Biomedical subjects

S Shimizu

Publications and source records attributed to S Shimizu.

At least 235 records · Page 13Linked to original sources

PubMed1999

A patient with rectal cancer associated with ulcerative colitis in whom endoscopic ultrasonography was useful for diagnosis.

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis.

Adenocarcinoma↗

PubMed1999

Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells.

The purpose of this study was to examine the effect of hydrogen peroxide (H2O2) on angiogenesis in cultured endothelial cells. Endothelial cells obtained from bovine thoracic aorta (BAECs) were cultured between two layers of collagen type I to measure the tube formation which is a marker for angiogenesis. Addition of H2O2 (0.1-10 microM) to endothelial cells for various periods increased the rate of tube formation. The maximum stimulation of the tube formation was obtained when cells were exposed to 1 microM H2O2 for 30 min, and the enhancement of tube formation was blocked by catalase (10 U/ml). Both proliferation and migration of BAEC which are known to affect angiogenesis, were also stimulated by the addition of H2O2 (0.1 and 1 microM). Thus relatively low concentrations of H2O2 stimulated angiogenesis, proliferation and migration. Ets-1 is a member of the ets gene family of transcription factors, which binds to the ets binding motif in the cis-acting elements and regulates the expression of certain genes such as proteases including urokinase plasminogen activator (u-PA) and matrix metalloproteinase-1 (MMP-1). Interestingly, H2O2 increased the ets-1 mRNA level in BAECs compared with the basal level. The H2O2-stimulated angiogenesis was completely blocked by an ets-1 antisense oligonucleotide, but not by a mismatched oligonucleotide. These findings indicate that low concentrations of H2O2 stimulate angiogenesis in BAECs, and the stimulation mechanisms may partially involve the enhancement of proliferation and migration. Moreover, the H2O2-induced angiogenesis is likely to be mediated by the transcription factor ets-1.

Animals↗

PubMed1999

Presence of excess tetrahydrobiopterin during nitric oxide production from inducible nitric oxide synthase in LPS-treated rat aorta.

Tetrahydrobiopterin (BH4) is one of the cofactors of nitric oxide synthase (NOS), and the synthesis of BH4 is induced as well as inducible NOS (iNOS) by lipopolysaccharide (LPS) and/or cytokines. BH4 has a protective effect against the cytotoxicity induced by nitric oxide (NO) and/or reactive oxygen species in various types of cells. The purpose of this study was to examine whether or not an excess of BH4 is present during the production of NO by iNOS in LPS-treated de-endothelialized rat aorta. Addition of LPS (10 microg/ml) to the aorta bath solution caused L-arginine (L-Arg)-induced relaxation from 1.5 hr after the addition of LPS in de-endothelialized rat aorta pre-contracted with 30 mM KCl. The L-Arg-induced relaxation was prevented by NOS inhibitors. BH4 content also increased from 3 hr after the addition of LPS. mRNAs of iNOS and GTP cyclohydrolase I (GTPCH), a rate-limiting enzyme of BH4 synthesis, were increased from 1.5 hr after addition of LPS. Although the expression of iNOS and GTPCH mRNAs was observed in the media, the expression levels in the media were much lower than those in the adventitia. Ten millimolar 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTPCH, strongly reduced L-Arg-induced relaxation, and decreased BH4 content to below the basal level in LPS-treated aorta, whereas 0.5 mM DAHP reduced the LPS-induced increase in BH4 content to the basal level but did not affect L-Arg-induced relaxation. The inhibition of L-Arg-induced relaxation by 10 mM DAHP was overcome by the addition of BH4 (10 microM). These results suggest that although BH4 is essential for NO production from iNOS, the increase in BH4 content above the basal level is not needed for eliciting L-Arg-induced relaxation by the treatment with LPS. Thus, an excess amount of BH4 may be synthesized during NO production by iNOS in LPS-treated rat aorta.

Animals↗

PubMed1999

Effect of amino acids and glucose on exercise-induced gut and skeletal muscle proteolysis in dogs.

