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Biomedical subjects

T Yoshikawa

Publications and source records attributed to T Yoshikawa.

At least 163 records · Page 9Linked to original sources

[Significance of laparoscopy for response assessment of chemotherapy in gastric cancer].

UNLABELLED: We performed laparoscopy before and after chemotherapy in two patients with relapsed and advanced gastric cancer, whose major metastatic sites had been diagnosed as being in the peritoneum. A change in tumor responses when assessed by laparoscopy was found. Case 1: A 63-year-old man presented with an umbilical metastasis and suspected peritoneal metastases after gastrectomy. Laparoscopy revealed peritoneal metastases before chemotherapy. After one course of chemotherapy the umbilical tumor disappeared (CR). Laparoscopy after two courses of chemotherapy revealed increasing peritoneal metastases (PD). The overall response was PD. Case 2: A 67-year-old woman was referred to our hospital with a diagnosis of type 4 gastric cancer. Staging laparoscopy revealed massive lymph node metastases and the patient was positive in peritoneal washing cytology. After four courses of chemotherapy, the primary tumor and the metastatic lymph nodes had decreased in size (PR). In contrast, laparoscopy revealed increasing peritoneal metastases (PD). The overall response was PD. CONCLUSION: In patients with peritoneal and other modes of metastasis, tumor response to chemotherapy may be misjudged by conventional imaging alone. Intraperitoneal examination by laparoscopy provides accurate information, including the tumor response to chemotherapy.

Aged↗

The effects of bonding system and light curing method on reducing stress of different C-factor cavities.

PURPOSE: The effect of the slow-start curing method on the marginal sealing and cavity wall adaptation on resin composite restorations with different C-factors was evaluated. METHODS: Cylindrical cavities, 1 mm deep and 3 mm in diameter (C-factor=2.3) or 2 mm in diameter (C-factor=3) were prepared on flat superficial bovine dentin surfaces. The teeth were restored with Clearfil Photo Bond, Clearfil Liner Bond 2 or Super-Bond D Liner adhesive systems followed by Photo Clearfil Bright composite. The resins were cured with a conventional method using 600 mW/cm2 (tip-to-resin distance 0 mm) for 60 s, or the slow-start curing method of 270 mW/cm2 (tip-to-resin distance 10 mm) for 10 s, followed by a 5-s interval, then 50 s at 600 mW/cm2. After thermocycling, a dye penetration test was carried out. The dye penetration length was calculated as a percentage of the total cavity wall length. RESULTS: Cavity-wall gap formation increased when the C-factor increased from 2.3 to 3, except in one material, Super-Bond D Liner, which showed good marginal sealing and resin composite adaptation to the cavity wall regardless of light curing method and C-factor. CONCLUSION: It is necessary to take care when a cavity with a high C-factor is to be restored with resin composite. The combination of a flexible adhesive and the slow-start curing method would seem to be effective in reducing polymerization contraction stress for large C-factor cavities.

Analysis of Variance↗

[Significance of radical recurrent tumor resection for recurrent gastric cancer as assessed by prognosis].

To evaluate the relationship between radical surgery of recurrent tumor and prognosis in cases of recurrent gastric cancer, we analyzed data on 202 patients with relapsed gastric cancer, focusing on surgical recurrent tumor removal. In our series, 18 of the 202 patients underwent radical recurrent tumor resection. Resected tumors were located in the ovarium (n = 4), colorectum (n = 3), liver (n = 3), lymph node (n = 2), locoregional stoma (n = 2), and peritoneum, adrenal gland, brain, and lung (n = 1 each). No surgery-related mortality occurred. One patient remains alive over 5 years after hepatectomy without recurrence, and 17 died within 3 years: 7 patients from primary recurrence and 10 from multiple modes of recurrence. Median survival after recurrence (MSTAR) in the 18 radical surgery patients was 14 months, against 5 months in those treated palliatively (p = 0.0001). MSTAR for the ovary and the liver were 30 months and 15 months in the radical surgery cases, and 2.5 months for the ovary and 5 months for the liver in the palliative cases. Significant differences were thus seen between radical and palliative cases in the ovary (p = 0.010) and in the liver (p = 0.036). Median survival after gastrectomy was 45 months in the radical surgery cases, and 28 months in the palliative cases (p = 0.024). In postoperative gastric cancer follow-up, early detection of recurrence and radical surgery may well benefit patients with relapse, especially in the liver and ovary, in terms of survival.

