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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 289 records · Page 16Linked to original sources
PubMed1999

Beta2-microglobulin and renal bone disease.

Dialysis-related amyloidosis (DRA) is characterized by amyloid deposition mainly in bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. Beta2-microglobulin has been demonstrated to be a major constituent of amyloid fibrils. DRA occurs not only in patients undergoing long-term hemodialysis, but also in patients undergoing continuous ambulatory peritoneal dialysis. The incidence of this complication increases with the duration of dialytic therapy and the age of the patient. While a definitive diagnosis of DRA can be made only by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies have, however, suggested a pathogenic role of a new modification of beta2-microglobulin in amyloid fibrils--that is, the advanced glycation end-products (AGEs) formed with carbonyl compounds derived from autoxidation of both carbohydrates and lipids ("carbonyl stress"). Therapy for DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.

Amyloid↗
PubMed1999

Clomipramine treatment of delusional disorder, somatic type.

Four patients of delusional disorder, somatic type, were treated with clomipramine 60-120 mg/day. All patients showed marked clinical improvement after 27-57 days of clomipramine treatment. In one case, previous treatments by various antipsychotic drugs including pimozide had been unsuccessful. This report suggests that clomipramine is effective at least for some patients with delusional disorder, somatic type, including pimozide-resistant cases. It is also suggested that there is some association between delusional disorder, somatic type, and serotonergic dysfunction.

Adult↗
PubMed1999

[Fenestrated basilar artery aneurysm: case report].

The authors reported an operated case with an aneurysm arising from the proximal end of basilar artery fenestration, and discussed its etiology and surgical strategy. A 47-year-old woman presented with slight memory disturbance. Neuroradiologic examination revealed an aneurysm located on the proximal end of the basilar artery 12 x 9 mm in size at the level of the outer auditory meatus. The union of vertebral arteries had deviated toward the right side, and the aneurysmal dome had projected into the fenestration. Through the right far lateral approach, we applied two straight fenestrated clips X configuration to the aneurysm. Several authors have reported a variety of approaches for vertebrobasilar aneurysms along the midline with consideration of the height of the aneurysmal. However, another point of view is that attention should be paid to the direction of the clip blade and applied at the final clipping, because, for vertebrobasilar aneurysms adjacent to the midline, the surgical view and working space are extremely restricted.

Basilar Artery↗
PubMed1999

[Emergency coronary artery bypass grafting for ischemic heart disease].

Between June, 1988 and May 1998, 524 patients underwent isolated coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass in our institution. The 74 patients who underwent CABG on emergency surgery were subjected in this study. Age was ranged 33 to 89 years (mean 65 +/- 1.1; 50 male, 24 female). Of 74 cases, 52 cases underwent emergency CABG due to UAP, and 22 cases were AMI. The hospital mortality rate in 74 cases was 19% (15/74) and 2.4% (11/450) in patients who had scheduled CABG (p < 0.0001). Mortality rate in AMI group was 41% (9/22) and 9.6% (5/52) in UAP (p < 0.005). Number of patients aged 75 years or elder was 14 (19%) in emergency CABG, and 43 (8.9%) in scheduled CABG (p < 0.05). To improve the operative results of emergency CABG, it is important to reduce the number of emergency CABG in elderly, by the careful diagnosis and aggressive surgical treatment as same as in younger patient.

Adult↗
PubMed1999

[Progressive mitral regurgitation which is necessitated the mitral valve replacement after partial left ventriculectomy (Batista procedure): a case report].

The patient is 61-year-old woman who underwent partial left ventriculectomy, (Batista procedure) due to dilated cardiomyopathy and multiple thromboembolism. Although postoperative course was uneventful, she has had clinical symptoms of the left heart failure due to the increased mitral valve regurgitation at the early postoperative period, gradually. Even though mitral valve regurgitation was severe, it was not apt to re-dilatate the left ventricular capacity evaluated by echocardiography. She underwent the mitral valve replacement on the 92nd postoperative day, and was once possible for weaning from cardiopulmonary bypass under the support of IABP. However, she died on the 19th postoperative day caused by sepsis. It is important to evaluate the accurate mitral valve regurgitation preoperatively for Batista procedure. Although there was the mild mitral valve regurgitation, it is essential to repair or replace the mitral valve for Batista procedure.

