Biomedical subjects

K Ushijima

Publications and source records attributed to K Ushijima.

At least 19 recordsLinked to original sources

PubMed2001

Localization of a novel susceptibility gene for familial ovarian cancer to chromosome 3p22-p25.

We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was >50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.

Adult↗

PubMed2001

Dantrolene ameliorates delayed cell death and concomitant DNA fragmentation in the rat hippocampal CA1 neurons subjected to mild ischemia.

The present study investigated whether dantrolene, which inhibits the Ca(2+) release from the intracellular Ca(2+) store sites, reduced nuclear DNA fragmentation and produced neuronal protection in a model of global forebrain ischemia. Male Wistar rats were subjected to four-vessel occlusion (4VO) for 5 min and then infused continuously with dantrolene or vehicle into the cerebral ventricle for 3 days. The intact rats did not undergo any intervention. The number of viable and DNA nick-end-labeled neurons in the hippocampal CA1 were evaluated 4 days after the ischemia. The number of viable neurons in the dantrolene-treated rats was significantly higher than that in the vehicle-treated rats and lower than that in the intact animals (P<0.01 and <0.05, respectively). The number of DNA nick-end-labeled nuclei was significantly lower in dantrolene-treated rats compared with the vehicle-treated animals (P<0.0001). No nick-end labeling was observed in the intact animals. A linear correlation was found between the number of viable cells and nick-end labeled nuclei in the CA1 (r=0.91, P<0.0001). These results suggest that the postischemic intraventricular dantrolene is effective in precluding neuronal death and concomitant nuclear DNA fragmentation following transient global ischemia.

Animals↗

PubMed2001

Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing imidazole and primary amine groups.

We have previously shown that RNA cleaving reagents with imidazole and primary amine groups on the 5'-end of antisense oligodeoxyribonucleotides could site-specifically cleave CpA as the target sequence of the substrate tRNA in vitro. In this study, a RNA cleaving reagent, composed of imidazole and primary amine groups on an antisense phosphorothioate oligonucleotide (Im-anti-s-ODN), was synthesized and evaluated for anti-HIV-1 activity in MT-4 cells. The sequence of the Im-anti-s-ODN was designed to be complementary to the HIV-1 gag-mRNA and to bind adjacent to the CpA cleavage site position. Im-anti-s-ODN encapsulated with the transfection reagent, DMRIE-C, had higher anti-HIV-1 activity than the unmodified antisense phosphorothioate oligonucleotide (anti-s-ODN) at a 2 microM concentration. Furthermore, the Im-anti-ODN encapsulated with DMRIE-C conferred sequence-specific inhibition.

Amines↗

PubMed2001

Characterization of the S-locus region of almond (Prunus dulcis): analysis of a somaclonal mutant and a cosmid contig for an S haplotype.

Almond has a self-incompatibility system that is controlled by an S locus consisting of the S-RNase gene and an unidentified "pollen S gene." An almond cultivar "Jeffries," a somaclonal mutant of "Nonpareil" (S(c)S(d)), has a dysfunctional S(c) haplotype both in pistil and pollen. Immunoblot and genomic Southern blot analyses detected no S(c) haplotype-specific signal in Jeffries. Southern blot showed that Jeffries has an extra copy of the S(d) haplotype. These results indicate that at least two mutations had occurred to generate Jeffries: (1) deletion of the S(c) haplotype and (2) duplication of the S(d) haplotype. To analyze the extent of the deletion in Jeffries and gain insight into the physical limit of the S locus region, approximately 200 kbp of a cosmid contig for the S(c) haplotype was constructed. Genomic Southern blot analyses showed that the deletion in Jeffries extends beyond the region covered by the contig. Most cosmid end probes, except those near the S(c)-RNase gene, cross-hybridized with DNA fragments from different S haplotypes. This suggests that regions away from the S(c)-RNase gene can recombine between different S haplotypes, implying that the cosmid contig extends to the borders of the S locus.

