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Biomedical subjects

M Tsuda

Publications and source records attributed to M Tsuda.

At least 199 records · Page 11Linked to original sources

[A case of pleural metastasis of invasive thymoma with pulmonary metastasis responding to chemotherapy with cyclophosphamide and prednisolone].

The patient, a 48-year old male, was seen with hoarseness in December 1990. A chest radiograph and chest CT scan showed an anterior mediastinal mass. Median sternotomy revealed epithelial thymoma with involved partial lung and pericardium. After surgery, he received external radiation to the mediastinum. One year later he was given another 40 Gy external radiation in the cervical and mediastinal recurrence region. In May 1994, a chest CT scan revealed an extrapleural and bilateral lung mass. Histological examination revealed recurrent epithelial thymoma in the left cervical muscle biopsy, so treatment with cyclophosphamide and prednisolone were begun. A dose of 100 mg/body/day of cyclophosphamide and a dose of 10 mg/body/day of prednisolone were administered every 2 week. Complete remission was induced with four cycles of this treatment of cyclophosphamide and prednisolone. The chemotherapy was thus continued for 20 cycles in 14 months. This chemotherapy with cyclophosphamide and prednisolone appeared to be useful and safe for recurrent thymoma at the outpatient clinic level.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 on alveolar macrophages in the acute stage of radiation-induced lung injury in rats.

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on alveolar macrophages and on lung tissue in the early stage of radiation-induced lung injury. Cells in the bronchoalveolar lavage and lung tissue were obtained from rats at various times between 1 and 8 weeks after 20 Gy of 60Co gamma irradiation of a hemithorax. These specimens were stained immunohistochemically with anti-ICAM-1 and anti-LFA-1alpha monoclonal antibodies. The expression of these factors was compared with that of a control group. The total number of alveolar macrophages in the bronchoalveolar lavage was significantly reduced from 1 to 3 weeks, and the number of neutrophils was significantly increased 2 and 3 weeks after irradiation. ICAM-1 and LFA-1 expression on alveolar macrophages was significantly increased starting 1 week after irradiation. The expression of ICAM-1 and LFA-1 on lung tissue was not elevated up to 8 weeks after irradiation. In conclusion, the increased expression of ICAM-1 and LFA-1 on alveolar macrophages as early as 1 week after irradiation suggests that adhesion molecules play a role in the development of radiation-induced lung injury.

Analysis of Variance↗

[Minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass: a case report].

A new coronary artery bypass grafting of the left anterior descending coronary arteries (LAD) with in situ internal thoracic artery (ITA) bypass grafts through a limited anterior thoracotomy was performed in a 70-year-old [correction of 60] patient. The left ITA-LAD anastomosis was completed without cardiopulmonary bypass and postoperative angiography showed a patent anastomosis. With this minimally invasive approach, the procedure should provide the benefits of ITA grafting with rapid recovery short hospital stay without complication associated with cardiopulmonary bypass in selected cases.

Aged↗

[Thoracoscopic cutting needle biopsy].

We presented a new method of percutaneous cutting needle biopsy under the thoracoscope. Percutaneous cutting needles for lung tumor have been abandoned because the risk of hemorrhage, death, and pneumothorax is much greater with these instruments than the computed tomographic guided needle aspiration. On the other hand, thoracoscopic stapled lung wedge resection is easy to obtain a good sample for any lung disease, but should be needed two or three staples, and waste a time, in the case following lobectomy was needed for malignancy. This thoracoscopic cutting needle biopsy was easy to obtain a specimen for the frozened section diagnosis. Under the view of thoracoscope, percutaneous cutting needle biopsy is safety, saving the cost for staples and easy to control the bleeding from the lung. The indication of this thoracoscopic cutting needle biopsy is the case that could not obtain the precise diagnosis by the preoperative biopsy and imaging diagnosis might be suspicious a malignant tumor.

Biopsy, Needle↗

Early damage to lung tissue after irradiation detected by the magnetic resonance T2 relaxation time.