The effect of amino acid and/or glucose administration before and during exercise on protein metabolism in visceral tissues and skeletal muscle was examined in mongrel dogs. The dogs were subjected to treadmill running (150 minutes at 10 km/h and 12% incline) and intravenously infused with a solution containing amino acids and glucose (AAG), amino acids (AA), glucose (G) or saline (S) in randomized order. The infusion was started 60 minutes before exercise and continued until the end of the exercise period. An arteriovenous-difference technique was used to estimate both tissue protein degradation and synthesis. When S was infused, the release of leucine (Leu) from the gut and phenylalanine (Phe) from the hindlimb significantly increased during exercise, thus indicating that exercise augmented proteolysis in these tissues. The balance of Leu across the gut during exercise demonstrated a net uptake with both AAG and AA, whereas a net release was observed for G and S. In addition, Leu uptake in the gut during the last 90 minutes of the exercise period tended to be greater with AAG versus AA (P = .06). Phe balance across the hindlimb during the late exercise period showed a significant release with S, AA, and G, whereas the balance with AAG did not show a significant release. These results suggest that exercise-induced proteolysis in the gut may be reduced by supplementation with AA, and this effect may be enhanced by concomitant G administration. However, in skeletal muscle, both AA and G may be required to prevent net protein degradation during exercise. G provided without AA did not achieve net protein synthesis in either tissue.

Amino Acids↗

PubMed1999

Dural arteriovenous malformation manifesting as dementia due to ischemia in bilateral thalami. A case report.

BACKGROUND: Although dementia is one of the curable manifestations of a dural arteriovenous malformation (AVM), the pathophysiology remains unclear. CASE DESCRIPTION: We describe an elderly patient who had an AVM in the tentorium and manifested signs of dementia from ischemia, predominantly in the bilateral thalami. Intravascular embolization of the dural AVM resulted in amelioration of signs of dementia, and this improvement was consistent with that of neuroradiological and hemodynamic conditions in the thalami. CONCLUSION: The coincidental improvement of CBF in the thalami and signs of dementia after embolization of the AV shunt supports the concept of primary participation of the thalami in the pathophysiology of dementia of vascular origin in our patient.

Aged↗

PubMed1999

Microbial enzymes: new industrial applications from traditional screening methods.

Enzymes have applications in many fields, including organic synthesis, clinical analysis, pharmaceuticals, detergents, food production and fermentation. The application of enzymes to organic synthesis is currently attracting more and more attention. The discovery of new microbial enzymes through extensive and persistent screening will open new, simple routes for synthetic processes and, consequently, new ways to solve environmental problems.

4-Butyrolactone↗

PubMed1999

Three-dimensional movement of a liver tumor detected by high-speed magnetic resonance imaging.

OBJECTIVE: Three-dimensional (3D) movement of a spherical liver tumor during respiration was investigated with magnetic resonance imaging (MRI) using a high-speed sequence. METHODS: A marker was placed on the surface of the patient as a reference of distance. Repetition time (TR) was 7.7 ms, echo time (TE) was 4.2 ms, flip angle was 20 degrees, section thickness was 8 mm, and a 256 x 128 matrix was used. The acquisition time was 1.0 s followed by an interval of 0.5 s. The 20 tumor contours extracted during 30 s were superimposed on sagittal and coronal MR images. RESULTS: The maximum value of tumor edge location was 3.9 cm in the cranio-caudal direction, 2.3 cm in the ventro-dorsal direction, and 3.1 cm in the lateral direction. The mean length of tumor displacement observed was 2.1 cm in the cranio-caudal direction, 0.8 cm in the ventro-dorsal and 0.9 cm in the left-right direction, respectively. The locus of the center of the tumor contour in the sagittal cross section was inclined at 23 degrees and in the coronal cross section was inclined at 18 degrees to the cranio-caudal axis of body. CONCLUSION: In conclusion, 3D movement of a spherical liver tumor was detected using rapid MRI sequential examinations. Magnetic resonance imaging has a potential to improve the accuracy of the planning target volume of a liver tumor.

Humans↗

PubMed1999

Risk factors for vertebral fractures in renal osteodystrophy.

