Search PubMed⌕ Search

Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 199 records · Page 11Linked to original sources
PubMed1999

Thymidine phosphorylase expression in progression of cervical cancer: correlation with microvessel count, proliferating cell nuclear antigen, and apoptosis.

AIMS: To determine how epithelial and stromal thymidine phosphorylase expression affects angiogenesis, rapid tumour growth, and decreased apoptotic activity in cervical cancer at varying stages of progression. METHODS: Epithelial and stromal thymidine phosphorylase expression, the microvessel count (reflected by factor VIII related antigen), and proliferating cell nuclear antigen (PCNA) were assessed immunohistochemically in 25 specimens of normal cervical epithelium, 35 of carcinoma in situ (CIS), 34 of microinvasive carcinoma, and 34 of invasive cervical squamous cell carcinoma. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method. The relation of epithelial and stromal thymidine phosphorylase expression to microvessel count, PCNA index, and apoptotic index was examined. RESULTS: Epithelial and stromal thymidine phosphorylase expression progressively increased along a continuum from normal epithelium to invasive squamous cell carcinoma. Epithelial and stromal thymidine phosphorylase expression showed a significant positive correlation with microvessel counts. Within each histological stage, CIS cases with high stromal thymidine phosphorylase expression, invasive squamous cell carcinoma cases with high epithelial thymidine phosphorylase expression, and microinvasive carcinoma cases with high thymidine phosphorylase expression in both epithelium and stroma had a significantly higher microvessel count. High epithelial thymidine phosphorylase expression was associated with a significantly higher PCNA index in CIS and microinvasive carcinoma, but not in invasive squamous cell carcinoma. No significant correlation was seen between apoptotic index and either epithelial or stromal thymidine phosphorylase expression or microvessel count. CONCLUSIONS: Epithelial and stromal thymidine phosphorylase expression may combine to promote angiogenesis during progression of cervical cancer, and epithelial thymidine phosphorylase expression may stimulate tumour cell proliferation in the early stages.

Apoptosis↗
PubMed1999

Detection of small-for-gestational-age infants with poor perinatal outcomes using individualized growth assessment.

OBJECTIVE: Our objective was to evaluate individualized growth assessment using the Rossavik growth model for detection of small-for-gestational-age (SGA) infants with a poor perinatal outcome. METHODS: Rossavik growth models derived from second-trimester ultrasound measurements were used to predict birth characteristics of 47 singleton SGA infants. Individual fetal growth curve standards for head and abdominal circumference, and weight were determined from the data of two scans obtained before 25 weeks' menstrual age and separated by an interval of at least 5 weeks. Comparisons between actual and predicted birth characteristics were expressed by the Growth Potential Realization Index (GPRI) and Neonatal Growth Assessment Score (NGAS). The proportions of perinatal outcomes [mechanical delivery, low Apgar score, abnormal fetal heart rate (FHR) patterns, neonatal acidosis, meconium staining of amniotic fluid, neonatal intensive care unit (NICU) admission and maternal complications] were compared between SGA infants with normal NGAS and those with abnormal NGAS. RESULTS: Of the 47 fetuses studied, 27 had normal growth outcomes at birth and 20 showed evidence of intrauterine growth restriction, based on NGAS. There were significant increases in mechanical deliveries, abnormal FHR patterns and meconium staining of amniotic fluid in cases of growth-restricted neonates, determined using the NGAS classification, when compared with events related to normally grown infants. However, there were no significant differences in low Apgar score, neonatal acidosis, NICU admission and maternal complications between the 2 groups. CONCLUSION: Individualized growth assessment should be useful for detection of SGA infants with poor perinatal outcomes.

Abdomen↗
PubMed1999

Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique.

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.

Administration, Oral↗
PubMed1999

The presence of an Na+/spermine antiporter in the rat renal brush-border membrane.

