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Biomedical subjects

T Shimamura

Publications and source records attributed to T Shimamura.

At least 37 records · Page 2Linked to original sources

Sagittal splitting laminoplasty for spinal canal enlargement for ossification of the spinal ligaments (OPLL and OLF).

Patients have been followed up radiologically after sagittal splitting laminoplasty (SSL) for ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum. The enlarged spinal canal was maintained satisfactorily in all the cases, and the posterior spinal elements were also almost completely restored. In most cases, the range of the vertebral motion was good with more than 50% of the preoperative status. Postoperative instability of the vertebral column was not identified in any case. Mild cervical kyphosis was noted in 6% of cervical OPLL patients. There were no patients with neurological deterioration. Using SSL, reconstruction and restoration of the posterior spinal elements and retention of the enlarged spinal canal were accomplished safely and adequately.

Female↗

Epigallocatechin gallate synergy with ampicillin/sulbactam against 28 clinical isolates of methicillin-resistant Staphylococcus aureus.

Compared with ampicillin, oxacillin, cefmetazole and imipenem, the combination of ampicillin and sulbactam at a constant ratio of 2:1 showed the greatest effect against 28 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), but MICs of ampicillin/sulbactam were still above the resistance breakpoint. When ampicillin/sulbactam was further combined with epigallocatechin gallate (EGCg, a main constituent of tea catechins), the MIC90 of ampicillin/ sulbactam was reduced to 4 mg/L, the susceptibility breakpoint. The fractional inhibitory concentration indices were between 0.19 and 0.56 in combination with 6.25 and 25 mg/L EGCg, respectively, indicating that ampicillin/sulbactam and EGCg combination may be effective against MRSA infections.

Ampicillin↗

Pharmacologic characterization of S-1255, a highly potent and orally active endothelin A receptor antagonist.

The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4-methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255 specifically bound to porcine aortic smooth muscle membranes expressing only ET(A) receptors with a Kd value of 0.39 nM. [3H]S-1255 binding was potently inhibited by ET-1 and selective ET(A) or ET(A)/ET(B) receptor antagonists, such as L-749329, SB209670, bosentan, and BQ-123, but the inhibitory effect of ET-3 and the selective ET(B) receptor antagonist, BQ-788, on the binding was weak. These inhibitory effects on [3H]S-1255 binding correlated well with those on [125I]ET-1 binding. S-1255 inhibited ET(A) receptor- and ET(B) receptor-mediated contractions in isolated rabbit femoral and pulmonary arteries with pA2 values of 8.8 and 6.3, respectively. The pA2 value of S-1255 for ET(B) receptor-mediated relaxation in isolated rabbit mesenteric artery was 7.4. Oral administration of S-1255 (0.3-10 mg/kg) caused dose-dependent inhibition of the pressor response to exogenous ET-1 (0.1 nmol/kg) in conscious normotensive rats, which was similar to that produced by intravenous administration (1 and 3 mg/kg). S-1255 (10 and 30 mg/kg, p.o.) significantly reduced blood pressure in deoxycorticosterone acetate-salt hypertensive rats from 6 h after administration, and the hypotensive effects were sustained up to 24-48 h. These results suggest that S-1255 is a highly potent and orally active ET(A) receptor antagonist.

Animals↗

Immunomodulatory effect of gold sodium thiomalate on murine acquired immunodeficiency syndrome.

Induction of IL-2 production and increased expression of CD25 were observed in C57BL/10 mice after weekly treatment with gold sodium thiomalate (GST). LP-BM5 murine leukemia virus (MuLV) infected mice treated with GST survived longer, had less cervical lymph node swelling, lower spleen weight, and fewer abnormalities in the expression of the cell surface markers, CD4, CD8a and CD45R/B220 on spleen cells than those that were not treated with GST. Thus, GST treatment may be beneficial through a decrease in disease progression via IL-2 induction in MuLV infected mice. This may have application in human immunodeficiency virus-infected individuals.

Animals↗

Mechanism of synergy between epigallocatechin gallate and beta-lactams against methicillin-resistant Staphylococcus aureus.

