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Biomedical subjects

Yasushi Mizutani

Publications and source records attributed to Yasushi Mizutani.

10 recordsLinked to original sources

Oligonucleotide-arrayed TFT photosensor applicable for DNA chip technology.

A thin film transistor (TFT) photosensor fabricated by semiconductor integrated circuit (IC) technology was applied to DNA chip technology. The surface of the TFT photosensor was coated with TiO2 using a vapor deposition technique for the fabrication of optical filters. The immobilization of thiolated oligonucleotide probes onto a TiO2-coated TFT photosensor using gamma-aminopropyltriethoxysilane (APTES) and N-(gamma-maleimidobutyloxy) sulfosuccinimide ester (GMBS) was optimized. The coverage value of immobilized oligonucleotides reached a plateau at 33.7 pmol/cm2, which was similar to a previous analysis using radioisotope-labeled oligonucleotides. The lowest detection limits were 0.05 pmol/cm2 for quantum dot and 2.1 pmol/cm2 for Alexa Fluor 350. Furthermore, single nucleotide polymorphism (SNP) detection was examined using the oligonucleotide-arrayed TFT photosensor. A SNP present in the aldehyde dehydrogenase 2 (ALDH2) gene was used as a target. The SNPs in ALDH2*1 and ALDH2*2 target DNA were detected successfully using the TFT photosensor. DNA hybridization in the presence of both ALDH2*1 and ALDH2*2 target DNA was observed using both ALDH2*1 and ALDH2*2 detection oligonucleotides-arrayed TFT photosensor. Use of the TFT photosensor will allow the development of a disposable photodetecting device for DNA chip systems.

Biosensing Techniques↗

Parathyroid hormone-related protein as a potential tumor marker: a case report of ovarian clear cell carcinoma.

Hypercalcemia is one of the important paraneoplastic syndromes, mostly occurring in patients with advanced cancer. Clear cell carcinoma is known to be one of the most common histological subtypes of ovarian tumor associated with hypercalcemia. We present a case of ovarian clear cell carcinoma with hypercalcemia caused by elevated serum parathyroid hormone-related protein (PTHrP). PTHrP mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemical analysis in the primary and metastasis lesions. Serum calcium and PTHrP levels returned to normal after antihypercalcemic treatment and a radical operation, but they elevated along with the recurrence. Because tumor markers such as carcinoembryonic antigen, carbohydrate antigen (CA)125 and CA19-9 were unstable owing to the patient's liver cirrhosis and were not reliable data for management, serum calcium and PTHrP levels are shown to have been a potential indicator of the recurrence in this case.

Adenocarcinoma, Clear Cell↗

SSX expression in gynecological cancers and antibody response in patients.

The SSX genes are members of the cancer-testis (CT) antigen family. SSX2, the prototype SSX gene, was found by serological analysis of antigens by recombinant expression cloning (SEREX). Since little is known about SSX expression in gynecological malignancies, we investigated SSX mRNA expression in 115 gynecological cancer specimens and 25 normal control samples by RT-PCR. We also tested the humoral immune response to SSX2 and SSX4 using recombinant proteins. We found relatively high SSX4 mRNA expression in endometrial cancer (24%), ovarian cancer (13%), and cervical cancer (20%). In contrast, SSX1 and SSX2 mRNA expression was detected in not more than 4% of the gynecological cancer specimens analysed. No SSX mRNA expression was found in 25 normal specimens. Two gynecological cancer patients had antibodies against SSX4, whereas no antibody reactivity to SSX4 was found in the sera of 40 normal individuals. This suggests that SSX4 is a potential target for cancer vaccines in gynecological cancer patients.

Antibodies, Neoplasm↗

A-kinase anchoring protein 3 messenger RNA expression in ovarian cancer and its implication on prognosis.