This study was aimed at determining the driving force for spermine transport in rat renal proximal tubular brush-border membrane. The uptake of spermine and trientine, a spermine-like drug used for treating Wilson's disease, into rat renal brush-border membrane vesicles was significantly stimulated by an outwardly directed Na+ gradient. The Na+-dependent uptake was temperature dependent and saturable. A kinetic analysis of the initial uptake of spermine with an Na+ gradient gave a Km value of 1.44 microM and a Vmax value of 6.31 pmol (mg protein)(-1)/30s. The Na+ dependent uptake of [3H]spermine was inhibited by spermine, trientine and tetraethylene-pentamine. Substrates of the H+/organic cation transporter (cimetidine and tetraethyl-ammonium), physiological polyamines (putrescine and spermidine) with 2 or 3 amino groups and aminoglycosides (amikacin and tobramicin) with 4 or 5 cationic amines did not affect the uptake of spermine in the presence of an outwardly directed Na+ gradient. These results suggest that the renal tubular secretion of spermine is mediated by an Na+/spermine antiport system which is specific for a straight-chain polyamine compound with more than 4 amino groups.

Animals↗
PubMed1999

Effect of dextran derivatives on arginine amidase activities released from isolated rabbit arteries.

In the present research we examined the levels and types of arginine amidase activities that were released from isolated rabbit arteries treated with heparin or chondroitin sulfate. Heparin accelerated the release of arginine amidase activity from the isolated rabbit ear artery, the induction was not significant; a slight increase in activity was observed in the level of arginine amidase released from isolated rabbit aorta, but no significant difference was observed. On the other hand, it was revealed that the addition of chondroitin sulfate, accelerated this release from isolated rabbit ear artery with 5% significant differences. After the addition of chondroitin sulfate, the arginine amidase activity released from isolated rabbit arteries was analyzed using various affinity adsorption methods. This analysis confirmed the presence of two types of fibrinolytic enzymes: plasminogen/plasmin activity and plasminogen activators, but no thrombin was detected.

Animals↗
PubMed1999

A competitive enzyme-linked immunosorbent assay-like method for the measurement of urinary hyaluronan.

A highly sensitive method for measurement of urinary hyaluronan with a minimum molecular mass of 2,000 Da was developed without using HPLC or radioisotopes. This competitive enzyme-linked immunosorbent assay-like method, used competitive binding of free hyaluronan in the sample and biotin-labeled standard hyaluronan to hyaluronan binding protein in solid phase. A total of 150 healthy individuals from both sexes at ages from 0 to 100 years was examined by the established method. Hyaluronan of 384 +/- 80 ng/mg creatinine (mean +/- SD) was constantly excreted into urine of 24-40-year-old healthy adults. The urinary hyaluronan levels were significantly higher before age 1 (p < 0.001) and rather high after 90 years compared to the other groups. The average molecular weight of urinary hyaluronan (5,500 Da) was constant through all generations. Sex difference of urinary hyaluronan was not observed both quantitatively or qualitatively.

Adolescent↗
PubMed1999

Diagnostic difficulty in polycystic ovary syndrome due to an LH-beta-subunit variant.

We initially failed to confirm a case of polycystic ovary syndrome (PCOS) because underestimation of LH concentrations due to a variant form of this hormone resulted in a misleadingly low LH/FSH ratio. A 26-year-old woman presented to our hospital with infertility. Given the presence of bilateral polycystic ovaries, oligomenorrhea and hirsutism. PCOS was suspected, but a normal LH/FSH ratio as measured by RIA led to diagnostic problems. When we remeasured LH and FSH using a chemical luminescence enzyme immunoassay (CLEIA), the ratio of the LH concentration measured by RIA to that measured by CLEIA was 0.29, and the ratio of LH to FSH measured by CLEIA was 3.3 compared with 0.81 measured by RIA. We then diagnosed PCOS. The point mutations Trp8 to Arg8 and Ile15 to Thr15 in the LH subunit were detected in the corresponding gene. The patient's LH status represented variant and wild-type LH equally. She was therefore diagnosed as heterozygous for the mutant LH-beta. Histologic assessment of ovarian tissue after laparoscopic biopsy was compatible with a polycystic ovary.

Adult↗
PubMed1999

Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B.

