Henoch-Schönlein Purpura After Living Donor Liver Transplantation: Report of the First Case.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting the small vessels that mainly presents in children and young adults. It is characterized by tissue deposition of immunoglobulin A (IgA) immune complexes with the classic manifestations of purpura, arthritis, arthralgia, and gastrointestinal and renal involvements. We report a case of HSP nephritis that occurred 2 years after living-donor liver transplantation (LDLT). After pulse steroid administration, the patient's symptoms disappeared and blood markers normalized. To the best of our knowledge, this is the first HSP case to be reported in a liver transplant recipient.

Case Report of Extensive Isolated Spontaneous Celiac Trunk Dissection After Liver Transplantation.

Arterial dissection is a rare complication after liver transplantation (LT). We report a case of extensive isolated spontaneous celiac trunk dissection (ISCTD) up to the proper hepatic artery, left gastric artery, and splenic artery after living donor liver transplantation. A 48-year-old woman with cryptogenic liver cirrhosis underwent living donor liver transplantation. Intraoperative and postoperative Doppler ultrasound revealed sufficient flow in the hepatic artery, portal vein, and hepatic vein. On postoperative day (POD) 10, Doppler ultrasound showed reduction of hepatic arterial flow. On POD 16, a contrast-enhanced computed tomography scan showed that the ISCTD extended to the proper hepatic artery, left gastric artery, and splenic artery with an entry tear on the proximal side of the celiac trunk. Although the computed tomography scan showed ischemia of a small part of the liver, blood flow to the liver was kept to some extent. Because all false lumens were occluded by thrombi and the liver enzyme levels normalized, we chose conservative therapy with antiplatelet agents. The patient was discharged on POD 53. She remains well without any liver dysfunction after 18 months with reduction in all false lumens and a patent hepatic artery. Several cases of ISCTD have been reported apart from LT, most of which were treated with conservative therapy. We conclude that conservative therapy could be the first choice in ISCTD even after LT.

Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases?: A systematic review.

PURPOSE: This study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival in patients with initially unresectable colorectal liver metastases (CRLM). METHODS: We reviewed the literature of prospective, controlled trials of systemic chemotherapy for patients with unresectable liver-only CRLM, including resectable extrahepatic metastases. Pearson's correlation coefficients were calculated. RESULTS: A total of 26 patient groups from 18 studies were reviewed. The response rate was significantly correlated with the conversion rate (r = 0.66) and R0 resection rate (r = 0.43) in overall patients. In subgroup analysis, only the conversion rate in patients with chemotherapy only (r = 0.75) and anti-EGFR therapy (r = 0.78) were significantly strongly correlated with the response rate. A non-significant strong trend toward correlation between response and conversion rates was observed in patients with bevacizumab (r = 0.73, p = 0.10). The regression line in the scatter plot of patients using bevacizumab showed a less steep slope. This indicated that conversion rates were relatively less affected by response rates under anti-VEGF therapy compared with the other patient groups. The response rate in chemotherapy-only patients was significantly correlated with median progression-free survival (r = 0.61) and overall survival (r = 0.66). CONCLUSIONS: Chemotherapy without molecular target agents and with anti-EGFR agents shows similar results of correlation between response and conversion/R0 resection rates. Under anti-VEGF therapy, conversion would be expected, even with a relatively lower response rate.

Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition.

Once inner ear hair cells (HCs) are damaged by drugs, noise or aging, their apical structures including the stereociliary arrays are frequently the first cellular feature to be lost. Although this can be followed by progressive loss of HC somata, a significant number of HC bodies often remain even after stereociliary loss. However, in the absence of stereocilia they are nonfunctional. HCs can sometimes be regenerated by Atoh1 transduction or Notch inhibition, but they also may lack stereociliary bundles. It is therefore important to develop methods for the regeneration of stereocilia, in order to achieve HC functional recovery. Espin is an actin-bundling protein known to participate in sterociliary elongation during development. We evaluated stereociliary array regeneration in damaged vestibular sensory epithelia in tissue culture, using viral vector transduction of two espin isoforms. Utricular HCs were damaged with aminoglycosides. The utricles were then treated with a γ-secretase inhibitor, followed by espin or control transduction and histochemistry. Although γ-secretase inhibition increased the number of HCs, few had stereociliary arrays. In contrast, 46 h after espin1 transduction, a significant increase in hair-bundle-like structures was observed. These were confirmed to be immature stereociliary arrays by scanning electron microscopy. Increased uptake of FM1-43 uptake provided evidence of stereociliary function. Espin4 transduction had no effect. The results demonstrate that espin1 gene therapy can restore stereocilia on damaged or regenerated HCs.

