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Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 199 records · Page 11Linked to original sources

Brain abscess due to infection with Entamoeba histolytica.

We successfully treated a serious case of Entamoeba histolytica infection showing brain abscess, meningitis, and liver abscess by oral administration of metronidazole, intramuscular injection of dehydroemetine, and drainage of the brain abscess. The diagnosis of amebic brain abscess was based on a combination of clinical symptoms and signs, computed tomography and magnetic resonance imaging findings, a positive serologic test result for E. histolytica, a dramatic response to anti-amebic drugs after an ineffective therapeutic history with antibacterial drugs, and application of the polymerase chain reaction method.

Administration, Oral↗

[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs].

Loading therapy consisting of the ACNU regimen was instituted as postoperative anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy. The former could be prevented by the administration of G-CSF, but platelet infusions were necessary in some patients for amelioration of thrombocytopenia. Gastroenterological symptoms, such as nausea and vomiting, were also frequently noted. Granisetron (Kytril), which is a recently developed selective competitive inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse effects, and was found to be clinically effective.

Adult↗

Clinical application and quantitative evaluation of generator-produced copper-62-PTSM as a brain perfusion tracer for PET.

UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF). METHODS: Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study. RESULTS: Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O-water PET demonstrated less contrast between high- and low-flow regions in 62Cu-PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion. CONCLUSION: Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF.

Adolescent↗

Effects of hyperglycemia on FDG uptake in human brain and glioma.

UNLABELLED: This study evaluates the effects of hyperglycemia on fluorodeoxyglucose (FDG) uptake in the human brain and in brain tumors. METHODS: We performed glucose loading during FDG PET studies in nine patients with brain tumors (eight gliomas and one brain metastasis) and one with resected glioma. Two FDG PET scans were obtained in all cases within 1 wk in a control state and with glucose loading by intravenous infusion of 10% glucose solution. Serial arterial blood sampling was performed in all cases to obtain fractional uptake of FDG normalized by the plasma integral uptake of radioactivity (FU). RESULTS: In all nine patients with brain tumors, the tumor was depicted more clearly with glucose loading than in the control state. Glucose loading decreased FU in the cerebral cortex (54.2% +/- 13.8%) nearly in inverse proportion to the plasma glucose level, while the tumors showed a decrease (42.5% +/- 15.6%), resulting in an increased tumor-to-cortex ratio by 26.0% +/- 5.7%. Fractional uptake in the cerebellum, white matter and the edematous area also decreased by glucose loading (53.9% +/- 13.2%, 49.6% +/- 10.3% and 34.9% +/- 9.6%, respectively). CONCLUSION: These results demonstrate the different effects of hyperglycemia on normal brain tissue and on tumor, suggesting that glucose loading may be a valuable adjunct to FDG PET to enhance detection of recurrent or residual brain tumors.

Adult↗

[Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11].

Camptothecin-11 (CPT-11) is a new derivation of camptothecin, a plant alkaloid antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was mediated through interaction of the drugs with its target enzyme, DNA topoisomerase I (topo I). In this study, we studied the relation between sensitivity to CPT-11 and topo I activity of glioma cells. Furthermore, we established CPT-11 resistant cell lines in order to elucidate potential mechanisms of drug resistance. A clear correlation between the sensitivities to CPT-11 and topo I activities in surgical glioma specimens was demonstrated. Activities of topo I in CPT-11 sensitive group (IC50 values for CPT-11; < 50 micrograms/ml) tended to be higher than those in CPT-11 resistant group (IC50 values; > or = 50). Topo I activity may serve as a novel marker to predict the sensitivity of gliomas to topo inhibitors. CPT-11 resistance cell lines (T98G/CPT-11 and C6) respectively exhibit a 5.4- and 7.3-fold increase in resistance to CPT-11. No differences in topo I activity and intracellular accumulation of CPT-11 were observed between parent and CPT-11 resistant lines. On the other hand, topo I from T98G/CPT-11 and C6/CPT-11 cells were at least 4- and 2-fold resistant to the inhibitory effect of the CPT-11 on the relaxation activity of topo I in comparison with their parent lines. This enzymological difference may be responsible for the resistance to CPT-11.

