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Biomedical subjects

Yoshiaki Okada

Publications and source records attributed to Yoshiaki Okada.

At least 19 recordsLinked to original sources
PubMed2006

A novel class of vascular endothelial growth factor-responsive genes that require forkhead activity for expression.

Recently, we have shown that transient phosphorylation and inhibition of the pro-apoptotic transcription factor, forkhead, by vascular endothelial growth factor (VEGF) is essential for endothelial cell (EC) survival and proliferation. The goal of the present study was to determine whether forkhead (FKHR) also plays a positive role in agonist-mediated gene induction. Human coronary artery ECs were transduced with adenovirus overexpressing constitutively active phosphorylation-resistant triple mutant FKHR or transfected with small interference RNA (siRNA) against FKHR. The cells were then treated in the absence or presence of VEGF and assayed for gene expression using quantitative real-time PCR and Northern blots analyses. The data revealed a novel set of VEGF-responsive genes that require FKHR activity for optimal expression in ECs, including bone morphogenic protein 2, cbp/p300-interacting transactivator 2, decay accelerating factor (DAF), vascular cell adhesion molecule-1 (VCAM-1), manganese superoxide dismutase, endothelial-specific molecule-1, RING1 and YY1-binding protein, and matrix metalloproteinase-10. Consistent with a positive role for FKHR in mediating VEGF induction of DAF and VCAM-1 mRNA, siRNA against FKHR attenuated the effect of VEGF on complement-mediated EC lysis and monocyte adhesion, respectively. VEGF induction of the forkhead-dependent genes was down-regulated by the NF-kappaB inhibitor, constitutively active Ad-IkappaB, and in some cases by the nuclear factor of activated T-cells (NF-AT) inhibitor, cyclosporin. Together, these findings suggest that the VEGF-forkhead signaling axis plays an important functional role in ECs beyond the regulation of cell survival/apoptosis and cell cycle.

Adenoviridae↗
PubMed2006

Diffusion-weighted MRI predicts prognosis in severe hypoglycemic encephalopathy.

A 20-year-old woman presented unconscious due to hypoglycemia after a self-administered insulin injection. Diffusion-weighted MRI (DWI), performed 5 days after admission, demonstrated heterogeneous high-intensity signal areas in both the cortex and subcortex but sparing the motor and sensory centers. On the 11th day after admission, she began making incomprehensible verbal sounds, eye opening spontaneously and moving her extremities with pyramidal tract signs. Three months later, she had aphasia, agnosia and apraxia but a normal gait without pyramidal tract signs or ataxia. DWI is thus considered useful to predict the functional outcome of patients with severe hypoglycemia.

Adult↗
PubMed2006

Evaluation of 10 commercial diagnostic kits for in vitro expressed hepatitis B virus (HBV) surface antigens encoded by HBV of genotypes A to H.

Genetic variability of the hepatitis B virus (HBV) constitutes one of the major challenges for diagnosis of HBV infection. It is plausible that amino acid substitutions in the "a" determinant of the HBV surface antigen (HBsAg) that affect antigenic sites, whether originating from genetic diversity or from mutations in the HBV strain itself, will affect the sensitivity of some diagnostic kits. In fact, recent studies have indicated that some diagnostic kits had false negative results with particular HBsAg mutants. There have been, however, few substantial studies evaluating sensitivities of diagnostic kits to the HBsAg encoded by different HBV genotypes. Our recent study found that 10 diagnostic kits available in Japan were able to detect HBsAg irrespective of whether it originated from HBV genotypes A, B or C, with the latter two genotypes being the dominant species in East Asia. In this study, we extended our previous efforts by assessing the ability of diagnostic kits to detect recombinant HBsAg derived from HBV genotypes A to H. Our results demonstrated that 9 out of 10 diagnostic kits evaluated were able to detect as low as 0.2 International Units (IU)/ml HBsAg, irrespective of HBV genotype. The genotypic differences in the HBV family thus appear to have little impact on the sensitivity of currently available HBsAg diagnostic kits.

Cell Line↗
PubMed2006

RUNX1 suppression induces megakaryocytic differentiation of UT-7/GM cells.

The transcription factor RUNX1 plays a crucial role in hematopoiesis. RUNX1 regulates both differentiation and proliferation of hematopoietic cells. Several reports have shown that RUNX1 participates in megakaryopoiesis, which is a process that leads to formation of platelets. However, to date, the mechanisms by which this occurs have not been fully elucidated. In the present study, we investigated whether siRNA-mediated depletion of RUNX1 affected megakaryopoiesis of UT-7/GM cells. The depletion of RUNX1 in UT-7/GM cells resulted in up-regulation of the expression of megakaryocytic markers and polyploidization, while cell proliferation was down-regulated. Furthermore, the overexpression of RUNX1 decreased the activity of megakaryocytic gene promoters. These results suggest that RUNX1 down-regulates terminal differentiation of megakaryocytes and promotes proliferation of megakaryocytic progenitors.

