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T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 91 records · Page 5Linked to original sources
PubMed1999

Complement C1s activation in degenerating articular cartilage of rheumatoid arthritis patients: immunohistochemical studies with an active form specific antibody.

OBJECTIVE: The first complement component C1s was reported to have novel functions to degrade matrix components, besides its activities in the classic complement pathway. This study explores participation of C1s in articular cartilage degradation in rheumatoid arthritis (RA). METHODS: Normal articular cartilage (n = 6) and cartilage obtained from joints with RA (n = 15) and osteoarthritis (OA, n = 10) were immunostained using anti-C1s monoclonal antibodies PG11, which recognises both active and inactive C1s, and M241, which is specifically reactive to activated C1s. The effects of inflammatory cytokines on C1s production by human articular chondrocytes were also examined by sandwich ELISA. RESULTS: In normal articular cartilage, C1s was negative in staining with both PG11 and M241. In contrast, degenerating cartilage of RA was stained with PG11 (14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was activated as revealed by M241 staining. In OA, C1s staining was restricted in severely degrading part of cartilage (5 of 10 cases), and even in that part C1s was not activated. In addition, C1s production by chondrocytes in vitro was increased by an inflammatory cytokine, tumour necrosis factor alpha. CONCLUSION: These results suggest that C1s activated in degenerative cartilage matrix of RA but not in that of OA. C1s is thought to participate in the pathogenesis of RA through its collagenolytic activity in addition to the role in the classic cascade.

Adolescent↗
PubMed1999

Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic acini.

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma and recently localized to PP cells of the pancreatic islets of Langerhans. Based on the pancreatic islet-acinar axis model, we investigated the effect of adrenomedullin on regulated exocytosis of exocrine pancreas. Using rat [125I]-adrenomedullin, specific binding sites were localized to rat pancreatic acini. We next examined the effect of adrenomedullin on 100 pM cholecystokinin (CCK)-stimulated amylase release from pancreatic acini. Adrenomedullin inhibited amylase secretion in a dose-dependent manner by approximately 50% at maximum, and the IC50 was 1.1 pM. However, adrenomedullin did not affect rat [125I]CCK binding to isolated acini or reduce the intracellular free Ca2+ concentration increased by CCK. Adrenomedullin also inhibited amylase secretion induced by 1 microM calcium ionophore A23187, suggesting that adrenomedullin inhibits stimulated amylase secretion by functioning at a step(s) distal to the ligand-receptor binding system and intracellular calcium mobilizing mechanism. In streptolysin-O permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve to the right, indicating that adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery. In addition, pretreatment of pancreatic acini with pertussis toxin abolished the inhibitory effect of adrenomedullin on CCK-stimulated amylase secretion. These results indicate that adrenomedullin inhibits stimulated amylase secretion by reducing the calcium sensitivity of the exocytotic machinery of the pancreatic acini. A pertussis toxin-sensitive GTP-binding protein(s) is also involved in this mechanism.

Adrenomedullin↗
PubMed1999

Double high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells for treatment of an elderly patient with small-cell lung cancer.

We report a 62-year-old male with extensive disease small-cell lung cancer (SCLC) who was successfully treated with double high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT). This patient achieved a partial response with 3 cycles of induction chemotherapy. After the peripheral blood stem cell mobilization, two cycles of high-dose ICE regimen (ifosfamide 3,000 mg/m2 at days 1 to 5, carboplatin 400 mg/m2 at days 1, 3, 5, and etoposide 500 mg/m2 at days 1, 3, 5) could be given with further regression of the tumor and acceptable toxicities. This successful case suggests the feasibility of double high-dose ICE with auto-PBSCT in elderly patients with SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Very young patient with peculiar squamous cell carcinoma of the lung.

A 20-year-old man with squamous cell carcinoma of the lung is described. Histology of the open lung biopsy specimen revealed squamous cell carcinoma with definite keratinization. Interestingly, the tumor cells were characterized by partial expression of CD34 antigen and neuroendocrine differentiation. The diagnosis was delayed in this case because of his young age. This delayed diagnosis resulted in rapid progression and short survival time. In our review of 667 cases of lung cancers at Okayama University Hospital, only 3 (0.4%) of them were under 30 years of age and also showed advanced stage and very poor prognosis. It is important to take note of lung cancer as a differential diagnosis to detect early-stage lung cancer in young patients when they present with abnormal shadow on chest radiograph.

