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Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.

Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives have been synthesized and found to be potent inhibitors of Escherichia coli peptide deformylase (PDF). Most of the compounds synthesized and tested displayed antibacterial activities that cover several pathogens found in respiratory tract infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The potential of these compounds as antibacterial agents is discussed with respect to selectivity, intracellular concentrations in bacteria, and potential for resistance development.

Amidohydrolases↗
PubMed2000

Novel mix-family homeobox genes in zebrafish and their differential regulation.

We report the isolation of two novel zebrafish mix-type homeobox genes, mtx1 and mtx2. The homeodomains of both Mtx1 and Mtx2 exhibited a 50% amino acid identity to other Mix-family protein homeodomains. mtx1 was expressed throughout the yolk syncytial layer (YSL), an extraembryonic structure in teleosts, from the late-blastula to the mid-gastrula period. mtx2 was first expressed in the dorsal blastomeres soon after the mid-blastula transition, and slightly later in the entire blastoderm margin. After the late blastula period, mtx2 transcripts were detected in the YSL, and they were restricted to the dorsal YSL by the early gastrula period. The expression of mtx2 was dependent on Wnt signals but not on Nodal signals. mtx1 expression was not regulated by either Wnt or Nodal signals. This is in complete contrast to the Nodal signal-dependent expression of mixer. These results indicate the complexity of the regulation of mix-type homeobox genes.

Amino Acid Sequence↗
PubMed2000

Reperfusion lung injury after cold preservation correlates with decreased levels of intrapulmonary high-energy phosphates.

BACKGROUND: To evaluate the role of energy state in primary graft dysfunction, which is crucial in lung transplantation, we investigated the relationship between intrapulmonary high-energy phosphate compounds and reperfusion lung injury after cold preservation. METHODS: Using an isolated rat lung perfusion model with fresh rat blood as perfusate, rat lungs were exposed to various cold preservation periods (0, 6, 9, and 12 hr) and reperfused. RESULTS: We found that extending the preservation period exacerbated the pulmonary hemodynamics after reperfusion. The levels of intrapulmonary high-energy phosphate compounds did not change during cold preservation, but these levels after reperfusion decreased as the preservation period was prolonged. The pulmonary hemodynamics after reperfusion were inversely correlated with the intrapulmonary high-energy phosphate compound levels after reperfusion. Total adenine nucleotide and ATP were sensitive indicators of reperfusion lung injury after cold preservation. Energy charge was not a sensitive indicator. The decreased levels of intrapulmonary high-energy phosphate compounds after reperfusion following cold preservation period were partially caused by their decreased production. CONCLUSIONS: These results demonstrated that reperfusion lung injury after cold preservation was closely correlated with decreased levels of intrapulmonary high-energy phosphate compounds after reperfusion, although the levels of the intrapulmonary high-energy phosphate compounds did not change during cold preservation of up to 12 hr.

Adenine Nucleotides↗
PubMed2000

Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the formation of the dorsal organizer in zebrafish.

In vertebrates, specification of the dorso-ventral axis requires Wnt signaling, which leads to formation of the Nieuwkoop center and the Spemann organizer (dorsal organizer), through the nuclear accumulation of beta-catenin. Zebrafish bozozok/dharma (boz) and squint (sqt), which encode a homeodomain protein and a Nodal-related protein, respectively, are required for the formation of the dorsal organizer. The zygotic expression of boz and sqt in the dorsal blastoderm and dorsal yolk syncytial layer (YSL) was dependent on the maternally derived Wnt signal, and their expression at the late blastula and early gastrula stages was dependent on the zygotic expression of their own genes. The dorsal organizer genes, goosecoid (gsc) and chordin (din), were ectopically expressed in wild-type embryos injected with boz or sqt RNA. The expression of gsc strictly depended on both boz and sqt while the expression of din strongly depended on boz but only partially depended on sqt and cyclops (cyc, another nodal-related gene). Overexpression of boz in embryos defective in Nodal signaling elicited the ectopic expression of din but not gsc and resulted in dorsalization, implying that boz could induce part of the organizer, independent of the Nodal proteins. Furthermore, boz; sqt and boz;cyc double mutants displayed a severely ventralized phenotype with anterior truncation, compared with the single mutants, and boz;sqt;cyc triple mutant embryos exhibited an even more severe phenotype, lacking the anterior neuroectoderm and notochord, suggesting that Boz/Dharma and the Nodal-related proteins cooperatively regulate the formation of the dorsal organizer.

Animals↗
PubMed2000

Prognostic significance of cyclin E overexpression in resected non-small cell lung cancer.