Base Sequence↗

PubMed2001

Weekly 1 hour paclitaxel infusion in patients with recurrent gynecological tumors: a pilot study.

BACKGROUND: Intensifying the dose of paclitaxel given in a weekly schedule is useful towards improving the therapeutic index of paclitaxel in treating a variety of advanced and recurrent malignancies and is suitable for outpatient administration. This pilot study was carried out to evaluate the safety of weekly paclitaxel administration by 1 h infusion in the outpatient setting. METHODS: Eleven patients with recurrent gynecological tumors who had previously been treated with at least one platinum-based chemotherapy regimen participated in the study between May 1999 and March 2000. Paclitaxel was given at a dose of 70 mg/m(2 ) as a 1 h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The 11 patients received a total of 166 cycles of therapy. All patients received 70 mg/m(2 ) doses of paclitaxel without treatment delay. No hypersensitivity reactions were elicited. Grade 3 or 4 leukopenia and neutropenia occurred in 9 and 36% of the patients, respectively. Granulocyte colony-stimulating factor was required for only one patient and no patients experienced febrile neutropenia. Neurotoxicity was the most serious adverse effect and all patients experienced grade 1 or 2 peripheral neuropathy. Grade 1 or 2 myalgias were observed in 45% of the patients. Alopecia was universal. No Grade 3 or higher non-hematological toxicities were observed. CONCLUSION: Weekly 1 h paclitaxel administration is considered safe as a salvage therapy for recurrent gynecological tumors, making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

Ambulatory Care↗

PubMed2001

Males in rural Bangladeshi communities are more susceptible to chronic arsenic poisoning than females: analyses based on urinary arsenic.

Spot urine samples were collected from the inhabitants of two rural communities in northwestern Bangladesh. We compared arsenic levels in the urine samples ([As](u); n = 346) with those in water from tube wells ([As](tw); range < 1-535 microg/L; n = 86) on an individual basis. The small variation of [As](u) within subjects and highly positive correlation with [As](tw) indicate that [As](u) is a useful indicator of exposure. Analyses of [As](u) showed that creatinine correction was necessary, that [As](u) only reflected recent exposure, and that there were substantial interindividual differences for a given [As](tw) level. To evaluate the toxic effects of arsenic exposure, we constructed a system for rating skin manifestations, which revealed distinct sex-related differences. Comparison of males and females in the same households confirmed that skin manifestations were more severe in the males, and in the males of one community a dose-response relationship between [As](u) and the degree of skin manifestation was evident. The results of this study indicate that [As](u) in spot urine samples can be used as an exposure indicator for As. They suggest that there might be sex-related, and perhaps community-related, differences in the relationship between [As](u) and skin manifestations, although several confounding factors, including sunlight exposure and smoking habits, might contribute to the observed sex difference. The existence of such differences should be further confirmed and examined in other populations to identify the subpopulations sensitive to chronic arsenic toxicity.

Adult↗

PubMed2001

Placental transport of bile acids: analysis of bile acids in maternal serum and urine, umbilical cord blood, and amniotic fluid.

To investigate the role of placental transport of bile acids in fetal bile acid metabolism, such as with regard to synthesis of the unusual bile acids (1 beta- and 6 alpha-hydroxylated and unsaturated bile acids), we measured the concentrations of bile acids in umbilical cord blood, amniotic fluid, maternal serum and maternal urine at delivery by means of gas chromatography-mass spectrometry. Serum and urine from healthy nonpregnant women were used as controls. We detected large amounts of unusual bile acids, especially hyocholic acid and 3 beta-hydroxy-delta 5 bile acids, in amniotic fluid and umbilical cord blood. The concentration of total bile acids in maternal serum was less than that of control serum and umbilical cord blood, and the concentration of total bile acids in maternal urine was higher than that of control urine and amniotic fluid. In conclusion, the fetus synthesized large amounts of unusual bile acids, and these compounds were transported from fetus to mother by placental transfer. We suggest that pregnant women may excrete large amounts of bile acids into the urine to control serum concentration of bile acids in fetus.

