PubMed Health⌕ Search

Biomedical subjects

Yasuhiro Kuroda

Publications and source records attributed to Yasuhiro Kuroda.

At least 37 records · Page 2Linked to original sources
PubMed2004

Transforming growth factor-beta in renal disease with glycogen storage disease I.

We report a 14-year-old patient with Japanese glycogen storage disease I (GSD-I) who was found to have proteinuria. Renal biopsy revealed massive tubular atrophy and interstitial fibrosis with mononuclear cell infiltration, but the glomeruli were almost normal. The epithelial cells of tubules contained periodic acid-Schiff-positive glycogen deposits digested by diastase. In an immunohistological study, transforming growth factor (TGF)-beta expression was increased in tubular epithelial cells compared with a normal control kidney specimen. These data suggest that increased TGF-beta expression is involved in the pathophysiology of renal interstitial fibrosis in a patient with GSD-I.

Adolescent↗
PubMed2004

Sisters with alpha-mannosidosis and systemic lupus erythematosus.

UNLABELLED: Alpha-mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal alpha-mannosidase (LAMAN). Here, we report two sisters with alpha-mannosidosis who developed systemic lupus erythematosus (SLE). The sisters were both homozygous for a one bp deletion within the LAMAN gene resulting in a truncated gene product. The coincidence of alpha-mannosidosis and SLE are discussed with regard to both clinical and molecular findings. CONCLUSION: alpha-mannnosidosis may contribute to the onset of systemic lupus erythematosus in predisposed patients.

Adult↗
PubMed2004

PDGF-BB enhances alpha1beta1 integrin-mediated activation of the ERK/AP-1 pathway involved in collagen matrix remodeling by rat mesangial cells.

Platelet-derived growth factor-BB (PDGF-BB) has been implicated in the pathogenesis of progressive glomerulonephritis (GN). Previous studies have reported that PDGF-BB stimulates mesangial cells (MCs)-induced collagen matrix remodeling through enhancement of alpha1beta1 integrin-dependent migratory activity. To determine the cell signaling pathway responsible for abnormal MC-related mesangial matrix remodeling in progressive GN, we studied the involvement of the extracellular signal-regulated kinase (ERK)/activator protein-1 (AP-1) pathway in PDGF-BB-enhanced collagen gel contraction. Western blotting and gel shift assay revealed that MC-induced gel contraction resulted in ERK activation in parallel with that of AP-1 binding, peaking at 4 h and lasting at least for 24 h. Application of the MEK inhibitor, U0126, and the c-jun/AP-1 inhibitor, curcumin, inhibited gel contraction and AP-1 activity, respectively, dose dependently. PDGF-BB enhanced not only gel contraction but ERK phosphorylation and AP-1 activity by MCs. Marked inhibitory effects on PDGF-BB-induced gel contraction and ERK/AP-1 activity were observed in the presence of either function blocking anti-alpha1- or anti-beta1-integrin antibody or U0126. Consistently, AP-1-inactive MCs expressing a dominant-negative mutant of c-jun showed a significant decrease of PDGF-BB-induced gel contraction as compared with mock-transfected MCs. Finally, migration assay showed that ERK/AP-1 activity is required for PDGF-BB-stimulated alpha1beta1 integrin-dependent MC migration to collagen I. These results indicated that PDGF-BB enhances alpha1beta1 integrin-mediated collagen matrix reorganization through the activation of the ERK/AP-1 pathway that is crucial for MC migration. We conclude that the ERK/AP-1 pathway plays an important role in PDGF-BB-induced alpha1beta1 integrin-dependent collagen matrix remodeling; therefore, the inhibition of its pathway may provide a novel approach to regulate abnormal collagen matrix remodeling in progressive GN.

Animals↗
PubMed2004

Peak negative myocardial velocity gradient and wall-thickening velocity during early diastole are noninvasive parameters of left ventricular diastolic function in patients with Duchenne's progressive muscular dystrophy.

