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M Yashiro

Publications and source records attributed to M Yashiro.

At least 91 records · Page 5Linked to original sources
PubMed1995

Dinuclear metal complexes for the efficient RNA hydrolysis.

Dinuclear Zn(II) and La(III) complexes with TPHP efficiently hydrolyze a dinucleotide, ApA, under mild conditions (TPHP = N, N, N', N'-tetrakis[(2-pyridyl)-methyl]-2-hydroxy-1,3-diaminopropane). [Zn2(TPHP)]3+ hydrolyzes ApA with an extremely high activity; The pseudo-first-order rate constant is 8.4 x 10(-4) h-1 at pH 7, 50 degrees C when [[Zn2 (TPHP)]3+] = 2.5 mM. Free Zn(II) ion shows no hydrolysis activity under the conditions. Enormous acceleration of the hydrolysis by the dinuclear complex formation was also observed for La(III) ion. Its activity for the ApA hydrolysis is 100-fold greater than that of free La(III) ion. These dinuclear complexes are promising for the active sites of artificial ribonucleases.

Binding Sites↗
PubMed1995

Synergism of Ce (IV) and Pr(III) for the fastest non-enzymatic DNA hydrolysis ever.

By the synergistic catalysis of Ce4+ and Pr3+, DNA is efficiently hydrolyzed at so far the highest rate. When [Ce4+] = 10 mM and [Pr3+] = 5 mM, the half-life of dinucleotide hydrolysis at pH 7 and 50 degrees C is only 24 min. This catalytic activity is 9 times as large as that of Ce4+, which is the only prominent catalyst hitherto reported. The Ce(4+)-Nd3+ combination is also effective. These bimetallic catalytic systems are eminent tools for the future molecular biology and biotechnology.

Catalysis↗
PubMed1994

Synthesis of naphthalenesulfonic acid small molecules as selective inhibitors of the DNA polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.

Over 25 selected naphthalenesulfonic acid derivatives were evaluated for their inhibitory effect on two different functional domains of the HIV-1 reverse transcriptase (RT), namely the ribonuclease H and DNA polymerase activities. Most of the analogues were found to be either specific toward the DNA polymerase activity or showed nonselective inhibition of both catalytic functions. The most active compounds are either symmetrical derivatives or nonsymmetrical derivatives containing a lipophilic appendage consisting of a palmitoyl or cholesteryl moiety. The six most active compounds in the preliminary screen, derivatives 6, 16, 17, 23, 26, and 27, were subjected to experiments to determine their 50% inhibitory concentration (IC50) values in the assays that measure RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) functions of HIV-1 RT. The most potent derivative was a nonsymmetric cholesterol-linked 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid analogue, compound 23, which demonstrated an IC50 value of 0.06 microM for inhibiting RDDP activity. Inhibition of DDDP and RNase H activity for this compound was demonstrated at concentrations that were over 100-fold of that for inhibiting RDDP activity. However, the potency of this active compound does not correlate in the whole virus assay, probably due to a lack of cellular entry. The cholesterol derivative, 23, also possesses HIV-1 protease inhibitory activity and belongs to a unique class of multifunctional HIV-1 inhibitors.

Cholesterol↗
PubMed1994

Role of orthotopic fibroblasts in the development of scirrhous gastric carcinoma.

We examined the interaction between scirrhous gastric cancer cells and organ-specific fibroblasts in vivo and in vitro. Co-inoculation of scirrhous gastric cancer cells with gastric fibroblasts into nude mice specifically increased tumorigenicity, compared with that of gastric cancer cells alone. Furthermore, the histologic findings of the xenograft produced by co-inoculation with gastric fibroblasts was similar to that of human scirrhous gastric carcinoma. Conditioned medium from gastric fibroblasts significantly stimulated the growth of gastric cancer cells. These findings suggest that the growth of scirrhous gastric cancer cells was affected by orthotopic fibroblasts.

