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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 19 recordsLinked to original sources
PubMed1995

Structural analysis of PKS1, a polyketide synthase gene involved in melanin biosynthesis in Colletotrichum lagenarium.

Albino mutants (Pks-) of Colletotrichum lagenarium form nonmelanized appressoria and possess little penetrating ability on the host plant. The defect in albino mutant 79215 (Pks-) is considered to lie in pentaketide biosynthesis and/or pentaketide cyclization during melanin biosynthesis. The cosmid pAC7, carrying the PKS1 gene, when transformed into the albino mutant restores the wild-type melanin phenotype. We have determine the DNA sequence and the transcriptional organization of the PKS1 gene. The PKS1 gene contains one open reading frame, consisting of 3 exons separated by two short introns. The predicted PKS1 polypeptide consists of 2187 amino acids and shows significant similarities with other polyketide synthases, particularly that encoded by wA in Aspergillus nidulans, involved in conidial pigmentation. The PKS1 gene contains highly conserved beta-ketoacyl synthase, acetyl/malonyl transferase, and acyl carrier protein domains. We propose that the C. lagenarium PKS1 gene encodes a polyketide synthase involved in melanin biosynthesis.

Amino Acid Sequence↗
PubMed1995

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Adolescent↗
PubMed1995

Epstein-Barr virus association with early cancers found together with gastric medullary carcinomas demonstrating lymphoid infiltration.

Seven early gastric cancers obtained from patients also demonstrating Epstein-Barr virus (EBV)-positive gastric medullary carcinoma with lymphoid infiltration were investigated using a combined polymerase chain reaction (PCR) and in situ hybridization (ISH) approach. Sharing the same background mucosa as gastric medullary cancers, they comprised four intramucosal carcinomas, predominantly well-differentiated adenocarcinomas, and three submucosal carcinomas, histologically showing mixtures of well and poorly differentiated adenocarcinoma. In the three cases of submucosal carcinoma, the presence of EBV was proven by means of both PCR and ISH. However, not all cancer cells were positive for EBV on the basis of ISH examination, in contrast to the large series of gastric carcinoma with lymphoid infiltration previously investigated. All four mucosal carcinomas were EBV-negative. Lymphocyte-determined membrane antigen (LYDMA) monoclonality, performed by PCR, and latent membrane protein-1 (LMP-1) and Epstein-Barr virus (EBNA2) expression, assessed immunohistochemically, were negative in all seven cases. The results suggest that EBV becomes associated with gastric medullary carcinoma with lymphoid infiltration (GMCL) at a relatively early stage of the disease, shortly after the tumour has initially progressed to an invasive form, and plays some role in the manifestation as GMCL.

Adenocarcinoma↗
PubMed1995

Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia.

The bcl-2 protooncogene was initially discovered at the t(14;18) chromosomal breakpoint in follicular lymphomas. It has been demonstrated that bcl-2 protein (Bcl-2) expression blocks apoptosis and plays an important role in cell development and maturation. In the present study, Bcl-2 expression was immunohistochemically examined in 103 cases of gastric carcinoma, as well as 64 cases of non-carcinous gastric mucosa, and its correlation with apoptosis, cell proliferation and p53 immunoreactivity was investigated. Bcl-2 was detected in 18.0% of differentiated-type gastric carcinomas (9 of 50) and 7.5% of the undifferentiated type (4 of 53). In adjacent intestinal metaplastic gastric epithelium, the incidence of Bcl-2 positivity in the incomplete type (21/23, 91.3%) was significantly higher than in the complete type (23/41, 56.1%) (P < 0.04). Double immunostaining for Bcl-2 and Ki-67 clearly revealed the majority of Bcl-2-positive cancer cells to be in a nonproliferating state, although some cancer cells expressed both proteins together. Statistical assessment demonstrated that the average Ki-67 labeling index and apoptotic labeling index in Bcl-2-positive foci were significantly lower than in Bcl-2-negative foci (P < 0.0001, P < 0.0003). In addition, a significant dissociation between Bcl-2 and p53 immunoreactivity was found in cancer tissues. These results indicate that aberrant Bcl-2 expression in gastric carcinomas possibly originates from intestinal metaplastic epithelium, and suggest a possible role in tumor development and growth.

