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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 163 records · Page 9Linked to original sources
PubMed2001

[A case of mucosa associated lymphoid tissue (MALT) lymphoma].

We examined a 49-year-old man, who was referred to our hospital for resection of abnormal findings on the X-ray. Before hospital admission, he was performed TBLB and aspiration biopsy in other hospital, but the results was not decided diagnosis. Because the possibility of the lung cancer was not completely nagated, we performed the tumor resection (partial pulmonary resection) in use of thoracoscopy. The tumor was diagnosed as a MALT (mucosa associated lymphoid tissue) lymphoma at histologically and immunohistologically (CD 79), and resectable lymph node did not detected malignant cell. He has had no evidence of recurrence for 5 months after the operation.

Humans↗
PubMed2001

[A case of carcinosarcoma of the lung].

A 63-year-old man was admitted to our hospital because of cough and slight fever up. A tumor shadow in right S6 and obstructive pneumonia was detected by X-ray and CT. Bronchoscopic study showed that right B6 bronchous was occluded by the tumor and in which malignant cell (squamous cell carcinoma suspect) were detected. Therefore right middle and lower lobectomy was performed. Histological examination of the resected specimen showed that the tumor was composed of poorly differentiated squamous cell carcinoma and abnormal spindle cell component. Both components of the tumor were mixed each other in part. Immunohistologically, malignant cell of sarcomatous elements were positively stained by vimentin and actine, but was not found such as osteosarcoma or rabdomyosarcoma. He was diagnosed as so-called carcinosarcoma of the lung.

Carcinosarcoma↗
PubMed2001

[Guidelines for antibiotic agents in the field of respiratory tract surgery].

This paper provides information on the use of antibiotic agents during the postoperative period from three aspects. 1) It is important to evaluate the risk factors of postoperative infection based on the patient's preoperative condition. Diseases treated with respiratory tract surgery are frequently caused by heavy smoking. Therefore it must be remembered that the patients may have low respiratory function. 2) In the prevention of postoperative infection, the special circumstances after respiratory surgery (e.g., the disintegration of the clearance system in the airway caused by the dissection of lymph nodes, the suppression of respiration, and cough caused by thoracotomy accompanied by resection of the ribs) must be considered. Therefore we usually administer antibiotic agents for 3 to 4 days. In general, we select second-generation cephalosporins, be cause gram-negative rod infection frequently occurs. 3) Postoperative infection is diagnosed based on fluctuations in fever, laboratory data (number of white blood cells and C-reactive protein), chest X-ray findings, and properties of drainage fluid. When bacteria are not identified, we must consider MRSA as a gram-positive bacterium and Pseudomonas aeruginosa as a gram-negative bacterium. After the identification of bacteria causing the infection, the antibiotic agents may be changed based on the results of sensitivity tests. The appropriate usage of antibiotic agents in the field of respiratory tract surgery is discussed based on actual clinical experience in our department.

Anti-Bacterial Agents↗
PubMed2000

Kheper, a novel ZFH/deltaEF1 family member, regulates the development of the neuroectoderm of zebrafish (Danio rerio).

Kheper is a novel member of the ZFH (zinc-finger and homeodomain protein)/deltaEF1 family in zebrafish. kheper transcripts are first detected in the epiblast of the dorsal blastoderm margin at the early gastrula stage and kheper is expressed in nearly all the neuroectoderm at later stages. kheper expression was expanded in noggin RNA-injected embryos and also in swirl mutant embryos and was reduced in bmp4 RNA-injected embryos and chordino mutant embryos, suggesting that kheper acts downstream of the neural inducers Noggin and Chordino. Overexpression of Kheper elicited ectopic expansion of the neuroectoderm-specific genes fkd3, hoxa-1, and eng3, and the ectopic expression of hoxa-1 was not inhibited by BMP4 overexpression. Kheper interacted with the transcriptional corepressors CtBP1 and CtBP2. Overexpression of a Kheper mutant lacking the homeodomain or of a VP16-Kheper fusion protein disturbed the development of the neuroectoderm and head structures. These data underscore the role of Kheper in the development of the neuroectoderm and indicate that Kheper acts as a transcriptional repressor.

Alcohol Oxidoreductases↗
PubMed2000

Significance of spiral ligament fibrocytes with cochlear inflammation.

It has been recently suggested that the spiral ligament fibrocytes, which interconnect with the basal cells of the stria vascularis via gap junctions, may be critical in maintaining cochlear homeostasis. In animal models of pathological conditions such as labyrinthitis and otitis media, reduced immunostaining for gap junction protein connexin 26 is observed in the spiral ligament. This suggests that disruption of the spiral ligament fibrocytes could be among the causes of cochlear dysfunction due to cochlear inflammation. Cultured spiral ligament fibrocytes have been shown to secrete chemokines and other mediators after stimulation of proinflammatory cytokine TNF-alpha or IL-1beta. Each of these mediators might induce inflammatory cell movement, which would prolong the inflammatory response. It is reasonable that such enhanced biological defense ability could be the cause of spiral ligament fibrocyte damage.