Adult↗
PubMed1999

Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.

Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.

Adenocarcinoma↗
PubMed1999

Lactonamycin, a new antimicrobial antibiotic produced by Streptomyces rishiriensis MJ773-88K4. II. Structure determination.

The absolute structure of a new antibiotic lactonamycin is described. The NMR studies deduced one of four possible structures for the aglycon attached by a rhodinose through glycosidic bond. The stereochemistry of the sugar obtained by an acid hydrolysis was determined to be L-form by measuring optical rotation. The stereochemistry of the aglycon was determined by X-ray crystallographic analysis.

Anti-Bacterial Agents↗
PubMed1999

[Phase 1 clinical study of 123I-IBF, a new radioligand for evaluating dopamine D2 receptor with SPECT (I); biodistribution and dosimetry].

A Phase 1 clinical study of 123I-IBF, (S)-5-iodo-7- N-[(1-ethyl-2-pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, developed for evaluation of dopamine D2 receptor (D2-R) with SPECT, was performed in 12 healthy male volunteers. No side effects due to 123I-IBF (i.v. 167 MBq) injection were observed. In sequential whole-body images, the radioactivity was distributed mainly in the liver, lungs and brain, and decreased gradually. No significant retention of radioactivity was seen in any organ at 24 hr after injection. The absorbed dose of 123I-IBF, calculated based on the whole-body pharmacokinetics, was equal to or less than those of other brain perfusion imaging agents. No significant problems were observed in terms of the safety, pharmacokinetics or absorbed dose of 123I-IBF.

Adult↗
PubMed1999

[Phase 1 clinical study of 123I-IBF, a new radioligand for evaluating Dopamine D2 receptor with SPECT (II); pharmacokinetics study and quantification in the brain].

The pharmacokinetics of (S)-5-iodo-7-N-[(1-ethyl- 2-pyrrolidinyl)methyl]carboxamido-2,3-dihydro-benzofuran (123I-IBF) in the brain were studied in 12 healthy male volunteers as a Phase I clinical study. The striatum-to-frontal cortex count ratio (-1) (St/Fc-1), which is a semi-quantitative index of the binding potential of 123I-IBF reached 1.81 +/- 0.19 and 2.21 +/- 0.39 at 90-120 min and 180-210 min after intravenous injection of 123I-IBF. St/Fc-1 obtained by SPECT at these times correlated well with the distribution volume ratio (-1) (Vd(St)/Vd(Fc)-1) based on three-compartment model analysis using an input function obtained by intermittent arterial sampling. The binding potential (BPR), calculated by the curve-fitting method using the time-activity curve in the reference region, also correlated well with the Vd(St)/ Vd(Fc)-1. The intra-observer and inter-observer reproducibilities of the striatum-to-cerebral cortex count ratios obtained using fixed-shape regions of interest (template ROIs) were superior to those obtained using manual ROIs. These results suggest that 123I-IBF is a promising agent for non-invasive quantification of the dopamine D2 receptor (D2-R) binding potential by SPECT.

Adult↗
PubMed1999

Hyperacute changes in glucose metabolism of brain tumors after stereotactic radiosurgery: a PET study.

UNLABELLED: Cultured tumor cells show a marked increase in deoxyglucose uptake as early as 3 h after single high-dose irradiation, reflecting hyperacute response of the cells to noxious intervention. To evaluate the hyperacute effect of high-dose irradiation on tumor glucose metabolism in vivo, we measured 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tumor uptake before and immediately after stereotactic radiosurgery. METHODS: A total of 19 brain tumors (17 metastatic and 2 primary, a meningioma and a central neurocytoma) in eight patients were treated with stereotactic radiosurgery. The received dose was between 24 and 32 Gy delivered to the central target point in the tumor. FDG PET was performed within 1 wk before radiosurgery and again 4 h after treatment. The net influx constant (Ki) was calculated on a pixel-by-pixel basis using graphical analysis, and the Ki ratio of tumor to ipsilateral cerebellum was used as an index of FDG uptake of the tumor. RESULTS: Eighteen of 19 irradiated tumors, all metastatic tumors and the meningioma, showed a 29.7% +/- 14.0% increase in the Ki ratio, which was significantly higher than that of nonirradiated tumors (4.1% +/- 3.6%, n = 8, P < 0.0001, analysis of variance). In metastatic tumors, an increase in the Ki ratio was significantly correlated with a decrease in the size of the irradiated tumors, as revealed by follow-up with CT or MRI (r = 0.61, P = 0.012, simple regression). The meningioma did not show a significant decrease in size, probably due to the short follow-up period. The central neurocytoma did not show any change in the Ki ratio or in tumor size. CONCLUSION: Serial FDG PET could be a potential tool for predicting the outcome of radiosurgery for brain tumors by detecting hyperacute changes in tumor glucose metabolism.

