[Boutonneuse fever].
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Anti-Bacterial Agents↗
Biomedical subjects
S Abe
Publications and source records attributed to S Abe.
Molecular characterization of the genomic breakpoint junction in a t(11;22) translocation in Ewing sarcoma.
Polymerase chain reaction (PCR)-based nucleotide sequence analysis was performed in 12 cases of Ewing sarcoma on the cDNA and/or genomic DNA breakpoint regions of a t(11;22)(q24;q12), which joins the EWS gene located on chromosome 22 with the FLI1 gene located on chromosome 11, in order to understand the molecular mechanism of this translocation. Reverse transcriptase-PCR on total tumor cell RNA from the examined cases showed five types of EWS-FLI1 chimeric product, resulting from various junctions between EWS exon 7 or 10 with FLI1 exon 5, 6, or 8. Sequencing of the genomic fusion junctions of EWS-FLI1 in seven cases showing three types of the chimeric cDNA products revealed that most of the breakpoint junctions shared common nucleotide(s) from both genes, and that the breakpoints in EWS introns 7 and 10 clustered within 100 bp and 300 bp, respectively. All the junctions were found to be flanked by various oligomers, among which a consensus sequence, 5'-AGAAAARDRR-3', was found near the breakpoints of both genes in four cases, suggesting that these oligomers may have a functional significance in the genesis of t(11;22). In addition to these oligomers, sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage sites were located near, or flanked, or even encompassed, the breakpoints in most of the cases examined. Thus, these sequences may also mediate DNA double-strand breakage and rejoining to generate the t(11;22). Genomic sequence analysis of both EWS-FLI1 and FLI1-EWS chimeric genes in three of the seven cases demonstrated a deletion and duplication of both EWS and FLI1 sequences in two cases and no gain or loss in one case. The present findings suggest that multiple mechanisms may be operative for the break and rejoining of the fragments of chromosomes 11 and 22 in the genesis of t(11;22), and that some of these translocations are asymmetric at the molecular level.
Adolescent↗
[Percutaneous transluminal septal ablation with ethanol in hypertrophic obstructive cardiomyopathy: a case report].
A 48-year-old man with hypertrophic obstructive cardiomyopathy was treated by nonsurgical septal ablation. He had previously received medical treatment using atenolol and verapamil, but severe symptoms of chest discomfort, dyspnea, and shortness of breath had persisted for 2 years. Under coronary angiography control, the first major septal branch of the anterior descending coronary artery was catheterized with a 2.0 mm coaxial percutaneous transluminal coronary angioplasty balloon catheter. After inflation of the balloon, 1.5 ml of absolute alcohol was slowly injected into the septal artery to induce a small septal infarction. The left ventricular outflow pressure gradient was decreased from 108 before to 30 mmHg after the procedure as measured by Doppler echocardiography. His chest symptom improved from New York Heart Association class III to II and left ventricular outflow gradient was maintained at 0 mmHg (at rest) at 3 months after treatment. This is a new, less invasive treatment using catheterization instead of surgical myectomy. The indication, complication, and long-term effect of the treatment must be carefully evaluated, but this is expected to become a useful method.
Angioplasty, Balloon, Coronary↗
[Detection size dependence of field factor for narrow beam].
An absorbed dose in the narrow beam is calculated based on the depth dose distribution and a field factor. The field factor has to be measured with especially high accuracy because it is highly variable. The field factor was calculated when detection size was changed, by using Monte Carlo simulation, which had no energy dependency or geometrical error. Then the relation between field factor and detection size in the narrow beam was investigated. An absorbed dose in peak depth and reference depth according to detection size was calculated for each field size. Detection size dependency was recognized in the case of measuring a field factor, because the absorbed dose tended to decrease as detection size increased. The absorbed dose in the narrow beam has to be calculated within a change of +/- 2%. The change in peak depth according to detection size was eliminated, and then the relation between an absorbed dose at the ideal detection size of 0 mm phi by extrapolation and detection size which has a deference of 2% from it, were acquired. In addition, the maximum usable detection size was estimated in the case of measuring the field factor.
Models, Theoretical↗
Deletion of the Sry region on the Y chromosome detected in a case of equine gonadal hypoplasia (XY female) with abnormal hormonal profiles.
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Animals↗
[Cytokines and surfactant as a factor of onset and progression of COPD].
Cigarette smoking is a most important factor of COPD. IL-8 is elevated by cigarette smoking and increases the number of neutrophils in the lung. Surfactant is a complex mixture of phospholipids (PL) and proteins (SP). Both PL and SPs (SP-A and SP-D) decrease in bronchoalveolar lavage fluid in smokers. Decrease of PL enhances injury by elastase secreted from neutrophils and induces collapse of bronchioles, and decrease of SP-A and SP-D attenuate the defense against microbial agents in peripheral airways. Surfactant is thereby associated with COPD. However, little is known about the interaction, which induces COPD, between cytokines and surfactant. Further investigations are needed to clarify the mechanism on onset of COPD.
Disease Progression↗
Role of human CYP2B6 in S-mephobarbital N-demethylation.