Cardiac Surgical Procedures↗
PubMed1999

[Risk factor of liver disorders caused by flutamide--statistical analysis using multivariate logistic regression analysis].

The antiandrogenic drug, flutamide (Odyne), is widely used in the treatment of carcinoma of prostate. It is well known that flutamide has adverse effects of liver disorders. To ascertain the risk of liver disorders before administering this drug, past history and lifestyle preferences were resurveyed in 123 patients who had been treated with flutamide. The results obtained were assessed in relation to the occurrence of liver disorders by multivariate logistic regression analysis. The incidence of liver disorders was 26% (33/123), with 64% of the disorders occurring within 9 months. The chi-square test for dependent variables revealed that three variables, i.e., body mass index, past history of liver disorders and elevated glutamic-pyruvic transaminase levels were significantly related to the incidence of liver disorders (p > 0.05). Multivariate analysis indicated that a history of liver disorders and elevated alanine aminotransferase (ALT) levels were related to a higher incidence of liver disorders. Elevated ALT levels were associated with a higher incidence of liver disorders and smoking was related to a lower incidence of the liver disorders.

Alanine Transaminase↗
PubMed1999

[Antiangiogenic and antitumor effect of BPHA, an orally-active matrix metalloproteinase inhibitor, in in vivo murine and human tumor model].

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.

Animals↗
PubMed1999

[The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis].

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.

Anti-Inflammatory Agents↗
PubMed1998

Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro.

Recently, a positive and a negative elongation factor, implicated in 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibition of transcription elongation, has been identified. P-TEFb is a positive transcription elongation factor and the DRB-sensitive kinase that phosphorylates the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II). PITALRE, a member of the Cdc2 family of protein kinases, is the catalytic subunit of P-TEFb. DSIF is a human homolog of the yeast Spt4-Spt5 complex and renders elongation of transcription sensitive to DRB. DRB sensitivity-inducing factor (DSIF) binds to RNA Pol II and may directly regulate elongation. Here we show a functional interaction between P-TEFb and DSIF. The reduction of P-TEFb activity induced by either DRB, antibody against PITALRE, or immunodepletion resulted in a negative effect of DSIF on transcription. DSIF acts at an early phase of elongation, and the prior action of P-TEFb makes transcription resistant to DSIF. The state of phosphorylation of CTD determines the DSIF-RNA Pol II interaction, and may provide a direct link between P-TEFb and DSIF. Taken together, this study reveals a molecular basis for DRB action and suggests that P-TEFb stimulates elongation by alleviating the negative action of DSIF.

Cyclin-Dependent Kinase 9↗
PubMed1998

Monolayer Behavior of Tetraphenylporphyrin Derivatives Containing Four Fluorocarbon Chains and Optical Properties of Their Monolayer Assemblies.

For tetraphenylporphyrin derivatives substituted with four fluorocarbon chains (TFPP), monolayers on the water surface were studied with the Brewster angle microscope together with pressure-area curves. It was found that heterogeneous aggregated structures of the monolayers were dependent upon the chain length of fluorocarbons, the metal-free or Mn-TFPP, and the periods after spreading. Polarized UV-visible spectra for the monolayer assemblies indicated that the porphyrin rings in the films were tilted on the average, but had a tendency to adopt an orientation more parallel to the water surface as the chain length of the fluorocarbon increased. The third-order nonlinear optical susceptibility for the monolayer assembly of TFPP with the shorter chains was found to be 7.0 x 10(-13) esu, and those of Mn-TFPP were enlarged. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat1 fibroblasts expressing insulin receptors.

