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Biomedical subjects

S Abe

Publications and source records attributed to S Abe.

At least 235 records · Page 13Linked to original sources

Thermal preconditioning protects rat cardiac muscle cells from doxorubicin-induced apoptosis.

Doxorubicin (DOX=adriamycine), an effective chemotherapeutic agents for cancers, has severe cardiotoxicity. In the paresent study, we examined the protective effect of thermal preconditioning (TP) against apoptosis of rat cardiac muscle cells induced by DOX. Treatment with DOX (10 microM) for 24 hrs resulted in apoptosis of cardiac muscle cells, which was evaluated by examining "DNA ladder" formation and TUNEL staining. The number of TUNEL-positive cells was significantly decreased in cells subjected to TP by incubation at 42 degrees C for 30 min, 24 hrs prior to DOX-treatment. Antisense oligonucleotides of the heat shock protein (HSP) 70 blunted this effect. These results indicate that DOX-induced apoptosis in cardiac muscle cells is prevented by TP, at least in part, via a HSP70-mediated mechanism.

Animals↗

Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca2+ concentration in rat pancreatic beta-cells.

Involvement of nitric oxide (NO) in the regulation of insulin secretion from pancreatic beta-cells was investigated by measuring cytosolic Ca2+ concentration ([Ca2+]i) in isolated rat pancreatic beta-cells. At 7.0 mM glucose, L-arginine (0.1 mM) elevated [Ca2+]i in about 50% of the beta-cells examined. The response was partially inhibited by an NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMA; 0.1 mM), suggesting that part of the response was mediated by the production of NO from L-arginine. D-Arginine at higher concentrations (3 or 10 mM) also increased [Ca2+]i at 7.0 mM glucose; however, the response was not affected by L-NMA (0.1 mM). Similar [Ca2+]i elevation was produced by NO (10 nM) and sodium nitroprusside (SNP; 10 microM) at 7.0 mM glucose. The SNP-induced increase in [Ca2+]i was abolished by nicardipine (1 microM), suggesting that the [Ca2+]i response is mediated by Ca2+ influx through L-type voltage-operated Ca2+ channels. In the presence of oxyhemoglobin (1 microM), the [Ca2+]i elevation induced by NO (10 nM) was abolished. Neither degradation products of NO, NO2- nor NO3-, caused any changes in [Ca2+]i. 8-Bromo-cyclic GMP (8-Br-cGMP; 3 mM) and atrial natriuretic peptide (0.1 microM) elevated [Ca2+]i at 7.0 mM glucose. We conclude that NO, which is produced from L-arginine in pancreatic islets, facilitates glucose-induced [Ca2+]i increase via the elevation of cGMP in rat pancreatic beta-cells. NO-cGMP system may physiologically regulate insulin secretion from pancreatic beta-cells.

Animals↗

Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients?

Thromboxane (TX) A2 is an important bronchoconstrictor in the pathogenesis of asthma. Seratrodast, known as AA-2414, is a new oral TXA2 receptor antagonist which is currently prescribed in asthma therapy in Japan. However its clinical effects have been very different in individual subjects. To assess whether the clinical efficacy of TXA2 antagonist is predictable on the basis of urinary arachidonic acid metabolites in urine of patients with asthma, an open and multicentre trial was conducted. Fifty adult asthmatic subjects (women/men = 28/22) were enrolled [resting mean forced expiratory volume in 1 sec (FEV1)% was 82%; range, 50-96%]. Urinary levels of 11-dehydro-TXB2, leukotriene (LT) E4, 2,3-dinor-6-keto-prostaglandin F1alpha and creatinine in 3-h urine collected in the morning at the start of seratrodast (80 mg day(-1), once a day at evening for 4 weeks) were measured. Responders were defined by improvements of asthma symptoms score and peak expiratory flow rate (PEFR). Of the 50 subjects, 45 completed this study. Eighteen patients were responders and the other 27 were nonresponders. There were no significant differences between the two groups in patients' characteristics, baseline lung functions, treatments and baseline urinary eicosanoids. The 11-dehydro-TXB2/LTE4 ratio of responders was significantly higher (P = 0.0091) than that of non-responders (mean +/- SE, 7.49+/-0.71 vs. 5.09+/-0.67). Eleven patients out of 18 responders agreed to continue this drug for 6 months, the 11-dehydro-TXB2/LTE4 ratio decreased during this period, but not significantly. Our data demonstrated that responders and non-responders to TXA2 receptor antagonist existed in patients with asthma, and it suggests that the ratio of urinary eicosanoids might be a possible predictor of the effects of TXA2 receptor antagonist.