The role of cytochrome P-450s (CYPs) in S-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbital N-demethylation. The apparent K(m) values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 microM). The N-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920, p<.001). Orphenadrine (300 microM), a CYP2B6 inhibitor, inhibited the N-demethylase activity of S-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes.
Anticonvulsants↗
[Compensatory increases in residual lobar volume following lung resection].
To investigate compensatory increases in residual lobar volume after lobectomy and pneumonectomy, we measured lung lobar volumes on the basis of pre- and postoperative computed tomographic (CT) images obtained on 40 patients (11 right upper, 7 right lower, 10 left upper, 8 left lower lobectomies and 4 left pneumonectomies). A personal computer image processing program was utilized to calculate lung lobar volumes from sequential CT images. Decreases in whole lung volume after lung resection averaged from 7.4% to 9.5% of preoperative whole lung volume in the lobectomy patients, and 30% in the patients who underwent left pneumonectomy. Those values were much smaller than the volumes of resected lobe, as measured on the basis of preoperative CT images. Increased residual lobar volume after lung resection averaged from 11% to 15% of preoperative whole lung volume in both the lobectomy and left pneumonectomy patient groups. Residual lobes compensated for approximately 60% of the resected lobar volume in the lobectomy patients, but only about 30% of resected lung volume in the left pneumonectomy patients. Increases in residual lobar volume tended to be larger in patients who underwent upper lobectomies, and on the operative side in patients other than those who underwent left lower lobectomies. We concluded that compensatory increases in residual lobar volume should be taken into full consideration when making predictions about postoperative pulmonary function.
Adult↗
[Antineoplastic effect of novel agents, UCN-01 on human tumor cells transplanted in nude mice].
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Alkaloids↗
[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome].
A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.
Autoantibodies↗
The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy.
BACKGROUND: To clarify the contribution of P-glycoprotein (P-GP) to drug resistance of gastric cancer, the correlation between chemosensitivity of the tumor and expression of P-GP was examined using human gastric cancer xenografts in nude mice. METHODS: Two strains, P-GP-positive and -negative, were established using primary explants from patients who had not received chemotherapy. Their stable growth was obtained by serial passages as subcutaneous tumors in nude mice. Mitomycin C (MMC, 3.25 mg/kg), adriamycin (ADR, 6mg/kg), or cisplatin (CDDP, 6mg/kg) was administered intraperitoneally once a week for 3 weeks. RESULTS: In the P-GP-negative strain, all three drugs significantly suppressed the tumor growth, while in the P-GP-positive strain, only MMC did so. However, the growth inhibition of MMC was apparently greater in the P-GP-negative strain than in the positive tumor. The expressions of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), and p53 were not different between the strains. Bcl-2 was expressed only in the P-GP-negative strain. Induction of P-GP expression was observed in some specimens after treatment with MMC and with CDDP. CONCLUSIONS: P-GP might affect inherent and acquired resistance against chemotherapeutic agents in gastric cancer.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Polymorphic microsatellite DNA markers in the field vole Microtus montebelli.
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Animals↗
[Outbreak of diarrhea due to SRSV infection].
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Adult↗
Differential regulation of mouse uncoupling proteins among brown adipose tissue, white adipose tissue, and skeletal muscle in chronic beta 3 adrenergic receptor agonist treatment.
Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters that dissipate the proton gradient, releasing stored energy as heat, without coupling to other energy-consuming processes. Therefore, the UCPs are thought to be important determinants of the metabolic efficiency. To elucidate relationships between the UCPs expressions and insulin sensitivity improvement, we treated KK-Ay mice with beta 3 adrenergic receptor agonist for 21 days and examined the changes of the UCPs mRNA expressions in various tissues. Chronic treatment of a specific beta 3 adrenergic receptor agonist, CL316,243 (0.2 mg/kg body weight/day s.c.) markedly increased the expressions of uncoupling protein 1 (UCP1), uncoupling protein 2 (UCP2), and uncoupling protein 3 (UCP3) by 14-fold, 6-fold, and 16-fold, respectively, in the brown adipose tissue (BAT). The UCP1 and UCP3 mRNA expressions in the white adipose tissue (WAT) were also increased by 12-fold and 9-fold, respectively, but the UCP2 mRNA expression was not changed in this tissue. Interestingly, the UCP2 and UCP3 mRNA expressions were strikingly decreased in the skeletal muscle and heart. Particularly, the UCP3 mRNA expression level in the skeletal muscle was dropped to 10% of that of the saline-treated control mice, indicating that the UCPs mRNA expressions are regulated in tissue-specific ways. The concentrations of plasma insulin and circulating free fatty acid (FFA) were significantly decreased, suggesting that they correlate with the reductions of the UCP2 and UCP3 mRNA expressions in the skeletal muscle and heart. It has been thought that the UCP1 and UCP3 mRNA expressions in the BAT and WAT are mainly controlled by the hypothalamus via the sympathetic nervous system, while the levels of insulin, FFA or both may play important roles in the control of the UCP2 and UCP3 mRNA expressions in the skeletal muscle an heart.
Adipose Tissue↗
The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats.
