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Biomedical subjects

T Sugita

Publications and source records attributed to T Sugita.

At least 19 recordsLinked to original sources

TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism.

Several mitogen-activated protein kinase kinase kinases (MAPKKKs), including NF-kappa B-inducing kinase (NIK), play critical roles in NF-kappa B activation. We isolated cDNA for human TGF-beta activated kinase 1 (TAK1), a member of the MAPKKK family, and evaluated its ability to stimulate NF-kappa B activation. Overexpression of TAK1 together with its activator protein, TAK1 binding protein 1 (TAB1), induced the nuclear translocation of NF-kappa B p50/p65 heterodimer accompanied by the degradation of I kappa B alpha and I kappa B beta, and the expression of kappa B-dependent reporter gene. A dominant negative mutant of NIK did not inhibit TAK1-induced NF-kappa B activation. These results suggest that TAK1 induces NF-kappa B activation through a novel NIK-independent signaling pathway.

Adaptor Proteins, Signal Transducing

Myxoma of the aortic valve.

Myxoma of the aortic valve is exceedingly uncommon. In this article, we report a 58-year-old man with myxoma arising from the aortic valve. Aortic valve replacement was performed, and postoperative histologic examination showed myxoma of aortic valve.

Aortic Valve

Suppression of arthritis by the inhibitors of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DP IV, CD26) is a serine exoprotease which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed as a surface marker on activated T cells. In order to assess the relevance of DP IV in immunological disorders, we evaluated the in vivo effects of specific DP IV inhibitors using two arthritis models, one which was induced by collagen one by alkyldiamine. These animal models share several pathological features associated with rheumatoid arthritis. The transition state substrate analog of DP IV, (S)-Alanylpyrrolidine-boronic Acid (Ala-boroPro), suppressed hind paw swelling, which was associated with collagen-induced and alkyldiamine-induced arthritis. A competitive inhibitor of DP IV, Lys(Z(NO2))-thiazolidide and an irreversible inhibitor, Ala-Pro-nitrobenzoylhydroxylamine also suppressed alkyldiamine-induced arthritis dose-dependently. We also analyzed the pharmacological effects of Lys(Z(NO2))-thiazolidide on several immune responses in vitro, in order to determine its mode of action. This inhibitor suppressed mitogen-induced and antigen-induced proliferation of T cells. However, studies using splenic cells from DP IV deficient rats showed that the inhibition of lymphocyte proliferation was not exerted through the inhibition of DP IV.

Animals

A case of type A dissection involving right aortic arch.

Aortic dissection involving right aortic arch (RAA) is quite rare. A patient with RAA and aberrant left subclavian artery (type 3 RAA) developed type A dissection, but successfully underwent ascending and hemiarch replacement under hypothermic circulatory arrest with continuous retrograde cerebral perfusion. We approached the lesion through a midline sternotomy and could reconstruct the first two arch vessels involved by the dissection. We would have added bilateral thoracotomy, if the distal arch vessels had required reconstruction. To our knowledge, this is the first report of successful surgical repair for type A dissection involving RAA.

Aortic Dissection

Constrictive pericarditis caused by an old hematoma.

A 46-year-old woman was admitted for surgery after diagnosis of a constrictive pericarditis. She had suffered from acute pericarditis and undergone pericardiocentesis to relieve pericardial effusion several times 10 years previously. Cardiac catheterization showed elevated mean right-atrial and pulmonary wedge pressures. Chest CT revealed only a calcified mass in the retrosternal space. At surgery, there was no severe adhesion between the pericardium and the epicardium, and the pericardium was thin and almost normal except over the right artio-ventricular groove, where a hard mass with an atheromatous content adhered to the epicardium. After resection of the mass, central venous pressure and pulmonary wedge pressure decreased. The mass was found to be an old hematoma by pathological examination. The patient was subsequently discharged from hospital in good condition.

Female

Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.

The cDNA encoding human 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase has been cloned from a placenta cDNA library, utilizing a PCR-derived probe. It encodes a peptide of 592 amino acids. The amino (N)-terminal sequence of this enzyme, purified from HeLa cells and CCRF-CEM cells, was found to be APGQLALF-. Both sequencing results revealed a difference of six N-terminal residues when compared to the reported sequence of cloned cDNA from a hepatoma cDNA library. Northern-blot analysis of human AICAR transformylase mRNA showed the expression of a single 2.0 kb mRNA in all tissues examined. With the cloned cDNA fragment, we constructed expression vectors for mature and GST-fused AICAR transformylase. Both recombinant molecules possessing AICAR transformylase activity were overproduced in Escherichia coli. GST-AICAR transformylase can be purified to homogeneity by a single-step affinity procedure with glutathione Sepharose. Mutational analysis, utilizing this expression system, showed that His213 and His267 were essential for AICAR transformylase activity.

