A novel and facile racemization of chiral 1,1'-biaryl-2,2'-dicarboxylic acids.
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Journal Article↗
Biomedical subjects
S Yamada
Publications and source records attributed to S Yamada.
Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population : Jichi Medical School Cohort Study.
The distribution of serum C-reactive protein (CRP) levels and their association with age, sex, and atherosclerotic risk factors were studied in a large Japanese population between 1992 and 1995. The subjects consisted of 2,275 males and 3,832 females aged 30 years and over. CRP was measured by nephelometry. The distribution of CRP was highly skewed toward a lower level than that of previous studies and seemed to be a combination of two separate distribution curves. The increase in CRP with age was statistically significant, and males had higher CRP levels than did females. Males who were current smokers had higher CRP levels than did nonsmokers. Age, systolic blood pressure, diastolic blood pressure, triglycerides, fibrinogen, and body mass index were all positively associated with CRP in both sexes, while total cholesterol and blood glucose were positively related in females only. High density lipoprotein cholesterol was inversely related in both sexes. Multiple logistic regression analysis showed that sex, age, systolic pressure, high density lipoprotein cholesterol, triglycerides, fibrinogen, and body mass index were significant independent variables. In conclusion, the distribution of CRP among the Japanese was quite different from that among Westerners, although CRP levels correlated with other atherosclerotic risk factors, similar to those in Westerners.
Adult↗
Structural characterization of heparan sulfate and chondroitin sulfate of syndecan-1 purified from normal murine mammary gland epithelial cells. Common phosphorylation of xylose and differential sulfation of galactose in the protein linkage region tetrasaccharide sequence.
Syndecan-1, present on the surfaces of normal murine mammary gland epithelial cells, is a transmembrane hybrid proteoglycan, which bears glycosaminoglycan (GAG) side chains of heparan sulfate (HS) and chondroitin sulfate (CS). Purified syndecan-1 ectodomains were analyzed for disaccharide composition and the GAG-protein linkage region after digestion with bacterial lyases. The HS chains contained predominantly a nonsulfated unit with smaller proportions of two monosulfated, two disulfated, and a trisulfated unit, whereas CS chains were demonstrated for the first time to bear GlcUA-GalNAc(4-O-sulfate) as a major component as well as GlcUA-GalNAc, GlcUA-GalNAc(6-O-sulfate), and an E disaccharide unit GlcUA-GalNAc(4,6-O-disulfate) as minor yet appreciable components. Two kinds of linkage region tetrasaccharides, GlcUA-Gal-Gal-Xyl and GlcUA-Gal-Gal-Xyl(2-O-phosphate), were found for the HS chains in a molar ratio of 55:45. In marked contrast, an additional sulfated tetrasaccharide, GlcUA-Gal(4-O-sulfate)-Gal-Xyl, was demonstrated only for the CS chains, and the unmodified phosphorylated and sulfated components were present at a molar ratio of 55:26:19. The present study thus provided conclusive evidence for the hypothesis that 4-O-sulfation of Gal is peculiar to CS chains in contrast to the phosphorylation of Xyl, which is common to both HS and CS chains. These modifications may be required for biosynthetic maturation of the linkage region tetrasaccharide sequence, which is a prerequisite for creating the repeating disaccharide region of GAG chains and/or biosynthetic selective chain assembly of CS and HS chains.
Animals↗
Observation of rho/omega meson modification in nuclear matter.
We measured the invariant mass spectra of electron-positron pairs in the target rapidity region of 12-GeV p+A reactions. We have observed a significant difference in the mass spectra below the omega meson between p+C and p+Cu interactions. This difference indicates that the spectral shape of mesons is modified at normal nuclear-matter density.
Journal Article↗
Efficient photocurrent generation in novel self-assembled multilayers comprised of [60]fullerene-cationic homooxacalix[3]arene inclusion complex and anionic porphyrin polymer.
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Journal Article↗
Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.
