Monocrotaline (Mo), toxic alkaloid with molecular weight 325, is known to inducpulmonary angiitis which results pulmonary hypertension in experimental rats. The patho-genesis of this lesion is thought to be the direct endothelial cell damage of Mo. The toxiceffects of Mo to the kidney have been already reported by Masugi, Allen, and recently by Kurosumi. However, the precise analysis of glomerular changes have not been described. We tried to investigate the morphological changes of glomerulus induced by the injection of Mo into rats. Single subcutaneous injection of Mo with 60 mg/kg (2 % soulution) were made to male Sprague Dawley rats weighting 60 g (4 weeks after birth) and sacrificed successively from 1 to 5 weeks after routine examinations of urine and blood. Autopsied kidney and lung tissues were subjected to the examination for routine LM, EM, and IF. Marked proteinuria and microhematuria appeared 3 to 4 weeks after the injection. LM disclosed marked diffuse endocapillary changes with mesangiolysis at 3 to 4 weeks. EM sho wed detachment of endothelial cells and insudation of plasma protein in subendothelial space and mesangial area during 1 and 4 week. By IF no remarkable deposits of Ig and C were observed. Renal function was normal through all the experimental period as far as serum Cr is conscerned. There were no specific changes in small blood vessels in the kidney although angiitis was seen in pulmonary small arteries. The mechanism of glomerular injury of Mo was thought as follows ; 1) injury of glomerular capillary endothelial cells by direct toxic action of Mo, 2) detachment of endothelial cells from GBM, 3) insudation of plasma protein in subendothelial space and mesangial area and 4) acute endothelial alterations and mesangiolysis.It was concluded that Mo induced glomerulopathy is to be one of the excellent model of human acute endocapillary glomerular injury.

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There were several reports that platelets may play an important role in the pathogenesis of golmerulonephritis. However, what stage of nephritis and what way they might be involved in are not exactly demonstrated yet. To clarify the questions, effects of thrombocytopenia on pathological changes in an early stage of acute immune complex glomerulonephritis (ICGN) of rabbits were investigated. Eighteen rabbits were injected with bovine serum albumin (BSA), intravenously twice after the immunization, to induce ICGN. On the 14th experimental day, the rabbits were sacrificed for histological examination. Eight of them were daily injected with goat anti rabbit platelet antiserum to induce thrombocytopenia (less than 5.104/.El) during the experimental time. On the 14th experimental day, there were no significant differences in serum creatinine, blood urea nitrogen and creatinine clearance between thrombocytopenic (T-) and control group (C-group). However, urinary protein excretion in T-group was 34% of that in C-group with a significant difference (p<0.01). On the 14th experimental day, the hypercoagulable state in ICGN was less severe in T-group than C-group. Fibrinolytic activity decreased in Cgroup because of the consumption of plasminogen activator, while it was almost normal in Tgroup. Histological examination by light microscopy revealed that glomeruli of C-group showed marked polymorphonuclear leukocyte infiltration, monocyte proliferation, exudation and glomerular enlargement. On the one hand, these changes were scarecely observed in the glomeruli of T-group except slight monocyte proliferation. When a scoring method was applied to evaluate above these findings, there were significant differences in these histological changes between C-group and T-group (p<0.01-0.05) respectively. These results suggest that platelets may play an essential role on the genesis of ICGN in the early stage, especially before IC deposition.

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This study was performed to investigate the role of cell-mediated immunity in primary glomerular diseases (PGD). The proportion of peripheral blood mononuclear cells was exa mined by flow cytometry using the monoclonal antibodies OKT and Leu series. The subjects included 29 cases with minimal change nephrotic syndrome (MCNS), 63 of IgA nephropathy (IgA-GN), 36 of non-IgA mesangial proliferative glomerulonephritis, 21 of membranous glomerulonephritis (MGN), 9 of membranoproliferative glomerulonephritis (MPGN) and 75 healthy volunteers as controls. Patients with MCNS nephrotics demonstrated a significantly decreased mean OKT 4/OKT 8 ratio due to both a decrease in OKT 4 positive cells and an increase in OKT 8 posi-tive cells. Patients with IgA-GN and MPGN showed a significant mean increase of OKM 1. The nephrotics with MCNS demonstrated a significantly mean reduction in Leu 3 a/Leu 2 a ratio secondary to both the depression of mean Leu 3 a values and the elevation of mean Leu 2 a values. Patients with IgA-GN demonstrated a significantly elevated mean Leu 3 a/ Leu 2 a ratio due to an increase in Leu 3 a positive cells and a reduction in Leu 2 a positive cells. Patients with MGN showed the significant elevations of LeuHLA-DR and Leu 7. Patients of MPGN showed a significant increase of Leu 7 positive cells.These data suggest that defects in T and NK/K cells are common in patients with PGD, and may be important in the development of PGD.