Animals↗

Immunotherapy for Stewart-Treves syndrome. Usefulness of intrapleural administration of tumor-infiltrating lymphocytes against massive pleural effusion caused by metastatic angiosarcoma.

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor-infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4+ T-cell clone and a CD8+ T-cell clone established from TIL had specific cytotoxicity to the tumor cells.

Breast Neoplasms↗

[Targeting therapy for lung cancer].

Many approaches have been developed to targeting therapy for lung cancer. The representatives types have included photodynamic therapy (PDT), bronchial arterial infusion of anticancer agent and/or embolization, intensification of the effect of drugs on tumor tissue and drug delivery systems (DDS) using liposomes. In our hospital, 195 lung cancer patients, including those with 56 early stage lesions, have been treated with PDT, and a CR rate of 65.2% was obtained. Bronchial arterial infusion (BAI) for clinical N2, in-operable non-small cell lung cancer patients has prolonged median survival time compared to the patients treated without BAI. Combined modalities of chemotherapy and low power laser (He-Ne Laser) irradiation in the experimental animal model have been shown. This combined therapy may permit enhancement of the antitumor effects of routine chemotherapy by reducing the side effects of the drug. DDS using liposomes may well be a major targeting therapy for lung cancer. In our data, trans-bronchial injection of chemotherapeutic drugs encapsulated with liposomes will be most effective for mediastinal lymph node metastasis of lung cancer.

Bronchial Arteries↗

Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and linearization based on permeability-surface area product model.

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.

Adult↗

SPECT images of technetium-99m-ethyl cysteinate dimer in cerebrovascular diseases: comparison with other cerebral perfusion tracers and PET.

UNLABELLED: To assess the clinical role of 99mTc-ethyl cysteinate dimer (ECD) as a cerebral perfusion tracer, 10 patients with unilateral cerebral infarction were studied. METHODS: ECD SPECT images were compared with IMP and/or HMPAO SPECT in nine patients, seven in chronic phases and two in subacute phases. Five of these patients and one additional patient with chronic infarction received PET imaging in order to compare ECD distribution with quantitative regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) images. RESULTS: In patients with chronic cerebral infarction, regression analysis showed excellent correlation between ECD and IMP in the uptake ratio of lesions-to-nonaffected cortices (r = 0.91). In two cases of subacute infarction, decreased uptake of ECD was observed in the area of "luxury perfusion," which showed elevated or preserved rCBF with diminished rCMRO2. On visual analysis, ECD image contrast was less prominent compared to that of IMP, but contrast was better than that of HMPAO. CONCLUSIONS: ECD uptake showed a curvilinear relationship against rCBF, suggesting flow-limited uptake in a high flow range. ECD is a clinically useful cerebral perfusion tracer with distinct characteristics when compared with other available agents.

Adult↗

HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs.

The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses.

Amino Acid Sequence↗

Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11.

Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid antitumor agent. Previous studies indicated that antitumor activity of CPT-11 was mediated through interaction of the drugs with its target enzyme, DNA topoisomerase I (topo I). In this study, we studied the relation between sensitivity to CPT-11 and topo I activity of glioma cells. Furthermore, we established CPT-11 resistant cell lines in order to elucidate the potential mechanisms of drug resistance. A clear correlation between the sensitivities to CPT-11 and topo I activities in surgical glioma specimens was demonstrated. Activities of topo I in the CPT-11-sensitive group (IC50 values for CPT-11; < 50 micrograms/ml) tended to be higher than those in the CPT-11-resistant group (IC50 values, > or = 50). Topo I activity may serve as a novel marker to predict the sensitivity of gliomas to topo inhibitors. CPT-11-resistant cell lines (T98G/CPT-11 and C6), respectively, exhibit a 5.4- and 7.3-fold increase in resistance to CPT-11. No differences in topo I activity and intracellular accumulation of CPT-11 were observed between the parent and CPT-11-resistant lines. On the other hand, topo I from T98G/CPT-11 and C6-CPT-11 cells was at least 4- and 2-fold resistant to the inhibitory effect of the CPT-11 on the relaxation activity of topo I, in comparison with their parent lines. This enzymological difference may be responsible for the resistance to CPT-11.

Animals↗

Cerebral retroflexion in holoprosencephaly developed following ventriculo-peritoneal shunting: a case report.