Compared to MICs (more than 800 microg/ml) of (-)-epigallocatechin gallate (EGCg) against Escherchia coli, MICs of EGCg against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) were 100 microg/ml or less. Furthermore, less than 25 microg EGCg per ml obviously reversed the high level resistance of MRSA to all types of tested beta-lactams, including benzylpenicillin, oxacillin, methicillin, ampicillin, and cephalexin. EGCg also induced a supersusceptibility to beta-lactams in MSSA which does not express mecA, encoding penicillin-binding protein 2' (PBP2'). The fractional inhibitory concentration (FIC) indices of the tested beta-lactams against 25 isolates of MRSA were from 0.126 to 0.625 in combination with 6.25, 12.5 or 25 microg of EGCg per ml. However, no synergism was observed between EGCg and ampicillin against E. coli. EGCg largely reduced the tolerance of MRSA and MSSA to high ionic strength and low osmotic pressure in their external atmosphere, indicating damage of the cell wall. Unlike dextran and lipopolysaccharide, peptidoglycan from S. aureus blocked both the antibacterial activity of EGCg and the synergism between EGCg and oxacillin, suggesting a direct binding of EGCg with peptidoglycan on the cell wall. EGCg showed a synergistic effect with DL-cycloserine (an inhibitor of cell wall synthesis unrelated to PBP2') but additive or indifferent effect with inhibitors of protein and nuclear acid synthesis. EGCg did not suppress either PBP2' mRNA expression or PBP2' production, as confirmed by reverse transcription-PCR and a semiquantitative PBP2' latex agglutination assay, indicating an irrelevance between the synergy and PBP2' production. In summary, both EGCg and beta-lactams directly or indirectly attack the same site, peptidoglycan on the cell wall. EGCg synergizes the activity of beta-lactams against MRSA owing to interference with the integrity of the cell wall through direct binding to peptidoglycan.

Anti-Bacterial Agents↗

Abundant expression of common cytokine receptor gamma chain (CD132) in rheumatoid joints.

OBJECTIVE: Activated macrophages upregulate surface expression of common cytokine receptor gamma chains (gammac, CD132), triggering of which induces secretion of proinflammatory cytokines. Rheumatoid synovial tissues contain a number of macrophages that play a pathogenic role by secreting proinflammatory cytokines. We studied the expression of gammac in the rheumatoid synovial tissues. METHODS: Cryosections of synovial tissues from patients with active rheumatoid arthritis (RA) or with osteoarthritis (OA) were stained with an anti-gammac Mab. Single-cell suspensions from the rheumatoid synovial tissues were stained with the same antibody and an anti-CD14 monoclonal antibody (Mab) for 2-color flow cytometric analysis. A soluble form of gammac in synovial fluids collected from rheumatoid or OA joints was quantitated by ELISA. RESULTS: Rheumatoid synovial tissues, but not the OA tissues, expressed gammac at a high level. Flow cytometric analysis showed that gammac were expressed by virtually all CD 14 positive synovial cells in RA. Synovial fluid derived from the rheumatoid joints contained a high concentration of soluble gammac. CONCLUSION: Membrane bound and soluble forms of gammac are abundant in rheumatoid joints. They might play a complex role in the pathology of RA.

Arthritis, Rheumatoid↗

[Dynamics of interleukin (IL)-18 in serum, synovial fluid and synovial membrane in the patients with rheumatoid arthritis].

OBJECTIVES: IL-18 is a novel cytokine that plays an important role in the Th1 response. The aim of this study is to investigate the dynamics of IL-18 in serum, synovial fluid and synovial membrane in the patients with rheumatoid arthritis. MATERIALS AND METHODS: The serum, synovial fluid and synovial membrane were obtained from RA patients at operation. The levels of IL-18 in the serum and synovial fluid were measured by ELISA. We then examined the expression of IL-18 in synovial tissues using anti-human IL-18 monoclonal antibody in immunohistochemical study. RESULTS: The levels of IL-18 in serum and synovial fluid in RA patients were 193.7 +/- 109.7 pg/ml and 258.8 +/- 238.0 pg/ml, respectively. Compared with OA patients and normal volunteers, the level of IL-18 in RA patients was higher in both serum and synovial fluid. (P < 0.05) In synovial membrane, the cells positive for anti IL-18 antibody were confirmed not only in RA (n = 26) but also in OA (n = 7) patients. The positive cells were the synovial lining cells, macrophages, fibroblasts and endothelial cells. However, a large number of positive cells were demonstrated in synovial tissues in RA compared with OA patients.

