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Biomedical subjects

Y Tomita

Publications and source records attributed to Y Tomita.

At least 19 recordsLinked to original sources
PubMed1999

The role of polymorphonuclear leukocyte infiltration in herpes simplex virus infection of murine skin.

We undertook the present study to investigate the role of polymorphonuclear leukocytes (PMN) in defending skin against herpes simplex virus (HSV) infection. For this purpose, we established a mouse model of cutaneous HSV infection. The hind limb footpad skin of 4-week-old ICR mice was abraded linearly once with a feather edge file and infected with various strains of HSV with different virulence. In uninfected control mice, PMN appeared at the abraded skin lesion within 24 h, and were eliminated from the epidermis after 3 days. Mice inducted with a highly virulent strain of HSV demonstrated wide and severe erythematous lesions of the footpad skin and histologically, virus antigen-positive ballooning degenerated keratinocytes were observed. However, in infections with attenuated strains of HSV, the epidermis was regenerated and a viral antigen was discharged within 5 days, together with any infiltrated PMN. Macrophages and NK cells numbered less than PMN. In mice treated with anti-PMN antiserum before HSV infection, PMN infiltration was significantly suppressed 1 day after infection, and these animals developed a severe cutaneous disease even if infected with an attenuated virus. These results indicate the importance of PMN in the control of HSV cutaneous infections, especially in the primary infectious phase.

Animals↗
PubMed1999

Interferon-alpha and 5-fluorouracil therapy in patients with metastatic renal cell cancer: an open multicenter trial. The Japanese Study Group Against Renal Cancer.

OBJECTIVES: Recent clinical trials have implied the cytotoxic and antiproliferative effects of combining 5-fluorouracil and interferon-alpha in the treatment of metastatic renal cell cancer. We therefore conducted an open multicenter trial to test the efficacy of such a combination on this cancer. METHODS: Human lymphoblastoid interferon (3 MIU per patient) was administered subcutaneously three times weekly for 12 weeks, while 5-fluorouracil was administered (600 mg/m2/day) as a continuous infusion for the first 5 days, followed by an intravenous bolus infusion of 600 mg/m2 once a week from the 3rd week until the 12th week. RESULTS: Of the 63 patients entered into the trial, 55 were eligible and evaluable for systemic toxicities, and 53 were evaluable for their response. All patients had undergone a prior nephrectomy, and their European Cooperative Oncology Group (ECOG) performance status ranged from 0 to 3 (median 0). Three complete and eight partial responses were induced, with an overall response rate of 20.0%. The median time to progression and the median survival time were 11 and 33 months, respectively. World Health Organization grade 3 toxicities were observed in 8 patients; however, no grade 4 toxicities or toxicity-related deaths were noted. CONCLUSIONS: Combination therapy of interferon-alpha plus 5-fluorouracil at the above-described dosage and schedule produced no better responses than interferon monotherapies. Prolongation of survival could be attributable to the fair performance status of the patients. This regimen has limited value for the treatment of patients with advanced renal cell cancer.

Adult↗
PubMed1999

[Extended resection of the great vessels for primary lung cancer and mediastinal tumor].

From 1973 to 1998, we resected and reconstructed the great vessels in 44 patients with primary lung cancer or mediastinal tumor. Among them, 39 patients (28 with lung cancer and 11 with mediastinal tumor) and 5 patients (all with lung cancer) underwent reconstruction of the superior vena cava (SVC) and aorta, respectively. The SVC was repaired by expanded polytetrafluoroethylene (EPTFE) graft (n = 8), prosthetic patch (n = 5) or direct suture (n = 26). The aorta was repaired with temporary subclavian artery-descending aorta (n = 3), or left atrium-femoral artery bypass (n = 2). No complication or operative death occurred after surgery. The survival rate of the patients with lung cancer who underwent SVC reconstruction at 3 year and 5 year were 26.2% and 11.2%, respectively. Five of 11 (45.5%) patients with mediastinal tumor are alive at 5 years. We concluded that extended resection for primary lung cancer or mediastinal tumor invading the SVC is acceptable operation method for some patients.

Adult↗
PubMed1999

Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods.

The purpose of the present study was to confirm the presence of beta3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (beta1, beta2, and beta3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta3-adrenoceptor agonists); and SR59230A (a putative selective beta3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta1-adrenoceptor-selective antagonist) and butoxamine (a beta2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that beta3-adrenoceptor may have some role in urine storage in the human urinary bladder.

Adrenergic beta-Agonists↗
PubMed1999

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder.

The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10(-10) M to 10(-6) M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3x10(-7) M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10(-10) M to 10(-6) M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10(-7) M to 10(-5) M) produced a marked shift to the right of the ET-1 concentration-response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2=7.96; slope=0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10(-7) M to 10(-5) M) had no effect on the ET-1 concentration-response curve. RT-PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

Aged↗
PubMed1998

Variable Bcl-2 phenotype in benign and malignant lesions of urothelium.

