Infliximab-associated lymphoproliferative disorders.
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Antibodies, Monoclonal↗
Biomedical subjects
Toru Sasaki
Publications and source records attributed to Toru Sasaki.
Adenosine A1 receptor mapping of the human brain by PET with 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine.
UNLABELLED: Adenosine is an endogenous modulator of synaptic functions in the central nervous system. To investigate the physiologic and pathologic roles of the adenosine receptors in the human brain, PET is a powerful in vivo technique. In this study, we quantitatively evaluated the distribution of a major subtype A(1) adenosine receptor in the human brain by PET with a newly developed radioligand, 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX). METHODS: In 5 healthy volunteers, after PET measurement of the regional cerebral blood flow (rCBF) with (15)O-H(2)O, a 60-min PET scan with (11)C-MPDX was performed. The distribution volume (DV) of (11)C-MPDX was quantitatively evaluated by Logan's graphical analysis. RESULTS: (11)C-MPDX was taken up at a high level, reaching a peak at 2-2.5 min, followed by a rapid decrease. The unchanged form of (11)C-MPDX in plasma was 75% at 60 min after injection. The DV of (11)C-MPDX was large in the striatum and thalamus, moderate in the cerebral cortices and pons, and small in the cerebellum. The distribution pattern of (11)C-MPDX in the brain was coincident with that of adenosine A(1) receptors in vitro, reported previously, but discretely different from that of rCBF. CONCLUSION: (11)C-MPDX PET has the potential for mapping adenosine A(1) receptors in the human brain.
Adult↗
[Management of the system to allow the terminal cancer patients and their families to choose from in-hospital care, outpatient care and home care at Matsuyama Bethel hospital].
Hospice ward at Matsuyama Bethel Hospital opened in April 2000. The hospice care has been provided for inpatients and outpatients. We considered a system that should be established to allow patients and their families to choose from in-hospital care, outpatient care and home care. The hospice consultation for outpatients opened in April 2004. The terminal cancer patients who are within 6 months of remaining days were hospitalized to the hospice ward. After making the hospice consultation for outpatients, hospice care services have been provided for terminal cancer patients including those with more than 6 months of remaining days under the coordination of palliative care for outpatients and inpatients.
Ambulatory Care↗
Subglottic leiomyosarcoma of the larynx; a case report.
Leiomyosarcoma of the larynx is very rare. We herein report an especially rare case of leiomyosarcoma originating in the subglottic mucosa. The majority of cases reported in the literature indicate that laryngeal leiomyosarcomas originate in the supraglottic or glottic area. Our patient underwent simple total laryngectomy and is free of disease 5 years after the operation. The literature is reviewed regarding the choice of treatment and the distribution of the reported sites of origin of laryngeal leiomyosarcoma.
Disease-Free Survival↗
[11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration.
To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.
Animals↗
Quantitative measurement of histamine H(1) receptors in human brains by PET and [11C]doxepin.
The aim of this study is to establish a method for quantitative measurement of histamine H(1) receptor (H1R) in human brain by PET and [(11)C]doxepin ([(11)C]DOX). The estimated parameters with a two-compartment model were stable for the initial values for parameter estimation but those with a three-compartment model were not. This finding suggests that the H1R measured by the [(11)C]DOX and PET can be evaluated with a two-compartment model.
Adult↗
Potential of [11C]TMSX for the evaluation of adenosine A2A receptors in the skeletal muscle by positron emission tomography.
We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.
Adult↗
Quantitative analysis of adenosine A1 receptors in human brain using positron emission tomography and [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine.
Fully quantitative analysis of the adenosine A(1) receptor (A1R) in the brain with (11)C-MPDX and positron emission tomography is reported. The kinetics is described using a two-tissue three-compartment model, and estimated binding potentials correspond well with the estimates made by Logan plot. The image of the binding potential of the MPDX is physiologically reasonable. We conclude that MPDX is applicable to the visualization of the A1Rs in the brain with Logan plot.
Adult↗
Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin.
The aim of this study was to develop simplified positron emission tomography measurement using [(11)C]doxepin ([(11)C]DOX) to evaluate histamine H(1) receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [(11)C]DOX, estimated quantitatively with a two-compartment model, and the [(11)C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [(11)C]DOX-H1R binding.
Adult↗
SF2809 compounds, novel chymase inhibitors from Dactylosporangium sp. 1. Taxonomy, fermentation, isolation and biological properties.
Six novel chymase inhibitors, SF2809-I, SF2809-II, SF2809-III, SF2809-IV, SF2809-V and SF2809-VI, were isolated from the fermentation broth of an actinomycete strain SF2809. The strain was identified as Dactylosporangium sp. by morphological, chemotaxonomical and phylogenetic studies. These six novel compounds inhibited recombinant human chymase in the range between IC50 of 0.014 and 7.3 microM. However, they showed little or no inhibitory activity against chymotrypsin or cathepsin G, even though these two and chymase belong to the chymotryptic serine protease family. This result indicates that these compounds work as specific chymase inhibitors.
Actinobacteria↗
SF2809 compounds, novel chymase inhibitors from Dactylosporangium sp. 2. Structural elucidation.
