Search PubMed⌕ Search

Biomedical subjects

Yuichi Yoshida

Publications and source records attributed to Yuichi Yoshida.

At least 19 recordsLinked to original sources
PubMed2006

C/EBPalpha and HNF6 protein complex formation stimulates HNF6-dependent transcription by CBP coactivator recruitment in HepG2 cells.

We previously demonstrated that formation of complexes between the DNA-binding domains of hepatocyte nuclear factor 6 (HNF6) and forkhead box a2 (Foxa2) proteins stimulated Foxa2 transcriptional activity. Here, we used HepG2 cell cotransfection assays to demonstrate that HNF6 transcriptional activity was stimulated by CCAAT/enhancer-binding protein alpha (C/EBPalpha), but not by the related C/EBPbeta or C/EBPdelta proteins. Formation of the C/EBPalpha-HNF6 protein complex required the HNF6 cut domain and the C/EBPalpha activation domain (AD) 1/AD2 sequences. This C/EBPalpha-HNF6 transcriptional synergy required both the N-terminal HNF6 polyhistidine and serine/threonine/proline box sequences, as well as the C/EBPalpha AD1/AD2 sequences, the latter of which are known to recruit the CREB binding protein (CBP) transcriptional coactivator. Consistent with these findings, adenovirus E1A-mediated inhibition of p300/CBP histone acetyltransferase activity abrogated C/EBPalpha-HNF6 transcriptional synergy in cotransfection assays. Co-immunoprecipitation assays with liver protein extracts demonstrate an association between the HNF6 and C/EBPalpha transcription factors and the CBP coactivator protein in vivo. Furthermore, chromatin immunoprecipitation assays with hepatoma cells demonstrated that increased levels of both C/EBPalpha and HNF6 proteins were required to stimulate association of these transcription factors and the CBP coactivator protein with the endogenous mouse Foxa2 promoter region. In conclusion, formation of the C/EBPalpha-HNF6 protein complex stimulates recruitment of the CBP coactivator protein for expression of Foxa2, a transcription factor critical for regulating expression of hepatic gluconeogenic genes during fasting.

Amino Acid Sequence↗
PubMed2006

Questionnaire on perioperative antibiotic therapy in 2003: postoperative prophylaxis.

We distributed a questionnaire to institutions accredited by the Japan Surgical Society asking about the use of antibiotics in digestive tract surgery in Japan in 2003, and compared the results with those of a similar questionnaire distributed in 1993. The period of antibiotic administration for esophageal resection was at least 6 days in 64.9% of the 1993 questionnaire responses, but less than 4 days in 60.4% of the present questionnaire responses. For distal gastrectomy, antibiotics were given for 5 days postoperatively at 53.0% of the responding institutions in the 1993 survey, but for only 3 days, at 72.4%, in the present survey. An oral antibiotic was given as part of antibacterial colon preparation before colon resection at 70% or more of the institutions in the 1993 survey, while no antibiotic colon preparation was given at 80% of the institutions in the present survey. The period of antibiotic administration for laparoscopic cholecystectomy was at least 4 days in 72% of the institutions in the 1993 survey, but this decreased remarkably to fewer than 2 days at 80.8% of the institutions in the current survey. There were no differences in the selection of antibiotics between the two surveys. The period of antibiotic administration has decreased remarkably in the last decade.

Anti-Bacterial Agents↗
PubMed2006

Creating a manual for proper hand hygiene and its clinical effects.

PURPOSE: To prevent cross-infections, we created a manual for the treatment of infectious wounds that clarifies when to wash one's hands and when to wear gloves. METHODS: Six patients with widespread infectious wounds caused by methicillin-resistant Staphylococcus aureus (MRSA) were treated. The bacterial count on the hands of the staff was calculated. We then compared the number of patients with MRSA isolated, and typed the MRSA isolates using pulsed-field gel electrophoresis (PFGE). RESULTS: The pathogenic bacterial count among hospital staff before treatment/before hand hygiene was 8.2 x 10 colony-forming units (cfu)/hand, which were not detected before treatment/after hand hygiene. The pathogenic bacterial count on the hands before hand hygiene/after treatment climbed to 9.1 x 10(5) cfu/hand, and after treatment/after hand hygiene decreased to 0.38 cfu/hand. The number of patients with MRSA isolates before this protocol was 15/402 (3.7%), but that level significantly decreased to 5/411 (1.2%) after implementation of the manual. There were 13 strains of type F by PFGE before the manual was adopted, but five strains of MRSA isolated after the present manual was enforced were all observed to have different migration patterns. CONCLUSION: A hand hygiene manual is effective for decreasing the rate of cross-infection.

