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Biomedical subjects

Hideki Ohta

Publications and source records attributed to Hideki Ohta.

12 recordsLinked to original sources
PubMed2006

Vasohibin prevents arterial neointimal formation through angiogenesis inhibition.

Vasohibin is a VEGF-inducible angiogenesis inhibitor in vascular endothelium. Here we examined the presence of vasohibin in human arterial wall, and found it in endothelium of adventitial microvessels in atherosclerotic lesion. Adventitial angiogenesis is involved in the progression of neointimal formation. Even in the presence of endogenous angiogenesis inhibitors, pathological angiogenesis persists. However, the supplementation of exogenous angiogenesis inhibitors can prevent pathological angiogenesis. We evaluated the potential role of vasohibin in neointimal formation. Adenovirus-mediated human vasohibin gene transfer in mouse liver resulted in the release of vasohibin in plasma and exhibited anti-angiogenic effects at remote sites. This gene transfer inhibited adventitial angiogenesis, macrophage infiltration, and neointimal formation after cuff placement on mouse femoral artery. Vasohibin exhibited no direct effect on migration and proliferation of smooth muscle cells. Thus, vasohibin has an activity to prevent neointimal formation by inhibiting adventitial angiogenesis.

Adult↗
PubMed2006

Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin.

OBJECTIVE: We recently isolated vasohibin, a novel vascular endothelial growth factor (VEGF)-inducible endothelium-derived angiogenesis inhibitor. Our aim is to find DNA sequences homologous to vasohibin and determine their expression profile. METHODS AND RESULTS: By the search of DNA sequences in the database, we found one homologous gene and designated it vasohibin-2. Overall amino acid sequence homology between the prototype vasohibin (vasohibin-1) and vasohibin-2 was >50%. Vasohibin-2 exhibited antiangiogenic activity. Vasohibin-2 expression in cultured endothelial cells was low and not inducible by the stimulation that induced vasohibin-1. However, the immunohistochemical analysis revealed that vasohibin-1 and -2 were diffusely expressed in endothelial cells in embryonic organs during mid-gestation. After that time point, vasohibin-1 and -2 became faint, but persisted to a certain extent in arterial endothelial cells from late gestation to neonate. Expression of vasohibin-1 and -2 could be augmented in vivo by local transfection with the VEGF gene in the embryonic brain or by cutaneous wounding in adult mice. CONCLUSIONS: These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.

Angiogenesis Inhibitors↗
PubMed2006

Multiple processing forms and their biological activities of a novel angiogenesis inhibitor vasohibin.

Vasohibin is a newly identified negative feedback regulator for angiogenesis. When expressed in cultured human endothelial cells, vasohibin polypeptides were detected in multiple distinct molecular weight forms, suggesting that some proteolytic events may occur within cells or the pericellular milieu. In order to identify the proteolysis sites, vasohibin cDNA mutants were generated to substitute some basic amino acids with alanine and then were transfected into endothelial cells. Western blots with anti-vasohibin monoclonal antibody following the transfection showed that there were at least two cleaving sites in the amino terminal region. Purified recombinant protein of the amino terminal truncated forms not only retained its inhibitory activity on angiogenesis in mouse corneal assay but also showed strong affinity to heparin. Moreover, deletion of some basic residues at the carboxyl terminal resulted in abrogation of both antiangiogenic and heparin-binding activities. Processing patterns and biological activities of the processed forms of this novel antiangiogenic factor are discussed.

Amino Acid Sequence↗
PubMed2005

Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells.

We recently reported that vasohibin is a negative feedback regulator of angiogenesis, and it is specifically expressed in endothelial cells. Here, we characterize the regulation of vasohibin expression. Two possible splicing variants were found, and the longer isoform was preferentially expressed. VEGF induced the expression of vasohibin, and this induction was abrogated by anti-VEGFR2 mAb but not by anti-VEGFR1 mAb. Pharmacological analysis revealed that the downstream targets of VEGFR2 were PKCs, especially PKCdelta. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon VEGF treatment, whereas cycloheximide completely abolished its induction. We tested the effect of various inflammatory cytokines on vasohibin expression. TNFalpha, IL1 and IFNgamma decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFalpha treatment. These results indicate that the expression of vasohibin in endothelial cells is regulated either positively or negatively by certain factors at the transcriptional level.

Angiogenesis Inhibitors↗
PubMed2005

Successful surgical treatment for diffuse esophageal spasm.

