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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 325 records · Page 18Linked to original sources

Fluorescence-labeled synthetic glycopolymers: a new type of sugar ligands of lectins.

Radical copolymerization of a polymerizable dansyl derivative, N-2-propenyl-(5-dimethylamino)-1-naphthalene sulfonamide, with sugar monomers and acrylamide proceeded smoothly in aqueous solution in the presence of ammonium persulfate and N,N,N',N'-tetramethylethylenediamine and afforded a novel type of water-soluble glycopolymers having fluorescent side-chains. Fluorescence emission spectra of these polymeric sugar-ligands by excitation at 340 nm revealed maxima at 448 and 528 nm. When the glycopolymer carrying galactose residues was saturated with Ricinus communis agglutinin (RCA60), the fluorescence emission maxima at 448 and 528 nm were not shifted significantly, although the fluorescence intensities were decreased by 20 and 14%, respectively. Polymeric sugar-cluster effects drastically enhanced the association constants of galactose residues with RCA60 in the order of 10(8) M-1. The significance for efficient binding of galactose density on the glycopolymer was also demonstrated by using glycopolymers with different degrees of galactose branching.

Allyl Compounds↗

Clinical significance of decreased myocardial uptake of 123I-BMIPP in patients with stable effort angina pectoris.

The aim of this study was to assess the feasibility of resting myocardial fatty acid metabolic imaging with 123I-beta-methyliodophenyl-pentadecanoic acid (123I-BMIPP) for the detection of patients with stable effort angina pectoris and to clarify the clinical significance of abnormal 123I-BMIPP images. Myocardial imaging with 123I-BMIPP at rest and 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) at rest and during treadmill exercise was performed in 46 patients with suspected effort angina pectoris. Resting 123I-BMIPP imaging detected 43% (17/40) of patients with significant (> or = 50%) coronary artery stenosis and 59% (17/29) of patients with exercise-induced myocardial ischaemia. The patients with abnormal 123I-BMIPP images terminated exercise after a shorter period (4.5 +/- 2.6 vs 6.7 +/- 4.1 min; P < 0.01) and at a lower rate pressure product (16,124 +/- 5211 vs 20,246 +/- 6564 mmHg x beats min-1; P < 0.01) than those with normal 123I-BMIPP images. The presence of ST depression during the exercise test (77 vs 52%; P < 0.05), severe coronary stenosis exceeding 90% (88 vs 43%; P < 0.01), collateral vessels (35 vs 9%; P < 0.01) and a wall motion abnormality of hypokinesis/akinesis (53 vs 30%; P < 0.05) were more frequently seen in patients with abnormal 123I-BMIPP images than in those with normal images. Resting 123I-BMIPP imaging was able to detect the presence of coronary artery stenosis and exercise-induced myocardial ischaemia with moderate sensitivity, and to determine the functional severity of coronary artery disease.

Angina Pectoris↗

Comparison of incorporation and extension of nucleotides in vitro opposite 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene.

DNA templates with 8-hydroxyguanine (7,8-dihydro-8-oxoguanine, oh8Gua) at a site corresponding to the first or second position of codon 12 of the c-Ha-ras gene were prepared, and the nucleotides inserted opposite the modified base were compared. The Klenow fragment (KF) of Escherichia coli DNA polymerase I inserted C opposite oh8Gua at both positions. Taq DNA polymerase incorporated C and A opposite oh8Gua, and the ratio of C to A was higher at the first position than at the second position. DNA polymerase alpha (pol alpha) inserted A and C at the first position, and A at the second position of codon 12, indicating that the ratio of C to A was higher at the first position. Moreover, we studied the extensions of bases paired with oh8Gua by DNA polymerases with or without 3'-5' exonuclease activity. G and T opposite oh8Gua were removed, and subsequently C was inserted by KF. We found that an oh8Gua:A pair was recognized by the exonuclease activity of the enzyme and that A was partially substituted by C. On the other hand, pol alpha extended only C and A opposite oh8Gua. No difference was observed with oh8Gua at the two positions. These results indicate that the ratio of nucleotides incorporated opposite oh8Gua depends on the sequence context, while there is no particular difference in the extension of base pairs involving oh8Gua by DNA polymerases.

Animals↗

Chemical synthesis of phosphopeptides using the arylthio group for protection of phosphate: application to identification of cdc2 kinase phosphorylation sites.