Adult↗

Endothelin receptor subtype antagonist activity of S-0139 in various isolated rabbit and canine arteries.

Vascular responses to endothelin peptides have been proposed to be mainly mediated via subtypes of the endothelin receptor, endothelin ET(A1), endothelin ET(B1), and endothelin ET(B2). The antagonist activity of 27-O-3-[2-(3-carboxy-acryloylamino)-5-hydroxyphenyl]acryloyloxy myricerone, sodium salt (S-0139) at these endothelin receptor subtypes was evaluated using isolated rabbit femoral, pulmonary, and mesenteric arteries. S-0139 competitively antagonized the endothelin-1-induced contraction mediated by the endothelin ET(A1) receptor in endothelium-denuded rabbit femoral arteries with a pA(2) value of 8.6+/-0.1. Endothelin ET(B2) receptor-mediated contraction induced by sarafotoxin S6c in endothelium-denuded rabbit pulmonary arteries was also inhibited by S-0139 with a pA(2) value of 5.6+/-0. 1. The pA(2) value of S-0139 for the endothelin ET(B1) receptor, evaluated from the endothelin-3-induced relaxant response in endothelium-intact rabbit mesenteric arteries, was 6.2+/-0.2. In isolated canine basilar, coronary, mesenteric and renal arteries, endothelin-1 caused concentration-dependent contractions with EC(50) values of 0.49+/-0.07, 0.61+/-0.25, 0.92+/-0.21 and 1.18+/-0.24 nM, respectively. S-0139 antagonized the endothelin-1-induced contraction in these arteries with pA(2) values of 8.0+/-0.1, 7. 6+/-0.2, 7.6+/-0.2 and 7.6+/-0.1, respectively. These results suggest that S-0139 is a potent and selective endothelin ET(A1) receptor antagonist, and that the contractions induced by endothelin-1 in canine basilar, coronary, mesenteric and renal arteries are mediated mainly via the endothelin ET(A1) receptor subtype.

Animals↗

SHP-2 can suppress transformation induced by platelet-derived growth factor.

Signaling by either the type alpha or type beta receptors of platelet-derived growth factor occurs by phosphorylation of at least 10 intra-cytoplasmic tyrosine residues and their subsequent association of secondary signaling molecules with Src homology 2 (SH2) domains. Although the role of several of these secondary signaling molecules in mitogenesis has become increasingly clear, their roles in morphological transformation are not as well defined. Here we present evidence that the SHP-2 phosphatase which associates with Tyr 1009 of the type beta receptor and Tyr 720 of the type alpha receptor may suppress transformation induced by the PDGF B chain. Cotransfection of a dominant negative mutant of the SHP-2 gene and the PDGF B chain gene into mouse fibroblasts that only poorly formed foci with the PDGF B chain alone resulted in larger and more prominent foci. Furthermore, introduction of a wild-type copy of the SHP-2 gene into a tumor cell line, U-87MG, which relies on PDGF expression to form foci in vitro, caused a reversion of phenotype.

3T3 Cells↗

Prolongation of canine liver allograft survival by a novel immunosuppressant, FTY720: effect of monotherapy and combined treatment with conventional drugs.

