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Biomedical subjects

Fumitake Gejyo

Publications and source records attributed to Fumitake Gejyo.

At least 91 records · Page 5Linked to original sources

A case of Takayasu arteritis complicated with glomerulonephropathy mimicking membranoproliferative glomerulonephritis.

We report on a 65-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria, hypertension, and renal dysfunction. Renal angiography demonstrated moderate irregular narrowing of both renal arteries. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening ("double contour") accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. Electron microscopy showed no subendothelial deposit and no circumferential mesangial interposition (CMI), and these findings are different from MPGN. In this report we present a case of Takayasu arteritis associated with glomerulonephropathy mimicking MPGN.

Aged↗

Renal function at the time of renal biopsy as a predictor of prognosis in patients with primary AL-type amyloidosis.

BACKGROUND: Amyloid light-chain (AL)-type amyloidosis is a plasma cell disorder with a poor prognosis for survival. Although prognostic factors, such as the number of organs involved and heart function or failure in respond to therapy have been clarified based on studies including a large series of patients, there are large interindividual differences in the prognosis of patients with primary AL-type renal amyloidosis. METHODS: To clarify the prognostic factors of AL-type renal amyloidosis, we retrospectively investigated the clinical manifestations, histopathological data, and prognosis of 21 patients with amyloidosis, who had been diagnosed by renal biopsy. RESULTS: Eleven patients died, at a mean observational time of 21.7 months after renal biopsy, whereas the mean observational time was 51.0 months for the 10 patients who survived. The creatinine clearance rate was significantly higher, and the serum creatinine concentration and the grade of interstitial damage were significantly lower in surviving patients (P < 0.05). The presence of amyloid fibrils in organs other than the kidney did not influence prognosis for survival. However, the intraventricular septum was thinner in surviving patients (P < 0.1). Thirteen patients had undergone melphalan-prednisolone therapy, but it did not affect prognosis for survival. Cox proportional hazard regression analysis revealed that the renal function at the time of diagnosis was a significant and independent prognostic factor for survival. CONCLUSIONS: Our study demonstrated that renal function at the time of biopsy and renal interstitial damage are the best predictors of survival in AL-type renal amyloidosis.

Amyloid↗

A case of pneumatosis cystoides intestinalis in a patient with polymyositis and interstitial pneumonia.

We report the case of a 49-year-old man who presented with pneumatosis cystoides intestinalis associated with polymyositis and interstitial pneumonia. Three months after the administration of prednisolone and cyclosporine, he noticed mild abdominal distension, and a radiographic examination showed intraperitoneal free gas and intramural gas, suggestive of pneumatosis cystoides intestinalis (PCI). Additional treatment with a combination of doxycycline and high-dose oxygen therapy was effective in relieving the clinical symptoms and reducing the intramural gas.

Journal Article↗

Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sjögren's syndrome.

BACKGROUND: To investigate the ratio of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) in primary Sjögren's syndrome (PSS), patients and healthy subjects MMP-2, 9 and TIMP-1, 2 levels were measured in saliva. METHODS: Stimulated whole-mixed saliva was collected from 32 patients and 26 healthy subjects. MMP-2, 9 and TIMP-1, 2 levels were measured using enzyme-linked immunosorbent assay (ELISA) and the sandwich enzyme immunoassay (sandwich EIA). Zymography and reverse zymography were used to identify MMPs and TIMPs. RESULTS: MMP-9 (gelatinase-B) level in saliva was significantly increased in the patients. MMP-9 (ng/ml): patients 231.02 +/- 151.77 (mean +/- S.D.), healthy subjects 145.87 +/- 111.65 (p < 0.05). MMP-2 levels were not detected with this system kit in either healthy subjects or patients. The differences in TIMPs were only trends and not statistically significant (p > 0.05). Accordingly, MMP-9/TIMP-1 was greatly increased in the patients (2.60 +/- 1.18) than in the healthy subjects (1.28 +/- 1.11) (p < 0.01). CONCLUSION: This study found that MMP-9/TIMP-1 and MMP-9 levels in the saliva were significantly higher in pSS patients than those in healthy subjects. Our results indicate that the increase in MMP-9/TIMP-1, rather than the increase in MMP-9, in pSS patients' saliva is strongly involved in destruction of glandular and salivary duct tissues.

