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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 37 records · Page 2Linked to original sources

[Clinical analysis of surgically resected multiple primary lung cancer].

Synchronous and metachronous lung cancer is occasionally encountered. Frequency of the occurrence is increasing because of recent progress of imaging technique such as high resolution CT and CT based annual lung survey. We analyzed clinical characteristics of both synchronous and metachronous lung cancer treated surgically in our facility. There were 20 cases of multiple lung cancer cases, which is consisted of 12 synchronous multiple lung cancer cases and 8 metachronous lung cancer cases. Mean age was 62 years old and there were 14 male and 6 female cases. Among synchronous group, 8 cases have multiple shadow in ipsilateral hemithorax and 4 cases in both side. Surgery was carried out according to the extent of the disease and lung reserve. Associated cancer was diagnosed stage IA or IB in all cases. Five-year survival was 58.9%. Meanwhile, as regards to metachronous group, mean interval between first cancer and second cancer was 73 months. Seven cases have contralateral second primary lung cancer and one case has ipsilateral second primary lung cancer. In 3 cases, histology of the first and the second disease were different and in 5 cases that were the same. The first procedures were complete resection with systemic mediastinal LN dissection. The second procedures were determined based on the lung reserve. Pathological stage of the second disease were either stage IA or IB. There were no operative mortality and 5 years survival was 75%. Since there is no operative mortality and the outcome seems satisfactory when the patient has enough lung reserve, aggressive surgical resection should be considered in the case of multiple primary lung cancer. There is an increasing chance of synchronous multiple primary lung cancer because of improvement of imaging system. We have to prepare new therapeutic strategy for those patients.

Aged↗

The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with their nuclear factor-kappa B activation.

Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-alpha (TNF-alpha) and cycloheximide induced neutrophil apoptosis, whereas the same treatment failed to induce significant apoptosis in salivary and synovial fluid neutrophils. Caspase-3 activation by TNF-alpha was observed in these tissue neutrophils, although its activity was significantly weaker than that in circulating blood neutrophils. In circulating blood neutrophils, TNF-alpha induced activation of nuclear factor-kappa B (NF-kappa B), whereas, in tissue neutrophils, NF-kappa B had been already activated without any stimulation, and no further activation was induced by the treatment with TNF-alpha. Furthermore, while pretreatment of neutrophils with an NF-kappa B inhibitor produced typical apoptotic changes in circulating blood neutrophils, this inhibitor did not produce any morphological apoptotic changes induced by TNF-alpha in tissue neutrophils. These results indicate that neutrophils undergo marked functional changes such as altered sensitivity to apoptosis-inducing stimuli in association with their exudation from blood into tissue, and that NF-kappa B activation is involved in the acquisition of resistance to TNF-alpha-induced apoptosis.

Apoptosis↗

Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo.

The effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF.

Animals↗

Inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 (D5(H)) of human high-molecular-weight kininogen and identification of a minimal amino acid sequence.

We found that human kinin-free high-molecular-weight kininogen (kf-HK) significantly inhibited vitronectin-mediated migration (haptotaxis) and invasive potentiation (haptoinvasion) of osteosarcoma (MG-63) cells but that HK, LK, the common heavy chain of HK and LK, and the light chain (D6(H)) of HK had no inhibitory effect. Recombinant GST-D5(H) (histidine-rich region of HK) obtained from Escherichia coli. (BL21) also inhibited both haptotaxis and haptoinvasion to about 30% of the control level in a dose-dependent manner. These findings suggest that a specific region of D5(H) is responsible for the inhibition of cell haptotaxis and haptoinvasion. Among the seven synthetic peptides covering D5(H), peptide H(479)KHGHGHGKHKNKGK(493) (P-5) inhibited both haptotaxis and haptoinvasion in a dose-dependent manner, suggesting that P-5 could possibly be utilized to prevent primary and secondary metastases of tumor cells.

Amino Acid Sequence↗

MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes.