Prediction of the remnant liver hypertrophy ratio after preoperative portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.

Histone deacetylase inhibition enhances adenoviral vector transduction in inner ear tissue.

Adenovirus vectors (AdVs) are efficient tools for gene therapy in many tissues. Several studies have demonstrated successful transgene transduction with AdVs in the inner ear of rodents [Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y (2003) J Neurosci 23:4395-4400]. However, toxicity of AdVs [Morral N, O'Neal WK, Rice K, Leland MM, Piedra PA, Aguilar-Cordova E, Carey KD, Beaudet AL, Langston C (2002) Hum Gene Ther 13:143-154.] or lack of tropism to important cell types such as hair cells [Shou J, Zheng JL, Gao WQ (2003) Mol Cell Neurosci 23:169-179] appears to limit their experimental and potential clinical utility. Histone deacetylase inhibitors (HDIs) are known to enhance AdV-mediated transgene expression in various organs [Dion LD, Goldsmith KT, Tang DC, Engler JA, Yoshida M, Garver RI Jr (1997) Virology 231:201-209], but their effects in the inner ear have not been documented. We investigated the ability of one HDI, trichostatin A (TSA), to enhance AdV-mediated transgene expression in inner ear tissue. We cultured neonatal rat macular and cochlear explants, and transduced them with an AdV encoding green fluorescent protein (Ad-GFP) under the control of a constitutive promoter for 24 h. In the absence of TSA, GFP expression was limited, and very few hair cells were transduced. TSA did not enhance transduction when applied at the onset of Ad-GFP transduction. However, administration of TSA during or just after Ad-GFP application increased GFP expression in supporting cells approximately fourfold. Moreover, vestibular hair cell transduction was enhanced approximately sixfold, and that of inner hair cells by more than 17-fold. These results suggest that TSA increases AdV-mediated transgene expression in the inner ear, including the successful transduction of hair cells. HDIs, some of which are currently under clinical trials (Sandor et al., 2002), could be useful tools in overcoming current limitations of gene therapy in the inner ear using Ad-GFP.

Significance of Tei-index alterations induced by acute preload reduction with hemodialysis.

AIM: The load dependence of Tei-index, an index to estimate combined systolic and diastolic ventricular functions, remains controversial. Moreover, its significance in the setting of acute preload reduction including hemodialysis (HD) remains unknown. Therefore, we examined the significance of the Tei-index in HD patients. PATIENTS AND METHODS: Doppler echocardiographic parameters of 42 patients with normal left ventricular ejection fraction (LVEF) were evaluated before and after HD. Based on the index of body water excess calculated using a Crit-Line monitor, the patients were assigned to Group A (normal hydration approximately overhydration) and Group B (risk of pulmonary congestion). RESULTS: Group A was younger and had a shorter isovolumic relaxation time (IRT) than Group B before HD. Hemodialysis significantly increased the Tei-index of Group A, which was derived from prolonging IRT and isovolumic contraction time and shortening the ejection time without changing LVEF. Changes in the Tei-index (DeltaTei-index) significantly correlated with the rate at which blood volume decreased. They were derived from graphs generated using the Crit-Line monitor. Furthermore, the DeltaTei-index inversely correlated with the Tei-index before HD. CONCLUSION: These findings suggest that the Tei-index is preload-dependent, which is related to changes in volume and speed. Thus, the Tei-index should be cautiously interpreted according to various hemodynamic situations. However, the correlation between the DeltaTei-index and the Tei-index before HD implies that the latter could be a good indicator of effective fluid removal by HD.

Pioglitazone treatment stimulates circulating CD34-positive cells in type 2 diabetes patients.