We have previously identified 204 partial cDNA fragments (ADRG1-204) as antidepressant related genes/expressed sequence tags. Then, we developed our original cDNA microarrays, on which the 194 clones out of ADRG1-204 were spotted. With this ADRG microarray, we found that the expression of a spot, ADRG55, which representing cysteine string protein (CSP), was significantly increased in rat brain after chronic treatment with a selective serotonin reuptake inhibitor, sertraline. In the present study, reverse transcription-polymerase chain reaction analysis confirmed the induction of CSP at mRNA levels in rat frontal cortex after chronic treatment with two different classes of antidepressants, imipramine or sertraline. Western blot analysis also revealed that CSP-immunoreactivity was increased after antidepressant treatment. In conclusion, our data suggest that CSP is one of the common functional molecules induced after chronic antidepressant treatment.
Animals↗
In vivo conversion of cellular prion protein to pathogenic isoforms, as monitored by conformation-specific antibodies.
The central event in prion disease is thought to be conformational conversion of the cellular isoform of prion protein (PrP(C)) to the insoluble isoform PrP(Sc). We generated polyclonal and monoclonal antibodies by immunizing PrP(C)-null mice with native PrP(C). All seven monoclonal antibodies (mAbs) immunoprecipitated PrP(C), but they immunoprecipitated PrP(Sc) weakly or not at all, thereby indicating preferential reactivities to PrP(C) in solution. Immunoprecipitation using these mAbs revealed a marked loss of PrP(C) in brains at the terminal stage of illness. Histoblot analyses using these polyclonal antibodies in combination of pretreatment of blots dissociated PrP(C) and PrP(Sc) in situ and consistently demonstrated the decrease of PrP(C) at regions where PrP(Sc) accumulated. Interestingly, same mAbs showed immunohistochemical reactivities to abnormal isoforms. One group of mAbs showed reactivity to materials that accumulated in astrocytes, while the other group did so to amorphous plaques in neuropil. Epitope mapping indicated that single mAbs have reactivities to multiple epitopes, thus implying dual specificities. This suggests the importance of octarepeats as a part of PrP(C)-specific conformation. Our observations support the notion that loss of function of PrP(C) may partly underlie the pathogenesis of prion diseases. The conversion of PrP(C) to PrP(Sc) may involve multiple steps at different sites.
Animals↗
Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.
Mutations in several genes encoding transcription factors of the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of early-onset diabetes mellitus. The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4alpha, suggested SHP as a candidate MODY gene. We screened 173 unrelated Japanese subjects with early-onset diabetes for mutations in this gene and found five different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, and R213C) in 6 subjects as well as one apparent polymorphism (R216H), all present in the heterozygous state. Interestingly, all of the subjects with the mutations were mildly or moderately obese at onset of diabetes, and analysis of the lineages of these individuals indicated that the SHP mutations were associated with obesity rather than with diabetes. Therefore, an additional group of 101 unrelated nondiabetic subjects with early-onset obesity was screened for mutations in the SHP gene. Two of the previously observed mutations (R34X and A195S) and two additional mutations (R57W and G189E) were identified in 6 subjects, whereas no mutations were identified in 116 young nondiabetic lean controls (P = 0.0094). Functional studies of the mutant proteins show that the mutations result in the loss of SHP activity. These results suggest that genetic variation in the SHP gene contributes to increased body weight and reveal a pathway leading to this common metabolic disorder in Japanese.
Adolescent↗
Effects of high ELF magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free DNA mismatch repair.
Environmental electromagnetic fields have been implicated in human cancers. We examined whether high extremely low frequency (ELF) AC magnetic fields could affect DNA synthesis, transcription or repair, using in vitro model systems with defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The efficiency of mutS dependent mismatch repair with human cell extracts was also not affected by the magnetic field exposure. The results suggest that the core processes related to the transmission of genetic information are stable under high ELF magnetic fields.
Animals↗
Exposure of Caenorhabditis elegans to extremely low frequency high magnetic fields induces stress responses.
