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Biomedical subjects

Yuji Hiramatsu

Publications and source records attributed to Yuji Hiramatsu.

45 records · Page 3Linked to original sources

Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

Surfactant treatment in infants with respiratory distress syndrome (RDS) has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT), surfactant protein-A (SP-A) and hepatocyte growth factor (HGF) in amniotic fluid as predicting markers for RDS. Of 55 amniotic fluid samples obtained by amniocentesis from women less than 37 weeks pregnant, the SMT values were as follows: sensitivity 76.5%, specificity 84.2%, positive predictive value 68.4%, negative predictive value 88.9% and overall accuracy 81.8%. For SP-A, the values were 88.2%, 65.8%, 53.6%, 92.6% and 72.7%, respectively. If we used both SMT and SP-A, we could diagnose with 100% accuracy that a case with measurements of SMT > or = 2 and SP-A > or = 420 ng/ml would not complicate with RDS (24/24). However, the RDS diagnostic accuracy of HGF does not equal to those of SMT and SP-A levels. We concluded that the rapidity, simplicity and reliability of SMT was very useful during 24-36 weeks of gestation as a bedside procedure to predict fetuses likely to develop RDS. We also noted the additive effect of SP-A in improving the accuracy of lung maturity diagnosis.

Amniotic Fluid↗

[Paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients].

To evaluate the validity of administration of paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients with gynecologic cancer, we explored the efficacy and safety of these regimens. From October 1, 1998 to September 30, 2001, we administered paclitaxel and carboplatin with or without THP-ADR pursuant to the chart we prepared originally as first line chemotherapy in patients with gynecologic cancer. Eleven elderly patients (age > 70 years) and 62 younger patients (age < 70 years) were entered into the present study. Paclitaxel was administered as a 3-hour intravenous (i.v.) infusion at dosages of 135 to 180 mg/m2 immediately followed by carboplatin over 60 minutes at dosages of area under the curve (AUC) 3 to 5, administered intravenously or intraperitoneally. We observed grade 3/4 anemia more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin without THP-ADR (9% v.s. 47%, p < 0.0001). Grade 3/4 anemia (10% v.s. 22%, p = 0.02) and grade 3/4 thrombocytopenia (7% v.s. 22%, p = 0.007), febrile neutropenia (14% v.s. 44%, p = 0.02) also occurred more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin with THP-ADR. The overall response rates were equivalent among elderly and younger patients (69% and 78%), respectively. The regimen consisting of paclitaxel and carboplatin without THP-ADR was applied safely to elderly patients.

Aged↗

Heparanase messenger RNA expression in epithelial ovarian tumor.

Endoglycosidic heparanase degrades heparan sulfate glycosaminoglycans, and may be important in cancer invasion and metastasis, although its expression in human epithelial ovarian cancer has not been characterized. Heparanase association with clinicopathological features regarding prognostic significance was examined in patients presenting with epithelial ovarian tumor. Gene expression of heparanase was assessed by reverse transcription-PCR in 5 borderline and 31 malignant epithelial ovarian tumors. Heparanase mRNA expression was high in 16 of 31 malignant epithelial ovarian tumors. In contrast, there was no specimen presenting high heparanase mRNA expression in five borderline epithelial ovarian tumors. Heparanase expression was significantly higher in tumors with massive ascites and high grade (p=0.049 and p=0.006, respectively). There was no association between heparanase expression and patient outcome. These findings provide evidence that heparanase expression may be associated with a high grade phenotype in this class of neoplasm.

Carcinoma↗

Overproduction of platelet microparticles in cyanotic congenital heart disease with polycythemia.

OBJECTIVES: We sought to clarify the role of platelets in the pathogenesis of abnormal coagulation in patients with cyanotic congenital heart disease (CCHD) with polycythemia; we evaluated the production of platelet microparticles (MPs), platelet degranulation and aggregation response, as well as the correlations of these variables with polycythemia. BACKGROUND: A shortened life span and suppressed aggregability of platelets are well known in patients with CCHD. Although platelet MPs are overproduced and play an important role in the coagulation process in various hematologic and cardiovascular disorders, the production of MPs remains to be elucidated in CCHD. We studied 19 patients who had CCHD with polycythemia and 21 age-matched subjects with acyanotic congenital heart disease (ACHD). Flow cytometry, using monoclonal antibodies, showed the presence of MPs as particles positive for the surface antigen (glycoprotein IIb/IIIa) specific to platelets, and platelet alpha-degranulation was recognized as platelets positive for the surface antigen of P-selectin. Platelet aggregation was assessed as the response to adenosine diphosphate (ADP). Relationships between these indexes and hematocrit (Hct) values were also evaluated. RESULTS: Production of MPs correlated positively with Hct and markedly increased at Hct values above 60% in patients with CCHD. Surface P-selectin and the mean platelet volume in patients with CCHD were comparable with those in patients with ACHD. The platelet aggregation response to ADP significantly and negatively correlated with Hct. In two subjects who showed hemoptysis and underwent phlebotomy, MPs were reduced 6 h after the procedure. CONCLUSIONS: Platelet MPs are overproduced in patients who have CCHD with polycythemia, probably due to a high shear stress derived from blood hyperviscosity. Circulating incompetent platelets, which have already been activated, as well as MPs, might play an important role in the coagulation abnormalities identified in such patients.