Adenocarcinoma↗
PubMed1995

Risedronate treatment does not increase microdamage in the canine femoral neck.

Cortical and trabecular bone from the femoral neck of 24 adult female beagle dogs was examined for microdamage following 2 years of treatment with risedronate (NE-58095). Specimens of the femoral neck, sectioned between the femoral head and the intertrochanteric groove, were bulk stained in 1% basic fuchsin in graded alcohols and embedded in methylmethacrylate. Five transverse sections of 100 microns from each specimen were examined for microdamage and measurement of cortical and trabecular area, and three sections from each specimen were measured for calculation of trabecular and cortical bone activation frequency (Ac.f) and bone formation rate (BFR/BV) in the superior and anterior regions of the femoral neck. Although no statistical differences were observed among groups for numerical density or length of microcracks, Kruskal-Wallis analysis showed differences among groups for both cortical and trabecular bone area (p < 0.05). Ac.f was significantly lower in both cortical bone (p < 0.05) and trabecular bone (p < 0.005) of the femoral neck at all dosage levels. No significant difference was observed among groups for trabecular mean wall thickness. The hypothesis that microdamage accumulation increases following reduction in Ac.f was not supported for the canine femoral neck in this experiment. This result could be explained by the fact that microdamage does not accumulate following treatment; that transient increases in microdamage at the beginning of the study period had been repaired; or finally, that the canine femoral neck does not reflect weight-bearing conditions of clinical relevance to humans for assessment of microdamage.

Animals↗
PubMed1995

Nucleolar organizer regions: a new prognostic factor for upper tract urothelial cancer.

PURPOSE: The prognostic significance of argyrophilic staining in the nucleolar organizer regions was studied in 63 patients with primary urothelial tumors of the renal pelvis and ureter. MATERIALS AND METHODS: Silver staining of paraffin embedded sections was performed using a 1-step technique. RESULTS: The prognosis for patients with a mean number of argyrophilic nucleolar organizer region proteins per nucleus (argyrophilic nucleolar organizer region score) of 8 or greater was significantly worse than that for patients with a score of less than 8 (P <0.001). CONCLUSIONS: Argyrophilic nucleolar organizer region score is a new prognostic factor in primary urothelial tumors of the renal pelvis and ureter, and it is particularly useful for patients with invasive tumors.

Adult↗
PubMed1995

Apoptosis in gastric carcinomas and its association with cell proliferation and differentiation.

The significance of apoptosis in human gastric carcinomas was investigated in comparison with proliferative activity and p53 accumulation, using an in situ DNA nick end labeling method and immunohistochemistry for both Ki-67 antigen and p53 protein. Apoptotic labeling indices (LI) of 51 differentiated carcinomas (21 of early and 22 of advanced stage) were significantly lower than for 33 undifferentiated tumors (9 of early and 24 of advanced stage) (P < 0.05). In both types, apoptotic LI of advanced stage lesions were significantly higher than for the early stage cases (P < 0.005, P < 0.03). The distribution of apoptotic cells was different from that of Ki-67-positive cells, generally exhibiting an inverse correlation for areas of predominance. In contrast, there was no significant correlation between p53 immunoreactivity and either apoptotic LI or Ki-67 LI. It is concluded that in human gastric carcinomas the susceptibility to apoptosis is related to tumor cell differentiation and depth of invasion, and may play a role in selection of clonal subpopulations with high growth potential.

Antigens, Neoplasm↗
PubMed1995

Mechanotransduction in bone: role of strain rate.

Bone tissue can detect and respond to its mechanical environment, but there is no consensus for how bone cells detect mechanical loads. Some think that cells sense tissue deformation (strain) and respond when strain is abnormally high. However, strains in bone tissue are usually very small, and it is questionable whether bone cells are sensitive enough to detect them. Another theory suggests that mechanical loads are coupled to the bone cells by stress-generated fluid flow within the bone tissue, which is dependent on the rate of change of bone strain. We applied bending loads to the tibiae of adult rats to create equivalent peak strains in the bone tissue but with varied rates of strain. Bone formation was significantly increased in the two experimental groups when the highest strain rates were compared with lower strain rates (P < 0.01), and the amount of new bone formation was directly proportional to the rate of strain in the bone tissue. These results suggest that relatively large strains alone are not sufficient to activate bone cells. High strain rates and possibly stress-generated fluid flow are required to stimulate new bone formation.