Adult↗

PubMed2001

[Low concentration/high volume is more effective than high concentration/low volume for postoperative continuous epidural analgesia with the combination of bupivacaine and fentanyl].

In 40 females undergoing gynecologic laparotomy, lumbar epidural analgesia using a disposable infusion pump was continued for postoperative 48 hours. Then the analgesic effect of epidural bupivacaine (4.8 mg.kg-1) plus fentanyl (12 micrograms.kg-1) diluted with normal saline was prospectively compared between the two groups; high concentration/low volume group (HC/LV, 96 ml of total volume and 2 ml.h-1 of infusion rate, n = 20) versus low concentration/high volume group (LC/HV, 240 ml of total volume and 5 ml.h-1 of infusion rate, n = 20). On postoperative day 1, LC/HV group showed the significantly lower visual analog scale and verbal pain score at rest than HC/LV group (P < 0.05). No significant differences in the incidence of side effects were observed between the groups. These results suggest that when the equivalent dose is given, the volume rather than the concentration of the solution is important for postoperative continuous epidural analgesia with the combination of bupivacaine and fentanyl.

Adolescent↗

PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗

PubMed2001

[Propofol-fentanyl anesthesia for a 13-year-old patient with Beckwith-Wiedemann syndrome].

We report anesthetic management of a 13-year-old boy with Beckwith-Wiedemann syndrome for urethral fistulectomy using propofol-fentanyl anesthesia. The syndrome has three major symptoms; exomphalos, macroglossia and gigantism. Other complications including neonatal hypoglycemia, visceromegaly, metabolic disorders, malignant tumors, and cardiovascular abnormalities may also be seen. This patient was complicated with gigantism, exomphalos, hypospadias, cryptorchidism, hepatoblastoma, accessory mammae, and left axis deviation with left anterior fascicular block. A comprehensive preoperative examination should include assessment of the airway, cardiovascular conditions, endocrine status, blood glucose, and electrolytes. In this patient, airway management was easy by laryngeal mask airway and the anesthetic course was uneventful.

Adolescent↗

PubMed2000

Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant.

Excessive glutamate accumulation in extracellular space due to ischemia in the central nervous system (CNS) is believed to initiate the cascade toward irreversible neuronal damage. An intravenous general anesthetic, propofol (2,6-diisopropylphenol) has been implicated to be neuroprotective against cerebral ischemia. The purpose of this study was to test the hypothesis that intracerebroventricular propofol produced a reduction in extracellular glutamate level during global ischemia and the resultant neuroprotection. Adult male Wistar rats were anesthetized with halothane in nitrous oxide/oxygen and mechanically ventilated. Propofol (3 or 10 mg/kg), Intralipid((R)) as a vehicle for propofol, or artificial cerebrospinal fluid (aCSF) was administered into the cerebral ventricles 15 min prior to a 10-min forebrain ischemia elicited by the four-vessel occlusion. Extracellular glutamate concentration in the hippocampal CA1 was continuously monitored during the peri-ischemic period with a microdialysis biosensor. Neuronal cell loss in the hippocampal CA1 was evaluated by cresyl-violet staining of sections 7 days later. Propofol (3 and 10 mg/kg) and Intralipid, compared with aCSF, similarly reduced the extracellular glutamate accumulation during the peri-ischemic period (P<0.05), indicating that the extracellular glutamate reduction that was seen primarily reflects the effect of Intralipid. The number of intact neurons in the hippocampal CA1 in propofol 10 mg/kg-treated rats was significantly higher than that in rats treated with propofol 3 mg/kg, Intralipid, or aCSF (P<0.05). We conclude that intracerebroventricular propofol exhibits neuroprotection against transient global forebrain ischemia; however, the extracellular glutamate level during ischemia is not a major determinant of this neuroprotection.

Animals↗

PubMed2000

Successful treatment of two patients with recurrent endometrial cancer by weekly paclitaxel.