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The morphological examination of rat kidney was studied before and after intra-renal perfusion of .A-globulin. The composition and modification of immune complex (IC) has been discussed recently and rheumatoid factor has been speculated to be the factors which promotes the enlargement of the IC deposited in the glomerulus, resulting in persistence or aggravation of renal diseases. On the other hand. reports have been made regarding the disappearance of not only IgG deposition from the glomerulus after incubation of frozen section with IgG in vitro, but also antigen from the glomerulus by administration of excess antigen in vivo. Based on these reports, we studied the direct effect of .A-globulin perfusion onto the IC deposition in the glomerulus. Membranous nephritis in rats were induced by daily injection of cationic BSA. The right side kidney was perf used with solution of BSA, rat .A-globulin, human IgG or saline after removing the left kidney which was studied as control. All rats developed granular deposition of rat IgG, the intensity of the IgG staining became brighter following days of immunization, whereas the deposition of the BSA staining remained faint throughout the experimental period. The intensity of BSA in the glomerulus appeared to increase after perfusion with BSA solution. The diminishment of C 3 from the glomerulus was observed in 2 out of 7 rats after perfusion of rat .A-globulin; complete or incomplete dispersion of IgG in the glomerulus was observed after perfusion with rat .Aglobulin or human IgG. In addition, electron dense deposition in the basement membrane changed to electron lucent deposition after perfusion with IgG by electron microscopy. From these obsevations, it is likely that the dissociation of IC deposited in the glomer-ulus might be mediated in part by the direct effect of .A-globulin perfusion.

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　原発性ネフローゼ症候群および原発性膜性腎症(経過中一度もネフローゼ症候群を示さなかったもの)を対象に,糸球体傷害度指数および平均尿細管萎縮度を測定し,下記の成績を得た。　1)ネフローゼを伴った原発性膜性腎症においては,腎機能と平均尿細管萎縮度とは良好な相関を示した。　2)ネフローゼを伴った原発性膜性腎症において,平均尿細管萎縮度の低下を認めた例では,治療の効果および腎機能の予後は不良であった。　3)ネフローゼを伴った原発性膜性腎症の平均尿細管萎縮度の低下の要因としては,加齢,再発,高血圧やネフローゼ状態の持続などが考えられた。　4)再生検にて,腎機能低下を認めた例では,膜性腎症では間質の変化が,増殖性糸球体腎炎では糸球体の病変が重要な要因と考えられた。稿を終るにあたり,御懇切な御指導と御校閲を賜った原耕平教授に深甚なる謝意を表するとともに,直接御指導を頂いた長崎大学第2内科原田孝司助手,堀田覚前助教授,伊万里市民病院院長緒方弘文博士,福岡大学第2病理竹林茂夫教授,田口尚助教授に深謝いたします。また終始研究に協力していただいた第2内科教室の腎臓グループの諸先生方に感謝いたします。　なお本論文の要旨は,第24,25回日本腎臓学会総会および第12回日本腎臓学会西部部会ワークショップ「膜性腎症」において発表した。

