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Biomedical subjects

S Sekiya

Publications and source records attributed to S Sekiya.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in Japanese population.

To investigate whether HPV16 E6 variants carry an elevated risk for cervical cancer in Japanese population, we investigated the E6 sequence variation in 40 cervical intraepithelial neoplasias (CINs) I-III and 43 invasive cervical cancers (ICCs), all positive for HPV16. HPV16 E6 variants were frequently found in ICCs than in CINs (88 vs. 65%, P=0.01). The E6 D25E, a rare variant in Western countries, was most frequently observed in ICC (44%). CIN I/II lesions with HPV16 variants were less likely to regress than those with HPV16 prototype (P=0.048). The finding that HPV16 E6 variants represent a significant risk factor is common between Western and Japanese women despite the different distribution of each variant.

Base Sequence↗
PubMed2000

Involvement of decidual Valpha14 NKT cells in abortion.

The immunological mechanisms that regulate abortion are largely unknown. Here, we found that a distinct subset of lymphocytes, Valpha14 NKT cells expressing an invariant antigen receptor encoded by Valpha14/Jalpha281 and Vbeta7 segments, accumulated in the decidua during pregnancy and provoked abortion upon stimulation with alpha-galactosylceramide (alpha-GalCer), a specific ligand for Valpha14 NKT cells. The alpha-GalCer-mediated abortion was not observed in Valpha14 NKT-, IFN-gamma-, tumor necrosis factor alpha-, or perforin-knock-out mice and appeared to be due to the degeneration of embryonic trophoblasts mediated by the activated Valpha14 NKT cells whose perforin-dependent killing and production of IFN-gamma and tumor necrosis factor alpha were essential. The possible role of the decidual Valpha14 NKT cells in the pathogenesis of abortion is discussed.

Abortion, Induced↗
PubMed2000

Human papillomavirus-positive well-differentiated villoglandular adenocarcinoma of the uterine cervix: A case report and review of the literature.

OBJECTIVE: A case of well-differentiated villoglandular adenocarcinoma of the uterine cervix, which was positive for human papillomavirus type 18, was reported. METHODS: The patient was a 52-year-old multipara who was referred to our department because of an abnormal Papanicolaou smear. A 4.0-cm exophytic lesion involving the cervix was detected. She was staged as FIGO IIa and radical hysterectomy combined with bilateral pelvic lymphadenectomy was performed. In addition to histopathological examination of the resected tumor, immunohistochemical studies of estrogen and progesterone receptors were performed using monoclonal antibodies. Detection of human papillomavirus DNA was attempted by polymerase chain reaction using consensus primers. RESULTS: The tumor was a typical well-differentiated villoglandular adenocarcinoma involving the vaginal wall. Both estrogen and progesterone receptors were negative. Human papillomavirus type 18 DNA was detected in the resected tumor. CONCLUSION: 'This is the first report of a case of typical well-differentiated villoglandular adenocarcinoma which was positive for human papillomavirus.

Adenocarcinoma↗
PubMed2000

Combination chemotherapy with methotrexate, etoposide, and actinomycin D for high-risk gestational trophoblastic tumors.

OBJECTIVES: The goal of this study was to evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with a methotrexate-etoposide-actinomycin D (MEA) regimen without cyclosphosphamide or vincristine. METHODS: Thirty-nine consecutive patients with high-risk GTTs (28 were defined high risk by WHO criteria) were treated with primarily the MEA regimen. Among them, 27 patients had received no prior chemotherapy and 12 had received prior chemotherapy. Survival, causes of treatment failure, and toxicity were analyzed retrospectively. RESULTS: After treatment with the MEA regimen, 29 of 39 patients achieved primary remission (74.4%), 8 developed resistance (20.5%), and 2 died of widespread metastases and chemotherapy-related toxicity. All 8 patients who developed resistance were treated with high-dose 5-fluorouracil and actinomycin D (FA); 6 were salvaged and 2 died of refractory disease. Three patients relapsed; 2 were controlled with FA or cisplatin-based chemotherapy and 1 who refused further treatment died. The disease-free survival rate was 87%. WHO grade 4 leukocytopenia and thrombocytopenia with the MEA regimen occurred in 5.3 and 6.4%, respectively, of the cycles; other toxic effects were acceptable and manageable. CONCLUSIONS: At present, MEA chemotherapy (without cyclophosphamide or vincristine) is our treatment of choice for patients with high-risk GTT. Its toxicity is predictable and manageable. For patients who become resistant to MEA, new salvage chemotherapy regimens are needed.