Shc is phosphorylated on Tyr-239/240 and/or Tyr-317, which serves as a docking site for Grb2. To clarify the relative involvement of Shc Tyr-239/240 and Tyr-317 in insulin-induced mitogenesis, we generated expression vectors for Y317F (1F)-Shc, Y239/240F (2F)-Shc, and Y239/240/317F (3F)-Shc, and stably transfected them into Rat1 fibroblasts expressing insulin receptors (HIRc). Insulin-induced Shc phosphorylation and subsequent association with Grb2 was enhanced in wild-type (WT)-Shc cell. In contrast, insulin-stimulated Shc phosphorylation and Shc.Grb2 association were significantly decreased in 1F-Shc and 3F-Shc cells, while these were only slightly affected and almost comparable in 2F cells compared with those in parental HIRc cells. The kinetics of MAP kinase activation closely paralleled the kinetics of Shc phosphorylation and Shc.Grb2 association. Thus, insulin stimulation of MAP kinase activation occurred more rapidly in WT-Shc cells, and the activation was delayed in 1F-Shc and 3F-Shc cells, while it was comparable in 2F-Shc cells compared with that in HIRc cells. Furthermore, WT-Shc cells displayed enhanced sensitivity to insulin stimulation of thymidine incorporation. Importantly, the sensitivity was significantly decreased in 1F-Shc and 3F-Shc cells, while it was almost comparable in 2F-Shc cells compared with that in HIRc cells. These results indicate that Shc Tyr-317 is more predominant insulin-induced phosphorylation site than Tyr-239/240 for coupling with Grb2 leading to MAP kinase activation and mitogenesis in Rat1 fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Casein kinase II interacts with the bZIP domains of several transcription factors.

Casein kinase II (CKII) is thought to regulate a broad range of transcription factors, but its mode of action is not well characterized. We previously showed that CKII is co-purified with the ATF family of transcription factors using DNA-affinity latex beads. Here we report a functional and physical interaction between CKII and transcription factors. We demonstrate that CKII binds through its catalytic alpha and alpha' subunits to the basic leucine zipper (bZIP) DNA-binding domains of many transcription factors, including ATF1. Kinetic analysis using a surface plasmon resonance sensor suggests that CKII loosely associates with ATF1 in vivo . Deletion of the bZIP domain of ATF1 markedly reduces its phosphorylation by CKII, suggesting that the bZIP recruits CKII to the vicinity of the target site. ATF1-CKII complex is also formed on DNA. Using CKIIalpha fusedto a heterologous DNA-binding domain, we also demonstrate that CKII, when bound to DNA, efficiently phosphorylates its substrate, which is bound to the same DNA molecule. Taken together, CKII may regulate transcription (and possibly other events) by phosphorylating proteins on DNA.

Activating Transcription Factor 1↗
PubMed1998

Developmental changes and functional properties of human memory T cell subpopulations defined by CD60 expression.

The present study was undertaken to examine developmental changes of T cells expressing CD60 and their functional properties. Three-color immunofluorescence analysis revealed that the CD60 antigen was preferentially expressed on a proportion of memory (CD45RO+) CD4+ T cells, but less on memory CD8+ T cells, while this antigen is undetectable in naive (CD45RO-) T cells. A frequency of memory CD4+ T cells expressing CD60 in the peripheral blood was negligible in newborns and gradually increased with advancing age. CD60+ memory CD4+ T cells showed stronger proliferative responses to PPD and produced higher levels of IL-4 and IL-10 than CD60- ones, whereas production of IL-2 and IFN-gamma was similarly found in both cell subpopulations. In addition, it was shown that efficient helper activity for Ig production by B cells was predominated in CD60+ memory CD4+ T cells. These results suggest that CD60 may be primarily expressed on the functionally differentiated memory effector cells among circulating CD45RO+ CD4+ T cells.

Adolescent↗
PubMed1998

Snurportin1, an m3G-cap-specific nuclear import receptor with a novel domain structure.

The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is dependent on the presence of a complex nuclear localization signal (NLS). The latter is composed of the 5'-2,2,7-terminal trimethylguanosine (m3G) cap structure of the U snRNA and the Sm core domain. Here, we describe the isolation and cDNA cloning of a 45 kDa protein, termed snurportin1, which interacts specifically with m3G-cap but not m7G-cap structures. Snurportin1 enhances the m3G-capdependent nuclear import of U snRNPs in both Xenopus laevis oocytes and digitonin-permeabilized HeLa cells, demonstrating that it functions as an snRNP-specific nuclear import receptor. Interestingly, solely the m3G-cap and not the Sm core NLS appears to be recognized by snurportin1, indicating that at least two distinct import receptors interact with the complex snRNP NLS. Snurportin1 represents a novel nuclear import receptor which contains an N-terminal importin beta binding (IBB) domain, essential for function, and a C-terminal m3G-cap-binding region with no structural similarity to the arm repeat domain of importin alpha.