Adenocarcinoma, Scirrhous↗
PubMed1994

Two-compartment model of cholesterol kinetics for establishment of treatment strategy of LDL apheresis in nephrotic hypercholesterolemia.

Cholesterol kinetics in the time course after LDL apheresis using a dextran sulfate cellulose column was analyzed by adapting a two-compartment cholesterol kinetic model. Fifteen sets of serial serum cholesterol concentrations after LDL apheresis from 4 patients with drug-resistant nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabolic rates (Kc; 0.171 +/- 0.073/day, mean +/- SD) were markedly decreased as reported in familial hypercholesterolemia (homo: 0.101/day, hetero: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/day, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg/dl/day). This result was compatible with an earlier report that Kc was reduced earlier than G in nephrotic hypercholesterolemia. The time average serum cholesterol concentrations (TAC) in the rebound phase after LDL apheresis can be simulated using these kinetic parameters by the Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficial effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, once-weekly treatment of LDL apheresis was sufficient to achieve this aim, but in the remaining 5 cases, more frequent LDL apheresis up to twice a week was necessary in the early phase of treatment. In conclusion, the two-compartment cholesterol kinetic model is useful in clarifying the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia.

Adolescent↗
PubMed1994

Correlations of C1q- and C3d-bearing circulating immune complexes with immunopathological disease activity in lupus nephritis patients.

The serum levels of circulating immune complexes (CIC) measured by three different types of enzyme immunoassay (EIA) using monoclonal anti-C1q and antibodies and C1q as solid phase reagents were compared with clinical disease activity and immunohistological glomerular lesions in 29 SLE patients. Three types of CIC measured by these assays (anti-C1q CIC, anti-C3d CIC and C1q SP CIC) showed significantly higher levels in patients than in controls and were significantly associated with the clinical and serological disease activities. Anti-C1q CIC showed good correlation not only with mesangial IgG depositions (P < 0.01), but also with that of C1q (P < 0.05). C1q SP CIC also showed a weak correlation with mesangial C1q deposition (P < 0.05). Serum levels of anti-C3d CIC increased with the degree of mesangial IgG and complement depositions. Analysis of the clinical course of a patient with active SLE revealed a more rapid decrease of anti-C1q CIC and anti-C3d CIC along with the improvement of disease activity, including the mesangial lesion, than that of C1q SP CIC. According to these results, the CIC detected with assays using monoclonal antibodies against complement fragments, especially the anti-C1q assay, is likely to provide specific information regarding the clinical, serological and immunohistological disease activity in lupus nephritis.

Antigen-Antibody Complex↗
PubMed1994

Does LDL-apheresis in steroid-resistant nephrotic syndrome affect prognosis?

Low-density lipoprotein apheresis (LDL-A) was performed for nine episodes of steroid-resistant nephrotic syndrome in eight patients. The clinical and immunohistological findings were analysed retrospectively. Six of the patients had focal glomerular sclerosis (FGS), one had minimal-change nephrotic syndrome (MCNS), and one had membranous nephropathy (MN) with FGS. The LDL-A treatment, carried out 2-13 times (mean 7.33 +/- 4.05) for one nephrotic episode, at average intervals of 3-16 days (mean: 8.5 +/- 5.1 days) and combined with steroid pulse therapy and the administration of an antihyperlipidaemic agent in some cases, led to rapid amelioration of hyperlipidaemia. In six nephrotic episodes (5 patients) more than 50% reduction of proteinuria occurred (less than 3.5 g/day) (response-group). A significant elevation of serum albumin (more than 3.0 g/dl) was obtained in five of these episodes. The other three patients were resistant (resistant-group). The number of and intervals between LDL-A treatments in the response group (5 +/- 2.8 times and 5.8 +/- 4.1 days) were significantly less than those in the resistant-group (12.0 +/- 0.8 times and 13.2 +/- 1.8 days) (P < 0.05). After LDL-A, significant reductions were observed in the serum total cholesterol (T-CHO), phospholipid (PL), triglyceride (TG), free-CHO (F-CHO), and beta-lipoprotein (beta-lipo) (P < 0.05). HDL-cholesterol (HDL-C) increased somewhat after LDL-A. Further, Ccr was elevated in all nephrotic episodes, except in one patient who manifested renal failure after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Waldenström's macroglobulinemia associated with amyloidosis and membranous nephropathy.