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The protective effects of PGI₂ and OP41483 a new PGI₂ analogue, on acute renal ischemia were investigated in rabbits. After the 24-hour deprivations of food and water, animals were anesthetized by the intravenous injection of pentobarbital. The left renal artery was completely occluded by a smooth surface clamp and the right kidney was removed. The animals were divided into four groups of six each. In three groups, after the 90-minute occlusion, each of furosemide, PGI₂ and OP41483 dissolved in Hartmann's solution (pH 8.0) was infused for 60 minutes at the rate of 2 mg/kg/min, 5 and 20 ng/kg/min, respectively, into the aorta at the proximal site of the left renal artery. In another group, same volume of Hartmann's solution was infused as a ischemic control. Simulataneousley, 1.3 ml/kg of 3% inulin was injected intravenously and serum inulin values 15 and 60 minutes after the injection (I₁₅ and I₆₀) were measured. To estimate the renal function, a decrescent rate of serum inulin (K) was calculated by the formula: (loge I₁₅-loge I₆₀)× 60 min/45 min. Renal function indicated by the K value was improved in the groups infused OP41483, PGI₂ and furosemide in order, as compared with the control group, although the statistical significance was seen only in the OP41483 infused group. At the end of the experiments, the kidneys in both ischemic and OP41483 group were cut in halves, fixed in 10% formalin and stained with hematoxylin and eosin. Both groups showed a slight dilata-tion and cell swelling of proximal tubule, and eosinophilic substance partly in Bowman's space. There were pathologically no significant difference between ischemic control and OP41483 and no relation between etiologic findings to renal functions. The results indicate that PGI₂ and its analogue may be effective to protect the renal function from the ischemic insults by their actions of vasodilatation and antiaggregation of platelets and that the strong effect of OP41483 is probably due to its stable property.

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The presence of impaired glucose metabolism in the patients with chronic renal failure (CRF) has long been recognized. Using euglycemic insulin clamp technique (insulin infusion plus variable amounts of glucose infusion), we quantitated insulin resistance in genesis of the glucose intolerance observed in the patients with CRF. Tissue sensitivity to insulin was evaluated in 10 patients with CRF (before, one week and four weeks after introduction of hemodialysis) and 19 healthy controls. The amount of glucose infused reflects the overall tissue sensitivity to insulin. Further, FFA and glycerol concentration were measured during the insulin clamp study. The glucose infusion rate in the patients with CRF (4.45±0.30 mg/kg/min) was significantly lower than in the controls (7.39±0.20 mg/kg/min) (p<0.01). The decreased glucose infusion rate in the patients with CRF increased to 5.80±0.40 mg/kg/min (p<0.02) one week after introduction of hemodialysis, and further improved to 7.46±0.90 mg/kg/min (p<0.02) four weeks after continuation of hemodialysis and daily physical activity. During the insulin clamp study, FFA decreased more rapidly in the patients with CRF (both before and after introduction of hemodialysis) than in the controls (p<0.05-0.001), while glycerol decreased gradually in both groups and showed only 50-60% reduction over 2 hours. From these results, it might be confirmed that glucose intolerance in the patients with CRF could be improved by the introduction and continuation of hemodialysis, and further could be improved by daily physical exercise.

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We have examined effects of latamoxef (LMOX) for platelet aggregation in chronic hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) patients. Six patients on regular hemodialysis (6 hour, three times per week) received 1 g i, v. dose of LMOX at the start and end of each dialysis for 8 days (four times of dialysis). During administration, ADP induced platelet aggregation was consistently suppressed and maximum suppression was observed 7 days later. The aggregation improved 7 days after cessation of the LMOX administration. For CAPD patients, intraperitoneal administration of LMOX was performed. Four patients suffering from CAPD peritonitis received four to eight exchanges of 2 liters dialysis fluid with the addition of 0.5 g LMOX to alternative exchange (1.0-2.0g/day). Their platelet aggregation, as well as hemodialysis patients, reduced during the administration and recovered after the antibiotic was washed out from blood. We have also investigated the suppression of platelet aggregation of LMOX in vitro. LMOX was added to platelet-rich plasma of eight healthy volunteers and six CAPD patients for final concentration of 300, 600, 1200 mu;g/ml. ADP induced platelet aggregation was suppressed at the concentration of 600 μg/ml. These results suggest that LMOX interfere with the platelet function at high concentration. Therefore, high dosage LMOX administration to patients with chronic renal failure may cause bleeding complication due to platelet dysfunction.

