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Biomedical subjects

M Ueki

Publications and source records attributed to M Ueki.

At least 19 recordsLinked to original sources
PubMed2006

Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254 patients with complete surgical staging.

A retrospective analysis was performed to evaluate the clinical characteristics and prognostic factors in the patients with clear cell carcinoma (CCC) of the ovary. After central pathological review and scanning of the medical records of nine Japanese institutions between 1992 and 2003, a total of 254 patients with CCC of the ovary were enrolled in the present study. Mean age was 52.4 years (range 23-73 years). Tumours were 13% (33/254) stage Ia, 36% (92/254) stage Ic, 13% (33/254) stage II, 30% (80/254) stage III, and 6% (16/254) stage IV. Five-year progression-free survival and overall survival was 84 and 88% in stage I, 57 and 70% in stage II, 25 and 33% in stage III and 0 and 0% in stage IV, respectively. Retroperitoneal lymph node metastasis was observed in 9% in pT1a tumours, 7% in pT1c tumours, 13% in pT2 tumours, and 58% in pT3 tumours, respectively. There was no survival benefit according to chemotherapeutic differences in the patients who received complete surgical staging procedures and conventional chemotherapy. Peritoneal cytological status was an independent prognostic factor in stage Ic patients (P=0.03) and only residual tumour diameter was an independent prognostic factor in stage III, IV patients (P=0.02). Our results suggest that cytoreductive surgery resulting in no residual tumour only could improve the prognosis of advanced CCC patients.

Adenocarcinoma, Clear Cell↗
PubMed2005

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status </=2 entered the study. Docetaxel 70 mg m(-2) was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39-74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1-50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3-4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.

Adenocarcinoma↗
PubMed2005

The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation.

Hyaluronan (HA) is one of the major extracellular matrix components in cartilage. In addition to the biomechanical functions, HA has various important roles in the differentiation of chondrocytes. The purpose of this study was to clarify the nature of HA synthesis during chondrocyte differentiation. Growth plate chondrocytes were isolated from rabbit ribs and cultured in chondrocyte differentiation medium. The amount of HA and HA synthase (HAS) mRNA levels were analyzed for each stage of chondrocyte differentiation by means of high-performance liquid chromatography (HPLC) and real-time PCR, respectively. The distribution of HA in cultured chondrocytes was observed by histochemical staining. The amount of HA, ranging widely in size, was increased substantially during the hypertrophic stage. The expression levels of HAS2 and HAS3 mRNAs were low during the matrix-forming stage. HAS2 mRNA level was substantially enhanced at the pre-hypertrophic stage, whereas HAS3 mRNA level exhibited a slight increase. HAS1 mRNA was not detected. The intensity of HA staining was high around the hypertrophic chondrocytes. These results suggest that HA metabolism in chondrocyte differentiation is regulated by the selective expression of HASs, and HAS2 and the related large size-HA may have a certain association with the hypertrophic changes of chondrocytes.

Animals↗
PubMed2005

The HDL2/HDL3 ratio in menopause.

OBJECTIVES: The influence of the menopause on the HDL2/HDL3 ratio was assessed in association with hypertriglyceridemia. METHODS: Fasting blood samples were collected from 607 patients. Commercially available enzymatic methods were used for determination of TG, and total HDL-C. HDL2 and HDL3 were measured by ultracentrifugation. RESULTS: The HDL2/HDL3 ratio had a strong negative correlation with TG (r=-0.272, P<0.0001 and r=-0.314, P<0.0001) in both pre- and postmenopausal women. No significant differences were observed in HDL2, HDL3, and HDL2/HDL3 ratio between pre- and postmenopausal women without hypertriglyceridemia. Postmenopausal women had a significantly higher HDL2/HDL3 ratio than premenopausal women with hypertriglyceridemia. CONCLUSIONS: These results indicate that menopausal status not only increases plasma LDL-cholesterol and triglyceride levels, but also increases the HDL2/HDL3 ratio when associated with elevation of plasma triglyceride levels. These changes may increase the risk for CHD due to enlargement of the lipid pool.