OBJECTIVE: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Paclitaxel (70 mg/m(2) by 1-h infusion weekly) was administered to two patients with recurrent endometrial cancer of the lung. RESULTS: After 5 cycles, both patients with platinum-resistant disease achieved clinical partial responses confirmed by computed tomography (CT) scan. The serum CA125 levels of case 1 decreased to cut-off level. The response duration of both patients was 4 months. The toxicity was acceptable and probably less pronounced than that characterize of the standard tri-weekly schedules. CONCLUSION: Although conclusions regarding survival are premature, weekly paclitaxel might offer better quality of life during treatment.

Adenocarcinoma↗

PubMed2000

Health surveillance in the population living in a methyl mercury-polluted area over a long period.

It is important to follow up on the health status of inhabitants living in the methyl mercury-polluted area surrounding Minamata City, paying particular attention to diseases not only of the central nervous system but also of other organs. We have been carrying out such concentric studies for more than 10 years. We have previously studied the cause-specific standard mortality ratios in Minamata disease patients and reported that the SMRs for liver disease and renal disease were significantly raised in male and female patients, respectively. It was also found that complications arising from diabetes could be due to the large number of old people among the autopsy cases. The next step was to clarify the actual prevalence and incidence of liver disease, renal disease, and diabetes mellitus epidemiologically among the population in this area. The aim of this study was to determine the actual prevalence of these diseases and complaints, and to investigate the contribution of various risk factors to these diseases in this area. The study was a population-based cross-sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors including methyl mercury exposure for these diseases. A mass multiple health examination survey was performed in 1500 subjects aged 40 years and older in Tsunagi Town, neighboring Minamata City, every summer since 1984. Tsunagi Town is located in a methyl mercury-polluted area and there are 36.9 certified Minamata disease patients per 1000 population. Data concerning liver disease, renal disease, and diabetes mellitus were collected on the basis of urine, hematological, physical, and ultrasonographic examinations. Data on risk factors and subjective complaints were collected by interview and other measures. The prevalence of these diseases was not higher in this methyl mercury-polluted area compared with other areas in Japan, contrary to what was expected based on standard mortality ratios and pathological findings. There were no positive correlations between those diseases and methyl mercury exposure. On the other hand, the population in the polluted area had more and a greater variety of complaints than those in the nonpolluted area. It is possible that not only neurological subjective complaints but also nonspecific complaints of the population in the polluted area might be influenced by past methyl mercury exposure. This health surveillance in the population living in a methyl mercury-polluted area must be maintained in the future.

Aged↗

PubMed2000

Serum MAGE-4 protein in ovarian cancer patients.

OBJECTIVE: We measured serum levels of MAGE-4 protein in patients with ovarian cancer to investigate the relationship between serum MAGE-4 positivity and prognosis. METHODS: Serum levels of MAGE-4 protein were measured with an ELISA system. RESULTS: Serum levels of MAGE-4 in patients with ovarian cancer were significantly higher than levels in patients with benign diseases. Serum MAGE-4 protein was considered positive in 22% of primary ovarian cancer patients. The positive rate was the highest in sera of patients with surface epithelial-stromal tumors, particularly serous adenocarcinomas (24%). The survival time after a primary surgical operation in ovarian cancer patients with serum MAGE-4 positivity was significantly shorter than that of MAGE-4-negative cases. CONCLUSION: These results suggest that serum MAGE-4 protein is a potential prognostic factor of reduced survival in ovarian cancer patients.

Adult↗

PubMed2000

Blood glucose and insulin concentrations are reduced in humans administered sucrose with inosine or adenosine.