Anti-Infective Agents, Local↗
PubMed2006

Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte proliferation during mouse liver regeneration.

BACKGROUND & AIMS: The hepatocyte nuclear factor 6 (HNF6 or ONECUT-1) protein is a cell-type specific transcription factor that regulates expression of hepatocyte-specific genes. Using hepatocytes for chromatin immunoprecipitation (ChIP) assays, the HNF6 protein was shown to associate with cell cycle regulatory promoters. Here, we examined whether increased levels of HNF6 stimulate hepatocyte proliferation during mouse liver regeneration. METHODS: Tail vein injection of adenovirus expressing the HNF6 complementary DNA was used to increase hepatic HNF6 levels during mouse liver regeneration induced by partial hepatectomy, and DNA replication was determined by bromodeoxyuridine incorporation. Cotransfection and ChIP assays were used to determine transcriptional target promoters. RESULTS: Elevated expression of HNF6 during mouse liver regeneration causes a significant increase in the number of hepatocytes entering DNA replication (S phase), and mouse hepatoma Hepa1-6 cells diminished for HNF6 levels by small interfering RNA transfection exhibit a 50% reduction in S phase following serum stimulation. This stimulation in hepatocyte S-phase progression was associated with increased expression of the hepatocyte mitogen tumor growth factor alpha and the cell cycle regulators cyclin D1 and Forkhead box m1 (Foxm1) transcription factor. Cotransfection and ChIP assays show that tumor growth factor alpha, cyclin D1, and HNF6 promoter regions are direct transcriptional targets of the HNF6 protein. Coimmunoprecipitation assays with regenerating mouse liver extracts reveal an association between HNF6 and FoxM1 proteins, and cotransfection assays show that HNF6 stimulates Foxm1 transcriptional activity. CONCLUSIONS: These mouse liver regeneration studies show that increased HNF6 levels stimulate hepatocyte proliferation through transcriptional induction of cell cycle regulatory genes.

Adenoviridae↗
PubMed2005

Drug susceptibility of isolates from severe postoperative intraperitoneal infections causing multiple organ failure.

PURPOSE: To select the most appropriate antibiotic regimens for life-threatening postoperative infections, we obtained isolates from patients with severe postoperative infections over a 12-year-period, and examined their drug susceptibility. METHODS: The subjects of this study were 55 patients with multiple organ failure (MOF) caused by postoperative infection. RESULTS: All strains of Methicillin-resistant Staphylococcus aureus (MRSA) were susceptible to Vancomycin (VCM) and Teicoplanin (TEIC). Only 0.3% of all the Pseudomonas aeruginosa strains were resistant to Imipenem (IPM), but 53.6% of the strains from the severe infections were resistant to IPM. On the other hand, there were few P. aeruginosa strains resistant to Meropenem (MEPM), Ceftazidime (CAZ), Ciprofloxacin (CPFX), and Pazufloxacin (PZFX), even among strains isolated from severe infections. The resistant rate of Bacteroides fragilis to Clindamycin (CLDM) was 35.9%, but there were strains resistant to IPM and Panipenem. CONCLUSION: These findings suggest that VCM or TEIC are most appropriate for severe abdominal abscess caused by MRSA, whereas MEPM, CAZ, CPFX, and PZFX are more effective against P. aeruginosa infections. The only antibiotic effective against B. fragilis infections in this study was IPM.

Abdominal Abscess↗
PubMed2005

Supplement of tetrahydrobiopterin by a gene transfer of GTP cyclohydrolase I cDNA improves vascular dysfunction in insulin-resistant rats.

Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction in the insulin-resistant state. We intended to develop a new gene transfer method by overexpression of its biosynthetic enzyme, GTP cyclohydrolase I (GTP-CH1). The GTP-CH1 cDNA was inserted into a pCAGGS vector, and then plasmid DNA was mixed with atelocollagen, and the aliquot was injected into thigh muscles of insulin-resistant Zucker fatty rats. After 4 weeks, pteridine derivative levels, superoxide anion (O2-), activity of endothelial nitric oxide synthase (eNOS), and endothelium-dependent relaxation were evaluated in the aortas obtained from Zucker lean or fatty rats. The BH4 contents and GTP-CH1 activity in Zucker fatty rats were 50%-55% less than those of Zucker lean rats. However, those impairments were significantly improved by a plasmid DNA injection, and aortic BH4 content reached more than 80% of the level of Zucker lean rats. Increased A23187-stimulated O2- production as well as decreased eNOS activity and endothelial function in insulin-resistant Zucker fatty rats were improved by a plasmid DNA injection to a level similar to that in Zucker lean rats. These findings suggest that intramuscular GTP-CH1 gene transfer using atelocollagen serves as a useful method of long-term systemic delivery of BH4 and the treatment of endothelial dysfunction.

Adipose Tissue↗
PubMed2005

Effects of growth factors on the growth and differentiation of mouse fetal liver epithelial cells in primary cultures.

BACKGROUND AND AIMS: Growth factors (GF) are thought to affect the growth and differentiation of hepatocytes during liver development. However, in the midfetal liver, little is known concerning the role of GF. METHODS: The DNA synthesis of fetal liver epithelial cells (FLEC) in monolayer culture and the liver-specific gene expressions of FLEC in 3-D culture were examined in medium supplemented with various GF. RESULTS: DNA synthesis of FLEC was higher than that of adult hepatocytes without GF, and was increased by hepatocyte growth factor (HGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). However, FLEC responded less to GF in terms of DNA synthesis than adult hepatocytes. The liver-specific gene expressions were increased in the presence of HGF, HB-EGF, bFGF and EGF. In embryonic day (E) 13.5 FLEC, this increase was more apparent in the presence of HB-EGF, whereas in E14.5 FLEC, it was more apparent in the presence of HGF. CONCLUSIONS: Hepatocyte growth factor, HB-EGF, bFGF, EGF and TGF-alpha increased DNA synthesis of FLEC. HGF, HB-EGF, bFGF and EGF led to an increase in liver-specific gene expressions; and their effects on differentiation differ as a function of gestation age.

Animals↗
PubMed2004

Recovery of the susceptibility of isolated bacterium achieved by giving long-established antibiotics as prophylaxis against postoperative infections.

PURPOSE: To evaluate the effectiveness of operative antibiotic therapy we changed the antibiotics and examined the susceptibility of the postoperative infection. METHODS: We studied 4 593 patients who underwent gastrointestinal surgery during the last 12.5 years, and examined the changes in intraoperative antibiotics, the return of bacteria isolated from infectious sites, the trends in frequency of Methicillin-resistant Staphylococcus aureus (MRSA) isolation, and changes in the antibiotic susceptibility of Pseudomonas aeruginosa and Bacterioides fragilis. We changed the antibiotics to Cefazolin (CEZ) for upper gastrointestinal tract surgery and cholecystectomy, and to Cefotiam (CTM) for colonic, liver, and pancreatic surgery. We also reduced the period of drug administration. RESULTS: The rate of MRSA infections decreased, the rate of P. aeruginosa infections was always under 20% and the rate of B. fragilis infections increased. After the guidelines of drug susceptibility were prepared, the minimum inhibitory concentrations (MICs) of Cefsulodin (CFS) and Piperacillin (PIPC) for P. aeruginosa and of Latamoxef (LMOX) and PIPC for B. fragilis, decreased. CONCLUSION: The use of antibiotics considered comparatively old for the prophylaxis of postoperative infection prevented the emergence of MRSA-like resistant strains, influenced changes in Gram-negative bacteria drug susceptibility, and led to an overall reduction in multiple drug resistance.

Anti-Bacterial Agents↗
PubMed2004

Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors.

