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Biomedical subjects

Hitoshi Takagi

Publications and source records attributed to Hitoshi Takagi.

At least 55 records · Page 3Linked to original sources
PubMed2005

Pancreatic and gastric metastases of leiomyosarcoma arising in the left leg.

Pancreatic or gastric metastases from other primary malignancies are rare, especially from leiomyosarcoma. We report a case of leiomyosarcoma in the left lower leg with metastases to the pancreas and stomach. A 61-year-old man had liver cirrhosis caused by hepatitis C virus infection and was followed up by his primary physician. Two years before presentation at our hospital, he had undergone surgical resection of leiomyosarcoma in the left lower leg and systemic chemotherapy for multiple metastatic tumors in the lung. On admission, endoscopic examination and computed tomography were performed for a routine checkup to exclude esophageal varices and liver tumor. Although the patient had no specific symptoms, multiple gastric and pancreatic metastases were identified by endoscopy and computed tomography, respectively. In general, metastases to the pancreas and stomach are rare. We discuss the clinical and diagnostic findings of pancreatic and gastric metastases by reviewing previously reported cases.

Humans↗
PubMed2005

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.

Angiopoietin-2↗
PubMed2005

Is removal of internal limiting membrane always necessary during stage 3 idiopathic macular hole surgery?

PURPOSE: To determine the indications for internal limiting membrane (ILM) removal in stage 3 idiopathic macular holes (MHs). METHODS: Focal posterior vitreous detachments (PVDs) at MH rims were examined preoperatively by optical coherence tomography and binocular slit-lamp fundus examination in 19 patients retrospectively. All eyes underwent pars plana vitrectomy and creation of a PVD, and some eyes underwent a second surgery to remove the ILM. Indications of ILM removal for MH closure were discussed. RESULTS: Preoperatively, 9 eyes did not (non-PVD group) and 10 eyes did (PVD group) have complete focal PVDs. In all nine eyes in the non-PVD group, MHs were closed after the creation of a PVD without ILM peeling (P <0.05, chi test). In the PVD group, 5 eyes (50%) had MHs closed by making PVD complete without ILM removal, and 5 eyes (50%) required ILM removal in a second surgery. In the end, closure of MHs was achieved in all eyes. CONCLUSION: Anatomic closure of stage 3 idiopathic MHs without a PVD at the rim of the hole may be achieved only by creating a PVD without ILM removal.

Adult↗
PubMed2005

Efficacy of surgical removal of the internal limiting membrane in diabetic cystoid macular edema.

PURPOSE: To evaluate the efficacy of surgical removal of the internal limiting membrane (ILM) in diabetic cystoid macular edema (CME). METHODS: Prospective, noncomparative, interventional case series including 21 eyes of 18 consecutive patients with diabetic CME. Vitrectomy with separation of the posterior hyaloid and induction of posterior vitreous detachment had been performed previously on nine eyes. Pars plana vitrectomy for removal of the ILM was performed. RESULTS: CME resolved in eyes that underwent initial vitrectomy and in those with long-standing (>1 year) CME after previous vitrectomy. Postoperative best-corrected visual acuity improved by >/=2 lines of a Snellen equivalent in 14 eyes (67%) (P < 0.01). The mean foveal thickness (distance between the inner retinal surface and the retinal pigment epithelium) decreased from 553 microm to 221 microm at 4 weeks (P < 0.001). No recurrences or deterioration of CME was observed during the entire follow-up period (mean, 17.8 months; range, 8-34 months). CONCLUSION: Surgical removal of the ILM might be an effective procedure for reducing CME in patients with diabetes. A prospective, randomized, controlled study is necessary to further evaluate the efficacy of the procedure.

Adult↗
PubMed2005

Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels.

