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Biomedical subjects

N Yoshikawa

Publications and source records attributed to N Yoshikawa.

At least 19 recordsLinked to original sources
PubMed2007

Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures.

This study investigated the relationship between plasma levels of ghrelin and postnatal growth in preterm infants. The levels of active ghrelin in cord blood and in plasma in 25 very low birthweight (VLBW) infants were measured. The results indicate that the levels of circulating active ghrelin markedly increases after birth in VLBW infants, and suggest that the increased levels of ghrelin reflects the maturation of ghrelin production in the stomach and an increased physiological need for ghrelin.

Anthropometry↗
PubMed2006

Exact static solutions for discrete phi4 models free of the Peierls-Nabarro barrier: discretized first-integral approach.

We propose a generalization of the discrete Klein-Gordon models free of the Peierls-Nabarro barrier derived in Spreight [Nonlinearity 12, 1373 (1999)] and Barashenkov [Phys. Rev. E 72, 035602(R) (2005)], such that they support not only kinks but a one-parameter set of exact static solutions. These solutions can be obtained iteratively from a two-point nonlinear map whose role is played by the discretized first integral of the static Klein-Gordon field, as suggested by Dmitriev [J. Phys. A 38, 7617 (2005)]. We then discuss some discrete phi4 models free of the Peierls-Nabarro barrier and identify for them the full space of available static solutions, including those derived recently by Cooper [Phys. Rev. E 72, 036605 (2005)] but not limited to them. These findings are also relevant to standing wave solutions of discrete nonlinear Schrödinger models. We also study stability of the obtained solutions. As an interesting aside, we derive the list of solutions to the continuum phi4 equation that fill the entire two-dimensional space of parameters obtained as the continuum limit of the corresponding space of the discrete models.

Journal Article↗
PubMed2006

Plasma angiotensin II concentrations in the early neonatal period.

BACKGROUND: There have been only a few reports on the renin-angiotensin system in low birthweight infants; in particular, plasma angiotensin II concentrations have not been studied. AIM: To investigate plasma angiotensin II concentrations in early neonatal infants including low birthweight infants. METHODS: Forty six patients were studied, of whom 14 weighed not less than 2500 g (normal birth weight), 16 weighed less than 2500 g but not less than 1500 g (moderately low birth weight), and 16 weighed less than 1500 g (very low birth weight). Blood samples were collected twice, on day 0 and day 7. Angiotensin II concentration was assayed using an enzyme immunoassay kit with a microplate. RESULTS: Geometric means of angiotensin II concentrations on day 7 were 19 pg/ml in the normal birthweight group, 28 pg/ml in the moderately low birthweight group, and 76 pg/ml in the very low birthweight group. The concentrations on day 7 in the very low birthweight group were significantly higher than those in the normal birthweight and moderately low birthweight groups (p = 0.005, p = 0.031). There were significant correlations between angiotensin II concentration on day 7 and gestational age (r(s) = -0.4, p = 0.007) and birth weight (r(s) = -0.36, p = 0.016). CONCLUSIONS: Specific physiological conditions associated with a very low birth weight are thought to be responsible for the increased concentration of angiotensin II on day 7. It is necessary to measure angiotensin II concentration for a longer period after birth and study the factors that could influence it.

Aging↗
PubMed2006

BRAF mutations and phosphorylation status of mitogen-activated protein kinases in the development of flat and depressed-type colorectal neoplasias.

Although some molecular differences between flat-depressed neoplasias (FDNs) and protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF mutations or the status of phosphorylated mitogen-activated protein kinase (p-MAPK) are different between theses two groups. We evaluated the incidence of BRAF and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the immunohistochemical status of p-MAPK in the nonserrated neoplasias (46 FDNs and 57 PNs). BRAF mutations were detected in four FDNs (9%) and none of PNs (P=0.0369 by Fisher's exact test). KRAS mutations were observed in none of FDNs and in 14 PNs (25%; P=0.0002 by Fisher's exact test). MSI-H was detected in seven out of 44 FDNs (16%) and in one out of 52 of PNs (2%) (P=0.022 by Fisher's exact test). Type B and C immunostaining for p-MAPK was observed in 34 out of 46 FDNs (72%), compared with 24 out of 55 PNs (44%; P=0.0022 by chi(2) test). There was no significant difference in the type B and C immunostaining of p-MAPK between FDNs with and without BRAF mutations. BRAF and KRAS mutations are mutually exclusive in the morphological characteristics of colorectal nonserrated neoplasia. Abnormal accumulation of p-MAPK protein is more likely to be implicated in the tumorigenesis of FDNs than of PNs. However, this abnormality in FDNs might occur via the genetic alteration other than BRAF or KRAS mutation.

Adenocarcinoma↗
PubMed2005

A movement protein and three capsid proteins are all necessary for the cell-to-cell movement of apple latent spherical cheravirus.

