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Biomedical subjects

Hirokazu Imai

Publications and source records attributed to Hirokazu Imai.

At least 19 recordsLinked to original sources
PubMed2006

Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy.

BACKGROUND: Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue. METHODS: We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment. RESULTS: Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia. CONCLUSIONS: Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation.

Creatinine↗
PubMed2006

Acute renal failure due to IgM-lambda glomerular thrombi and MPGN-like lesions in a patient with angioimmunoblastic T-Cell lymphoma.

A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-lambda). Renal biopsy showed membranoproliferative glomerulonephritis-like lesions with azan-red-stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-lambda stained strongly in the glomerular capillary lumen, equal to the azan-red-stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-lambda, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma.

Acute Kidney Injury↗
PubMed2006

Early estimation of high peritoneal permeability can predict poor prognosis for technique survival in patients on peritoneal dialysis.

At the beginning of continuous ambulatory peritoneal dialysis (CAPD), different patients exhibit large differences in peritoneal permeability. To determine if early estimation of peritoneal permeability can predict the prognosis of CAPD, we used data from a personal dialysis capacity (PDC) study group in Japan to investigate patient and technique survival rates. Based on the data from a previously reported, prospective multicenter study encompassing eight dialysis centers in Japan (Am J Kidney Dis 2002; 40:1045-54), we recalculated patient and technique survival data. We reviewed the records of 139 patients newly initiated on CAPD from January 1995 to December 1999. Peritoneal permeability was estimated by PDC test within the first year after initiation. We divided the patients into paired groups according to several peritoneal permeability variables as calculated by the PDC test (area, plasma loss, and peritoneal creatinine clearance), and we compared patient and technique survival rate between the groups. The mean age of the patients was 49.6 years +/- 14.9 years (standard deviation). The mean pore area of peritoneum was 19,936 +/- 8383 cm/1.73 m2. Estimation of patient survival by the Kaplan-Meier method showed 94.2%, 88.4%, 84.1%, and 79.7% at 1, 2, 3, and 5 years respectively. Estimated technique survival (including death as an endpoint) by the Kaplan-Meier method showed 90.6%, 76.8%, 67.4%, and 54.3% at 1, 2, 3, and 5 years respectively. In the high peritoneal permeability group (high area and high plasma loss), the technique survival at 5 years was significantly lower than in the low peritoneal permeability group [area: 55.9% (high) vs. 72.7% (low), p = 0.0459; plasma loss: 43.3% (high) vs. 62.8% (low), p = 0.0197). We observed no significant difference in patient survival between the high and low peritoneal permeability patients. In the high peritoneal creatinine clearance group, patient and technique survival were both significantly lower than in the high peritoneal creatinine clearance group. Patients with high peritoneal permeability as calculated by the PDC test at the start of PD had a poor prognosis for technique and patient survival on CAPD. We conclude that early estimation of high peritoneal permeability can predict poor outcome for patients on CAPD.

Creatinine↗
PubMed2005

The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis.

A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8 mg/dl) and creatinine (3.4 mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11 EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500 mg/day, 3 days) and 45 mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11 EU/ml to 116 EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.

Anti-Inflammatory Agents↗
PubMed2005

Medical decision-making in membranous nephropathy: how to use limited clinical research evidence in patient management.

Evidence-based medicine (EBM) originally referred to the use of a combination of clinical expertise and research evidence to make medical decisions, while carefully considering the patient's preference. In Japan, however, EBM has been misunderstood as the more abstract pursuit of acquiring research evidence and building medical guidelines. This review aims to summarize the available data regarding therapy for membranous nephropathy (MN), a field in which no consensus has been reached, and to discuss medical decision-making by using a decision tree in several model cases. In clinical practice, we have to consider both the risks and benefits of treatment. These are evaluated by their therapeutic effect (the rate of improvement, no change, or worsening) and by the patients' quality of life (QOL). This process is compatible with the essential concept of EBM.

Adult↗
PubMed2005

[Extracellular-superoxide dismutase production in mesangial cell growing in extracellular matrix].

To study the protective function against oxygen radicals in the mesangial area, we assessed extracellular superoxide dismutase (EC-SOD) production in mesangial cells (MCs) in vitro. These cells have a major protective function against oxygen radicals in the extracellular space. In two different kinds of culture conditions: "growth medium" with fetal cow serum, and "differentiation medium" with reduced growth factor, and four extracellular matrixes; type I collagen, type IV collagen, laminin and fibronectin, were added to the MC culture. With the difference in the culture media, differentiation medium induced EC-SOD hyper-production associated with the both of the slowing down of cell proliferation and the suppression of IL-6 and IL-8 production. With difference in the extracellular matrix, the presence of type VI collagen and laminin promoted higher production of EC-SOD than fibronectin and type I collagen. Type IV collagen and laminin associated with the physiological condition of the glomeruli promoted EC-SOD production compared with the presence of type I collagen and fibronectin dominantly located in pathological condition. Suppression of EC-SOD production in growth medium along with MC proliferation and chemokine hyper-production compared with production in differentiation medium might mimic reduction of the protective capacity against oxygen radical toxity during mesangial proliferation in the glomerular nephritis. MC proliferation with type I collagen and fibronectin might enhance oxygen radical toxity in the glomeruli, and accelerate glomerular sclerosis through the suppression of EC-SOD production.

