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E Imai

Publications and source records attributed to E Imai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy.

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

Adolescent↗
PubMed2001

Application of bone marrow-derived stem cells in experimental nephrology.

Recent advancement in developmental biology has led to the discovery of immature mesenchymal stem cells in bone marrow and several established organs. The therapeutic potentials of such stem cells for treating serious diseases constitute a major rationale for every research effort, and clinical trials for replacing some damaged tissues such as cartilage are currently under way. Although the feasibility of such stem cell therapies for renal diseases remains unknown, it is worthy of pursuing possibilities. As an experimental tool, we have made chimeric rats that carry the bone marrow of transgenic rats expressing green fluorescent protein (GFP) throughout the body. All marrow lineages can be traced with bright green fluorescence regardless of their terminal phenotypes in chimeric rats. When compared with other conventional strategies for tracking bone marrow-derived cells, our system is highly sensitive and allows us to take advantage of the rat nephrology. Using this system, we have reported that bone marrow provides mesangial cells during repair process. In this manuscript, we briefly summarize our experiences.

Animals↗
PubMed2001

[Gene therapy and tissue engineering in nephrology and renal transplantation].

Human genome project will be completed in 2003 and we will soon obtain the information of the whole DNA sequence of the human genome. This should affect the therapy of progressive renal diseases since we have no effective remedy to cure the renal diseases. Gene therapy, renal engineering and generation of new drug can be achieved by using the information of human genome. In this context, we described our recent endeavors concerning the gene therapy of transplant kidney, seeking the renal stem cells and reprogramming factors, and exploring genes related to renal fibrosis. Completion of bioinformatics, can facilitate the above post-genome project.

Animals↗
PubMed2000

Clinicopathological evaluation in non-episode biopsies of renal transplant allograft.

Histopathological findings in renal allograft with stable function remain unclear. We therefore performed non-episode biopsy in the long-surviving renal allograft to investigate the histopathological changes. Our data show that, although arteriolopathy is characteristic of drug-induced nephropathy, it is unrelated to dosage and concentration of cyclosporine or tacrolimus in non-episode biopsy. We evaluated therefore the clinicopathological findings of arteriolopathy in this study. Non-episode biopsy was defined as follows: as serum creatinine level lower than, 2.0 mg/dl and a urinary protein level lower than 500 mg/day. A total of 65 biopsy specimens were enrolled in this study as non-episode biopsy. Twenty-nine specimens revealed arteriolopathy. There were no statistically significant differences between arteriolopathy and dosage or concentration of cyclosporine or tacrolimus. Arteriolopathy in non-episode biopsy was related to time of biopsy, kidney age, hypertension, and hyperlipidemia, suggesting that it is important for graft survival to strictly control blood pressure and blood lipid level.

Adult↗
PubMed2000

Differential diagnosis of prerenal azotemia from acute tubular necrosis and prediction of recovery by Doppler ultrasound.

Acute renal failure (ARF) is a life-threatening disease that often causes multiple organ dysfunction. The accurate and rapid diagnosis of the cause of ARF is particularly important for selecting the appropriate therapy. Ultrasound Doppler is a noninvasive diagnostic method that has recently been introduced to clinical nephrology. We report the diagnostic value of Doppler ultrasound in differentiating acute tubular necrosis (ATN) from prerenal azotemia by comparing this study with the fractional excretion of sodium (FENa), renal failure index (RFI), and urinary/serum creatinine (Cr) ratio. Doppler ultrasound was able to differentiate prerenal azotemia from ATN, equivalent to FENa, RFI, and the urinary/serum Cr ratio. Doppler ultrasound does not require blood or urine samples and can be performed at the bedside. Of note, Doppler is unaffected by changes in Na or Cr in urine or serum after diuretics or hemodialysis. Furthermore, one can predict recovery from ATN by Doppler findings. Thus, we consider Doppler ultrasound an effective diagnostic tool in ARF.

