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Biomedical subjects

Takashi Taguchi

Publications and source records attributed to Takashi Taguchi.

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

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy.

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.

Acute Disease↗
PubMed2004

Autoimmune hepatitis in a patient with systemic lupus erythematosus: a case report.

A 48-year-old woman was admitted to our hospital because of ascites. Laboratory data indicated the presence of systemic lupus erythematosus (SLE) with nephrotic syndrome and elevated hepatic enzymes. Treatment with prednisolone resulted in a marked clinical improvement in renal and liver dysfunction. Histopathologic analysis of renal and liver tissues showed lupus nephritis and liver cirrhosis, respectively. According to the autoimmune hepatitis scoring system, the patient had both SLE and autoimmune hepatitis.

Journal Article↗
PubMed2004

Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice.

Fibroblast growth factor-23 (FGF-23), a recently identified molecule that is mutated in patients with autosomal dominant hypophosphatemic rickets (ADHR), appears to be involved in the regulation of phosphate homeostasis. Although increased levels of circulating FGF-23 were detected in patients with different phosphate-wasting disorders such as oncogenic osteomalacia (OOM) and X-linked hypophosphatemia (XLH), it is not yet clear whether FGF-23 is directly responsible for the abnormal regulation of mineral ion homeostasis and consequently bone development. To address some of these unresolved questions, we generated a mouse model, in which the entire Fgf-23 gene was replaced with the lacZ gene. Fgf-23 null (Fgf-23-/-) mice showed signs of growth retardation by day 17, developed severe hyperphosphatemia with elevated serum 1,25(OH)2D3 levels, and died by 13 weeks of age. Hyperphosphatemia in Fgf-23-/- mice was accompanied by skeletal abnormalities, as demonstrated by histological, molecular, and various other morphometric analyses. Fgf-23-/-) mice had increased total-body bone mineral content (BMC) but decreased bone mineral density (BMD) of the limbs. Overall, Fgf-23-/- mice exhibited increased mineralization, but also accumulation of unmineralized osteoid leading to marked limb deformities. Moreover, Fgf-23-/- mice showed excessive mineralization in soft tissues, including heart and kidney. To further expand our understanding regarding the role of Fgf-23 in phosphate homeostasis and skeletal mineralization, we crossed Fgf-23-/- animals with Hyp mice, the murine equivalent of XLH. Interestingly, Hyp males lacking both Fgf-23 alleles were indistinguishable from Fgf-23/-/ mice, both in terms of serum phosphate levels and skeletal changes, suggesting that Fgf-23 is upstream of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (Phex) and that the increased plasma Fgf-23 levels in Hyp mice (and in XLH patients) may be at least partially responsible for the phosphate imbalance in this disorder.

Alleles↗
PubMed2004

Hepatitis C virus NS5A protein interacts with 2',5'-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner.

The non-structural protein 5A (NS5A) of hepatitis C virus (HCV) has been implicated in inhibition of antiviral activity of IFN. While previous studies have suggested an interaction between NS5A and the double-stranded RNA-dependent protein kinase (PKR), the possibility still remains that interaction with another molecule(s) is involved in the NS5A-mediated inhibition of IFN. In the present study, we investigated a possible interaction between NS5A and 2',5'-oligoadenylate synthetase (2-5AS), another key molecule in antiviral activity. We observed that NS5A physically interacted with 2-5AS in cultured cells, with an N-terminal portion of NS5A [aa 1-148; NS5A(1-148)] and two separate portions of 2-5AS (aa 52-104 and 184-275) being involved in the interaction. Single point mutations at residue 37 of NS5A affected the degree of the interaction with 2-5AS, with a Phe-to-Leu mutation (F37L) augmenting and a Phe-to-Asn mutation (F37N) diminishing it. Virus rescue assay revealed that the full-length NS5A (NS5A-F) and NS5A(1-148), the latter of which contains neither the IFN sensitivity-determining region (ISDR) nor the PKR-binding domain, significantly counteracted the antiviral activity of IFN. Introduction of a F37N mutation into NS5A(1-148) impaired the otherwise more significant IFN-inhibitory activity of NS5A(1-148). It was also found that the F37N mutation was highly disadvantageous for the replication of an HCV RNA replicon. Taken together, our results suggest the possibility that NS5A interacts with 2-5AS and inhibits the antiviral activity of IFN in an ISDR-independent manner.

2',5'-Oligoadenylate Synthetase↗
PubMed2004

Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.

This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.

Adult↗
PubMed2004

[A case of chronic renal insufficiency due to vascular injury of systemic sclerosis].

A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.

Arthritis, Rheumatoid↗
PubMed2003

Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner.

