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Biomedical subjects

T Sumi

Publications and source records attributed to T Sumi.

At least 19 recordsLinked to original sources

Measurement of acoustic output power in a traveling wave engine.

We built and tested a double-loop thermoacoustic cooler consisting of an engine-loop, a branch resonator, and a cooler-loop. The cooling power of 6.4 W was obtained at the cooling temperature of 0 degrees C, when the input heat power of 416 W was supplied to the engine-loop. We measured the acoustic power and found that the output power emitted from the engine-loop was 12 W, and that the input acoustic power entering the cooler-loop was 6 W.

Journal Article↗

Interleukin 10 and transforming growth factor beta contribute to the development of experimentally induced allergic conjunctivitis in mice during the effector phase.

AIM: To investigate the involvement of interleukin (IL)10 and transforming growth factor (TGF) beta in the development of experimentally induced allergic conjunctivitis in mice. METHODS: Balb/c mice were actively sensitised with ragweed in alum, and then challenged with ragweed in eye drops after 10 days. 24 h later, the conjunctivas, spleens and blood were collected for histological and cytokine expression analyses, proliferation and cytokine production assays and measurement of immunoglobulin (Ig) levels. Mice developing experimentally induced allergic conjunctivitis were injected intraperitoneally with 200 microg of anti-IL10 or anti-TGF beta antibodies at 0, 2, 4, 6 and 8 days (induction phase treatment) or 500 microg of antibodies 2 h before ragweed challenge (effector phase treatment). Normal rat IgG was used for control injections. RESULTS: Treatment with either anti-IL10 or anti-TGF beta antibodies during the induction phase did not affect eosinophil infiltration into the conjunctiva. By contrast, treatment with either antibody during the effector phase suppressed infiltration. During the effector phase, treatment with anti-TGF beta antibody, but not the anti-IL10 antibody, markedly up regulated proliferation and Th2 cytokine production by splenocytes. IL1alpha levels in the conjunctiva were reduced after treatment with either antibody; in addition, eotaxin and tumour necrosis factor alpha levels were reduced after treatment with antibody to TGF beta. CONCLUSIONS: IL10 and TGF beta do not have immunosuppressive roles in the development of experimentally induced allergic conjunctivitis. Rather, they augment the infiltration of eosinophils into the conjunctiva during the effector phase of experimentally induced allergic conjunctivitis.

Adoptive Transfer↗

Enhancement of antitumor activity of herpes simplex virus gamma(1)34.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide.

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.

Acetamides↗

Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol.

PKC inhibitor safingol suppressed the growth of human oral squamous cell carcinoma (SCC) cells significantly at concentrations that inhibit PKC isoforms. Safingol inhibited the translocation of PKC following treatment with 12-o-tetradecanoylphorbol 13-acetate (TPA) in PKC alpha-EGFP-transfected cells, but not in PKC beta-EGFP- transfected cells, indicating selective inhibition for PKC alpha in oral SCC cells. Flow cytometric analysis and DNA analysis by agarose gel electrophoresis revealed an increase in the proportion of sub-G(1) cells and DNA fragmentation in safingol-treated cells. Mitochondrial membrane potential was decreased, and cytochrome c was released from mitochondria. However, the safingol-induced cell death was not accompanied by activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). The broad-spectrum caspase inhibitor BD-fmk failed to prevent safingol-induced cell death. Another apoptogenic factor endonuclease G, but not apoptosis-inducing factor (AIF), was also released from mitochondria and translocated to the nucleus. These results suggest that PKC alpha inhibitor safingol induces an endonuclease G- mediated apoptosis in a caspase-independent manner.

Apoptosis↗

Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma.

TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.

Administration, Oral↗

Search for low-mass exoplanets by gravitational microlensing at high magnification.

Observations of the gravitational microlensing event MOA 2003-BLG-32/OGLE 2003-BLG-219 are presented, for which the peak magnification was over 500, the highest yet reported. Continuous observations around the peak enabled a sensitive search for planets orbiting the lens star. No planets were detected. Planets 1.3 times heavier than Earth were excluded from more than 50% of the projected annular region from approximately 2.3 to 3.6 astronomical units surrounding the lens star, Uranus-mass planets were excluded from 0.9 to 8.7 astronomical units, and planets 1.3 times heavier than Saturn were excluded from 0.2 to 60 astronomical units. These are the largest regions of sensitivity yet achieved in searches for extrasolar planets orbiting any star.

Journal Article↗

Effect of Ca2+-dependent cell death on the release of herpes simplex virus.

The effect of a variety of cell death-inducing reagents on the release of herpes simplex virus type 1 (HSV-1) was examined. Ionomycin was found to increase the release of HSV-1, whereas no significant increase was observed by the treatment with TNF-alpha, anti-Fas antibody, C2-ceramide, sphingosine, H-7, tyrphostin and camptothecin. Ionomycin induced an immediate early peak and a subsequent long-lasting elevation of intracellular Ca(2+) concentration ([Ca(2+)]i). In the absence of extracellular Ca(2+), ionomycin neither elevated [Ca(2+)]i nor increased the release of HSV-1 from the infected cells, indicating that Ca(2+) influx play an important role in the release of HSV-1. Studies with trypan blue and annexin V staining revealed that the ionomycin-induced alteration of [Ca(2+)]i was accompanied by cell death of the infected cells. Disintegration of cell membrane, cytoplasmic vacuole formation and the leakage of virus particles from the cell surface were observed by electron microscopy. These results indicate that Ca(2+)-dependent cell death showing necrotic alteration is responsible for the enhanced release of HSV-1. The data also give some initial insights into the functional importance of cell death during the late stages of HSV-1 infection.