A 74-year-old man, who had previously received curative distal gastrectomy for gastric cancer, was admitted to our hospital with severe dysphagia and weight loss. Barium swallow examination revealed the esophagus to have the corkscrew appearance characteristic of diffuse esophageal spasm (DES). This diagnosis was confirmed by esophageal manometry, which revealed intermittent, simultaneous, high-amplitude (30-100 mmHg) contractions after 65% of wet swallows. The muscle layer was also found to be thickened throughout the spastic region. Long esophagomyotomy with fundoplication was performed after treatment with medication proved ineffective. Myotomy proceeded superiorly to the area under aortic arch and inferiorly 3 cm into the cardiac portion. Fluoroscopy of the esophagus after the operation showed the spastic changes to be absent, and the patient showed improved clinical signs. We therefore recommend long myotomy of the esophageal wall with antireflux surgery for DES with sever dysphagia that is resistant to conservative treatment.

Aged↗
PubMed2005

[Chemotherapy for an esophageal cancer patient undergoing continuous ambulatory peritoneal dialysis for chronic renal failure and measurement of plasma concentration of the drug].

We administered chemoradiotherapy consisting of 5-fluorouracil (5-FU) combined with cisplatin, radiation and sequential chemotherapy using nedaplatin for an esophageal cancer patient undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure. There are no reports in the literature of chemotherapy for a patient maintained on CAPD. The dosage of each drug was based on that for a patient undergoing hemodialysis, and the plasma concentration of each drug was examined. Chemotherapy consisted of 3-10 mg/body of cisplatin with 60-min infusion and 450 mg/body of 5-FU with continuous infusion over 5 days. There were no side effects and no increase in the concentration of either of the drugs. Subsequently, 50 mg/body of nedaplatin, which is half the dose for a patient with normal renal function, was administered. The area under the blood concentration time curve (AUC) of nedaplatin was 15.85 microg/ml, which was slightly low compared with that after infusion of 80 mg/m2 in patients with normal renal function. Grade 3 leukopenia and thrombocytopenia occurred. As a final result, a partial response was obtained, and the patient was able to eat solid food after treatment. Although chemotherapy consisting of low-doses of cisplatin and 5-FU and a half dose of nedaplatin was administered safely, further study is needed to determine the suitable regimens for a patient maintained on CAPD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis.

Negative feedback is a crucial physiological regulatory mechanism, but no such regulator of angiogenesis has been established. Here we report a novel angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA microarray analysis to survey VEGF-inducible genes in human ECs. We characterized one such gene, KIAA1036, whose function had been uncharacterized. The recombinant protein inhibited migration, proliferation, and network formation by ECs as well as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the protein did not affect the migration of smooth muscle cells or fibroblasts. Specific elimination of the expression of KIAA1036 in ECs restored their responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was selective to ECs, and hypoxia or TNF-alpha abrogated its inducible expression. As this molecule is preferentially expressed in ECs, we designated it "vasohibin." Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect the proliferation of cancer cells in vitro, but did inhibit tumor growth and tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived negative feedback regulator of angiogenesis.

Amino Acid Sequence↗
PubMed2002

High-throughput miniaturized immunoassay for human interleukin-13 secreted from NK3.3 cells using homogenous time-resolved fluorescence.

A miniaturized immunoassay for human interleukin-13 (IL-13) using homogeneous time-resolved fluorescence (HTRF) has been developed. In this assay, IL-13 which was secreted from NK3.3 cells stimulated with interleukin-2 (IL-2) was detected by measuring the time-resolved fluorescence after adding a mixture of three reagents, biotinylated anti-IL-13 monoclonal antibody, europium cryptate (fluorescence donor)-labeled different anti-IL-13 monoclonal antibody and crosslinked allophycocyanin (fluorescence acceptor)-conjugated with streptavidin in a 384-well assay plate. The detection limit of IL-13 using this immunoassay was estimated to be less than 600 pg/ml and IL-13 levels measured by this method were very close to those measured by enzyme linked immunosorbent assay (ELISA; the correlation coefficient was 0.9535). The proposed assay requires only a fourth of the quantities of all reagents compared with the assay using a conventional 96-well microtiter plate. Furthermore, there is no need to transfer the culture supernatant to another assay plate and wash the plate. Therefore, this miniaturized immunoassay is economical and efficient and is particularly suitable for high-throughput drug screening.

Antibodies, Monoclonal↗