We sought to determine whether nuclear magnetic resonance relaxation times of water in tissue would be useful to detect molecular damage in lung tissue within 2 weeks after irradiation. Tissue samples were obtained from the lungs of rats at various times between 1 and 14 days after exposure of a hemithorax to 20 Gy 60Co gamma irradiation. The spin-lattice relaxation time, T1, was measured by the inversion recovery method, and the spin-spin relaxation time, T2, was measured by both the Hahn spin-echo (Hahn T2) and the Carr-Purcell-Meiboom-Gill (CPMG T2) methods. The T2 of lung tissue could be divided into two components, T2 fast (T2f) and T2 slow (T2s), which reflected changes in the intracellular and extracellular water, respectively. The CPMG T2f increased significantly 3 days after irradiation (66.3 +/- 2.3 ms compared to 60.8 +/- 2.6 ms), and the CPMG T2s increased significantly 1 day after irradiation (155 +/- 11 ms compared to 138 +/- 7 ms), prior to the observation of abnormalities upon examination of the lung by light microscopy. The CPMG T2 values increased further up to 14 days after irradiation when significant increases were observed in values for T1, Hahn T2 and water content. Our results indicate that the molecular derangement in irradiated lung tissue was detected by the CPMG T2 measurement in the very early stage, and that MRI may be superior to conventional radiographs for detecting the early damage to lung tissue after irradiation.

Animals↗

[A case of huge abscess extended from anterior neck to left lung and lateral chest wall].

62-year-old woman admitted our hospital with pain of left upper extremity from the left chest and dysphasia. Chest X-ray showed the huge mass shadow in the left lung field. Diabetes mellitus and inflammatory reaction such as high fervor, leukocytosis, CRP and ESR accentuation were recognized. Conservative therapy was done at first, but mass shadow on X-ray increased, and swelling appeared from the neck to the left lateral chest wall. And the same site appeared like subcutaneous emphysema. Computed Tomography showed mass shadow which was enlarged and spread in lung parenchyma and left chest wall with bubble image. Incision and open drainage was performed for the left chest wall but origin bacteria was detected in neither anaerobic nor aerobic culture of pus. Inflammation and mass shadow of left upper lung field have decreased gradually. The patient discharged without bronchoalveolar fistula. Abscess extending from the neck or chest wall with diabetes mellitus is very rare.

Abscess↗

[Significance of ICH--toxicokinetics guidance and its practice--a useful approach for safety drug development].

In the International Conference on Harmonization (ICH), "Note for Guidance on Toxicokinetics: the Assessment of Systemic Exposure in Toxicity Studies (ICH Harmonized Tripartite Guideline)" was signed off in October 1994 by 6 parties of Japan, EU and the United States. The Ministry of Health and Welfare, Japan, has issued the notification "Upon the Guidance for Toxicokinetics (Assessment of Systemic Exposure in Toxicity Studies)" (Yakushin No. 443 dated July 2, 1996). The notification stated that pivotal toxicity study which initiates on and after January 1st, 1997 should includes appropriate Toxicokinetic study. In the ICH Guidance for pharmaceuticals, TK is defined as the generation of pharmacokinetic data, either as an integral component in the conduct of non-clinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. These data may be used in the interpretation of toxicology findings and their relevance to clinical safety issues. TK study is considered to be indispensable for safety assessment, and thus should be conducted in compliance with the GLP regulations. The ICH guidance also emphasizes that the exposure assessment in individual toxicity studies should be based on a flexible and step by step and a case by case decision making process. In this review article, the background for the introduction of this TK Guidance, the outline of the ICH-TK Guidance, the definition and fundamental principles of the ICH-TK, and its toxicological significance and practical problems in the conduct of TK study are described.

Animals↗

BDNF gene can Be activated by Ca2+ signals without involvement of de novo AP-1 synthesis.

Although stimulation of N-methyl-D-aspartate receptors or voltage-dependent calcium channels induces both the activation of c-fos and brain-derived neurotrophic factor (BDNF) genes, it is not certain how the activation of these genes is related. Using primary cultures of rat hippocampal neurons, we found that exposing the cells to cycloheximide allowed subsequent activation of BDNF mRNA expression, although activation of AP-1 DNA-binding activity resulting from the c-fos induction was abolished. Super-induction of BDNF gene was also caused by cycloheximide. The estimated half-life of BDNF mRNA was approximately 2.5 hrs, which was almost identical to that of c-fos mRNA. These results indicate that nascent AP-1 is not required for the activation of BDNF gene, leading to the notion that the BDNF gene can be activated by Ca2+ signals as an immediate early gene.