Responses of the small heat shock protein gene, hsp-16, were examined in transgenic Caenorhabditis elegans exposed to electromagnetic fields. Expression of the hsp-16-lacZ gene was enhanced when transgenic animals were exposed to magnetic fields up to 0.5 T at 60 Hz. The hsp-16 promoter was more efficiently expressed at the embryonic than at the post-embryonic stage irrespective of exposure. Promoter activity was more sensitive to the stimulus in the intestine at the post-embryonic stage. Evidence is presented that the induction occurs at the transcriptional step of hsp-16.
Animals↗
Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cells.
Transcription factor Ets-1 is induced in endothelial cells (ECs) by angiogenic factors, and promotes angiogenesis by inducing angiogenesis-related genes such as MMPs and integrin beta3. Here, we examined the effect of Ets-1 on apoptosis in ECs. Overexpression of Ets-1 in human umbilical vein endothelial cells (HUVECs) induced apoptosis under the serum-deprived condition. VEGF inhibited apoptosis and augmented the DNA binding of Ets-1 in HUVECs. The inhibition of transcriptional activity of endogenous Ets-1 by a dominant negative molecule intensified the anti-apoptotic effect of VEGF. Caspase inhibitors blocked apoptosis of HUVECs induced by Ets-1. DNA array analysis showed that Ets-1 up-regulated pro-apoptotic genes such as Bid, cytochrome p450, caspase-4, p27, and p21 more than 2 fold, and down-regualted anti-apoptotic genes such as DAD-1, AXL, Cox-2, IAP-2, and MDM-2 less than 0.5 fold in HUVECs. These results indicate that Ets-1 itself is pro-apoptotic to ECs by modulating the expression of apoptosis-related genes.
Adenoviridae↗
A serine protease inhibitor, N-alpha-tosyl-l-lysine chloromethyl ketone, prolongs rat hepatic allograft survival.
BACKGROUND: Serine protease inhibitors have profound suppressive effects on cellular and humoral immune responses. We investigated the effect of a serine protease inhibitor, N-alpha-tosyl-l-lysine chloromethyl ketone (TLCK), on hepatic allograft survival in rats. Methods. Orthotopic hepatic transplantation was performed in an ACI (RT1(a))-to-LEW (RT1(1)) rat combination. TLCK was administered continuously at a dose of 4.4 mg/kg/day using an osmotic subcutaneous infusion minipump. RESULTS: TLCK prolonged hepatic allograft survival. Histologic staging of acute rejection based on Banff criteria in TLCK-treated hepatic allografts was significantly lower than in untreated allografts. TLCK significantly reduced serum concentrations of interferon (IFN)-gamma and tumor necrosis factor (TNF) alpha in allograft recipients. TNF-alpha mRNA levels in TLCK-treated allografts were significantly lower than in untreated allografts. TLCK also decreased perforin mRNA levels in hepatic allografts. Hepatic infiltrates eluted from TLCK-treated allografts showed significantly lower cell-mediated lympholytic activity against donor Con A blast cervical lymph node cells than those from untreated allografts. In vitro, TLCK suppressed interleukin-2 production and [(3)H]thymidine incorporation into an allogeneic mixed lymphocyte reaction. CONCLUSION: TLCK suppressed acute allograft rejection, suggesting a novel immunosuppressive strategy for therapy of acute organ rejection.
Animals↗
Differential splenic migration of dendritic cells after immunologic unresponsiveness in rat hepatic allografts induced by pretransplant donor-specific transfusion.