Adult↗
PubMed2000

Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy.

Diffuse proliferative immunoglobulin A (IgA) nephropathy has the potential risk for end-stage renal disease. However, treatment of IgA nephropathy has not been well established. To determine whether early treatment with corticosteroids ameliorates the proliferative lesions of diffuse proliferative IgA nephropathy, we conducted a prospective, randomized, controlled trial. Inclusion criteria were as follows: duration of abnormal urinalysis results less than 36 months, proteinuria less than 1.5 g/d of protein, serum creatinine level less than 1.5 mg/dL, and mesangial cell proliferation or matrix accumulation involving more than 50% of glomeruli. Twenty-one patients were randomly assigned to two groups: the corticosteroid group and the antiplatelet group. After 1 year of treatment, repeated renal biopsy was performed in 19 patients. We evaluated glomerular filtration rate, blood pressure, proteinuria, and histological parameters, including light microscopic findings and staining of alpha-smooth muscle actin (alphaSMA), as a marker of myofibroblast-like cells and fibronectin EDA (EDA-FN) as an indicator of renal fibrosis. After 1 year of treatment, proteinuria significantly decreased in the corticosteroid group. Histological findings, such as mesangial cell proliferation, mesangial matrix accumulation, and cellular crescents, showed significant improvement in the corticosteroid group but not in the antiplatelet group. Expression of alphaSMA in glomeruli significantly decreased in the corticosteroid group but not in the antiplatelet group. EDA-FN did not change in either group. We conclude that early treatment with corticosteroids for adult diffuse proliferative IgA nephropathy is effective in reducing renal injury.

Adult↗
PubMed2000

Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure.

The optimal target hematocrit (Ht) level in recombinant human erythropoietin (rHuEPO) therapy remains controversial and has hardly been investigated in predialysis patients. We prospectively studied the regression of left ventricular hypertrophy (LVH) on echocardiography in nine predialysis patients with chronic renal failure after a partial correction (target Ht, 30%) and normalization (target Ht, 40%) of the Ht with rHuEPO treatment. Twenty-four-hour ambulatory blood pressure monitoring was also performed. The administration of rHuEPO significantly increased Ht to the target values. The rate of renal failure progression did not change during rHuEPO treatment for 12 months (Cr, from 6.2 +/- 2.0 to 5.5 +/- 2.1 mg/dL). The left ventricular mass index (LVMI) tended to decrease after a partial correction of anemia (Ht, 32.1% +/- 1.8%) at 4 months, whereas it tended to significantly decrease after normalization of Ht (Ht, 39.1% +/- 2.4%) at 12 months (baseline, 140.6 +/- 12.1 g/m2; partial correction, 126.9 +/- 10.0 g/m2; normalization, 111.2 +/- 8.3 g/m2). All patients had received antihypertensive medication before rHuEPO administration, and additional drugs were also required in four cases during the study. As a result, a good overall blood pressure control was obtained without any adverse effects on the circadian blood pressure rhythm. In conclusion, from the perspective of LVH regression, the normalization of Ht was found to be more effective than that associated with a partial correction of anemia during rHuEPO therapy.

Aged↗
PubMed2000

Synthesizing oligomers from monomeric nucleotides in simulated hydrothermal environments.

Dimers and trimers of adenosine monophosphate (AMP) were synthesized from AMP in environments simulating hot vents on the sea floor of the primitive Earth. The simulated environments were made in the flow reactor, in which an aqueous solution of reactants was circulated from the hot to the cold region repeatedly. The oligomerization proceeded most significantly when the hot reaction solution at about 110 degrees C was abruptly ejected into the cold environment maintained at about 0 degree C.

Adenine Nucleotides↗
PubMed2000

Hydrothermal circulation of seawater through hot vents and contribution of interface chemistry to prebiotic synthesis.