BACKGROUND: Adiponectin is a hormone secreted by adipocytes and has anti-diabetic and anti-atherogenic properties. Hypoadiponectinemia is associated with insulin-resistant diabetes and liver dysfunction. The aim of this study was to determine plasma adiponectin and insulin levels in patients with liver cirrhosis. METHODS: Adiponectin and insulin levels were determined in 38 patients with cirrhosis and 30 healthy controls, and were correlated with various clinical and biochemical parameters. Patients included 21 with Child A, eight Child B, and nine with Child C liver cirrhosis. RESULTS: Log adiponectin and insulin levels were significantly elevated in patients with cirrhosis compared with the control. In liver cirrhosis, the level of adiponectin increased proportionately with the Child's classification score. In control subjects, plasma adiponectin correlated inversely with insulin levels. In contrast, plasma adiponectin correlated positively with insulin levels in patients with liver cirrhosis. Plasma adiponectin levels did not correlate with age, sex, body mass index, total bilirubin, aspartate aminotransferase, and fasting blood sugar levels in both groups, while alanine aminotransferase correlated negatively with adiponectin in control subjects as reported previously. CONCLUSION: Our results of high plasma adiponectin in patients with liver cirrhosis could reflect an imbalance between its production by adipocytes and metabolism in the liver.

Adiponectin↗
PubMed2005

Long-term outcome of interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.

BACKGROUND: Autoimmune thyroid disorders are among the well-known adverse effects of interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis C. However, there are few reports regarding the long-term outcome of this complication. We aimed to evaluate the natural history of IFN-alpha-induced autoimmune thyroid disorders with long-term follow-up. METHODS: Four hundred and thirty-nine patients with chronic hepatitis C were treated with IFN-alpha for 24 weeks between March 1993 and April 1998. Seventeen of 439 (3.9%) patients developed symptomatic autoimmune thyroid disorders including nine cases of hyperthyroidism and eight cases of hypothyroidism. The patients with hypothyroidism were all women. These 17 patients were followed up for 71.1 +/- 17.8 months (48-120 months) and were evaluated for long-term outcome. RESULTS: Eight patients could discontinue the thyroid medication (2-36 months, median 10 months). Nine patients needed the thyroid medication at the follow-up period. The patients with hyperthyroidism who needed long-term thyroid medication had a significantly high titer of TSH receptor antibody on onset compared with the patients who could discontinue the thyroid medication. There were no significant differences in age, type of IFN, duration from IFN administration to onset, cessation of IFN, genotype of hepatitis C virus and thyroid hormone levels on onset between the patients who needed long-term thyroid medication and the patients who could discontinue the thyroid medication. CONCLUSION: All patients with IFN-alpha-induced thyroid disorders could be controlled with medication. However, the IFN-alpha-induced thyroid disorders are not always reversible. One must be careful about not only the development of autoimmune thyroid disorders during IFN-alpha therapy but also the outcome of the thyroid disease.

Adult↗
PubMed2005

Interferon-alpha-induced changes in metallothionein expression in liver biopsies from patients with chronic hepatitis C.

An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy (P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection.

Antiviral Agents↗
PubMed2005

Type 2 diabetes mellitus complicated with smoldering myeloma and non-alcoholic steatohepatitis.

We report a 59-year-old woman with type 2 diabetes mellitus (DM) complicated with smoldering myeloma and non-alcoholic steatohepatitis. A diagnosis of smoldering myeloma was made on the basis of elevation of IgA, M-protein (type:IgA-lambda) and histological findings of bone marrow without bone lesion. As to liver dysfunction, anti-HBV, anti-HCV and a series of auto-immune antibody were negative. She had no alcohol drinking habit and histological findings showed pericellular fibrosis without fatty degeneration, suggesting liver cirrhosis due to non-alcoholic steatohepatitis (NASH). To date, there are no reports of cases with DM, NASH and myeloma. Particular attention may be necessary for these complications.

Diabetes Mellitus, Type 2↗
PubMed2004

Efficient formation of vesicular stomatitis virus pseudotypes bearing the native forms of hepatitis C virus envelope proteins detected after sonication.