Animals↗
PubMed2000

Novel design of nonpeptide AVP V(2) receptor agonists: structural requirements for an agonist having 1-(4-aminobenzoyl)-2,3,4, 5-tetrahydro-1H-1-benzazepine as a template.

The discovery of a series of nonpeptide arginine vasopressin V(2) receptor agonists is described. After identifying the aniline derivative 8 as our lead compound from the metabolites of compound 7 that showed antidiuretic activity by po administration to Brattleboro rats, improvements in the in vitro potency involving evaluations of the structural requirements for agonist action and optimizing the structure of the benzoyl moiety have been intensively undertaken. These studies led to compounds 16g, 19a, and 23b,h,i that show potent agonist activity for the V(2) receptor.

Administration, Oral↗
PubMed2000

Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons.

HuC encodes an RNA binding protein homologous to Drosophila elav that serves as an excellent early marker for differentiating neurons. We have characterized the promoter of the zebrafish HuC gene by examining the ability of 5'-upstream fragments to drive expression of green fluorescent protein (GFP) in live embryos. We determined that 2.8 kb of the 5'-flanking sequence is sufficient to restrict GFP gene expression to neurons. The core promoter spans 251 base pairs and contains a CCAAT box and one SP1 sequence but no TATA box is present near the transcription start site. A putative MyT1 binding site and at least 17 E-box sequences are necessary to maintain the neuronal specificity of HuC expression. Interestingly, sequential removal of the putative MyT1 binding site and 14 distal E boxes does not appear to abolish neuronal expression; rather, it leads to a progressive expansion of GFP expression into muscle cells. Further removal of the three proximal E boxes eliminates neuronal and muscle specificity of GFP expression and leads to ubiquitous expression of GFP in the whole body. Identification of key components of the HuC promoter has led to the establishment of a stable zebrafish transgenic line (HuC-GFP) in which GFP is expressed specifically in neurons. We crossed mind bomb (mib) fish with this line to visualize their neurogenic phenotype in live mib(-/-) mutant embryos. This cross illustrates how HuC-GFP fish could be used in the future to identify and analyze zebrafish mutants with an aberrant pattern of early neurons.

Animals↗
PubMed2000

Learning and memory.

Memory is one of the most fundamental mental processes. Neuroscientists study this process by using extremely diverse strategies. Two different approaches aimed at understanding learning and memory were introduced in this symposium. The first focuses on the roles played by synaptic plasticity, especially in long-term depression in the cerebellum in motor learning, and its regulatory mechanism. The second approach uses an elegant chick-quail transplantation system on defined brain regions to study how neural populations interact in development to form behaviorally important neural circuits and to elucidate neurobiological correlates of perceptual and motor predispositions.

Animals↗
PubMed2000

Differential inhibitory effects of sophoricoside analogs on bioactivity of several cytokines.

Effects of sophoricoside and its analogs on proinflammatory cytokines have been investigated. Sophoricoside, genistein and orobol exhibited inhibitory effects on IL-5, IL-3, GM-CSF and IL-6 bioactivities. Genistin showed inhibitory effects on IL-5 and IL-3 bioactivities, but did not inhibit GM-CSF and IL-6 bioactivities. None of the sophoricoside analogs showed inhibitory effects on both IL-1beta and TNF-alpha bioactivities. Among the compounds, sophoricoside exhibited the highest inhibitory effects on IL-5, IL-3 and IL-6 bioactivities with IC50 values of 1.9 microM, 6.9 microM and 6.0 microM, respectively and orobol did show on GM-CSF bioactivity with an IC50 value of 18.0 microM. The result would provide an additional mechanism by which the compounds exert immunosuppressive and anti-inflammatory effects.

Animals↗
PubMed2000

Dual roles of the 11S regulatory subcomplex in condensin functions.

Condensin is a multisubunit protein complex that reconfigures DNA structure in an ATP-dependent manner in vitro and plays a central role in mitotic chromosome condensation in Xenopus egg cell-free extracts. The Xenopus 13S condensin complex (13SC) is composed of two subcomplexes: an 8S core subcomplex (8SC) consisting of two structural maintenance of chromosomes (SMC) subunits (XCAP-C and -E) and an 11S regulatory subcomplex (11SR) containing three non-SMC subunits (XCAP-D2, -G, and -H). We report here the biochemical and functional dissection of this chromosome condensation machinery. Although both 8SC and 13SC can bind to DNA in vitro and contain the SMC ATPase subunits, only 13SC is active as a DNA-stimulated ATPase and supports ATP-dependent supercoiling activity. In the cell-free extracts, 13SC is the active form that binds to chromosomes and induces their condensation. Neither 11SR nor 8SC alone is able to bind to chromatin. Our results suggest that the non-SMC subunits have dual roles in the regulation of condensin functions: one is to activate SMC ATPases and the other is to allow the holocomplex to associate with chromatin in a mitosis-specific manner.

Adenosine Triphosphatases↗
PubMed2000

Asymmetric p38 activation in zebrafish: its possible role in symmetric and synchronous cleavage.