BACKGROUND/AIMS: Evidence that bone marrow cells have trans-differentiating potential to hepatocytes has been described in recent reports. However, the molecular mechanism underlying this phenomenon is unclear. To address this issue, we investigated the parameters involved in the trans-differentiation of bone marrow cells into a hepatic lineage. METHODS: Mouse BM cells were cultured in a collagen gel without or with growth factors including basic fibroblast growth factor. The expression of hepatocyte-specific markers, cholangiocyte-specific marker and liver-enriched transcription factors was identified by RT-PCR and immunohistochemistry. RESULTS: Basic fibroblast growth factor was found to be the most effective for inducing albumin in cultured BM cells. Furthermore, on stimulation of basic fibroblast growth factor, BM cells were found to express other hepatocyte-specific markers and a cholangiocyte-specific marker. This conversion was found to be associated with the induction of transcription factors including hepatocyte nuclear factors and GATA family proteins. CONCLUSIONS: We established an in vitro culture system in which mouse bone marrow cells could trans-differentiate to hepatic lineage cells in response to growth factors, without cell fusion. In particular, basic fibroblast growth factor has the ability to induce the trans-differentiation into hepatic lineage cells from BM cells.

Albumins↗
PubMed2004

Subcutaneous solitary fibrous tumor.

We describe a unique case of subcutaneous solitary fibrous tumor (SFT) in a 56-year-old female patient. The patient had been aware of a painless soft mass in her back for ten years. The lesion was surgically excised. Histological examination revealed that the well-defined mass was composed of a proliferation of spindle-shaped fibroblastic cells and polygonal cells embedded in a fibrous matrix corresponding to the so-called "patternless pattern". A prominent pericytomatous pattern (hemangiopericytoma-like structures), focal myxoid changes, and thick hyalinized collagen fibers were also observed. Immunohistochemical stainings for CD34 and bcl-2 were positive in the tumor cells. These features are compatible with SFT. We suggest that SFT should be included in the differential diagnosis of subcutaneous spindle cell tumors.

Antigens, CD34↗
PubMed2004

Thymoma.

Explore the source record for details and available documents.

Humans↗
PubMed2003

Gab1 is required for EGF receptor signaling and the transformation by activated ErbB2.

Grb2-associated binder-1 (Gab1) is a pleckstrin homology (PH) domain-containing adapter molecule that is believed to function downstream of receptors for growth factors and cytokines. We previously found that deficiency in the mouse Gab1 gene led to embryonic lethality and defects in ERK activation in response to growth factors and cytokines. Here, we established immortalized Gab1-/- cell lines and analysed roles of Gab1 in growth factor-mediated signaling and oncogenesis. EGF-dependent activation of c-Raf and Mek1/2, which function upstream of ERKs, was perturbed in Gab1-/- cells. EGF-mediated upregulation of GTP-bound form of Ras was also reduced in these cells. EGF-dependent GTP/GDP exchange activity for Ras was suppressed in the Gab1-/- cells and expression of a constitutively active Sos restored ERK activation in these cells, indicating that Gab1 functions upstream of Ras. Furthermore, activated form of ErbB2 (active ErbB2)-mediated transformation, such as colony formation in soft agar and tumor formation in nude mice, was strongly suppressed when the Gab1-/- cells were transfected with active ErbB2, whereas the active Sos efficiently induced transformation of Gab1-/- cells. The data show that Gab1 plays an essential role in EGF-receptor/ErbB-mediated cell proliferation and oncogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2003

iC3b arrests monocytic cell differentiation into CD1c-expressing dendritic cell precursors: a mechanism for transiently decreased dendritic cells in vivo after human skin injury by ultraviolet B.