Myocardial velocity gradient and wall-thickening velocity were measured in the interventricular septum and left ventricular posterior wall (LVPW) by color-coded M-mode Doppler tissue echocardiography in patients with Duchenne's progressive muscular dystrophy (DMD) with a normal shortening fraction (n = 14) and age-matched control subjects (n = 40). In the LVPW, peak myocardial velocity gradients during systole and early diastole were significantly lower for patients with DMD than in control subjects (P <.0005, and P <.0001, respectively). Peak myocardial wall-thickening velocities of the LVPW during systole and early diastole were also lower for patients with DMD (P <.0005 and P <.0001, respectively). Mitral peak atrial to early filling velocity ratio was not significantly different between the 2 groups. The cut-off values of peak myocardial velocity gradients and wall-thickening velocities of the LVPW during early diastole for differentiation between patients with DMD and control subjects were -5.8/s and -6.0 cm/s, respectively (sensitivity/specificity: 93%/93% and 93%/85%, respectively). In conclusion, wall thinning during early diastole is frequently abnormal in patients with DMD, even when conventional echocardiographic findings are normal.

Adolescent↗
PubMed2004

Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels.

BACKGROUND: Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. METHODS: The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. RESULTS: Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal. CONCLUSIONS: These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.

ATP-Binding Cassette Transporters↗
PubMed2004

Effect of propofol on hypotonic swelling-induced membrane depolarization in human coronary artery smooth muscle cells.

BACKGROUND: Stretch (mechanical stress)-induced membrane depolarization of smooth muscle may contribute to basal vascular tone and myogenic control. Propofol induces vasodilation and inhibits myogenic control. Hypotonic swelling was used as a model of mechanical stress. The authors investigated the effects of propofol and 5-nitro-2-(3-phenylpropylamino)benzoic acid, a chloride channel and nonselective cation channel blocker, on hypotonicity-induced membrane depolarization in cultured human coronary artery smooth muscle cells. METHODS: A voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. The cells were continuously perfused with Earle's balanced salt solution containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed sequentially to isotonic and hypotonic medium. In a second series of experiments, the cells were exposed to hypotonic media in the presence and absence of 5-nitro-2-(3-phenylpropylamino)benzoic acid or propofol. RESULTS: The relative fluorescence values at 10, 20, and 30% hypotonicity were 147 +/- 29, 214 +/- 74, and 335 +/- 102% of baseline, respectively. The changes were all significantly different from the isotonic time control group. In the presence of 200 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or 0.1, 1, 10, or 100 microg/ml propofol, the relative fluorescence values at 30% hypotonicity were 87 +/- 17, 194 +/- 27, 160 +/- 18, 130 +/- 18, and 84 +/- 15%, respectively. These changes were significantly less than the 30% for the hypotonic control (246 +/- 23%). CONCLUSION: These results suggest that volume-sensitive chloride channels and nonselective cation channels may participate in hypotonicity-induced membrane depolarization and that propofol inhibits hypotonicity-induced membrane depolarization in coronary artery smooth muscle.

Anesthetics, Intravenous↗
PubMed2004

Molecular mechanisms of the inhibitory effects of bupivacaine, levobupivacaine, and ropivacaine on sarcolemmal adenosine triphosphate-sensitive potassium channels in the cardiovascular system.

BACKGROUND: Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. METHODS: The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. RESULTS: Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. CONCLUSIONS: Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

ATP-Binding Cassette Transporters↗
PubMed2004

Successful management of intractable epilepsy with lidocaine tapes and continuous subcutaneous lidocaine infusion.

PURPOSE: We report the successful management of a 10-year-old girl with intractable frontal lobe epilepsy by using lidocaine tapes and continuous subcutaneous lidocaine infusion. METHODS: This patient's seizures were refractory to conventional antiepileptic drugs (AEDs) and mexiletine, but they responded well to the intravenous infusion of lidocaine. The intravenous infusion of lidocaine was replaced by lidocaine tape therapy, and subsequently by continuous subcutaneous lidocaine infusion therapy. The lidocaine tape (Penles, Nihon Lederle, Tokyo Japan) used was a stamp-sized (30.5 x 50.0 mm) tape containing 18 mg of lidocaine. We used 25 lidocaine tapes every 12 h (50 tapes/day). Lidocaine hydrochloride (10%) was administered continuously at a dose of 1.5 mg/kg/h (0.3 ml/hour) through a 27-G needle that was inserted in the subcutaneous tissue. RESULTS: Lidocaine tape therapy showed good efficacy for 1 year. After that, six lidocaine tapes were added 6 h after the exchange of 25 lidocaine tapes [62 tapes/day (25,6,25,6)], because the seizures became frequent when the lidocaine tapes were being exchanged. The seizures were then well controlled, but dermatitis due to the lidocaine tapes grew serious, and lidocaine tape therapy had to be stopped. Continuous subcutaneous infusion of lidocaine applied in place of lidocaine tapes provided long-term seizure control without remarkable side effects. CONCLUSIONS: Lidocaine tape therapy and continuous subcutaneous lidocaine infusion therapy were considered to be useful for controlling this patient's seizures. This is the first report to describe the efficacy of continuous subcutaneous lidocaine infusion therapy for epilepsy.

