PubMed Health⌕ Search

Biomedical subjects

Keisuke Kato

Publications and source records attributed to Keisuke Kato.

33 records · Page 2Linked to original sources
PubMed2004

Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma.

To investigate the various genetic characteristics of and differences between early- and advanced-stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two-way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these NB tumors. Although 9 of the 13 early-stage tumors (69%) and 4 of the 6 advanced-stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early- and advanced-stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of NB. These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real-time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early-stage group than in the advanced-stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early-stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB.

Biomarkers, Tumor↗
PubMed2004

Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma.

This study concerns the significance of nuclear/cytoplasmic expression of beta-catenin and mutation of the beta-catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of 'palisading cells', 'stellate cells', and 'ghost cells'. In addition, 'whorl-like arrays' of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta-catenin predominantly in cohesive cells within the whorl-like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki-67 was almost absent. The cohesive cells in the whorl-like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta-catenin accumulation showed heterozygous one-base substitution mutation of the beta-catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl-like arrays and ghost cells rather than as simple proliferation stimuli.

Adolescent↗
PubMed2004

Synthesis of carbocyclic analogues of 4'-ethynyl- and 4'-cyano-d4T.

Synthesis of carbocyclic analogues of 4'-ethynyl and cyano-d4T (4 and 5) was investigated. The ethynyl or cyano group was constructed by conversion of the ester function of key intermediate 13. The carbocyclic unit 12 was prepared from readily available beta-keto ester 6.

Acids, Carbocyclic↗
PubMed2004

Chemoenzymatic synthesis of n-hexyl and O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranosides.

Direct beta-glucosidation between 1,6-octanediol (5) and D-glucose (3) using the immobilized beta-glucosidase (EC 3.2.1.21) from almonds with the synthetic prepolymer ENTP-4000 gave a mono-beta-glucoside (6) in 61.4% yield, which was converted into the n-hexyl beta-D-glucopyranoside (1) by means of a chemoenzymatic method. The coupling of the n-hexyl beta-D-glucopyranoside congener (13) and 2,3,4-tri-O-acetyl-beta-D-xylosyl congener (14), followed by deprotection, afforded the synthetic n-hexyl O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside (2), which was identical to the natural 2 with respect to the spectral data and specific rotation.

Enzymes, Immobilized↗
PubMed2004

Determination of the absolute structure of (+)-cystothiazole B.

Palladium-catalyzed cyclization-methoxycarbonylation of (2R,3S)-3-methylpenta-4-yne-1,2-diol (6) derived from (2R,3S)-epoxy butanoate 5, followed by methylation, gave the tetrahydro-2-furylidene acetate (-)-7, which was converted to the left-half aldehyde (+)-3. A Wittig reaction between (+)-3 and the phosphoranylide derived from the bithiazole-type phosphonium iodide 4 using lithium bis(trimethylsilyl)amide afforded (+)-cystothiazole B (2), the spectral data of which were identical to those of the natural product (+)-2. Thus the stereochemistry of cystothiazole B (2) was confirmed to be [4R, 5S, 6(E)].

Molecular Structure↗
PubMed2004

Maternal, neonatal, and placental features associated with diffuse chorioamniotic hemosiderosis, with special reference to neonatal morbidity and mortality.

OBJECTIVE: Our purpose was to examine the significance of diffuse chorioamniotic hemosiderosis (DCH) on neonatal morbidity and mortality. METHODS: Using data from a retrospective case-control study, we analyzed 46 singleton placentas with DCH from infants who were delivered and/or admitted to the neonatal intensive care unit of Kanagawa Children's Medical Center during 1987-2001 and 92 control placentas without DCH from infants of comparable gestational age, birth weight, and duration. RESULTS: Mean and standard deviation of gestational age and infants' birth weight at delivery from the DCH group were 27 +/- 3 weeks and 939 +/- 342 g, respectively. Macroscopically, the placentas with DCH were more likely to show old peripheral blood clots (46% in the DCH group vs 8% in control group), subchorionic hematoma (20% vs 1%), and circumvallation (13% vs 1%). Histologically, amniotic necrosis was significantly more frequent in the DCH group (63% vs 24%). Of the obstetric factors, incidence of recurrent episodes of vaginal bleeding (70% vs 11%), oligohydramnios (59% vs 8%), and chronic abruption-oligohydramnios sequence (57% vs 5%) were significantly higher in the DCH group. Of the neonatal factors, persistent pulmonary hypertension of the newborn (29% vs 8%) and dry lung and/or pulmonary hypoplasia (20% vs 4%) were more common. However, respiratory distress syndrome was rare (15% vs 45%) in the DCH group. Neonatal death including stillbirth was increased in the DCH group but was not significant (24% vs 15%). Of infants who survived beyond day 28, chronic lung disease (CLD) was more frequent in the DCH group (51% vs 22%). The association of DCH, especially accompanied by amniotic necrosis, with CLD was still evident using likelihood ratio test. CONCLUSION: DCH is closely associated with preterm delivery, pulmonary hypertension of the newborn, and dry lung syndrome and is a significant risk factor for CLD.