Amino Acid Sequence

Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy. Case report.

A 60-year old male patient who had locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy underwent neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP), followed by concurrent radiotherapy and chemotherapy using protracted low-dose continuous infusion of 5-FU and CDDP. The treatment brought about complete remission in the primary lesion and good partial remission in the upper abdominal lymphadenopathy. He subsequently underwent trans-hiatal esophagectomy after one cycle of adjuvant chemotherapy because local recurrence was suspected. Histopathologic study of the resected specimen demonstrated no malignant tissue in the primary lesion and the lymph nodes. The patient is still alive and disease-free at 26+ months. This result suggests that neoadjuvant chemotherapy followed by concomitant chemotherapy and radiotherapy for patients who have locally advanced squamous cell carcinoma of the esophagus with intensive abdominal lymphadenopathy may offer some chance for sterilization of local and regional metastases and longer survival.

Antineoplastic Combined Chemotherapy Protocols

Partial sequences of large subunit ribosomal DNA of a new yeast species, Trichosporon domesticum and related species.

We determined the partial sequences of large subunit rDNA of a new yeast species, Trichosporon domesticum, which was isolated from the house of a summer-type hypersensitivity pneumonitis patient. Phylogenetically, T. domesticum was positioned in the taxonomic group containing T. montevideense and T. brassicae, which indicated an identical serotype. A phylogenetic relationship among all species of the genus Trichosporon which belong to the basidiomycetous yeast is clarified.

Alveolitis, Extrinsic Allergic

Effect of genotype on the angiotensin-converting enzyme mRNA level in human atria.

1. To clarify the mechanism of the association between I/D polymorphism of the angiotensin-converting enzyme (ACE) gene and various cardiovascular disease, ACE mRNA levels in human atrial appendages were assessed in relation to the genotype of the ACE gene. 2. Angiotensin-converting enzyme mRNA levels were positively correlated with age and tended to show a positive correlation with mean pulmonary pressure (mPA). Multiple regression analysis indicated that age and mPA, but not the genotype of the ACE gene, were predictors of ACE mRNA levels in human atrial appendages. 3. The present study indicates that I/D polymorphism of the ACE gene is not simply reflected in ACE mRNA levels and that further study is needed to determine the mechanism of the association between this polymorphism and various cardiovascular diseases.

Adolescent

Partial purification and characterization of manganese-oxidizing factors of Pseudomonas fluorescens GB-1.

The Mn(2+)-oxidizing bacterium Pseudomonas fluorescens GB-1 deposits Mn oxide around the cell. During growth of a culture, the Mn(2+)-oxidizing activity of the cells first appeared in the early stationary growth phase. It depended on the O2 concentration in the culture during the late logarithmic growth phase. Maximal activity was observed at an oxygen concentration of 26% saturation. The activity could be recovered in cell extracts and was proportional to the protein concentration in the cell extracts. The specific activity was increased 125-fold by ammonium sulfate precipitation followed by reversed-phase and gel filtration column chromatographies. The activity of the partly purified Mn(2+)-oxidizing preparation had a pH optimum of circa 7 and a temperature optimum of 35 degrees C and was lost by heating. The Mn(2+)-oxidizing activity was sensitive to NaN3 and HgCl2. It was inhibited by KCN, EDTA, Tris, and o-phenanthroline. Although most data indicated the involvement of protein in Mn2+ oxidation, the activity was slightly stimulated by sodium dodecyl sulfate at a low concentration and by treatment with pronase and V8 protease. By polyacrylamide gel electrophoresis, two Mn(2+)-oxidizing factors with estimated molecular weights of 180,000 and 250,000 were detected.

Bacterial Proteins

The novel anti-rheumatic drug TA-383 has a macrophage migration enhancing activity.