Our previous data indicated that C3, its bioactive product iC3b, and the iC3b ligand CD11b are critical for ultraviolet-induced immunosuppression. We thus hypothesized that iC3b is an important skin-based factor regulating CD11b+ monocytic cell function in the acute post-ultraviolet period. Although monocytic cell migration peaked at 1-3 d after ultraviolet exposure of skin, dermal CD1c dendritic cells underwent a rapid and prolonged depletion that did not recover until day 7. Because ultraviolet-induced iC3b deposits are reciprocally maximal on day 3, but fade by day 7, we next hypothesized that iC3b can be responsible for the delay in differentiation into dendritic cells of monocytic cells migrating into ultraviolet-exposed skin. Analysis of dermal cells derived from keratome biopsies suggested that iC3b exposure could inhibit the development of CD1c+ dermal cells. To model newly immigrating blood monocytes entering ultraviolet-exposed, iC3b-containing dermis, purified monocytes from human blood were induced with granulocyte-macrophage colony stimulating factor to generate a population of dendritic cell precursors expressing CD1c. Incubation with iC3b markedly inhibited the appearance of CD1c+ cells (p<0.05) and induced CD1c-CD14+ cells. This inhibition was reversed by coincubation with an anti-CD11b antibody that blocks the iC3b binding site. Other functions associated with dendritic cell maturation were also inhibited by iC3b, such as interleukin-12p70 production as well as CD80 and CD40 expression. Restimulation of monocytes for DC maturation revealed that iC3b induced a temporary inhibition of DC differentiation. Thus, a human skin response in which iC3b is transiently (3-7 d) generated in dermis, such as ultraviolet, can arrest monocytic skin-infiltrating cells from undergoing dendritic cell precursor differentiation.

Animals↗
PubMed2003

Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy.

BACKGROUND & AIMS: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is synthesized in the form of a membrane-anchored precursor (proHB-EGF), which subsequently is processed proteolytically to mature HB-EGF. This study describes the effects of HB-EGF on liver regeneration after 70% partial hepatectomy in proHB-EGF transgenic mice with liver-specific expression. METHODS & RESULTS: No significant differences in liver/body weight ratios and in bromodeoxyuridine (BrdU)-labeling index (the ratios of BrdU-positive hepatocyte nuclei) were found between adult transgenic and wild-type mice. However, in regenerating liver after partial hepatectomy, transgenic mice had higher liver/body weight ratios than wild-type mice and at 120 hours reached a level equal to that before partial hepatectomy. The BrdU-labeling index was about 5 times higher in the livers of transgenic mice compared with the wild type (51.5% vs. 10.2%, respectively; P < 0.01) at 48 hours after partial hepatectomy. Activation of microtubule-associated protein kinase after partial hepatectomy was higher and earlier in the transgenic mice as compared with the wild-type mice. Soluble HB-EGF was increased in the liver (at 8 min) after partial hepatectomy, indicating that the shedding of proHB-EGF occurred after partial hepatectomy. CONCLUSIONS: The transgenic expression of HB-EGF accelerates the proliferation of hepatocytes after partial hepatectomy, suggesting that HB-EGF functions as a hepatotrophic factor in vivo.

Animals↗
PubMed2003

Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.

BACKGROUND & AIMS: Obesity is one of the risk factors for liver fibrosis, in which plasma adiponectin, an adipocytokine, levels are decreased. Hepatic stellate cells play central roles in liver fibrosis. When they are activated, they undergo transformation to myofibroblast-like cells. Adiponectin suppresses the proliferation and migration of vascular smooth muscle cells, whose characteristics are similar to those of hepatic stellate cells. Adiponectin could have biological significances in liver fibrosis. METHODS: The role of adiponectin on liver fibrosis induced by the administration of carbon tetrachloride twice a week for 12 weeks was tested by using adiponectin-knockout mice and an adenovirus-mediated adiponectin-expression system. We also investigated the effect of adiponectin in activated hepatic stellate cells. RESULTS: When mice were administered carbon tetrachloride (300 microL/kg body weight) twice a week for 12 weeks, knockout mice showed extensive liver fibrosis with an enhanced expression of transforming growth factor-beta 1 and connective tissue growth factor compared with wild-type mice (P < 0.05). Injection of adenovirus producing adiponectin (AdADN) before carbon tetrachloride (1000 microL/kg body weight) treatment prevented liver fibrosis in wild-type mice (P < 0.001). Injection of AdADN at 6 weeks attenuated liver fibrosis even though carbon tetrachloride was given for an additional 6 weeks (total of 12 weeks). In cultured hepatic stellate cells, adiponectin suppressed platelet-derived growth factor-induced proliferation and migration and attenuated the effect of transforming growth factor-beta 1 on the gene expression of transforming growth factor-beta 1 and connective tissue growth factor and on nuclear translocation of Smad2. CONCLUSIONS: The findings indicate that adiponectin attenuates liver fibrosis and could be a novel approach in its prevention.

Active Transport, Cell Nucleus↗