Adult↗
PubMed2000

Prenatal findings in Brachmann-de Lange syndrome.

We present a case of Brachmann-de Lange syndrome, in which prenatal ultrasonographic evaluation demonstrated increased nuchal translucency, early onset of intrauterine growth retardation, and limb abnormalities in the first, second, and third trimester, respectively.

Adult↗
PubMed2000

Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung.

A common amplification target encompassing chromosome region 3q25 to q27 has been identified by comparative genomic hybridization analyses in tumors of the cervix, ovary, endometrium, lung, and head and neck. Because this segment spans at least 30 megabases, we undertook a molecular analysis of copy number to more precisely define the amplification domain. Our Southern blot and fluorescence in situ hybridization results with the use of 17 markers confirmed the presence of low-level 3q amplification events in cervical, ovarian, and variant SCLC tumors. Most of the tumor types studied appeared to have similar, broad amplification domains centered within 3q26.2, suggesting that the same target is being affected in all. The ovarian carcinoma cell line NIH:OVCAR3 had a highly restricted amplification domain spanned by four overlapping YAC clones, suggesting a small target. The region of highest amplification included the gene for the RNA component of telomerase (hTR), supporting it as a potential target. Although the importance of low-level amplification is unknown, the consistent and reproducible nature of this event in a variety of carcinomas suggests that 3q26.2 harbors an oncogene whose low-level amplification has a significant influence on tumor biology.

Blotting, Southern↗
PubMed2000

Isolation and characterization of RNA aptamers specific for the hepatitis C virus nonstructural protein 3 protease.

Nonstructural protein 3 (NS3) from hepatitis C virus (HCV) is a serine protease that provides an essential function in maturation of the virus by cleaving the nonstructural regions of the viral polyprotein. The goal of this work was to isolate RNA aptamers that bind specifically to the NS3 protease active site in the truncated polypeptide DeltaNS3. RNA aptamers were selected in vitro by systematic evolution of ligands by exponential enrichment (SELEX). The RNA pool for SELEX had a 30-nucleotide randomized core region. After nine selection cycles, a pool of DeltaNS3-specific RNA aptamers were obtained. This RNA pool included 45 clones that divided into three main classes (G9-I, II and III). These classes include the conserved sequence GA(A/U)UGGGAC. These aptamers bind to DeltaNS3 with a binding constant of about 10 nM and inhibit approximately 90% of the protease activity of DeltaNS3 and MBP-NS3 (full-length of NS3 fused with maltose binding protein). In addition, these aptamers inhibited approximately 70% of the MBP-NS3 protease activity in the presence of the NS4A peptide P41. G9-I aptamer appeared to be a noncompetitive inhibitor for DeltaNS3 with a Ki approximately 100 nM in the presence of P41. These results suggest that the pool of selected aptamers have potential as anti-HCV compounds. Mutational analysis of the G9-I aptamer demonstrated that the sequences required for protease inhibition are in stem I, stem III and loop III of the aptamer. These regions include the conserved sequence GA(A/U)UGGGAC.

Base Sequence↗
PubMed2000

Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan.

A national collaborative study was conducted in Japan to evaluate the clinical course and the sequelae of patients with hydatidiform mole coexistent with twin live fetus (HMTF). Seventy-two cases of HMTF were diagnosed based on gross appearance and histopathological criteria. In 18 cases, the molar parts were cytogenetically confirmed to be of androgenetic origin (complete mole). The overall incidence of persistent trophoblastic tumour (PTT) in patients with HMTF was 30.6%, and it increased to 50.0% in the 18 patients with proven androgenetic complete mole coexistent with twin live fetus (CHMTF). Among these patients, the mean gestational age at termination of pregnancy or delivery in those who developed PTT (n = 9) and those who did not (n = 9) were 20.6 and 19.4 weeks respectively. The incidence of severe maternal complications was significantly higher in patients who subsequently developed PTT (P < 0.05). The rate of subsequent development of PTT in patients with CHMTF was found to be considerably higher than in a previous study of patients with single complete mole (50 and 12.5% respectively). However, since the risk of malignancy is unchanged with advancement of gestational age, continued pregnancy may be allowed in patients with HMTF provided that severe maternal complications are controlled and fetal karyotype and development are normal.

Abortion, Induced↗
PubMed2000

Analysis of interaction between RNA aptamer and protein using nucleotide analogs.