BACKGROUND: The immunosuppressive effect and other properties of a novel immunosuppressant, FTY720, have been studied mostly in the experimental transplantation of various extrahepatic organs. In this experiment, we evaluated the antirejection potency and adverse effects of this agent on liver grafts using a canine liver transplantation model. METHODS: Forty-eight orthotopic liver transplantations were performed by the standard technique under a veno-venous bypass. Liver recipients were divided into two studies: a single-dose study with FTY720 at various doses and a combined dose study with conventional immunosuppressants (cyclosporine or tacrolimus) alone and combined with FTY720. Survival, biochemical and hematological tests, blood levels of immunosuppressants, and postmortem histology were determined. RESULTS: The median survival of untreated control animals was 9 days, whereas treatment with FTY720 at a dose of 0.1 mg/kg/day prolonged graft survival to 49.5 days. FTY720 at 1 mg/kg/day showed a slight but insignificant prolongation to 16 days, but when the dose was increased to 5 mg/kg/day, the graft was rejected at 10 days. The combination of FTY720, 0.1 mg/kg/day, with a subtherapeutic dose of cyclosporine, 5 mg/kg/ day, prolonged median animal survival from 40 days with cyclosporine alone to 74 days. A combination of FTY720 (0.1 mg/kg/day) with tacrolimus (0.5 mg/kg/ day) compromised animal survival, reducing survival from 83.5 days with tacrolimus alone to 30.5 days due to infectious complication and emaciation by overimmunosuppression. No evident drug-induced side effects were observed. CONCLUSIONS: FTY720 has a potent immunosuppressive effect when used alone at 0.1 mg/kg/day in canine liver transplantation. FTY720 is a promising candidate for future clinical application in orthotopic liver transplantation.

Animals↗

Reduction of tetrazolium salt XTT by aminoreductone formed during the Maillard reaction of lactose.

Lactose, a reducing disaccharide abundant in milk, reacts extensively with the amino groups of protein through the Maillard reaction. The Maillard reaction products showed 3'-[1-[(phenylamino)carbonyl]-3,4-tetrazolium]bis(4-methoxy-6-nitro)benzensulfonic acid hydrate (XTT) reducibility. The objective of this study was to clarify the Maillard reaction products responsible for the XTT reducibility. When lactose and butylamine were heated at 100 degrees C, the characteristic UV maximum at 320 nm was recognized and the relationship between the XTT reducibility and the compound with absorption maximum at 320 nm was investigated. The time course and the dependence on the heating temperature of the formation of the compound with absorption maximum at 320 nm were similar to those of the XTT reducibility. Their relationship showed a significant correlation (r = 0.967, n = 19). Furthermore, the spectrum change of the heated model solution by the addition of XTT suggested that the compound with absorption maximum at 320 nm would be involved in the reduction of XTT. Because the compound with absorption maximum at 320 nm was identified as an aminoreductone, 1-(butylamino)-1,2-dehydro-1,4-dideoxy-3-hexulose, by NMR analysis, it can be concluded that this was the main XTT-reducing substance.

Animals↗

Relationship between the reduction of tetrazolium salt XTT and DNA strand breakage with aminosugars.

Dihydropyrazine derivatives formed by the self-condensation reaction of D-glucosamine have the DNA breaking activity. To establish the monitoring method of the biological active dihydropyrazines, we investigated the relationship between the XTT (3'-[1-[(phenylamino)-carbonyl]-3, 4-tetrazolium]bis(4-methoxy-6-nitro)benzensulfonic acid hydrate) reducibility and the DNA breaking activity of aminosugars. Aminosugar in 50 mM sodium phosphate buffer (pH 7.4) was incubated at 37 degrees C. At a given time, the XTT reducibility and the DNA breaking activity of the incubated aminosugar were measured. Both XTT reducibility and DNA breaking activity showed a maximum value within 1-4 h after the incubation and then gradually decreased with the incubation time. Superoxide anion was suggested to involve in both of the DNA breaking activity and the XTT reducibility by the addition of the radical scavengers into those assay mixtures. The quantity of remaining covalently closed circular DNA and the XTT reducibility of all aminosugars showed a good correlation (r = 0.825, n = 26). This means that the XTT assay is applicable for the monitoring of those biologically active products derived from aminosugars when the participation of superoxide anion in DNA scission is recognized.

DNA↗

Mucosectomy for gastric cancer: current status in Japan.