Adult↗
PubMed2004

A single amino acid substitution can shift the optimum pH of DNase I for enzyme activity: biochemical and molecular analysis of the piscine DNase I family.

We purified four piscine deoxyribonucleases I (DNases I) from Anguilla japonica, Pagrus major, Cryprus carpio and Oreochromis mossambica. The purified enzymes had an optimum pH for activity of approximately 8.0, significantly higher than those of mammalian enzymes. cDNAs encoding the first three of these piscine DNases I were cloned, and the sequence of the Takifugu rubripes enzyme was obtained from a database search. Nucleotide sequence analyses revealed relatively greater structural variations among the piscine DNase I family than among the other vertebrate DNase I families. From comparison of their catalytic properties, the vertebrate DNases I could be classified into two groups: a low-pH group, such as the mammalian enzymes, with a pH optimum of 6.5-7.0, and a high-pH group, such as the reptile, amphibian and piscine enzymes, with a pH optimum of approximately 8.0. The His residue at position 44 of the former group is replaced by Asp in the latter. Replacement of Asp44 of piscine and amphibian DNases I by His decreased their optimum pH to a value similar to that of the low-pH group. Therefore, Asp44His might be involved in an evolutionarily critical change in the optimum pH for the activity of vertebrate DNases I.

Amino Acid Sequence↗
PubMed2004

Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint.

Hyaluronan (HA) synthesis in the synovial membrane is affected by various chemical mediators. It is hypothesized that transforming growth factor-beta 1 (TGF-beta 1) would be a mediator to modulate HA synthesis in cultured synovial membrane fibroblasts of the temporomandibular joint (TMJ). Fibroblasts were extracted from the TMJ synovial membrane of four-week-old Japanese white rabbits. The amount of HA and expression levels of HA synthase (HAS) mRNAs induced by TGF-beta 1 treatment were analyzed by means of high-performance liquid chromatography and real-time polymerase chain-reaction, respectively. Both medium and large amounts of HA were enhanced by the stimulation of TGF-beta 1. HAS2 mRNA expression was enhanced 13-fold after six-hour stimulation with TGF-beta 1 (10 ng/mL), whereas HAS3 mRNA expression was not changed significantly. These results suggest that TGF-beta 1 enhances the expression of HAS2 mRNA in the TMJ synovial membrane fibroblasts and may contribute to the production of high-molecular-weight HA in the joint fluid.

Animals↗
PubMed2003

Mechanical stimuli enhances the expression of RGD-CAP/betaig-h3 in the periodontal ligament.

RGD-CAP, a member of the fasciclin family, is expressed in the periodontal ligament (PDL). Since the PDL is continually subjected to mechanical forces from such orofacial functions as mastication, biting, speech and swallowing, the mechanical stimuli is thought to be associated with the expression of RGD-CAP. Furthermore, the adhesive functions of RGD-CAP may contribute to the maintenance or regeneration of PDL architecture. The objective of this study was to examine whether mechanical stimuli modulate the expression of RGD-CAP in the human PDL, and to examine the effects of recombinant RGD-CAP on the adhesion of PDL cells. During experimental tooth movement, the expression of RGD-CAP was significantly enhanced in the PDL. In vitro experiments with cultured PDL cells showed that the expression of RGD-CAP mRNA was significantly enhanced by mechanical tensile force of 15.4kPa for 48h. The induction of RGD-CAP mRNA, meanwhile, was completely inhibited by cycloheximide which is an inhibitor of protein synthesis. Furthermore, neutralising antibody against TGF-beta also suppressed the mechanical induction of RGD-CAP. The adhesion of cultured PDL cells onto plates coated with recombinant RGD-CAP increased significantly compared with the controls. These findings suggest that RGD-CAP, induced by TGF-beta expressed in response to mechanical stimuli, plays an important role in modulating the homeostasis of PDL.

Blotting, Western↗
PubMed2003

Use of perfluorocarbon liquid during vitrectomy for severe proliferative diabetic retinopathy.