Cell Differentiation↗
PubMed2006

Medium (DMEM/F12)-containing chitosan hydrogel as adhesive and dressing in autologous skin grafts and accelerator in the healing process.

Autologous skin grafts are considered necessary for the treatment of extensive skin defects. However, skin graft by suturing is a time-consuming medical handling and rather stressful event for recipients. To that end, tissue adhesives have been suggested in skin grafts. Chitosan hydrogel is well known as a wound dressing and tissue adhesive material showing biocompatibility, anti-infective activity, and the ability to accelerate wound healing. In this report, we evaluated the application of the chitosan hydrogel as a tissue adhesive in skin grafts. Although chitosan hydrogel shortened the operation time and resulted in a high graft absorption rate in comparison with suturing, wound epithelization was rather retarded. On the other hand, chitosan hydrogel was found more biocompatible than the commonly used tissue adhesive octyl-2-cyanoacrylate. When the chitosan hydrogel was premixed with a serum-free tissue culture medium DMEM/F12, it was found to easily degrade and promote wound epithelization. Histological examination revealed that the medium (DMEM/F12)-containing chitosan hydrogel was associated with the accumulation of polymorphonuclear leukocytes and neovascularization. In addition, immunohistochemical staining showed that the vascular endothelial growth factor (VEGF) was localized in the chitosan hydrogel degraded matrices. And infiltration of leukocytes determined the degradation activity with the D-glucose in the medium (DMEM/F12) suggested to play a central role in chitosan hydrogel degradation. Therefore, the medium (DMEM/F12)-containing chitosan hydrogel may become commonly accepted as a beneficial wound dressing and tissue adhesive in extensive wound management and skin grafts.

Animals↗
PubMed2006

Photoacoustic monitoring of neovascularities in grafted skin.

BACKGROUND AND OBJECTIVE: In skin grafting, evaluation of graft adhesion to the recipient site in the early postgrafting period is important. However, conventional diagnoses such as visual observation and thermography required about 1 week to obtain results and these methods cannot give quantitative information on the adhesion of a skin graft. We proposed a new method for monitoring adhesion of grafted skin that is based on measurement of photoacoustic signals. To investigate the validity of the method, we performed experiments using rat autografts models. STUDY DESIGN/MATERIALS AND METHODS: Grafted skin in a rat was irradiated with 200 microJ, 532-nm nanosecond laser pulses, and photoacoustic signals were detected with a piezoelectric transducer placed on the skin at various postgrafting time. Temporal profiles of the signals were converted to depth profiles using an assumed sound velocity of 1,500 m/second. Histological analysis was performed to observe neovascularities formed in the grafts. RESULTS: At 6 hours postgrafting, a photoacoustic signal peak appeared in the depth region corresponding to the graft. The results of histological analysis also showed formation of neovascularities in the graft after 6 hours postgrafting, indicating that photoacoustic signal peaks observed in the graft originated from the neovascularities, which are an indication of graft adhesion. For up to 24 hours postgrafting, no significant difference was observed between the results of visual observation and laser Doppler imaging of the same grafted skins. CONCLUSION: We have demonstrated that photoacoustic signals originating from neovascularities in grafts can be sensitively detected in the early postgrafting period, suggesting the validity of photoacoustic measurement for adhesion monitoring of skin grafts.

Acoustics↗
PubMed2006

Indications and limitations of induced hypothermic therapy for out-of-hospital cardiopulmonary arrest.

PURPOSE: To identify candidates indicated to undergo induced hypothermic therapy (IHT) among comatose survivors of out-of-hospital cardiopulmonary arrest (CPA) based on a retrospective review of medical charts. METHODS: Between 1995 and 2004, 49 patients who recovered from CPA and treated by IHT were analyzed. The subjects were divided into 2 groups. The first group (GR, n = 16) consisted of patients with a recovery of consciousness and the second group (VD, n = 33) consisted of patients who either remained unconscious or who died. RESULTS: Using a multiple logistic regression analysis, out-of-hospital return of spontaneous circulation was the only factor independently associated with the outcome (odds ratio, 0.03; 95% confidence interval, 0.00-0.23; P = .001). CONCLUSION: IHT may be beneficial for CPA patients with out-of-hospital return of spontaneous circulation. Because of the small sample size, further large human studies are warranted.

Adult↗
PubMed2006

Suppression of RUNX1 by siRNA in megakaryocytic UT-7/GM cells.

RUNX1 is a transcription factor that plays critical roles in hematopoietic proliferation and differentiation. Megakaryocyte is a precursor cell of platelets. Several reports have implied that RUNX1 is important in megakaryocytic differentiation and proliferation. However, the mechanism is not well understood. In this study, we employed a megakaryocytic cell line UT-7/GM and suppressed the RUNX1 gene expression by siRNA. Knocking down of RUNX1 induced the increase of megakaryocyte-specific gene expression and down-regulation of polyploidization. RUNX1 overexpression decreased the PF4 and GPIIb promoter activities. These results suggest that RUNX1 promotes proliferation of megakaryocytic cell line but not megakaryocytic gene expression in UT-7/GM cells.