Synthesis of two O-phosphorylated dipeptides, N-Boc-O[S,S-bis(p-methoxyphenyl)phosphorodithioyl] -serylproline and N-Boc-O-[S,S-bis(p-methoxyphenyl) phosphorodithioyl]threonylproline, as new O-phosphorylated dipeptide building blocks for the synthesis of O-phosphorylated peptides, is described. Peptides containing phosphoserine or phosphothreonine were prepared by use of these building blocks in the Boc mode of liquid-phase peptide synthesis. Sites phosphorylated by cdc2 kinase were easily identified using these chemically synthesized phosphopeptides.

Amino Acid Sequence↗

Minigemistocytic astrocytoma with frequent apoptoses: analysis of tumor growth.

A rare glial tumor known as 'minigemistocytic astrocytoma (gliofibrillary oligodendroglioma)' is reported in a 73 year old Japanese male. A low-density area found by computed tomography and thought to be an operative scare remaining after hematoma in the right frontal lobe of the cerebrum had been followed for 10 years. This area, however, had been accompanied by a cyst for 2 years and had developed gradually for 1 year prior to dissection. The tumor was poorly demarcated from the surrounding normal tissue macroscopically at operation. Microscopically, the tumor consisted of small gemistocytic cells in uniform sheets intersected by a small vascular stroma with frequent eosinophilic granular bodies, mitoses and apoptotic bodies. Immunohistochemical examination for glial fibrillary acidic protein (GFAP) revealed remarkable positive reactivity in the perinuclear cytoplasm, but no immunoreactivity for vimentin or Leu 7 was found. Electron microscopically, rich filaments arranged in parallel bundles were found in the neoplastic cells. These histological findings are closely consistent with those of previously reported minigemistocytic astrocytoma cases. The GFAP-rich minigemistocytic astrocytoma with granular bodies and frequent mitoses in the present case is considered to indicate a higher degree of astrocytic differentiation and malignant potential than previous cases. The frequent apoptoses, however, might inhibit tumor growth in this case.

Aged↗

Extramedullary megakaryoblastic tumors following an indolent phase of myelofibrosis.

A 59-year-old man developed multiple subcutaneous and bone tumors after 2 years' duration of indolent myelofibrosis. These tumors exhibited a diffuse proliferation of pleomorphic blast cells. The skeletal x-rays showed disseminated osteolysis and osteosclerosis. Blast cells obtained from the pleural effusion did not react with myeloperoxidase, sudan black B or non-specific esterase. Genotypic analysis of DNA samples at autopsy did not demonstrate rearrangements of T-cell receptor beta-chain or immunoglobulin heavy-chain genes. Frozen-section immunohistochemical studies revealed that the neoplastic cells were derived from megakaryocytic lineage. The present case represents a novel and unusual subtype of megakaryocytic neoplasm.

Bone Neoplasms↗

IgA nephropathy associated with hyper IgAnemia, psoriasis or pustulosis and ossification.

This is a report on two cases of IgA nephropathy associated with psoriasis vulgaris, having hyper IgAnemia (above 500 mg/dl) and ossification. Case 1 is a 47-year-old woman with a 7-year history of psoriasis vulgaris, and case 2 is a 57-year-old man with a 17-year history of this disease. IgA was 526 and 1,356 mg/dl, respectively. HLA analysis showed A2, A26 (10), Bw62 (15), Bw46, Cw3, DRw12 (5), and DRw8 in the former, and A2, A11, B13, Bw46, Cw11, DR4, and DRw8 in the latter. Renal biopsy specimens disclosed mild mesangial proliferative glomerulonephritis and moderate mesangial proliferative glomerulonephritis with predominant IgA deposition in mesangial area, respectively. A bone-scintigraphy revealed a high uptake of radioisotopes in the left shoulder, the vertebra, the sacroiliac joint, both sides of the knees and ankles, and the sterno-cost-clavicular area. An X-ray study showed ossification of the posterior longitudinal ligament (OPLL) in the former, and ankylosing spinal hyperostosis (ASH) in the latter. A review of the literature discloses three other case reports of hyper IgAnemia, IgA nephropathy, psoriasis or pustulosis, and ossification. The alertness of dermatologists, orthopedic surgeons, rheumatologists, and general practitioners will be required to attain to a more frequent diagnosis of the above combination.

Female↗

[The changes in nuclear DNA content in acquisition of a high capacity for metastasis of human cell lines].