Colonic Neoplasms↗

[Temporary placement of inferior vena cava filter prior to transcatheter arterial embolization (TAE) for hepatocellular carcinoma with IVC tumor thrombus--prevention of pulmonary tumor emboli after TAE].

A 66-year-old-man with a right huge hepatocellular carcinoma (HCC) extending into both the right portal vein and the right atrium underwent transcatheter arterial embolization (TAE) via the right hepatic artery. Prior to the TAE, a temporary inferior vena cava (IVC) filter was placed suprarenally for prevention of pulmonary tumor emboli. When we replaced the temporary IVC filter with a new one 7 days after the TAE, the filter which was pulled out of the IVC captured a fragment of the tumor thrombus. A histopathological specimen demonstrated only ghost cells. The patient has been followed at our outpatient clinic without any tumor thrombus or pulmonary infarction for 13 months after this procedure.

Aged↗

Crystallization in low-energy deposition of titanium ions.

To investigate crystallization in the ion beam deposition process, titanium ions were deposited on silicon wafers at 105 and 55 eV. As titanium is an active metal, titanium compounds are formed by absorbing backfilled or residual gas. At energy levels of 105 or 55 eV, titanium crystallizes in a NaCl-type titanium compound with the backfilling of air. In all samples, (110)-oriented crystals grew with a rectangular lattice arrangement of titanium atoms. The open channel <110> of preferentially oriented crystal growth was parallel to the direction of incident ions normal to the substrate surface.

Journal Article↗

Enhancement of the in vivo osteogenic potential of marrow/hydroxyapatite composites by bovine bone morphogenetic protein.

A composite of marrow mesenchymal stem cells and porous hydroxyapatite (HA) has in vivo osteogenic potential. To investigate factors enhancing the osteogenic potential of marrow/HA composites, we prepared a bone morphogenetic protein (BMP) fraction from the 4M guanidine extract of bovine bone by heparin-sepharose affinity chromatography. Marrow/HA composites or composites containing marrow mesenchymal stem cells, BMP, and HA (marrow/BMP/HA composites) were implanted subcutaneously in 7-week-old male Fischer rats. BMP/HA composites and HA alone were also implanted. The implants were harvested after 2, 4, or 8 weeks and were prepared for histological and biochemical studies. Histological examination showed obvious de novo bone formation together with active osteoblasts at 2 weeks, as well as more extensive bone formation at 4 and 8 weeks in many pores of the marrow/BMP/HA composites. The marrow/HA composites did not induce bone formation at 2 weeks, but there was moderate bone formation at 4 weeks. At 2 weeks, only marrow/BMP/HA composites resulted in intensive osteogenic activity, judging from alkaline phosphatase and osteocalcin expression at both the protein and gene levels. These results indicate that the combination of marrow mesenchymal stem cells, porous HA, and BMP synergistically enhances osteogenic potential, and may provide a rational basis for their clinical application, although further in vivo experiment is needed.

Alkaline Phosphatase↗

Is gastric carcinoma different between Japan and the United States?

