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Norishige Yoshikawa

Publications and source records attributed to Norishige Yoshikawa.

At least 19 recordsLinked to original sources
PubMed2006

The effect of aldosterone blockade in patients with Alport syndrome.

Recent studies indicate that adding the mineralocorticoid receptor antagonist spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI and angiotensin receptor blocker (ARB), which is known as a triple blockade, enhances the more beneficial effects on urinary protein excretion of patients with chronic kidney diseases. In this study, we explored the effects of SP on urinary protein excretion in patients with Alport syndrome featuring persistent proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and ARB (candesartan). Five patients with Alport syndrome were enrolled and SP treatment (25 mg/day) was started. At the start of SP administration, all patients showed good renal function and none of them suffered from hypertension. We decided to assess the effect of SP by determining the morning urinary protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR). After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and 18 months, while EGFR did not change. The drop in systolic and diastolic blood pressure was statistically significant and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l). These results suggest that aldosterone receptor blockade combined with ACEI and ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome as in those with other chronic kidney diseases. SP can thus be expected to constitute a good renoprotective agent for Alport syndrome. These preliminary data indicate that large-scale trials of this therapy should be done.

Adolescent↗
PubMed2006

High-dose mizoribine treatment for adolescents with systemic lupus erythematosus.

BACKGROUND: In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150 mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose-dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE. METHODS: The authors administered oral MZR at 300 mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment. RESULTS: Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300 mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 microg/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months. CONCLUSION: MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.

Adolescent↗
PubMed2005

Long-term follow-up of atypical membranoproliferative glomerulonephritis: are steroids indicated?

Atypical membranoproliferative glomerulonephritis (MPGN) has been reported to have a good prognosis when treated with corticosteroids. However, this recommendation is based on uncontrolled trials and is associated with many complications. The purpose of our study is to determine whether steroid therapy is indicated for atypical MPGN. The cases of seven patients with atypical MPGN are reported in this study. Urinary abnormalities of five of them were detected by urine screening at school, of two because of macrohematuria. Hypocomplementemia was noted in six patients. All but one patient were treated without corticosteroids, and five with angiotensin-converting enzyme inhibitors (ACEI) and/or the Chinese herbal medicine Sairei-to (TJ-114). One patient recovered spontaneously from proteinuria and was therefore not treated, and one who developed severe proteinuria during observation was treated with corticosteroids. After an average follow-up period of 10.0 years, five patients showed normal urinary findings, one had hematuria and one proteinuria. At the most recent follow-up, the renal function of all patients remained within the normal range, and serum C3 had returned to normal levels in five out of six. These findings suggest that the indication of steroid therapy for atypical MPGN should be re-examined, since most of the patients with atypical MPGN seem to have an excellent prognosis without treatment with corticosteroids.

Adolescent↗
PubMed2005

Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome.

A 12-year-old Japanese boy who underwent kidney transplantation with a kidney from his mother developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS) and electron microscopic examination of the renal biopsy showed foot process fusion, we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney. Four months after the transplantation, posttransplant lymphoproliferative disorder (PTLD) developed, which was pathologically diagnosed as diffuse large B cell lymphoma. Treatment consisting of a reduction in immunosuppression resulted in improvement in PTLD a month after the start of treatment. However, relapse occurred 2 months after the first onset of PTLD, which we treated with rituximab (CD-20 monoclonal antibody 375 mg/m2) once weekly for a total of four doses. The PTLD resolved immediately after the rituximab treatment was started, and, interestingly, urinary protein levels also improved at the same time. Three years later, the boy shows no signs of PTLD, and no proteinuria has been detected. These findings suggest that rituximab may be an effective treatment for recurrence of nephrotic syndrome after transplantation and that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation.

Antibodies, Monoclonal↗
PubMed2005

Cyclosporin A absorption profiles in children with nephrotic syndrome.

A single blood concentration measurement of Neoral 2 h after administration (C2) is a new concept in therapeutic drug monitoring (TDM). In most adult patients, the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral administration. Therefore, monitoring the area under the concentration-time curve over the first 4 h post-dose (AUC0-4) is considered to be the most reliable strategy for Neoral TDM. In addition, C2 is considered to be the most accurate predictor of AUC0-4, with which C2 correlates best. Thus, in adult patients, C2 monitoring is recommended as the best single-point TDM method for Neoral. However, in paediatric patients, the effectiveness of C2 monitoring is still unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in 60 patients (1 to 20 years old, mean age 7.42+/-0.67 years) who had nephrotic syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38 patients (early peak group) and C3 or C4 in 22 patients (late peak group). C2 in the late peak group was significantly lower than that in the early peak group (422+/-50.1 vs. 665 +/-53.8 ng/ml, P =0.0008), although the administered doses of Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the same standard as in the early peak group might result in an overdose of CyA in the late peak group. As the concentration peaked at 3 h or more after Neoral administration in the late peak group, AUC0-4 does not necessarily reflect the Neoral absorption profile. As more than 33% of the paediatric patients were in the late peak group, TDM by AUC0-4 or C2 should be used carefully in paediatric patients treated with Neoral.