Cell Proliferation↗
PubMed2006

Effect of induction rate for mild hypothermia on survival time during uncontrolled hemorrhagic shock in rats.

BACKGROUND: Rapid induction of hypothermia has been shown to improve survival in uncontrolled hemorrhagic shock (UHS) rat studies. We hypothesized that prolonged induction of hypothermia would be equally beneficial for survival during UHS. METHODS: Light anesthesia was induced with halothane in 30 rats, and spontaneous breathing was maintained. Rectal temperature (Tr) was monitored and maintained at 38 degrees C. UHS was induced by blood withdrawal of 2.5 mL/100 g during a 15-minute period, followed by 75% tail amputation. Immediately after cutting the tail, rats were randomized into three groups of 10 rats each: Group 1, maintained at Tr 38 degrees C; group 2, passively cooled to 34 degrees C by exposure to room temperature (23 degrees C); and group 3, actively cooled to 34 degrees C by applying alcohol to the skin and under an electric fan. Next, rats were controlled at each target Tr and observed without fluid resuscitation until either death or a maximum of 240 minutes. RESULTS: Cooling rate was -0.09 +/- 0.01 degrees C/min in group 2 and -0.36 +/- 0.9 degrees C/min in group 3 (p < 0.01). Mean survival time was 72 +/- 21 minutes in group 1 (38 degrees C), and was nearly doubled by hypothermia to 132 +/- 62 minutes for group 2 (p < 0.01 vs. group 1) and 150 +/- 69 minutes for group 3 (p < 0.01 vs. group 1). No significant difference in survival was noted between groups 2 and 3. Additional blood loss from the tail stump did not differ significantly between groups. CONCLUSION: Therapeutic mild hypothermia, induced either slowly (approximately -0.1 degrees C/min) or rapidly (approximately -0.4 degrees C/min) prolongs survival during lethal UHS in rats.

Animals↗
PubMed2006

Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection.

Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.

Animals↗
PubMed2006

[A case of difficulty for differential diagnosis between encephalitis and acute disseminated encephalomyelitis].

A seventy-four-male with disorientation and convulsion was transferred to this hospital after three days fever which was unknown origin. Because the examination of cerebrospinal fluid were; cell count 1,560/3 (N : L = 4 : 1), protein 305 mg/dl, sugar 91 mg/dl, he was treated as encephalitis. However, MRI of the 18th hospital day revealed bilateral thalamic lesion and disseminated white matter lesions, suggesting acute disseminated encephalomyelitis. He left dementia after treatment and transferred to another hospital. Since, it is difficult to make a differential diagnosis between encephalitis and acute disseminated encephalomyelitis, early establishment of diagnostic criteria for acute disseminated encephalomyelitis is required.

Aged↗
PubMed2005

Intubation without premedication may worsen outcome for unconsciousness patients with intracranial hemorrhage.

To clarify the influence of an intubation maneuver with or without premedication for an intracranial hemorrhage in an unconsciousness patient, we retrospectively analyzed 70 patients who had received intubation for unconsciousness and in whom a nontraumatic intracranial hemorrhage was found by CT over a 6-year period. They were divided into 2 groups, consisting of a drug group (n=15), wherein drugs were used before intubation, and control group (n=55), wherein no drugs were used before were intubation. The physical findings on admission, CT findings, Glasgow Outcome Score (GOS) at 3 months from admission were analyzed between the groups. There were no significant differences in the backgrounds of the subjects between the groups. The GOS in the control group was significantly higher than in the drug group (P<.001). In cases of intubation for unconscious patients who may have intracranial hemorrhaging, premedication is considered associated with a more favorable outcome.

Analgesics, Opioid↗
PubMed2005

Lymphocytosis without anemia in a patient presenting with anaphylactic shock.

We retrospectively investigated whether anaphylactic shock tends to be associated with lymphocytosis or not. We reviewed the medical charts of patients who had shock between January 1999 and September 2004. The subjects were divided into 4 groups, consisting of anaphylactic, hemorrhagic, cardiogenic, and septic groups. The results of laboratory examinations were analyzed. Regarding cellular differences, the lymphocyte-total leukocyte ratio in the anaphylactic group was significantly greater than that in the other groups. The average number of lymphocytes in the anaphylactic group was also significantly greater than that in both the hemorrhagic and septic groups. In addition, the average value of hemoglobin in the anaphylactic group was significantly greater than that in the other groups. The identification of lymphocytosis without anemia may therefore enable clinicians to accurately differentiate various states of shock in patients presenting with shock at the ED.

Age Distribution↗