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Biomedical subjects

A Ando

Publications and source records attributed to A Ando.

At least 91 records · Page 5Linked to original sources
PubMed1998

Isochronous storage ring of the New SUBARU project.

The aims of the New SUBARU project are to promote industrial applications in the VUV and soft X-ray region and to develop research and development towards new light sources. The main facility of the New SUBARU project is the 1.5 GeV electron storage ring which is under construction at the SPring-8 site in Harima Science Garden City, Japan. The storage ring is quasi-isochronous and has variable momentum dispersion for the deep study of beam dynamics in very short bunches.

Journal Article↗
PubMed1998

A crowbarless power supply for klystrons.

A new crowbarless power supply is to be installed at the New SUBARU storage ring. A high-power switching inverter unit eliminates the need for expensive and unstable crowbar circuits for the klystron power supply. It also realizes a very small voltage ripple in the low-frequency region. This is an important characteristic, especially in a quasi-isochronous storage ring such as New SUBARU.

Journal Article↗
PubMed1998

Proposal of a high-field superconducting wiggler for a slow positron source at SPring-8.

A low-energy positron beam is a unique probe of materials. In high-energy electron and positron storage rings it is possible to generate intense synchrotron radiation with a photon energy of 1-3 MeV by installing a high-field (8-10 T) superconducting wiggler. High-energy photons are converted to low-energy positrons by using a suitable target-moderator system. For an 8 GeV electron storage ring at a beam current of 100 mA, final yields are estimated to be about 10(8)-10(10) slow-e(+) s(-1) or larger depending on the moderation efficiency, with the size of the positron source 10(1)-10(2) cm(2). In the present work a wiggler magnetic system of 10 T is proposed. The main parameters of the superconducting wiggler are presented.

Journal Article↗
PubMed1998

Species distributions, land values, and efficient conservation

Efforts at species conservation in the United States have tended to be opportunistic and uncoordinated. Recently, however, ecologists and economists have begun to develop more systematic approaches. Here, the problem of efficiently allocating scarce conservation resources in the selection of sites for biological reserves is addressed. With the use of county-level data on land prices and the incidence of endangered species, it is shown that accounting for heterogeneity in land prices results in a substantial increase in efficiency in terms of either the cost of achieving a fixed coverage of species or the coverage attained from a fixed budget.

Journal Article↗
PubMed1998

Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region.

To elucidate the complete gene structure and to identify new genes involved in the development of HLA class I antigen-associated diseases in the class I region of the human major histocompatibility complex on chromosome 6, a YAC clone (745D12) covering the 146-kb segment around the IkBL and MICA loci was isolated from a YAC library constructed from the B-cell line, BOLETH. A physical map of this region was constructed by isolation of overlapping cosmid clones derived from 745D12. Of these, five contiguous cosmids were chosen for DNA sequencing by the shotgun strategy to give a single contig of 146,601 bp from 2.8 kb telomeric of the IkBL gene to exon 6 of MICA. This region was confirmed to contain five known genes, IkBL, BAT1, MICB, P5-1, and HLA-X (class I fragment), from centromere to telomere, and their exon-intron organizations were determined. The 3.8-1 homologue gene (3.8-1-hom) showing 99.7% identity with the 3.8-1 cDNA clone, which was originally isolated using the 3.8-kb EcoRI fragment between the HLA-54/H and the HLA-G genes, was detected between MICA and MICB and was suggested to represent the cognate 3.8-1 genomic sequence from which the cDNA clone was derived. No evidence for the presence of expressed new genes could be obtained in this region by homology and EST searches or coding and exon prediction analyses. One TA microsatellite repeat spanning 2545 bases with as many as 913 repetitions was found on the centromeric side of the MICA gene and was indicated to be a potential hot spot for genetic recombination. The two segments of approximately 35 kb upstream of the MICA and MICB genes showed high sequence homology (about 85%) to each other, suggesting that segmental genome duplication including the MICA and MICB genes must have occurred during the evolution of the human MHC.

Carrier Proteins↗
PubMed1998

Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Mendenhall's syndrome.