A 61-year-old man with massive proteinuria and hyper gamma-globulinemia was admitted to hospital because of massive edema and pulmonary infection. He showed significantly high level of serum IgM (3244 mg/dl) with lambda-type M-protein and Bence Jones protein detected by immunoelectrophoresis. Renal biopsy specimen showed not only the diffuse amorphous amyloid deposition in mesangial area but global thickening of capillary wall with spike formation by silver staining which was similar to the spicular formation. Immunofluorescence disclosed find granular deposition of IgG and C3 along the capillary wall and the electromicroscopic findings clearly showed both massive amyloid fibril at mesangial area and diffuse epimembranous electron dense deposits. lambda-type Bence Jones protein in macroglobulinemia was suggested not only the cause of renal amyloidosis but also the antigenic origin of membranous nephropathy in this case.

Amyloidosis↗
PubMed1993

Molecular design of artificial hydrolytic nucleases and ribonucleases.

Artificial nucleases and ribonucleases, which selectively hydrolyze the specific phosphodiester linkages in DNAs and RNAs, are prepared by the attachment of organic and inorganic catalysts to DNA oligomers as sequence-recognizing moieties. A hybrid of ethylenediamine and a 19-mer DNA selectively hydrolyzes tRNA(Phe) at the 3'-side of C63. Site-selective hydrolysis of DNAs has been accomplished by the lanthanide complexes bound to DNA oligomers. No concurrent oxidative cleavage of the ribose or the deoxyribose takes place.

Base Sequence↗
PubMed1993

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with Kawasaki disease-like coronary aneurysms.

A patient with recurrent renal failure due to massive interstitial nephritis caused by Leu 3a + 3b-positive T-cell infiltration and associated with multiple thromboembolic attacks is reported. He died of gastrointestinal bleeding after treatment with anticancer agents. At autopsy, diffuse necrosis of the bilateral kidneys was noted as well as giant coronary aneurysms filled with thrombus that resembled those seen in Kawasaki disease and multiple old myocardial infarcts were also present. Among the various Epstein-Barr virus (EBV)-specific antibodies, the titers anti-viral capsid antigen (VCA) and anti-early antigen (EBEA) IgG antibody were always very high in contrast to the relatively low titers of anti-EB nuclear antigen (EBNA) antibodies. DNA extracted from kidney tissue obtained at autopsy was analyzed by Southern blot hybridization after the amplification of EBV-specific DNA by the polymerase chain reaction. In situ hybridization of kidney tissue obtained at biopsy was also performed using an enzyme-linked probe derived from the EBV-encoded RNA 1 (EBER1) gene. As a result, the EBV genome was found both at autopsy and in the biopsy tissue, which clearly revealed EBER1 in the interstitial cells. Taking account of the progressive ST-T changes of the electrocardiograms which were normal early in his course, multiple myocardial infarction associating multiple giant aneurysms probably occurred during this disease process. Thus, it could be concluded that chronic active EBV infection contributed massive interstitial nephritis mediated by the activation of Leu 3a + 3b-positive T cells.

Adult↗
PubMed1992

Enormous catalyses of lanthanide metal ions for unprecedentedly fast hydrolysis of 3',5'-cyclic adenosine monophosphate.

3',5'-cyclic adenosine monophosphate (cAMP) is efficiently hydrolyzed by use of lanthanide metal(III) ions as catalysts. The acceleration by 10(-2) M of Ce(III) is remarkable (more than 10(11) fold) at pH 8.0, 30 degrees C, decreasing the half-life from a half million years to 35 seconds. The catalytic activity is in the following order: Ce >> Pr > Nd, La > Y, Sm, Dy > others. The catalysis is ascribed to cooperation of three or four lanthanide metal ions.

