Search PubMed⌕ Search

Biomedical subjects

S Takayama

Publications and source records attributed to S Takayama.

At least 73 records · Page 4Linked to original sources
PubMed2000

An application of apo(a) isoforms for the clinical assessment of Lp(a).

To examine whether or not Lp(a) is applicable as a diagnostic marker for atherosclerosis, we studied the correlation between Lp(a) levels and molecular weights of apo(a) isoforms in sera from both normal healthy adults and diabetic patients. Serum Lp(a) level was measured by turbidimetric immunoassay (TIA) and the molecular weight of apo(a) isoform was determined by Western blotting analysis. The serum Lp(a) levels of the diabetic patients (25.0 mg/dl +/- 2.2 [mean +/- SE], n = 54) were significantly higher than those of the normal subjects (14.4 mg/dl +/- 0.57, n = 500). With respect to the correlation between serum Lp(a) levels and the molecular weights of apo(a) isoforms, there was an inverse correlation in sera from normal subjects (n = 298), whereas there was no correlation in sera from the diabetic patients. Statistical significant inverse correlation (r = -0.91, y = 224.25 - 3.07x) was especially observed in 50 representative apo(a) isotypes from the normal subjects. By applying a standardized curve based on the significant inverse correlation to serum Lp(a) levels, 40.7% (22/54) of the diabetic patients were revealed to have an abnormally high value of serum Lp(a). Moreover, it was found that the significantly higher mean value of serum Lp(a) in the diabetic group was caused by the 22 patients with higher value of Lp(a). The present findings suggest that determination of apo(a) isoform size provides estimation of the serum Lp(a) value and that the inverse correlation curve between serum Lp(a) level and the molecular weight of apo(a) isoform may be applicable to the clinical use of Lp(a).

Adult↗
PubMed2000

Synergistic effect of Bcl-2 and BAG-1 on the prevention of photoreceptor cell death.

PURPOSE: Ectopic expression of Bcl-2 in photoreceptors of mice with retinal degenerative disease slows progression of the disease. BAG-1 has previously been shown to augment the inhibitory effect of Bcl-2 on programmed cell death in cultured cell systems. This study was designed to determine whether the coexpression of BAG-1 and Bcl-2 in the photoreceptors of mice with an autosomal dominant form of retinitis pigmentosa (RP) would enhance the protective effect provided by Bcl-2 alone. METHODS: An expression vector using the 5' regulatory region of the murine opsin gene was used to target the expression of BAG-1 specifically to photoreceptor cells of mice. The BAG-1 transgenic mice were crossed to Bcl-2 transgenics to obtain animals that coexpress the two transgenes in photoreceptor cells. BAG-1/Bcl-2 animals were then crossed to an RP mouse model (a transgenic line overexpressing the S334ter rhodopsin mutant) to assess the effect of coexpression of BAG-1 and Bcl-2 on retinal degeneration. Morphologic analysis was performed on retinas isolated at various times after birth to monitor disease progression. RESULTS: High levels of BAG-1 expression resulted in retinal degeneration that was not prevented by Bcl-2 expression. However, coexpression of appropriate levels of BAG-1 and Bcl-2 was found to have a profound inhibitory effect on retinal degeneration caused by overexpression of a mutant rhodopsin transgene. Whereas expression of Bcl-2 alone was previously found to delay degeneration of the retina from 2 weeks to approximately 4 weeks of age, coexpression of BAG-1 and Bcl-2 inhibited photoreceptor cell death for as long as 7 to 9 weeks. CONCLUSIONS: The synergistic effect against photoreceptor cell death produced by the coexpression of Bcl-2 and BAG-1 indicates that these proteins can function in concert to prevent cell death. At the correct dosage, coexpression of Bcl-2 and BAG-1 may serve as a potential means to treat retinal degenerative diseases.

Animals↗
PubMed2000

[Chemo/endocrine therapy for breast cancer patients].

Standard adjuvant chemo/endocrine therapy for breast cancer patient is based upon St. Gallen's consensus 1998. Recent development in the field of adjuvant chemo/endocrine therapy is an usage of LH-RH analogue with tamoxifen for premenopausal hormone receptor positive women, and also an emerging role of taxans. Orally given 5-FU derivatives may work in adjuvant settings. The third generation aromatase inhibitors have established their role in second line hormone therapy for the advanced or recurrent breast cancer patients. High dose chemotherapy should not be used in outside clinical trials.

Anastrozole↗
PubMed1999

Differential effects of the hsp70-binding protein BAG-1 on glucocorticoid receptor folding by the hsp90-based chaperone machinery.