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A simplified rapid method by gas chromatography has been developed for the determination of total body water (TBM). For the purpose of studying the dynamic distribution of deuterium oxide in a body, 16 ml of 99.75% deuterium oxide in 30 ml tap water was administrated orally to the patients with chronic renal failure and normal persons. After 3 hours to allow the dose to equilibrate within the body water pool, a blood sample was obtained. The TBW to body weight (BW) ratio was higher in 15 just after hemodialysis patients (60.8±6.9%) than in 4 normal subjects (58.1±4.8%). During the interval of hemodialysis, the mean BW of nine patients was changed from 40.6±6.8 kg to 48.1±7.0 kg, while the TBW was from 27.2±4.1 kg to 23.8±4.4 kg. The results of this investigation showed the sufficient accuracy on measuring the TBW of hemodialysis patient.

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To evaluate the role of prostaglandins (PGs) in natriuresis of normotensive Wistar rat with salt loading, urinary PGE excretion and pressure-natriuresis curve of perfused kidney in situ were estimated. Rats were fed on high salt diet (8% NaCl) or regular salt diet (0.61% NaCl) for 2 weeks, and urinary PGE was measured by radioimmunoassay. Kidney was perfused in situ with Krebs-Ringer bicarbonate buffer solution in constant perfusion flow (4.3 ml/min) or in various perfusion pressures (60 mmHg-120 mmHg) in order to obtain pressure-natriuresis curve. Urinary PGE excretion of rats loaded with high salt diet was significantly increased as compared with that of rats loaded with regular salt diet. In constant perfusion flow, sodium excretion of perfused kidney with salt loading was significantly increased, however this enhanced natriuresis was inhibited by pretreatment with indomethacin. Moreover, the pressure-natriuresis curve of kidney loaded with high salt diet shifted to left upward as compared with that of kidney loaded with regular salt diet and this shift of pressure-natriuresis curve was recovered to control level by pretreatment with indomethacin. These phenomena may suggest an enhanced production of natriuretic PG and other factors in salt loading. Summarizing these results, the enhanced production of PGE and the increased excretion of PGE in the kidney of rat loaded with high salt diet can participate in an augmented natriuresis and shift the pressure-natriuresis curve to left upward, a condition in which salt can be excreted more efficiently with lower perfusion pressure of the kidney. These facts suggest that the renal PGE would play an important role in the adaptation of the rats to high salt diet conditions.

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　1.非透析,透析慢性腎不全患者の大動脈,皮膚,毛髪,爪のCa,Mg含量およびAlなどの微量元素含量を測定した。測定は大型原子炉を用いた非破壊放射化分析法によった。　2.人動脈組織では,非透析,透析を含めた腎不全群のAl,Mg含量は,対照に比し有意に高値を示した。Ca含量はその平均値において腎不全群が高かったが,統計学的な有意差はなかった。　3.皮膚組織では,非透析群のMg含量が対照群に比し有意に低かったが,この意味は明らかにしえなかった。非透析群,透析群とも,Ca含量の平均値は対照群より25%高値を示したが,統計学的に有意とは言えなかった。　4.毛髪中では,非透析群,透析群とも有意のCaおよびAl含量の高値をみている。また非透析群でZnの有意の減少,透析群でVの有意の増加をみた。　5.爪組織では,非透析群で,As,Mn,Cuの有意の増加をみた。6.Alは大動脈,毛髪で増加を示し,脳,骨のみでなく,他臓器でも蓄積していることを示唆した。Caは,丘髪で有意の増加を示し大動脈,皮膚でも増加を示唆する成績であり,二次性副甲状腺機能亢進症のため組織中Ca沈着が起きていると考えられた。　7.毛髪が最も腎不全による病態をよく反映していると考えられ,腎不全患者の微量元素異常を非侵襲的に知るための最もよい材料と思われた。

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The renal cortical and medullary blood flows (RCBF and RMBF) were measured by electrolytic hydrogen gas clearance method in rabbits. The following results were obtained. 1. RCBF gradually decreased from the outer layer to the inner one, while RMBF was stable through all layers. 2. The sham blood flow by diffusion was stabilized about 25 minutes after cardiac arrest. 3. The repeatability of this method was found to be very good. 4. The values by this method well correlated with that by inhalation method. As the electrolytic hydrogen gas clearance method is safe and simple, it may be used in clinical applications.

