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Biomedical subjects

Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 73 records · Page 4Linked to original sources
PubMed2000

p53-regulated GML gene expression in non-small cell lung cancer. a promising relationship to cisplatin chemosensitivity.

The GML gene (glycosylphosphatidylinositol-anchored molecule-like protein gene) is a novel gene specifically induced by wild-type p53, which may participate in cell cycle control or the cell apoptotic pathway. Recent experiments suggest that the expression of this novel gene in cancer cells is closely associated with sensitivity to certain anticancer drugs. To elucidate the role of the gene expression in cisplatin (CDDP) chemosensitivity of non-small cell lung cancer (NSCLC), 30 surgically resected materials were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). GML gene expression was detected in 9 (30%) samples. Its incidence was significantly higher in immunohistochemically p53-negative (P=0.040) or wild-type p53 tissues (P=0.041). On in vitro chemosensitivity testing using 29 primary tissues, six samples with GML gene expression showed good sensitivity to CDDP. In particular, in tissues with immunohistochemically p53-negative accumulation, those with GML gene expression showed significantly better in vitro sensitivity to CDDP (P=0.012). Clinically a good response to CDDP-based chemo(thermo)therapy for NSCLC patients with tumour residue or recurrence, was observed only in those with p53-negative accumulation and GML gene expression, in agreement with in vitro results. Thus, although the number of tested samples was small, GML gene expression is commonly detected in immunohistochemically p53-negative NSCLCs in close association with good sensitivity to CDDP. GML gene expression analysis may serve as a predictor of CDDP-based chemotherapy for patients with NSCLC.

Antineoplastic Agents↗
PubMed2000

Isolation and characterization of human NBL4, a gene involved in the beta-catenin/tcf signaling pathway.

beta-Catenin, a key regulator of cellular proliferation, is often mutated in various types of human cancer. To investigate cellular responses related to the beta-catenin signaling pathway, we applied a differential display method using mouse cells transfected with an activated form of mutant beta-catenin. This analysis and subsequent northern-blot hybridization confirmed that expression of a murine gene encoding NBL4 (novel band 4.1-like protein 4) was up-regulated by activation of beta-catenin. To examine a possible role of NBL4 in cancer, we isolated the human homologue of the murine NBL4 gene by matching mNBL4 against the human EST (expressed sequence tag) database followed by 5' rapid amplification of cDNA ends (5'RACE). The cDNA of hNBL4 encoded a protein of 598 amino acids that shared 87% identity in amino acid sequence with murine NBL4 and 71% with zebrafish NBL4. A 2.2-kb hNBL4 transcript was expressed in all human tissues examined with high levels of expression in brain, liver, thymus and peripheral blood leukocytes and low levels of expression in heart, kidney, testis and colon. We determined its chromosomal localization at 5q22 by fluorescence in situ hybridization. Expression of hNBL4 was significantly reduced when beta-catenin was depleted in SW480 cells, a human cancer cell line that constitutionally accumulates beta-catenin. The results support the view that NBL4 is an important component of the beta-catenin / Tcf pathway and is probably related to determination of cell polarity or proliferation.

Amino Acid Sequence↗
PubMed2000

Prognostic significance of occult bone marrow micrometastases of breast cancer detected by quantitative polymerase chain reaction for cytokeratin 19 mRNA.

Amplification of cytokeratin 19 (CK19) transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a highly sensitive assay for the detection of bone marrow micrometastases (BMM) of breast cancer, but recent studies have demonstrated the occurrence of false-positive results due to low-level, illegitimately transcribed CK19 in normal bone marrow tissue. One approach to solve this problem is to develop a quantitative CK19 RT-PCR assay and to introduce a cut-off value which can distinguish between illegitimate expression and cancer-specific expression levels. In the present paper, we describe a quantitative CK19 RT-PCR assay using a real-time automated PCR system. The number of CK19 transcripts was normalized to that of GAPDH transcripts as an internal control for quality and quantity of cDNA. The cut-off value for the ratio of CK19 to GAPDH transcripts was set at 10(-4) since the ratio never exceeded this value in the control bone marrow samples (n = 12). In total, 117 bone marrow aspirates from stage I - III patients with invasive breast cancers were subjected to CK19 RT-PCR assay and immunocytological examination. Forty (34.2%) were found to be BMM-positive by CK19 RT-PCR assay whereas only three (2.6%) were found to be BMM-positive by immunocytology. Multivariate analysis has shown that occult BMM detected by CK19 RT-PCR is a significant risk factor for relapse, being independent of axillary lymph node metastases.

