Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 19 recordsLinked to original sources

PubMed2001

Prognostic value of performance status assessed by patients themselves, nurses, and oncologists in advanced non-small cell lung cancer.

Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable, advanced non-small cell lung cancer were investigated prospectively. Weighted Kappa statistics for inter-observer agreement were 0.53 between oncologists and patients and 0.63 between oncologists and nurses. There was a significant difference among the assessments by the three groups (P < 0.001). Oncologists gave the healthiest performance status assessment, nurses an intermediate assessment, and patients the poorest. When included separately in the Cox model, the assessment by each group was significantly correlated with survival. However, the assessment by the patients themselves failed to distinguish survival of patients with performance status 1 and 2. Among the three models including patient-, nurse-, and oncologist-assessed PS, that including oncologist-assessed PS best fitted to the observed survival data. These results showed that the assessment by the patients themselves is different from those by the nurses and the oncologists and provided additional support for the use of the assessment by oncologists in clinical oncology.

Aged↗

PubMed2001

Enhancer regions of ovine interferon-tau gene that confer PMA response or cell type specific transcription.

Interferon-tau (IFNtau), produced by the trophectoderm of peri-implantation conceptuses in ruminant ungulates, attenuates the uterine production of a luteolytic factor, prostaglandin F(2alpha), resulting in the maintenance of corpus luteum function. However, molecular mechanisms regulating the temporal/spatial expression of IFNtau gene are not clearly understood. The 5'-upstream region of the sheep IFNtau (oIFNtau) gene was examined for its transcriptional regulation in two different cell types; JEG3 cells supported the transactivation of oIFNtau-reporter construct, but HeLa cells did not. In a heterologous SV40 enhancer-oIFNtau promoter or oIFNtau enhancer-SV40 promoter systems, elements required for such cell specific transactivation were localized between -654 and -555 bases, the enhancer, but not the basal promoter region of the oIFNtau gene. In these combinations, high degrees of transactivation were observed in JEG3 cells and the activity was further enhanced by the addition of phorbol 12-myristate 13-acetate (PMA), while those responses were absent in HeLa cells. To identify nucleotide sequences responsible for cell specific expression, transient transfection studies with sequential point mutations in the enhancer elements were executed. Transactivation of oIFNtau enhancer-reporter constructs was primarily regulated by three regions containing AP-1 site, GATA like sequence and site(s) unidentified. In gel mobility shift assays (GMSAs), the AP-1 site located in the enhancer region was recognized by nuclear extracts from both cell types. However, one of the GMSA probes containing GATA-like sequence exhibited different DNA-protein complex patterns in JEG3 and HeLa cells. Observations, in which the same upstream sequence behaved differently due possibly to kinds of nuclear factors available in these cell lines, suggest that such a sequence may be involved in cell specific transactivation of the oIFNtau gene. Furthermore, the same enhancer sequences were also recognized by nuclear extracts from sheep trophoblasts, suggesting that the enhancer sequences between -654 and -555 bases of oIFNtau gene may be functioning in vivo.

Animals↗

PubMed2001

Hormonal regulation of mitochondrial Tim23 gene expression in the mouse mammary gland.

Tim23, a mitochondrial inner membrane protein, is essential for cell viability. Mouse Tim23 cDNA consisted of 1142 nucleotides plus poly(A) at the 3' end. In situ hybridization showed that mammary epithelial cells expressed Tim23 mRNA during pregnancy. In order to examine the hormonal regulation of the Tim23 gene expression at lactogenesis, the quantity of Tim23 mRNA in the mammary gland was determined by the competitive RT-PCR. The level of Tim23 mRNA was low until mid-pregnancy, increased toward the end of pregnancy and was the highest on day 18 of pregnancy. On day 13 of pregnancy, Tim23 mRNA increased 2.7-fold between 8 and 16 h after ovariectomy but this increase was cancelled out by the simultaneous operation of adrenalectomy. In adreno-ovariectomized mice, the administration of cortisol increased Tim23 mRNA 2-fold but with progesterone, the stimulatory action of cortisol was no longer observed. The results indicated that the expression of the Tim23 gene became active in response to glucocorticoid.