BACKGROUND: Analyses of surgical results for gastric carcinoma often lead to the conclusion that gastric carcinoma occurring in Japan is different from that diagnosed in the U.S. METHODS: To elucidate factors that might explain the differences in surgical results between the two countries, the authors compared data from a cancer center and a university hospital in Japan and a specialist cancer hospital in the U.S (Memorial Sloan-Kettering Cancer Center [MSKCC]). RESULTS: The mean age and body mass index were significantly greater in patients in the U.S. The N category appeared to be determined less accurately at MSKCC compared with the Japanese centers. The occurrence of early gastric carcinoma was not confined to Japanese patients because 20% of U.S. patients who underwent surgery were determined to have early stage disease. However, mucosal (in situ) carcinoma was detected rarely, and the proportion of advanced stage disease was greater in the U.S. Lesions in the upper gastric body, including the gastroesophageal junction, occurred in > 50% of cases at MSKCC but in only 20% of cases at the Japanese centers (P < 0.001). D2 lymph node dissection was possible with low morbidity and minimum mortality (31% and 3%, respectively, at MSKCC). The 5-year survival rates, stratified by tumor location and T category, revealed more similar results between Japan and the U.S. than had been reported previously. The marked difference between Japanese and American institutions only was observed for T1 and T2 tumors occurring in the lower gastric body and for T3 tumors occurring in the middle and upper third of the stomach. CONCLUSIONS: Based on the findings of the current study, it would appear that the more favorable outcome noted for gastric carcinoma patients in Japan primarily is explained by the differences in tumor location, a greater frequency of early stage disease, and more accurate staging compared with gastric carcinoma patients in the U.S. Results of gastric carcinoma treatment comparable to those obtained in Japan can be obtained in Western centers.

Adult↗

Sterol regulatory element-binding protein-1 is regulated by glucose at the transcriptional level.

In vivo studies suggest that sterol regulatory element-binding protein (SREBP)-1 plays a key role in the up-regulation of lipogenic genes in the livers of animals that have consumed excess amounts of carbohydrates. In light of this, we sought to use an established mouse hepatocyte cell line, H2-35, to further define the mechanism by which glucose regulates nuclear SREBP-1 levels. First, we show that these cells transcribe high levels of SREBP-1c that are increased 4-fold upon differentiation from a prehepatocyte to a hepatocyte phenotype, making them an ideal cell culture model for the study of SREBP-1c induction. Second, we demonstrate that the presence of precursor and mature forms of SREBP-1 protein are positively regulated by medium glucose concentrations ranging from 5. 5 to 25 mm and are also regulated by insulin, with the amount of insulin in the fetal bovine serum being sufficient for maximal stimulation of SREBP-1 expression. Third, we show that the increase in SREBP-1 protein is due to an increase in SREBP-1 mRNA. Reporter gene analysis of the SREBP-1c promoter demonstrated a glucose-dependent induction of transcription. In contrast, expression of a fixed amount of the precursor form of SREBP-1c protein showed that glucose does not influence its cleavage. Fourth, we demonstrate that the glucose induction of SREBP could not be reproduced by fructose, xylose, or galactose nor by glucose analogs 2-deoxy glucose and 3-O-methyl glucopyranose. These data provide strong evidence for the induction of SREBP-1c mRNA by glucose leading to increased mature protein in the nucleus, thus providing a potential mechanism for the up-regulation of lipogenic genes by glucose in vivo.

Animals↗

Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene.

Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis as a key regulator of fuel metabolism. SREBP-1c regulates its downstream genes by changing its own mRNA level, which led us to sequence and analyze the promoter region of the mouse SREBP-1c gene. A cluster of putative binding sites of several transcription factors composed of an NF-Y site, an E-box, a sterol-regulatory element 3, and an Sp1 site were located at -90 base pairs of the SREBP-1c promoter. Luciferase reporter gene assays indicated that this SRE complex is essential to the basal promoter activity and confers responsiveness to activation by nuclear SREBPs. Deletion and mutation analyses suggest that the NF-Y site and SRE3 in the SRE complex are responsible for SREBP activation, although the other sites were also involved in the basal activity. Gel mobility shift assays demonstrate that SREBP-1 binds to the SRE3. Taken together, these findings implicate a positive loop production of SREBP-1c through the SRE complex, possibly leading to the overshoot in induction of SREBP-1c and its downstream genes seen in the livers of refed mice. Furthermore, reporter assays using larger upstream fragments indicated another region that was inducible by addition of sterols. The presence of the SRE complex and a sterol-inducible region in the same promoter suggests a novel regulatory link between cholesterol and fatty acid synthesis.

Animals↗

Isolation of a cDNA for a novel human RING finger protein gene, RNF18, by the virtual transcribed sequence (VTS) approach(1).