We determined the prevalence of vertebral fractures in hemodialysis (HD) patients, investigated whether low bone mineral density (BMD) is predictive of vertebral fracture, and evaluated the effect of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) levels on vertebral fracture. One hundred eighty-seven male HD patients were assessed for vertebral fractures, and lumbar-spine and total-body BMD were measured by dual-energy x-ray absorptiometory. Thirty-nine patients (20.9%) had vertebral fractures. Each standard deviation (SD) decrease in lumbar-spine BMD increased the age-adjusted odds ratio of vertebral fracture 2.0 times (95% confidence interval [CI], 1.4 to 2.0) and 1.6 times (95% CI, 1.1 to 1.6) for total-body BMD. The area under the receiver operating characteristic curve for lumbar-spine BMD was significantly greater than that for total-body BMD (P < 0.05). Patients with serum iPTH levels in the lowest tertile had a 2.4-fold greater risk for vertebral fracture than those in the middle tertile and a 1.6-fold greater risk than those in the highest tertile (P < 0.05). When the two criteria of lowest tertile of serum iPTH level and highest tertile of serum ALP level were combined, the prevalence of vertebral fractures was the greatest. Similarly, when the lowest tertile of serum iPTH level and lowest tertile of serum ALP level were combined, the prevalence was the second greatest among the combined groups according to tertiles of serum iPTH and ALP levels. We conclude that low lumbar-spine BMD might be a sensitive predictor of vertebral fracture in HD patients, and patients with relatively low iPTH levels would have a greater risk for vertebral fracture than those with hyperparathyroidism.

Absorptiometry, Photon↗

PubMed1999

Comparison of treatments for hepatolithiasis: hepatic resection versus cholangioscopic lithotomy.

BACKGROUND: Hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCSL) are the two main approaches to the treatment of hepatolithiasis, but comparisons of longterm followup results have not been adequately reported. STUDY DESIGN: Of 86 patients with hepatolithiasis admitted to our institution between 1980 and 1996, we reviewed 54 patients: 26 who underwent hepatic resection and 28 who underwent PTCSL. Five patients who underwent postoperative cholangioscopic lithotomy were included in the former group. The remainder of the hepatolithiasis patients were not treated by hepatic resection or PTCSL and, therefore, were excluded from this study. Hepatic resections were mainly indicated for left-sided localized intrahepatic calculi, atrophic liver, and possible presence of cholangiocellular carcinoma. PTCSL was performed for right-sided, bilateral or recurrent stones at an average of 6 treatments (range 1 to 20 treatments) for each patient. There were no differences between the two groups in terms of gender or age. The recurrence rate of stones and longterm prognosis were analyzed using the Kaplan-Meier method, and other clinical factors listed below were statistically compared. RESULTS: The rate of complete removal of stones was similarly high in each group (96.2% in the hepatic resection group versus 96.4% in the PTCSL group). The complication (38.5% versus 21.4%) and 5-year survival (85.6% versus 100%) rates were comparable. Remaining bile duct stricture (18.2% versus 60.9%, p < 0.01) and 5-year recurrence rates (5.6% versus 31.5%, p < 0.05) were statistically lower in the hepatic resection group than in the PTCSL group. CONCLUSIONS: Hepatic resection, when combined with postoperative cholangioscopic lithotomy, is a preferable treatment for left-sided stones with strictures and bilateral stones.

Adult↗

PubMed1999

Intraosseous squamous cell carcinoma arising in association with a squamous odontogenic tumour of the mandible.

We report a rare occurrence of intraosseous squamous cell carcinoma (SCC) arising in association with a squamous odontogenic tumour (SOT), which had not previously been documented in the literature. A 53-year-old man had, for 5 years, a well-demarcated radiolucency attached to the impacted third molar of the mandible. The enucleated specimen had a characteristic pattern of SOT, but in which a few epithelial islands showed atypical features suggestive of SCC. Intense p53-, proliferating cell nuclear antigen- and Ki-67-positive cells were detected in carcinoma areas. Within 2 months, aggressive bone destruction showing typical findings of intraosseous SCC appeared. The present tumour is presumably a malignant variant of SOT.

Ameloblastoma↗

PubMed1999

Diversity of 4-chloroacetoacetate ethyl ester-reducing enzymes in yeasts and their application to chiral alcohol synthesis.