6-Ketoprostaglandin F1 alpha↗

Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma.

Vascular endothelial growth factor (VEGF) is a major angiogenic factor. Osteosarcoma is characterised by hypervascularity and metastatic potential. We examined VEGF mRNA expression, VEGF isoform pattern and VEGF receptor (flt-1 and KDR) by RT-PCR analysis in 30 osteosarcomas. All 30 osteosarcomas expressed VEGF mRNA. 17 osteosarcomas (57%) expressed flt-1 mRNA, whilst 20 (67%) expressed KDR mRNA. 6/30 (20%) osteosarcomas were positive for VEGF121 only, 8 (27%) for VEGF121 + VEGF165, and 16 (53%) for VEGF121 + VEGF165 + VEGF189. Patients with osteosarcomas with VEGF165 (n = 24) had significantly poorer prognosis in comparison with those without VEGF165 (P = 0.022, Wilcoxon's test). The osteosarcomas with VEGF165 had significantly increased vascularity assessed on sections immunostained for CD34 (P < 0.001, Mann-Whitney U test). Although VEGF165 is a soluble isoform, it is also retained on the cellular surface. These results suggest that cell-retained VEGF isoforms (VEGF165, VEGF189) might be essential for neovascularisation in osteosarcoma, whilst the soluble VEGF121 isoform is not sufficient to stimulate neovascularisation in this type of neoplasm.

Adult↗

Differentiation of Z and W chromosomes revealed by replication banding and FISH mapping of sex-chromosome-linked DNA markers in the cassowary (Aves, Ratitae).

We identified sex chromosomes of the double-wattled cassowary (Casuarius casuarius) by a replication banding method. The acrocentric Z chromosome, the fifth largest pair in males and slightly smaller W chromosome show no sign of heterochromatinization and share a nearly identical banding pattern in the distal half of the long arm. These chromosomes were further characterized by FISH with three probes linked either to Z or W chromosome in most avian species examined thus far. Contrary to the situation in the chicken, we obtained positive signals with Z-specific ZOV3 and W-specific EEO.6 in the distal region of both Z and W chromosomes. However, IREBP signals localized to the proximal half of the Z chromosome were not detected on the W chromosome. Thus, structural rearrangements such as deletions and inversions might have been the initial step of W chromosome differentiation from an ancestral homomorphic pair in this species.

Animals↗

Effects of chronic administration of interferon alpha A/D on serotonergic receptors in rat brain.

The effects of chronic administration of interferon (IFN; recombinant human IFN-alphaA/D) on serotonergic binding sites in rat brain were investigated. IFN was injected daily for 2 weeks at a dose of 100000 I.U./kg, (i.p.) in male Wistar rats. IFN did not alter either [3H]ketanserin binding to 5-HT2A receptors or [3H]paroxetine binding to 5-HT transporters. Scatchard analysis of [3H]8-hydroxy-dipropylaminotetraline (8-OH-DPAT) binding to 5-HT1A receptors demonstrated the presence of high- and low-affinity binding sites in both treatment and control groups. IFN significantly increased both Kd and Bmax measures of [3H]8-OH-DPAT binding at low-affinity binding sites, but not at the high-affinity sites. These results suggest that IFN affects the low-affinity 5-HT1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Leukotriene (LT)-receptor antagonist is more effective in asthmatic patients with a low baseline ratio of urinary LTE4 to 2,3-dinor-6-keto-prostaglandin (PG)F1alpha.

BACKGROUND: To test the hypothesis that urinary levels of arachidonic acid metabolites may be a predicting factor of the effects of pranlukast, a selective leukotriene (LT) antagonist, on chronic adult asthma, we investigated the relationship between its clinical efficacy and urinary eicosanoid levels. METHODS: An open, multicenter trial was conducted involving 38 stable moderate and severe asthmatic patients (mean percent predicted FEV1 was 71%). All patients received pranlukast (225 mg twice daily) for 4 weeks after a 2-week run-in period. Urinary levels of LTE4, 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha, and creatinine were measured in 3-h urine collected on day 1 of the treatment. The responder was defined by an improvement of asthma symptom scores and peak expiratory flow rate (PEFR). RESULTS: One patient was excluded because of an adverse effect, nausea. Thirteen out of 37 subjects were responders and 24 were nonresponders. There were no significant differences in patients' backgrounds and urinary arachidonate levels between the two groups. The urinary LTE4 to 2,3-dinor-6-keto-PGF1alpha ratio in the responder was significantly lower (P=0.01) than that in the nonresponder. In all patients, a significant inverse correlation was revealed between the baseline urinary LTE4/2,3-dinor-6-keto-PGF1alpha ratio and the improvement of PEFR in the morning (r=-0.43, P=0.007). CONCLUSIONS: These data suggested that the urinary ratio of LTE4 to 2,3-dinor-6-keto-PGF1alpha might be one of the predictive markers of the clinical efficacy of this LT-receptor antagonist in asthmatic subjects.