AIM: To evaluate the value of using perfluorocarbon liquid (PFCL) during vitrectomy in eyes with proliferative diabetic retinopathy (PDR). METHODS: The surgical records of eyes with PDR (291 eyes of 228 patients) that underwent vitrectomy in the vitreoretinal service of Osaka Medical College (April 1999 to October 2001) were reviewed. From these, 18 eyes of 15 patients had PFCL used during vitrectomy, and the preoperative and postoperative findings of these eyes were analysed. RESULTS: All of the 18 eyes had advanced PDR with tractional and/or rhegmatogenous retinal detachment. PFCL enabled easier flattening of the retinal folds and effective endophotocoagulation. In two cases, PFCL was used to flatten a bullous retinal detachment that developed when a tight vitreoretinal adhesion was loosened. In two other cases with combined traction/rhegmatogenous retinal detachment, PFCL was used to tamponade the detached retina which then allowed successful membrane dissection. Anatomical success was obtained in 16 of the 18 cases (mean follow up time 13.3 months) with visual acuity of 20/200 or better in nine eyes (50%). CONCLUSIONS: PFCL is considered to be a useful adjunct during vitrectomy for the treatment of severe PDR.

Adult↗
PubMed2003

Inverse correlation between serum leptin concentration and vertebral bone density in postmenopausal women.

Although the protective effect of obesity on bone mass has been ascribed to high body fat content, this is still controversial. The present study of 215 postmenopausal Japanese women investigated whether circulating leptin concentration was correlated with per cent fat mass or age-adjusted bone mineral density (Z-score). In this study population, the mean circulating leptin concentration was 10.15 +/- 5.42 (range 1.7-29.6) ng/ml. Significant correlations were found between circulating leptin concentrations and per cent fat mass (r = 0.514, p < 0.0001) and Z-score (r = -0.516, p < 0.0001), confirming the existence of an inverse relationship between leptin concentration and postmenopausal bone density. By contrast, no significant correlation was found between per cent abdominal fat mass and vertebral bone mineral density (r = -0.071). Serum leptin concentration reflects fat mass and postmenopausal bone mass in human subjects. Increased serum leptin levels might cause bone loss in postmenopausal Japanese women, and our results do not support the hypothesis that leptin induces or mediates the bone-protective effects of obesity.

Abdomen↗
PubMed2002

Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis.

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.

Cadherins↗
PubMed2001

Effects of the combined use of calcitonin and 1 alpha-hydroxycholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin.

OBJECTIVES: The present study investigates the effect of long-term and continuous treatment with low dose calcitonin in combination with 1 alpha-hydroxycholecalciferol on vertebral bone mass in early postmenopausal women. METHODS: A total of 202 postmenopausal women between 53 and 58 years of age were recruited individually and randomly assigned to one of four groups. Comparisons were made among groups of women receiving calcitonin alone (10 IU i.m. twice a month), 1 alpha-hydroxycholecalciferol alone (0.5 microg orally twice daily), a combination of the above two agents, or no treatment. Bone mineral density (BMD) of lumber spine (L2-4) was determined using Dual Energy X-ray Absorptiometry. The study was carried out prospectively over a 2-year period. RESULTS: We observed a significant increase in vertebral bone mass in the combined treatment regimen of calcitonin and 1 alpha-hydroxycholecalciferol (3.44% at 12 months in the combination group vs 1.40,0.92, and -0.70% in the calcitonin alone, 1 alpha-hydroxycholecalciferol alone, and control groups, respectively; 4.51% at 24 months in the combination group vs 2.21,1.04, and -3.61% in the calcitonin alone, 1 alpha-hydroxycholecalciferol alone, and control groups, respectively). Serum PTH, osteocalcin levels and alkaline phosphatase activity decreased significantly within 12 months whereas urinary pyridinoline/creatinine ratio decreased at 24 months in the combination group. We observed mild adverse effects in 25.0% (7/28) and 30.0% (6/20) of combination regimen and calcitonin treatment cases, respectively. CONCLUSIONS: The results of the study suggest that the combination treatment regimen increased vertebral bone loss in early postmenopausal women to a greater extent than did calcitonin alone or 1 alpha-hydroxycholecalciferol alone.