Circulating bone marrow derived immature cells, including CD34-positive (CD34(+)) cells, contribute to maintenance of the vasculature, not only as a pool of endothelial progenitor cells (EPCs), but also as a source of growth/angiogenesis factor. We hypothesized that the thiazolidineone compound pioglitazone could stimulate the circulating CD34(+) cells in diabetic patients. Thirty-four patients with type 2 diabetes received 15-30 mg pioglitazone for 24 weeks. The number of circulating CD34(+) cells significantly increased at 12 and continued this effect for 24 weeks (1.08+/-0.39, 1.34+/-0.34 and 1.32+/-0.28cells/microl at 0, 12 and 24 weeks, respectively). The change of CD34(+) cell levels (DeltaCD34(+) cells) between 0 and 12 weeks was significantly correlated with the change of high sensitive C reactive protein levels (Deltahs-CRP) and change in adiponectin levels (Deltaadiponectin) (r=-0.412, r=0.359, respectively). Our study demonstrated that pioglitazone treatment increased circulating CD34(+) cells, suggesting that this effect may at least partly contribute to the anti-atherosclerotic action of pioglitazone.

Influence of hemodialysis on echocardiographic Doppler indices of the left ventricle: changes in parameters of systolic and diastolic function and Tei index.

AIMS: Numbers of previous studies have evaluated the influence of dialysis-induced altered loading condition on Doppler-echocardiographic indices of left ventricle in patients with chronic renal failure. It has been suggested that most of Doppler-derived indices are preload-dependent. On the other hand, there are no studies that have evaluated the influence of hemodialysis on Tei index; a new Doppler-derived index obtained by isovolumetric contraction time plus isovolumetric relaxation time divided by ejection time. The aim of this study is to evaluate whether Tei index is also influenced by dialysis-induced altered loading condition as well as other Doppler-derived indices, and to assess the possibility that Tei index is also preload-dependent. PATIENTS AND METHODS: Thirty-two patients with chronic renal failure (21 men and 11 women, aged 48-93 years) on maintenance hemodialysis were evaluated for Doppler-derived indices before and after hemodialysis. We studied parameters of diastolic function (peak velocities of mitral inflow in early diastole (E) and late diastole from atrial filling (A), ratio of A to E (A/E), deceleration time (DT), and isovolumetric relaxation time (IRT)), parameters of systolic function (ejection time (ET), pre-ejection period (PEP), ratio of PEP to ET (PEP/ET), and isovolumetric contraction time (ICT)) and Tei index. RESULTS: Hemodialysis resulted in significant decreases in E, increase in A/E, prolongation of IRT, no change in A and DT; significant prolongation of ICT and PEP, shortening of ET, and increase in PEP/ET and a significant increase in Tei index (0.42 +/- 0.16 vs 0.51 +/- 0.16, p < 0.0001). When patients were subdivided into 2 groups based on weight loss after hemodialysis (> or = 1.5 kg and < 1.5 kg), only the group that lost > or = 1.5 kg had significant change in Tei index before and after hemodialysis (0.40 +/- 0.15 vs 0.52 +/- 0.17, p = 0.0002). CONCLUSION: This study demonstrates that not only most of Doppler-derived indices but also Tei index is affected by dialysis-induced altered loading condition and suggests that Tei index is possibly preload-dependent.

Suppression of tumor necrosis factor-alpha production and neutrophil infiltration during ischemia-reperfusion injury of the liver after heat shock preconditioning.

BACKGROUND/AIMS: Heat shock preconditioning provides the liver with ischemic tolerance. In this study we examined the effects of heat shock preconditioning on hepatic nonparenchymal cells in light of tumor necrosis factor-alpha (TNF-alpha) production and neutrophil infiltration. METHODS: Rats were exposed to heat shock pretreatment at 42 degrees C in the heat shock group (group HS) and at 37 degrees C in the control group (group C). After a 48-h recovery, the left hepatic lobes were given a 90-min ischemia and reperfused. Plasma concentrations of TNF-alpha, cytokine-induced neutrophil chemoattractant (CINC) and alanine aminotransferase (ALT) were measured. Liver tissues were checked for the presence of TNF-alpha mRNA. Histological staining for CINC and polymorphonuclear leukocyte (PMN) was also evaluated. RESULTS: In group HS, plasma TNF-alpha levels were significantly more suppressed than in group C (P<0.0001). Expressions of TNF-alpha mRNA in the liver was suppressed in group HS. Production of CINC 2 h after reperfusion was reduced in group HS (P<0.05). PMN infiltration was significantly reduced in group HS (P<0.01). In group HS, liver histology revealed less cellular damage and the plasma level of ALT was significantly reduced (P<0.0001). CONCLUSIONS: Heat shock preconditioning suppressed the production of TNF-alpha and CINC in the liver during reperfusion and consequently reduced neutrophil infiltration.