Novel chymase inhibitors, SF2809-I, II, III, IV, V and VI, were isolated from the fermentation broth of Dactylosporangium sp. SF2809, and their structures were determined by spectroscopic analyses. SF2809 compounds commonly contain a substituted indole moiety and a quinolinone moiety. The two moieties are connected to a methylene carbon in SF2809-I and III. The other compounds, SF2809-II, IV, V and VI, have an additional moiety, a p-hydroxyphenyl group or a phenyl group. In these compounds, all of three moieties are connected to a methine carbon. Furthermore, studies concerning the stereochemistry of SF2809-V revealed that the isolated compound was racemic, and the isomer possessing (R)-configuration was about thirty times more potent than another isomer.
Chemical Phenomena↗
[A case of 10-year survival after combination chemotherapy of 5'-deoxy-5-fluorouridine and cisplatin and adjuvant surgery for gastric cancer with liver metastasis].
A 36-year-old woman was diagnosed with type 3 advanced gastric cancer with multiple liver metastases in March 1992. The patient was treated with systemic chemotherapy of 5'-deoxy-5-fluorouridine and cisplatin. After 4 courses of chemotherapy, the primary lesion responded and the multiple liver metastases disappeared. Therefore, total gastrectomy with perigastric lymphadenectomy and splenic preservation was performed. Two additional courses of the same chemotherapy were administered after the surgery. The patient has been alive without recurrence for 10 years after the curative resection.
Adenocarcinoma↗
[Combination chemotherapy of TS-1 +cisplatin for inoperable gastric cancer].
There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.
Antineoplastic Combined Chemotherapy Protocols↗
Lymphoid enhancer factor 1 makes cells resistant to transforming growth factor beta-induced repression of c-myc.
The activation of lymphoid enhancer factor (LEF)/T-cell factor (TCF)-mediated transcription by sustained expression of beta-catenin and the loss of transforming growth factor beta (TGF-beta) signaling are essential steps in carcinogenesis, particularly for cancers of the colon, breast, and liver. The oncogene c-myc is a common target of both of these signaling pathways and a key regulator of cell cycle progression. Here we have identified a novel LEF/TCF-responsive element in the promoter of the human c-myc gene. beta-Catenin activated the transcriptional activity of the c-myc promoter by binding to this element in various cell lines. When TCF-4 was bound to this element, TGF-beta dissociated beta-catenin and repressed the transcriptional activity of the c-myc promoter. However, TGF-beta could not dissociate beta-catenin and could not repress c-myc transcription when LEF-1 was bound to the element instead of TCF-4. These findings suggest that enhanced expression of LEF-1, which occurs frequently in colon cancer, may make cells refractory to the down-regulation of c-myc and the subsequent growth arrest induced by TGF-beta.
3T3 Cells↗
Imaging of adenosine A1 receptors in the human brain by positron emission tomography with [11C]MPDX.
We report the first clinical PET study using [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([11C]MPDX) for imaging adenosine A1 receptors in the human brain. The binding of [11C]MPDX evaluated quantitatively as the distribution volume by a graphical analysis was high in the striatum and thalamus, and low in the cerebellum. The distribution pattern of [11C]MPDX was coincident with that of adenosine A1 receptors in vitro reported previously, and was different from those of blood flow and [18F]FDG. The [11C]MPDX PET has the potential for mapping adenosine A1 receptors in the human brain.
Brain↗
Endoscopic mucosal resection (EMR) for the management of poorly differentiated adenocarcinoma of the stomach: a patient who had recurrence and died 4 years after EMR.
Recent studies have explored the possibility of using endoscopic mucosal resection (EMR) to treat lesions with a relative indication for endoscopic therapy. We used EMR to manage poorly differentiated adenocarcinoma, a relative indication for endoscopic treatment, in a patient who requested such treatment and refused surgical intervention. We describe our experience with this patient, who died of tumor recurrence 4 years after the EMR. This case describes the problems of using EMR for the treatment of poorly differentiated adenocarcinoma.
Adenocarcinoma↗
[Cardiovascular imaging in-a month. A case of abnormal cardiac border accidentally detected on chest roentgenogram. Pericardial cyst].
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Aged↗
Three-dimensional solution structure of the sodium channel agonist/antagonist delta-conotoxin TxVIA.
The three-dimensional solution structure of delta-conotoxin TxVIA, a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional (1)H NMR spectroscopy with simulated annealing calculations. A total of 20 converged structures of delta-conotoxin TxVIA were obtained on the basis of 360 distance constraints obtained from nuclear Overhauser effect connectivities, 28 torsion angle constraints, and 27 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.35 +/- 0.07 A for the backbone atoms (N, C(alpha), C) and 0.98 +/- 0.14 A for all heavy atoms of the entire peptide. The molecular structure of delta-conotoxin TxVIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. However, the three-dimensional structure of delta-conotoxin TxVIA has an unusual hydrophobic patch on one side of the molecule, which may play an important role in the sodium channel binding. These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel interaction and insight into the discrimination of different ion channels.
Amino Acid Sequence↗