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Biomedical subjects

H Kurata

Publications and source records attributed to H Kurata.

At least 37 records · Page 2Linked to original sources

[Tension pneumothorax after simultaneous bilateral lung resection].

A 72-year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray film. Chest CT showed a mass 6 cm in diameter in left S1 + 2, and a small round mass in right S2. Left side mass was diagnosed squamous cell carcinoma by transbronchial biopsy, but right side mass was unidentified. We performed partial resection for a right S2 mass with VATS, and then left upper lobe lobectomy and mediastinal lymph node dissection simultaneously. Pathological examination revealed the right mass was hamartoma. He discharged on 16 postoperative days uneventfully. But 3 days after he was sent to our hospital on emergency because dyspnea and unconscious. Chest X-ray revealed right side tension pneumothorax, then he was recovered by chest tube insertion. At re-thoracotomy we confirmed air leakage was occurred from a ruptured bulla that was leaved at first operation.

Aged↗

Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster.

During the differentiation of naive Th cells into Th2 effector cells, the entire IL-4/IL-13 locus is remodeled into an accessible chromatin conformation. Here we show that ectopic expression and activation of Stat6 or GATA-3 in Th cells developing under Th1-polarizing conditions lead to the induction of chromatin remodeling not only at the flanking regions of the IL-4 and IL-13 genes but also at the IL-4/IL-13 intergenic regulatory region for the IL-4/IL-13/IL-5 gene cluster. Furthermore, we demonstrate that GATA-3 and another Th2-specific, inducible protein complex interact with the IL-4/IL-13 intergenic DNase I hypersensitive region specifically in Th2 cells.

Animals↗

Glucocorticoid-induced expression of a foreign gene by the GVG system in transformed tobacco BY-2 cells.

A glucocorticoid-induced target gene expression system was used to control the expression of the uidA gene, whose product was beta-glucuronidase (GUS), in tobacco BY-2 cell suspension culture. This targeting system showed quick, sensitive, and reversible response to dexamethazone (DEX), an artificial glucocorticoid hormone. Addition of DEX greatly and quickly enhanced uidA gene expression, whose level was as high as that under the control of the CaMV 35S promoter whereas in the absence of DEX, the GUS specific activity was suppressed to be as low as that of nontransformed BY-2 cells. The dilution of DEX decreased GUS specific activity showing that the concentration of DEX plays a major role in controlling the expression level of the target. The use of the glucocorticoid-induced system in plant cell suspension culture was demonstrated to precisely control target gene expression.

Journal Article↗

Reduction of inflammatory cytokines and prostaglandin E2 by IL-13 gene therapy in rheumatoid arthritis synovium.

The rheumatoid arthritis (RA) joint is characterized by an inflammatory synovial pannus which mediates tissue destruction. IL-13 is a cytokine that inhibits activated monocytes/macrophages from secreting a variety of proinflammatory molecules. The aim of this study was to examine whether gene therapy-delivered IL-13 could reduce the production of key proinflammatory mediators in RA synovial tissue (ST) explants. Adenoviral vectors encoding the genes for human IL-13 (AxCAIL-13) and bacterial beta-galactosidase were generated and examined for protein production. Vectors were used to infect RA ST explants and RA synovial fibroblasts, and conditioned medium (CM) was collected at various times for analysis by ELISA and competitive immunoassay. AxCAIL-13 decreased the production of RA ST explant proinflammatory IL-1beta by 85% after 24 h. Likewise, TNF-alpha levels were decreased by 82 and 75% whereas IL-8 levels were reduced 54 and 82% after 24 and 48 h, respectively, in RA ST explant CM. Monocyte chemotactic protein-1 concentrations were decreased by 88% after 72 h in RA ST explant CM. RA ST explant epithelial neutrophil-activating peptide-78 concentrations were decreased 85 and 94% whereas growth-related gene product-alpha levels were decreased by 77 and 85% at 24 and 48 h, respectively, by AxCAIL-13. Further, IL-13 significantly decreased PGE2 and macrophage inflammatory protein-1alpha production. These results demonstrate that increased expression of IL-13 via gene therapy may decrease RA-associated inflammation by reducing secretion of proinflammatory cytokines and PGE2.

Adenoviridae↗

GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells.

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine-inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3-expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure-function analyses of GATA-3 revealed that the NH(2)-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH(2)-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3-expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.