Calcium↗

Uterine cervical adenofibroma associated with Turner's syndrome in a young woman.

A 32-year-old woman with Turner's syndrome complained of abnormal genital bleeding, which was diagnosed as a delivered myoma. Vaginal myomectomy was performed, and the tumor was histopathologically diagnosed as an adenofibroma of the uterine corpus. As these are extremely rare, we report this case with a review of some of the literature.

Adenofibroma↗

Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma.

Malignant transformation of a mature cystic teratoma of the ovary is rare, that of an adenocarcinoma is extremely rare. A 32-year-old woman was suspected as having a malignant transformation of her mature cystic teratoma of the ovary because the preoperative level of carcinoembryonic antigen (CEA) was extremely high. Resections of her ovarian cysts were performed, and this particular tumor was histopathologically diagnosed as an adenocarcinoma arising from a mature cystic teratoma of the left ovary. Because adenocarcinomas arising from mature cystic teratomas of the ovary are extremely rare, we report this case with a review of some of the literature.

Adenocarcinoma↗

Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha.

LIM kinases (LIMK1 and LIMK2) regulate actin cytoskeletal reorganization through cofilin phosphorylation downstream of distinct Rho family GTPases. Pak1 and ROCK, respectively, activate LIMK1 and LIMK2 downstream of Rac and Rho; however, an effector protein kinase for LIMKs downstream of Cdc42 remains to be defined. We now report evidence that LIMK1 and LIMK2 activities toward cofilin phosphorylation are stimulated in cells by the co-expression of myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha), an effector protein kinase of Cdc42. In vitro, MRCKalpha phosphorylated the protein kinase domain of LIM kinases, and the site in LIMK2 phosphorylated by MRCKalpha proved to be threonine 505 within the activation segment. Expression of MRCKalpha induced phosphorylation of actin depolymerizing factor (ADF)/cofilin in cells, whereas MRCKalpha-induced ADF/cofilin phosphorylation was inhibited by the co-expression with the protein kinase-deficient form of LIM kinases. These results indicate that MRCKalpha phosphorylates and activates LIM kinases downstream of Cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of ADF/cofilin.

Animals↗

Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase.

LIM-kinase 1 (LIMK1) and LIM-kinase 2 (LIMK2) regulate actin cytoskeletal reorganization via cofilin phosphorylation downstream of distinct Rho family GTPases. We report our findings that ROCK, a downstream protein kinase of Rho, specifically activates LIMK2 but not LIMK1 downstream of RhoA. LIMK1 and LIMK2 activities toward cofilin phosphorylation were stimulated by co-expression with the active form of ROCK (ROCK-Delta3), whereas full-length ROCK selectively activates LIMK2 but not LIMK1. Activation of LIMK2 by RhoA was inhibited by Y-27632, a specific inhibitor of ROCK, but Rac1-mediated activation of LIMK1 was not. ROCK directly phosphorylated the threonine 505 residue within the activation segment of LIMK2 and markedly stimulated LIMK2 activity. A LIMK2 mutant with replacement of threonine 505 by valine abolished LIMK2 activities for cofilin phosphorylation and actin cytoskeletal changes, whereas replacement by glutamate enhanced the protein kinase activity and stress fiber formation by LIMK2. These results indicate that ROCK directly phosphorylates threonine 505 and activates LIMK2 downstream of RhoA and that this phosphorylation is essential for LIMK2 to induce actin cytoskeletal reorganization. Together with the finding that LIMK1 is regulated by Pak1, LIMK1 and LIMK2 are regulated by different protein kinases downstream of distinct Rho family GTPases.

Actin Depolymerizing Factors↗

KDN-containing glycoprotein from loach skin mucus.