Adult↗

Dog-bite injuries to the breast in children: deformities to secondary sex characteristics and their repair in an extended follow-up.

Injuries from dog bites are not uncommon among children. However, the site of the wound is rarely on the breast. The authors report two cases of nipple-areolar injuries caused by dog bites. The affected children were followed during the development of secondary sex characteristics. In one child, this follow-up period was more than 10 years. In treating such wounds to the breast, subsequent growth of the nipple-areolar complex should be considered, particularly in girls because of the area's importance as a secondary sex characteristic.

Animals↗

Influence of treated blood pressure on progression of silent cerebral infarction.

PURPOSE AND METHODS: To examine whether treatment for hypertensive patients prevents the progression of cerebral infarction, we performed magnetic resonance imaging (MRI) repeatedly at mean intervals of 22 months on 117 Japanese subjects aged 65-89 (mean 74 years), including 84 hypertensive patients. The patients were given various anti-hypertensive agents, and the blood pressure of each patient was monitored periodically during the observation period. Depending on the average blood pressure at the end of the follow-up period, hypertensive patients were classified into three subgroups: normotension (N), borderline (B) and hypertension (H). None had a prior history of symptomatic cerebral infarction and neurological abnormalities. The number of infarcted lesions were determined on brain MRI by two independent observers. RESULTS: Silent cerebral infarction (SCI) lesions were observed in 42 hypertensive subjects (50.0%) and in eight control subjects (24.2%) on enrollment. The numbers of SCI lesions increased in 33 hypertensive subjects (39.3%) and three control subjects (9.1%) during the observation period. In the hypertensive subjects, an increased number of infarcted lesions was found in six of 28 subjects in group N (21.4%), 17 of 44 in group B (38.6%), and 10 of 12 in group H (83.3%). Thus, blood pressure controlled to the normal level appears to result in a lower incidence of progression of infarcted areas in patients with hypertension (N versus H, P < 0.001). CONCLUSION: Our data indicate that an appropriate anti-hypertensive treatment reduces the risk of a cerebrovascular accident in hypertensive patients.

Aged↗

The available period and kind of exercise for increasing osteo sono assessment index in women.

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.

Adult↗

Elastofibroma dorsi: CT, MRI, and pathologic findings.

We report two cases of elastofibroma dorsi and discuss the CT and MR findings and histopathology of these tumors. Increased awareness of the characteristic MR patterns should lead to reduced misdiagnosis of such lesions as malignant and prevent unnecessary wide excision.

Female↗

Evaluation of an enzyme-linked immunosorbent assay based on binding inhibition for type-specific quantification of poliovirus neutralization-relevant antibodies.

To detect neutralization-relevant antibodies against 3 types of poliovirus (PV) without using tissue cultures and live viruses, an enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody-binding inhibition was evaluated using sera from 80 vaccinated Japanese children and 60 Pakistani poliomyelitis patients. Compared with the neutralization test, the sensitivity of the inhibition ELISA was 100% (111/111) for detection of anti-PV1 antibody, 98.3% (118/120) for anti-PV2, and 96.5% (82/85) for anti-PV3, and the specificity was 93.1% (27/29), 100% (20/20), and 92.7% (51/55), respectively. Thus, the inhibition ELISA showed excellent potential as a seroepidemiologic tool in both vaccinated and naturally-infected populations.

Animals↗

Effective inhibition of Candida albicans growth by the combination of murine peritoneal neutrophils and activated macrophages.