The heat shock protein hsp70/hsc70 is a required component of a five-protein (hsp90, hsp70, Hop, hsp40, and p23) minimal chaperone system reconstituted from reticulocyte lysate that forms glucocorticoid receptor (GR).hsp90 heterocomplexes. BAG-1 is a cofactor that binds to the ATPase domain of hsp70/hsc70 and that modulates its chaperone activity. Inasmuch as BAG-1 has been found in association with several members of the steroid receptor family, we have examined the effect of BAG-1 on GR folding and GR.hsp90 heterocomplex assembly. BAG-1 was present in reticulocyte lysate at a BAG-1:hsp70/hsc70 molar ratio of approximately 0.03, and its elimination by immunoadsorption did not affect GR folding and GR. hsp90 heterocomplex assembly. At low BAG-1:hsp70/hsc70 ratios, BAG-1 promoted the release of Hop from the hsp90-based chaperone system without inhibiting GR.hsp90 heterocomplex assembly. However, at molar ratios approaching stoichiometry with hsp70, BAG-1 produced a concentration-dependent inhibition of GR folding to the steroid-binding form with corresponding inhibition of GR.hsp90 heterocomplex assembly by the minimal five-protein chaperone system. Also, there was decreased steroid-binding activity in cells that were transiently or stably transfected with BAG-1. These observations suggest that, at physiological concentrations, BAG-1 modulates assembly by promoting Hop release from the assembly complex; but, at concentrations closer to those in transfected cells and some transformed cell lines, hsp70 is continuously bound by BAG-1, and heterocomplex assembly is blocked.

Animals↗
PubMed1999

Partial nucleotide sequencing of the NS3/helicase region of hepatitis G virus to prove vertical transmission.

To study non-parental transmission of hepatitis G virus and/or GB virus C (HGV/GBV-C), we sequenced and compared the NS3/helicase region of the virus for five HGV/GBV-C RNA-positive mothers and their 11 children who had experienced neither blood transfusion nor overt hepatitis and were negative for HBV, HCV and HIV, except in one mother coinfected with HCV. The nucleotide sequences of the familial HGV/GBV-C isolates showed high similarity of 99-100% (mean 99.8%, 100% at the deduced amino acid level) between mother and her child(ren) in each family. These findings strongly suggest the spontaneous occurrence of mother-to-child transmission of HGV/GBV-C as reported previously. They also suggest that nucleotide sequence analysis on the NS3/helicase region of HGV/GBV-C may be a useful tool to study HGV/GBV-C transmission.

Adult↗
PubMed1999

BAG-1 accelerates cell motility of human gastric cancer cells.

BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of human gastric cancer cells. Two independent in vitro migration assays showed that the BAG-1-expressing MKN74 cells exhibited more active migration compared with control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor migration responses to HGF. The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. In BAG-1 transfected gastric cancer MKN74 cells, BAG-1 colocalized with cytokeratin as well as actin filaments, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA). Taken together, these studies demonstrate that BAG-1 has a novel function as promoter of cell migration in human gastric cancer cells, possibly through cooperation with cytoskeletal proteins.

Actins↗
PubMed1999

Patterning cells and their environments using multiple laminar fluid flows in capillary networks.

This paper describes the use of laminar flow of liquids in capillary systems to pattern the cell culture substrate, to perform patterned cell deposition, and to pattern the cell culture media. We demonstrate the patterning of the cell culture substrate with different proteins, the patterning of different types of cells adjacent to each other, the patterned delivery of chemicals to adhered cells, and performing enzymatic reactions over select cells or over a portion of a cell. This method offers a way to simultaneously control the characteristics of the surface to which cells are attached, the type of cells that are in their vicinity, and the kind of media that cells or part of a cell are exposed to. The method is experimentally simple, highly adaptable, and requires no special equipment except for an elastomeric relief that can be readily prepared by rapid prototyping.

Animals↗
PubMed1999

Multiple infection of TT virus (TTV) with different genotypes in Japanese hemophiliacs.

To clarify the persistent TT virus (TTV) infection, we studied a possibility of multiple TTV infection by genotype analysis of isolated TTV obtained from seven Japanese hemophiliacs. The nucleotide sequences including 222 bp in the open reading frame 1 (ORF1) region of 10 TTV isolates from each patient were analyzed and classified into various TTV genotypes such as G1 to G6 by phylogenetic analysis using a N-J method. Multiple TTV genotypes were observed in all the hemophiliacs: three different TTV genotypes were found in three patients, whereas four different TTV genotypes were observed in the other three patients. The remaining patient was also infected with TTV of five different genotypes. Moreover, new TTV genotypes were found in these seven patients and tentatively designated as G7. The present findings indicate that multiple TTV infection with different TTV genotypes has occurred in Japanese hemophiliacs. They also provide valuable information to understand persistent TTV infection.