Quantification of nuclear DNA content in cancer is considered a prognostic factor, and several investigators have demonstrated that aneuploid tumors are more aggressive than diploid tumors. In this report, we investigated the relationship between metastatic capacity and nuclear DNA content using gastric and colon cancer cell lines. We established a highly peritoneal metastatic cell line (2M-D3) from a gastric cancer cell line (2M) and a highly liver metastatic cell line (LM-H3) from colon cancer cell line (LM) in our laboratory. Both the highly metastatic cell lines have more capacity for growth and metastasis, but lower nuclear DNA content and chromosome numbers than these parental cell lines. The results indicated that metastatic capacity was inversely proportional to nuclear DNA content. We cannot provide a satisfactory explanation for this inverse correlation between metastatic capacity and nuclear DNA content, but it is supposed that each cancer cell may have suitable and stable nuclear DNA content in metastasis.

Animals↗

[Correlation between malignancy of gastric cancer and c-myc DNA amplification or overexpression of c-myc protein].

The amplification of c-myc DNA for fresh frozen tissue of 31 gastric adenocarcinomas was examined with dot blot hybridization method. Using the avidin-biotin peroxidase complex method, the expression of c-myc protein was examined immunohistochemically for formalin-fixed paraffin embedded tissue of 51 gastric adenocarcinomas including the same cases for c-myc DNA analysis. c-myc DNA amplification was detected in only 4 cases (12.9%). However, c-myc protein overexpression was recognized in 21 cases (41.2%). Only one of 4 cases showing c-myc DNA amplification indicated overexpression of c-myc protein. There was no statistically significant relation of c-myc protein overexpression with clinicopathological factors (histology, depth of invasion, invasion of the vessels, metastasis, intraabdominal dissemination and histological staging). These results suggest overexpression of c-myc protein could be recognized even in early gastric cancer indicating the relation of this gene product with proliferation of gastric cancer cells, although its role in the progression and metastasis of gastric adenocarcinoma might be minimal.

Adenocarcinoma↗

[Role of tripeptide Arg-Gly-Asp (RGD) on adhesiveness of human pancreatic cancer cell, PANC-1 to extracellular matrix].

Tumor cell invasion and metastasis are likely to be complex processes involving a variety of cell surface receptors mediating interactions with a number of extracellular matrix molecules, including fibronectin, laminin, and collagen. We have applied this interaction of receptors for specific adhesive substrates in vitro, using specific monoclonal antibody and biologically active synthetic peptides with human pancreatic carcinoma cell, PANC-1. Tripeptide Arg-Gly-Asp (RGD) inhibited adhesion on PANC-1 cells to fibronectin but less effective in blocking adhesion to laminin and collagen, although anti beta 1-integrin antibody significantly inhibited adhesion of fibronectin but less inhibited to laminin, collagen. Our studies emphasize the importance of synthetic tripeptide RGD in adhesion on PANC-1 to extracellular matrix protein, as well as indicating the specificity of cell surface receptor, beta 1 integrin.

Amino Acid Sequence↗

[Efficacy of smoking cessation instruction for general smokers at an annual physical examination].

A randomized controlled trial was conducted to evaluate the efficacy of smoking cessation instruction given to general smokers at an annual physical examination. Four hundred and twenty-six male and 42 female clients were randomly assigned to an intervention group (I), and 413 males and 76 females were assigned to a control (C) group. The I group was given an approximately 2-minute smoking cessation instruction by physicians, answered a quiz concerning tobacco, chose their own behavioral goals and were handed a leaflet on how to quit smoking. Subjects in both groups responded to a self-administered questionnaire and a 6-month and 12-month follow-up was performed by post card or telephone. The I group received an encouragement card one month after instruction and abstainers of the I group were awarded a telephone card at the 6-month follow-up. The results were as follows: 1) The male I group exhibited 7.3% (6 months), 10.1% (12 months) abstinence rates and the male C group 4.4% (6 months), 5.3% (12 months), respectively. The difference in 12-month abstinence rates was statistically significant. 2) The female I group exhibited abstinence rates of 16.7% (6 months), 23.8% (12 months) and the female C group 14.5% (6 months), 17.1% (12 months), respectively. 3) A multivariate analysis of smoking cessation showed that lower nicotine dependency, strong determination for smoking cessation, and being female were significant factors for abstinence at the 6-month follow-up. At 12 months, the smoking cessation instruction also became a significant factor. These data suggest that a simple smoking cessation instruction at an annual physical examination was effective for general smokers.

Adult↗

[Somatosensory evoked potentials in severely handicapped patients].