Abruptio Placentae↗
PubMed2003

Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma.

This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL.

Child↗
PubMed2003

Asthma health status: influence of disease severity categorized by peak expiratory flow.

To evaluate the health status of patients with stable asthma and determine how disease severity affects the status, 68 consecutive patients were recruited from an outpatient clinic at an university hospital. Health status was assessed with the St. George's Respiratory Questionnaire and the Asthma Quality of Life Questionnaire (AQLQ). The results of the questionnaires revealed that the mean % predicted peak expiratory flow (PEF) in the preceding 2 weeks correlated most significantly with each total score for the two health status measures. We also found that, in the groups classified by mean % predicted PEF (mild, PEF > or = 80%; moderate, 60 to 79%; severe, < 60%), there were significant differences in all SGRQ scores (p < 0.05). In a subgroup analysis, the scores for moderate and severe patients were significantly worse than for mild patients in all four components (p < 0.05). Almost the same tendency was observed in the score distribution on the AQLQ. We conclude that mean % predicted PEF correlated most with the health status of the patients. Patients with PEF higher than 80% of predicted value generally maintained a better health status than did those with less than 80% of predicted PEF. Achieving higher than 80% of predicted PEF is important in managing asthma from the viewpoint of health status.

Adult↗
PubMed2003

A case of nosocomial Legionella pneumophila pneumonia.

We report a case of Legionella pneumophila pneumonia in a patient with interstitial lung disease. Intensive environmental investigations revealed that a system of all-day-running bathwater was the source of infection. In this case, the concentration of L. pneumophila in the hospital bathwater was low. We therefore emphasize that even a low concentration of L. pneumophila in environmental water can cause serious infections to immunocompromised patients in a hospital.

Aged↗
PubMed2002

Increased Ras expression and caspase-independent neuroblastoma cell death: possible mechanism of spontaneous neuroblastoma regression.

BACKGROUND: Neuroblastoma undergoes spontaneous regression frequently during its natural course. Although programmed cell death (PCD) has been implicated in this process, accumulating evidence suggests that apoptosis, a form of PCD that is regulated by caspases, may not play a major role. We examined the mechanism(s) of spontaneous regression of neuroblastoma, focusing on the role of Ras, a favorable prognostic marker of neuroblastoma. METHODS: Tumor tissues were analyzed by light microscopy, electron microscopy, and immunohistochemistry to examine cell degeneration and expression of Ras and several indicators of PCD. Cell degeneration was also studied in vitro in neuroblastoma cells transfected with the H-ras gene. All statistical tests were two-sided. RESULTS: Immunohistochemical analyses revealed that Ras expression was increased in areas of cellular degeneration lacking apoptotic characteristics. The degenerating cells were fragmented without nuclear condensation and, essentially, lacked caspase-3 activation and apoptotic DNA fragmentation. These cells had ultrastructural features of autophagic degeneration, another form of PCD that is distinct from apoptosis. Focal areas of degeneration associated with Ras expression were seen more frequently in tumors from patients detected in a mass-screening program (53 [60.9%] of 87) than in tumors from clinically detected, advanced-stage patients over 1 year of age (7 [29.2%] of 24) (P =.006; chi-square test), suggesting a positive relationship between Ras-associated degeneration and probability of spontaneous regression/favorable prognosis. The characteristic features of Ras-associated nonapoptotic degeneration observed in tumor samples were recapitulated in vitro by transfection-mediated Ras expression, and Ras-mediated degeneration was augmented by TrkA, another favorable prognostic marker. CONCLUSIONS: High-level expression of H-Ras in neuroblastoma cells is associated with caspase cascade-independent, nonapoptotic PCD. This Ras-mediated nonapoptotic tumor cell death may play a key role in spontaneous regression of neuroblastoma.

