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K Fukushima

Publications and source records attributed to K Fukushima.

At least 37 records · Page 2Linked to original sources
PubMed2002

Evaluation of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients.

This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.

Adult↗
PubMed2002

Increased expression of sialyl Lewis(x) antigen in penetrating growth type A early gastric cancer.

Early gastric cancer can be divided morphologically into two categories, penetrating growth type-A (Pen-A type) and other growth types (non-Pen-A types). Sialyl Lewis(x) antigen has been demonstrated to play an important role in tumor metastasis by serving as a functional ligand in the cell adhesion system. The aim of this study is to ascertain whether or not sialyl Le(x) antigen expression correlates with tumor growth patterns of early gastric carcinoma. An immunohistochemical assay was performed using monoclonal antibody CSLEX1 in 12 Pen-A type and 79 non-Pen-A type cancers. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%). Lymph node metastasis was found more frequently in Pen-A type than non-Pen-A type cancers (P=0.0004). Furthermore, sialyl Le(x) antigen high expression was detected more often in Pen-A type cancers (7 out of 12; 58.3%) than non-Pen-A type cancers (13 out of 79; 16.5%) (P=0.0036). Multivariate logistic regression analysis showed that these variables are related independently to the Pen-A type and the non-Pen-A type tumor growth patterns. These data suggest that the difference in sialyl Le(x) antigen expression between the Pen-A type and non-Pen-A type tumor growth patterns of early gastric cancer may, at least partially, reflect different biological behavior during tumor progression.

Adenocarcinoma↗
PubMed2001

Ménière's disease in childhood.

We report 3 rare cases of Ménière's disease in children. In Case 1 and 3, vertigo, hearing loss and tinnitus recovered soon after medical therapy. In Case 2, however, vertigo recurred and the hearing level on the right side markedly deteriorated. The equal-loudness contours on three-dimensional audiogram showed that right-sided aggravated hearing loss fluctuated for 4 years at middle-and low-frequencies despite medication. Finally intratympanic injection of gentamicin sulfate was performed. The patient has had no definitive spell of vertigo after gentamicin therapy. At our department, the incidence of Ménière's disease in pediatric patients with vertigo was 2.9%.

Adolescent↗
PubMed2001

Quantification of TECTA and DFNA5 expression in the developing mouse cochlea.

TECTA and DFNA5 are the mouse orthologues of the human deafness-associated genes TECTA and DFNA5. To determine how expression of these genes is regulated during development, relative mRNA abundance was examined in mice by non-radioactive RT-PCR. TECTA mRNA was detected on embryonic day 15 (E15), increased to its highest level on postnatal day 3 (P3) and then dramatically decreased by P15. Low levels persisted (adulthood, P45 to 67) with mean mRNA abundance after P15 less than 25% of P3 levels. DFNA5 mRNA expression was constant throughout these time points. These results imply that TECTA is transcribed at a particularly high level during tectorial membrane morphogenesis. In contrast, DFNA5 is present in both the developing and mature cochlea.

Aging↗
PubMed2001

Entactin-induced inhibition of human amyloid beta-protein fibril formation in vitro.

Amyloid beta-protein (Abeta) fibril in senile plaques may possibly be related to the pathogenesis of Alzheimer's disease (AD). Basement membrane (BM) components are localized to the plaques. Entactin binds the plaque associated BM components. We investigated the potential of entactin to prevent Abeta fibril formation. Thioflavin T fluorometric assay and electron microscopy revealed that entactin significantly inhibited Abeta1-40 (Abeta40) fibril formation at an Abeta40:entactin molar ratio of 50:1. The inhibitory effect of entactin was displayed in a dose-dependent manner. Circular dichroism spectroscopy data indicated that entactin induced a random coil structure in Abeta40. We propose that the ability of entactin to induce random structure is linked to the inhibition of Abeta fibril formation. Entactin may be related to the pathogenesis of AD by regulating Abeta40 fibril formation.

Amyloid beta-Peptides↗
PubMed2001

Carbohydrate recognition site of interleukin-2 in relation to cell proliferation.