We have recently developed a novel database system, designated as the virtual transcribed sequence (VTS) which efficiently extracts many genes from public human genome databases, and tested the feasibility of this novel computational approach (N. Miyajima, C. Burge, T. Saito, Biochem. Biophys. Res. Commun. 272 (2000) 801; http://host45.maze.co.jp/vts/). In this study, using the VTS approach, we isolated a cDNA for a novel human gene with RING finger motif (C(3)HC(4)), which is not deposited in public EST databases. The isolated cDNA clone is 2163 bp in length, and contains an open reading frame of 452 amino acids. We designated the novel gene as RNF18. A database search showed that the RNF18 gene had the moderate similarity to SS-A/Ro52 protein, which is a ribonucleoprotein reactive with autoantibodies in patients with Sjögren's syndrome and systemic lupus erythematosus. Tissue distribution analyses by Northern blot and RT-PCR methods demonstrated that the RNF18 messenger RNA was preferentially expressed in testis. The exon-intron boundaries of RNF18 gene were determined by aligning the cDNA sequence with the corresponding genome sequence. The isolated cDNA consists of eight exons that span about 11 kb of the genome DNA. The precise chromosomal location of the RNF18 gene was determined by PCR-based radiation hybrid mapping, and the gene was located to centromere region of chromosome 11 between markers NIB1900 and D11S1350. Taken together, the VTS approach should provide a novel cDNA cloning strategy for isolating unidentified genes, which are not found even in EST databases but are detectable computationally.

Amino Acid Sequence↗

Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction.

BACKGROUND: No-reflow phenomenon after primary coronary angioplasty is associated with poorer left ventricular (LV) function and prognosis after acute myocardial infarction (AMI). The purpose of this study was to determine the clinical significance of preinfarction angina in the no-reflow phenomenon. METHODS AND RESULTS: A total of 40 patients with first anterior AMI were examined. All patients underwent primary balloon angioplasty or stenting within 12 h of the onset of AMI. No-reflow, defined as TIMI grade 2 flow or less without residual stenosis after angioplasty, was observed in 15 patients. Patients with no-reflow were older (67+/-9 vs. 58+/-10 years, P=0.006) and had a lower incidence of preinfarction angina (7% vs. 48%, P=0.01) than those without no-reflow. Patients with no-reflow had poorer LV function at predischarge and a higher incidence of pump failure, LV aneurysm, malignant ventricular arrhythmias or cardiac death during the hospital course in association with higher peak serum C-reactive protein levels (12.7+/-8.0 vs. 7.1+/-5.5 mg/dl, P=0.02). Multivariate analysis showed that the absence of preinfarction angina was a major independent determinant of no-reflow (RR=17.1, P=0.02). CONCLUSIONS: The absence of preinfarction angina is more frequently observed in patients with no-reflow. The beneficial effect of preinfarction angina on LV function may be explained, at least in part, by prevention of no-reflow after reperfusion.

Adult↗

Isolation of novel mouse genes differentially expressed in brain using cDNA microarray.

The major issue in the post-genome sequencing era is determination of gene expression patterns in variety of biological systems. A microarray system is a powerful technology for analyzing the expression profile of thousands of genes at one experiment. In this study, we identified highly expressed genes in mouse brain using the cDNA microarray carrying 2304 cDNAs derived from oligo-capped mouse cDNA library. Nine genes were highly expressed in adult mouse brain compared to kidney, liver, and skeletal muscle. Tissue distribution analysis by reverse transcription-coupled polymerase chain reaction (RT-PCR) revealed that consistent with the microarray data, all of the selected 9 genes were predominantly expressed in the brain. A database search showed that 5 of the 9 genes, MBP, SC1, HiAT3, S100 protein-beta, and SNAP25, were previously known to be expressed at high level in the brain and in the nervous system. One gene was highly sequenced similar to rat S-Rex-s/human NSP-C, suggesting that the gene is a mouse homologue. The remaining three genes did not match to known genes in the GenBank/EMBL database, indicating that these are novel genes highly expressed in the brain. Taken together, our cDNA microarray system can be an excellent tool for identifying differentially expressed genes in mouse brain.

Animals↗

Cross-protection against a lethal influenza virus infection by DNA vaccine to neuraminidase.