Apoptosis↗
PubMed2002

Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules.

The salient histopathologic features of low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include complex glandular structures and morules with biotin-rich optically clear nuclei. Interestingly, these characteristic features are shared by the cribriform-morular variant of papillary thyroid carcinoma, whose morphology is identical to that of familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore, the single reported case of lung cancer associated with FAP was L-FLAC/WDFA. These observations lead us to hypothesize that up-regulation of the Wnt signaling pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11 cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high-grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta-catenin. All cases of L-FLAC/WDFA showed predominantly aberrant nuclear/cytoplasmic expression, especially in budding glands and morules, whereas six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic expression restricted to the distal branching airway epithelium. Mutational analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA showed a point mutation at codon 34 and codon 37 in two cases, respectively. The present study indicates that up-regulating disturbances in the Wnt signaling pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L-FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that of the developing fetal lung airway. With the expression pattern of beta-catenin as a marker, most cases of H-FLAC as well as CAC appear to have different oncogenic pathways from cases of L-FLAC/WDFA. The present study together with other available data also suggests that abnormal up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors with morular formation from a variety of anatomic sites.

Adenocarcinoma↗
PubMed2002

Re-evaluation of chorioamnionitis and funisitis with a special reference to subacute chorioamnionitis.

Our purpose is to prove that prolonged inflammation of the chorionic plate, which we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and should be differentiated from acute chorioamnionitis (ACAM) because it is an excellent prognostic indicator of chronic lung disease (CLD), including Wilson-Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33 placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation- and birthweight-matched placentas without chorioamnionitis were selected as control. To determine the risk factors for CLD, 27 clinical and 6 histological variables were analyzed. Logistic regression analysis showed that amniotic necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major contributing risk factors for CLD. SNF was not significantly related to CLD. Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion, SCAM, especially when associated with AN, seems to be a unique prognostic indicator of CLD.

Amnion↗
PubMed2002

Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the testis.

This study concerns the immunohistochemical localization of S-100 alpha, S-100 beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5 ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8 LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells. S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli cells, rete testis, Schwann cells, and some endothelial cells. The results indicate that S-100 alpha and S-100 beta can potentially be used as immunohistochemical markers for LCCSCT, especially when differentiating it from LCT, which may mimic LCCSCT on routine histopathology. Although the biological significance of both S-100 subunits expression in LCCSCT remains unknown, these notable calcium-binding proteins may be associated with the characteristic calcification in LCCSCT through regulation of calcium levels in the tumor cells.

Biomarkers↗
PubMedDate not supplied

Pancreatoblastoma. A case report with special emphasis on squamoid corpuscles with optically clear nuclei rich in biotin.

BACKGROUND: Pancreatoblastoma (PBL) is a rare neoplasm that generally occurs in the pediatric age group and shows unique histopathology, including squamoid corpuscles that may contain tumor cells with optically clear nuclei (OCN) rich in biotin. In the English-language literature there have been two reports on the cytology of PBL, but neither of them refers to the cytologic features of squamoid corpuscles. CASE: A 3-year-old boy with nausea and general fatigue was referred to our center. Imaging studies showed an approximately 7.5-cm, left-sided abdominal mass and multiple metastases in the lung. The abdominal mass was biopsied, and its histology showed solid cellular nests with occasional acinar differentiation and squamoid corpuscles. Imprint cytology of the biopsied sample displayed cellular epithelial nests with focal acinar structures and foci composed of larger cells with a low nuclear/cytoplasmic ratio. These foci contained a few tumor cells with biotin-rich OCN and were determined to be squamoid corpuscles. CONCLUSION: Detection of occasional squamoid corpuscles with biotin-rich OCN can be useful in making a diagnosis of PBL on cytologic samples.

Biomarkers, Tumor↗