Recently we found that some nucleosides such as inosine or adenosine inhibited alpha-glucosidase from rat intestine. The aim of this study was to determine whether these nucleosides are sucrase inhibitors in humans as well as rats. Blood glucose and insulin responses were examined in 23 healthy volunteers (18 males and 5 females) administered sucrose with inosine and 8 (males) administered sucrose with adenosine. The initial increase in plasma glucose and serum insulin concentrations at 30 min after loading sucrose (50 g) alone were significantly reduced by co-administration of inosine (2.5 and 1.0 g) or adenosine (2.5 g). The total increases in the areas under the plasma glucose and serum insulin concentration curves for 3 h after administration of the same amount of sucrose with inosine were also significantly less than those when the volunteers were administered sucrose alone. These results in humans agree with the findings obtained in our previous studies in rats. These nucleosides may be used as one of the components of artificial sweeteners when mixed with sucrose and may be useful as food additives to suppress increases in blood glucose and insulin.

Adenosine↗

PubMed2000

Alterations of endothelium and smooth muscle function in monocrotaline-induced pulmonary hypertensive arteries.

We examined how monocrotaline (MCT), which impairs the endothelium and causes pulmonary hypertension, altered the endothelial regulation of pulmonary artery functions. Rats were given a single injection of MCT (60 mg/kg sc). Pulmonary arteries were depolarized to -48.3 +/- 2.6 and -39.8 +/- 2.2 mV at 2 and 3 wk after treatment with MCT, respectively (control arteries -59.9 +/- 1.9 mV). The basal tone in the resting state was only slightly elevated at 3 wk in endothelium-intact arteries. Removal of the endothelium caused further depolarization in MCT-affected arteries at 2 wk, but not at 3 wk, and greatly elevated the basal tone at 2 and 3 wk. N(omega)-nitro-L-arginine (200 microM), a nitric oxide synthase inhibitor, also caused depolarization in endothelium-intact arteries in both groups and elevated the basal tone of MCT-affected arteries. The relaxant responses of pulmonary arteries to ACh and A-23187 were depressed at 2 and 3 wk after MCT treatment. Thus chronic impairment of the endothelium altered the property of the pulmonary artery leading to depolarization. During the early stage of depolarization, a rise in the basal tone was offset by nitric oxide released from the injured endothelium.

Animals↗

PubMed2000

[New regimens for the treatment of gynecologic cancers].

Until the late-1980s, combination CDDP (or CBDCA)/cyclophosphamide (CPA) and CDDP (or CBDCA)/CPA/adriamycin (ADM) were the two most common choices for treating patients with ovarian cancer. In the last several years, the identification of paclitaxel (TXL) activity in previously treated ovarian cancer patients has led to its incorporation into primary chemotherapy regimens for newly diagnosed patients. Based on prospective trials by the Gynecologic Oncology Group (GOG) and European-Canadian investigators, CDDP/TXL became the new standard regimen in 1998. Now, three randomized trials by the GOG (158), AGO, and a Dutch group comparing CDDP/TXL and carboplatin (CBDCA)/TXL are also in progress. These study groups recommended that CBDCA/TXL be used as the standard regimen in 1999 because CBDCA/TXL is less toxic, allows a better quality of life during treatment, and results in an equivalent response rate and progression-free survival. In patients with high-risk corpus cancer, clinical trials comparing platinum/TXL or platinum/ADM/TXL versus platinum/ADM are in progress. In Japan, CPT-11/CDDP has been shown to be an effective and safe regimen in patients with advanced ovarian cancer, especially clear cell carcinoma and cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[An electrosurgical burn possibly caused by radio-frequency leakage current through a stainless forceps].

A 73-year-old operated female got burned on the skin probably nipped by a stainless forceps. An active cable had been coiled around the forceps throughout the surgery. Consequently, an electrosurgical burn was possibly caused by radio-frequency leakage current (RFLC) via the metallic forceps. The authors experimentally coiled active cables around a stainless forceps, then measured RFLC produced by four kinds of electrosurgical units in the modes of cutting, blend, coagulation, spray coagulation, and argon beam coagulation. The maximum of RFLC was 81 mA, which met the JIS or IEC standard (150 mA). However, the critical current density causing electrosurgical burns (> 25-70 mA.cm-2) was suggested to be produced by RFLC through a metallic forceps with a small diameter. Of great importance is not to coil active cables around electro-conductible instruments during surgery.

Aged↗