Brain↗
PubMed1999

Noninvasive measurement of cerebral metabolic rate of glucose using standardized input function.

UNLABELLED: The purpose of this study was to propose and validate a method for the noninvasive measurement of cerebral metabolic rate of glucose (CMRGlc) by fluorodeoxyglucose (FDG) PET with a standardized input function (SIF) and an autoradiographic method. METHODS: Plasma input functions, measured by intermittent arterial blood samplings after the intravenous injection of FDG, in 44 patients who had fasted for at least 6 h, were used to generate the SIF. The input function of each patient was normalized with the net injected dose (nID) of FDG and body mass as indicated by body surface area (BSA) or body weight (BW). The SIF was generated as an average of 44 normalized input functions. The estimation of the input function and CMRGlc with SIF was validated in 10 additional patients, who underwent FDG PET after fasting for at least 6 h. CMRGlc was estimated with a simulated input function (IFsim) generated with the following equation: IFsim = SIF x (nID/body mass). The estimated CMRGlc was compared with the measured CMRGlc. RESULTS: Based on BSA, the percentage error of the area under the curve of IFsim was 3.5%+/-2.2%. The percentage error of CMRGlc was 2.9%+/-1.9% in gray matter and 3.4%+/-2.2% in white matter. A similar percentage error was obtained based on BW. CONCLUSION: The proposed method is noninvasive and accurate, and therefore is clinically acceptable for measuring CMRGlc in patients in fasting states.

Autoradiography↗
PubMed1999

Expression of the thrombospondin 1 receptor CD36 is correlated with decreased stromal vascularisation in colon cancer.

Vascularisation is determined by the balance between various angiogenic and angio-inhibitory factors in cancer stroma. CD36 is a cell adhesion receptor shown to interact with the ligand thrombospondin 1 (TSP1). It has not been determined whether the interaction of TSP1 and its receptor CD36 is correlated with vascularisation or clinical outcome of malignant tumours in vivo. We studied the correlations between expression of TSP1, CD36 and vascularisation and prognosis in 65 colon cancers. Various levels of TSP1 gene expression were observed in 27 of 65 colon cancers. CD36 expression was detected in 33 of 65 cancers, and was significantly correlated with decreased stromal vascularisation (P<0.001). The colon cancers expressing CD36 showed better prognosis (P<0.01). TSP1 expression levels did not affect CD36 expression. These results suggested that CD36 expression which decreased stromal vascularisation is correlated with better prognosis of colon cancer.

CD36 Antigens↗
PubMed1998

Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells.

We have evaluated the efficacy of an anti-K-ras hammerhead ribozyme targeted against GUU-mutated codon 12 of the K-ras gene in a cell-free system as well as in cultured pancreatic carcinoma cell lines. In the cell-free system, the anti-K-ras ribozyme specifically cleaved K-ras RNA with GUU-mutation at codon 12, but not other triplet sequences at codon 12 of K-ras RNA. In the cell culture system, the anti-K-ras ribozyme significantly reduced K-ras mRNA level (GUU-mutated codon 12) in Capan-1 pancreatic carcinoma cells, but less significantly suppressed K-ras mRNA in Capan-2 (GUU/GGU heterozygous-mutation at codon 12) or MIA PaCa-2 (UGU-mutated codon 12) pancreatic carcinoma cells. The ribozyme inhibited proliferation of transfected Capan-1 cells. These results suggest that this ribozyme selectively recognizes single-base mutation of K-ras mRNA and is able to reverse the malignant phenotype in human pancreatic carcinoma cells.

Adenocarcinoma↗