Administration, Oral↗
PubMed2001

Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas.

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the adenomatous polyposis coli (APC)/ beta-catenin/Tcf pathway in human tumorigenesis, there have been very few reports on mutations of the beta-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma cell lines for mutations in exon 3 of the beta-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the gamma-catenin gene. Mutational analysis for the entire coding region of beta-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical carcinoma cell lines. Deletion of most beta-catenin coding exons was confirmed in line NCI-H28 (lung mesothelioma) and a silent mutation at codon 214 in exon 5 was found in HeLa (cervical adenocarcinoma). A missense mutation at codon 19 and a silent mutation at codon 28 in the NH2-terminal regulatory region of the gamma-catenin gene were found in H1726 (squamous cell lung carcinoma) and H1048 (small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that beta- and gamma-catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian carcinomas.

Cytoskeletal Proteins↗
PubMed2001

Tissue-specific in vivo inhibition of DNase I gene expression by somatostatin.

Administration of somatostatin to rats induced a transient reduction of serum levels of deoxyribonuclease I (DNase I) activity in a dose-dependent manner, followed by a substantial decrease of DNase I activity in the lower gut. Activity in the parotid gland, liver, and kidney did not change. Real-time PCR analysis of the DNase I gene transcript in ileum indicated that the decrease was due to down-regulation of gene expression. Based on these responses, rat tissues expressing DNase I could be classified into two types, somatostatin-sensitive and somatostatin-resistant, and the level of DNase I activity in the lower gut seems to be controlled by somatostatin.

Animals↗
PubMed2001

The fibronectin-derived antiadhesive peptides suppress the myofibroblastic conversion of rat hepatic stellate cells.

We previously found that fibronectin (FN) had a functional site (YTIYVIAL sequence in the 14th type III module) suppressing the integrin-mediated cell adhesion to extracellular matrix. FN-derived peptides containing this antiadhesive site were also shown to regulate cellular processes such as proliferation, differentiation, and apoptosis. The present study shows that the FN-derived antiadhesive peptides suppress the myofibroblastic conversion of rat hepatic stellate cells (HSC). Freshly isolated HSC underwent myofibroblastic conversion during culture in the presence of FBS, as evaluated by indices representing the phenotypic activation of HSC, including increased proliferation, consumption of vitamin A-enriched lipid droplets, and expression of alpha-smooth muscle actin. However, appearance of these myofibroblastic characters was suppressed by coculturing HSC with the FN-derived antiadhesive peptides. On the other hand, the activated HSC, which had already acquired the myofibroblastic phenotype through repeated subculture, secreted FN and then stimulated matrix assembly of ED-A (+) cellular FN as well as plasma FN, while the FN-derived antiadhesive peptides inhibited them. Furthermore, the FN-derived antiadhesive peptides suppressed the integrin-mediated adhesion of the primary HSC to plasma FN and ED-A (+) cellular FN substrates. These results suggested that the FN-derived antiadhesive peptides down-regulated the myofibroblastic conversion of HSC in an indirect manner by inhibiting the integrin-mediated adhesive interaction of HSC with ED-A (+) cellular FN.

Amino Acid Sequence↗
PubMed2001

Correlation between thymidine phosphorylase expression and invasion phenotype in cervical carcinoma cells.

The correlation between thymidine phosphorylase (dThdPase) expression and invasion phenotype in human uterine cervical carcinoma cells was investigated using 10 cervical carcinoma cell lines. Semi-quantitative reverse transcription-polymerase chain reaction analysis was performed to investigate the mRNA levels of dThdPase and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. dThdPase protein expression levels were detected by highly sensitive enzyme-linked immunosorbent assay. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. Although dThdPase mRNA and protein expression levels differed remarkably among the cell lines, there was a statistical correlation between them (r = 0.743, p = 0.0139). dThdPase gene and protein expression levels were well correlated with the number of cells that migrated and invaded (p < 0.05). Moreover, there was a close correlation between MMP-2 gene and dThdPase gene and protein expression levels (p < 0.05). Tumor cells that produce dThdPase may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.

Carcinoma, Squamous Cell↗