Adolescent↗

Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat.

The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-alpha-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate limiting enzyme of polyamine synthesis was administrated to pregnant rats so that we obtained rat fetuses with IUGR. The changes of maternal nutrition, damage of the placenta, and the direct effect of DFMO on the fetus were examined in this IUGR model. Administration of DFMO did not induced changes of maternal nutrition except for triglyceride and the fetal metabolic state. But the placental weight, ODC activity, and DNA in the placenta were decreased significantly. The ODC activity in the total placenta decreased to less than 10% of that of the control. Depression of ODC activity in the placenta may be the major cause of IUGR induced by DFMO administration, and polyamines play important roles to carry pregnancy.

Animals↗

Ligands have various potential effects on the degradation of pregnane X receptor by proteasome.

The degradations of several nuclear receptors are involved in the proteasome-mediated pathway. In our recent experiments, we found that mouse pregnane X receptor (PXR) interacted with suppressor for gal1 (SUG1), a component of the proteasome, in a progesterone-dependent manner, but that endocrine-disrupting chemicals (EDCs), phthalic acid and nonylphenol, which activated PXR-mediated transcription, did not enhance this interaction. PXR protein levels were markedly increased in the presence of proteasome inhibitors, suggesting that PXR may be degraded by proteasome. Furthermore, in the absence of ongoing protein synthesis, there is much slower degradation of PXR in the presence of phthalic acid compared with that in the presence of progesterone. The transient expression studies demonstrated that overexpression of wild-type SUG1 generated proteolytic PXR fragments, and these productions were blocked by a proteasome inhibitor. Functionally, expression of SUG1 inhibited PXR- and progesterone-mediated transcription. Moreover, in the presence of EDCs, SUG1 had no effect on the transcription. These findings indicate that the interaction between PXR and SUG1 may be involved in the proteasome-mediated degradation. Moreover, an EDC strongly blocks the degradation of PXR compared with progesterone, suggesting that EDCs may affect PXR-mediated transcription of target genes through up-regulation of the PXR protein level.

ATPases Associated with Diverse Cellular Activitie↗

Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy.

Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess glucose has been implicated in vascular complications of diabetes. Its involvement in diabetic embryopathy has not been established. We examined DAG production and PKC activities in embryos and decidua of streptozotocin (STZ)-diabetic or transiently hyperglycemic mice during neural tube formation. STZ diabetes significantly increased DAG and total PKC activity in decidua (1.5- and 1.4-fold, respectively) and embryos (1.7- and 1.3-fold, respectively) on day 9.5. Membrane-associated PKC alpha, betaII, delta, and zeta were increased in decidua by 1.25- to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo on day 9.5. Notably, membrane-associated PKC activity was increased 24-fold in embryos of diabetic mice with structural defects. These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects.

Animals↗

[The effect of L-Glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced myalgia/arthralgia].

Myalgia/arthralgia is a crucial side effect of paclitaxel, and may become the major dose-limiting side effect. However, this is a situation where there is little effective preventive treatment. L-Glutamine was reported as a neuroprotective agent for vincristine-induced neurotoxicity. In Japan, there have been reports on steroid and Shakuyaku-Kanzou-to (a herbal medicine) for paclitaxel-induced myalgia/arthralgia. This study aimed to compare the effect of L-Glutamine and Shakuyaku-Kanzou-to, and to discuss the validity of these agents for the paclitaxel-induced myalgia/arthralgia. Our results suggested that Shakuyaku-Kanzou-to showed no remarkable effects against paclitaxel-induced myalgia/arthralgia as had been reported before; however, both L-Glutamine and Shakuyaku-Kanzou-to decreased the duration of grade 2 toxicity (CALGB Expanded Common Toxicity Criteria) in comparison with those who were not treated. L-Glutamine and Shakuyaku-Kanzou-to might therefore a preventive effect against moderate or severer myalgia/arthralgia during paclitaxel-treated chemotherapy. Further trials are needed to confirm the value of these drugs.

Antineoplastic Agents, Phytogenic↗

Biventricular repair of Ebstein's anomaly with pulmonary atresia in a low birth weight neonate.

Cyanotic neonates with Ebstein's anomaly associated with pulmonary atresia are a subgroup with the high mortality rate in pediatric cardiac surgery. We report a case of a severely symptomatic low birth weight neonate with Ebstein's anomaly and pulmonary atresia. A biventricular repair with Danielson-type tricuspid valve repair was performed. The baby tolerated the procedure with adequate hemodynamics, but died of peritoneal hemorrhage on the second postoperative day. This report could be an addition to the recent literature regarding the feasibility of biventricular repair for symptomatic neonates with Ebstein's anomaly even in low birth weight neonates.

Abnormalities, Multiple↗