Animals↗

PubMed2001

Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of irinotecan combined with carboplatin, to evaluate its efficacy and toxicity for patients with lung cancer, and to examine its pharmacokinetics and pharmacodynamics. METHODS: The dose of irinotecan was escalated from 40 mg/m2 per week in increments of 10 mg/m2. Carboplatin was fixed at 300 mg/m2. Multivariate regression models with an interaction term were used to evaluate synergistic pharmacodynamic interactions. RESULTS: The MTD and recommended dose of irinotecan were 60 and 50 mg/m2, respectively. Dose-limiting toxicities were grade 4 neutropenia and grade 3 or 4 diarrhea. In phase II studies, response rates were 81.3% (95% confidence interval 61.8-100%) in 16 patients with small-cell lung cancer and 22.2% (2.7-41.8%) in 18 patients with non-small-cell lung cancer. Two patients (6%) experienced grade 4 neutropenia, thrombocytopenia, and grade 3 diarrhea. The area under the plasma concentration versus time curve (AUC) of carboplatin ranged from 2.87 to 9.31 mg x min/ml, with a median of 4.66 mg x min/ml. In pharmacodynamic analyses, the log-transformed surviving fraction in platelet count (SFp) showed a significant association with the AUC of carboplatin (P=0.010), while that in neutrophil count (SFn) was not significantly correlated with any pharmacokinetic parameter. The interaction term was not significant in either case. CONCLUSIONS: These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy. A more sensitive method for predicting life-threatening toxicities is needed, however, because traditional pharmacokinetic parameters were not adequate tools for identifying patients at high risk of severe neutropenia and diarrhea. This combination regimen has only modest activity, and further studies are necessary to evaluate a different dose schedule.

Adult↗

PubMed2001

MR imaging findings of uterine endometrial stromal sarcoma: differentiation from endometrial carcinoma.

Endometrial stromal sarcoma (ESS) is a rare malignant neoplasm of the uterus. We retrospectively analyzed pelvic MR imaging in 8 cases of ESS to determine the characteristic MR findings of ESS. Magnetic resonance images of 8 cases of ESS were evaluated for findings including the size, margin of the tumor, nodular lesions at the tumor margin, intramyometrial worm-like nodular extension, multiple nodular mass formation, hemorrhage, and necrosis in the tumor. The degree of contrast enhancement was also analyzed. The MR imaging findings of 21 consecutive cases of endometrial carcinoma (EC) were also evaluated and compared with those of ESS. The mean and the standard deviation of the maximum diameter of ESS and EC were 8.80 +/- 4.99 and 3.93 +/- 2.47 cm, respectively. Increased enhancement in at least a part of the tumor was observed in five of the six analyzed ESS cases and in 2 of 12 analyzed EC cases. The irregular margin, nodular lesions at the margin, intramyometrial nodular extension, and multiple nodular mass formation were more frequently seen in cases of ESS than in cases of EC. Magnetic resonance imaging can play a role in both diagnosing ESS as well as in differentiating ESS from EC.

Aged↗

PubMed2001

Isolation of a MADS-box gene (ERAF17) and correlation of its expression with the induction of formation of female flowers by ethylene in cucumber plants (Cucumis sativus L.).