Enzymes which reduce 4-chloroacetoacetate ethyl ester (CAAE) to (R)- or (S)-4-chloro-3-hydroxybutanoate ethyl ester (CHBE) were investigated. Several microorganisms which can reduce CAAE with high yields were discovered. An NADPH-dependent aldehyde reductase, ARI, and an NADPH-dependent carbonyl reductase, S1, were isolated from Sporobolomyces salmonicolor and Candida magnoliae, respectively, and enzymatic synthesis of chiral CHBE was performed through the reduction of CAAE. When ARI-overproducing Escherichia coli transformant cells or C. magnoliae cells were incubated in an organic solvent-water diphasic system. CAAE was stoichiometrically converted to (R)- or (S)-CHBE (> 92% enantiomeric excess), respectively. Multiple CAAE-reducing enzymes were present in S. salmonicolor, C. magnoliae and bakers' yeast. Comparison of the primary structures of these CAAE-reducing enzymes with other protein sequences showed that CAAE-reducing enzymes are widely distributed in various protein families, and various physiological roles of these enzymes in the cell were speculated.

Journal Article↗

PubMed1999

Characterization of the second form of NADH-cytochrome b5 reductase gene from arachidonic acid-producing fungus Mortierella alpina 1S-4.

The second type of cytochrome b5 reductase (Cb5R-II) gene was characterized in the arachidonic acid-producing fungus Mortierella alpina 1S-4. Its cDNA (897 bp) and predicted amino acid (298 aa) sequences show more than 70% similarity to the previously isolated first type of Cb5R. Highly conserved exon-intron organization suggests that the two genes evolved from the duplication of a common ancestral gene. Cb5R-II has a flavin-binding domain at its highly hydrophobic N-terminal and an NADH-binding domain at the C-terminal. In comparison with Cb5R genes from other sources, high homology (46-54%) was found for yeast and plant genes. Phylogenetic analysis revealed that microbial and plant Cb5R genes represent a gene family evolved from one prototype and are different from mammalian Cb5R genes.

Journal Article↗

PubMed1999

Biosynthesis and regulation of microbial polyunsaturated fatty acid production.

Growing interest in polyunsaturated fatty acid (PUFA) applications in various fields coupled with their significance in health and dietary requirements has focused attention on the provision of suitable sources of these compounds. Isolation of highly efficient oleaginous microorganisms has led to the development of fermentation technologies as an alternative to agricultural and animal processes. Particularly active in PUFA synthesis are the Zygomycetes fungi and certain microalgae. Emphasis is placed on increasing the product value by employing new biotechnological strategies (e.g. mutation techniques, molecular engineering and biotransformations) which allow the regulation of microbial PUFA formation with satisfactory yield in order to be competitive with other sources. Comparative successes in fungal PUFA production demonstrate microbial potential to synthesize high-value oils and provide the main stimulus for their applications.

Journal Article↗

PubMed1999

Occurrence of multiple ethyl 4-chloro-3-oxobutanoate-reducing enzymes in Candida magnoliae.

Multiple ethyl 4-chloro-3-oxobutanoate (COBE)-reducing enzymes were isolated from a cell-free extract of Candida magnoliae. A NADPH-dependent COBE-reducing enzyme, distinct from the carbonyl reductase and aldehyde reductase previously reported, was purified to homogeneity using five steps, including polyethylene glycol treatment. The relative molecular mass of the enzyme was estimated to be 86,000 on high performance gel-permeation chromatography and 29,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme catalyzed the reduction of COBE to the corresponding (S)-alcohol with a 51% enantiomeric excess. The substrate specificity of the enzyme was different from those of the other COBE-reducing enzymes of the same strain. The partial amino acid sequences of the enzyme showed that it belongs to the short chain alcohol dehydrogenase/reductase (SDR) family. This is the first report of multiple COBE-reducing enzymes with various stereoselectivities occurring in the same strain but belonging to different (super)families.

Journal Article↗

PubMed1999

Cancer gene therapy using a pro-apoptotic gene, caspase-3.

Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis. We applied the human caspase-3 gene as a novel form of anticancer gene therapy. Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by the addition of etoposide. In an AH130 liver tumor model, transduction of human caspase- 3, but not the empty vector, induced extensive apoptosis and reduced tumor volume when combined with etoposide administration. However, this effect was not observed with a Bcl-2 overexpressing tumor. In conclusion, caspase-3 gene transduction accompanied by an additional death stimulus may be a useful method of anticancer gene therapy, except for Bcl-2 overexpressing tumors.

Adenoviridae↗

PubMed1999

Activation of EVI1 transcripts with chromosomal translocation joining the TCRVbeta locus and the EVI1 gene in human acute undifferentiated leukemia cell line (Kasumi-3) with a complex translocation of der(3)t(3;7;8).