AML1-MTG8 chimeric oncogene is generated in acute myelogenous leukemia with t(8;21), and seems to be responsible for the pathogenesis of the disease. However, the role of MTG8 is ambiguous. Here we found that MTG8 interacted with the regulatory subunit of type II cyclic AMP-dependent protein kinase (PKA RIIalpha). The binding site of MTG8 was NHR3 domain, and that of RIIalpha was the N-terminus for interacting with PKA anchoring proteins (AKAPs). NHR3 contains a putative alpha-amphipathic helix which is characteristic in binding of AKAPs with RII. Indirect immunofluorescence microscopy showed that MTG8 and RIIalpha were overlapped at the centrosome-Golgi area in lymphocytes. These findings suggest that MTG8 may function as an AKAP at the centrosome-Golgi area in lymphocytes.

Amino Acid Sequence↗

Magic numbers in exotic nuclei and spin-isospin properties of the NN interaction.

The magic numbers in exotic nuclei are discussed, and their novel origin is shown to be the spin-isospin dependent part of the nucleon-nucleon interaction in nuclei. The importance and robustness of this mechanism is shown in terms of meson exchange, G-matrix, and QCD theories. In neutron-rich exotic nuclei, magic numbers such as N = 8, 20, etc. can disappear, while N = 6, 16, etc. arise, affecting the structure of the lightest exotic nuclei to nucleosynthesis of heavy elements.

Journal Article↗

Energy-transfer rate in crystals of double-complex salts composed of [Ru(N-N)3](2+) (N-N = 2,2'-bipyridine or 1,10-phenanthroline) and [Cr(CN)6](3-): effect of relative orientation between donor and acceptor.

A block single-crystal was obtained using a diffusion method with a concentrated acetone-water (vol. 1/1) solution of [Ru(phen)(3)]Cl(2).6H(2)O (phen = 1,10-phenanthroline) and a concentrated aqueous solution of K(3)[Cr(CN)(6)], without evaporating solvents. The crystal was identified as a double-complex salt including two acetone and fourteen solvent water molecules, [Ru(phen)(3)](2)[Cr(CN)(6)]Cl.2(CH(3))(2)CO.14H(2)O (1). Measurement of the X-ray diffraction pattern of the double-complex salt was performed using an X-ray diffractometer with an Imaging-Plate (IP) Weissenberg camera. 1 crystallizes in the triclinic space group P1, with a = 13.930(5) A, b = 14.783(5) A, c = 11.137(6) A, alpha = 89.87(4) degrees, beta = 107.47(3) degrees, gamma = 96.68(3) degrees, and Z = 2. The crystal structure is very different from that of [Ru(bpy)(3)](2)[Cr(CN)(6)]Cl.8H(2)O (2) (bpy = 2,2'-bipyridine), which could be obtained using the same procedure and crystallizes in the monoclinic space group C2, with a = 22.414(2) A, b = 13.7686(15) A, c = 22.207(2) A, beta = 90.713(8) degrees, and Z = 4. The distance between the central-metal ions of ruthenium(II) and chromium(III) complexes in [Ru(phen)(3)](2)[Cr(CN)(6)]Cl.2(CH(3))(2)CO.14H(2)O (7.170 A) is shorter than that in [Ru(bpy)(3)](2)[Cr(CN)(6)]Cl.8H(2)O (9.173 A) by about 2 A, while the rate of energy transfer from the (3)MLCT state of [Ru(N-N)(3)](2+) to the (2)E(g) state of [Cr(CN)(6)](3-) in the former salt (9.5 x 10(5) s(-1)) is far slower than that in the latter one (6.0 x 10(6) s(-1)) at 77 K. These results indicate that the energy-transfer rate strongly depends, not upon the distance between central metal ions, rather, upon the mutual relative orientation between the donor and the acceptor complexes in double-complex salts.

Journal Article↗

Oxytocin enhances presynaptic and postsynaptic glutamatergic transmission between rat olfactory bulb neurones in culture.