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with non-small cell lung cancer remains unknown. We examined the expression of cyclin E in 242 resected non-small cell lung cancer in pathological stages I-IIIa and analyzed its relation to clinicopathological factors. Cylin E overexpressions were observed frequently in deeply invasive tumors. Multivariate analysis revealed that complete resection, pathological stage, and cyclin E expression were independent prognostic indicators. When cyclin E and proliferating cell nuclear antigen are combined, the cases negative for both had a significantly better prognosis than the other cases. We concluded that cyclin E overexpression relates to deeply invasive tumors and is correlated with poor prognosis. New therapeutic options may be provided by combination of cyclin E expression and proliferating cell nuclear antigen overexpression.

Adenocarcinoma↗
PubMed2000

Regulation and reversibility of vacuolar H(+)-ATPase.

Arabidopsis thaliana vacuolar H(+)-translocating pyrophosphatase (V-PPase) was expressed functionally in yeast vacuoles with endogenous vacuolar H(+)-ATPase (V-ATPase), and the regulation and reversibility of V-ATPase were studied using these vacuoles. Analysis of electrochemical proton gradient (DeltamuH) formation with ATP and pyrophosphate indicated that the proton transport by V-ATPase or V-PPase is not regulated strictly by the proton chemical gradient (DeltapH). On the other hand, vacuolar membranes may have a regulatory mechanism for maintaining a constant membrane potential (DeltaPsi). Chimeric vacuolar membranes showed ATP synthesis coupled with DeltamuH established by V-PPase. The ATP synthesis was sensitive to bafilomycin A(1) and exhibited two apparent K(m) values for ADP. These results indicate that V-ATPase is a reversible enzyme. The ATP synthesis was not observed in the presence of nigericin, which dissipates DeltapH but not DeltaPsi, suggesting that DeltapH is essential for ATP synthesis.

Adenosine Triphosphate↗
PubMed2000

Altered plasma antigen levels of tissue factor pathway inhibitor during open-heart surgery.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic pathway of the coagulation cascade that is activated by cardiopulmonary bypass (CPB) during open-heart surgery. In the present study, we investigated whether the plasma TFPI antigen increases during CPB in 12 patients who underwent bypass procedures. The plasma levels of free and total TFPI antigens were measured using an enzyme-linked immunosorbent assay, and heparin concentrations were measured using a chromogenic substrate assay. We found that changes in the total plasma TFPI antigen level were significantly dependent on the level of free TFPI antigen (r = 0.96, P < 0.0001) which increased significantly after heparin injection (P < 0.0001), and increased further during the bypass period (P < 0.005). The increased free TFPI antigen level during CPB correlated with the duration of bypass (r = 0.65, P = 0.02). When heparin was neutralized by protamine, the free TFPI antigen level decreased immediately, but remained higher than the preoperative level (P < 0.005). These results suggest that plasma TFPI antigen levels increase during CPB.

Anticoagulants↗
PubMed2000

A 37-kDa peroxidase secreted from liverworts in response to chemical stress.

A peroxidase was purified from the culture medium of a suspension culture of Marchantia polymorpha (liverwort) after treatment with bornyl acetate, which acts as a chemical stress agent to the cells. The peroxidase was characterised as a glycoprotein of molecular mass 37-kDa having a pl of about 10 and an optimal pH of 6.5. The peroxidase was thermally stable at 50 degrees C for up to 60 min. The partial amino acid sequence of the peroxidase was determined and found to be dissimilar to the amino acid sequences of other higher plant peroxidases. The oxidative polymerization of lunularin by this peroxidase was examined and the formation of a dimer, a trimer and a tetramer was demonstrated by negative ion Fast Atom Bombardment (FAB)-mass spectroscopy of the reaction products.

Bibenzyls↗
PubMed2000

A 38 kDa allylic alcohol dehydrogenase from the cultured cells of Nicotiana tabacum.

An NADP+-dependent alcohol dehydrogenase (allyl-ADH) was isolated from the cultured cells of Nicotiana tabacum. The allyl-ADH was found to be efficient for the dehydrogenation of secondary allylic alcohols rather than saturated secondary alcohols and it was specific for the S-stereoisomer of the alcohols. The enzyme catalyzed the reversible reaction whereby the carbonyl group of enones is reduced to the corresponding allylic alcohol or vice versa. Two possible primary structures of the allyl-ADH were deduced by the sequence analyses of full-length cDNAs (allyl-ADH1 and ally-ADH2), which were cloned by the PCR method. These analyses indicated that the allyl-ADHs are composed of 343 amino acids having the molecular weights 38083 and 37994, respectively, and they showed approximately 70% homology to the NADP+-dependent oxidoreductases belonging to a plant zeta-crystallin family.

Alcohol Dehydrogenase↗
PubMed2000

A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells.

Leukocyte chemoattractants are involved in the inflammatory response act via G protein-coupled receptors. We report the cloning of a novel human gene encoding the putative orphan receptor, C5L2, belonging to a subfamily of C3a, C5a and formyl Met-Leu-Ph receptors that are related to the chemokine receptor family. C5L2 transcript levels were abundant in granulocytes and immature dendritic cells but not in mature dendritic cells. We speculate that this receptor may regulate the activation of immature dendritic cells and play a role in the chemoattraction of leukocytes to inflammatory regions.