BACKGROUND: Donor dendritic cells migrate into the recipient spleen after hepatic transplantation. We previously reported that immunologic unresponsiveness to rat hepatic allografts can be induced by prior donor-specific blood transfusion (DST). We investigated the phenotype and splenic distribution of donor dendritic cells after allografting and DST. METHODS: Donor dendritic cells were identified with anti-rat dendritic cell (OX-62) and anti-donor class II MHC (RT1B(a)) (OX-76) antibodies. The phenotype of dendritic cells was determined with antibodies to CD45RC, CD62L, and the maturation markers CD80 (B7-1) and CD86 (B7-2). The cytokine profile of sorted CD45RC(+) OX-62(+) and CD45RC(-) OX-62(+) dendritic cells was analyzed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Pretransplant DST significantly prolonged rat hepatic allograft survival. Immunostaining revealed OX76(+)/OX-62(+) cells in the splenic red pulp of animals receiving pretransplant DST and in the white pulp of untreated animals after transplantation. The ratio of splenic CD45RC(-) OX-62(+) cells to CD45RC(+) OX-62(+) cells was significantly higher in DST recipients than in untreated animals. CD62L, CD80, and CD86 were lower on CD45RC(-) OX-62(+) than CD45RC(+) OX-62(+) cells. RT-PCR revealed that sorted CD45RC(-) OX-62(+) cells expressed interleukin (IL)-4 and IL-10. In contrast, sorted CD45RC(+) OX-62(+) cells expressed only IL-2 and interferon gamma (IFN-gamma). CONCLUSION: Differential splenic migration of CD45RC(-) dendritic cells is associated with immunologic unresponsiveness to rat hepatic allografts.
Animals↗
Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome.
We assessed the in vitro chemosensitivity of acute erythroblastic and megakaryoblastic leukemia cells from children with Down syndrome (DS) compared to non-DS children. We conducted in vitro tests using the MTT assay of bone marrow samples from 12 children with DS and 16 children without DS. Patients were newly diagnosed based on the morphology and expression of platelet-specific antigens. Induction failure occurred more frequently in the non-DS group (n = 4) than in the DS group (n = 0, P = .053). Children with DS had a superior event-free survival (EFS) probability of 0.750 at 4 years, compared to an EFS probability of 0.375 for non-DS children (P = .049). Blast cells from DS patients were significantly more sensitive to daunorubicin, melphalan, mitoxantrone, 4-hydroperoxy-cyclophosphamide, vincristine, etoposide, bleomycin, and pirarubicin than those from non-DS patients. Four of the 16 non-DS patients were found to have acquired an extra chromosome 21 in their leukemia cells: blasts from these patients also tended to have greater chemosensitivity than those from patients without an extra chromosome 21. Blast cells from DS patients are markedly sensitive to various drugs. These results suggest that the fragility of blast cells derived from DS patients may be related to an increased susceptibility to apoptosis.
Antineoplastic Combined Chemotherapy Protocols↗
Cytocidal effect and DNA damage of nedaplatin: a mathematical model and analysis of experimental data.
PURPOSE: Cell cycle non-specific anticancer agents such as cis-diamminedichloroplatinum(II) are believed to depend linearly on the value of the area under the drug concentration time curve, which is supported by a mathematical model. However, the quantitative non-linear phenomena of both the cytocidal effect and DNA crosslink formation by cisdiammine(glycolato)platinum (nedaplatin) have been shown in vitro. Therefore, we developed a new mathematical model to explain these phenomena. METHODS: We assumed that nedaplatin enters intracellular fluid from medium through simple diffusion to form DNA crosslinks that kill cells. We developed a mathematical model to represent this assumption using differential equations that we then solved using an original computer program. The calculated results were compared with the experimental data. RESULTS: The drug's simple diffusion rate constant, the DNA crosslink formation rate constant, and the crosslink-dependent cell death rate constant in the model were 1.8 x 10(-14) (l h-1), 1.6 x 10(8) (l mol-1/2 h-1), 5.45 x 10(1) (mol-1), respectively. The model fits the experimental results statistically. The model also demonstrated theoretical proof that continuous exposure at a low dose was superior to the short exposure at a high dose seen in published experimental data. CONCLUSIONS: We developed a mathematical model to describe the non-linear pharmacodynamic effect of nedaplatin in vitro. This model may provide a novel drug infusion procedure for cancer patients.