Cell Proliferation↗
PubMed2004

Lamina-selective changes in the density of synapses following perturbation of monoamines and acetylcholine in the rat medial prefrontal cortex.

The rat medial prefrontal cortex is known to have diverse brain functions such as learning and memory, attention, and behavioral flexibility. Although these functions are affected by monoamines (dopamine (DA), noradrenaline (NA) and serotonin (5-HT)) and acetylcholine (ACh), the detailed mechanisms remain unclear. These neuromodulators also have effects on synapse formation and maintenance, and regulate plasticity in the central nervous system (CNS). To clarify the effects of these neuromodulators on changes in the density of synapses in the rat medial prefrontal cortex, we separately administered a D1- or D2-antagonist, NA neurotoxin, 5-HT synthetic inhibitor, or muscarinic ACh antagonist for 1 week, and counted the number of synapses on electron microscopic photographs taken from the prelimbic area of the medial prefrontal cortex. The density of synapses in lamina I was regulated by DA via D1-like receptors, and that in laminae II/III was decreased by depletion of NA or ACh. However, 5-HT did not have a regulatory effect on the synaptic density throughout the layers in this brain region. The data in this study and our previous studies indicate that there are appreciable regional differences in the magnitude of biogenic amine-mediated synaptic plasticity in the rat CNS. These neuromodulators may have a trophic-like effect on the selected neuronal circuit to maintain synaptic contacts in the rat CNS. The synaptic density in the medial prefrontal cortex regulated by monoamines and ACh could be important not only for synaptic plasticity in this region but also for pharmacotherapeutic drug treatment.

Acetylcholine↗
PubMed2004

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.

Adult↗
PubMed2004

Establishment of anti-rat-Cu,Zn-superoxide dismutase monoclonal antibodies applied to a highly sensitive immunoassay and immunohistochemistry system.

The superoxide anion has been implicated in a wide range of diseases. The major protector against superoxide anion in the cell cytosol is Cu,Zn-superoxide dismutase (Cu,Zn-SOD). In this study, anti rat Cu,Zn-SOD was established in murine monoclonal antibodies for the first time. These antibodies were applied to both a highly sensitive EIA system in serum and immunohistochemical methods for detection in gastric mucosa tissues. The proposed EIA method had a high sensitivity within the assay range, 10-300 pg/mL, good percentage, 96.9 +/- 5.60%, and good reproducibility; within-day assay CV = 8.6-10.2%, between-day assay CV = 6.5-11.7%. Inmmunohistochemically, Cu,Zn-SOD localized in the esophagus epithelial cells, gastric oxyntic cells, surface of the gastric lumen side in the small intestine and colonic epithelial cells. The establishment of anti-rat CuZn-SOD monoclonal antibody allows both specific analysis of immunoquantitation in rat Cu,Zn-SOD and highly specific detection of Cu,Zn-SOD location by immunohistochemical methods.

Animals↗
PubMed2004

Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy.

BACKGROUND: Several studies have shown a predominant glomerular deposition of IgG4 in patients with idiopathic membranous nephropathy (MN), whereas significant depositions of other IgG subclasses have been shown in patients with lupus-associated MN and bucillamine-induced MN. METHODS: We examined the distribution patterns of glomerular IgG subclass deposits in 10 patients with malignancy-associated MN (M-MN) and in 15 patients with idiopathic MN by immunofluorescence (IF) microscopy. RESULTS: The glomerular IF intensities of IgG1 and IgG2 were significantly stronger in the malignancy group than in the idiopathic group (P<0.05). In contrast, there were no differences in glomerular IF intensities of IgG3 and IgG4 between the two groups. CONCLUSION: Our findings suggest that the distribution patterns of glomerular IgG subclass deposits are different in idiopathic MN and M-MN. The strong IF intensity of glomerular IgG1 and IgG2 in M-MN may provide a possible predictor for this condition.

Adult↗
PubMed2003

Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis.

Although the pathogenesis of idiopathic focal segmental glomerulosclerosis (FSGS) may be heterogeneous, autosomal dominant and recessive forms of FSGS are recognized. Recently, mutations in alpha-actinin 4 (ACTN4) and podocin genes were reported in patients with such familial FSGS. However, whether mutations in ACTN4 and podocin genes are associated with sporadic FSGS has not been determined. In the present study, we clarified the relation between mutations in ACTN4 and podocin genes and sporadic FSGS. We analyzed these reported mutations in ACTN4 and podocin in five patients with chronic renal failure due to therapy-resistant FSGS by direct sequencing of polymerase chain reaction products of ACTN4 and podocin. We found a C to T transition at nucleotide 465 in the ACTN4 gene in all of patients, and a T to C transition at nucleotide 954 in exon eight of podocin gene in two of five patients, resulting in no amino acid substitutions. Other mutations were not found in ACTN4 and podocin genes. Our findings suggest that sporadic FSGS is a heterogeneous disease, since ACTN4 and podocin genes are not found in our patients with sporadic FSGS.

Actinin↗