Although oxytocin (OT) within the olfactory bulb has been implicated in maternal behaviour and olfactory recognition, the cellular mechanisms of action remain to be clarified. We examined the effects of OT on glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) in cultured granule cells with the use of whole-cell patch-clamp recordings. OT reversibly increased both the frequency and amplitude of sEPSCs. The effects of OT on sEPSCs were blocked by the selective OT receptor antagonist desGly-NH(2)(9),d (CH(2))(5)-[Thy(Me)(2),Thr(4)]-ornithine vasotocin. OT had no detectable effect, however, on high voltage-activated Ca2+ currents in mitral/tufted cells, suggesting that OT acts presynaptically on step(s) in the release process downstream from calcium influx. OT augmented the membrane current in granule cells evoked by exogenous application of glutamate, indicating a postsynaptic site of action. These results indicate that OT facilitates sEPSCs in granule cells by both pre- and postsynaptic mechanisms.

Animals↗

Transition from spherical to deformed shapes of nuclei in the Monte Carlo shell model.

The transition from spherical to deformed shapes is studied in terms of large-scale shell-model calculations for Ba isotopes as a function of valence nucleon number with fixed single-particle space and Hamiltonian. A new version of the Monte Carlo shell model is introduced so as to incorporate pairing correlations efficiently, by utilizing condensed pair bases. The energy levels and electromagnetic matrix elements are described in agreement with experiments throughout the transitional region. The orbital M1 sum rule is calculated as a measure of the deformation evolution, and the Q-phonon picture is shown to be reasonable from spherical to deformed nuclei.

Journal Article↗

Long-range magnetic order in Mn[N(CN)2]2(pyz) (pyz = pyrazine). Susceptibility, magnetization, specific heat, and neutron diffraction measurements and electronic structure calculations.

Using dc magnetization, ac susceptibility, specific heat, and neutron diffraction, we have studied the magnetic properties of Mn[N(CN)2]2(pyz) (pyz = pyrazine) in detail. The material crystallizes in the monoclinic space group P2(1)/n with a = 7.3248(2), b = 16.7369(4), and c = 8.7905 (2) A, beta = 89.596 (2) degrees, V = 1077.65(7) A(3), and Z = 4, as determined by Rietveld refinement of neutron powder diffraction data at 1.35 K. The 5 K neutron powder diffraction data reflect very little variation in the crystal structure. Interpenetrating ReO3-like networks are formed from axially elongated Mn(2+) octahedra and edges made up of mu-bonded [N(CN)2](-) anions and neutral pyz ligands. A three-dimensional antiferromagnetic ordering occurs below T(N) = 2.53(2) K. The magnetic unit cell is double the nuclear one along the a- and c-axes, giving the (1/2, 0, 1/2) superstructure. The crystallographic and antiferromagnetic structures are commensurate and consist of collinear Mn(2+) moments, each with a magnitude of 4.15(6) mu(B) aligned parallel to the a-direction (Mn-pyz-Mn chains). Electronic structure calculations indicate that the exchange interaction is much stronger along the Mn-pyz-Mn chain axis than along the Mn-NCNCN-Mn axes by a factor of approximately 40, giving rise to a predominantly one-dimensional magnetic system. Thus, the variable-temperature magnetic susceptibility data are well described by a Heisenberg antiferromagnetic chain model, giving g = 2.01(1) and J/k(B) = -0.27(1) K. Owing to single-ion anisotropy of the Mn(2+) ion, field-induced phenomena ascribed to spin-flop and paramagnetic transitions are observed at 0.43 and 2.83 T, respectively.

Journal Article↗

Predominance of Th1 immune response in diffuse proliferative lupus nephritis.

OBJECTIVE: Lupus nephritis, which shows various histologic patterns, is a serious complication of systemic lupus erythematosus (SLE). We previously demonstrated the importance of Thl cell-mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study was to examine the relationship between the peripheral blood Th1/Th2 balance and the intrarenal immune response. METHODS: The Th1:Th2 ratio in peripheral blood was measured by intracellular staining for cytokines with flow cytometry. Immunohistochemical analysis of renal biopsy specimens was performed to clarify the characterization of local infiltrating cells in 3 groups of subjects: SLE patients with World Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE patients with WHO class V nephritis (group II; n = 9), and patients with minor glomerular lesions (group III; n = 7). In addition, the histologic activity index and chronicity index were evaluated and correlated with the Th1:Th2 ratio. RESULTS: Immunohistochemical studies showed higher numbers of CD68+ macrophages, CD3 + T cells, and interferon-gamma-positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up-regulation of expression of osteopontin and CD40, with a small number of infiltrating T cells expressing interleukin-4. Overall, the Thl:Th2 ratio in group I patients (SLE with DPLN) was high and correlated significantly with the histologic activity index, but not with the chronicity index. CONCLUSION: We have identified a predominance of Thl-type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Thl response.