Rabson-Mendenhall's syndrome is one of the most severe forms of insulin resistance syndrome. We analyzed an English patient described elsewhere and found novel mutations in both alleles of the insulin receptor gene. One is a substitution of G for A at the 3' splice acceptor site of intron 4, and the other is an eight-base pair deletion in exon 12. Both decrease mRNA expression in a cis-dominant manner, and are predicted to produce severely truncated proteins. Surprisingly, nearly normal insulin receptor levels were expressed in the patient's lymphocytes, although the level of expression assessed by immunoblot was approximately 10% of the control cells. Insulin binding affinity was markedly reduced, but insulin-dependent tyrosine kinase activity was present. Analyzing the insulin receptor mRNA of the patient's lymphocytes by reverse transcription PCR, we discovered aberrant splicing caused by activation of a cryptic splice site in exon 5, resulting in a four-amino acid deletion and one amino acid substitution, but restoring an open reading frame. Skipped exon 5, another aberrant splicing, was found in both the patient and the mother who had the heterozygotic mutation, whereas activation of the cryptic splice site occurred almost exclusively in the patient. Transfectional analysis in COS cells revealed that the mutant receptor produced by cryptic site activation has the same characteristics as those expressed in patient's lymphocytes. We speculate that this mutant receptor may be involved in the relatively long survival of the patient by rescuing otherwise more severe phenotypes resulting from the complete lack of functional insulin receptors.

Alleles↗
PubMed1998

Tctex3, related to Drosophila polycomblike, is expressed in male germ cells and mapped to the mouse t-complex.

Tctex3 showing restricted expression in male germ cells has been isolated during the process of chromosome walking in the mouse t-complex region. The total sequence of Tctex3 cDNA predicts a protein of 580 amino acids with two C4HC3 type PHD fingers. The region containing this conserved motif is shared among members of the Polycomblike proteins that include the mouse M96 and Drosophila Polycomblike. A partial cDNA for a human homolog of Tctex3, HUTEX3, has also been isolated. Mouse Tctex3 gene was mapped adjacent to Tsc2 gene on mouse Chromosome (Chr) 17, and HUTEX3 was located closely to HSET gene in the HLA class II region of chromosome 6.

Amino Acid Sequence↗
PubMed1998

Up-regulation of HSP47 in the mouse kidneys with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is a well established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO are beginning to be elucidated. In the progression of interstitial fibrosis in UUO, up-regulation of collagen synthesis is commonly observed. HSP47 is a collagen-binding stress protein and is thought to be a collagen-specific molecular chaperone, which plays a pivotal role during the biosynthesis and secretion of collagen molecules in the endoplasmic reticulum. The synthesis of HSP47 has been demonstrated to always parallel that of collagen in physiological and pathophysiological conditions. It is well recognized that renin-angiotensin system (RAS) is enhanced in the setting of UUO and that enhanced RAS has been implicated in the pathogenesis of interstitial fibrosis in the obstructed kidneys. METHODS: To investigate the role of HSP47 in the progression of interstitial fibrosis in mouse UUO, the expression of HSP47 was examined by Northern blotting, immunohistochemistry and in situ hybridization in the obstructed kidneys. To test the possible involvement of enhanced RAS on the HSP47 expression, we examined the effects of lisinopril, an angiotensin converting enzyme inhibitor, on interstitial fibrosis. HSP47 and type I collagen mRNA expression. RESULTS: By Northern blot analysis, HSP47 mRNA was significantly up-regulated at 12 hours (about twice that of sham operated kidneys) after the onset of ureteral obstruction, further increased and stayed at the increased level until seven days (about 8 times that of sham operated kidneys). HSP47 mRNA and protein expression were observed in the periglomerular and peritubular interstitial regions of the obstructed kidneys. Distribution of smooth muscle alpha actin and type I collagen immunoreactivity were similar to the HSP47 distribution pattern, suggesting that HSP47 was up-regulated in the myofibroblasts. Lisinopril ameliorated the expansion of cortical interstitium in the obstructed kidneys at four and seven days after ureteral obstruction. HSP47 mRNA expression was suppressed at four and seven days, whereas type I collagen mRNA was suppressed only at seven days after the onset of ureteral obstruction. CONCLUSIONS: These results demonstrate the early and persistent up-regulation of HSP47 during the progression of interstitial fibrosis in mouse UUO kidneys, and further suggest the potential role of HSP47 in the pathogenesis of interstitial fibrosis in the obstructed kidneys. Partial suppression of HSP47 mRNA expression by lisinopril at day 4 and day 7 after ureteral obstruction suggests that there are other immediate trigger(s) that induce the HSP47 mRNA expression. Identification of the molecular mechanism of HSP47 induction during UUO may give an insight into the novel aspects of the molecular pathophysiology of interstitial fibrosis in obstructive nephropathy.