Bone Marrow Neoplasms↗
PubMed2000

Molecular and biological analysis of carcinoma of the small intestine: beta-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype.

The genetic mechanisms of carcinomas of the small intestine are not well understood. We report the results of analysis of genetic alterations in a case of small intestinal carcinoma. A tumor in the terminal ileum was resected in a 59-yr-old woman. Histologically, the tumor was classified as well-differentiated adenocarcinoma. We screened for genetic alterations in adenomatous polyposis coli (APC), beta-catenin, K-ras, and p53 genes, as well as microsatellite instability, which are known to be involved in colorectal tumorigenesis. The tumor exhibited somatic interstitial deletion of 425-bp, which included the entire exon 3 in beta-catenin gene. Immunohistochemical staining confirmed accumulation of aberrant beta-catenin protein in the cytoplasm and nuclei of the malignant tissue. Furthermore, a frameshift mutation in the transforming growth factor beta receptor type II gene with replication error phenotype was detected in the tumor DNA. In contrast, no genetic alterations were found in the APC, K-ras, and p53 genes. Our results suggested that both beta-catenin gene mutation and replication error phenotype might contribute to carcinogenesis of the small intestinal tumor in our case. This is the first report that activation of beta-catenin gene by somatic gene mutation is involved in the development of carcinoma of the small intestine.

Amino Acid Sequence↗
PubMed2000

[Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer].

BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA.

Aged↗
PubMed2000

[Selection guide of incinerator on medical organizations].

A countermeasure to dioxin is implementation of the so-called "3T" principle (Temperature, Time, Turbulence), and prevent re-synthesis of dioxin in the treatment process of exhaust gas. To prevent dioxin re-synthesis, the temperature of exhaust gas after exiting incinerator should immediately be cooled to less than 200 degrees C, and the dust in the exhaust gas should be removed by a high quality collector. As the exhaust gas contains a high concentration of HCl, the selection of materials to treat the exhaust gas should be carefully considered.

Air Pollution↗
PubMed2000

[Neurosarcoidosis with girdle sensation and polyradiculoneuropathy masquerading as Guillain-Barré syndrome].

We herein report two patients with neurosarcoidosis presenting girdle sensation in the trunk and polyradiculoneuritis. The first patient, a 53-year-old woman, manifested subacute progressive paresthesia in all four limbs and below the Th 3 level with girdle sensation from the thorax to lower abdomen and mild weakness in the left upper limb and the bilateral lower limbs. The patient was diagnosed to have sarcoidosis based on a biopsy of the scalenus anticus lymph nodes. The second patient, a 63-year-old woman, showed an acute onset of weakness and paresthesia in all four limbs and girdle sensation from the Th 5 to Th 8 level. On examination, she demonstrated diminished tendon reflexes in all four limbs, mild to severe weakness in all four limbs, paresthesia in all four limbs and below the Th 5 level. Although Guillain-Barré syndrome was initially suspected in this patient, the presence of girdle sensation led us to examine the possibility of neurosarcoidosis. Her examination demonstrated an abnormal accumulation of gallium in the bilateral hilar lymph nodes and mediastinum on scintigraphy, an elevated CD 4/CD 8 ratio in the bronchoalveolar lavage fluid, a negative tuberculin reaction, and elevated serum lysozyme level. These findings thus fulfilled the clinical criteria for sarcoidosis. None of the two patients showed any abnormalities in the thoracic cord MRI. In the first patient F wave was not evoked in either upper or lower limbs, while in the second patient temporal dispersion on M wave was observed in the right median and both ulnar nerves. We therefore consider the girdle sensation to have not been caused by myelopathy but instead by polyradiculopathy. When sarcoid peripheral neuropathy masquerades as Guillain-Barré syndrome, then the presence of girdle sensation may help diagnosis of neurosarcoidosis.

Diagnosis, Differential↗
PubMed2000

Free-floating left atrial ball thrombus early after mitral valve replacement.