It has been widely recognized that the mucus coat of fish plays a variety of important physical, chemical, and physiological functions. One of the major constituents of the mucus coat is mucus glycoprotein. We found that sialic acids in the skin mucus of the loach, Misgurnus anguillicaudatus, consisted predominantly of KDN. Subsequently, we isolated KDN-containing glycoprotein from loach skin mucus and characterized its chemical nature and structure. Loach mucus glycoprotein was purified from the Tris-HCl buffer extract of loach skin mucus by DEAE-cellulose chromatography, Nuclease P1 treatment, and Sepharose CL-6B gel filtration. The purified mucus glycoprotein was found to contain 38.5 KDN, 0.5% NeuAc, 25.0% GalNAc, 3.5% Gal, 0.5% GlcNAc and 28% amino acids. Exhaustive Actinase digestion of the glycoprotein yielded a glycopeptide with a higher sugar content and higher Thr and Ser contents. The molecular size of this glycopeptide was approximately 1/12 of the intact glycoprotein. These results suggest that approximately 11 highly glycosylated polypeptide units are linked in tandem through nonglycosylated peptides to form the glycoporotein molecule. The oligosaccharide alditols liberated from the loach mucus glycoprotein by alkaline borohydride treatment were separated by Sephadex G-25 gel filtration and HPLC. The purified sugar chains were analyzed b --> 6GalNAc-ol, KDNalpha2 --> 3(GalNAcbeta1 --> 14)GalNAc-ol, KDNalpha2 --> 6(GalNAcalpha1 --> 3)GalNAc-ol, KDNalpha2 --> 6(Gal3alpha1--> 3)GalNAc-ol, and NeuAcalpha2 --> 6Gal NAc-ol. It is estimated that one loach mucus glycoprotein molecule contains more than 500 KDN-containing sugar chains that are linked to Thr and Ser residues of the protein core through GalNAc.

Amino Acids↗

Primary abdominal pregnancy associated with severe ovarian hyperstimulation syndrome.

An uncommon case of primary abdominal pregnancy that was detected after rapid resolution of OHSS is reported. A 27-years-old nulligravida woman underwent ovarian hyperstimulation with human menoposal gonadotrophin (hMG) at another clinic and was admitted to our hospital with severe OHSS. Intravenous fluid therapy, albumin supplementation, and abodminal paracentesis was performed. The patient's massive ascites rapidly resolved, and she was discharged from our hospital. However, 4 weeks later, at about the 8th gestational week, she was readmitted to our hospital because of strong suspicion of abdominal pregnancy. Ultrasonography revealed a gestational sac (GS) and fetus with heartbeat in Douglas' pouch and an emergency laparotomy was performed. Both fallopian tubes, both ovaries and the uterus were completely intact and the GS was found on the anterior surface of the rectum. After removing GS, the muscle layer and serosal layer of the rectum were repaired. No bowel complications developed, and the post operative course was uneventful. To our knowledge, this is the first report of this very rare variant of ectopic pregnancy complicated by OHSS.

Adult↗

Vascular endothelial growth factor levels in pleural and peritoneal fluid in Meigs' syndrome.

We report that we found differences in changes in vascular endothelial growth factor (VEGF) levels in pleural effusion and ascites after removal of ovarian tumor complicated by Meigs' syndrome. Postoperative VEGF levels decreased in the patient's pleural fluid but not in the peritoneal fluid. The mechanism of the development of the pleural effusion and ascites in Meigs' syndrome may differ.

Ascitic Fluid↗

Purification and identification of N-glycolylneuraminic acid (Neu5Gc) from the holothuroidea Gumi, Cucumaria echinata.

N-Glycolylneuraminic acid (Neu5Gc), precious sialic acid which could not be synthesized by a chemical method, occurrs in the body of holothuroidea, Gumi Cucumaria echinata. Gumi contains 85% of total sialic acid, as Neu5Gc, in the body. Neu5Gc was purified from dry powder of the body using Dowex 1-x8 (HCOO* form) anion exchange chromatography after mild acid hydrolysis with 0.1 N trifluoroacetic acid. Using GC-MS and 1H-NMR spectroscopy, the purified Neu5Gc was correctly identified to be Neu5Gc. The purity of Neu5Gc was more than 99%. This is the first report of purification and identification of Neu5Gc from holothuroidea by using anion exchange chromatography, GC-MS, and 1H-NMR.

Animals↗

Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits.

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2-tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end-labeling assay. Plasma of the tumor-bearing rabbits was perfused repeatedly through non-coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3-methylhistidine / creatinine ratio (3-MH / Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3-MH / Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but improved LBM, DNA synthesis, and 3-MH / Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Animals↗

Expression of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing rabbits.

We reported finding that apoptosis occurred in skeletal muscle in the early stage after implantation. In the present study, we investigated expression of the apoptosis-related proteins Bax and Bcl-2 to determine the mechanism of the apoptosis. In the early stage of tumor bearing, 20 days after implantation, lean body mass (LBM) was reduced by 5.06 +/- 1.10% in the tumor-bearing group, compared with an increase of 4.96 +/- 1.26% in the control group. The apoptotic index (AI) of the skeletal muscle in the tumor-bearing group increased to 40.5 +/- 3.20% but was 0% in the control group, and Bax expression was strongly positive in 5 of the 10 rabbits in the tumor-bearing group, and significantly stronger than in the control group (P = 0.0002). In the late stage of tumor bearing, 40 days after implantation, the AI had declined to 0.93 +/- 0.96% in the tumor-bearing group, but was still 0% in the control group. Bax expression was rarely detected in either the tumor-bearing group or the control group, and there was no significant difference between the two groups (P = 0.706). No significant changes in Bcl-2 were observed in either group. The above results showed that apoptosis via Bax played a role in muscle wasting associated with progression of the malignant tumor. However, the apoptosis and expression of Bax were seen only in the early stage, within 20 days after implantation, not in the late stage. This suggested that the muscle wasting in the early stage might be caused by a different mechanism from that in the late stage.

Animals↗