Animals↗

Simple purification and functional reconstitution of octopus photoreceptor Gq, which couples rhodopsin to phospholipase C.

In invertebrate photoreceptors, illuminated rhodopsin activates multiple G proteins, which are assumed to initiate multiple phototransduction cascades. In this paper, we focused on one of the phototransduction cascades, which utilizes rhodopsin, a Gq-like G protein, and phospholipase C (PLC). A Gq-like G protein from octopus photoreceptors was successfully purified to apparent homogeneity as an active form by simple two-step chromatography. The purified G protein had an alpha beta gamma-trimeric structure consisting of 44-kDa alpha, 37-kDa beta, and 9-kDa gamma subunits. The 44-kDa alpha subunit was assigned to the Gq class by western blot with antiserum against mammalian Gq alpha and by partial amino acid sequencing of its proteolytic fragments. Light-dependent binding of GTP gamma S was observed when the purified octopus Gq was reconstituted with octopus rhodopsin that had been integrated into phospholipid vesicles. Octopus Gq activated PLC beta 1 purified from bovine brain dose-dependently in the presence of A1F4-. Finally, light- and GTP-dependent activation of PLC beta 1 was observed in a reconstitution system consisting of octopus rhodopsin, Gq, and bovine PLC beta 1.

Aluminum Compounds↗

Rapid attenuation of AP-1 transcriptional factors associated with nitric oxide (NO)-mediated neuronal cell death.

Stimulation of glutamate receptors causes several intracellular reactions including activation of activator protein-1 (AP-1) production and nitric oxide (NO) generation. Exposing mouse cerebellar granule cells to N-methyl-D-aspartate or kainate (KA) in culture induced an increase of AP-1 DNA binding activity that was blocked by further addition of sodium nitroprusside (SNP), a typical NO donor. Immunoblotting using anti-c-Fos antiserum revealed the specific attenuation of AP-1, although total protein synthesis was not affected. Since the level of c-fos mRNA expression stimulated by KA remained constant even after exposure to SNP, the AP-1 attenuation can be post-transcriptionally induced. SNP did not affect the Ca2+ influx into the cells stimulated by KA. The involvement of NO in the AP-1 attenuation was supported by the fact that potassium ferrocyanide (K4Fe(CN)6), an analogue of SNP but devoid of NO, failed to inhibit the AP-1 DNA binding activity stimulated by KA. SNP alone induced neuronal cell death, which was blocked by the simultaneous addition of antioxidants, superoxide dismutase and catalase, and an NO scavenger, suggesting a direct role of peroxynitrite in the cell death. In good agreement with these effects, the AP-1 attenuation by SNP was also blocked by antioxidants. These results indicated that post-transcriptional attenuation of AP-1 is involved in the early processes of NO-mediated neuronal cell death.

Animals↗

Ultraviolet resonance Raman evidence for the absence of tyrosinate in octopus rhodopsin and the participation of Trp residues in the transition to acid metarhodopsin.

The ultraviolet (244 nm) resonance Raman spectra of octopus rhodopsin and its photoproduct, acid metarhodopsin, do not give any evidence for a tyrosinate. This finding excludes the possibility that Tyr-112 serves as the counter anion to the protonated Schiff base as does Glu-113 in bovine rhodopsin. Upon photoconversion from rhodopsin to acid metarhodopsin, Trp and Tyr Raman bands decrease in intensity and concomitantly a Trp band shifts in frequency. The changes of Trp Raman bands are ascribed to changes in hydrophobic interactions and conformation, suggesting a possible role of Trp in the photoconversion process of octopus rhodopsin.

Animals↗

Characterization of a 115-kDa protein that binds to SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in Chinese hamster ovary cells.