Hepatitis C virus (HCV) causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in addition to acute hepatitis. The HCV genome encodes two envelope glycoproteins, E1 and E2. To investigate the role of E1 and E2 in HCV infection, we used a recombinant vesicular stomatitis virus (VSV), VSVdeltaG*, harboring the green fluorescent protein gene instead of the VSV G envelope protein gene. It was complemented with the native form of E1 and E2, or E1 or E2 alone, to make HCV pseudotypes VSVdeltaG*(HCV), VSVdeltaG*(E1), and VSVdeltaG*(E2). Neither E1 nor E2 expression was detected on the cell surface, as reported. Unlike previous reports, infectious activities of VSVdeltaG*(HCV), VSVdeltaG*(E1) and VSVdeltaG*(E2) pseudotypes were detected under conditions where VSV was completely neutralized by anti-VSV. We could enhance the infectious titers 100-fold by sonication upon virus harvest. Bovine lactoferrin efficiently inhibited infection by VSVdeltaG*(HCV) as well as VSVdeltaG*(E2), as the interaction between E2 and lactoferrin has been thought to contribute to the inhibition of HCV infectivity. VSVdeltaG*(HCV) infected many adherent cell lines, including hepatic cell lines, but not most hematopoietic cell lines. Treatment of cells with trypsin, tunicamycin, or sulfated polysaccharides before infection reduced the infectivity of VSVdeltaG*(HCV) by about 90%, suggesting that a cell surface protein(s) with sugar chains plays an important role in HCV infection. The VSV pseudotypes developed here would be useful for analyzing the early stages of HCV infection.

Cell Line↗
PubMed2004

Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats.

PURPOSE: The angiopoietin (Ang)/Tie-2 system may play a role in vascular integrity and angiogenesis. In this study, we investigated alterations of the gene expression of Ang-1 and Ang-2 in the retinas of streptozotocin (STZ) induced diabetic rats. METHODS: In situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses were performed to determine the mRNA and protein content for Ang-1 and Ang-2 and the Tie2 receptor in the retinas of STZ diabetic and age matched control rats. RESULTS: Using in situ hybridization analysis, Ang-1, Ang-2, and Tie2 mRNA expression was observed in the ganglion cell layer (GCL) and the inner nuclear layer (INL). While Ang-2 mRNA expression did not changed after 2 weeks, 1 month, or 3 months of STZ induced diabetes, it was increased in the GCL and slightly elevated in the INL after 6 months of diabetes. In contrast, Ang-1 and Tie2 mRNA expression was stable at every timepoint during 6 months of STZ induced diabetes. RT-PCR and western blot analyses confirmed the increase of Ang-2 expression after 6 months of diabetes. Furthermore, double staining of alpha-smooth muscle actin (alphaSMA) and Ang-2 mRNA demonstrated that the SMA positive cells surrounding Ang-2-expressing cells were decreased in the GCL. CONCLUSIONS: Diabetes increases Ang-2 expression in the GCL accompanied by a reduction of alphaSMA positive perivascular cells. These changes may suggest a role for Ang-2 in the mechanism of pericyte loss in diabetic retinopathy.

Angiopoietin-1↗
PubMed2004

Phosphatidylinositol 3-kinase/Akt regulates angiotensin II-induced inhibition of apoptosis in microvascular endothelial cells by governing survivin expression and suppression of caspase-3 activity.

Angiotensin II (Ang II) plays essential roles in vascular homeostasis, neointimal formation, and postinfarct remodeling. Although Ang II has been shown to regulate apoptosis in cardiomyocytes and vascular smooth muscle cells, its role in vascular endothelial cells (ECs) remains elusive. To address this issue, we first performed TUNEL and caspase-3 activity assays with porcine microvascular ECs challenged by serum deprivation. Ang II significantly reduced the ratio of apoptotic cells and caspase-3 activity. The Ang II type 1 receptor (AT1) was responsible for these effects. Among the signaling molecules downstream of AT1, we revealed that PI3-kinase/Akt pathway plays a predominant role in the antiapoptotic effect of Ang II. Interestingly, the expression of survivin, a central molecule of cell survival, increased after Ang II stimulation. Overexpression of a dominant-negative form of Akt abolished both Ang II-induced antiapoptosis and survivin protein expression. In a murine model of hyperoxygen-induced retinal vascular regression, AT1a knockout mice showed a significant increase in retinal avascular areas. Our data indicate that Ang II plays a critical antiapoptotic role in vascular ECs by a mechanism involving PI3-kinase/Akt activation, subsequent upregulation of survivin, and suppression of caspase-3 activity.

