にHLA抗原頻度に有意な差をみなかった.しかし慢性活動性肝炎のうち,橋本病合併(1例),Sjogren症候群合併(3例)と抗核抗体やLE細胞が陽性(4例)のいわゆる自己免疫性肝炎ではHLA-A9, BW35ハプロタイプの増加の傾向が示唆された.以上より自己免疫性肝炎とHLA抗原との間の相関性が示唆された.

The role of intravascular coagulation in the progression of immune complex induced nephritis (BSA nephritis) was examined in the albino rabbits, and the effects of urokinase and ancrod were tested.Non-treated group revealed hyperfibrinogenemia, high level of serum FDP and low plasminogen activator activity accompanying endocapillary proliferation after BSA treatment.By daily infusion of urokinase (3, 000U/day), the activity of plasminogen activator was conserved and the glomeruli showed more mild lesions than that of non-treated group.By ancrod infusion (2U/kg/day; iv), the degree of endocapillary proliferation decreased accompanying hypofibrinogenemia.These results suggest that intravascular coagulation plays an important role of BSA nephritis.