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Biomedical subjects

K Date

Publications and source records attributed to K Date.

At least 37 records · Page 2Linked to original sources

Amplification on double-minute chromosomes and partial-tandem duplication of the MLL gene in leukemic cells of a patient with acute myelogenous leukemia.

Partial-tandem duplication (PTD) of an internal portion of MLL occurs in some cases of acute myelogenous leukemia (AML) with trisomy 11 or a normal karyotype. This type of MLL rearrangement may be transcribed into an mRNA species that is capable of encoding a partially duplicated protein associated with leukemogenesis. However, although several kinds of oncogenes, especially MYC, are often amplified on double-minute chromosomes (dmins) in hematological malignancies, no amplification of MLL has been reported in AML. Here, we report the first documented case of a patient with AML whose leukemic cells exhibited amplification of MLL on dmins. Furthermore, in this patient, MLL was rearranged in a PTD manner, with in-frame fusion of exons 2 and 6.

Chromosome Aberrations↗

[Genetic alterations in gallbladder carcinoma: a review].

Earlier evidence suggests that gallbladder carcinoma (GBC) has three carcinogenic pathways; de novo development; adenoma-carcinoma sequence; and hyperplasia-carcinoma sequence associated with an anomalous arrangement of the pancreaticobiliary duct (AAPBD). We review gene abnormalities in GBC reported to date. p53 mutation and its protein overexpression are frequently observed in de novo carcinoma and GBC with AAPBD, but never found in carcinoma with adenoma. The incidence of K-ras codon 12 mutation in GBCs with AAPBD is significantly higher than that in the other types. Mutation of K-ras is never detected in carcinoma with adenoma. These findings suggest that diverse genetic pathways may exist in gallbladder carcinogenesis and reflect morphologic variations.

Adenoma↗

HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor.

We prepared a specific antagonist for hepatocyte growth factor (HGF) and designated it HGF/NK4. HGF/NK4 is composed of N-terminal 447 amino acids of the alpha-chain of HGF, thus contains the N-terminal hairpin domain and subsequent four kringle domains. HGF/NK4 competitively inhibited the specific binding of HGF to the receptor. Importantly, HGF/NK4 neither stimulated DNA synthesis of primary cultured rat hepatocytes (mitogenesis) nor induced cell scattering (motogenesis) and branching tubulogenesis (morphogenesis) of MDCK renal epithelial cells, however, HGF/NK4 almost completely inhibited the mitogenic, motogenic, and morphogenic activities of HGF. HGF/NK4 also suppressed tyrosine phosphorylation of the c-Met/HGF receptor induced by HGF. Apparently this is the first documentation of a specific antagonist which abrogates the mitogenic, motogenic, and morphogenic activities of HGF.

Animals↗

Successful treatment of blunt trauma involving complete laceration of the pancreas and duodenum in a 7-year-old child: report of a case.

The acute onset of peritoneal signs and shock in a 7-year-old boy who had been hit in the epigastrium by a log-seesaw mandated surgical treatment. Enhanced computed tomography (CT) demonstrated complete laceration of the pancreas as well as duodenal injury, and a duodenoduodenostomy with distal pancreaticogastrostomy was subsequently performed. Temporary external drainage of the stomach and distal pancreas led to an uneventful recovery in the early postoperative period. Although the patient's postoperative development was appropriate for his age, the orifice of the distal pancreas spontaneously closed 2.5 years following surgery. We present this report to stress the fact that every effort should be made to preserve the pancreas following abdominal injury in children.

Child↗

[Two cases of tracheobronchial disruption due to blunt trauma].

Tracheobronchial disruption by blunt trauma is relative rate, but clinical course is various and sometimes fatal. A 22-year-old man (case 1) was admitted with traffic accident. Chest CT demonstrated pneumomediastinum and left pneumothorax. Bronchoscopy showed tracheal tear, but conservative therapy was selected because the peritracheal sheath remained intact. The second case was 27-year-old man, who was admitted with traffic accident. Pneumomediastinum and left tension pneumothorax were diagnosed, but bronchoscopy could not confirm the tracheobronchial disruption. As bronchial injury, lacerations and contusions of the lingular division were found in the thoracotomy, segmentectomy was carried out. When pneumomediastinum or pneumothorax is recognized in the patient of the blunt trauma, more careful examination of bronchoscopy is necessary to confirm the tracheobronchial disruption.