Antineoplastic Agents↗
Molecular properties and gene expression of albumin in the skeletal muscle following hindlimb immobilization in a shortened position.
We investigated the effect of immobilization of hindlimb in a shortened position on proteins in the mouse soleus muscle and determined the molecular properties of a protein that had changed specifically in the atrophied muscle. A protein of 67.5 kDa was increased significantly (P<0.001) by 1.9-fold in the atrophied muscle compared to the control muscle as shown by sodium dodecyl sulfate-polyacrylamide (SDS-PAGE). The isoelectric point of the protein was pH 6.3 in two-dimensional PAGE. We carried out N-terminal and peptide mapping analyses to identify the primary structure of the protein. A 17-amino acid sequence showed 100% homology with the mouse serum albumin precursor. A peptide map of the 67.5-kDa protein was similar to that of mouse serum albumin. Mass spectrometry also showed the protein to be most similar to mouse serum albumin. Thus, based on these criteria, the 67.5-kDa protein was indistinguishable from mouse serum albumin. An immunohistochemical study showed that the 67.5-kDa protein was located mainly in the endomysium of the control muscle and had accumulated in the widened interstitial spaces of the atrophied muscle. A reverse transcription-PCR assay revealed that the albumin gene was expressed in skeletal muscle tissue, but that its expression was significantly lower in the atrophied muscle than in the control muscle (P<0.001). We conclude that albumin is increased in atrophied muscle and suggest that this may be of clinical importance for analyzing the process of muscular atrophy.
Albumins↗
Argyrophilic grain disease mimicking temporal Pick's disease: a clinical, radiological, and pathological study of an autopsy case with a clinical course of 15 years.
This report concerns an autopsy case of argyrophilic grain disease (AGD) mimicking temporal Pick's disease. The patient was a Japanese woman without hereditary burden who was 89 years old at the time of death. She developed memory impairment and began wandering at the age of 74, followed by prominent character changes about 6 years after disease onset. A neurological examination 5 months before her death revealed poor rapport, unconcern, severe dementia, and double incontinence, without aphasia or muscle rigidity. Serial neuroradiological examination revealed progressive enlargement of the bilateral inferior horns of the lateral ventricle, reflecting progressive atrophy of the medial temporal lobes. Macroscopically, neuropathological examination showed circumscribed atrophy of the bilateral amygdalae, hippocampi, parahippocampal gyri, and lateral occipitotemporal gyri. Histologically, there was neuronal loss in the areas mentioned above, the caudate nucleus, putamen, thalamus, substantia nigra, and locus ceruleus, with ballooned neurons in the cerebral cortex and amygdala. Numerous argyrophilic grains with coiled bodies were present not only in the limbic system, but also in the affected cerebrum. Rare neurofibrillary changes were present in the limbic areas, consistent with Braak stage II, with no senile plaques. Based on these findings and a review of the literature, we note that AGD is clinicopathologically similar not only to mesolimbocortical dementia, but also to atypical senile dementia of Alzheimer type. This report may contribute to the elucidation of the clinicopathological hallmarks of AGD.
Aged↗
The STR locus D11S554: allele frequencies and sequence data in a Japanese population.
A population study on the short tandem repeat (STR) locus D11S554 was carried out in a sample of 362 unrelated Japanese individuals living in the Gifu Prefecture. A total of 46 different alleles ranging from 180 bp to 340 bp and 135 genotypes were revealed. Sequence analysis of alleles was carried out for 185 samples. The sequence structures of the repeat regions of the alleles were found to be complex and the alleles were classified into nine sequence types, including four new sequence types. According to the system of Adams et al. (1993), we designated the new sequence types IA3, IA4, IA5 and IB3, respectively. Out of the 46 different alleles, 11 showed sequence heterogeneity. The results of this study demonstrated that the D11S554 locus is a powerful and useful genetic marker for forensic practice in the Japanese population.
Alleles↗