Absorption↗
PubMed2005

Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled study.

Bovine lactoferrin (bLF) has antibacterial activity against Helicobacter pylori in vitro and is effective to suppress bacterial colonization in mice. The aim of our study was to evaluate the efficacy of orally administered bLF on H. pylori colonization in humans by a randomized, double-blind, placebo-controlled study. Fifty-nine healthy subjects positive for H. pylori infection were recruited. Subjects were randomized into two groups. The bLF group received bLF tablets at a dosage of 200 mg b.i.d. for a period of 12 weeks, and the control group received placebo tablets without bLF. The (13)C-urea breath test (UBT) was performed before, during, and at the end of administration, and again 4 weeks after administration. Positive response was defined as more than 50% decrease of the UBT value at the end of administration. Positive response was observed in 10 of 31 bLF-treated subjects (32.3%) and 1 of 28 control subjects (3.6%), indicating that the rate of positive response in the bLF group was significantly higher than that in the control group (bLF vs. control, P < 0.01). These results suggested that bLF administration is effective to suppress H. pylori colonization.

Adolescent↗
PubMed2005

A polymorphism in plasma platelet-activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease.

OBJECTIVE: To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). STUDY DESIGN: The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele-specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]-acetyl-PAF. RESULTS: There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) +TT (homozygous deficient) group required additional IVIG (52% vs 14%, P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P <.0001). CONCLUSION: We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Non-myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma.

The prognosis of patients with relapsed osteosarcoma is dismal despite the use of intensive chemotherapy. We describe a patient with refractory osteosarcoma who underwent non-myeloablative peripheral blood stem cell transplantation (PBSCT) from an human leukocyte antigen (HLA)-identical sibling during a third complete remission. The patient suffered pulmonary relapse after the transplantation. Cyclosporin A withdrawal induced a graft-vs.-osteosarcoma effect and graft-vs.-host disease, but eventually the tumor progressed. Although our experience in this case suggested the presence of a graft-vs.-osteosarcoma effect during non-myeloablative allogenic PBSCT, this strategy might have limited value for refractory osteosarcoma with rapid growth kinetics.

Adolescent↗
PubMed2005

Helicobacter pylori infection in children with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Recently a high prevalence of Helicobacter pylori infection has been reported in adult patients with chronic idiopathic thrombocytopenic purpura (cITP). Furthermore, after H. pylori eradication therapy in such patients, their platelet counts have been observed to increase, suggesting that H. pylori may be a causative agent of adult cITP. However, there have been only a few reports of children with cITP. The purpose of the present paper was to examine the association between H. pylori infection and cITP in Japanese children. METHODS: Helicobacter pylori stool antigens (HpSA) were measured and the prevalence of H. pylori infection was determined in 10 children with cITP. RESULTS: Helicobacter pylori infection was found in only two of the subjects. In a boy, the urea breath test (UBT) was also positive and the patient received eradication therapy using amoxicillin, clarithromycin, and lansoprazole for 1 week. The therapy was successful and the patient's platelet count increased. The response was maintained throughout more than 1 year of follow up. CONCLUSIONS: The prevalence of H. pylori infection in children with cITP is not high. However, the platelet count increased after eradication therapy in a boy with cITP. It is suggested that the eradication of H. pylori infection would be valuable in children, as well as in adults, with cITP.

Adult↗
PubMed2005

Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome (CNS) causes significant renal failure, and is classified into two types: (1) Finnish type; and (2) other, including diffuse mesangial sclerosis. Mutations of NPHS1 and NPHS2, which encode the slit diaphragm components nephrin and podocin, cause CNS and autosomal-recessive familial steroid-resistant nephrotic syndrome, respectively. Most patients with Finnish-type CNS in Europe and the United States have NPHS1 mutations. However, NPHS2 mutations have been detected in some cases. Mutations in ACTN4, encoding alpha-actinin-4, cause an autosomal-dominant focal segmental glomerulosclerosis. alpha-actinin-4 stabilizes the podocyte cytoskeleton structure, connecting with actin filaments. WT1 mutations, causing Wilm's tumor, have been demonstrated in some CNS patients with diffuse mesangial sclerosis. Systematic investigation of genes for CNS in Japan has never been performed. METHODS: To clarify the role of mutations in these four genes, we used polymerase chain reaction (PCR) and direct sequencing to investigate all exons and exon-intron boundaries for these genes in 13 unrelated CNS patients from regional pediatric kidney disease centers in Japan. RESULTS: A novel homozygous nonsense mutation of NPHS1, E246X in exon 7, and a novel homozygous deletion mutation of NPHS1, 2156_2163del in exon 16 were detected in one patient each. A novel homozygous nonsense mutation of NPHS2, R196X in exon 5, was found in one patient, and the same heterozygous nonsense mutation was detected in another. No ACTN4 or WT1 mutations were detected. CONCLUSION: These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.