Enzyme-Linked Immunosorbent Assay↗

Visualization of a functional KSHV episome-maintenance protein LANA in living cells.

The latency-associated nuclear antigen (LANA) of Kaposi's saroma-associated herpesvirus (KSHV) can maintain a plasmid containing the KSHV origin of DNA replication (oriP) as episomes in dividing human cells. Hence, LANA is considered to play crucial roles in persistent KSHV infection in human cells. In this study, we characterized a LANA fusion protein of green fluorescent protein (GFP-LANA). Like the wild-type LANA, GFP-LANA interacted tightly with mitotic chromosomes, and maintained the plasmid selectively with the KSHV oriP for more than three weeks in a human B cell line. Moreover, equivalent amount of GFP-LANA protein was segregated into two daughter cells in living metaphase cells. Our results suggested that the activity of LANA serves the segregation of equivalent amounts of viral genomes tethered with LANA into two daughter progeny cells during cell division. Thus, GFP-LANA is a useful tool for the analyses of the functions and dynamics of LANA in living cells.

Antigens, Viral↗

Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome.

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p-aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26 +/- 0.04 to 0.23 +/- 0.03 (P < 0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.

Aged↗

Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. METHODS: Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. RESULTS: Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001). CONCLUSION: Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.

Adolescent↗

A clinicopathological study on the long-term efficacy of tonsillectomy in patients with IgA nephropathy.

Our study evaluated the clinical efficacy of tonsillectomy on the long-term renal survival in patients with primary IgA nephropathy (IgAN). Forty-six patients underwent tonsillectomy, and 74 patients did not. The mean of follow-up duration of all patients was 197.0+/-29.3 months (61-339 months). The baseline clinical and histological data at renal biopsy were not statistically different between the two groups with and without tonsillectomy. Five (10.9%) of the tonsillectomy group reached end stage renal failure (ESRF), whereas 19 (25.8%) of the non-tonsillectomy group did. The chi-square test between the two groups showed a significant difference (p <0.05). The renal survival of the tonsillectomy group was significantly higher than that of the non-tonsillectomy group by the Kaplan-Meier method with log-rank test (p <0.05). The Cox regression model also revealed that tonsillectomy had a significant favorable impact on the renal survival in long-term follow-up duration (p <0.05). Although our study was done by retrospective analyses, all the results proved that tonsillectomy had significant favorable effects on the long-term renal survival in patients with IgAN.

Adult↗

Rhabdomyolysis after simvastatin therapy in an HIV-infected patient with chronic renal failure.

We encountered a 49-year-old HIV-infected man with chronic renal insufficiency who developed rhabdomyolysis after treatment with simvastatin. He recovered after initiating hemodialysis and discontinuing oral medications. Rhabdomyolysis most likely resulted from an excessive blood concentration of simvastatin caused by concomitant use of fluconazole in the presence of renal insufficiency.

Adult↗

Intact PTH assay overestimates true 1-84 PTH levels after maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Although the so-called intact parathyroid hormone (iPTH) assay detects not only true 1-84 PTH (1-84PTH) but also large C-terminal PTH fragments, it remains inconclusive whether the 1-84PTH assay is more useful in clinical practice. Previous studies have shown that the results of these two PTH assays in dialysis patients are closely correlated. METHODS: Chronic dialysis patients whose plasma iPTH levels were >400 pg/ml were selected for inclusion in the present study. Following a 4 week wash-out time during which all vitamin D administration was halted, maxacalcitol was intravenously injected at the end of dialysis sessions three times per week for 24 weeks, at an initial dosage of 10 micro g. RESULTS: Ninety-seven patients with secondary hyperparathyroidism were included in our analysis. Their serum calcium levels were elevated from the start levels while phosphate levels remained unchanged. The plasma 1-84PTH levels constantly declined throughout the 24 weeks. Although the patients' plasma 1-84PTH and iPTH levels were closely correlated with each other both at the beginning of the study and after 24 weeks of maxacalcitol therapy, the ratio of 1-84PTH/iPTH consistently decreased throughout the study period (P<0.01). The changes in the ratio were significantly correlated with changes in serum calcium levels. CONCLUSIONS: Twenty-four weeks of intravenous maxacalcitol injection therapy significantly reduced the 1-84PTH/iPTH ratio. Estimated 1-84PTH levels from iPTH levels using a conversion formula obtained before the treatment were 21.0+/-20.4% higher than measured 1-84PTH levels after the therapy. Thus, iPTH measurement has a potential risk to overestimate 1-84PTH levels when evaluating the efficacy of maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