Amino Acid Sequence↗
PubMed1998

IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice.

CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL-Fas(lpr) kidney, infiltrating T cells that secrete IFN-gamma are a hallmark of disease. To examine the impact of IFN-gamma on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-gamma R-deficient strain. In MRL-Fas(lpr) mice lacking IFN-gamma R, circulating and intrarenal CSF-1 were absent, TNF-alpha was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-gamma R induced CSF-1 and TNF-alpha in MRL-Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-gamma R induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-alpha induces apoptosis in MC, but not TEC, of the MRL-Fas(lpr) strain. Thus, IFN-gamma is directly and indirectly responsible for apoptosis of TEC and MC in MRL-Fas(lpr) mice, respectively. In conclusion, IFN-gamma R signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.

Animals↗
PubMed1998

Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase.

The elevated exogenous-methionine dependency of tumors for growth has been observed in all major cancer cell types. We have previously cloned a methioninase (rMETase) from Pseudomonas putida to deplete methionine. Growth inhibition followed by apoptotic cell death was induced by treatment of tumor cells with rMETase in vitro. A single i.p. injection of 300 units of rMETase can lower the serum methionine level in the mice from 70 microM to less than 1 microM within 2 h and maintain this depleted level for 8 h. Repeated dosing of rMETase of tumor-bearing mice could be administered without acute immune-hypersensitivity. rMETase treatment demonstrated growth inhibitory activity against human tumors in nude mice, including those which were multiple drug-resistant. No body weight loss or hematotoxicity, except a slight anemia, was found throughout the therapy. The combined treatment of the Lewis lung carcinoma with a fixed rMETase dose and increasing doses of 5-fluorouracil (5-FU) resulted in a dose-dependent enhanced antitumor efficacy for survival as well as tumor growth inhibition. Thus, methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU. The data presented in this report thus indicate that rMETase is active alone, is synergistic in combination with 5-FU, and has negligible toxicity suggesting a novel clinical approach for effective cancer therapy.

Animals↗
PubMed1998

IFN-gamma limits macrophage expansion in MRL-Fas(lpr) autoimmune interstitial nephritis: a negative regulatory pathway.

IFN-gamma is capable of enhancing and limiting inflammation. Therefore, an increase in IFN-gamma in autoimmune MRL-Fas(lpr) mice could exacerbate or thwart renal injury. We have established a retroviral gene transfer approach to incite interstitial nephritis in MRL-Fas(lpr) mice that is rapid, enduring, and circumscribed. Renal tubular epithelial cells (TEC) were genetically modified to secrete macrophage (Mphi) growth factors (CSF-1-TEC, GM-CSF-1-TEC) and infused under the renal capsule. To determine the impact of IFN-gamma in Mphi growth factor-incited renal injury, we constructed a MRL-Fas(lpr) IFN-gamma-receptor (IFN-gammaR)-deficient strain. Gene transfer of CSF-1 or GM-CSF incited more severe interstitial nephritis in IFN-gammaR-deficient than in IFN-gammaR-intact MRL-Fas(lpr) mice, consisting of an increase of Mphi. To determine the mechanism responsible for the increase in Mphi in IFN-gammaR-deficient MRL-Fas(lpr) mice, we evaluated Mphi proliferation, apoptosis, and recruitment. Proliferation of bone marrow Mphi from IFN-gammaR-intact MRL-Fas(lpr) costimulated with CSF-1 or GM-CSF and IFN-gamma was reduced twofold, while the IFN-gammaR-deficient MRL-Fas(lpr) bone marrow Mphi remained stable. Furthermore, we detected more proliferating and fewer apoptotic Mphi within the interstitium in IFN-gammaR-deficient MRL-Fas(lpr) mice. Using unilateral ureteral ligation we established that IFN-gammaR signaling does not alter Mphi recruitment into the kidney. Thus, the increase in Mphi elicited by Mphi growth factors in IFN-gammaR-deficient MRL-Fas(lpr) mice is a result of enhanced proliferation and decreased apoptosis, and is independent of recruitment. Taken together, we suggest that IFN-gamma provides a negative regulatory pathway capable of limiting Mphi-mediated renal inflammation.

Animals↗