Actinin↗
PubMed2005

Polymerase chain reaction--restriction fragment length polymorphism analysis of clarithromycin-resistant Helicobacter pylori infection in children using stool sample.

BACKGROUND: To analyze clarithromycin-resistant Helicobacter pylori infection in children, we developed a method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using stool samples. MATERIALS AND METHODS: Twenty-three children without significant upper abdominal symptoms were included (mean age 7.0 years). Of these, 18 and five were diagnosed as H. pylori-positive and -negative, respectively, by the H. pylori stool antigen test (HpSA). The DNA from the stool samples was purified using the QIAamp DNA Stool Minikit (QIAGEN). The PCR was performed on the purified DNA using oligonucleotide primers designed to amplify the 23S rRNA gene of H. pylori. The PCR products were reacted with restriction enzymes MboII, BceAI, and BsaI to detect mutations A2142G, A2142C, and A2143G, respectively. RESULTS: Sixteen of the 18 HpSA-positive samples were PCR-positive, and all five HpSA-negative samples were PCR-negative. Thus, the PCR had 89% sensitivity and 100% specificity, with 91% accuracy in reference to HpSA. Of the 16 PCR-positive samples, one and four were digested with MboII and BsaI, respectively, indicating 31% prevalence of CAM-resistance. CONCLUSIONS: We conclude that the PCR-RFLP using stool samples is a rapid and reliable method to noninvasively detect clarithromycin-resistant H. pylori infection in children. It may be useful before choosing regimens of H. pylori eradication.

Adolescent↗
PubMed2005

Macrophage activation syndrome in children with systemic-onset juvenile chronic arthritis.

Macrophage activation syndrome (MAS) is a life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile chronic arthritis (SOJCA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study assessed the clinical features of nine MAS events in five children with SOJCA. Nonremitting fever and decreased platelet and white blood cell counts led to a diagnosis of MAS. The urinary beta2-microglobulin (beta2MG) level was a sensitive indicator of MAS. Serum levels of beta2MG and soluble interleukin-2 receptor were also elevated. These biologic markers reflecting hyperactivated cellular immunity are useful indicators of MAS. Four children treated with cyclosporin A (CSP) achieved rapid and complete recovery, but one patient without CSP died due to rapidly progressive respiratory failure. All children treated with CSP responded quickly, and fever abated within 36 h of initiation of treatment. CSP should be added to first-line therapy of MAS.

Adolescent↗
PubMed2004

Role of p38 MAP kinase pathway in a toxin-induced model of hemolytic uremic syndrome.

The role of proinflammatory cytokines in a rat model of toxin-induced hemolytic uremic syndrome (HUS) was studied. Male Sprague-Dawley rats underwent continuous saline infusion (6 ml/h) via a tail vein and received a bolus injection of saline (control), lipopolysaccharide (LPS, 10 microg/100 g body weight), ricin (6.7 microg/100 g body weight), or ricin with LPS (ricin+LPS). They were then observed for 8 h. Blood samples and kidney tissues were obtained at the end of the experiment. The effects of FR 167653, a potent inhibitor of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production, were also examined in ricin+LPS-treated rats. Only ricin+LPS-treated rats developed significant thrombocytopenia, hemolysis, and oliguric acute renal failure with extensive glomerular thrombotic microangiopathy, which was characterized by glomerular microthrombi and apoptosis of glomerular endothelial cells. Thrombotic microangiopathy was not detected in other organs, including the brain, liver, spleen, pancreas, lung, colon, and intestine. Significantly elevated levels of serum IL-1beta and TNF-alpha were detected only in ricin+LPS-treated rats. Treatment of ricin+LPS-treated rats with FR 167653 significantly reduced the serum levels of IL-1beta and TNF-alpha, accompanied by improvement of the oliguric renal failure and glomerular thrombotic microangiopathy. These findings indicate that the increased serum levels of IL-1beta and TNF-alpha, which probably result in the apoptosis of glomerular endothelial cells, play a pivotal role in the development of this rat model of toxin-induced HUS. The findings also suggest that inhibition of these proinflammatory cytokines may prevent the development of HUS.

Animals↗