We examined Bcl-2, Bax and p53 expression in transitional epithelium, benign lesions derived from transitional epithelium (Brunn's nests and inverted papillomas) and transitional cell cancer (TCC) of the upper urinary tract and urinary bladder using immunostaining of cryostat sections. We also performed Western blot analysis of normal urothelium and TCCs for Bcl-2 and p53. Immunohistochemical staining showed that Bcl-2 was expressed only on basal layer cells, whereas Bax expression was restricted to superficial layers in normal transitional epithelium. Benign lesions of the urinary bladder (Brunn's nests and inverted papillomas) showed strong immunoreactivity to Bcl-2. Taken together, 16 (17%) TCCs were positive for Bcl-2, 62 (64.6%) TCCs were positive for Bax and 28 (29%) TCCs were positive for p53. The expression of Bcl-2 on TCC had a statistical correlation with tumor stage, histopathologic grade and p53 protein accumulation. The results suggest that although Bcl-2 overexpression is detected in normal urothelium and benign lesions of the urinary bladder, it might also contribute to the high grade tumor malignancy of TCC.

Adult↗
PubMed1998

Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of TRP, expressed in Xenopus oocytes.

To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4 homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for TRP-R. While non-injected oocytes elicited an SOC response, significantly larger responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC response was inhibited by injection of antisense oligodeoxyribonucleotide for mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50 value was much smaller in oocytes expressing TRP-R than that of non-injected oocytes. These results suggest that TRP-R functions as SOC having higher sensitivity to external Ca2+ than amphibian TRP1 channel.

Animals↗
PubMed1998

Distribution of glycoproteins with beta-N-acetylgalactosaminylated N-linked sugar chains among bovine tissues.

Only a small number of glycoproteins has been reported to contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure. Our previous studies showed that most glycoproteins from bovine milk fat globule membranes contain beta-N-acetylgalactosaminylated N-linked sugar chains [Sato et al., J. Biochem. 114 (1993) 890-900]. In order to study how widely this glycosylation occurs, lectin blot analysis of membrane glycoproteins from 12 bovine tissues was performed using Wistaria floribunda agglutinin (WFA), which interacts with oligosaccharides terminating with N-acetylgalactosamine. The WFA-positive bands were detected in samples from most tissues except for intestine although the number and reactivity of bands to lectin varied among the tissues. Upon pretreatment of blotted filters with Bacillus beta-N-acetylgalactosaminidase or N-glycanase, no lectin binding was observed. WFA-agarose column chromatography of oligosaccharides released by hydrazinolysis from membrane glycoproteins of bovine tissues except for intestine revealed that a few to 18% of the released oligosaccharides bind and are eluted from the column with 100 mM N-acetylgalactosamine. These results indicate that many glycoproteins from a variety of bovine tissues contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure, suggesting a wider occurrence of this glycosylation in bovine tissues.

Acetylgalactosamine↗
PubMed1998

Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: comparison with the human fibronectin crystal structure.

We report the three-dimensional solution structure of the mouse fibronectin cell attachment domain consisting of the linked ninth and tenth type III modules, mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment activity of intact fibronectin. Essentially complete signal assignments and approximately 1800 distance and angle restraints were derived from multidimensional heteronuclear NMR spectra. These restraints were used with a hybrid distance geometry/simulated annealing protocol to generate an ensemble of 20 NMR structures having no distance or angle violations greater than 0.3 A or 3 degrees. Although the beta-sheet core domains of the individual modules are well-ordered structures, having backbone atom rmsd values from the mean structure of 0.51(+/-0.12) and 0.40(+/-0.07) A, respectively, the rmsd of the core atom coordinates increases to 3.63(+/-1.41) A when the core domains of both modules are used to align the coordinates. The latter result is a consequence of the fact that the relative orientation of the two modules is not highly constrained by the NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR structures are very similar to the core domains of the crystal structure of hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a less extended and more flexible structure than the fully extended rod-like crystal structure. The radius of gyration, Rg, of mFnFn3(9,10) derived from small-angle neutron scattering measurements, 20.5(+/-0.5) A, agrees with the average Rg calculated for the NMR structures, 20.4 A, and is ca 1 A less than the value of Rg calculated for the X-ray structure. The values of the rotational anisotropy, D ||/D perpendicular, derived from an analysis of 15N relaxation data, range from 1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7 (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative the crystal structure having calculated anisotropies in best agreement with experiment. In addition, the relaxation parameters indicate that several loops in mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to picosecond time-scale. Taken together, our results suggest that, in solution, the limited set of interactions between the mFnFn3(9,10) modules position the RGD and synergy regions to interact specifically with cell surface integrins, and at the same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for some variation in integrin structure or environment.