Retroflexion of the hypoplastic fused cerebrum is a rare condition in holoprosencephaly. We describe a new case of this entity in a 7-year-old boy with alobar holoprosencephaly whi developed retroflexion of the holosphere 7 years after a ventriculo-peritoneal shunt was placed. The radiological findings revealed retroflexion of the cerebrum anchored to the cranial vault between the precerebral space and the dorsal sac, which were open to each other. In patients with holoprosencephaly, the possibility of retroflexion of the holosphere should be considered after placement of a ventriculo-peritoneal shunt for associated hydrocephalus.

Brain↗

Diagnostic significance of nailfold bleeding in scleroderma spectrum disorders.

BACKGROUND: The early detection of scleroderma spectrum disorders (SSD) is important. OBJECTIVE: Our purpose was to determine the prevalence of nailfold bleeding in SSD. METHODS: We examined patients for nailfold bleeding in the following three groups: (1) 81 patients with SSD including 50 patients with scleroderma, 10 with mixed connective tissue disease, and 21 with Raynaud's phenomenon having specific antinuclear antibody (ANA); (2) 99 patients with other connective tissue diseases or primary Raynaud's phenomenon; and (3) 200 patients with common skin diseases. RESULTS: The frequency of nailfold bleeding was significantly higher in SSD (75.3%) than in other connective tissue diseases (12.1%) and in controls (3.0%). The presence of nailfold bleeding in two or more fingers showed a 98.3% specificity for SSD. Among the patients with SSD, the incidence of nailfold bleeding in scleroderma, mixed connective tissue disease, and Raynaud's phenomenon with specific ANA was similar. Nailfold bleeding strongly correlated with the presence of anticentromere antibody. CONCLUSION: The presence of nailfold bleeding is useful for the early detection of SSD.

Antibodies, Antinuclear↗

Folliculo-stellate cells in the human anterior pituitary express cytokeratin.

Recent studies have suggested that the anterior pituitary is derived not from Rathke's pouch, but instead from neuroectoderm. To address this controversy and the differentiation of the adenohypophysis, we evaluated folliculo-stellate cells from 7 human pituitaries using a panel of immunohistochemical stains. The panel included antibodies to a low molecular weight cytokeratin (CK-8), a broad spectrum of cytokeratins (AE 1/AE 3), S-100 protein, vimentin, and glial fibrillary acid protein. The most intense immunostaining was observed with the antibody to broad spectrum cytokeratins. Less intense immunohistochemical staining of folliculo-stellate cells was observed with the antibodies against glial fibrillary acidic protein and S-100 protein. Immunoblotting of anterior pituitary tissue obtained from 3 autopsied patients showed that cytokeratins identified in the anterior pituitary were of low molecular weight (40 to 56 Kd). These results indicate that folliculo-stellate cells show epithelial differentiation, and support the hypothesis that the anterior pituitary is derived from Rathke's pouch.

Blotting, Western↗

Metastatic behavior and tumorigenicity of a human melanoma cell line (MM-RU) after injection into nude mice.

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10(6) cells, all injected mice (n = 21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%-23% in three independent experiments. Survival time after i.v. inoculation was 63 +/- 7 days (mean +/- SD) (n = 20). Within 20 days, subcutaneous inoculation of 5 x 10(6) cells resulted in tumor growths of 13 +/- 3 mm (mean +/- SD) at the inoculation sites in all nude mice (n = 12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.

Animals↗

Short report: effect of sucralfate on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers in rats.

We investigated the effect of sucralfate on angiogenesis in granulation tissue of gastric ulcers induced by acetic acid in rats using the carmine dye method. Intragastric administration of sucralfate at a dose of 500 mg/kg twice daily for 9 days significantly accelerated ulcer healing and significantly increased the extent of angiogenesis in the ulcer base on the tenth day after ulcer induction. As we reported previously, intragastric administration of cimetidine at a dose of 100 mg/kg once daily for 9 days decreased the extent of angiogenesis on the tenth day. However, combination treatment using sucralfate and cimetidine accelerated ulcer healing significantly, without altering the extent of angiogenesis. It is concluded, therefore, that the treatment with sucralfate may be effective in peptic ulcer disease from the standpoint of angiogenesis in the ulcer base.

Animals↗