Prognosis of patients with rounded atelectasis undergoing long-term hemodialysis.

We present 4 patients undergoing hemodialysis in whom thoracic computed tomography (CT) suggested a diagnosis of rounded atelectasis (RA) with pleural effusion. The clinical setting and follow-up CT of all 4 patients confirmed this diagnosis. The pleural fluid of each appeared serosanguineous or hemorrhagic and predominantly consisted of lymphocytes. Biochemical analysis of this fluid revealed high levels of total protein, lactate dehydrogenase and glucose. Bacterial culture and polymerase chain reaction for Mycobacterium tuberculosis DNA was negative. Pleural biopsy specimens from 2 of the 4 patients showed evidence of fibrinous change and mesothelial cell hyperplasia. Pleural effusion from all 4 patients did not respond to either fluid restriction or aggressive hemodialysis-induced dehydration. The subsequent clinical course and thoracentesis were repeated, and in 1 patient, this was followed by tetracycline pleurodesis. However, 2 patients died during pre-pleurodesis and 1 died during post-pleurodesis, all due to respiratory failure. We propose that the clinical setting and follow-up thoracic CT and thoracentesis of patients receiving long-term hemodialysis confirmed a diagnosis of rounded atelectasis with uremic pleural effusion. We also propose that the prognosis of patients with refractory pleural effusion receiving long-term hemodialysis would be improved by early pleurodesis.

In situ pedicle resection in left trisegmentectomy of the liver combined with reconstruction of the right hepatic vein to an inferior vena caval segment transpositioned from the infrahepatic portion.

A combination of an in situ pedicle resection of the liver and a hepatic vein reconstruction using a cranially transpositioned segment of the IVC after implantation of an ePTFE graft at the missing IVC was useful in treating a patient who suffered from a huge liver tumor involving all of the hepatic venous confluence and the IVC. Although early tumor recurrence remains an unresolved problem for such patients, a surgical approach is feasible. This technique can be justified as a therapeutic modality, not only because it improves quality of life, but also because it provides patients with an opportunity for additional treatment.

Interaction between cytochrome P450 and other drug-metabolizing enzymes: evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase.

Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions.

Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS: We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had end-stage renal disease prior to induction of CAPD. RESULTS: In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD. CONCLUSION: Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.

[A case of systemic lupus erythematosus associated with minimal change nephrotic syndrome].

A case of systemic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) in a 25-year-old female is described. The patient suddenly manifested butterfly rash and proteinuria was first pointed out on March, 1994. On admission, her skin biopsy indicated SLE. Subsequently, she developed nephrotic syndrome. Urinalysis showed heavy proteinuria (4.1 g/day), with no other abnormalities in the urinary sediment. Immunological examination revealed positive antinuclear antibody at a titer of 1:80 with a speckled pattern. Anti-ssDNA and anti-SS-A antibodies were positive, but other antibodies were negative. Serum complement (CH50) was within the normal range (30.5 U/ml). The renal biopsy showed no apparent cellular proliferation or increase of extracellular matrices in glomeruli by light microscopy. Slight deposition of IgG, IgM, C3 and C1q was focally seen in the mesangium and capillary wall by immunofluorescence. Electron microscopic examination revealed small and scattered dense deposits in the mesangium, subepithelium and subendothelium, associated with diffuse fusion of the foot processes of epithelial cells along the glomerular basement membrane. According to the WHO classification, the histological features were compatible with those of lupus nephritis (LN), class Ib. The patient was treated with PREDNISOLONE, Mizorbine and Dilazep, resulting in the disappearance of proteinuria and a normal serum level of total protein. The association of LN and MCNS is very rare. We also investigated the relationship between the intensity of proteinuria and histological types of 53 cases with LN examined in our laboratory. The cases with heavy proteinuria were mostly classified as WHO-Class IV and Class V. We report here a case of LN associated with MCNS and also review the literatures.