The effect of leukocytes on the anti-Candida activity of neutrophils was examined. Murine neutrophils which were purified from casein-induced peritoneal cells inhibited the mycelial growth of Candida albicans. This anti-Candida activity of neutrophils was augmented by the addition of spleen cells prepared from mice pretreated with bacterial lipopolysaccharide 3 hr before, but not from non-treated mice. The population in the spleen cells, which enhanced the anti-Candida activity of neutrophils, was plastic-plate adherent, nylon-fiber columns adherent and anti-Mac-1 antigen-positive. These immunological profiles suggested that the enhancing cells are classified to splenic macrophages. Peritoneal-exudated macrophages from mice treated with lipopolysaccharide also augmented the anti-Candida activity of neutrophils. These results suggest that the anti-Candida activity of neutrophils may be upregulated by activated macrophages.

Animals↗

Enhancement of cisplatin sensitivity in high mobility group 2 cDNA-transfected human lung cancer cells.

To elucidate the role of high mobility group 2 protein (HMG2) in cis-diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2-transfected human non-small cell lung cancer cell line, PC-14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC-14 and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in the extracts of PC-14 and PC-14/CMV. This complex formation was subject to competition by CDDP-treated non-specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum content of PC-14/HMG2 after exposure to 300 microM CDDP was 1.1 and 1.5 times that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross-links determined by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.

Carboplatin↗

A case of granulocyte-colony stimulating factor producing gallbladder cancer.

Ever since the identification of the colony-stimulating factor (CSF), granulocyte-CSF (G-CSF)-producing tumors have often been reported, and have been attracting attention, especially in pulmonary cancer. However, there have been only a small number of reports of G-CSF-producing tumors in cases of gastrointestinal cancer, and only four cases of G-CSF-producing gallbladder cancer have been reported so far. Recently, we encountered a 73-yr-old man with G-CSF-producing gallbladder cancer. The leukocyte count in the peripheral blood increased to the maximum of 75,200/mm3 during the course of observation, and mature neutrophils accounted for 97% (segmented forms: 89%, band forms: 8%). The serum G-CSF concentration was high (129 pg/ml). The leukocyte count became normalized postoperatively, and the serum G-CSF concentration also decreased (50 pg/ml). The tumor was diagnosed as undifferentiated adenocarcinoma of the pleomorphic type on the histopathologic examination. Numerous tumor cells were stained with the anti-G-CSF antibody. Detailed findings of the patient are presented here together with some discussion of the literature.

Adenocarcinoma↗

Ribosomal RNA gene loci and silver-stained nucleolar organizer regions associated with heterochromatin in Alaskan char Salvelinus malma and chum salmon Oncorhynchus keta.

Nucleolus-forming 5.8S, 18S and 28S ribosomal RNA gene (rDNA) loci were assigned by fluorescence in situ hybridization (FISH) to the distal half of the short arms of a large-sized submetacentric pair in the Alaskan char (Salvelinus malma) and to the distal region of the long arms of a medium-sized submetacentric pair in the chum salmon (Oncorhynchus keta), respectively. In each species, heteromorphic FISH signals, spanning whole satellite region and secondary constriction, imply an intraspecific variation in the size of rDNA loci. Size variation of silver-stained nucleolar organizer regions (AgNORs) was also apparent between or within the assigned rDNA loci in each species, suggesting a possible inter- or intralocus inactivation of rDNAs. C-band positivity of assigned rDNA loci and AgNORs unequivocally showed their association with heterochromatin in these species.

Animals↗

Synchrotron microangiography reveals configurational changes and to-and-fro flow in intramyocardial vessels.

In 8 dogs, in situ microangiography using synchrotron radiation visualized penetrating transmural arteries (PTAs) with a diameter of >60 micrometers and allowed quantitation of vessel diameters of >140 micrometers. Myocardial contraction reduced the vascular short-axial diameters to 87 +/- 17% (n = 62, P < 0.001, paired t-test) of the end-diastolic values and increased the longitudinal dimension to 129 +/- 5% (n = 45, P < 0.001). The diameter reduction in the subendocardial PTA segments was significantly more marked than that in the subepicardial PTA segments (60 +/- 12 vs. 88 +/- 12%, n=13, P < 0.001, paired t-test). Intracoronary administration of dobutamine (0.1 micrograms. kg-1. min-1) increased, and in contrast, partial clamping of the coronary artery (ischemia) decreased, the configurational changes. To-and-fro blood flow was clearly observed in PTAs with visual identification of capacitive backflow, resistive forward flow during ischemia on coronary arteriography, and even under baseline conditions in coronary venography. Thus this method advances our understanding of mechanical influences on the coronary circulation.

Animals↗