Catalysis↗
PubMed1991

Different appearance and pathogenic roles of serum IgA against autologous IgG Fc and Fab in patients with IgA nephropathy.

The serum levels of IgA class antibodies against autologous IgG Fc and Fab fragments were measured by ELISA in 62 patients with primary IgA nephropathy (IgAN) and 20 normal healthy volunteers. Both antibodies were significantly higher in the patients (P less than 0.01). The total IgA levels were correlated with those of IgA anti-IgG Fc antibodies (IgA anti-Fc) (rs = 0.57, P less than 0.001), but not with those of the IgA anti-IgG Fab antibodies (IgA anti-Fab). A histopathological comparison revealed that the sera of patients with severe glomerulonephritis had significantly higher levels of IgA anti-Fc than those with milder lesions (P less than 0.01). On the other hand, no correlation was observed between the serum levels of IgA anti-Fab and the histopathological severity. A comparison before and after treatment in 12 patients demonstrated a significant decrease of IgA anti-Fc (P less than 0.01) and an increase of IgA anti-Fab (P less than 0.05) after the treatment. Size analysis in serial sera from 3 patients was performed using HPLC under neutral (pH = 7.0) and under acid (pH = 3.5) buffer conditions. A markedly increased ratio of both antibodies with the polymeric form was observed in the active phase. In the remission phase, the amounts of acid-dissociable polymeric form IgA anti-Fc were decreased. In contrast, high levels of polymeric form IgA anti-Fab continued to be observed in 2 patients at this phase. These results suggest that abnormally stimulated production of IgA class autoantibodies especially with the polymeric form against both IgG Fc and Fab fragments, occurs in IgAN, involving separate regulation with differing reactions to treatment and a distinct relationship between IgA anti-Fc and active histopathological lesions.

Adolescent↗
PubMed1991

Pathogenic role of polyclonal and polymeric IgA in a murine model of mesangial proliferative glomerulonephritis with IgA deposition.

Molecular size and charge distribution of IgA of sera and glomerular eluates were investigated in ddY mice, spontaneously developing mesangial proliferative glomerulonephritis (GN) with IgA deposition after 40 weeks of age. Serum IgA levels were increased in aged ddY mice more than 40 weeks old with a significant increase (P less than 0.01) at the age of 60 weeks, comparing with those of BALB/c mice. The isoelectric focusing (IEF) spectrotype of pooled serum IgA in 60-week-old mice ranged from 4.2 to 5.5, being similar to those in younger ddY (16 weeks old) and control BALB/c mice (12 weeks old) without enhanced expression of specific IgA peaks. However, IgA in the glomerular eluate from the 60-week-old mice showed limited anionic spectrotypes from pH 4.2 to 4.8. HPLC of IgA in pooled sera and glomerular eluates of 16-, 40- and 60-week-old ddY mice, revealed markedly increased ratios of the dimeric IgA (dIgA) and polymeric IgA (pIgA) in the total IgA with age. In the contrast to serum profiles, monomeric IgA (mIgA) was always detected as the smallest peak of the IgA fractions in glomerular eluates. Furthermore, aged mice with severe GN showed a higher percentage of dIgA and pIgA in total IgA (80%) in the sera than that of the mice with mild GN (64%). HPLC analysis under acid condition of glomerular IgA from 40-week-old ddY mice showed a similar pattern of dIgA and pIgA peaks in neutral buffer without the appearance of mIgA. These findings suggest that there is a selective mechanism for glomerular accumulation of more acid IgA among the polyclonally expanded IgA in old ddY mice, and that the polymeric form of IgA plays a pathogenic role in the development of mesangial proliferative GN in these mice.

Animals↗