A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation

Shimizu T, Tanabe K, Tokumoto T, Shimmura H, Koga S, Ishikawa N, Oshima T, Toma H, Yamaguchi Y. A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 11–15. ©Munksgaard, 2001
A 46-yr-old Japanese male who underwent a second cadaveric kidney transplantation on 31 October 1996 after suffering Type II diabetic mellitus for 25 yr was admitted to our institute on 23 January 1999, because of colicky abdominal pain and abdominal discomfort. Elevated levels of serum creatinine, severe proteinuria and microscopic haematuria were observed. The allograft biopsy specimen disclosed crescentic glomerulonephritis. Immunofluorescence showed granular deposits of mainly IgA and C3 along glomerular capillary walls and mesangial areas. Electron microscopy showed extensive subepithelial and mesangial electron dense deposits. Rapid and irreversible worsening of graft function led to resumption of haemodialysis on 31 May 1999. We speculated that this case was an atypical form of de novo Henoch–Schönlein purpura nephritis (HSPN) in transplanted kidney because of the histopathological findings of the allograft biopsy and clinical symptoms.     

In-vivo 19F-MRS study of 5-fluorouracil (5-FU) metabolism on tumors

5-Fluorouracil (5-FU) metabolism on tumors was studied by in-vivo 19F-MRS (magnetic resonance spectroscopy). In this study, two kinds of tumors were used, i.e., Yoshida sarcoma implanted subcutaneously to the abdomen of rats and drug-induced tumors in the rats livers. Sequential 19F spectra were obtained just after 150 mg/kg 5-FU injected intravenously. In Yoshida sarcoma, the accumulation of 5-FU was observed and disappearance of 5-FU was slower compared to the normal tissue. However, synthesis of fluoronucleotides (Fnct) could not be detected. In drug-induced liver tumors, the peak of fluoro-beta-alanine (FBAL) was observed. Disappearance of 5-FU and catabolism to FBAL in the liver tumors group were slower compared to the normal liver. Synthesis of Fnct did not increase in the liver tumor group. The results in the liver tumor group are considered to be the confined result of the hepatocytes and tumors cells. It was considered that the delayed catabolism to FBAL in the liver tumor group showed metabolic dysfunction of the liver. Also the synthesis of Fnct in tumors could not be detected by in-vivo 19F-MRS. 19F-MRS method could not detect Fnct in tumors in-vivo. However, the accumulation of 5-FU could be assessed by this method. It is expected that the evaluation of 5-FU pooling in tumors could be used for the index of chemotherapeutic effect.     

Quantitative analysis of lung perfusion in patients with primary pulmonary hypertension.

The aim of this study was to evaluate quantitatively the heterogeneity of lung perfusion scans in patients with primary pulmonary hypertension (PPH) and to compare it with the severity of disease. METHODS: Lung perfusion scans were obtained on 22 patients with PPH and 12 age-matched control subjects. The perfused area rates (PARs) were calculated by dividing the lung area in each 10% threshold width from 10% to 100% of maximal counts by total lung area. The total absolute difference in the PAR between each patient and the mean control value was assumed as the perfusion index of the lung (P index). The P index was compared with hemodynamic parameters and the right ventricular ejection fraction (RVEF), including 7 patients who received long-term vasodilator therapy. RESULTS: The P index correlated significantly with mean pulmonary arterial pressure (P < 0.001) and RVEF (P < 0.05). In patients with vasodilator therapy, the P index was improved significantly after therapy (P < 0.05) and was associated with a reduction in pulmonary arterial pressure. CONCLUSION: Quantitative assessment of lung perfusion irregularity might provide useful information about the severity of disease and the effect of therapy in addition to the routine visual representation.     

Survival of bacteria, and release of the endotoxin from the bacterial cells in the dialysates]

Survival of bacteria and release of the endotoxin from the bacteria with and without ultraviolet irradiation in three kinds of dialysate were investigated. The results obtained are as follows: (1) No growth of S. aureus, E. coli, P. aeruginosa, Aspergillus and C. albicans in the saturated dialysates tested were observed. (2) All of the bacterial cells tested here is gradually, and naturally spontaneously inactivated in all the dialysates. (3) Among the dialysates tested, the saturated dialysate, AF-2, is the most effective for inactivating P. aeruginosa ATCC, but the effect depends upon the isolates of P. aeruginosa. (4) The inactivating effect was somewhat decreased when the saturated AF-2 solution was diluted, but the killing effect was still maintained. (5) The bacterial cells are constantly and significantly inactivated by UV irradiation, especially by the direct irradiation. The indirect irradiation, i.e., through glass, has remarkably less effective than the direct one. However, a tendency of the decrease of bacterial cells by the indirect irradiation is maintained with the killing effect of the dialysated, especially in the case of AF-2 solution. (6) No significant increase of endotoxin was observed, even when the bacterial cells were killed by UV irradiation. Therefore, it is recommended to use UV irradiation for inactivating the bacteria. From the results obtained here, it is indicated that there is no possibility of the growth of naturally contaminated bacteria in the dialysates, and is an effectiveness of the use of UV irradiation for inactivating the bacteria cells, in terms of release of the endotoxin from the dead cells.     