The activation of mitogen-activated protein kinase (MAP kinase) and the regulation of cyclooxygenase 2 (COX-2) were investigated in the human endometrial adenocarcinoma cell line HEC-1B by treatment with platelet-activating factor (PAF) and hCG. Pre-treatment of the cells with both oestradiol and medroxyprogesterone acetate was required for MAP kinase activation and COX-2 expression to respond to PAF and hCG. PAF-induced MAP kinase activation was sensitive to MAP kinase kinase (MEK) inhibitor, PD098059, and phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. In contrast, hCG-induced MAP kinase activation was sensitive to PD098059 and protein kinase A inhibitor, H-89, but not to wortmannin. PAF-induced COX-2 expression was insensitive to PD098059 but sensitive to wortmannin, whereas hCG-induced COX-2 expression was sensitive to PD098059 and H-89 but insensitive to wortmannin. 8-(4-chlorophenylthio)-cAMP, a potent cAMP analogue, induced activation of MAP kinase and expression of COX-2. These results indicate that MAP kinase is activated with PAF and hCG in HEC-1B cells. In addition, COX-2 expression is stimulated through the MAP kinase activation pathway with hCG and the wortmannin sensitive pathway with PAF in HEC-1B cells. These results also imply that protein kinase A remains upstream of hCG-induced activation of MAP kinase in HEC-1B cells.

Adenocarcinoma↗
PubMed1999

Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway.

Hyaluronan (HA) triggers a wide variety of cellular functions, yet its signaling pathway remains largely unclear. We found that HA-treatment of 3Y1 cells activated tyrosine phosphorylation of cellular proteins and mitogen-activated protein (MAP) kinase in a time- and dose-dependent manner, and, subsequently, stimulated cell growth. This HA-activity was resistant to boiling at 100 degrees C but completely abolished by treatment with hyaluronidase, suggesting that HA itself, but not any HA-associated proteins, has the activity. In addition, we found that HA-dependent activation of MAP kinase was strongly suppressed by the expression of dominant negative ras (S17N ras). These results suggest that Ras-MAP kinase pathway is activated by HA and may play an important role in HA-dependent signaling.

Adjuvants, Immunologic↗
PubMed1999

Multiplicity of the H+-dependent transport mechanism of dipeptide and anionic beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane.

To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles. The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar. The results provide an evidence that several transporters with different features are potentially responsible for the uptake of beta-lactam antibiotics into the intestinal cells. It is suggested that the dianionic beta-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption.

Animals↗
PubMed1999

[Successful combination chemotherapy for a case of small cell carcinoma of the rectum with multiple liver metastasis].

A 69-year-old-man with small cell carcinoma of the rectum and multiple liver metastases was admitted in December 1996. Poorly differentiated adenocarcinoma was preoperatively diagnosed in a biopsy specimen from the rectum. Chemolipiodolization using 50 mg DXR and 6 ml lipiodol was performed for the multiple liver metastases. Ten days later, he underwent rectal amputation including lymph node dissection combined with the implantation of reservoir for hepatic arterial infusion chemotherapy. After operation 5-FU (500 mg, days 1-5) and CDDP (10 mg, days 1-5) were injected for 3 weeks through hepatic arterial route. The metastatic lesions in the liver represented a good response to the chemolipiodolization, though the metastatic tumor in the liver S4 region did not disappear on CT scan. The histological diagnosis of the resected rectum revealed small cell carcinoma so we attempted additional chemotherapy according to the regimen for treatment of small cell lung cancer. ETP + CDDP therapy was performed, in which ETP (100 mg, days 1-3) and CDDP (80 mg, day 1) were intraarterially infused. After three courses of this therapy, he achieved a complete response (CR) for the liver metastasis. Two courses of ETP + CDDP therapy were additionally performed in the outpatient department, and treatment is currently continued by oral administration of ETP (75 mg/day). He has been free of the disease for 16 months with few side effects. The combination therapy of chemolipiodolization and hepatic arterial infusion chemotherapy with ETP and CDDP may assure a good prognosis for multiple liver metastases of small cell rectal cancer.