Immunoblot analysis of apple latent spherical cheravirus (ALSV)-infected leaves using a polyclonal antibody against the 21 C-terminal amino acids of a 53 K/42 K movement protein (MP) showed that a protein with an Mr of 42 kDa (42KP) is the dominant form found in vivo, which could indicate that the second AUG is used as an initiation codon of a ORF in RNA2. Co-expression of GFP with 42KP in tobacco epidermal cells showed that 42KP is able to facilitate cell-to-cell trafficking of GFP that is expressed in the same cells. The analysis of deletion mutants on each of MP, Vp24, Vp20, or Vp25 using an ALSV vector that stably expresses GFP indicated that an MP and three capsid proteins are all indispensable for the cell-to-cell movement of the virus. In ultrathin sections of infected leaves, a file of virus-like particles passing through the plasmodesmata connecting neighboring cells and tubular structures containing virus-like particles extending into the cytoplasm were observed. These results show that ALSV moves from cell to cell as virus particles.

Blotting, Western↗
PubMed2004

Stable expression of foreign proteins in herbaceous and apple plants using Apple latent spherical virus RNA2 vectors.

Infectious cDNA clones of Apple latent spherical virus (ALSV)-RNA1 (pEALSR1) and -RNA2 (pEALSR2) were constructed using an enhanced 35S promoter. A viral vector was constructed from pEALSR2 by creating artificial protease processing sites by duplicating the Q/G protease cleavage site between 42KP and Vp25. Eight RNA2-derived vectors expressing GFP with varied sizes of duplications around the 42KP/Vp25 junction were constructed and tested for infectivity in Chenopodium quinoa. The results indicated that greater than five aa from the C-terminus of 42KP and N-terminus of Vp25 in duplication are necessary for systemic infection. In infected C. quinoa plants, GFP fluorescence was observed in both inoculated and upper leaves. Serial passages of the viruses derived from the above vectors in C. quinoa showed that the size of duplications affected the stability of the GFP gene. The version of the RNA2-vector (pER2L5R5GFP) with the shortest duplications and its silent mutant version could stably express GFP in leaves even after at least nine serial passages. ALSV-RNA2 vector has a capacity to maintain a DNA insert as long as 1300 bp because Apple chlorotic leaf spot virus movement protein (50KP) gene could be expressed in C. quinoa. Inoculation of a virus derived from pER2L5R5GFP to apple seedlings resulted in the expression of GFP fluorescence in uninoculated upper leaves, indicating that the vector is available for the expression of foreign genes in apple trees.

Blotting, Western↗
PubMed2003

MxA expression in patients with viral infection after allogeneic stem cell transplantation.

Many patients suffer febrile diseases soon after allogeneic stem cell transplantation (SCT). Some of the symptoms of viral infections and acute GVHD are often difficult to distinguish. However, an accurate diagnosis is important since the treatments for these conditions are different. It is known that MxA protein is specifically induced in patients with several viral infections. We investigated the cytoplasmic expression of MxA in the peripheral blood mononuclear cells (PBMCs) of patients with fever after allogeneic SCT using a newly generated monoclonal antibody (KM1135) and flow cytometry. The level of MxA expression was significantly higher in patients diagnosed with viral infections (n=6, cytomegalovirus in three, Epstein-Barr virus in one, human herpesvirus-6 in one, adenovirus in one) than control individuals (n=9) (P<0.05, Mann-Whitney test). The level of MxA in patients with aGVHD (n=7) was identical to that in controls. The level of MxA correlated well with the amount of the cytomegalovirus antigen-positive cells in the presence of acute GVHD in two patients. The measurement of MxA is simple and useful in distinguishing viral disease from acute GVHD after allogeneic SCT.

Adolescent↗
PubMed2003

The 50-kDa protein of Apple chlorotic leaf spot virus interferes with intracellular and intercellular targeting and tubule-inducing activity of the 39-kDa protein of Grapevine berry inner necrosis virus.

To understand why transgenic Nicotiana occidentalis plants expressing a functional movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV) show specific resistance to Grapevine berry inner necrosis virus (GINV), the MPs of ACLSV (50KP) and GINV (39KP) were fused to green, yellow, or cyan fluorescent proteins (GFP, YFP, or CFP). These fusion proteins were transiently expressed in leaf cells of both transgenic (50KP) and nontransgenic (NT) plants, and the intracellular and intercellular trafficking and tubule-inducing activity of these proteins were compared. The results indicate that in epidermal cells and protoplasts from 50KP plant leaves, the trafficking and tubule-inducing activities of GINV-39KP were specifically blocked while those of ACLSV-50KP and Apple stem grooving virus MP (36KP) were not affected. Additionally, when 39KP-YFP and 50KP-CFP were coexpressed in the leaf epidermis of NT plants, the fluorescence of both proteins was confined to single cells, indicating that 50KP-CFP interferes with the cell-to-cell trafficking of 39KP-YFP and vice versa. Mutational analyses of 50KP showed that the deletion mutants that retained the activities described above still blocked cell-to-cell trafficking of 39KP, but the dysfunctional 50KP mutants could no longer impede cell-to-cell movement of 39KP. Transgenic plants expressing the functional 50KP deletion mutants showed specific resistance against GINV. In contrast, transgenic plants expressing the dysfunctional 50KP mutants did not show any resistance to the virus. From these results, we conclude that the specific resistance of 50KP plants to GINV is due to the ability of the 50KP to block intracellular and intercellular trafficking of GINV 39KP.