Actins↗
PubMed1998

Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

BACKGROUND: Activation and consequent phenotypic modulation of mesangial cells is considered to play a crucial role in the process of glomerular disease progression. Caldesmon, a calmodulin and actin-binding protein, is a molecular marker of the phenotypic change in smooth-muscle cells. SUBJECTS AND METHODS: We studied whether the expression of caldesmon in mesangial cells was enhanced in the process of IgA nephropathy and whether it would be a marker of mesangial activation indicating prognostic significance in specific disease states. We performed immunohistochemical staining with anticaldesmon and alpha-smooth-muscle actin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. RESULTS: The glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We compared caldesmon expression with composite histological scores (cell score and matrix score), clinical parameters and expressions of alpha-SMA. There was a statistically significant correlation between the caldesmon score and the histological scores (cell score and matrix score, P<0.0001, P<0.01 respectively). Patients showing a high intensity of caldesmon expression (defined as caldesmon score > or = 35; H-group) had significantly higher urinary protein excretion than those showing a low intensity of caldesmon expression (defined as caldesmon score < 35; L-group) (1.2 +/- 1.2 g/24 h vs 0.41 +/- 0.53 g/24 h, P<0.05). Caldesmon and alpha-SMA expression had a statistically significant correlation (P<0.000). Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks and re-biopsies were performed. After the therapy, the caldesmon and alpha-SMA scores were significantly lower than those before the therapy (P<0.01). DISCUSSION: These results suggest that the expression of caldesmon in glomeruli is associated with the progression of IgA nephropathy, and that glucocorticoid heparin therapy may reverse the phenotype of mesangial cells during the disease process of glomerulonephritis.

Actins↗
PubMed1998

Genomic structure of the spermatid-specific hsp70 homolog gene located in the class III region of the major histocompatibility complex of mouse and man.

The Hsc70t gene is a Hsp70 homolog gene expressed constitutively in spermatids in mice. This gene is linked to two heat-inducible Hsp70 genes, Hsp70.1 and Hsp70.3, located in the MHC class III region. The syntenic region of human chromosome 6 contains the HSPA1B, HSPA1A, and HSPA1L genes. Here, we have isolated a HSPA1L cDNA clone from human testicular cells. The HSPA1L gene contained an intron 13 bp upstream of the initiating ATG. A similar genomic structure was found in the Hsc70t gene. The transcription initiation site of the Hsc70t gene was located at ca. 600 bp upstream of the heat-inducible Hsp70.3 gene, linked head-to-head. Sequence alignment of the mouse and human genes revealed that the human HSPA1L and HSPA1A genes were orthologous to the mouse Hsc70t and Hsp70.3 genes, respectively. Conserved sequence stretches observed in the 5' flanking region and the first exon of the spermatid-specific Hsp70 gene may be involved in regulation of the specific gene expression.

Animals↗
PubMed1998

Extended HLA haplotypes in Japanese homozygous typing cells.

We have defined extended HLA haplotypes including the HLA class II genes, the non-HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)n microsatellite repeats within the NOTCH4 gene between DRA and 21OH in 33 Japanese HLA homozygous typing cells (HTC). These conserved haplotypes characterized by unique linkage might be maintained as a result of functional co-operation among them in the antigen presentation pathway. These HTCs can be served as an original and ethnic-specific standard panel, providing useful genetic markers in haplotypic diversity, disease association, and anthropology studies.

HLA Antigens↗
PubMed1998

Age-related changes in aortic sensitivity to noradrenaline and acetylcholine in rats.

1. The purpose of the present study was to determine the relationship between plasma and tissue lipid levels and the effects of age on vascular responses to noradrenaline (NA) and acetylcholine (ACh). 2. Studies were performed in young and aged rats and the response of endothelium-intact and -denuded aortic rings to NA and to ACh was measured. The plasma concentration of cholesterol (total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)) and 17 beta-oestradiol was determined, as was the aortic tissue content of phospholipids, cGMP and cholesterol (total, free and esterified). 3. Levels of all types of cholesterol in plasma and aorta increased with age; cholesterol levels in plasma correlated with those in the aorta; levels of phospholipid in the aorta did not increase with age but correlated with those of LDL cholesterol in plasma; levels of 17 beta-oestradiol did not change, but those of cGMP increased with age. 4. In endothelium-intact rings, the maximum tension developed by exposure to NA did not change, but the EC50 of NA increased with age and correlated with total cholesterol in the plasma and with the levels of all types of cholesterol in the aorta. In rings precontracted with NA, age decreased the maximum relaxation induced by ACh. The EC50 of ACh decreased with age and was inversely correlated with levels of cholesterol in the plasma and aorta. Treatment with NA increased cGMP levels in aged rats. Removal of the endothelium abolished the response to ACh and heightened the sensitivity to NA in young and aged rats. 5. Aortic endothelial cells seem to inhibit amine-induced contraction, while age-related changes in the levels of cholesterol in aortic tissue affect the sensitivity of the tissue to NA and ACh.