Angiotensin II↗
PubMed2004

Laser photocoagulation of indocyanine green angiographically identified feeder vessels to idiopathic polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the efficacy of laser photocoagulation of indocyanine green angiographically identified feeder vessels to idiopathic polypoidal choroidal vasculopathic lesions. DESIGN: Interventional case series. METHODS: Fifteen eyes of 14 consecutive patients with idiopathic polypoidal choroidal vasculopathy lesions treated by laser photocoagulation of indocyanine green angiographically identified feeder vessels were investigated. RESULTS: In 10 of the 15 eyes, serous retinal detachment of sensory retina in the macula disappeared after photocoagulation of the feeder vessels. The best-corrected visual acuity improved by 2 or more lines in eight of the 15 eyes and worsened in two eyes during the mean follow-up period of 13.6 months. CONCLUSIONS: Laser photocoagulation targeted exclusively to the feeder vessels supplying the idiopathic polypoidal choroidal vasculopathy lesions is a safe and effective method and can improve vision in eyes in which a serous retinal detachment is present in the macula. Indocyanine green angiography-guided laser photocoagulation should be considered as an optional treatment for idiopathic polypoidal choroidal vasculopathy.

Aged↗
PubMed2004

Delayed absorption of macular edema accompanying serous retinal detachment after grid laser treatment in patients with branch retinal vein occlusion.

PURPOSE: To study the detailed process of macular edema (ME) absorption after grid laser photocoagulation in patients with branch retinal vein occlusion (BRVO). The influence of pretreatment serous retinal detachment (SRD) at the fovea on patient outcome was also evaluated. DESIGN: Retrospective, interventional, comparative case series. PARTICIPANTS: Thirty-seven BRVO patients presenting with severe ME. METHODS: Patients were treated with grid laser photocoagulation with 6 months of follow-up examinations. Baseline and post-treatment examinations included measurements of visual acuity (VA), fluorescein angiography, and detailed imaging of ME by optical coherence tomography (OCT). Macular thickness was defined as the distance from the inner retinal surface to the outer border of the sensory retina (foveal retinal thickness) and also to the inner border of the retinal pigment epithelium including the SRD (total foveal elevation). MAIN OUTCOME MEASURES: Post-treatment macular thickness with OCT, VA converted to the logarithm of the minimum angle of resolution, and absorption of SRD, and correlations of macular thickness and VA both before and after treatment. RESULTS: Total foveal elevation and VA were significantly improved at 1, 3, and 6 months after treatment. There was also a significant correlation between reduction of total foveal elevation and increase in VA. Fourteen eyes (37.8%) displayed SRD, as evidenced by OCT at the baseline. In eyes without SRD, foveal retinal thickness and VA had significantly improved in a time-dependent manner. However, although SRD itself was almost absorbed 6 months after treatment, the improvement of both VA and total foveal elevation in eyes with pretreatment SRD was not significant compared with baseline conditions. Both post-treatment total foveal elevation and VA of eyes with SRD tended to be worse than eyes without SRD. CONCLUSION: The presence of subfoveal SRD retards the absorption of ME and recovery of VA after grid laser photocoagulation in patients with BRVO.

Absorption↗
PubMed2004

Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization.

Transcription factor Ets-1 has been reported to regulate angiogenesis in vascular endothelial cells. Here, we investigated a mechanism that may regulate the expression of Ets-1 in vascular endothelial growth factor (VEGF)- and hypoxia-induced retinal neovascularization and that may have potential to inhibit ocular neovascular diseases. VEGF and hypoxia increased Ets-1 expression in cultured bovine retinal endothelial cells. The VEGF-induced mRNA increase of Ets-1 was suppressed by a tyrosine kinase inhibitor (genistein), by inhibitors of MEK (mitogen-activated protein and extracellular signal-regulated kinase kinase) (PD98059 and UO126), and by inhibitors of protein kinase C (GF109203X, staurosporine, and Gö6976). Dominant-negative Ets-1 inhibited VEGF-induced cell proliferation, tube formation, and the expression of neuropilin-1 and angiopoietin-2. In a mouse model of proliferative retinopathy, Ets-1 mRNA was up-regulated. Intravitreal injection of dominant-negative Ets-1 suppressed retinal angiogenesis in a mouse model of proliferative retinopathy. In conclusion, VEGF induces Ets-1 expression in bovine retinal endothelial cells and its expression is protein kinase C/ERK pathway-dependent. Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases.

Adenoviridae↗