A 61-year-old woman was found to have a free-floating ball, thrombus in the left atrium on echocardiographic examination 2 weeks after mitral valve replacement and tricuspid, annuloplasty. The free-floating thrombus was successfully, removed by an open-heart procedure without clinical sequelae. The diagnostic value of routine echocardiography on follow-up of valve surgery is emphasized.

Female↗
PubMed2000

[Results of treatment for germ cell tumor--dose intensity of chemotherapy and residual masses after chemotherapy].

We reviewed the treatment results in 44 patients with germ cell tumor and the significance of % dose intensity of Cisplatin and tumor marker half-life of induction chemotherapy and discussed the necessity of surgical resection of the postchemotherapy residual tumor. The 5-year survival rate calculated by the Kaplan-Meier method was 83.6% in total, and 95.2, 75.8 and 47.6% for good, intermediate and poor prognosis, respectively. Of the 29 metastatic cases treated by chemotherapy, 5 (17.2%) achieved complete response (CR) and 15 (51.7%) partial response, and % dose intensity of Cisplatin were 75.4% in total and 86.4 +/- 8.6, 71.6 +/- 11.1, 84.3 +/- 8.3 and 62.2 +/- 11.0% in CR, PR, NC and PD. Dose intensity was correlated with the clinical response and the prognosis. Of the 12 PR cases without teratoma elements, two had salvage surgery, five had additional chemotherapy and five were followed by surveillance. One case followed by surveillance died of the disease, another one with additional chemotherapy was alive with the disease and the others were alive with no evidence of disease. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered in the cases without teratoma elements.

Adult↗
PubMed2000

[Repeated deterioration of tuberculous meningitis due to a reduction in the corticosteroid dosage during chemotherapy].

A 17-year-old man with a high fever, confusion and neck stiffness was diagnosed to have tuberculous meningitis, and was immediately placed on prednisolone (40 mg/day) as well as standard antituberculosis drugs (isoniazid, rifampicin and pyrazinamide). The clinical symptoms improved rapidly and the number of cerebrospinal fluid(CSF) cells decreased from 1837/mm3 on admission to 76/mm3 on the 7th day. Thereafter the dosage of prednisolone was gradually reduced. As a result, however increased nuchal rigidity, papilloedema and an increase in the number of CSF cells of 934/mm3 were all observed on the 35th day. Prednisolone thus again administered at the original dosage and the patient quickly showed a clinical improvement. CSF cells decreased to 271/mm3 on the 70th day. When prednisolone was again tapered down, increased nuchal rigidity, abducent nerve palsy and papilloedema appeared again with a marked increase in the number of CSF cells of 1309/mm3 on the 91th day. Therefore, we continued to treat the patient with prednisolone, in addition to the standard antituberculosis treatment, at a dose of 80 mg/day and tapered off very slowly over six months. This treatment resulted in a marked recovery with no recurrence. In this case, prednisolone was indispensable for treating tuberculous meningitis in combination with appropriate antituberculosis drugs, though the role of corticosteroids has remained controversial over the years. This case might be an example of paradoxical progression in tuberculous meningitis.

Adolescent↗
PubMed1999

Transformation and morphological changes of murine L cells by transfection with a mutated form of beta-catenin.

To shed light on the oncogenic nature of mutant beta-catenin, we introduced a form of the cDNA that lacked an entire exon 3 into L cells derived from murine s.c. tissue. Aberrant beta-catenin protein accumulated in the cytoplasm and nuclei of these cells (designated L-MT), whereas in L cells transfected with wild-type beta-catenin (designated L-N), normal beta-catenin protein was expressed at a level similar to that of parental cells. L-MT cells also changed morphologically from a fibroblast-like appearance to a more cuboidal shape. Their rate of proliferation was the same as that of L cells and L-N cells, but the saturation density of L-MT cells appeared to increase in association with a multilayer growth pattern. Furthermore, L-MT cells required a lower concentration of serum in the growth medium than did parental cells. These alterations in cell growth and morphology suggested that mutated beta-catenin was stabilized in the transfected cells and induced the oncogenic phenotype.

Animals↗
PubMed1999

Telomerase activity in oral cancer.