Adaptation, Physiological↗
PubMed1995

Changes in 3H-quinuclidinyl benzilate binding and protein synthesis in the striatum following chronic administrations of muscarinic agonist.

Injection of the muscarinic agonist oxotremorine into rat striatum for seven consecutive days resulted in a 44% reduction in 3H-quinuclidinyl benzilate (3H-QNB) binding, and it caused decreases in binding affinity to agonists. Furthermore, it eliminated the shift from the high affinity site to the low affinity site that occurs in the presence of 5'-guanylyl imidodiphosphate (Gpp (NH)p). In addition, oxotremorine caused a 1.5-fold increase in the incorporation of 3H-leucine into the striatum, suggesting that it increased the syntheses of proteins other than the muscarinic receptor protein. The present results show that chronic treatment of the striatum with oxotremorine causes alterations in not only the quantity, but also the sensitivity of muscarinic receptors to guanine nucleotide.

Animals↗
PubMed1995

Responses of immunocompetent cells to cavity preparation in rat molars: an immunohistochemical study using OX6-monoclonal antibody.

Responses of immunocompetent cells, especially class II major histocompatibility complex (MHC) antigen-expressing cells, were investigated after cavity preparation in the erupted upper first molar teeth of rats, by immunohistochemistry using OX6-monoclonal antibody. In control teeth, OX6-immunopositive cells were predominantly located beneath the odontoblast layer in the dental pulp. Cavity preparation caused an acute edematous reaction between the injured odontoblasts and predentin, and most of OX6-immunopositive cells in the affected site shifted away from the pulp-dentin border. After 12-24 hours, many OX6-immunopositive cells accumulated along the pulp-dentin border and extended their cytoplasmic processes into the exposed dentinal tubules. After 72 hours, newly differentiated odontoblasts replaced the degenerated odontoblasts, and few OX6-immunopositive cells remained along the pulp-dentin border. Our data suggest that some of the class II MHC antigen-expressing cells in the dental pulp participate in the initial defense reaction and presumably serve as a biological sensor for the external stimuli arriving through the exposed dentinal tubules.

Animals↗
PubMed1995

Immunohistochemical characterization and localization of MHC class II antigen-presenting cells in the periodontal ligament of rat incisors.

Dendritic cells have been identified both in lymphoid and nonlymphoid tissues as non-phagocytic antigen-presenting cells, equipped with extensive flamelike cytoplasmic projections. Our immunohistochemical study revealed presence of a large population of dendritic cells and other immunocompetent cells, showing a region-specific distribution, in the lingual periodontal ligament of continuously erupting rat incisors. This study aims to reveal the kinetics and cytological characterization of immunocompetent cells in the periodontal ligament of rat incisors with special reference to their differentiation pathway in the unique local environment.

Alveolar Process↗
PubMed1995

Enamel mineralization and the role of ameloblasts in calcium transport.

Amelogenesis is a dynamic and unique process of cell-matrix interactions in that matrix synthesis, degradation and resorption all proceed simultaneously, coupled with mineral depositions in a compartment between ameloblasts and dentin or dental papilla. Accumulation of data suggest the role of ameloblasts in tooth morphogenesis and matrix formation, but no fully acceptable explanation has been given concerning the role of ameloblasts in calcium transport. In this article, old and new points of issue raised regarding the role of ameloblasts in calcium acquisition are reviewed and possible mechanisms whereby the ameloblasts prevent the rise of cytosolic calcium while actively or less actively transporting calcium are elaborated upon based on recent findings.

Ameloblasts↗
PubMed1995

[A study of chemotherapy for patients with severely advanced gastric cancer--comparison of chemotherapy and route].