Synthesizing oligopeptides from glycine and alanine in a flow reactor, which stimulates constant hydrothermal circulation of seawater through hot vents on the primitive Earth, demonstrated that an exponential growth of the products is possible. The initial rapid growth of the product is a consequence of using the products formed in one cycle as the starting materials for the cycle of synthesis.

Alanine↗
PubMed2000

Arteriolopathy in non-episode biopsies of renal transplant allograft.

PURPOSE: We have been performing protocol biopsies since 1995 to predict the outcome of renal allograft. However, histopathological findings in renal allograft with stable function remain unclear. For this reason, we performed non-episode biopsy on long-surviving renal allograft and investigated the histopathological changes. Among the several diseases seen in non-episode biopsies, arteriolopathy, such as drug-induced nephropathy, is one of the most frequent diseases. However, it is unrelated to the dosage and the concentration of cyclosporine or tacrolimus. Consequently, we evaluated the clinicopathological findings of arteriolopathy in this study in order to clarify whether cyclosporine (CsA) or tacrolimus (FK506) is responsible for these findings. MATERIALS AND METHODS: We defined non-episode biopsy as a case with a serum creatinine level less than 2.0 mg/dL and containing less than 500 mg/dL of urinary protein. Final results showed that 71 cases were identified as non-episode biopsy. We then evaluated the histopathological findings and the clinical characteristics of these cases. RESULTS: Thirty-two of the 71 non-episode biopsy specimens showed findings of arteriolopathy. The frequency and the severity of arteriolopathy are not concerned with dosage and concentration of CsA or FK506. The arteriolopathy seen in non-episode biopsy was related to the time of the biopsy and the kidney age. Arteriolopathy in nonepisode biopsy also had a relationship with hypertension, suggesting that it is important to strictly control blood pressure for graft survival.

Adult↗
PubMed2000

A case of relapse of C-ANCA-associated glomerulonephritis in post-transplant patients.

We experienced a case of relapse of proteinase 3-specific antineutrophil cytoplasmic autoantibody (C-ANCA)-associated rapid progressive glomerulonephritis (RPGN) in a patient after renal transplantation. A 19-yr-old man, who underwent a living donor kidney transplantation, presented a rapid renal function deterioration along with a sign of infection. Initially he was treated as acute rejection, but renal function did not improve. Renal biopsy revealed crescentic glomerulonephritis, and C-ANCA titer was 12 EU/mL, resulting in the diagnosis of C-ANCA-associated RPGN. He was treated with three consecutive methylprednisolone pulses twice in addition to the basal immunosuppressive medications (cyclosporine A and mizoribine), then his renal function improved to normal. Bearing the possibility of recurrence of glomerulonephritis in mind, we re-evaluated the nature and disease course of renal failure of original kidney. He experienced a rapid deterioration of renal function in 1992, and eventually CAPD was started in 1992. His serum in 1992 revealed high titer of C-ANCA (24 EU/mL), and renal biopsy performed in 1992 showed a crescentic glomerulonephritis. Taken together, we diagnosed this event as a relapse of C-ANCA-associated GN. Lessons from our experience are: 1) steroid pulse and high-dose corticosteroid therapy may be useful for the treatment of relapse of C-ANCA-associated GN patients after renal transplantation; 2) the possibility of a relapse of C-ANCA-associated GN following renal transplantation has to be kept in mind, especially when infection precedes the deterioration of allograft kidney function.

Adult↗
PubMed2000

Gene transfer targeting interstitial fibroblasts by the artificial viral envelope-type hemagglutinating virus of Japan liposome method.