Ethylene regulates sex expression in cucumber (Cucumis sativus L.) plants. When the apices of monoecious cucumber seedlings (cv. Shimoshirazu-jibai) were treated with the ethylene-releasing compound, ethephon, female flowers were induced at the nodes. To clarify the action of ethylene in the regulation of sex expression, we attempted to isolate genes whose expression changed during induction of the formation of female flowers at the apices of these cucumber plants upon treatment with ethephon. Using the differential-display method, we identified 20 clones (#1 to #20) that reflected differences in the accumulation of transcripts in apices treated or not treated with ethephon. Sequence analysis of cDNA fragments revealed that the cDNA #17 had the sequence of a MADS-box gene. We isolated the full-length cDNA and showed that it included both a MADS box and a K box, and the corresponding gene was designated ERAF17. We examined the expression of ERAF17 in the apices of cv. Shimoshirazu-jibai and in those of a gynoecious cultivar (Rensei). In these cultivars, the timing and levels of expression of the ERAF17 transcript were correlated with the development of female flowers. Induction of the synthesis of the ERAF17 transcript by ethephon occurred within 4 h of the start of treatment and continued for 4 days at least. Expression of ERAF17 at apices was localized in the floral buds of the gynoecious cultivar, and expression was maintained in female flowers thorough their development. Our results suggest that the induction of the formation of female flowers by ethylene might be regulated by the expression of ERAF17 in floral buds at the apices of cucumber plants and that expression of this gene might also be involved in the development of female flowers.

Amino Acid Sequence↗

PubMed2001

Determinants of masticatory performance in dentate adults.

Masticatory performance results from a complex interplay of direct and indirect effects, yet most studies employ univariate models. This study tested a multivariate model of masticatory performance for dentate subjects. Explanatory variables included number of functional tooth units, bite force, sex, age, masseter cross-sectional area, presence of temporomandibular disorders, and presence of diabetes mellitus. The population-based sample consisted of 631 dentate subjects aged 37-80 years. Covariance structure analysis showed that 68% of the variability in masticatory performance could be explained by the combined effects of the explanatory variables. Age and sex did not show a strong effect on masticatory performance, either directly or indirectly through masseter cross-sectional area, temporomandibular disorders, and bite force. Number of functional tooth units and bite force were confirmed as the key determinants of masticatory performance, which suggests that their maintenance may be of major importance for promoting healthful functional status.

Adult↗

PubMed2001

Synthesis and transport characterization of alginate/aminopropyl-silicate/alginate microcapsule: application to bioartificial pancreas.

To develop a novel type of immunoisolation membrane for a microcapsule-shaped bioartificial pancreas, we attempted to use a sol-gel synthesized silicate. An aminopropyl-silicate membrane derived from 3-aminopropyltrimethoxysilane and tetramethoxysilane was formed on Ca-alginate gel beads via electrostatic interaction. The positively charged amino groups remaining on the surface of the resultant gel beads were neutralized by immersion in an aqueous Na-alginate solution. From measurements of the partition coefficients and effective diffusivities of different substances to the gel beads, it was found that the aminopropyl-silicate membrane prepared under optimized composition of silicon alkoxide precursors successfully rejected gamma-globulin, giving good permeability to substances having a low molecular weight. Islets could be encapsulated within the newly developed microcapsules while retaining their ability to secrete insulin.

Alginates↗

PubMed2001

Pyridinyl imidazole inhibitor SB203580 activates p44/42 mitogen-activated protein kinase and induces the differentiation of human myeloid leukemia cells.

Various inhibitors of protein kinases regulate the growth and differentiation of human leukemic cell lines. The pyridinyl imidazole inhibitor SB203580 has been widely used to elucidate the role of p38 kinase in a wide array of biological systems. In the present investigation, we found that SB203580 effectively induced the granulocytic differentiation of human promyelocytic HL-60 cells. In addition to morphological differentiation, it also induced NBT-reduction, lysozyme activity and growth-inhibition. It also induced the differentiation of human myeloid leukemia HT93 and ML-1 cells, but not of other cell lines, such as NB4, U937, THP-1, K562 and HEL. This differentiation was not associated with the inhibition of p38 kinase activity, but was closely associated with the activation of extracellular signal-regulated kinase. These results demonstrate a new activity for this drug.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Bioanalytical screening methods for dioxins and dioxin-like compounds a review of bioassay/biomarker technology.