We analyzed the clinical response, toxicities, ambulatory and overall survival time among 51 patients with inoperable gastric cancer, to evaluate chemotherapies and drug delivery routes. Twenty-nine patients were treated by Methotrexate/5-FU (FMTX) therapy and 22 by 5-FU/CDDP (FP) therapy. Twenty-five patients were treated by intra-arterial (IA) route and 26 by intra-venous (IV). The response rate of IA therapy was higher than that of IV therapy (p < 0.05), 48% and 19%, respectively. Median survival times of FMTX and FP were 361 and 289 days, respectively, and the 1-year survival rates of FMTX and FP were 44% and 33%, respectively, with no significant differences. Duration of home chemotherapy with FMTX was longer than that with FP, at 130 and 85 days, respectively. There was no difference between duration of home chemotherapy of IA and that of IV. IA chemotherapy showed a higher response rate than IV, but there were no differences in the incidence of side effects and ambulatory and overall survival time.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Effect of low dose CDDP/5-fluorouracil therapy on PCNA labeling index and TS inhibition rate of gastric cancer].

The response of gastric cancer to intravenous application of low-dose CDDP plus 5-fluorouracil (FP) was assessed by changes in DNA indices (DIs) and PCNA labeling indices (LIs) by flow cytometry, and by the thymidylate synthetase inhibition rate (TSIR). Pretherapy samples were compared to specimens resected at operation. FP therapy was performed in 10 of 26 specimens and not in the others (C). There was no difference between change in DIs of FP group and that of C group. In FP group, PCNA LI of resected specimen was higher than that of biopsy, although they showed almost the same values in C group. Change in PCNA LIs correlated to TSIR in FP group. These results suggest that FP therapy affects gastric cancer cells in PCNA LIs and TSIR, and that PCNA LIs could be an indicator of the effect of FP therapy as TSIR.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Affinity of T-3761 to ocular melanin and intraocular dynamics].

The affinity of T-3761 to melanin was examined with synthetic melanin comparing other quinolones. The binding rates with synthetic melanin were from 37% to 48% for tosufloxacin, sparfloxacin, ciprofloxacin and norfloxacin. Binding rate of ofloxacin at 28% was lower and T-3761 was lowest at 22%. Intraocular dynamics of T-3761 and ofloxacin were investigated in pigmented rabbits after a single oral administration at a dose of 20 mg/kg. In both drugs, the concentrations in the melanin bearing tissues were higher and the disappearances from the melanin bearing tissues were more slowly than those of the non-melanin bearing tissues. T-3761 concentrations in the melanin bearing tissues were significantly lower than ofloxacin. In vitro uptake amount to melanin bearing tissue of ofloxacin was 1.4-2.4 times larger than that of T-3761.

Animals↗
PubMed1995

[Placental transfer and mammary excretion of [14C] T-3761 in rats and mice].

Placental transfer and mammary excretion of radioactivity were investigated in the pregnant rats on day 19 of pregnancy, in the pregnant mice on day 18 of pregnancy, and in the lactating rats after oral administration of 5 mg/kg of [14C] T-3761. 1. Transfer of radioactivity to fetus was observed in rats and mice and the concentration in fetus was 0.2-0.5 times higher than the maternal plasma. 2. The radioactivity was excreted into the milk and the concentration in milk was higher than those of blood levels (milk/blood = 1.3-5.8). The radioactivity in milk declined more slowly than in blood.

Animals↗
PubMed1995

[A case of lung cancer with choroidal metastasis].

A 72-year-old woman was admitted to our hospital because of a mass shadow in the left upper lobe on chest roentgenograms. She had noticed floaters in both visual fields 2 months before admission. Percutaneous aspiration of the lung lesion was done, and revealed poorly differentiated squamous cell carcinoma. Metastatic tumors were noted in the choroid of both eyes and in both kidneys. These lesions responded partially to systemic chemotherapy and the floaters disappeared. There have been few reports of metastatic choroidal tumors, but most cite the lung and the breast as the primary sites. We should pay attention to ophthalmologic findings because lung cancer may metastasize to the choroid.

Aged↗