Adolescent↗
PubMed1999

An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators.

Heat Shock Protein 70 kDa (Hsp70) family molecular chaperones play critical roles in protein folding and trafficking in all eukaryotic cells. The mechanisms by which Hsp70 family chaperones are regulated, however, are only partly understood. BAG-1 binds the ATPase domains of Hsp70 and Hsc70, modulating their chaperone activity and functioning as a competitive antagonist of the co-chaperone Hip. We describe the identification of a family of BAG-1-related proteins from humans (BAG-2, BAG-3, BAG-4, BAG-5), the invertebrate Caenorhabditis elegans (BAG-1, BAG-2), and the fission yeast Schizosaccharomyces pombe (BAG-1A, BAG-1B). These proteins all contain a conserved approximately 45-amino acid region near their C termini (the BAG domain) that binds Hsc70/Hsp70, but they differ widely in their N-terminal domains. The human BAG-1, BAG-2, and BAG-3 proteins bind with high affinity (KD congruent with 1-10 nM) to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. The findings suggest opportunities for specification and diversification of Hsp70/Hsc70 chaperone functions through interactions with various BAG-family proteins.

Adenosine Triphosphatases↗
PubMed1999

Oxidation of Benzyl Alcohol with Cu(II) and Zn(II) Complexes of the Phenoxyl Radical as a Model of the Reaction of Galactose Oxidase.

Profound insights into the catalytic mechanism of galactose oxidase (GO) are offered by new models of the active form of the metalloenzyme. The important role of the Cu(II) center in the oxidation of benzyl alcohol to benzaldehyde by the Cu(II)-phenoxyl radical complex of ligand 1 has been revealed by comparison with the reactivity of the corresponding Zn(II)-phenoxyl radical complex; py=2-pyridyl.

Journal Article↗
PubMed1999

In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection.

Interleukin-18 (IL-18), originally called interferon-gamma (IFN-gamma)-inducing factor is a novel cytokine which exhibits pleiotropic immunomodulatory activities such as the activation of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In this study, the efficacy of IL-18 on viral infection in mice was investigated. IL-18 treatment significantly suppressed pock formation on the tails of BALB/c mice inoculated intravenously with vaccinia virus when the cytokine was administered intraperitoneally on days 0, 2 and 4 after infection. Sequentially, NK and CTL activity of the infected mice were significantly augmented by IL-18 injection. The in vivo anti-vaccinia virus activity of IL-18 was only partially inhibited by treating the infected mice with anti-asialo GM1 antibody. When infected mice were injected with anti-IFN-gamma antibody only, severe deterioration of health and significant body weight loss were observed, suggesting that IFN-gamma is very important in protecting mice against vaccinia virus infection. Interestingly, IL-18 injection visibly improved the severe vaccinia virus-induced symptoms in mice treated with anti-IFN-gamma antibody, even though a pivotal involvement of IFN-gamma in IL-18-mediated anti-vaccinia virus effect is not yet determined. Taken together, these results indicate that the IL-18-elicited anti-vaccinia virus effect in the acute phase of infection would be raised by the sum of various host defence mechanisms including NK cells and CTL, and not from a specific immunocompetent cell population or effector molecule.

Animals↗
PubMed1999

Effects of long-term oral administration of DDT on nonhuman primates.

Because of reports on tumorigenic activity in different animal species exposed to DDT a decision was made in 1969 to evaluate the long-term effects of DDT on 24 cynomolgus and rhesus monkeys. DDT (20 mg/kg) was given in the diet for 130 months, followed by an observation period that ended in 1994. The two cases of malignant tumor detected in the DDT group included a metastatic hepatocellular carcinoma in a 233-month-old male and a well-differentiated adenocarcinoma of the prostate in a 212-month-old monkey. Benign tumors detected in the DDT group included three cases of leiomyoma, two of which were uterine and one, esophageal. No tumor was detected in the control group of 17 monkeys. Fatty changes in the liver were observed in 52.9% of the DDT group and 29.4% of the control group. More specific signs of hepatotoxicity were documented microscopically in seven DDT monkeys. Severe tremors and histological evidence of CNS and spinal cord abnormalities were observed in six DDT monkeys. The present findings show clear evidence of hepatic and CNS toxicity following long-term DDT administration to cynomolgus and rhesus monkeys. However, the two cases involving malignant tumors of different types are inconclusive with respect to a carcinogenic effect of DDT in nonhuman primates.