We previously demonstrated that Irs2-/- mice develop diabetes due to beta-cell growth failure and insulin resistance; however, glucose-induced insulin secretion was increased in islets isolated from Irs2-/- mice. Pdx-1, a transcription factor important for maintenance of the beta-cell function, was recently reported to be severely reduced in Irs2-/- murine beta-cells. We report herein that Pdx-1 expression, including the amount of Pdx-1 localized in the nucleus, is not down-regulated in our Irs2-/- murine beta-cells with a C57BL/6 background. We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3beta and HNF1alpha, as well as its downstream genes, including insulin, Glut2, and Nkx6.1, to be well preserved. We have further demonstrated Pdx-1 expression to also be preserved in beta-cells of 30-week-old diabetic Irs2-/- mice. In addition, surprisingly, even in Irs2-/- mice on a high fat diet with markedly elevated blood glucose, exceeding 400 mg/dl, Pdx-1 expression was not reduced. Furthermore, we found Pdx-1 to be markedly decreased in certain severely diabetic Irs2-/- mice with a mixed C57BL/6J x 129Sv background. We conclude that 1) Pdx-1 expression in Irs2-/- mice is regulated in a strain-dependent manner, 2) Irs2-/- mice develop diabetes associated with beta-cell growth failure even when Pdx1 expression is preserved, and 3) Pdx-1 expression is preserved in severely hyperglycemic Irs2-/- mice with a C57BL/6 background on a high fat diet.

Animal Feed↗
PubMed2003

Pulmonary fibrosis: cellular and molecular events.

Connective tissue remodeling of the interstitium is an important feature of chronic lung diseases encompassing interstitial inflammatory changes and subsequent pulmonary fibrosis. The early inflammatory phase is usually associated with the release of several cytokines and chemokines by activated resident cells and infiltrating cells which, in turn, help further recruit inflammatory mononuclear cells. Cytokines and growth factors secreted by inflammatory cells and by interstitial cells (fibroblasts and myofibroblasts) play an important role in the fibrogenic phase of pulmonary fibrosis by inducing matrix synthesis. In addition, matrix-degrading enzymes and their inhibitors also contribute to extracellular matrix (ECM) remodeling in pulmonary fibrosis. This review addresses the pathophysiology of wound healing and different phases of pulmonary fibrosis.

Cytokines↗
PubMed2003

Expression of the c-Met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia.

c-Met is a tyrosine kinase receptor for hepatocyte growth factor and suggested to be involved in oncogenesis ormetastatic phenotypes in many malignancies. Adult T-cell leukemia (ATL) is a neoplasia characterized by massive invasion of the leukemic cells into various organs. Recently, we have reported frequent hepatic involvement and the relationship between liver invasion and the poor prognosis in ATL. In the present study, we investigated the expression of c-Met in ATL cells and its relation to liver dysfunction. In three of four human T-cell lymphotrophic virus-I-positive T-cell lines, c-Met was expressed both at mRNA and protein levels, whereas it was not expressed in human T-cell lymphoma virus-I-negative T-cell lines. The expressed c-Met should be functional, because hepatocyte growth factor could induce the autophosphorylation of c-Met. Although the viral-transactivating protein Tax has been shown to be involved in the deregulated expression of cellular genes, Tax mRNA was not detected in c-Met mRNA-expressed cell lines. From freshly isolated peripheral blood mononuclear cells, the expression of c-Met mRNA was detected in 10 of 16 ATL patients but not from healthy individuals. Finally, serum transaminase levels were significantly increased in c-Met-positive ATL cases, and all of the infiltrated c-Met-positive cells into liver were shown to be multilobularly nucleated phenotype. Taken together, these data suggest for the first time that c-Met is involved in the liver invasive phenotype of ATL.

Blotting, Western↗
PubMed2002

Cellular and molecular events leading to renal tubulointerstitial fibrosis.

Connective tissue remodeling of the extracellular matrix (ECM) is an essential and dynamic process associated with both physiological responses, such as wound healing, and pathological conditions, such as renal tubulointerstitial fibrosis (TIF). Data from the published literature indicate that collagens and several non-collagenous ECM glycoproteins actively contribute to TIF. The early phase of TIF is usually associated with an inflammatory process mediated by soluble factors released by activated resident cells and by infiltrating cells. Fibrogenic cytokines and growth factors secreted by inflammatory cells and fibroblasts are actively involved in connective tissue remodeling, possibly by regulating the rate of synthesis and degradation of the ECM. An uncontrolled balance of this process usually results in TIF. We review the physiology of wound healing and the pathology of fibrosis, emphasizing TIF.

Extracellular Matrix↗