Acetylcholine↗
PubMed1998

Genetic analysis of Histoplasma capsulatum strains isolated from clinical specimens in thailand by a PCR-based random amplified polymorphic DNA method.

Thirteen strains of Histoplasma capsulatum were isolated from clinical specimens, including those from AIDS patients, in Thailand. Random amplified polymorphic DNA (RAPD) analysis with three different PCR primers showed that the DNA fingerprint patterns of the Thai isolates were very similar to each other and homogeneous, with only one exceptional strain, although the patterns were clearly different from those of a reference North American strain with all primers tested. Although the difference in the DNA fingerprinting patterns was minor, Thai isolates could be classified into two to four groups. A common PCR band (about 700 bp) in the patterns of all H. capsulatum strains was extracted, and its DNA sequence was determined. A new PCR primer set for the identification of H. capsulatum species was developed based on this sequence information. This primer set was 100% successful in the identification of the reference strain as well as all Thai isolates. The results of specificity tests of the primer set for the identification of the fungus are also discussed.

AIDS-Related Opportunistic Infections↗
PubMed1998

177Lu-EDTMP: a potential therapeutic bone agent.

Lutetium-177 (177Lu) has both beta particle emissions for a therapeutic effect and gamma emissions for imaging. This study was undertaken to synthesize and evaluate 177Lu-EDTMP (ethylenediaminetetramethylene phosphonic acid) as a therapeutic radiopharmaceutical for the palliation of pain from bone metastases. Chelation of 177Lu to EDTMP was obtained by heating for 30 min in boiling water at pH 8.8, resulting in a radiochemical yield of over 99%. The compound was stable for 20 days without any appreciable dissociation. Biodistribution studies in normal rats indicated selective bone accumulation, showing faster blood clearance, higher bone uptake and higher bone-to-soft tissue ratios than 99Tcm-MDP. In conclusion, 177Lu-EDTMP has favourable biological and physical characteristics for the palliative treatment of painful bone metastases.

Animals↗
PubMed1998

Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells.

PURPOSE: To investigate the relationship between ornithine-delta-aminotransferase (OAT) deficiency and ornithine accumulation and the specific degeneration of retinal pigment epithelial (RPE) cells in gyrate atrophy. METHODS: Human RPE cells, human hepatoma cells, and human fibroblast cells were treated with 5-fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT. Ornithine cytotoxicity was determined by using a [3H]thymidine incorporation assay and immunohistochemical staining for cytokeratin. The effects of various metabolites of ornithine and arginine, such as creatine, creatine phosphate, I-delta 1-pyrroline-5-carboxylic acid (L-P5C), and proline, which may be deficient in gyrate atrophy on RPE cell damage by ornithine, were determined by the same procedures. RESULTS: When the human RPE cells, HepG2 hepatoma cells, and WI-38 fibroblast cells were treated with 0.5 mM 5-FMOrn for 30 minutes, which inactivated OAT, ornithine exhibited severe time- and dose-dependent inhibition of DNA synthesis in the human RPE cells but not in the HepG2 hepatoma cells or WI-38 fibroblast cells. The inhibition of DNA synthesis was accompanied by drastic changes in morphologic appearance, disorganization of the cytoskeleton, and cell death. Ornithine or 5-FMOrn alone did not exhibit such cytotoxicity to the RPE cells. Proline prevented the cytotoxicity of ornithine. CONCLUSIONS: These findings suggest that an elevated level of ornithine combined with an increased sensitivity to ornithine as a result of OAT deficiency may be crucial to the specific RPE degeneration in gyrate atrophy. They suggest also that abnormalities of proline metabolism may be involved in the progress of gyrate atrophy.

Arginine↗
PubMed1998

[A case of hepatocellular carcinoma with reduction of primary tumor and disappearance of multiple lung metastasis].

A 56-year-old male had suffered from hepatocellular carcinoma treated by operation, PHoT and TAE since 1994. In December 1995, he had multiple metastases of lung in addition to recurrence of primary hepatic lesions. We discontinued treatment of TAE and decided to administer UFT (400 mg/day) orally as an outpatient. After seven months, the primary hepatic lesions were decreased in size, and metastatic lesions of lung were completely eliminated with reduction of AFP level. Generally, hepatocellular carcinoma with metastasis is refractory to treatment. However, this result suggests that UFT is one of the effective treatments for such advanced cases as having lung metastasis.

Administration, Oral↗