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An altered erythrocyte sodium ion transport of essential hypertensive subjects has been observed in relation to the pathogensis of hypertension. In this study, erythrocyte sodium ion transport systems as well as sodium and potassium content were examined and the following results were obtained in DOCA- salt (DSH), two-kidney, one clip Goldblatt (2KH) and spontaneously hypertensive rats (SHR). 1. Erythrocyte sodium content was significantly higher in SHR than in controls (p <0.01).In DSH and 2KH, erythrocyte sodium content was similar with controls. 2. Erythrocyte potassium content was significantly lower in DSH than in controls (p <0.01).In 2KH and SHR, erythrocyte potassium content was similar with controls. 3. The Na⁺-K⁺ pump activity was significantly higher in SHR than in controls (p <0.01). Significant differences in Nay-K pump activity, however, could not be demonstrated in DSH and 2KH compared to controls. 4. The Na⁺-K⁺ cotransport was similar with controls in all hypertensive rats. 5. The passive Na⁺ permeability was significantly higher in SHR than in controls (p <0.01). In DSH and 2KH, the passive Na⁺permeability was similar with controls. 6. An increase in erythrocyte Na⁺- K⁺pump activity in SHR might reflect compensatory mechanism for the increased inward leak of sodium and the increased content of erythroctye sodium might be related to the pathogenesis of hypertension. 7. In DSH and 2KH, none of the erythrocyte abnormalities observed in the SHR were present, suggesting that latter alteration are probably genetically determined and not a consequence of elevated arterial pressure.

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Up until today, diagnosis of MCTD (mixed connective tissue disease) was confusing, because some authors advocated various criteria. Nephropathy was rare complications of patients with MCTD previously, but recently some authors reported nephropathy of MCTD. In this paper, analysis of pathological and clinical findings of MCTD was carried on. Furtherworse significance of anti-ENA antibody in SLE and MCTD was analyzed. Studies were carried on 10 cases of MCTD and 7 cases of SLE with anti-ENA antibody in the early stage of onset. The diagnosis of MCTD was based on presence of anti-RNP antibody and clinical over lapping features. In the patients with MCTD, all cases were high titer of anti-RNP antibody, but no case had anti-Sm antibody and hypocomplementemia. So this group was homogenous. Renal biopsy specimen was obtained from 8 out of 10 patients with MCTD. 1 out of 8 patients was feature of membranous nephropathy, and other cases was minor glomerular abnormality, on light microscopic findings. Renal biopsy revealed no characteristic findings on MCTD. In the patients with SLE, high titer of anti-DNA antibody and hypocomplementemia were recognized in all cases. In pathological findings, the conception that anti-ENA antibody protected the glomerulus from DNA anti-DNA antibody immunocomplex system was not recognized.

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A hemodialysis patient with congenital solitary kidney and various anomalies is presented. This 51-year-old woman was admitted to our institution because of hypertension and proteinuria which were noticed for the first time 9 years ago. Family history was significant, in which her father died of kidney disease and four brothers had deafness. Physical examination on admission revealed slight disturbance of growth, mental retardation, teleangiectasia of face, left strabismus divergens, atrophy of retina, perceptive deafness and auditory hallucination. Blood pressure was 160/110 mmHg. Abnormal laboratory findings were as follows : proteiuria 1 g/day, BUN 65 mg/dl Creatinine 5.6 mg/dl, plasma renin activity 0.2 ng/ml/h, plasma aldosterone concentration (PAC) 53.7 ng/dl. The left kidney was not visualized on both renoscintigraphy and abdominal computed tomography. The adrenal glands were normal in size on I-131-adosterol scintigraphy. Proline was not high in the plasma aminogram. Aortography showed hypoplastic right renal artery and non-visualized left renal artery. The left ureteral orifice was missing on cystoscopy. In summary, congenital solitary kidney with various other anomalies is the most likely diagnosis in this case, although familial nephritis can not be completely ruled out. High blood pressure might be related to high PAC. No case such as this has ever been reported in the literature.

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