Interleukin-2 (IL-2) is a cytokine with important roles in the immune system. IL-2 initially binds a high mannose-type glycan and a specific peptide sequence of the IL-2 receptor alpha-subunit and sequentially forms a high affinity complex of IL-2.IL-2 receptor alpha-, beta-, and gamma-subunits. This formation induces cellular signaling and cell proliferation (Fukushima, K., and Yamashita, K. (2001) J. Biol. Chem. 276, 7351-7356). To determine the carbohydrate-binding site of IL-2, we prepared wild-type and point-mutated (35)S-IL-2 by an in vitro transcription and translation method. We found that wild-type (35)S-IL-2 tends to form a dimer spontaneously, and the dimeric form has both carbohydrate recognition activity and cell proliferation activity. Moreover, substitution of Asn-26 in IL-2 with Gln or Asp conserved the dimeric form and affected the carbohydrate recognition activities in correspondence with the cell proliferation activities, suggesting that Asn-26 in IL-2 is involved in the carbohydrate recognition site. These results suggest that the carbohydrate recognition of IL-2 dimer triggers formation of high affinity complex (IL-2.IL-2Ralpha, -beta, -gamma)(2), and the hetero-octamer stimulates IL-2-dependent T-cell proliferation by intensifying cellular signaling.

Animals↗
PubMed2001

beta-amyloid induces caspase-dependent early neurotoxic change in PC12 cells: correlation with H2O2 neurotoxicity.

We examined neurotoxic effects of Abeta(25-35), an active fragment of beta-amyloid (Abeta), and compared the effect with H2O2 neurotoxicity in PC12 cells. Abeta(25-35) induced the loss of mitochondria function as detected using a tetrazolium salt (WST-1) reduction assay and decreased the number of cells adhering to collagen type 1-coated plates. Abeta(25-35) did not induce cell death, as detected by Hoechst 33342/propidium iodide staining. The caspase tetrapeptide inhibitor z-IETD-fluoromethylketone (FMK) and z-LEHD-FMK inhibited the attenuation of WST-1 reduction induced by Abeta(25-35) and H2O2, while the caspase-3 inhibitor z-DEVD-FMK afforded protection only against H2O2 neurotoxicity. Caspase-3 protease activity was increased by treatment of H2O2 but not Abeta(25-35). Thus, Abeta(25-35) induces early neurotoxic events by activating caspases other than caspase-3. H2O2 -induced oxidative stress may not be implicated in Abeta-induced neurotoxic pathways.

Amyloid beta-Peptides↗
PubMed2001

Correlation between p21(waf1) and p16(INK4a) expression in hepatocellular carcinoma.

Background: The cyclin dependent kinase p21(waf1) plays a crucial role in the regulation of cell cycle. The family of p53 proteins has the ability to induce p21(waf1), whereas p16(INK4a) modulates post-transcriptionally the expression of p21(waf1). Methods: Total 36 hepatocellular carcinomas (HCCs) and 24 paired adjacent liver tissues were evaluated for the following: (1) expression of p21(waf1) and p16(INK4a); (2) that of p21(waf1), p73 and p63 mRNAs; (3) genomic mutations and the loss of heterozygosity of p73 and p53; and (4) frequency of methylation in the 5'CpG promoter region of p16(INK4a). Results: In HCCs compared with the adjacent non-cancerous liver tissues, the expression of p21(waf1) and p16(INK4a) was reduced. Indeed, p21(waf1) was not detected in 36% (8/22) of HCCs in spite of the presence of p21(waf1) mRNA: among them, mutations of p53 gene were found in 50%, whereas a lack of p16(INK4a) expression in all of them. p21(waf1) and p16(INK4a) were reduced in proportion to the degree of methylation in p16(INK4a) gene. p73 did not mutated, and p63 did not expressed in HCCs. Conclusion: Methylation status of p16(INK4a) gene will play a part for reducing constitutive expression of p16(INK4a) and of p21(waf1) coordinately in HCCs.

Journal Article↗
PubMed2001

Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus.

DFNA16 is a form of autosomal dominant non-syndromic hearing loss (ADNSHL) characterized by fluctuating progressive hearing impairment. Earlier, we mapped the deafness-causing gene to chromosome 2q23-24.3. In this paper, we describe fine mapping results using additional markers tightly linked to the DFNA16 candidate region. Critical recombinants at markers D2S354 and D2S124 define a 3.5-cM interval that contains the DFNA16 gene. Positional candidate genes include two members of the voltage-gated sodium channel family, the type 2 alpha subunit (SCN2A) and the type 3 alpha subunit (SCN3A). After showing that SCN2A is expressed in human fetal cochlea, we determined its genomic structure to facilitate mutation screening in our DFNA16 kindred. We also determined the genomic structure of SCN3A. These two genes are oriented head-to-head, with their 5' ends separated by approximately 40 kb; their homology is 82% at the nucleotide level, and 85% for identities and 90% for positives at the amino acid level. They share similar genomic structures and have alternative splice isoforms that are developmentally regulated and highly conserved between species. Although no DFNA16-causing mutations were found in either gene, haplotype analysis with polymorphic markers in SCN2A introns further narrowed the candidate gene interval to the region flanked by D2S354 and STS SHGC-82894.