Adult↗

Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis.

OBJECTIVE: To investigate whether a polymorphism(s) or mutation(s) in the tumor necrosis factor receptor II (TNFRII) gene is involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: All 10 exons of the TNFRII gene were analyzed by exon-specific polymerase chain reaction-single-strand conformation polymorphism, followed by nucleotide sequencing of exons that displayed aberrant bands. To analyze the function of the TNFRII polymorphisms, the full-length TNFRII complementary DNA of each allele was transfected in HeLa cells and then studied for specific binding of 125I-TNFalpha, as well as interleukin-6 (IL-6) production and cytotoxic activity after treatment with recombinant human TNFalpha. RESULTS: We identified 4 polymorphisms, at codons 56, 181, 196, and 232. The latter 2 had amino acid substitutions M196R and E232K, respectively. Only the 196R allele was significantly associated with SLE in our 105 Japanese SLE patients, with an allele frequency of 20.5%, compared with 12.6% in 99 healthy controls (P = 0.0335). More importantly, using TNFRII-transfected HeLa cells, we demonstrated significantly increased IL-6 production by 196R TNFRII compared with 196M TNFRII. The cytotoxic activity induced by 196R TNFRII was also increased compared with that of 196M TNFRII. This increase was achieved without affecting the binding affinity of TNFalpha to TNF-RII, as demonstrated by the finding that specific TNFalpha binding to the HeLa transfectants of 196R and 196M TNFRII was similar, with Kd values of 3.12 x 10(-10)M and 4.34 x 10(-10)M, respectively. CONCLUSION: These results suggest that 196R TNFRII, which transduces the signals of TNFalpha more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE.

Adolescent↗

Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction.

The utility of the VZV skin test in detecting individual susceptibility to varicella and zoster was determined. Its specificity particularly with regard to herpes simplex was also established. The VZV skin test was negative or weakly positive during the early stage of herpes zoster, and strongly positive during recovery from that disease. A small-scale clinical trial to immunize elderly individuals has been performed for the purpose of preventing herpes zoster, and, perhaps, severe post-herpetic neuralgia as well. Sixty individuals > or = 50 years old were screened for VZV antibodies by IAHA test and were given a VZV skin test for cell-mediated immunity. All were seropositive, but eight were skin-test negative. Thirty-seven individuals including the eight with negative skin tests were immunized with one dose of varicella vaccine (3.0 x 10(4) PFU/dose). After 5-7 weeks, the skin test reaction showed increased positivity, with a change in score from (-) to (+, ++) in 7/8 subjects, from (+) to (++, +++) in 3/5 subjects, and from (++) to (+++) in 6/10 subjects. Enhancement of the VZV antibody titer (defined as twofold or greater) was observed in all 15 vaccine recipients with a prevaccination titer of < or = 1:16, and in 19 of 24 subjects with a prevaccination titer of > or = 1:32. These results indicate that giving live varicella vaccine with a high viral titer can induce a good boost immunity particularly cell-mediated immunity to VZV in the elderly.

Aged↗

Surgical management of multidrug-resistant tuberculosis.

We report surgical resections in 3 patients with active multidrug-resistant tuberculosis. All cases involved strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin and patients who were poor candidates for medical therapy alone. We conducted pulmonary resections (partial resection in case 1, lobectomy in case 2, and segmentectomy in case 3). The optimum multiple-drug regimen, based on drug susceptibility studies, was used preoperatively and postoperatively. In all cases, sputum smears and cultures yielded negative results postoperatively, and continue to be negative for Mycobacterium tuberculosis to date. It is recommended that, if localized disease is present and medical treatment is likely to fail, pulmonary resection be conducted for multidrug-resistant Mycobacterium tuberculosis.