Amino Acid Sequence↗
PubMed1998

Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia.

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.

Administration, Oral↗
PubMed1998

Purification and characteristics of membrane-bound chitinase of anaerobic ruminal fungus Piromyces communis OTS1.

A membrane-bound chitinase from cell wall fractions of the anaerobic ruminal fungus, Piromyces communis OTS1, was purified by affinity chromatography, gel filtration, and chromatofocusing. The molecular size of the chitinase was estimated by gel filtration to be 42.4 kDa and by SDS-PAGE to be 44.8 kDa, and its pI was 4.4. Activity was inhibited by Hg2+ and allosamidin. The activity at 39 degrees C was greatest at pH 6.0. It had an 'endo' type action. Solubilization tests indicated that plasmalemma-bound chitinase was held in place by an electrostatic type interaction. Characterization of the membrane-bound chitinase was more similar to that of extracellular chitinase than cytosolic chitinase. This suggested that membrane-bound chitinase was the origin of extracellular chitinase.

Anaerobiosis↗
PubMed1998

Morphologic changes in long head of biceps brachii in rotator cuff dysfunction.

Morphologic changes in the long head of the biceps brachii (LHB) and bicipital groove associated with cuff tears were studied in 170 cadavers. In specimens with minimum or moderate cuff tears, the primary finding was relative stenosis at the bicipital groove induced by enlargement of the LHB. However, this stenosis was not apparent in specimens with massive cuff tears and in these specimens, the medial wall of the groove exhibited wear and tear, a potential cause of LHB instability. We suggest that the long head of the biceps brachii muscle can potentially compensate for inadequate rotator cuff function. This increasing activity could lead to enlargement of the tendon and cause deterioration of the bicipital gliding mechanism.

Adult↗
PubMed1998

Effects of surfactants on glucosyltransferase production and in vitro sucrose-dependent colonization by Streptococcus mutans.

The presence of Tween 80 in media was associated with a significant increase in three glucosyltransferases(GTFs)(I, SI and S), especially GTF-I, produced by Streptococcus mutans strain PS14, indicating that the surfactant is a major cause of the enhanced GTF production observed in cultures in M4 medium. Lecithin and Tween 20 also enhanced GTF-I production, while Triton X-100 depressed it. At a lot concentration of 0.00125%, Tween 80 enhanced markedly only GTF-I production and its effect reached maximum at a concentration of 0.0025%. Water-insoluble glucan synthesis and artificial plaque formation (in vitro sucrose-dependent colonization) by PS14 were significantly enhanced by the addition of Tween 80 at concentrations over 0.00125%. These results suggest that surfactants might vary the cariogenic potential of Strep. mutans even at low concentrations.

Bacterial Adhesion↗
PubMed1998

Use of the harmonic scalpel for nephron sparing surgery in renal cell carcinoma.

PURPOSE: The harmonic scalpel is a new tool for excising and coagulating tissue with ultrasound using higher frequencies than an ultrasonic aspirator. We evaluated the usefulness of the harmonic scalpel in nephron sparing surgery. MATERIALS AND METHODS: We used the harmonic scalpel to incise the renal parenchyma during nephron sparing surgery in 10 patients with renal cell carcinoma. RESULTS: Bleeding from the renal parenchyma was minimal but hemostasis of the larger vessels was not obtained even when the harmonic scalpel was used at maximal coagulation power. The cut surface of the kidneys, especially the vessels, were more clearly recognized than if an ultrasonic aspirator had been used, enabling hemostasis by figure-of-8 suture. CONCLUSIONS: The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.

Carcinoma, Renal Cell↗
PubMed1998

Recognition of B-CLL cells experimentally infected with EBV by autologous T lymphocytes.

We compared 5-day-old cultures of two B-CLL clones experimentally infected with EBV for their interaction with autologous T lymphocytes. The clone which was strongly activated by the virus stimulated autologous T cells. It was also damaged by the cytotoxic T cells which were generated in mixed cultures with autologous lymphoblastoid cell lines (LCL). Cultured, non-infected CLL cells were not lysed by these effectors. The other B-CLL clone, which was activated to considerably lesser extent by the virus, did not stimulate the autologous T lymphocytes. While, also in this case cytotoxic function was generated in the mixed T cell-LCL culture, the effectors did not damage the EBV-infected CLL cells. The results with B-CLL cells can be regarded as a model for the EBV genome carrier normal B lymphocytes. They substantiate the current concept that such cells persist in seropositive healthy individuals undisturbed by the specific immune response as long as they maintain the phenotype of resting cells. However, after activation they can be recognized and eliminated by T cells.

B-Lymphocytes↗