Administration, Cutaneous↗
PubMed2004

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight.

OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.

Adiponectin↗
PubMed2004

Analysis of maternal and neonatal factors that influence the nucleated and CD34+ cell yield for cord blood banking.

BACKGROUND: It would be beneficial to be able to predict the cord blood (CB) cell yield from volunteer donors before cell processing. STUDY DESIGN AND METHODS: The maternal and neonatal factors that influence the total nucleated cell (TNC), CD34+ cell, and CFU-GM yields in CB collected for the Chugoku-Shikoku Cord Blood Bank were evaluated. RESULTS: In a univariate analysis, the volume of CB collected was significantly correlated with the TNC, CD34+ cell, and CFU-GM yields (p < 0.001). A longer cord (p < 0.001), larger placenta (p < 0.001), and bigger baby (p < 0.001) were associated with a greater volume of CB. A female baby (p < 0.05) and longer gestational age (p < 0.005) were associated with a higher TNC concentration. A younger maternal age (p < 0.05), larger birth weight (p < 0.001), shorter gestational age (p < 0.001), and shorter time from collection to processing (p < 0.05) were associated with a higher CD34+ cell concentration. A multivariate linear regression analysis was performed to predict the yield and determine first-level selection criteria to start processing when the volume of CB units was on the borderline. However, this formula might not be suitable for actual use. CONCLUSION: Maternal and neonatal factors appeared to affect CB cell yields. These findings might be useful for efficiently collecting more qualified CB units.

Age Factors↗
PubMed2004

Single-strand conformation polymorphism analysis of the FMR1 gene in autistic and mentally retarded children in Japan.

Fragile X syndrome is one of the most common causes of mental retardation in males, and patients with fragile X syndrome occasionally develop autism. It is usually caused by an expansion of the trinucleotide repeat in the 5'-untranslated region of the FMR1 gene, but in a small number of patients deletions and point mutations have been identified. We screened all 17 exons of the FMR1 gene for mutations in 90 autistic or mentally retarded children using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. No mutations were found in 76 male patients. However, one female patient was heterozygous for a normal allele and a mutant allele with an A to C substitution at nucleotide 879 in exon 9. This mutation was not found in 50 controls. Reverse transcription-PCR revealed that a large proportion of the mutant transcripts were spliced aberrantly, causing premature termination of the protein synthesis. Although uncommon, point mutations in the FMR1 gene may be a cause of autism and mental retardation in Japanese patients.

Alternative Splicing↗
PubMed2004

[Efficacy of secretin for the treatment of autism].

We administered secretin intravenously to 14 patients with autism (9 to 14 years, 10 males; 4 females), and evaluated its clinical effect. We also measured cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxy-indole-3-acetic acid (5HIAA) before and after 4 weeks treatment, and compared them with the grade of improvement of the clinical symptoms assessed by the scores of Autism Diagnostic Interview-Revised (ADI-R). After injection of secretin, the ADI-R score increased in 8 patients, but declined in 3. Improvement was observed in functions such as sociability (interpersonal relationships), communication and speech improved, whereas in the others. symptoms such as hyperkinesias and stereotyped behavior became worse. The CSF levels of HVA was significantly increased in all of the patients showing an improvement in the ADI-R score. SHIAA levels also tended to increase, although this increase was not significant. These findings suggest that secretin promotes the metabolism of serotonin and dopamine in the central nervous system, which may contribute to improvement in clinical symptoms of autism.

Adolescent↗
PubMed2004

[Case of methylmalonic acidemia presenting clinically Leigh encephalopathy].

A 1-year-old boy with methylmalonic acidemia had symmetrical lesions of the bilateral basal ganglia, which suggested Leigh encephalopathy. The findings on brain magnetic resonance imaging (MRI) and his physical condition greatly improved by the intravenous administration of vitamin B1. We hypothesized that in this case, clinical Leigh encephalopathy was caused by a impairment of the activity of pyruvate carboxylase induced by the accumulation of methylmalonyl CoA and an impairment of energy production due to a lack of vitamin B1, especially impairment of the activity of pyruvate dehydrogenase complex during an acute worsening of methylmalonic acidemia. Thus, in the treatment of methylmalonic acidemia, attention should be paid to vitamin B1 deficiency. During an acute worsening, vitamin B1 should be administered by intravenous drip injection.