Adult↗

Popliteal pseudoaneurysm simulating soft-tissue sarcoma: complication of osteochondroma resection.

Pseudoaneurysm complicating osteochondroma is extremely rare. We describe a pseudoaneurysm in the popliteal fossa of a 21-year-old man, occurring 5 years after apparently incomplete resection of an osteochondroma at that site. We found magnetic resonance imaging and magnetic resonance angiography to be of great diagnostic value. Resection of the pseudoaneurysm and anastomosis of the popliteal artery were successful, with no recurrence detected for almost 7 years since the operation.

Adult↗

Results of surgery and radio-hyperthermo-chemotherapy for patients with soft-tissue sarcoma.

BACKGROUND: Between 1990 and 1999, we performed radio-hyperthermo-chemotherapy (RHC) in 44 patients with high-grade soft-tissue sarcomas of the limbs. METHODS: Radiotherapy involved the delivery of radiation at a dose of 2 Gy once daily on 16 days, to give a total dose of 32 Gy. Hyperthermia was conducted once a week, with a total of five sessions. Chemotherapy was performed by implanting a reservoir and administering cisplatin (3 mg/kg) three times, and pinorubin (an adriamycin derivative; 1 mg/kg) twice by intra-arterial infusion, at weekly intervals. These drugs were administered alternately during hyperthermia sessions. RESULTS: Tumor shrinkage was observed in 98% (43/44) of the patients. Of the 36 patients with M0 tumors, 30 were disease-free at final follow-up, 2 had no evidence of disease, 1 was alive with disease, and 3 had died of the disease. Amputation was required only in the first patient, and the affected limb was preserved in the other 43 patients. The surgical margin was wide in 9 patients and marginal in 29 patients, and intralesional excision was performed in 5 patients. There was recurrence in only 1 of the 44 patients. CONCLUSION: RHC is currently the most potent and relatively safe treatment method for high-grade soft-tissue sarcomas that is available clinically.

Adolescent↗

IL-1beta-induced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27).

The purpose of this study was to examine how chondrocytes are involved in the molecular mechanism of inflammation in rheumatoid arthritis (RA). A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-1beta (IL-1beta). Changes in the expression levels of matrix metalloproteinase-1 (MMP-1), metalloproteinase-13 (MMP-13), and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) were assessed by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. IL-1beta induced the expressions of MMP-1, MMP-13, and GLS mRNAs and proteins in a dose-dependent manner. Selective inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway with SB 203580 and SB 202190 blocked the expression of MMP-1, MMP-13, and GLS more strongly than selective in hibition of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway by PD 98059. These findings suggest that chondrocytes may intensify cartilage destruction and inflammation in RA by the induction of MMP-1, MMP-13, and GLS by IL-1beta and that the p38 MAPK pathway plays an important role in these inductions.

Base Sequence↗

Factors associated with anxiety, depression and suicide ideation in female outpatients with SLE in Japan.

The subjects consisted of 84 female SLE outpatients who were all over 20 years of age. These patients were able to maintain relatively stable physical conditions and lead normal daily lives, and they were regularly treated at the outpatient clinic. All subjects were Japanese. Psychological features (trait anxiety, state anxiety, depression and suicide ideation) were evaluated using psychological tests, and the relationships between the respective psychological features and background factors were statistically evaluated using stepwise multiple logistic regression analyses. In this study, we found that 'the self-evaluation of not having understood SLE at the time of starting SLE treatment' was the background factor significantly affecting depression or trait anxiety. 'No spouse' had a statistically significant effect on depression, and 'self-awareness as problems of side-effects due to steroids' had a statistically significant effect on state anxiety. We also found 'human relations among family members' and 'high daily steroid dosage' to be significantly correlated with suicide ideation. However, there were no correlations between the psychological features and 'disease activity at the time of investigation' or 'history of neuropsychiatric diseases'. In female SLE outpatients, performing psychological approaches focusing on 'understanding SLE at the beginning of treatment', 'the human relationships among family members', or 'issues related to steroid therapy' may be useful for the early treatment or prevention of various major mental problems.

Adult↗