Adult↗

[A new handpiece attachment for Nd:YAG laser ablation of emphysematous bullae].

Recently, attention has been drawn to lung volume reduction for bullous emphysema by wedge excision or laser ablation. We used a neodymium: yttrium-aluminum garnet (Nd:YAG) laser with a free-beam mode to ablate peripheral emphysematous areas of lung tissue. To aid us in this procedure, we developed an attachment consisting of a stainless steel rod 3 cm in effective length, with a 1.8-cm diameter ring attached to its tip, and installed it on the tip of the laser handpiece used for free-beam laser ablation. This device has the following distinct advantages: 1) the distance between the tip of the laser and the pleura can easily be held constant, 2) the angle of irradiation can easily be maintained at 90 degrees. These result in 3) a constant area of irradiation (one square centimeter), and 4) an irradiated area that is clearly distinguished by the ring. In addition, the attachment is 5) simple and easy to construct. Three patients with bullous emphysema underwent unilateral laser ablation of the visceral pleura with the new device. All patients recovered completely. We found this rod-and-ring attachment to be useful for free-beam laser ablation.

Aged↗

Hepatocyte growth factor in lung morphogenesis and tumor invasion: role as a mediator in epithelium-mesenchyme and tumor-stroma interactions.

Hepatocyte growth factor (HGF), a ligand for Met tyrosine kinase, is a mesenchyme- or stroma-derived multipotent factor that regulates the growth, motility, and morphogenesis of various types of cells. During lung development, Met/HGF receptor mRNA was localized in lung epithelial cells, whereas HGF mRNA was localized in lung mesenchymal cells in rat embryos. Antisense HGF oligonucleotides specifically inhibited epithelial branching morphogenesis in cultured lung rudiment isolated from day-13 rat embryos, whereas recombinant HGF stimulated branching morphogenesis. Thus, HGF seems to be at least one of the mesenchyme-derived factors that support branching morphogenesis during lung development. Together with the finding that HGF plays important roles in organogenesis and morphogenesis of organs such as the liver and kidney, HGF seems to be a mediator in epithelium-mesenchyme interactions during organogenesis. Extending the conceptual framework of epithelium-mesenchyme (or epithelium-stroma) interactions, we next examined the possible involvement of HGF in tumor-stroma interactions, because the growth and motility of carcinoma cells are regulated through their interactions with host stromal cells. HGF induced in vitro migration and invasion of GB-d1 gallbladder carcinoma cells into basement membrane components and collagen-gel matrix; however, several other growth factors did not induce marked migration and invasion of the carcinoma cells. GB-d1 cells do not produce HGF, but they produce in inducing factor for HGF production in fibroblasts; the inducing molecule was identified as interleukin 1 beta. Cocultivation of GB-d1 cells with stromal fibroblasts embedded in a collagen-gel matrix induced invasion of GB-d1 cells into the collagen gels, but invasion was inhibited by a specific antibody against HGF. This indicates that in vitro invasion of GB-d1 cells depends on stromal fibroblasts and that the fibroblast-derived invasion factor is HGF. Since HGF stimulated in vitro migration and invasion of various carcinoma cells and several carcinoma cells produced inducing factors for HGF production in stromal fibroblasts, the looped interaction of carcinoma cells and stromal fibroblasts mediated by HGF and HGF inducers may be a mechanism responsible for acquisition of the malignant phenotype through tumor-stroma interactions.

Animals↗

Acquisition of invasive phenotype in gallbladder cancer cells via mutual interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor.