Determination of environmental pollutants utilizing biodetectors such as bioassays, biomarkers, enzyme immunoassays (EIAs), or other bioanalytical tools is a continuously growing area. The present literature review describes the principles and advantages/limitations of several bioanalytical detection methods (BDMs) for the screening and diagnosis of dioxin and dioxin-like compounds. This study characterizes briefly the family of dioxin and dioxin-like compounds, discusses potential Ah receptor (AhR) ligands and cytochrome P-450 (CYP) 1A1-enzyme-inducing compounds. 'Milestones' in the development of BDMs are summarized and explained in detail for a number of bioanalytical tools that can be used to detect these classes of dioxin-like persistent bioaccumulative toxicants (PBTs). The design of a screening profile with a battery of bioassays/biomarkers coupled with the chemical analysis is evaluated. The relative potencies (REPs) to 2,3,7,8-TCDD for dioxin-like compounds are reviewed for various BDMs and the differences are noted.

Animals↗

PubMed2001

Combinatorial bio/chemical analysis of dioxin and dioxin-like compounds in waste recycling, feed/food, humans/wildlife and the environment.

The present review describes international activities using bioassays/biomarkers in combination with chemical analysis to measure the effects of dioxin and dioxin-like compounds (DLCs) in the environment. The above authors reviewed already the state-of-art bioanalytical detection methods (BDMs) for dioxins and DLCs [Environ Int (2001)]. The aim of this study will be to review applications of these bioassays/biomarkers to evaluate potential dioxins and DLCs. The present literature study lists relative potencies (REPs) of polyhalogenated dibenzo-p-dioxins and -furans (PXDD/Fs; X = Cl, Br, F), their thio analogues polychlorinated dibenzothiophenes (PCDTs) and thianthrens (PCTAs), polyhalogenated biphenyls (PXBs), polychlorinated naphthalenes (PCNs) and other Ah receptor agonists measured by several biodetectors (Tier 3 screening). The authors will discuss some examples of the applications of some of these biodetectors in biomonitoring programmes and recently occurred dioxin crisis in feed/food. The diagnosis of the biopotency of these pollutants in technical processes like thermally treated waste, waste water treatment, landfill leachate treatment, commercial PCB-mixtures, the release into the environment (soil, air and water) and the final intake into wildlife and humans will be reviewed.

Animal Feed↗

PubMed2001

Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound.

OBJECTIVES: Mechanical and structural characteristics of vulnerable plaques were evaluated using coronary angioscopy and intravascular ultrasound. BACKGROUND: Mechanical stress and composition of plaques play an important role in plaque disruption. METHODS: Thirty-eight lesions in 38 patients were examined pre-interventionally. The plaques were classified as either yellow or white using coronary angioscopy. Intravascular ultrasound imaging was performed simultaneously with electrocardiographic and intracoronary pressure recordings to calculate distensibility index and stiffness beta. Moreover, the type of remodeling was classified. RESULTS: We identified 27 patients with yellow plaques and 11 patients with white plaques. Patients with yellow plaques presented acute coronary syndromes more frequently than stable angina (85% vs. 36%, p < 0.01). The distensibility index in yellow plaques was significantly greater than it was in white plaques (2.7 +/- 0.8 mm Hg(-1) vs. 0.7 +/- 0.8 mm Hg(-1), p < 0.0001), while stiffness beta for white plaques was significantly greater than it was for yellow plaques (34.9 +/- 16.3 vs. 8.7 +/- 2.7, p < 0.0001). Compensatory enlargement occurred more frequently with yellow plaques than with white plaques (56% vs. 9%, p < 0.01), while paradoxical shrinkage occurred more frequently with white plaques than it did with yellow plaques (64% vs. 4%, p < 0.001). CONCLUSIONS: Yellow plaques with an increased distensibility and a compensatory enlargement may be mechanically and structurally weak. As a result, mechanical "fatigue," caused by repetitive stretching, may lead to plaque disruption. Plaques with a high distensibility and a compensatory enlargement may be vulnerable.