Calcitriol↗

Glycosaminoglycans enhance the trifluoroethanol-induced extension of beta 2-microglobulin-related amyloid fibrils at a neutral pH.

beta(2)-Microglobulin-related (A beta 2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis, and beta(2)-microglobulin is a major structural component of A beta 2M amyloid fibrils. Several biologic molecules inhibiting the depolymerization of A beta 2M amyloid fibrils at a neutral pH were found recently. The effect of trifluoroethanol and glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was investigated with the use of fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at concentrations of up to 20% (vol/vol) caused fibril extension of heparin-stabilized seeds, inducing a subtle change in the tertiary structure of beta(2)-microglobulin and stabilizing the fibrils at a neutral pH. This extension reaction followed a first-order kinetic model. In addition, some GAG, especially heparin, dose-dependently enhanced the fibril extension. These results suggest that some GAG, especially heparin, may bind to the fibrils and enhance their deposition in vivo. Thus, the experimental system described here should be useful to search for the factors that accelerate A beta 2M amyloid deposition in vivo. In addition, the interference of the binding of GAG to A beta 2M amyloid fibrils may be an attractive therapeutic modality.

Amyloid↗

Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy.

Although there are many papers about IgA nephropathy (IgAN) and tonsils, respectively, reviews about the relationship between tonsils, tonsillitis, tonsillectomy, and IgAN are limited. In this review, we introduced the structure, development, and function of tonsils, difference of tonsils with and without IgAN, consistency of both tonsillar IgA and glomerular IgA, the effect of tonsil stimulation, tonsil infection, and tonsillectomy on IgAN showed some evidences in which tonsils were closely related to IgAN and polymeric IgA1 deposited in glomerular mesangium were at least in part of tonsillar origin. Tonsillectomy can improve the urinary findings, keep stable renal function, improve mesangial proliferation and IgA deposit, have a favorable effect on long-tern renal survival in some IgAN patients, and do not cause significant immune deficiency and do not increase incidence of the upper respiratory tract infections, and can be used as a potentially effective treatment. The indications of tonsillectomy in patients with IgAN include mainly the deterioration of urinary findings after tonsillar infection, mild or moderate renal damage. However, tonsillectomy may not be enough and may not change the prognosis in IgAN patients with marked renal damage.

Bacterial Infections↗

Real-time observation of glomerular hemodynamic changes in diabetic rats: effects of insulin and ARB.

BACKGROUND: The progression of diabetic nephropathy is closely related to disturbances in glomerular hemodynamics, such as glomerular hypertension and/or hyperperfusion. The aim of this study was to observe and to analyze glomerular hemodynamics in rats with diabetes mellitus (DM) in vivo using confocal laser scan microscopy (CLSM). We also examined the effects of candesartan cilexetil (TCV-116), a selective angiotensin II type 1 receptor blocker (ARB), on glomerular hemodynamics in DM. METHODS: Munich-Wistar rats were divided into six groups: (1) four-day control; (2) four-day DM; (3) 28-day control; (4) 28-day DM; (5) DM treated with insulin; (6) DM treated with TCV-116. The kidney-to-body weight ratio, glomerular volume, and proteinuria were estimated. Glomerular hemodynamic changes were observed using CLSM and renal expression of endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) was evaluated by immunofluorescence. RESULTS: The kidney-to-body weight ratio, glomerular volume, the diameters of afferent arterioles (AA) and efferent arterioles (EA), erythrocyte velocities within glomeruli, and volume flow in glomerular capillary loops in four-day DM were significantly higher than in control rats, and increases were even more pronounced in the 28-day DM. TCV-116 treatment ameliorated all these findings and significantly decreased proteinuria, but there was no effect on the blood glucose level. On the other hand, insulin treatment was followed by normalization of all these changes induced in DM. Enhanced renal expression of eNOS in DM was suppressed when treated with either TCV-116 or insulin, while expression of nNOS was unaltered among the four groups. CONCLUSION: This imaging procedure allowed us to evaluate glomerular microcirculation in vivo, including the diameters of AA and EA, erythrocyte velocity, and volume flow. DM significantly induced glomerular hemodynamic alteration and renal hypertrophy. DM treated with either insulin or ARB ameliorated these changes. This study shows that progress in imaging technology promises to make major contributions to revealing the involvement of hemodynamic changes in glomerular diseases, aiding prognosis and the monitoring of therapeutic effects, as well.