Non-structural protein 3 (NS3) derived from Hepatitis C virus (HCV) is essential for viral proliferation and has two functional domains; trypsin-like serine protease and helicase. Recently we obtained three types of RNA aptamers (G9-I, -II and -III) bound to NS3 protease domain (delta NS3) by in vitro selection and confirmed their strong inhibition for protease activity. These aptamers have a common sequence, 5'-GA(A/U)UGGGAC-3', forming a loop structure by Mulfold secondary structure modeling. G9-I shows a three-way junction and G9-II and -III have four-way junction structures. To characterize the active structure of these aptamers, we applied modification interference analysis using nucleotide analogs and identified common important nucleotides in these three aptamers.

Base Sequence↗
PubMed2000

Analysis of aptamer binding site for HCV-NS3 protease by alanine scanning mutagenesis.

Nonstructural protein 3 (NS3) of Hepatitis C virus (HCV) is a multifunctional protein and possesses protease, nucleotide triphosphatase and helicase activities. The N-terminal domain of NS3 (amino acids 1027-1218; delta NS3) has a trypsin-like protease activity and is essential for processing of viral polyprotein. Accordingly it is a potential target for anti-HCV drugs and we isolated RNA aptamers (Kd = 10 nM, Ki = 100 nM) using in vitro selection strategy. To study the interaction between delta NS3 and its aptamer, we applied alanine scanning mutagenesis and constructed seven mutant proteins at positive amino acid residues on the surface of delta NS3. Binding and inhibitory activities of the NS3 aptamer against mutant proteins were kinetically analyzed. These results clarified that especially Arg161 and Arg130 are important for interaction with the NS3 aptamer.

Base Sequence↗
PubMed2000

[Comparison between cytomegalovirus hepatitis and Epstein-Barr virus hepatitis in healthy adults].

In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis in previously healthy adults, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed. CMV hepatitis showed a tendency to increase in our department. In comparison with EBV hepatitis, CMV hepatitis occurred in significantly older hosts than EBV hepatitis. We found that lymphadenopathy, cough and sore throat was more common in EBV hepatitis than in CMV hepatitis. The number of peripheral white blood cell count and atypical lymphocytes, and serum GOT, GPT, LDH and CRP levels of CMV and EBV hepatitis showed no significant differences.

Adolescent↗
PubMed2000

RGS domain in the amino-terminus of G protein-coupled receptor kinase 2 inhibits Gq-mediated signaling.

We have previously shown that not only G protein-coupled receptor kinase (GRK) 2, but also a catalytically inactive Lys220Trp GRK2 decreases endothelin (ET)-1-induced inositol 1,4,5-trisphosphate (IP3) formation, and demonstrated the presence of phosphorylation-independent desensitization mechanism. To clarify the role of GRK2 other than that as a kinase, we characterized an RGS (regulator of G protein signaling)-like domain in the amino-terminus of GRK2. Both GRK2(1-181) and GRK2(54-174) suppressed Ca2+ responses induced by angiotensin II (Ang II) and ET-1, and bound directly with Galphaq but not Galphas nor Galphai3 in the presence of GDP and AlF4-. These results demonstrate that GRK2 regulates Gq-mediated signaling negatively by direct interaction between its RGS domain and the transitional state of Galphaq, as well as through phosphorylation of activated receptors by its kinase domain.

Aluminum Compounds↗
PubMed2000

[Evaluation of adverse effects including neurotoxicity of combination chemotherapy with paclitaxel and carboplatin].

The adverse effects of combination chemotherapy with paclitaxel and carboplatin, including neurotoxicity, arthralgia and muscle pain, were evaluated in 21 patients (30 courses) using questionnaires of the Gynecologic Oncology Chemotherapy Joint Research Group. The scores of pain and numbness peaked from the third to fourth day of treatment. Although the pain score improved subsequently, the numbness score persisted at a high level. Compared to the first and second courses, the peak pain score was higher and persisted for a longer duration in the fifth and sixth courses. Using the questionnaires, we were able to recognize a high incidence of numbness and pain in patients on combination chemotherapy with paclitaxel and carboplatin, and identify the degree and temporal changes of the adverse effects. Our results suggest that the questionnaires used in this study are clinically useful for evaluating the degree and clinical course of pain and numbness in anticancer chemotherapy.

Antineoplastic Agents↗
PubMed1999

An enhancer element for expression of the Ncx (Enx, Hox11L1) gene in neural crest-derived cells.