A-kinase anchoring protein 3 (AKAP3) is a sperm protein and its expression appears to be restricted to the testis in normal adult tissues. We investigated AKAP3 mRNA expression in 20 normal ovaries and 54 ovarian cancers of different histological types, grades and stages by reverse transcription-polymerase chain reaction (RT-PCR). The PCR products were analyzed by conventional agarose gel electrophoresis and capillary electrophoresis on a microtip device to determine the expression semiquantitatively. Little or no expression was observed in the 20 normal ovarian specimens. High AKAP3 mRNA expression was observed in 15 ovarian cancer specimens (28 %). The expression was correlated with the histological grade and clinical stage. AKAP3 mRNA was observed at a significantly higher frequency in poorly differentiated (p = 0.009) and advanced stage (III and IV, p = 0.014) tumors. No correlation was found between AKAP3 mRNA expression and other variables. In Cox multivariate analysis, AKAP3 mRNA expression was found to be a significant predictor of both overall and progression-free survival in patients with poorly differentiated tumors.

A Kinase Anchor Proteins↗

[Home palliative care--2 case reports: a long-term cancer pain management with transdermal fentanyl].

Transdermal Fentanyl was released in March 2002 in Japan after the acceptance of the insurance under the office of public health. Transdermal therapy is especially effective for patients having difficulty of oral intakes, and for home care cancer patients who suffer from chronic pain only if the therapy is feasible on the long-term basis. We report our cases for long-term cancer pain management with transdermal fentanyl. A total of 52 long-term patients with chronic cancer pain (28 men and 24 women with an average age of 63.5 years, range 46-74 years) were evaluated. The most prevalent cancers were colorectum (n=14), stomach (n=10), breast (n=8), esophagus (n=6), pancreas (n=6), and others. The duration of the transdermal therapy varied from minimum of 2 days to maximum of 630 days. Two patients on this therapy were longer than 500 days. The transdermal therapy was discontinued 2-37 days for 8 patients due to uncontrolled pain relief. Case report 1: A 72-year-old woman suffering from a relapse of pancreatic cancer with chronic back pain experienced a good pain relief after switching from 60 mg/day sustained oral release morphine to 2.5 mg transdermal fentanyl. During the long-term treatment, the transdermal fentanyl dosage had to be increased. Transdermal therapy was continued until the patient's death on day 601. The last fentanyl dosage was 7.5 mg. Transdermal therapy was given 319/601 days at home and 282/601 days in the hospital. Meanwhile, a little rescue suppository morphine was used as an adjuvant during the duration of transdermal therapy. Case report 2: A 73-year-old man suffered a relapse of rectal cancer. He experienced adequate pain relief with 40 mg oral sustained release morphine, but he was switched to 2.5 mg transdermal fentanyl. Transdermal therapy was continued until today on day 630. At present, fentanyl dosage is 20 mg. The patient has been treated at home for 622/630 days. He was hospitalized only once for 8 days because of dehydrations, and has been treated at home. Only a little rescue powder morphine was needed as an adjuvant during the duration of transdermal therapy. In these 2 cases of long-term cancer pain management, transdermal therapy has resulted in good pain reduction and the side effects with transdermal therapy were not noted. Transdermal fentanyl can be recommended for treatment of palliative cancer pain at home.

Administration, Cutaneous↗

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↗

Optimal surgery and diagnostic approach of stage IA2 squamous cell carcinoma of the cervix.

BACKGROUND: Most patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2 squamous cell carcinoma of the cervix, opt for radical surgery at present. OBJECTIVE: To review surgical and diagnostic approaches in such patients. STUDY DESIGN: Our patient population consisted of 394 patients with a diagnosis of stage I squamous cell cervical carcinoma (with depth of stromal invasion 10mm or less) according to the 1995 FIGO definition. Biopsy and surgical specimen slides were reassessed retrospectively in all cases. The findings of T2-weighted MR imaging were available from the individual medical charts. RESULTS: None of the patients with stromal invasion of 5mm depth or less showed pelvic lymph node metastasis. However, metastasis to the parametrial connective tissue was found in one case with stage IA1 exhibiting marked lymph-vascular space involvement. There were no deaths due to disease in cases with stromal invasion of 5mm depth or less. The lesions were detected in all 20 cases exhibiting stromal invasion of greater than 5mm in depth. In contrast, the lesions were not detected with T2 imaging in four of six cases (67%) with stage IA2. CONCLUSION: Simple or modified radical hysterectomy with pelvic lymph node dissection may be sufficient for cases of stage IA2 cervical squamous cell carcinoma where lymph-vascular space involvement is absent. T2-weighted MR imaging with no detectable tumor would prove beneficial in the selection of these patients.

Adult↗

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↗

[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↗