Animals↗

Intermittent light irradiation with second- or hour-scale periods controls anthocyanin production by strawberry cells*

Anthocyanin production by strawberry cells depends not only on light intensity but also on the light/dark cycle operation with hour- or second-scale periods. These findings are useful for designing and operating photobioreactors for enhanced anthocyanin production. Intermittent illumination with a second-scale period produces the same amount of anthocyanin as continuous light, suggesting that the light intensity distribution within a photobioreactor does not cause suppressed production. In the hour-scale cycle, continuous light operation enhanced anthocyanin production more than the light/dark cycle process.

Journal Article↗

The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1.

To search for the intracellular signaling pathway critical for the secretion of matrix metalloproteinases (MMP), we studied the effects of dominant negative Ras (S17N Ras) and dominant negative MEK1 (MEK1AA) expression in v-crk-transformed 3Y1. Expression of either S17N Ras or MEK1AA dramatically suppressed the augmented secretion of MMP-2 and MMP-9 in v-crk-transfected 3Y1. Similarly, a Ras farnesyltransferase inhibitor, manumycin A, and a MEK1 inhibitor, U0126, suppressed MMP secretion in a dose-dependent manner, whereas a PI3 kinase inhibitor, wortmannin, could not. In addition, the suppression of MMP secretion by S17N Ras showed good correlation with the inhibition of in vitro invasiveness of the cells. In contrast, expression of dominant negative C3G did not suppress MMP secretion, although it substantially blocked the c-Jun N-terminal kinase activation. Taken together, the Ras-MEK1 pathway, but not the C3G-JNK pathway, seems to play a key role in the activation of MMP secretion and, hence, the invasiveness of v-crk-transformed cells.

Androstadienes↗

Molecular cloning and characterization of a novel human gene (NESCA) which encodes a putative adapter protein containing SH3.

A full-length cDNA encoding a novel protein was isolated and sequenced from a human placental cDNA library. This cDNA consists of 1990 bp and has a predicted open reading frame encoding 433 amino acids. It possesses an Src homology 3 (SH3) motif, a leucine zipper motif and no catalytic domain, suggesting that it seems to be an adapter protein. PCR-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 1q21-22.

Adaptor Proteins, Signal Transducing↗

v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells.

We investigated the effect of cell transformation by v-src on the expression and tyrosine phosphorylation of SHPS-1, a putative docking protein for SHP-1 and SHP-2. We found that transformation by v-src virtually inhibited the SHPS-1 expression at mRNA level. While nontransforming Src kinases including c-Src, nonmyristoylated forms of v-Src had no inhibitory effect on SHPS-1 expression, transforming Src kinases including wild-type v-Src and chimeric mutant of c-Src bearing v-Src SH3 substantially suppressed the SHPS-1 expression. In cells expressing temperature sensitive mutant of v-Src, suppression of the SHPS-1 expression was temperature-dependent. In contrast, tyrosine phosphorylation of SHPS-1 was rather activated in cells expressing c-Src or nonmyristoylated forms of v-Src. SHPS-1 expression in SR3Y1 was restored by treatment with herbimycin A, a potent inhibitor of tyrosine kinase, or by the expression of dominant negative form of Ras. Contrary, active form of Mekl markedly suppressed SHPS-1 expression. Finally, overexpression of SHPS-1 in SR3Y1 led to the drastic reduction of anchorage independent growth of the cells. Taken together, our results suggest that the suppression of SHPS-1 expression is a pivotal event for cell transformation by v-src, and the Ras-MAP kinase cascade plays a critical role in the suppression.

3T3 Cells↗

Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2.

We investigated the role of MEK1 signaling in MMP-2 activation by use of constitutive active/dominant negative forms of MEK1 and MEK1-specific inhibitor. We found that cell transformation with active forms of MEK1 dramatically increased secretion and proteolytic activation of MMP-2 and subsequently stimulated invasiveness of cells. Contrary, expression of dominant negative form of MEK1 in v-src-transformed cells or in Con A-activated cells resulted in the suppression of the augmented secretion and proteolytic activation of MMP-2. In addition, treatment of v-src-transformed cells with PD98059, a MEK1-specific inhibitor, strongly suppressed the secretion and activation of MMP-2, whereas treatment with wortmannin, a PI3 kinase inhibitor, showed no clear effect on MMP-2 secretion. Taken together, these results strongly suggest that MEK-MAP kinase signaling, but not PI3 kinase signaling, plays a critical role in the activation of MMP-2 secretion and, subsequently, in the invasiveness of v-src-transformed cells.