Cross-protection against a lethal influenza virus infection was examined in BALB/c mice immunized with plasmid DNAs encoding the neuraminidase (NA) from different subtype A viruses. Each NA-DNA was administered twice, 3 weeks apart, at the dose of 1 microg per mouse by particle-mediated DNA transfer to the epidermis (gene gun) or at a dose of 30 microg per mouse by electroporation into the muscle. Three weeks after the second vaccination, the mice were challenged with lethal doses of homologous or heterologous viruses and the ability of each NA-DNA to protect the mice from influenza was evaluated by determining the lung virus titers, body weight and survival rates. The H3N2 virus NA-DNA conferred cross-protection against lethal challenge with antigenic variants within the same subtype, but failed to provide protection against infection by a different subtype virus (H1N1). The degree of cross-protection against infection was related to titers of the cross-reacting antibodies. These results suggest that NA-DNA can be used as a vaccine component to provide effective protection against infection not only with homologous virus but also with drift viruses.

Amino Acid Sequence↗

Induction of aldose reductase in cultured human microvascular endothelial cells by advanced glycation end products.

Accelerated formation and accumulation of advanced glycation end products, as well as increased flux of glucose through polyol pathway, have been implicated in the pathogenesis of diabetic vascular complications. We investigated effects of advanced glycation end products on the levels of aldose reductase mRNA, protein, and activity in human microvascular endothelial cells. When endothelial cells were cultured with highly glycated bovine serum albumin, aldose reductase mRNA in endothelial cells demonstrated concentration-dependent elevation. The increase in aldose reductase mRNA was accompanied by elevated protein expression and enzyme activity. Significant increase in the enzyme expression was also observed when endothelial cells were cultured with serum obtained from diabetic patients with end-stage renal disease. Pretreatment of the endothelial cells with probucol or vitamin E prevented the advanced glycation end products-induced increases in aldose reductase mRNA and protein. Electrophoretic mobility shift assays using the nuclear extracts of the endothelial cells treated with advanced glycation end products showed enhancement of specific DNA binding activity for AP-1 consensus sequence. These results indicate that accelerated formation of advanced glycation end products in vivo may elicit activation of the polyol pathway, possibly via augmented oxidative stress, and amplify endothelial cell damage leading to diabetic microvascular dysfunction.

Aldehyde Reductase↗

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.

The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.

Adenocarcinoma↗

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Adenocarcinoma↗

Postanoxic T lymphocyte-endothelial cell interactions induce tumor necrosis factor-alpha production and neutrophil adhesion: role of very late antigen-4/vascular cell adhesion molecule-1.

The objective of this study was to define the influence of postanoxic T-lymphocyte-endothelial cell interactions on anoxia-reoxygenation (A/R)-induced neutrophil-endothelial cell adhesion and cell adhesion molecule (CAM) expression on human umbilical vein endothelial cells (HUVECs). HUVEC monolayers were exposed to 60 minutes of anoxia, followed by 24 hours of reoxygenation, wherein freshly isolated human T lymphocytes were added at 6 hours during reoxygenation. After an additional 18 hours of incubation (ie, total of 24 hours of reoxygenation), the T-cell/endothelial cell (TC/EC) coculture media were collected and added to naive HUVEC monolayers incubated with neutrophils. Although the A/R-conditioned media per se had no effect on neutrophil adhesion, the media from TC/EC cocultures significantly increased the adhesion response. This enhanced adhesive interaction was associated with significant increases in tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) levels in the TC/EC coculture media and was accompanied by a pronounced increase in endothelial E-selectin expression. Treatment of the TC/EC coculture media with anti-TNF-alpha or anti-IL-8 antibodies reduced the media-induced neutrophil adhesion response. The enhanced neutrophil adhesion and the elevated medium levels of TNF-alpha, but not IL-8, were markedly reduced by inserts that prevented direct TC/EC contact and by monoclonal antibodies directed against vascular cell adhesion molecule-1 (VCAM-1) or very late antigen-4 (VLA-4). Collectively, these findings show that VLA-4-/VCAM-1-mediated interactions between T lymphocytes and postanoxic endothelial cells stimulates TNF-alpha production, which in turn elicits endothelial cell adhesion molecule expression and a corresponding increase in neutrophil adhesion.

Cell Adhesion↗