We have investigated the effect of a novel anti-rheumatic drug, cis-2-(4-chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride (TA-383), on macrophages. TA-383 (> or = 10(-9) M) significantly stimulated rabbit alveolar macrophage (AM) migration, and its migration-stimulatory activity was more potent than those of L-fucose (5 x 10(-3) M), lobenzarit disodium, bucillamine (SA-96) and salazosulfapyridine. In addition, TA-383 enhanced the production and/or release of macrophage migration enhancement factor by rabbit spleen cells. In vivo, TA-383 (0.4 mg/kg, p.o.) has suppressive effects on picryl chloride-induced delayed type hypersensitivity and type II collagen-induced arthritis in mice. These results suggest that the anti-rheumatic activity of TA-383 may be exerted through the dispersion of macrophages from inflammatory sites.

Animals

Domon L, an immunopotentiating agent, acts as an NF-kappaB activator.

Domon L, a heat-treated component of gram-negative bacterium Achromobacter stenohalis, is used for the treatment of infectious diseases of animals. Here, we investigated the immunopotentiating potential of Domon L. In vitro studies showed that Domon L enhanced nitric oxide (NO) formation from murine macrophage RAW264.7 cells in concert with interferon (IFN)-gamma. The effect of Domon L on NF-kappaB activation was investigated, in order to understand the molecular mechanisms of enhanced NO formation by Domon L. Domon L induced translocation of NF-kappaB to the nucleus in RAW264.7 cells. Induction of NF-kappaB dependent gene expression by Domon L was further confirmed using a transfectant containing an NF-kappaB-luciferase reporter gene. In vivo injection of Domon L elevated both serum IL-6 and mucoprotein, whose gene expression is partly under the control of NF-kappaB. The spleen cells of rats treated with Domon L produced much more NO when stimulated with LPS + IFN gamma than spleen cells of untreated rats. These results suggest that Domon L acts as an anti-infectious agent via NF-kappaB activation.

Achromobacter

Pathological evaluation of effect of anti-rheumatic drugs on type II collagen-induced arthritis in Lewis rats.

The effects of anti-rheumatic drugs (dexamethasone 0.1 mg/kg and naproxen 5 mg/kg) were evaluated immunologically and histopathologically on type II collagen-induced arthritis in Lewis rats. Increased paw volume in the hind limbs was significantly suppressed in the groups treated with dexamethasone or naproxen, but noticeable retardation of body weight gain was observed in the group treated with dexamethasone. Serum anti-type II collagen IgG was significantly suppressed in the group treated with dexamethasone but not naproxen. Histopathological evaluation by our grading system, classification of the stages in arthritic lesion development, revealed suppression of the inflammatory changes in the tarsal joints of the animals treated with dexamethasone or naproxen. From our results, histopathological evaluation is considered to be more suitable for assessment of the efficacy of anti-rheumatic drugs on type II collagen-induced arthritis, an animal model for human rheumatoid arthritis.

Animals

TMC-2A, -2B and -2C, novel dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. I. Taxonomy of producing strain, fermentation, and biochemical properties.

TMC-2A(1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with IC50 value of 8.1 microM, 17 microM, and 20 microM, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.

Animals

TMC-2A, -2B and -2C, new dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. II. Isolation and structure determination.

New dipeptidyl peptidase IV inhibitors, TMC-2A, -2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono- or dihydroxy-L-leucine and highly substituted isoquinoline.

Amino Acids

[Emergent coronary artery bypass grafting in a patient with mirror-image dextrocardia].

A 49 year-old-man with known situs inversus totalis was admitted to our hospital with a history of angina pectoris of 4 months duration. Coronary arteriography revealed that the left main trunk had a 90% stenosis. After the arteriography, the patient's hemodynamics was deteriorated, and he required a support of intraaortic balloon pumping. He underwent emergent coronary artery bypass grafting with saphenous veins the following day, and recovered uneventfully. Technical problems in this patient from a surgical viewpoint were discussed. As far as we know, this is the first case of coronary bypass grafting on a patient with mirror-image dextrocardia and a stenosis of the left main trunk.

Coronary Artery Bypass

Valve repair with chordal replacement for traumatic tricuspid regurgitation.

A 70-year-old woman who had fatiguability due to right heart failure seven years after receiving blunt chest trauma in a road traffic accident presented to our hospital. Preoperative echocardiography revealed severe tricuspid regurgitation resulting from prolapse of the anterior leaflet. The valve was repaired by chordal replacement with expanded polytetrafluoroethylene sutures and DeVega annuloplasty. At three months after surgery, the patient is in good clinical condition, and repeat echocardiography revealed only mild tricuspid regurgitation.

Accidents, Traffic