The mechanisms responsible for myocardial injury and cell death in myocarditis are still unclear. We examined whether myocardial cell death occurs via apoptosis in myosin-induced autoimmune myocarditis in rats and whether the Fas/Fas ligand (FasL) system plays a role in this apoptosis. On days 14, 17, 21, and 35 after immunization with porcine heart myosin, some cardiomyocytes and infiltrating lymphocytes were found to be apoptotic on in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay, but none was on day 60 and in control rats. Apoptotic indices peaked at day 17, and laddering of genomic DNA from the affected myocardium was observed on days 17 and 21 on agarose gel electrophoresis. The expression of Fas mRNA and protein was detected on days 17 and 21 in some cardiomyocytes and infiltrating lymphocytes by Northern blot analysis and immunohistochemistry, respectively. In addition, FasL was detected in some infiltrating lymphocytes on days 14, 17, and 21 by both in situ hybridization and immunostaining, and FasL-positive lymphocytes were mainly CD4+ cells. Some rats were injected with anti-Fas Ab (0.1 mg/kg) or anti-FasL Ab (0.1 mg/kg), and subsequently, inflammatory lesions exhibited less severe than did untreated rats with myocarditis. These findings suggest that cell death via apoptosis of cardiomyocytes and lymphocytes is one of the mechanisms of myocardial injury in autoimmune myocarditis, and that the Fas/FasL system might play a role in the induction of this apoptosis.
Acute Disease↗
Detection of human seminal gamma-glutamyl transpeptidase in stains using sandwich ELISA.
A sensitive and specific sandwich ELISA for human seminal gamma-glutamyl transpeptidase (gamma-GTP) was developed using a combination of monoclonal antibodies. SG1 and SG3, which we produced. For semen identification in forensic samples, we modified the assay so as to be more sensitive and to establish efficient extracting conditions. After testing the extracting abilities of several detergents, CHAPS and deoxy-BIGCHAP were chosen as the solubilizer. Polystyrene beads coated with SG1 were incubated with samples extracted by the detergents, and further with biotinylated SG3, followed by peroxidase-labeled streptavidin. gamma-GTP was detected only in seminal samples. The sensitivity of this assay was 0.01 ng/ml of seminal gamma-GTP equivalent to 10(7) times diluted semen, which was ten times as compared with the previous plate assay. No significant seminal gamma-GTP was detected in other biological stains such as blood, saliva and vaginal smear. The extract of a 500 fold diluted seminal stain, 8 months old, showed the detection limit. Seminal gamma-GTP was detectable even in 14-year-old stains.
Antibodies, Monoclonal↗
Enhanced anti-Candida activity of neutrophils and azole antifungal agents in the presence of lactoferrin-related compounds.
We investigated the effects of lactoferrin (Lf)-related compounds on growth inhibition of Candida albicans by neutrophils or antifungal agents in vitro. Human neutrophils partially inhibited the growth of C.albicans. The growth inhibition caused by human neutrophils was augmented by the addition of human Lf at concentrations which did not show any inhibitory effect in the absence of neutrophils. Similar observations were obtained also with the following combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and murine neutrophils + iron saturated bovine Lf, but not in the case of murine neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide "lactoferricin B" (Lfcin B). Other types of antifungal agents, amphotericin B, nystatin, and flucytosine did not show such combined effects with these Lf-related compounds. The anti-Candida activity of bovine Lf or Lfcin B in combination with clotrimazole was shown to be synergistic by checkerboard analysis. Clinically isolated azole-resistant C. albicans strains were more susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing growth of an azole-resistant strain in the presence of fluconazole was reduced by the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest that Lf-related compounds even at relatively low concentrations may function as an antifungal effector in combination with neutrophils thereby modulating azole antifungal efficacies in vivo.
Animals↗
BAL surfactant protein A and Clara cell 10-kDa protein levels in healthy subjects.
Lung surfactant protein A (SP-A) and Clara cell 10-kDa protein (CC10) are the most abundant proteins produced locally in the lower respiratory tract, as assessed in bronchoalveolar lavage (BAL) analysis. However, it is not known what factors influence SP-A and CC10 levels in BAL fluids, and the relationship between SP-A and CC10 levels in BAL fluids has been unclear. We measured SP-A and CC10 concentrations in BAL fluids from 11 healthy nonsmokers and 12 healthy smokers by enzyme-linked immunosorbent assays using specific antibodies. Mean SP-A and CC10 levels in BAL fluids of healthy smokers were significantly lower than those of healthy nonsmokers. SP-A values correlated significantly with CC10 and phospholipid values in BAL fluids. On BAL examinations using three 50-ml aliquots, the mean SP-A level in the second lavage was 2.0-fold and 2.4-fold, respectively, of that in the first and third lavages, and the mean CC10 level in the first lavage was 5.0-fold and 5.6-fold, respectively, of that in the second and third lavages. We conclude that BAL fluid SP-A and CC10 levels are influenced by the BAL methods and by cigarette smoking. There is a significant positive correlation between SP-A and CC10 values in BAL fluids of healthy subjects.
Adult↗