Somatosensory evoked potentials (SSEPs) were investigated to evaluate the function of the central nervous system in 53 severely handicapped patients. P9-P13 interpeak latencies of these patients were within normal limits in comparison with those of normal controls. But P13-N20 interpeak latencies showed various abnormalities including prolongation or absence. On etiological study, prenatal onset cases, especially in migration disorders, had markedly prolonged P13-N20 and postnatal onset cases frequently showed the absence of N20. Most of the patients showing diffuse brain destruction on CT scan revealed the absence of N20.

Adolescent↗

p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia.

Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic, and smoldering. We studied the relationship between p53 gene alteration and clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and five crisis type transformed from chronic type. Using a polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by nucleotide sequencing, we detected mutations of the p53 gene in six of the 14 acute type patients, two of the five crisis type, and one of the 15 chronic type patients. Gene dosage studies, using PCR amplification and Southern blotting, showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type patients, two of the five crisis type, and one of 14 chronic type patients examined. These observations indicated that the frequency of p53 gene alterations in the acute and crisis types of ATL was markedly higher than that in chronic type, suggesting that p53 gene alteration plays a role in the disease progression of ATL.

Adult↗

[Establishment of a new scirrhous gastric cancer cell line OCUM-2M from a primary gastric tumor].

We report on the establishment and characterization of a scirrhous gastric cancer cell line, designated OCUM-2M, derived from a 49-year-old Japanese female. OCUM-2M was derived from a primary tumor of stomach taken by total gastrectomy. The cell line grew singly or in clusters in the cultured medium. The cell line continued to multiply for more than one year. Doubling time was 37.3 hours, chromosomal mode was 70. The DNA ploidy pattern was aneuploid and DNA index was 1.59. It produced several tumor-associated antigens such as CEA, CA19-9, SLX and SPan-1. The cell line was transplantable in athymic BALB/c nude mice, and histological findings of the xenografted tumor showed poorly differentiated adenocarcinoma. The growth of OCUM-2M was stimulated following the addition of EGF, b-FGF and KGF, and decreased following the addition of TGF-beta 1. This cell line is useful in vitro and in vivo systems for studies of the biology of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin.

Recent studies have indicated that aspirin promotes neutrophil adherence to endothelium via CD11/CD18-dependent interactions with intercellular adhesion molecule 1, which subsequently leads to neutrophil-mediated cell injury. The objectives of the present study were to determine the role of neutrophil-endothelial cell interactions and lipid peroxidation in aspirin-induced gastric mucosal injury in rats. Oral administration of aspirin and HCl produced hemorrhagic erosions in the stomach of rats. Myeloperoxidase (MPO) activity in the gastric mucosa, an index of neutrophil infiltration, significantly increased 3 h after aspirin administration. The concentration of thiobarbituric acid-reactive substances (TBA-RS) in the gastric mucosa, an index of lipid peroxidation, increased slightly 3 h after aspirin administration. In rats treated with antineutrophil serum, both the total area of gastric erosions and MPO activity were significantly reduced. In addition, pretreatment with anti-CD18 monoclonal antibodies significantly attenuated gastric mucosal damage and inhibited the increases in both MPO activity and TBA-RS in the gastric mucosa after aspirin administration. These observations suggest that CD18-dependent neutrophil-endothelial cell interactions and lipid peroxidation play an important role in the pathogenesis of gastric mucosal lesions induced by aspirin.

Animals↗

Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats.

Oxygen free radicals have been implicated in the pathogenesis of gastrointestinal mucosal injury. However, their effect on the quality of experimental gastric ulcer healing has not been investigated previously. Gastric ulcers were produced on the anterior wall of the stomach of rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcers were treated with scavengers for 6 weeks. Rats received either a daily dose of 20,000 U/kg of recombinant human Cu,Zn-SOD, a 1% solution of DMSO administered orally ad libitum, or 50 mg/kg/day of allopurinol administered orally. The quality of ulcer healing was evaluated by histologic and biochemical parameters: ulcer area, lipid peroxide levels, abnormality of regenerated mucosa, angiogenesis, and fibrosis as assessed by Azan staining, mucin content as assessed by the PAS-positive area, and polymorphonuclear leukocyte (PMN) infiltration. The treatments with SOD, DMSO, or allopurinol did not affect the ulcer area or lipid peroxide levels in the gastric mucosa, and SOD did not affect the histologic abnormality score, PMN infiltration in regenerated mucosa, the collagen fiber proliferation index, or the PAS-positive mucous score. DMSO and allopurinol significantly increased the collagen fiber proliferation index and the PAS-positive mucous score compared with controls. These results indicate that scavenging hydroxyl radicals or inhibiting xanthine oxidase enhances the quality but not the speed of gastric ulcer healing.

Animals↗