Animals↗

Patient reminder letters to promote annual mammograms: a randomized controlled trial.

BACKGROUND: This study assessed the effects of a reminder letter from a physician (relative to a mammography facility letter or no letter) on appointment compliance among women 50-74 years of age due for an annual screening mammogram. METHODS: A total of 1,562 women were randomly as signed to the groups. Each Group 1 subject received a reminder letter from her physician, each Group 2 subject received a reminder letter from her mammography facility, and Group 3 served as a control group. RESULTS: The return rates for Groups 1, 2, and 3 were 47.7, 46.6, and 28.3%, respectively; the overall difference was significant using a chi(2) analysis (P < 0.001). Bonferroni pairwise comparisons indicated no difference between Groups 1 and 2 but significant differences (P < 0.001) between Group 3 and the other two groups. Logistic regression indicated that relative to Group 3, the adjusted odds of returning for Groups 1 and 2 were 2.37 and 2.24, respectively. CONCLUSIONS: Mammography providers and their patients likely will benefit from in-reach reminder systems. Physicians who do not use reminder systems should refer their patients to facilities that use these systems.

Aged↗

Branching ratio and L2 + L3 intensities of 3d-transition metals in phthalocyanines and the amine complexes

L(2,3) inner-shell excitation spectra were obtained by electron energy-loss spectroscopy (EELS) for the divalent first transition series metals in phthalocyanine complexes (MPc) such as titanium oxide phthalocyanine (TiOPc), fluoro-chromium phthalocyanine (CrFPc), manganese phthalocyanine (MnPc), iron phthalocyanine (FePc), cobalt phthalocyanine (CoPc), nickel phthalocyanine (NiPc) and copper phthalocyanine (CuPc). It was found that the value of normalized total intensity of I(L2 + L3) was nearly proportional to the formal electron vacancies of each 3d-state, and the values of the branching ratio, I(L3)/I((L2 + L3), represented a high-spin-state rather than low-spin-state for MnPc, FePc and NiPc. EELS was also applied to charge-transfer complexes of FePc with an amine such as pyridine or gamma-picoline. It was concluded that their I(L2 + L3) intensity of Fe showed the decrease in vacancies of 3d-states on the formation of the charge-transfer complex with these amines, which suggests some electron transfer from the amine to Fe in phthalocyanine. The EELS study provides beneficial information for investigating the electronic states of the specific metal sites in organic materials.

Journal Article↗

In vitro synergism between nyasol, an active compound isolated from Anemarrhena asphodeloides, and azole agents against Candida albicans.

The antifungal activity of nyasol (NYS) alone or with various antifungal agents was measured in vitro against Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. NYS is a compound recently purified from a medicinal plant, Anemarrhena asphodeloides. Among 12 agents, miconazole (MCZ), ketoconazole (KCZ), clotrimazole (CTZ), and cerulenin showed marked synergistic effects against C. albicans. The fractional inhibition concentration (FIC) indices against 4 strains of C. albicans were 0.067-0.31 for MCZ plus NYS, 0.078-0.31 for KCZ plus NYS, and 0.098-0.13 for CTZ plus NYS. These values indicate the possibility of using NYS as an adjuvant to azole agents in the chemotherapy of candidiasis.

Antifungal Agents↗

On the grain boundary segregation of Sn in indium-tin-oxide thin films

The determination of Sn segregation by means of electron energy loss spectroscopy and X-ray photoelectron spectroscopy has been attempted on indium-tin-oxide thin films prepared by various processes: (a) as-deposited at room temperature; (b) after annealing at 533 K in vacuum; (c) after annealing in air; and (d) as-deposited at 473 K. The occurrence of Sn segregation both at the surface and at the grain boundary was proved. The degree of segregation detected, varied depending on the preparation process of the films.

Journal Article↗

Regulation of hepatic high density lipoprotein binding protein, HB2, expression after administration of simvastatin to rabbits.