BACKGROUND: Tubulointerstitial inflammation and fibrosis are commonly associated with most human glomerular diseases. The degree of tubulointerstitial damage, rather than the glomerular injury, could correlate with the degree of renal functional impairment and accurately predict long-term prognosis. In an effort to understand the pathogenesis of the progressive interstitial fibrosis, we developed a new strategy of gene transfer to the interstitial fibroblasts. METHODS: Either fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleotides (ODNs) or pEBAct-NlacF expression vector was introduced into the kidney of normal rats retrogradely via ureter by using the artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome method. RESULTS: FITC-labeled ODNs were accumulated diffusely in the nuclei of the interstitial cells in the transfected kidney 10 minutes after transfection, and the interstitial cells were identified as interstitial fibroblasts by immunostaining with ER-TR7. To examine the gene expression in the interstitium, pEBAct-NlacF gene-conjugated HVJ liposome was injected retrogradely through the ureter, and in consequence, nuclear beta-galactosidase activity was continuously observed in interstitial cells at least two weeks after transfection. CONCLUSION: This new strategy of gene transfer to the interstitial fibroblasts is useful for the investigation of the pathophysiology of tubulointerstitial lesion, and furthermore, it may be a promising new therapeutic method for the progression of interstitial fibrosis.

Animals↗
PubMed2000

Gene expression profiles of the collecting duct in the mouse renal inner medulla.

UNLABELLED: Gene expression profiles of the collecting duct in the mouse renal inner medulla. BACKGROUND: Gene expression profiles, constructed from 1000 to 2000 cloned cDNA sequences, depict their relative abundance of expression in a tissue. Establishing such a profile for mouse inner renal medullary collecting ducts (IMCDs), we compared expression patterns with those in other tissues including proximal tubule. METHODS: A nonbiased 3'-end cDNA library was prepared from microdissected mouse IMCDs. Single-pass sequencing of 2000 randomly selected cDNA clones collected short sequences (approximate length, 250 bp) following poly (A), called gene signatures (GS). Identical sequences were considered a single GS. GS occurrence was quantitated to yield a list of expressed genes indicating their abundance. RESULTS: Among 2000 clones, 1613 types of transcripts were found in IMCDs; 155 were identical or homologous to reported genes. The gene most expressed in IMCDs was alphaB-crystallin, a small stress (heat-shock) protein that is also a major structural protein in the ocular lens. According to Northern analysis, renal expression of this mRNA was induced by dehydration, presumably via tissue hypertonicity. However, expression did not change with acute NaCl loading. Also, a new member of the glutathione-S-transferase family was identified by comparing the IMCD expression profile with those of other tissues. CONCLUSION: With our database of genes expressed in mouse IMCDs, we are devising an IMCD-specific microarray to study gene-expression responses to various physiologic alterations.

Amino Acid Sequence↗
PubMed2000

Quantitation of mRNA expression in glomeruli using laser-manipulated microdissection and laser pressure catapulting.

BACKGROUND: Laser-manipulated microdissection (LMM) is a method to cut out a single cell or limited tiny region from a specimen under microscopic observation by a laser beam. Laser pressure catapulting (LPC) is a method to push up and collect samples that were microdissected using a strong laser. METHODS: To induce experimental glomerulonephritis, anti-Thy1.1 monoclonal antibody (OX-7) was injected intravenously into rats. Control and disease model kidneys were obtained. Six-micrometer thick cryostat sections were mounted onto a 1.35 microm thin polyethylene membrane. Ten glomeruli were collected from 6 microm frozen sections of rat kidney by LMM and LPC. Isolated glomeruli were used to quantitate the expression of mRNA by real-time polymerase chain reaction (PCR). RESULTS: Transforming growth factor-beta1 (TGF-beta1) mRNA was not detected in glomeruli isolated by the LMM and the LPC methods on day 0, although G3PDH mRNA was measurable in the same samples. On day 7 after the treatment with OX-7, the ratio of TGF-beta1/G3PDH mRNA was 1.89 +/- 0.96 (N = 6). CONCLUSIONS: We established methods to isolate glomeruli from standard histochemical specimens by LMM and LPC, and to quantify mRNA expression in the targeted glomeruli using real-time PCR. We confirmed the up-regulation of TGF-beta1 mRNA expression in isolated glomeruli from frozen sections of the anti-Thy1.1 glomerulonephritis model.

Animals↗
PubMed2000

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.

Adult↗