Alternative Splicing↗
PubMed2001

MYO1F as a candidate gene for nonsyndromic deafness, DFNB15.

BACKGROUND: Earlier studies have mapped the autosomal recessive nonsyndromic deafness locus, DFNB15, to chromosomes 3q21.3-q25.2 and 19p13.3-13.1, identifying one of these chromosomal regions (or possibly both) as the site of a deafness-causing gene. Mutations in unconventional myosins cause deafness in mice and humans. One unconventional myosin, myosin 1F (MYO1F), is expressed in the cochlea and maps to chromosome 19p13.3-13.2. OBJECTIVE: To evaluate MYO1F as a candidate gene for deafness at the DFNB15 locus by determining its genomic structure and screening each exon for deafness-causing mutations to identify possible allele variants of MYO1F segregating in the DFNB15 family. METHODS: We used radiation hybrid mapping to localize MYO1F on chromosome arm 19p. We next determined its genomic structure using multiple long-range polymerase chain reaction experiments. Using these data, we completed mutation screening using single-stranded conformational polymorphism analysis and direct sequencing of affected and nonaffected persons in the original DFNB15 family. RESULTS: Radiation hybrid mapping placed MYO1F in the DFNB15 interval, establishing it as a positional candidate gene. Its genomic structure consists of 24 coding exons. No mutations or genomic rearrangements were found in the original DFNB15 family, making it unlikely that MYO1F is the disease-causing gene in this kindred. CONCLUSIONS: Although we did not find MYO1F allele variants in one family with autosomal recessive nonsyndromic hearing loss, the gene remains an excellent candidate for hereditary hearing impairment. Given its wide tissue expression, MYO1F might cause syndromic deafness.

Alleles↗
PubMed2001

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Adaptation, Physiological↗
PubMed2001

Recognition of partly occluded patterns: a neural network model.

Human beings are often able to read a letter or word partly occluded by contaminating ink stains. However, if the stains are completely erased and the occluded areas of the letter are changed to white, we usually have difficulty in reading the letter. In this article I propose a hypothesis explaining why a pattern is easier to recognize when it is occluded by visible objects than by invisible opaque objects. A neural network model is constructed based on this hypothesis. The visual system extracts various visual features from the input pattern and then attempts to recognize it. If the occluding objects are not visible, the visual system will have difficulty in distinguishing which features are relevant to the original pattern and which are newly generated by the occlusion. If the occluding objects are visible, however, the visual system can easily discriminate between relevant and irrelevant features and recognize the occluded pattern correctly. The proposed model is an extended version of the neocognitron model. The activity of the feature-extracting cells whose receptive fields cover the occluding objects is suppressed in an early stage of the hierarchical network. Since the irrelevant features generated by the occlusion are thus eliminated, the model can recognize occluded patterns correctly, provided the occlusion is not so large as to prevent recognition even by human beings.

Artificial Intelligence↗
PubMed2001

Laparascope-assisted versus conventional restorative proctocolectomy with rectal mucosectomy.

To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.

Adenomatous Polyposis Coli↗
PubMed2001

Random amplified polymorphic DNA analysis applied to acute otitis media caused by penicillin non-susceptible Streptococcus pneumoniae.

The spread of penicillin non-susceptible Streptococcus pneumoniae (PNSSP) is an emerging problem for the treatment of acute otitis media (AOM). Attendance of children at day care centers, as well as the spread of PNSSP, is a risk factor for AOM. The status of the spread of PNSSP during the acute infection phase of AOM has not been evaluated. We examined the clonality of samples from seven children in a day care center who simultaneously developed AOM caused by PNSSP. The seven isolates from the children, and six control samples were grouped by serotyping, by determining resistance to antimicrobial agents, and by genotyping, carried out by sequencer-based random amplified polymorphic DNA (RAPD), and validated by bootstrap analysis. There was no evidence to indicate the direct dissemination of PNSSP among these patients in the day care center, although the simultaneous occurrence of PNSSP AOM had initially suggested a clonal outbreak. The possible presence of a common ancestral strain suggested the importance of surveillance during the carrier state. The result of RAPD genotyping was highly reproducible, as validated by the high bootstrap score. The use of an automated sequencer, in combination with a careful choice of primers, and commercially established kits, played a significant role in the reproducibility of the studies.

Child↗
PubMed2001

Relationship between age, histological type, and size of ovarian tumors.