Aged↗

PubMed2001

Characterization of a major form of human isatin reductase and the reduced metabolite.

Isatin, an endogenous indole, has been shown to inhibit monoamine oxidase, and exhibit various pharmacological actions. However, the metabolism of isatin in humans remains unknown. We have found high isatin reductase activity in the 105,000 g supernatants of human liver and kidney homogenates, and have purified and characterized a major form of the enzyme in the two tissues. The hepatic and renal enzymes showed the same properties, including an M(r) of 31 kDa, substrate specificity for carbonyl compounds and inhibitor sensitivity, which were also identical to those of recombinant human carbonyl reductase. The identity of the isatin reductase with carbonyl reductase was immunologically demonstrated with an antibody against the recombinant carbonyl reductase. About 90% of the soluble isatin reductase activity in the liver and kidney was immunoprecipitated by the antibody. The Km (10 microm) and k(cat)/K(m) (1.7 s(-1) x microm(-1)) values for isatin at pH 7.0 were comparable to those for phenanthrenequinone, the best xenobiotic substrate of carbonyl reductase. The reduced product of isatin was chemically identified with 3-hydroxy-2-oxoindole, which is also excreted in human urine. The inhibitory potency of the reduced product for monoamine oxidase A and B was significantly lower than that of isatin. The results indicate that the novel metabolic pathway of isatin in humans is mediated mainly by carbonyl reductase, which may play a critical role in controlling the biological activity of isatin.

Alcohol Oxidoreductases↗

PubMed2001

Adrenal cyst: a review of the Japanese literature and report of a case.

Adrenal cysts are a rare condition and are usually non-functioning and asymptomatic. A 44-year-old man was referred from another hospital because a left retroperitoneal tumor was incidentally found by abdominal echography. Laboratory findings including adrenal hormonal study were within the normal range. It showed homogeneously low intensity on T1-weighted images and high intensity on T2-weighted images on magnetic resonance imaging (MRI). Angiography demonstrated that the tumor was avascular and of left adrenal origin. The patient was diagnosed with left adrenal cyst and was intensively followed up with plans for examination with diagnostic imaging.

Adrenal Gland Diseases↗

PubMed2001

Localization of imidazolone in the peritoneum of capd patients: a factor for a loss of ultrafiltration.

The presence of dicarbonyl compounds, potent precursors of advanced glycation end products (AGEs), has been recognized in unused peritoneal dialysis (PD) fluids. Accumulation of AGEs has been implicated in the alteration of peritoneal membrane properties during continuous ambulatory peritoneal dialysis (CAPD) therapy. To determine whether imidazolone, an AGE specifically derived from 3-deoxyglucosone (3-DG), contributes to a decrease in ultrafiltration (UF) capacity of the peritoneal membrane in CAPD patients, we immunohistochemically evaluated the localization of imidazolone in peritoneal tissues from CAPD patients. Mesothelial thickening in the peritoneum was found in six of seven CAPD patients. Imidazolone distinctly accumulated in peritoneal tissues of CAPD patients, whereas it was hardly detected in those of patients with nonrenal disease. CAPD patients with a low UF capacity showed more extensive peritoneal deposition of imidazolone and more pronounced mesothelial thickening than those with a normal UF capacity. A CAPD patient with sclerosing peritonitis showed the most abundant localization of imidazolone among all CAPD patients. Gas chromatography/mass spectrometry showed that unused PD fluids contained high 3-DG concentrations (mean, 34.6 +/- 14.1 [SD] microgram/mL). In conclusion, the accumulation of imidazolone was noted in peritoneal tissues of CAPD patients, which preceded a decrease in UF capacity. Imidazolone modification may alter the quality of peritoneal membranes, presumably leading to a loss of UF and finally the development of sclerosing peritonitis.

Epithelium↗

PubMed2001

Mandibular range of motion after bilateral sagittal split ramus osteotomy with wire osteosynthesis or rigid fixation.