Adenocarcinoma↗
PubMed1999

Clinicopathological study of background gastric mucosa during long-term conservative maintenance therapy for intractable peptic ulcer.

We studied the background gastric mucosa in eight patients with intractable peptic ulcer in whom gastric cancer developed during more than 4 years' administration of histamine (H)2-receptor antagonists (H2-RAs), and in two patients with intractable gastric ulcer without gastric cancer in whom H2-RAs were administered for 4 years. As controls, we studied background mucosa in seven patients with combined gastroduoderal ulcers not treated with H2-RAs. The cancers were differentiated adenocarcinomas in all eight patients. The characteristic features of these patients and of the two patients with intractable gastric ulcer were: expansion of the generative cell zone, poor differentiation of the goblet cells, mild cellular atypia, and abnormal branching and anastomosis of glands, as well as wide areas of incomplete-type intestinal metaplasia. The sites of the differentiated adenocarcinomas were classified by mucin histochemistry as intestinal-type mucosa in all patients. A special type of incomplete intestinal metaplasia, of the intestinal type and which retained gastric-type properties, was present in some areas, and p53-positive cells were observed in some areas. In patients with intractable gastric ulcer in whom the background gastric mucosa had been exposed to more than 4 years of H2-RA treatment, it was considered possible that the preconditions for cancerous lesions were present.

Adenocarcinoma↗
PubMed1999

Patterning proteins and cells using soft lithography.

This review describes the pattering of proteins and cells using a non-photolithographic microfabrication technology, which we call 'soft lithography' because it consists of a set of related techniques, each of which uses stamps or channels fabricated in an elastomeric ('soft') material for pattern transfer. The review covers three soft lithographic techniques: microcontact printing, patterning using microfluidic channels, and laminar flow patterning. These soft lithographic techniques are inexpensive, are procedurally simple, and can be used to pattern a variety of planar and non-planar substrates. Their successful application does not require stringent regulation of the laboratory environment, and they can be used to pattern surfaces with delicate ligands. They provide control over both the surface chemistry and the cellular environment. We discuss both the procedures for patterning based on these soft lithographic techniques, and their applications in biosensor technology, in tissue engineering, and for fundamental studies in cell biology.

Animals↗
PubMed1999

Selective inhibition of beta-1,4- and alpha-1,3-galactosyltransferases: donor sugar-nucleotide based approach.

A combined rational and library approach was used to identify bisphosphonates (IC50 = 20 microM) and galactose type 1-N-iminosugar (IC50=45 microM) as novel motifs for selective inhibition of beta-1,4-galactosyltransferase (beta-1,4-GalT) and alpha-1,3-galactosyltransferase (alpha-1,3-GalT), respectively. Our results demonstrate that, though these two galactosyltransferases both utilize the same donor sugar-nucleotide (UDP-Gal), the difference in their mechanisms can be utilized to design donor sugar or nucleotide analogues with inhibitory activities selective for only one of the galactosyltransferases. Investigation of beta-1,4-GalT inhibition using UDP-2-deoxy-2-fluorogalactose (UDP-2-F-Gal), UDP, and bisphosphonates, also led to the observation of metal dependent inhibition of beta-1,4-GalT. These observations and the novel inhibitor motifs identified in this study pave the way for the design and identification of even more potent and selective galactosyltransferase inhibitors.

Animals↗
PubMed1999

Prevalence and persistence of a novel DNA TT virus (TTV) infection in Japanese haemophiliacs.

To clarify the clinical implication of a newly discovered 'TT virus (TTV)', we assayed TTV DNA in sera from 50 haemophiliacs by a seminested-PCR. TTV DNA was detected in 75% (35/50), which was a much higher prevalence than for HBV (HBc-Ab), HCV RNA, or HGV RNA. In particular, TTV DNA was found in 44.4% (4/8) of patients who had been treated only with virally inactivated factor VIII concentrates. Elevated ALT levels were observed in patients with HCV RNA and TTV DNA; however, the elevation in TTV DNA was obtained from patients co-infected with HCV RNA (62.9%, 22/35). There was no significant difference in ALT levels between TTV DNA-positive and DNA-negative in patients without HCV RNA. 85.3% (35/41) of TTV DNA-positive sera in 1990 were again positive for TTV DNA in 1995. These findings suggest that many haemophiliacs have been infected with TTV. Although TTV infection was not associated with serum ALT elevation, persistent TTV infection may contribute to cryptogenic hepatic failure in haemophiliacs.

Adolescent↗