Brain↗
PubMed2003

Dissociation between titer of anti-ganglioside antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.

Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.

Adult↗
PubMed2003

The role of mast cells in acute tubulo-interstitial nephritis with uveitis.

UNLABELLED: We describe the clinicopathological characteristics of two patients with acute tubulo-interstitial nephritis with uveitis (TINU) with mast cells infiltrating the interstitium. The pathogenesis of TINU remains unknown, but a T-cell-mediated immune response was suggested to be involved. Recent studies have shown that infiltrating mast cells are closely associated with the development of renal interstitial fibrosis in glomerulonephritis. To address the role of mast cells in the renal interstitial injury in TINU, immunohistochemical studies were performed in renal biopsy sections using anti-human mast cell tryptase antibody specific for mast cells. In addition, we tried to detect CD68-positive macrophages to compare with the localisation of mast cells within the renal interstitium. Mast cells and macrophages could be detected in renal interstitial lesions of both patients. Massive infiltration of macrophages into interstitial lesions was observed, whereas mast cells were detected in a sporadic rather than a clustered manner, and associated with fibrotic lesions. Repeat renal biopsy findings suggested the involvement of these cells in the renal interstitial injury because the number of infiltrating mast cells and macrophages in the interstitium decreased with the improvements in clinical symptoms and pathological lesions. CONCLUSION: The present study showed that mast cells might play an important role in the development of renal interstitial injury in tubulo-interstitial nephritis with uveitis.

Acute Disease↗
PubMed2003

Effect of granulocyte colony-stimulating factor on bone metabolism during peripheral blood stem cell mobilization.

Granulocyte colony-stimulating factor (G-CSF) has been shown to affect the biochemical markers of bone metabolism, including serum bone alkaline phosphatase (BALP), serum osteocalcin, and urine deoxypyridinoline. To determine the association between bone resorption and formation and the G-CSF-induced mobilization of peripheral blood stem cells (PBSC), we examined these markers during mobilization in 19 healthy donors. The average (+/- SEM) serum BALP level before treatment was 81.6 +/- 17.0 IU/dL, and the level increased significantly to 117.7 +/- 15.8 IU/dL on day 5 of G-CSF administration (P < .0001). The urine deoxypyridinoline level before treatment was 12.3 +/- 2.4 nmol/mmol creatinine, and this level also increased significantly to 19.4 +/- 3.0 nmol/mmol creatinine on day 5 of G-CSF administration (P < .0001). In contrast, the average level of serum osteocalcin significantly decreased from 8.07 +/- 2.88 ng/mL to 1.53 +/- 0.18 ng/mL on day 5 (P = .0353). During G-CSF administration, we also studied the serum levels of various cytokines (IL-1beta, osteoclastogenesis inhibitory factor [OCIF], IL-6, tumor necrosis factor alpha, transforming growth factor beta, interferon-gamma, macrophage colony-stimulating factor) related to bone metabolism. Only the kinetics of OCIF were significantly affected. The serum level of OCIF increased immediately after the start of G-CSF administration and remained high during G-CSF administration. These results demonstrate that high-dose G-CSF affects bone metabolism and that OCIF may play a role in bone metabolism. Consistent with the notion that G-CSF affects bone metabolism, a significant correlation was observed between CD34+ cell yield and the increase in urine deoxypyridinoline but not for the changes in serum BALP and osteocalcin levels. This result suggests that bone resorption is either directly or indirectly related to the mobilization of PBSC by G-CSF.

Adolescent↗
PubMed2003

Successful unrelated cord blood transplantation in an infant with Wiskott-Aldrich syndrome following recurrent cytomegalovirus disease.

We describe successful unrelated cord blood transplantation in a 14-month-old boy with Wiskott-Aldrich syndrome. He had been suffering from recurrent cytomegalovirus (CMV) pneumonia. Ganciclovir was given pretransplantation and posttransplantation, and CMV antigenemia was monitored as a marker of reactivation. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 9.0 x 10(7)/kg. Neutrophil engraftment was achieved on day +20, and a platelet count greater than 50 x 10(9)/L was achieved on day +51. A normal lymphoproliferative response to phytohemagglutinin mitogen was detectable 7 months posttransplantation. Long-term use of ganciclovir prevented CMV reactivation and did not compromise engraftment.

Antiviral Agents↗