SH-PTP2, a non-transmembrane-type protein-tyrosine phosphatase with two Src homology 2 domains, was previously shown to play a positive signaling role in the insulin-induced activation of Ras and mitogen-activated protein kinase. SH-PTP2 was shown to associate with a 115-kDa tyrosine-phosphorylated protein (pp115), as well as with insulin receptor substrate 1, in insulin-stimulated Chinese hamster ovary cells that overexpress human insulin receptors (CHO-IR cells). In vivo and in vitro binding experiments revealed that SH-PTP2 bound to pp115 through one or both of its SH2 domains. The pp115 protein was partially purified from insulin-stimulated CHO-IR cells that overexpress a catalytically inactive SH-PTP2 by a combination of immunoaffinity and lectin-affinity chromatography. A monoclonal antibody to pp115 was then generated by injecting the partially purified protein into mice. Experiments with this monoclonal antibody revealed that pp115 is a transmembrane protein with a domain exposed on the cell surface and that it binds to SH-PTP2 in response to insulin. The insulin receptor kinase appeared to phosphorylate pp115 on tyrosine residues both in vivo and in vitro. The extent of tyrosine phosphorylation of pp115 associated with SH-PTP2 was greatly increased in CHO-IR cells that overexpress catalytically inactive SH-PTP2 compared with that observed in CHO-IR cells overexpressing wild-type SH-PTP2. Furthermore, recombinant SH-PTP2 preferentially dephosphorylated pp115 in vitro, indicating that SH-PTP2 may catalyze the dephosphorylation of phosphotyrosine residues in pp115 after it binds to this protein. These results suggest that pp115 may act as a transmembrane anchor to which SH-PTP2 binds in response to insulin. Furthermore, pp115 may be a physiological substrate for both the insulin receptor kinase and SH-PTP2.

Animals↗

Mecamylamine-precipitated nicotine-withdrawal aversion in rats.

The present study examined a rapid and convenient model for evaluating nicotine dependence using the conditioned place preference paradigm. Rats were chronically infused subcutaneously with 9 mg/kg per day nicotine using an osmotic minipump. After nicotine infusion for 7 days, the nicotinic receptor antagonist mecamylamine produced a place aversion in nicotine-dependent rats, but not in acute nicotine-treated rats or sham-operated rats. These results suggest that the mecamylamine-precipitated withdrawal aversion in rats chronically treated with nicotine may result from physical dependence on nicotine, and may be useful for studying the physical dependence on nicotine.

Analysis of Variance↗

A genetic analysis system of Burkholderia cepacia: construction of mobilizable transposons and a cloning vector.

A genetic analysis system of Burkholderia cepacia (Bc) was developed which included transposon mutagenesis and complementation of mutation with the cloned genes of interest. To deliver the transposon in this multidrug-resistant microorganism, two plasmids, pKN30 and pKN31, were constructed which contained Tn5 derivatives, Tn5-30Tp and Tn5-31Tp, respectively, carrying KmR and TpR genes. The plasmids have the origin of ColE1 replication and the mobilization gene of RP4. Tn5-31Tp was mobilized to Bc KF1, a strain isolated from a pneumonia patient, by the transfer system of RP4 integrated in the chromosome of Escherichia coli (Ec). Selection with trimethoprim resulted in generation of a number of transposants of Bc KF1. Fourteen protease-deficient mutants were isolated, all of which contained a single transposon marker in the chromosome. Thirteen protease-deficient mutants were also lipase deficient. An Ec-Bc shuttle plasmid, pTS1209, was constructed that consists of oriColE1, oripSa, ApR and CmR genes, and several unique restriction sites for cloning. Plasmid pTS1209 was successfully employed for cloning genes of Bc involved in protease production.

Burkholderia cepacia↗

Mutational analysis of the CitA citrate transporter from Salmonella typhimurium: altered substrate specificity.

The CitA citrate transporter in Salmonella typhimurium is encoded by the citA gene and consists of 434 amino acid residues that probably include 12 membrane-spanning segments [Shimamoto. T., et al. (1991) J. Biochem. 110, 22-28]. CitA mutants with altered substrate specificities were isolated by in vitro mutagenesis using nitrous acid. The mutants could grow on isocitrate as a sole carbon source which normally cannot be transported well by the CitA transporter of S. typhimurium. The mutation sites in the citA gene of the nine mutants were determined to involve single residues at seven sites (one mutation per mutant). The original amino acid residues at these sites (Arg-19, Ala-38, Glu-51, Gly-132, Ala-169, Pro-262 and Leu-271) were identified to be responsible for the altered substrate specificity. All these amino acid residues were conserved in four other homologous citrate transporters from Escherichia coli, Citrobacter amalonaticus and Klebsiella pneumoniae and are suggested to be involved in substrate recognition by the CitA transporter.

Amino Acid Sequence↗