Gene Expression Regulation, Plant↗
PubMed2001

Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB-dependent transcription by ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) is the current mainstay of treatment for various liver diseases including primary biliary cirrhosis. UDCA acts as a bile secretagogue, cytoprotective agent, immunomodulator, and inhibitor of cellular apoptosis. Despite this cumulative evidence of the cytoprotective and immunosuppressive effects of UDCA, both the target molecule and pathway of UDCA action remain unknown. We previously described that, in the absence of glucocorticoid ligand, UDCA activates the glucocorticoid receptor (GR) into DNA binding species but does not elicit its transactivational function in a transient transfection assay. Here we further studied the molecular mechanism of UDCA action and revealed that the ligand binding domain of the GR is responsible for UDCA-dependent nuclear translocation of the GR. Indeed, we demonstrated that UDCA acts on the distinct region of the ligand binding domain when compared with the classical GR agonist dexamethasone, resulting in loss of coactivator recruitment and differential regulation of gene expression by the GR. Our data clearly indicated that UDCA, at least in part via activation of the GR, suppresses NF-kappaB-dependent transcription through the intervention of GR-p65 interaction. Together with the established clinical safety of UDCA, we may propose that UDCA could be a prototypical compound for development of a novel and selective GR modifier.

Active Transport, Cell Nucleus↗
PubMed2001

Direct catalytic enantio- and diastereoselective aldol reaction using a Zn-Zn-linked-BINOL complex: a practical synthesis of syn-1,2-diols.

[reaction: see text] The direct catalytic enantio- and diastereoselective aldol reaction with 2-hydroxy-2'-methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked-BINOL complex 2, to afford alpha,beta-dihydroxy ketones in a highly syn-selective manner (up to syn/anti 97/3) and in excellent yields (up to 95%) and ees (up to 99%). Efficient transformations of the alpha,beta-dihydroxy ketone into an alpha,beta-dihydroxy ester and an alpha,beta-dihydroxy amide via regioselective rearrangements are also described.

Journal Article↗
PubMed2001

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy.

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32 +/- 1.42 versus 0.75 +/- 0.78 g/day; P = 0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45 +/- 1.50 versus 0.63 +/- 0.56 g/day; P = 0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children.

Adolescent↗
PubMed2001

Pathophysiology and treatment of IgA nephropathy in children.

IgA nephropathy is the most-common primary glomerulonephritis worldwide, and about 20%-50% of patients develop progressive renal failure. The pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end-stage renal disease is also becoming apparent in children. This review focuses on the pathophysiology and treatment of IgA nephropathy in children.

Child↗
PubMed2001

Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome.

Cyclosporine (CS) is well recognized to be effective in the treatment of children with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use can result in chronic nephrotoxicity. The histological changes that occur after CS discontinuation are unknown. Therefore, we examined the histological changes [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal glomerular lesions] in renal biopsy specimens after the drug had been discontinued in eight children with idiopathic nephrotic syndrome (NS). These children had been treated with long-term moderate-dose CS and had shown mild-to-moderate chronic CS nephrotoxicity. The degree of CAA improved significantly after CS discontinuation (mean CAA grade from 1.30+/-0.46 to 0.25+/-0.46, P=0.028). CAA disappeared in six of these children after CS discontinuation. However, the tubulointerstitial lesions and the focal glomerular lesions did not change after CS discontinuation. In conclusion, in children with idiopathic NS, CAA is improved by discontinuation of CS, but tubulointerstitial changes and focal glomerular lesions do not regress with drug discontinuation.

Arteries↗
PubMed2001

Transforming growth factor-beta1 expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation.

The main cause of late graft loss or declining long-term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF-beta1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta1 in the graft using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1. The change in creatinine clearance between 100 d and 3 yr after transplantation (DeltaCcr) was used as an index of long-term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome-stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as DeltaFI. DeltaCcr was -4.2+/-9.4 mL/min in subjects with minimal early immunoreactivity for CC and -20.5+/-15.9 mL/min in subjects with strong reactivity (p<0.05). DeltaCcr was -14.5+/-18.6 mL/min in subjects with minimal early immunoreactivity for LC and -11.7+/-12.8 mL/min in those with strong reactivity. DeltaFI in subjects with minimal CC reactivity (1.28+/-4.11%) tended to be lower than that in subjects with strong reactivity (8.45+/-15.47%). Neither fibrosis at 100 d nor DeltaFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF-beta1 expression in grafts at 100 d after transplantation is associated with a long-term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.

Adolescent↗
PubMed2001

Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis.

BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Angiotensin-Converting Enzyme Inhibitors↗