OBJECTIVE: To clarify the relationship between age, histological type, and size of ovarian tumors. METHOD: A review was made of 1648 cases of histopathologically diagnosed ovarian tumors and tumor-like lesions, and information on the age of the patients and size of the tumor was obtained. Statistical analysis was performed using Kruskal-Wallis tests or Mann-Whitney U-tests. RESULTS: There were 840 (51%) cases of benign tumors, 73 (4%) cases of tumors of low malignant potential (LMP), 268 (16%) cases of malignant tumors and 467 (28%) cases of tumor-like lesions. The age of the patients was significantly different among tumor-like lesions (34.6+/-8.1 years), benign tumors (39.8+/-16.4 years), LMP tumors (45.2+/-18.3 years) and malignant tumors (51.9+/-13.0 years) (P<0.0001). The maximum diameter of the tumors was significantly different among tumor-like lesions (7.1+/-3.3 cm), benign tumors (10.9+/-5.6 cm), malignant tumors (13.6+/-6.5 cm) and LMP tumors (18.5+/-6.8 cm) (P<0.0001). CONCLUSION: The distribution of tumor histological type (tumor-like lesions, benign, LMP and malignant) was correlated against patient age and lesion diameter, with tumors in older patients or larger tumors more likely to be malignant.

Adult↗
PubMed2001

Prognostic significance of thrombomodulin expression and vascular invasion in stage I squamous cell carcinoma of the lung.

Thrombomodulin (TM) is an important modulator of intravascular coagulation. TM exists on endothelial cells and on several types of tumor cells, especially squamous cell carcinoma cells. Tumor cell TM is thought to be associated with progression and metastasis of the tumor. To evaluate the prognostic significance of TM in lung cancer, we examined TM expression and vascular invasion in surgical specimens obtained from 90 patients with completely resected stage I non-small cell lung cancer (NSCLC). In addition, we correlate these pathologic data to other clinicopathologic data, including the outcome of the patients. Squamous cell carcinomas had a significantly higher incidence (P<0.0001) of TM expression (22/36 cases, 61%) than adenocarcinomas (9/54 cases, 17%). In 36 squamous cell carcinoma patients, both vascular invasion (P=0.0153; risk ratio 6.507) and TM non-expression (P=0.0282; risk ratio 3.584) were significant for a poor prognosis. Univariate analysis of patient survival rates also revealed that vascular invasion and TM expression were significant prognostic factors (P=0.0036 and 0.012, respectively). Further, combination analysis of vascular invasion and TM expression in the squamous cell carcinoma patients showed that the 5-year survival rate was 90% in patients with TM expression and without vascular invasion, but 21% in patients with vascular invasion and without TM expression (P=0.0004). Since our results suggest that vascular invasion and TM expression are independent prognostic factors of stage I squamous cell carcinoma of the lung, and since the two factors play different roles in the metastatic process of cancers (promotion of metastasis by vascular invasion and inhibition of metastasis by TM expression), the combination evaluation of vascular invasion and TM expression may be very significant in evaluating the prognosis of patients with completely resected stage I squamous cell carcinoma.

Adult↗
PubMed2001

Hypophysis surgery with or without endoscopy.

OBJECTIVE: Hardy's operation with microscope has long been the standard method for pituitary adenoma. But a new approach via the nasal cavity using an endoscope has been adopted recently. In this study, the postoperative outcome as well as the preoperative evaluation of endoscopic hypophysectomy and non-endoscopic one were compared at our faculty. METHOD: We performed the non-endoscopic transnasal hypophysectomy on 18 patients and the endoscopic transnasal hypophysectomy on thirteen patients who had a pituitary lesions from February 1996 to October 1999. As to these patients the situations from preoperation through postoperation such as chief complaints, serum hormone level, final diagnosis, tumor size, as well as operating time or blood loss during the operation were discussed precisely. Then the merits and demerits of endoscopic hypophysectomy were discussed. RESULT: Five PRL-producing adenoma, three GH-producing adenoma, nine non-functioning adenoma, and two ACTH or TSH-producing adenoma were included in this discussion as endoscopic group. The age of non-endoscopic group are from 23 to 73 (49.4 in average), and they include ten males and eight females. On the other hand three PRL-producing adenoma, two GH-producing adenoma, two non-functioning adenoma, and one Rathke's cyst were included in this discussion as endoscopic group. The age of endoscopic group are from 19 to 73 (49.1 in average), and they include seven males and six females. As to non-endopscopic group the blood loss during each operation is 568 ml and operating time is 256 min in average. For endoscopic group the blood loss is 296 ml and operating time is 234 min in average. CONCLUSION: By microsurgery in the pituitary operation with endoscopy, the minimal invasive surgery becomes possible by reducing blood loss and shortening operating time. During the operation cooperation between neurosurgeon and ENT surgeon is indispensable in order to perform hypophysectomy smoothly. The development of optical better aids and operation instruments for endonasal hypophysectomy is desired in the future. The navigation system was more useful than X-ray fluoroscopy to obtain the detailed information.

Adenoma↗