Cleavage is one of the initial steps of embryogenesis, and is characterized by a series of symmetric and synchronous cell divisions. We showed that p38 MAP kinase (p38) is asymmetrically activated on one side of the blastodisc during the early cleavage period in zebrafish (Danio rerio) embryos. When a dominant negative (DN) form of p38 was uniformly expressed, blastomere cleavage was impaired on one side of the blastodisc, resulting in the formation of blastomeres with a large mass of cytoplasm and an enlarged nucleus on the affected side. The area affected by the DN-p38 expression did not correlate with the initial cleavage plane, but coincided with the side where dharma/bozozok, a dorsal-specific zygotic gene, was expressed (Yamanaka et al. 1998). Furthermore, UV irradiation and removal of the vegetal yolk mass before the first cleavage, both of which inhibit the initiation of the dorsalizing signals, abolished the asymmetric p38 activation. Our findings suggest that asymmetric p38 activation is required for symmetric and synchronous cleavage, and may be regulated by the same machinery that controls the initiation of dorsalizing signals.

Animals↗
PubMed2000

Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice.

Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n): 6000, M(w)/M(n): 1.14) with the aid of 4,4'-azobis(4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP. PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.

Animals↗
PubMed2000

Identification and characterization of SA/Scc3p subunits in the Xenopus and human cohesin complexes.

A multisubunit protein complex, termed cohesin, plays an essential role in sister chromatid cohesion in yeast and in Xenopus laevis cell-free extracts. We report here that two distinct cohesin complexes exist in Xenopus egg extracts. A 14S complex (x-cohesin(SA1)) contains XSMC1, XSMC3, XRAD21, and a newly identified subunit, XSA1. In a second 12.5S complex (x-cohesin(SA2)), XSMC1, XSMC3, and XRAD21 associate with a different subunit, XSA2. Both XSA1 and XSA2 belong to the SA family of mammalian proteins and exhibit similarity to Scc3p, a recently identified component of yeast cohesin. In Xenopus egg extracts, x-cohesin(SA1) is predominant, whereas x-cohesin(SA2) constitutes only a very minor population. Human cells have a similar pair of cohesin complexes, but the SA2-type is the dominant form in somatic tissue culture cells. Immunolocalization experiments suggest that chromatin association of cohesin(SA1) and cohesin(SA2) may be differentially regulated. Dissociation of x-cohesin(SA1) from chromatin correlates with phosphorylation of XSA1 in the cell-free extracts. Purified cdc2-cyclin B can phosphorylate XSA1 in vitro and reduce the ability of x-cohesin(SA1) to bind to DNA or chromatin. These results shed light on the mechanism by which sister chromatid cohesion is partially dissolved in early mitosis, far before the onset of anaphase, in vertebrate cells.

Amino Acid Sequence↗
PubMed2000

Full oncogenic activities of v-Src are mediated by multiple signaling pathways. Ras as an essential mediator for cell survival.

Tyrosine kinase oncoproteins cause simultaneous activation of multiple intracellular signaling pathways. However, the precise mechanisms by which individual pathways induce oncogenesis are not well understood. We have investigated the roles of individual signaling pathways in v-Src-dependent cell growth and survival by inhibiting one particular pathway. v-Src induced constitutive activation of signal transducers and activators of transcription 3 (STAT3), phosphatidylinositol 3-kinase, and Ras in murine Ba/F3 cells and led to factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and phosphatidylinositol 3-kinase (Deltap85) inhibited v-Src-dependent growth by approximately 60 and approximately 40%, respectively. Moreover, dominant-negative Ras (N17) induced severe apoptosis, which was accompanied by down-regulation of Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase-3 inhibitors remained viable even when N17 was expressed, the growth was reduced by approximately 85%. During N17- and STAT3D-induced growth suppression, expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17, whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D. Thus, v-Src-activated Ras and STAT3 are involved in distinct but partly overlapping transcriptional regulation of cell cycle regulatory molecules. These results suggest that the full oncogenic activity of v-Src requires simultaneous activation of multiple signalings, in which Ras is particularly required for survival.

Animals↗
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

Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.

Members of the IL-6 cytokine family are involved in a variety of biological responses, including the immune response, inflammation, hematopoiesis, and oncogenesis by regulating cell growth, survival, and differentiation. These cytokines use gp130 as a common receptor subunit. The binding of ligand to gp130 activates the JAK/STAT signal transduction pathway, where STAT3 plays a central role in transmitting the signals from the membrane to the nucleus. STAT3 is essential for gp130-mediated cell survival and G1 to S cell-cycle-transition signals. Both c-myc and pim have been identified as target genes of STAT3 and together can compensate for STAT3 in cell survival and cell-cycle transition. STAT3 is also required for gp130-mediated maintenance of the pluripotential state of proliferating embryonic stem cells and for the gp130-induced macrophage differentiation of M1 cells. Furthermore, STAT3 regulates cell movement, such as leukocyte, epidermal cell, and keratinocyte migration. STAT3 also appears to regulate B cell differentiation into antibody-forming plasma cells. Since the IL-6/gp130/STAT3 signaling pathway is involved in both B cell growth and differentiation into plasma cells it is likely to play a central role in the generation of plasma cell neoplasias. Oncogene (2000).

Animals↗