Mechanism of uricosuric action of AA-193 in DBA/2N mice

Six strains of mice were investigated to find an animal model suitable for researching the mechanism of uricosuric agents. A clearance method and a pyrazinamide suppression test were used to examine the mechanism of urate excretion in the kidney and the mode of action of uricosurics, respectively. The negative correlation between the urinary urate excretion and the endogenous plasma urate level was observed, suggesting the net reabsorption of urate may vary between strains. DBA/2N mice showed the lowest fractional excretion of urate (0.278), and the effects of uricosurics on DBA/2N mice are analogous to those of humans. Our extensive study of the mechanism of urate excretion in DBA/2N mice has proven that the mouse strain is a useful model for the study of uricosurics. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carb oxylic acid) is a potent new uricosuric agent developed in our laboratory. In the present study, AA-193 was tested in DBA/2N mice and found to have a mode of action different from well-known uricosuric agents. It appeared to inhibit presecretory reabsorption in the proximal tubules.     

Promoting effects of both dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters.

The effects of dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 120 female Syrian golden hamsters. BOP (70 mg/kg body weight) was injected s.c. once at the beginning of the experiment. Starting 2 weeks later, the animals were then maintained on basal diet or diets containing either 0.5% cholesterol or 1% cholestyramine for a further 16 weeks. All surviving hamsters were killed at week 18, and the pancreas tissues examined histologically. The incidences of pancreatic carcinomas in hamsters fed cholesterol and the cholestyramine supplement were 40.0 and 30.0% respectively; in both cases significantly higher than the 6.9% incidence in the basal diet group. Cholesterol contents of the serum, pancreas and liver were significantly increased by cholesterol feeding and significantly decreased by the cholestyramine diet. The cholesterol diet also significantly increased pancreatic protein and DNA contents, and the concentration of total bile acids and the level of lithocholic acid in gallbladder bile. The cholestyramine diet significantly increased total pancreatic DNA and protein contents, and pancreatic weight. The results thus indicated that both dietary cholesterol and cholestyramine can enhance BOP-initiated pancreatic carcinogenesis in hamsters.     

Ultrasonographic prediction of patients' outcome in hyperacute ischemic stroke.

OBJECTIVE: We examined whether carotid ultrasonographic (US) findings in hyperacute ischemic stroke are useful to predict patients' outcome. METHODS: We studied 73 consecutive patients with carotid stroke using both computed tomography (CT) and duplex carotid ultrasonography within 6 h of stroke onset. We evaluated early CT findings defined as obscuration of the lentiform nucleus, loss of the insular ribbon and/or cortical effacement, and US findings indicating internal carotid artery (ICA) or middle cerebral artery trunk occlusion. The National Institute of Health Stroke Scale (NIHSS) at admission and modified Rankin scale on day 30 were assessed. RESULTS: According to multiple logistic regression analysis, positive US findings (P = 0.0045, odds ratio, 11.1) provided the best predictor of modified Rankin scale score > or =3 compared with a baseline NIHSS> or =16 (P = 0.036, odds ratio, 7.9) and early CT findings (P = 0.18). CONCLUSION: US findings of hyperacute stroke may provide a better predictor of patients' outcome.     

Delayed Maturation of Fetal Lung in Yellow KK Mice

Yellow KK mice have the A^y allele and spontaneously develop non-insulin dependent diabetes mellitus (NIDDM). In the present study, female yellow KK mice were mated at 7 or 13 weeks of age (the average blood glucose levels were ca. 260 and 500 mg/dl, respectively), and their fetuses were examined on days 18 or 19 of gestation. The fetuses from 13-wk-old dams were smaller than those from 7-wk-old dams. The average lung weight on day 19 of gestation was slightly greater in the fetuses from 13-wk-old dams than in those from 7-wk-old dams (23.3 vs 21.2 mg). Histologically, alveolar spaces were smaller and alveolar walls were thicker in the fetuses from 13-wk-old dams than in those from 7-wk-old dams. Morphometric analysis revealed that the percentage area of the fetal lung occupied by alveolar spaces was significantly smaller in the former fetuses than in the latter. Day-15 fetal lungs of KK mice, which do not have the A^y allele, were cultured in hyperglycemic media (glucose levels: 400 and 700 mg/dl) for 48 hr. The development of alveoli was inhibited in hyperglycemic media as compared to the development of the lungs grown in the control medium. The inhibitory effect was dependent on the glucose concentration in the media. Thus, it seems that maternal hyperglycemia itself is a major cause of the delayed maturation of the fetal lung in NIDDM mice.     

Decreased perfusion in myocardial region of normal donor artery secondary to collateral development. Stress 201Tl myocardial emission CT performed in patients with single vessel exertional angina having collaterals.

Thirty-one patients suffering from single vessel exertional angina with collaterals (Group A) were evaluated by stress 201T1 myocardial emission CT (Tl-SPECT) with 16 controls of severely stenotic single vessel exertional angina without collaterals (Group B). Group A included 21 patients (68%) who showed an extensive perfusion defect in double artery myocardial regions, including the normal donor artery myocardial region (DMR). However, there were no such cases in Group B, giving a significant difference between these 2 groups (p less than 0.001). Four patients in Group A, having a perfusion defect both in DMR and in the collateral dependent myocardial region (CMR) underwent a successful percutaneous transluminal coronary angioplasty (PTCA) with disappearance of collaterals. Tl-SPECT findings after PTCA showed no perfusion defect either in CMR or in DMR. This has been explained on the basis that the coronary collaterals stole blood and produced perfusion defect in DMR.