Telomerase activity can be detected in most human cancers. This is consistent with the telomere hypothesis, which predicts upregulation of telomerase expression after a number of mitotic divisions to prevent the progressive and catastrophic loss of telomeres. However, telomerase has not been fully analyzed in oral cancers. In this report, telomerase activity was analyzed in 31 human oral malignant tumors, 11 leukoplakias, three pleomorphic adenomas, and 40 samples taken from normal tissues of the oral cavity, using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Telomerase activity was detected in most oral cancers [squamous cell carcinoma (SCC), non-Hodgkin's lymphoma, adenoid cystic carcinomas, mucoepidermoid carcinoma, osteosarcoma, acinic cell carcinoma, rhabdomyosarcoma]. None of the normal tissues or pleomorphic adenomas displayed telomerase activity. In leukoplakia, telomerase activity was seen in moderate or severe dysplastic tissue and carcinoma in situ. Mild dysplasia did not reveal telomerase activity. In SCC, there was no clear association between relative telomerase activity and grade or stage. These results suggest that detection of telomerase activity in oral tissues could be used to differentiate malignant from benign or normal tissues.

Aged↗
PubMed1999

Frequent loss of expression or aberrant alternative splicing of P2XM, a p53-inducible gene, in soft-tissue tumours.

We investigated expression of a human p53-inducible gene, P2XM, a member of the P2X-receptor family of ATP-gated ion channels, in 56 human primary soft-tissue tumours including 47 sarcomas and nine benign tumors. Among the 47 sarcomas examined by reverse transcription polymerase chain reaction, 12 had lost expression of this gene and 22 revealed altered splicing patterns; among the nine benign tumours, four showed no expression of P2XM and three revealed aberrant splicing patterns involving transmembrane domains M1 and/or M2. As the aberrant transcripts lacked either or both of those domains, the protein products probably lacked normal function. We also looked for p53 mutations and mdm2 overexpression in the same panel of tumours and found them in 13 tumours, all but three of which had shown altered expression of P2XM. However, 31 (72%) of the 43 tumours that carried wild-type p53 without mdm2 overexpression had revealed aberrant P2XM expression. Our results suggest that disorder of P2XM expression may play a crucial role in the genesis of benign and malignant tumours in soft tissues, and that one or more genetic factors other than p53 or mdm2 contribute significantly to aberrant P2XM expression.

Amino Acid Sequence↗
PubMed1999

Correlation between beta2-glycoprotein I valine/leucine247 polymorphism and anti-beta2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome.

OBJECTIVES: Beta2-Glycoprotein I (beta2GPI) exon 7 polymorphism leads to a valine leucine amino acid exchange at position 247 in domain 5 of beta2GPI, between the phospholipid binding site and the cryptic site of the epitopes for anti-beta2GPI antibodies. Therefore, position 247 polymorphism may affect the conformational change of beta2GPI and the exposure of the epitopes for anticardiolipin antibodies (aCL) (= anti-beta2GPI antibodies). In this study we analysed the genetic polymorphism of beta2GPI in a British cohort of well-defined antiphospholipid syndrome (APS) patients. METHODS: This study comprised 88 Caucasoid patients with APS [57 with primary APS and 31 with APS secondary to systemic lupus erythematosus (SLE)]. Polymorphism assignment was determined by polymerase chain reaction followed by allele-specific restriction enzyme digestion (PCR-RFLP). The presence of anti-beta2GPI antibodies was detected by ELISA utilizing irradiated ELISA plates. RESULTS AND CONCLUSIONS: Anti-beta2GPI antibodies were present in 28 of 57 primary APS patients (49%) and in 19 of 31 secondary APS patients (61%). The allele containing valine247 was significantly more frequent in primary APS patients with anti-beta2GPI antibodies than in controls (OR = 2.51, 95%, CI 1.03-6.13, P = 0.0396) or in primary APS patients without anti-beta2GPI antibodies (OR = 2.92, 95% CI 1.16-7.39, P = 0.0204). This tendency was not found in the secondary APS group. In conclusion, the beta2GPI polymorphism, valine/leucine247, is correlated with anti-beta2GPI antibody production in patients with primary APS, and valine247 may be important in the formation of beta2GPI antigenicity.

Adolescent↗