Induction of rat hepatic cytochrome P450 2B subfamily by azidophenobarbital, as a possible photoaffinity probe for the putative phenobarbital receptor: comparative study with modified phenobarbitals with different functional groups.

To study the specific target to which phenobarbital (PB) binds, resulting in the induction of cytochrome P450, we prepared two azido-PBs (AZPBs) as photoaffinity ligands. The azido substituent was introduced at the para- or meta-position of the PB aromatic ring. In this study, we estimated the utility of these compounds by examining their inducing activities in vivo in rats. Induction was assessed by immunoblotting with anti-CYP2B1/2 antibody and measuring testosterone-metabolizing activity, using hepatic microsomes. Administration of p-AZPB to rats increased hepatic CYP2B1/2 protein and testosterone 16beta-hydroxylase activity, although the effects were less than those of unmodified PB. m-AZPB showed no effect in the induction of CYP2B1/2. To assess the specificity of the effects of substituents, we compared the inducing activities of p/m-nitro-PBs, p/m-amino-PBs, and p/m-hydroxy-PBs with those of AZPBs. The results showed that p-nitro-PB, m-amino-PB, and p-hydroxy-PB were also potent inducers for CYP2B1/2, with lower activity than that of unmodified PB, whereas the other three isomers had no effect. These results suggest that 1) the absence of any substituents on the aromatic ring of PB is needed for maximal inducing activity and 2) substitution at the meta-position of the PB aromatic ring tends to reduce effectiveness as an inducer more than does substitution at the para-position. Because p-amino-PB and p-acetylamino-PB, the minor and major metabolites of p-AZPB, respectively, were without effect in the induction of CYP2B1/2, the effect of p-AZPB was considered to be due to the unchanged compound itself. The present study demonstrates that, based on the weak but positive ability to induce CYP2B1/2, p-AZPB may be a useful tool for identifying the putative PB receptor.

Visualization of RNA secondary structures using highly parallel computers.

Results of RNA secondary structure prediction algorithm are usually given as a set of hydrogen bonds between bases. However, we cannot know the precise structure of an RNA molecule by only knowing which bases form hydrogen bonds. One way to understand the structure of an RNA molecule is to visualize it using a planar graph so that we can easily know the geometric relations among the substructures such as stacking regions and loops. To do this, we consider bases to be particles on a plane and introduce a repulsive force and an attractive force among these particles and determine their positions according to these forces. A naive algorithm requires O(N2) time but we can reduce it to O(NlogN) with an approximation algorithm which is often used in the area of N-body simulation. Our program is written in parallel object-oriented language 'Schematic' which is recently developed. Efficiency of our implementation on a parallel computer and results of visualization of secondary structures are presented using cadang-cadang coconut viroid as an example.

Nephrotic syndrome in the elderly--clinicopathological study.

Clinical and pathological findings and the effects of therapy were investigated in 90 cases of nephrotic syndrome (NS) in elderly patients aged over 60 years. Membranous nephropathy was the most frequent type of primary NS. Amyloidosis and malignancy were common causes of secondary NS. Damage to the interstitium in the kidney, such as focal mononuclear cell infiltration, fibrosis and thickening of the small arterial wall in membranous cases, was often observed. Stage I and II based on electron-microscopy, were mainly observed in the patients, with membranous nephropathy. Prednisolone and immunosuppressive agent were most effective in these patients with membranous nephropathy. Prednisolone alone was the most effective on minimal change NS in the elderly. In the course of therapy, side effects such as pneumonia, sepsis due to fungus infections, such as aspergillus and candida, and infection, such as cytomegalovirus and herpes zoster, were more frequently observed, especially in the cases of MPGN, DPGN with moderate to severe mesangial proliferation, with a decline in renal function (Ccr < 50 L/day) and secondary NS. In secondary NS, the prognosis of amyloidosis was very poor and the findings pointed to a relationship between malignancy and nephrotic syndrome.