Aged↗
PubMed1999

Prognosis of patients with stage IIIb-IVa squamous cell carcinoma of the cervix following intra-arterial neoadjuvant chemotherapy.

Our purpose was to determine the long-term prognosis in patients with stage IIIb-IVa squamous cell carcinoma of the cervix who were treated with intra-arterial neoadjuvant chemotherapy (NAC), and to analyze factors related to prognostic value. We assessed the disease-free survival of 21 patients with FIGO stage IIIb-IVa squamous cell carcinoma of the cervix treated with intra-arterial NAC (cisplatin 70 mg/m2 and peplomycin sulfate 30 mg/m2) followed by irradiation therapy. Before chemotherapy, five factors (age, clinical stage, histologic type, parametrial involvement and serum level of SCC) were evaluated for their correlation with disease-free survival. The absolute 5-year disease-free survival rate for the entire group was 52%, with a median follow-up time in disease-free survivors of 87 months. Among the prognostic factors, age was the only one to be significantly correlated with disease-free survival; older (> 60 years) patients showed a significantly better disease-free survival rate than did younger (< 60 years) patients (p < 0.05, log-rank test). The absolute 5-year disease-free survival rate was 69% for older patients and 25% for younger patients. Univariate Cox's proportional hazard model also demonstrated that age was a significant prognostic factor as a continuous variable (p < 0.01). Intra-arterial NAC thus appeared to be effective in treating older patients with stage IIIb-IVa squamous cell carcinoma of the cervix.

Adult↗
PubMed1999

Co-expression of vascular endothelial growth factor and thymidine phosphorylase in endometrial cancer.

OBJECTIVE: To examine expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) together with microvessel count in endometrial cancer, and to investigate the relationship with clinicopathological and biological factors. METHODS: VEGF expression, TP expression, the microvessel count (factor VIII-related antigen positive cells), bcl-2 expression, proliferating cell nuclear antigen (PCNA) index, and p53 expression were determined in 50 resected endometrial cancer specimens, using immunohistochemistry. The relationship between VEGF and TP expression and correlation between expression and microvessel count were also given attention. These 3 factors were analyzed with regard to clinicopathological factors, bcl-2 expression, PCNA index, and p53 expression. RESULTS: Staining status of VEGF and TP was identical in 37 (74%) of 50 tumors, the correlation being statistically significant (p < 0.01). Combined analysis of VEGF and TP status showed that tumors which were VEGF-positive and/or TP-positive had a significantly higher microvessel count than did tumors which were both VEGF-negative and TP-negative (p < 0.001 and p < 0.05, respectively). TP expression correlated with bcl-2 expression, and VEGF expression inversely correlated with the PCNA index. Although clinical stage (p < 0.01), PCNA index (p < 0.01), and p53 expression (p < 0.01) significantly correlated with disease-free survival, neither VEGF/TP expression nor microvessel count contributed to prognostic estimates. CONCLUSIONS: VEGF and TP may cooperatively promote angiogenesis in endometrial cancer, but these expressions may have limited additional prognostic value.

Adult↗
PubMed1999

[Anti-tumor effects of carmofur on human 5-FU resistant cells].

As a part of studies to clarify the efficacy mechanism of carmofur (HCFU), a 5-FU analog, the degree of cross-resistance to HCFU of cell lines of cultured human colon cancer DLD-1 and a stomach cancer NUGC-3, both of which had acquired resistance to 5-FU, was studied in vitro and in vivo. In vitro, both resistant cell lines showed no or little cross-resistance to HCFU under a short-term drug exposure, and very low cross-resistance to HCFU, as compared to resistance to 5-FU, under a long-term drug exposure. In therapeutic experiments using nude mice bearing parent or subcutaneously transplanted 5-FU-resistant DLD-1 cells, HCFU exerted almost the same growth-inhibitory effects on both tumors. These results suggest that HCFU itself may have its own anti-tumor mechanism, different from that of 5-FU.

Animals↗