The murine Ncx (Enx, Hox11L1) gene is specifically expressed in a neuronal subset of neural crest-derived tissues. In attempts to elucidate the regulatory DNA element of the tissue-specific expression, we sequenced the 5'-flanking region of the Ncx gene. The transcriptional initiation site was determined at 297 nucleotides (-297) upstream from the ATG start codon (+1). A retinoic acid response element was located on the region between -1163 and -1150. Transient transfection assays with the 5'-flanking sequences fused to the luciferase gene showed that the region between -1387 and -1368 was crucial for the tissue-specific enhancer activity. Furthermore, nuclear proteins extracted from neural crest-derived cells such as murine and human neuroblastoma cells bind to the DNA region between -1387 and -1368. This DNA element was also conserved in the 5'-flanking region of the human NCX gene. Our observations strongly suggest that the DNA element (between -1387 and -1368) contributes to tissue-specific expression of the Ncx gene in murine and human species.

Animals↗
PubMed1999

Androgenetic complete mole coexistent with a twin live fetus.

OBJECTIVE: The aim of this study was to evaluate the clinical course and the management policy of complete mole coexistent with a twin live fetus confirmed with DNA polymorphism in a single hospital. METHODS: From 1981 to 1995, six patients with androgenetic complete hydatidiform mole coexistent with a twin live fetus were diagnosed by DNA polymorphism analysis. The clinical course of these six patients was analyzed. RESULTS: Two patients chose to terminate pregnancies and four patients desired to continue the pregnancy. However, the pregnancy had to be interrupted in two patients because of severe preeclampsia and sudden intrauterine fetal death. In two patients, fetuses were growing unremarkably and normal babies were delivered at term. The development of persistent trophoblastic tumor (PTT) in these rare pregnancies was higher (50.0%: 3/6) than that of single complete mole. In three patients, serum hCG titers during pregnancy were monitored. Although serum hCG levels progressively decreased during pregnancy in one patient without PTT, hCG levels initially decreased, but subsequently increased or showed a plateau with advancing gestational age in two patients with PTT. CONCLUSIONS: In patients with complete mole coexistent with a live fetus, the pregnancy may be allowed to continue when the fetal karyotype and development are normal and serum hCG titers are constantly falling with advancing gestational age.

Adult↗
PubMed1999

Relationship of amniotic fluid index and cord blood erythropoietin levels in small for and appropriate for gestational age fetuses.

OBJECTIVE: To determine whether low amniotic fluid index (AFI) reflects an increase in cord blood erythropoietin levels and is a marker of antenatal fetal hypoxia in small for gestational age (SGA) and appropriate for gestational age (AGA) fetuses in the third trimester. METHODS: Erythropoietin levels in cord blood were measured in 134 high-risk obstetric patients, including 40 with low AFI (7 cm or less) and 94 with normal AFI (greater than 7 cm), which were sampled at elective cesarean delivery of fetuses with a gestational age of 32 to 39 weeks. The infants were divided into the SGA and AGA groups based on birth weight. Partial correlations of AFI with cord blood erythropoietin levels were evaluated by Pearson correlation coefficient after logarithmic transformation of erythropoietin levels in each group. RESULTS: Cord blood erythropoietin levels in SGA fetuses with low AFI (n = 24) were significantly higher than those in SGA fetuses with normal fluid volume (n = 16) (171.6 +/- 207.4 mIU/dL compared with 36.1 +/- 24.1 mIU/dL, P < .001). Conversely, cord blood erythropoietin levels in AGA fetuses with low AFI (n = 16) were not significantly different than those in AGA fetuses with normal fluid volume (n = 78) (32.1 +/- 18.7 mIU/dL compared with 29.5 +/- 15.3 mIU/dL). A significant partial correlation between AFI and erythropoietin levels was demonstrated only within the SGA group (P < .001, r = -.67). CONCLUSION: Low AFI could indicate the degree of antenatal fetal hypoxia in SGA fetuses. The impact of a reduced amniotic fluid volume on antenatal fetal condition might be less severe in AGA fetuses than in SGA fetuses.

Adult↗
PubMed1999

Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan.

Various risk factors were investigated in 167 cervical intra-epithelial neoplasia (CIN) case and control pairs in Japan. CIN cases showed evidence of nine known risk factors including smoking and sexual behaviour. However, after adjustment for papillomavirus infection, the highest determinant, the only remaining risk factors were: being married, early age at first pregnancy and multiparity.

Adult↗