Angiotensin II Type 1 Receptor Blockers↗

Arresting dialysis-related amyloidosis: a prospective multicenter controlled trial of direct hemoperfusion with a beta2-microglobulin adsorption column.

We investigated the clinical efficacy of direct hemoperfusion with a beta2-microglobulin (beta2-m) adsorption column for the treatment of patients with dialysis-related amyloidosis. A 2-year prospective controlled study was performed to compare the effects of passaging blood through a (beta2-m) adsorption column (Lixelle) before it is passaged through the dialysis polysulfone membrane on the severity of amyloidosis in these individuals. Patients (n = 22) whose blood went through the Lixelle column prior to dialysis had a higher beta2-m removal rate compared to an equal number of controls, and they showed earlier improvement in their symptoms which included impaired daily activities, joint stiffness, and pain. The appearance of additional bone cysts was prevented in pre-adsorbed patients but not in the controls. Thus, the Lixelle column is useful in preventing the progression of dialysis-related amyloidosis and in ameliorating or arresting the progression of the symptoms of this disorder.

Activities of Daily Living↗

2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic hemodialysis patients. We advocate an initial dosage of 1500 U three times per week. The fifth section deals with the factors refractory to treatment with rHuEPO. If the patient shows an inadequate response to the usage of 9000 U per week, this condition defines the inadequate response to rHuEPO in Japan. Blood transfusion must be avoided where possible. The reasons for this and the adverse effects are interpreted in section six. In the final section, the adverse effects of rHuEPO are listed. Among them, hypertension, thrombotic events and secondary red cell aplasia were emphasized as the major complications.

Anemia↗

Differentiation-induced cultured podocytes express endocytically active megalin, a heymann nephritis antigen.

BACKGROUND/AIMS: Megalin is a multiligand endocytic receptor expressed in a number of epithelia. In the Lewis rat kidney, podocytes, as well as proximal tubule cells, express megalin that acts as a pathogenic antigen for Heymann nephritis (HN), an experimental model of membranous nephropathy. To obtain a tool to investigate the molecular mechanisms of megalin-mediated endocytosis and the pathogenesis of HN, we examined whether a differentiation-inducible mouse podocyte cell line expressed endocytically active megalin. METHODS: Immunofluorescence and immunoprecipitation analyses with an anti-rat megalin antibody were carried out to investigate whether megalin was expressed in the differentiated and undifferentiated podocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to elucidate whether the cells synthesize megalin mRNA. 125I-labeled receptor-associated protein (RAP), an endocytic ligand for megalin, was used for cellular internalization and degradation assays. RESULTS: Immunofluorescence, immunoprecipitation and RT-PCR analyses revealed that megalin was synthesized in both differentiated and undifferentiated cells and localized to the cell surfaces. Effective endocytosis of RAP via megalin was shown under the differentiated condition. CONCLUSION: Endocytically active megalin is expressed in differentiation-induced cultured podocytes. This cell line could be a useful tool for studies on megalin-mediated endocytosis and the pathogenesis of HN.

Animals↗

Expression of osteopontin in cisplatin-induced tubular injury.

Osteopontin (OPN) is considered as a key protein in cell regeneration. OPN is thought to have many functions in cell-cell binding and cell-matrix binding via OPN receptors in various organs. But there is little information on the precise role of OPN. To clarify the functional role of OPN in tubular injury, we performed in situ hybridization and immunohistochemical analysis of the expression of OPN in a renal cortical necrosis model induced by cisplatin from the acute injury to late recovery phases. In the acute injury phase, both mRNA and protein of OPN were markedly induced in damaged tubular lumens with cell debris. In the late recovery phase, on the other hand, OPN protein and mRNA were observed in dilated and flattened tubular epithelial cells showing a regenerative appearance. Most of these cells were also immunostained with CD44, a receptor of OPN. PCNA staining was also co-localized with these expressions. In light of the CD44 function regulating cell proliferation, these findings suggest that OPN may contribute to regeneration of tubular epithelial cells during the acute to late recovery phases of cortical tubular damage induced by cisplatin.

Animals↗