Amino Acid Sequence↗
PubMed2000

Expression of the zinc finger gene fez-like in zebrafish forebrain.

Anterior-posterior (A-P) patterning in the neuroectoderm is established during gastrulation in zebrafish and amphibians. We isolated a novel zinc-finger gene fez-like (fezl) from zebrafish, which displays sequence similarities to Xenopus Fez. The fezl transcripts were detected in the anterior edge of neuroectoderm, the prospective dorsal forebrain, from the late gastrula (80% epiboly stage) to the mid-segmentation period. fezl was also expressed in the ventral forebrain overlying the prechordal plate at these stages. The expression of fezl was enhanced in embryos expressing the Wnt inhibitor Dkk1 and reduced in embryos expressing Wnt8b. The expression in the ventral forebrain was eliminated in the one-eyed pinhead mutant and the antivin RNA-injected embryos, which lack the prechordal plate. Radiation hybrid mapping revealed that the fezl gene is localized to linkage group 11.

Amino Acid Sequence↗
PubMed2000

Prognostic significance of proliferative activity in pN2 non-small-cell lung carcinomas and their mediastinal lymph node metastases.

OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in both primary tumor and lymph node metastases of pathologic stage IIIA N2 non-small-cell lung carcinoma (NSCLC) and the relation to prognosis. SUMMARY BACKGROUND DATA: Although the prognosis of pN2 NSCLC is poor in general, long-term survivors have been reported among patients with completely resected or clinical N0 disease and those with skip metastasis. However, few reports are available on preoperative prognostic predictors. Expression of PCNA is known to be associated with tumor proliferation and is correlated with the prognosis of several carcinomas. METHODS: Clinicopathologic factors were investigated in relation to prognosis in 76 patients with pathologic stage IIIA pN2 NSCLC from whom resected surgical specimens were available from both the primary tumor and lymph node metastases for evaluation of PCNA expression. RESULTS: A significant correlation was observed between PCNA labeling index in the primary tumor and that in lymph node metastases. The prognosis in patients with PCNA-negative primary tumor (5-year survival rate, 66.0%) was significantly more favorable than that of patients with PCNA-positive primary tumor (5-year survival rate, 21.5%). The prognosis in patients with PCNA-negative metastases was significantly more favorable than that of patients with PCNA-positive metastases. For clinical N2 disease also, the prognosis of patients with PCNA-negative primary tumor was favorable (5-year survival rate, 66.1%). Multivariate analyses showed that PCNA expression and complete resection were significant prognostic factors. CONCLUSIONS: Preoperatively diagnosed N2 NSCLC exhibiting negative PCNA expression in primary tumor or lymph node metastases is expected to result in a favorable postoperative prognosis and may be an indication for primary resection.

Aged↗
PubMed2000

Preserving normal ventricular activation versus atrioventricular delay optimization during pacing: the role of intrinsic atrioventricular conduction and pacing rate.

The purpose of the study was to compare the effects of DDD pacing with optimal AV delay and AAI pacing on the systolic and diastolic performance at rest in patients with prolonged intrinsic AV conduction (first-degree AV block). We studied 17 patients (8 men, aged 69 +/- 9 years) with dual chamber pacemakers implanted for sick sinus syndrome in 15 patients and paroxysmal high degree AV block in 2 patients. Aortic flow and mitral flow were evaluated using Doppler echocardiography. Study protocol included the determination of the optimal AV delay in the DDD mode and comparison between AAI and DDD with optimal AV delay for pacing rate 70/min and 90/min. Stimulus-R interval during AAI (ARI) was 282 +/- 68 ms for rate 70/min and 330 +/- 98 ms for rate 90/min (P < 0.01). The optimal AV delay was 159 +/- 22 ms. AV delay optimization resulted in an increase of an aortic flow time velocity integral (AFTVI) of 16% +/- 9%. At rate 70/min the patients with ARI < or = 270 ms had higher AFTVI in AAI than in DDD (0.214 +/- 0.05 m vs 0.196 +/- 0.05 m, P < 0.01), while the patients with ARI > 270 ms demonstrated greater AFTVI under DDD compared to AAI (0.192 +/- 0.03 m vs 0.166 +/- 0.02 m, P < 0.01). At rate 90/min AFTVI was higher during DDD than AAI (0.183 +/- 0.03 m vs 0.162 +/- 0.03 m, P < 0.01). Mitral flow time velocity integral (MFTVI) at rate 70/min was higher in DDD than in AAI (0.189 +/- 0.05 m vs 0.173 +/- 0.05 m, P < 0.01), while at rate 90/min the difference was not significant in favor of DDD (0.149 +/- 0.05 m vs 0.158 +/- 0.04 m). The results suggest that in patients with first-degree AV block the relative impact of DDD and AAI pacing modes on the systolic performance depends on the intrinsic AV conduction time and on pacing rate.

Aged↗