Advances in techniques of image diagnosis have enabled the detection of minute or small cancer lesions in the stomach. Patients with such cancer, in principle, were treated surgically, but accumulated histopathological data on surgical cancer specimens revealed that many of these patients did not have any metastatic lesions. For those localized cancers, local treatment of primary lesions by endoscopy gives curative results. It has been demonstrated that endoscopic therapy is curative in mucosal well-differentiated adenocarcinoma not more than 20 mm in diameter without ulceration. Efforts to cure early gastric cancer without surgery yielded fruitful results and a new treatment concept was established. Even if there is a recurrence of the residual or metachronous lesions, they can be treated by further endoscopic treatment.

Endoscopy↗

Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens.

BACKGROUND: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours. METHODS: Using nested reverse-transcription-polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and fit-1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens. RESULTS: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non-tumour portion of the specimens in eight patients (57%; P= 0.08). No differences were found between the tumour portion and the corresponding non-tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and fit-1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non-tumour portions, respectively (chi2 test: KDR, P< 0.01; fit-1, P= 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non-tumour portions (Mann-Whitney U-test: P<0.001) but no differences were detected for fit-1. CONCLUSIONS: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.

Aged↗

Living donor liver transplantation in adults: outcome in Japan.

1. Twenty centers in Japan performed 308 living donor liver transplants (LDLT) in adults. 2. Right lobe grafts were used in the minority of cases (27.1%); most had left lobe grafts (72.9%). Survival was not influenced by the type of graft. 3. There were no donor deaths (0%); 9.3% of donors experienced mild to moderate complications. Biliary complications were the most frequent. 4. Overall recipient survival was 72.4%.

Adult↗

A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury.

BACKGROUND: Reactive oxygen species have been considered to be involved in liver injury at the procurement, preservation, and transplantation from donors without beating hearts. A novel hydroxyl radical scavenger, nicaraven with hydrophilic and lipophilic properties, infiltrates both intracellular and extracellular spaces where it effectively scavenges reactive oxygen species. Protection by nicaraven against ischemia and reperfusion damage of the brain, heart, and kidneys has been shown. The effect of this agent on the liver remains unclear. METHODS: Two-hour total hepatic vascular exclusion was used. Eighteen beagle dogs were randomly assigned to 2 groups: 12 animals were not treated (group I) and 6 were treated with nicaraven (group II). Nicaraven was administered intravenously (2mg/kg/min) for 60 minutes before ischemia and for 3 hours, starting 30 minutes before reperfusion. RESULTS: Two-week survival rates were 25% in group I and 100% in group II (P <.01). Nicaraven inhibited lipid peroxidation in the liver, improved hepatic and systemic hemodynamics and energy metabolism, and suppressed liver enzyme release, endothelin-1 elevation in hepatic venous blood, histologic damage, and neutrophil infiltration into the liver. CONCLUSIONS: Nicaraven exerted hepatic protection against warm ischemia and reperfusion injury. This may indicate nicaraven as a potential candidate to attenuate liver injury from warm ischemia and preservation in transplantation from donors without beating hearts.

Adenine Nucleotides↗

Meniscal tearing after ACL reconstruction.

The knees of 72 patients with unilateral anterior-cruciate- ligament (ACL) injury were analyzed before ACL reconstruction as well as by follow-up arthroscopy on the day of staple removal. At ACL reconstruction 31 lateral menisci and 40 medial menisci were found to be normal. 28 lateral menisci and 24 medial menisci were treated surgically, while 13 lateral menisci and 8 medial menisci with small or incomplete meniscal tearing were not treated. At follow-up arthroscopy there were 3 new cases of lateral meniscal tearing and 3 new cases of medial meniscal tearing in the groups diagnosed as normal prior to surgery. Two of the 13 cases with small or incomplete lateral meniscal tearing required resection, 8 healed and the other 3 demonstrated no progressive change. Four of the 8 cases with small or incomplete medial meniscal tears healed, 3 exhibited no progressive change and one required surgical treatment. There was no correlation between meniscal tearing and knee instability as indicated by a positive Lachman test or a positive pivot shift sign. The results of the present study indicate that ACL reconstruction prevents progressive changes in meniscal tears and will prevent secondary osteoarthritis, and that some small tears of the lateral meniscus require no surgical treatment.

Journal Article↗