HB2 a candidate HDL receptor, is quite distinct from other HDL receptors in its structure. However, while changes in cellular cholesterol content, or a reduction in cholesterol biosynthesis accompany corresponding changes in HB2 expression, the level at which these changes occur have not been determined and the regulation and the function of HB2 remain uncertain. In order to further investigate the regulation of HB2, we administered simvastatin to rabbits to reduce cholesterol biosynthesis and follow changes in HB2 mRNA in various tissues. Six rabbits were given 15 mg/kg of simvastatin by oral administration daily and another six rabbits were given the same volume of saline as a control, for 21 days. They were then sacrificed to obtain samples of blood, liver, lung, jejunum and brain. Simvastatin reduced plasma total cholesterol by 47% and free cholesterol concentrations in liver and lung by 25 and 10%, respectively. Northern blot analysis showed that simvastatin lowered the expression of HB2 significantly in the liver and lung by 54% and 42% respectively but not in the jejunum or brain. These results support the findings of a previous study showing that HDL binding activity of both HB1 and HB2, which was determined by ligand blotting using HDL3 as a ligand, were reduced after administering cholesterol lowering agents. (Arteriosclerosis, 10: 1045-1050,1990). The present study suggests that simvastatin down-regulated HB2 at the transcriptional stage. Although the complete physiological function of HB2 is unclear, it appears to play some role in the cholesterol metabolism, warranting further studies to elucidate the nature of this interaction.

Animals↗

Inhibition of low-density lipoprotein oxidation by astaxanthin.

Marine animals produce astaxanthin which is a carotenoid and antioxidant. In this study we determined the in vitro and ex vivo effects of astaxanthin on LDL oxidation. The oxidation of LDL was measured in a 1 ml reaction system consisting of increasing concentrations of astaxanthin (12.5, 25.0, 50.0 microg/ml), 400 microM V-70 (2, 2'-azobis(4-methoxy-2, 4-dimethylvaleronitrile)), and LDL (70 microg/ml protein). Astaxanthin dose, dependently significantly prolonged the oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min). For the ex vivo study 24 volunteers (mean age 28.2 [SD 7.8] years) consumed astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg per day for 14 days. No other changes were made in the diet. Fasting venous blood samples were taken at days 0, +14. LDL lag time was longer (5.0, 26.2, 42.3 and 30.7% respectively) compared with day 0 after consuming astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg for 14 days compared with day 0, but there was no difference in oxidation of LDL between day 0 (lag time 59.9+/-7.2 min) and day 14 (57.2+/-6.0 min) in the control group. Our results provide evidence that consumption of marine animals producing astaxanthin inhibits LDL oxidation and possibly therefore contributes to the prevention of atherosclerosis.

Adult↗

[Mediastinal mature teratoma perforated into the pericardial sac: a case report].

Mature teratomas occasionally rupture into adjacent organs such as lung, bronchus, mediastinum and pericardial sac. However, perforation into the pericardial sac is rare. We experienced a case of mediastinal mature teratoma perforated into the pericardial sac. A 16-year-old man was admitted to our hospital due to sudden severe anterior chest pain. Chest X-ray showed a mass shadow in the right middle lung field. Chest CT scan and MRI demonstrated a heterogeneous mass with fat component in the right anterior mediastium adjacent to the pericardium. Some squamous cells were obtained from the mass by CT guided percutaneous needle biopsy. Operation was performed with the diagnosis of mediastinal teratoma. The mass adhered to the pericardium and turbid pericardial effusion was noted. The mass was removed with the pericardium. The mass was 9 x 6.5 x 6 cm in size, which contained yellow sebaceous material and a tuft of white hair. The pathological diagnosis of the mass was mature cystic teratoma with perforation into the pericardial sac.

Adolescent↗

[Renal cell carcinoma in a horseshoe kidney with abdominal aortic aneurysm: a case report].

We herein report a case of renal cell carcinoma in a horseshoe kidney with an abdominal aortic aneurysm in a 69-year-old man. Radiological examinations showed a left renal tumor, horseshoe kidney and abdominal aortic aneurysm. We performed a left radical nephrectomy with the division of the isthmus and artificial graft through an abdominal transperitoneal approach. Histological findings revealed clear cell type renal cell carcinoma without invasion of the capsule or renal pelvis. Only 31 cases of renal cell carcinoma in a horseshoe kidney have been reported in Japan, and our case is the 32nd. No case with abdominal aortic aneurysm has been reported previously. We assume that abdominal aortic aneurysm was associated with renal cell carcinoma by chance in the horseshoe kidney in this case. The arterial and venous supplies vary from case to case. We emphasize that arteriography and venography are very important preoperative procedures.

Aged↗