OBJECTIVES: An analysis was conducted to compare mandibular range of motion among Class II patients treated with wire osteosynthesis or rigid internal fixation after surgical mandibular advancement. STUDY DESIGN: Patients randomly received wire osteosynthesis and 8 weeks of maxillomandibular fixation (n = 49) or rigid internal fixation (n = 78). Mandibular range of motion was measured 2 weeks before surgery and 8 weeks, 6 months, and 1, 2, and 5 years after surgery. RESULTS: Both groups showed decreased mobility in all movement dimensions that progressively recovered to near presurgical levels over the 5-year follow-up period. The difference in range of motion between treatment groups was not statistically significant. Changes in proximal and distal segment position could not explain decreased mobility. CONCLUSIONS: Similar decreases in mandibular mobility occurred with wire and rigid fixation of a bilateral sagittal split ramus osteotomy after surgery. Long-term changes were statistically, but not clinically, significant.

Adult↗

PubMed2001

Administration of isoferulic acid improved the survival rate of lethal influenza virus pneumonia in mice.

BACKGROUND: Isoferulic acid (IFA) is a main active ingredient of the rhizoma of Cimicifuga beracleifolia, which is used frequently in Japanese traditional medicine as an anti-inflammatory drug. It has been revealed that IFA inhibits the production of macrophage inflammatory protein-2 (MIP-2), which is a murine counterpart of the chemokine family that may contribute to the pathogenesis of inflammatory diseases through the chemotactic activity for inflammatory and immune effector cells. AIM OF THE STUDY: In this study, we investigated the therapeutic effect of IFA on the progression of lethal influenza virus pneumonia in mice by comparison with that of dexamethasone (DX), a potent inhibitor for various inflammatory cytokines including MIP-2. METHODS: Mice were infected by intranasal inoculation of influenza virus under ether anesthesia. The IFA or DX was given by oral administration once daily for 4 days after infection. After infection, the survival rate and the change in body weight were daily monitored. RESULTS: IFA administration markedly improved the survival rate and body weight loss of influenza virus-infected mice in a suitable dose range (0.5 mg/day). However, DX administration did not show a beneficial effect at any dose. CONCLUSION: These data suggested that IFA is a novel tool not only for the intervention therapy, but also for the studies on the pathogenesis of influenza virus-induced pneumonia.

Animals↗

PubMed2001

Posttranscriptional regulation of cyclin A1 and cyclin A2 during mouse oocyte meiotic maturation and preimplantation development.

A shift from a meiotic cell cycle to a mitotic cell cycle occurs following fertilization. The molecular basis for this transition, however, is poorly understood. Although cyclin A1 is proposed to regulate M phase in the meiotic cell cycle, and cyclin A2 is proposed to regulate S and M phases in the mitotic cell cycle, little is known about changes in the expression levels of cyclin A1 and A2 during meiotic and mitotic cell cycles in mammalian oocytes. We report that the mRNA levels of both cyclins A1 and A2 decrease during oocyte maturation. The amount of cyclin A1 mRNA then increases between the one-cell and blastocyst stages, whereas that of cyclin A2 remains relatively constant. The amount of cyclin A1 protein declines during maturation and is not readily detected from the two-cell to the blastocyst stage. In contrast, cyclin A2 is not readily detected in the oocyte and metaphase II-arrested egg but is detected following fertilization and throughout the subsequent stages of preimplantation development. The appearance of cyclin A2 protein following fertilization positively correlates with an increase in the size of the mRNA. This increase, as well as the increase in the amount of cyclin A2 protein, is prevented by 3'-deoxyadenosine (3'-dA), an inhibitor of polyadenylation. Consistent with a role for cyclin A2 in regulating the G1/S transition, 3'-dA also inhibits DNA replication in treated one-cell embryos. These results suggest that regulation of expression of cyclins A1 and A2 is under posttranscriptional regulation and that the observed changes in their expression may be involved in the transformation of a meiotic cell cycle to a mitotic cell cycle following fertilization.

Animals↗