A cell line (Kasumi-3) established from acute myeloid leukemia (AML-M0) had unique phenotypes of undifferentiated leukemia cells with expression of both T cell and myeloid antigens. Kasumi-3 cells with t(3;7)(q26;q22) highly expressed a 6 kb transcript of EVI1, which is located on chromosome 3q26. Therefore, we further characterized the chromosomal breakpoint by pulsed-field gel electrophoresis near EVI1. We identified and isolated the chromosomal breakpoint at approximately 80 kb upstream from the 5' end of EVI1. Sequence analysis of the breakpoint revealed that the whole Vbeta region from T cell receptor beta (TCRbeta) at 7q35 was translocated to the upstream of EVI1. A 1.0 kb TCRbeta transcript was expressed in the Kasumi-3 cells, suggesting that TCRbeta rearrangement occurred as Dbeta-Jbeta joining events. Fluorescence in situ hybridization analysis revealed that the inverted chromosome 7q22-q35 segment between TCRbeta and the region proximal to the erythropoietin gene at 7q22 was translocated to the region distal to EVI1 in der(3). Since the telomeric region of chromosome 8 q was also translocated to the inverted chromosome 7q22-q35 segment in der(3), the chromosomal abnormalities of der(3) were defined as being der(3)t(3;7;8)(3pter-3q26::7q35-7q22::8q22 -8qter). It is suggested that a translocated enhancer element in the TCRbeta locus and/or loss of a negative regulatory element near EVI1 might function to enhance the EVI1 expression. Therefore, the enhanced EVI1 expression may contribute to the development of a subset of undifferentiated leukemia.

Acute Disease↗

PubMed1999

Detection of MUM1/IRF4-IgH fusion in multiple myeloma.

MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) gene has been identified as an oncogene transcriptionally activated by t(6;14)(p25;q32) chromosomal translocation in multiple myeloma (MM). The significance of this alteration in MM remains unknown, as it is not detectable by means of conventional cytogenetic analysis. To address this issue, we established diagnostic procedures based on pulsed-field gel electrophoresis (PFGE) analysis and double color fluorescence in situ hybridization (DCFISH) using DNA probes derived from the MUM1 and the immunoglobulin heavy chain (IgH) gene loci. Among a panel of 17 MM cell lines, three (17.6%) showed fusions between these two loci, which resulted in the juxtaposition of the MUM1 to the IgH 3' alpha-enhancer region by virtue of t(6;14) or insertion of the IgH sequences into the vicinity of the MUM1 gene and in the concomitant overexpression of the MUM1 mRNA. With similar results, fusions between MUM1 and IgH loci were observed by means of interphase DCFISH in eight (21.1%) out of the 38 MM cases, although no definite relationships between MUM1 status and specific clinical findings could be established.

Aged↗

PubMed1999

Delta 9-fatty acid desaturase from arachidonic acid-producing fungus. Unique gene sequence and its heterologous expression in a fungus, Aspergillus.

Based on the sequence information for delta 9-desaturase genes (from rat, mouse and yeast), which are involved in the desaturation of palmitic acid and stearic acid to palmitoleic acid and oleic acid, respectively, the corresponding cDNA and genomic gene were cloned from the fungal strain, Mortierella alpina 1S-4, which industrially produces arachidonic acid. There was a cytochrome b5-like domain linked to the carboxyl terminus of this Mortierella desaturase, as also seen in the yeast delta 9-desaturase. The Mortierella delta 9-desaturase genomic gene had only one intron, in which a novel phenomenon was observed: there was a GC-end at the 5'-terminus instead of a GT-end that is, in general, found in introns of eukaryotic genes. The full-length cDNA clone was expressed under the control of an amyB promoter in a filamentous fungus, Aspergillus oryzae, resulting in drastic changes in the fatty acid composition in the transformant cells; the contents of palmitoleic acid (16:1) and oleic acid (18:1) increased significantly, with accompanying decreases in palmitic acid (16:0) and stearic acid (18:0). These changes were controlled by the addition of maltose as a carbon source to the medium. Also, the expression of the gene caused a significant change in the lipid composition in the Aspergillus transformant. Genomic Southern blot analysis of the transformant with the Mortierella delta 9-desaturase gene as a probe confirmed the integration of this gene into the genome of A. oryzae.

Amino Acid Sequence↗