Growth and motility of carcinoma cells are regulated through their interactions with host stromal cells, i.e., tumor-stromal interactions. Hepatocyte growth factor (HGF), a ligand for c-Met tyrosine kinase, is a stromal-derived regulator of growth, motility, and morphogenesis. HGF stimulated proliferation and motility of GB-d1 gallbladder carcinoma cells from a patient with gallbladder cancer. HGF induced in vitro invasion of GB-d1 cells into a collagen gel matrix, and this potent, invasive effect was not seen with epidermal growth factor, transforming growth factor-beta 1, basic fibroblast growth factor, or platelet-derived growth factor. Although GB-d1 did not produce HGF, the cells did produce a factor which enhances HGF production in human skin fibroblasts, and this factor proved to be interleukin-1 beta (IL-1 beta). When GB-d1 cells were co-cultured with fibroblasts such that a collagen gel matrix was layered between the GB-d1 cells and fibroblasts, GB-d1 cells invaded the gel, but invasion of the cells in the co-culture system was inhibited by antibodies against HGF and partially inhibited by antibodies against IL-1 beta. Thus, GB-d1 cell-derived IL-1 beta stimulates HGF production in stromal fibroblasts and HGF up-regulated in the fibroblasts induces invasion of GB-d1 cells. The looped interaction of carcinoma cells and stromal fibroblasts mediated by HGF and a HGF-inducer such as IL-1 beta may be one mechanism which would explain the acquisition of malignant phenotype through tumor-stromal interactions.

Cell Communication↗

Frequent deletions of material from chromosome arm 1p in oligodendroglial tumors revealed by double-target fluorescence in situ hybridization and microsatellite analysis.

We undertook a cytogenetic analysis of 29 human brain tumors using double-target fluorescence in situ hybridization (FISH) and focusing on chromosome arm 1p. One or more tumor suppressor genes in this arm have been suggested to be important in a variety of neuroectodermal tumors. The series included 9 oligodendrogliomas, 4 mixed gliomas, 10 astrocytomas, 4 glioblastomas, and 2 central neurocytomas. We hybridized pericentromeric (1q12) and subtelomeric (1p36) DNA probes to cell nuclei prepared from paraffin-embedded tissues and observed a strikingly high incidence of deletion of at least part of 1p in oligodendrogliomas (100%) and mixed gliomas (75%). The results of the FISH analyses were confirmed by demonstration of loss of heterozygosity for a microsatellite polymorphism in 10 of the 29 tumors. As well as supporting the feasibility of FISH for detecting allelic deletions in chromosomes from paraffin-embedded tumor samples, the alteration of 1p reported here will contribute to an understanding of the molecular genetic events in oligodendroglial tumor development.

Brain Neoplasms↗

Induction of invasive growth in a gallbladder cancer cell line by hepatocyte growth factor in vitro.

To study the mechanism of invasion and metastasis of gallbladder cancer cells, we established a cancer cell line, GB-d1, from a metastatic lymphnode of poorly differentiated adenocarcinoma of the gallbladder. GB-d1 cells proliferate well in a dish culture and form small cystic cell clusters in a collagen gel containing 10% fetal bovine serum. A conditioned medium of human embryonic lung fibroblasts (HEL) stimulated the proliferation of GB-d1 cells and induced cell scattering in the dish culture. In the gel culture, the conditioned medium induced a transformation of the spherical clusters to arborizating colonies with tubular projections that mimicked an invasion of cancer cells into the surrounding tissue. Similar results were obtained when 10 ng/ml of human recombinant hepatocyte growth factor (h-rHGF) was added to the culture medium. The proliferative and morphological changes induced by the conditioned medium were inhibited by antiserum against h-HGF. HEL and human gallbladder stromal fibroblast-like cells produced substantial levels of HGF in the culture media, while GB-d1 did not produce any detectable level of HGF. These results suggest that HGF promotes the invasive growth of gallbladder cancer cells in vitro, and it was also suggested that stromal fibroblasts may play an important role in the invasive progression of gallbladder cancer in a paracrine fashion.

Adenocarcinoma↗

Kinetic analysis of cadmium toxicity to red sea bream, Pagrus major.

The sensitivity of red sea bream (Pagrus major) at various body sizes to Cd was investigated. The LC50 values for juvenile fish weighing over 0.16 g increased disproportionately with body weight and varied as the reciprocal of the rate of Cd accumulation in the body. The rate of accumulation and Cd concentration were much higher in the viscera than in the gills and remaining tissue. Cd elimination from the tissues was biphasic. Gel filtration studies revealed that metallothionein induction in the viscera of red sea bream was detected not after 4 hr, but after 24 hr postintoxication. This indicates that smaller juvenile fish with a higher rate of accumulation concentrate a larger amount of Cd before metallothionein synthesis and suffer more severe toxic effects.

Animals↗

Limited vertical skin incision for median sternotomy.

The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease.

Adolescent↗