Search PubMed⌕ Search

Biomedical subjects

S Kawamoto

Publications and source records attributed to S Kawamoto.

At least 163 records · Page 9Linked to original sources
PubMed1997

[Analysis of induction of MDR1 gene expression by anticancer chemotherapy in bladder cancer].

Using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based quantitative analysis method, we investigated MDR1 mRNA expression levels in 58 bladder cancer specimens to determine whether MDR1 gene expression was induced or enhanced in bladder cancers during chemotherapy. In bladder cancer specimens which were obtained from patients treated with anticancer drugs, significantly higher expression levels of MDR1 mRNA were observed than in those from patients not treated with any anticancer drugs (p = 0.0134, Mann-Whitney U test). From 14 patients who had bladder cancer, clinical specimens were obtained before and after neoadjuvant intra-arterial chemotherapy. The expression levels of MDR1 mRNA were significantly higher in the post-treatment specimens than in the pre-treatment specimens (p = 0.0298, Wilcoxon signed-rank test). Of these 14 patients, 7 patients exhibited increased levels of MDR1 mRNA expression after chemotherapy. In 6 patients, there were no changes in the MDR1 mRNA expression levels before and after chemotherapy. Only one patient exhibited decreased levels of MDR1 mRNA expression after chemotherapy. No significant correlations were observed, between MDR1 mRNA expression levels and effect of the chemotherapy determined microscopically, dosage of anticancer drugs, or patient outcome. In conclusion, this study indicates that MDR1 gene expression in bladder cancers is induced and enhanced during chemotherapy. This overexpression of the MDR1 gene may contribute to resistance to anticancer drugs after repeated chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Cytokeratin 8 and 19 as antigens recognized by adenocarcinoma-reactive human monoclonal antibody AE6F4.

The human monoclonal antibody (MAb) AE6F4 is secreted by a human-human hybridoma line established from the in vitro immunization of normal human peripheral blood lymphocytes with the human lung adenocarcinoma cell line, A549. This MAb is strongly reactive to lung cancer tissues. In the previous study, the antigens recognized by the MAb AE6F4 were purified from A549 cells and identified as 14-3-3 protein and 31 kDa cytosolic phospholipase A2 (cPLA2). The MAb AE6F4 also binds two kinds of antigens (53 kDa and 40 kDa), which are not related to 14-3-3 protein or 31 kDa cPLA2, in the human breast adenocarcinoma cell line, MCF-7. We purified a 38 kDa antigen, which is a degradation product of 53 kDa antigen from breast adenocarcinoma MCF-7 cells using ion-exchange and hydroxyapatite column chromatography. Two partial amino acid sequences of the purified 38 kDa antigen showed 95-100% homology to human cytokeratin 8 (CK8). Two-dimensional gel electrophoresis and immunoblot analysis of intermediate filament fraction separated from MCF-7 cells demonstrated that the 53 kDa and 40 kDa antigens were CK8 and CK19, respectively. Antigenic determinants on CK8 and CK19 recognized by the MAb AE6F4 were resistant to sodium periodate treatment, although antigenic determinant on 31 kDa antigen (14-3-3 protein and(or) cPLA2) was sensitive to this treatment. These results suggest that the MAb AE6F4 reacts with both carbohydrate and peptide antigenic determinants.

Adenocarcinoma↗
PubMed1997

[A case of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica].

We describe the first case, to the best of our knowledge, of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica (PMR). A 50-year-old woman was admitted with a dry cough and a bilateral basilar reticulonodular shadows on chest X-ray. Bronchoalveolar lavage fluid analysis revealed lymphocytosis and a decreased CD4/CD8 ratio. A thoracoscopic lung biopsy specimen showed evidence of non-specific interstitial pneumonia. During her clinical course, she began suffering from psoriasis vulgaris and polymyalgia rheumatica. Corticosteroid therapy had no effect, but maintained a stable condition during a follow-up period of 4 years.

Female↗
PubMed1996

Expression profiles of active genes in human and mouse livers.

An expression profile of active genes in the human liver was obtained by collecting sequences with a 3'-directed cDNA library that faithfully represents composition of the mRNA population. The results show the relative activity of ca. 600 genes in maintaining the hepatocytes and sustaining their liver-specific phenotypes. The most active group of genes are those for the production of plasma proteins, followed by the genes for the synthesis of lipoproteins, protease inhibitors, coagulation factors, and complements. This balance of gene activity was maintained for four independently obtained expression profiles from human livers, including those of adult and fetus. The expression profiling was extended to the liver of adult mouse, used as a model for the molecular etiology of hepatocytes and for examining the effects of drugs. Subtle biological differences between the human and mouse livers are reflected in the global expression profiles of active genes, especially with regard to the synthesis of plasma proteins, lipoproteins and complements. This comparative analysis using expression profiling should find a wide application in comparative biology.

Adult↗
PubMed1996

Purification and characterization of LasR as a DNA-binding protein.

In Pseudomonas aeruginosa, the activator protein LasR and a cognate autoinducer (AI) are required for expression of the elastase gene (lasB). In the present study, we investigated the binding properties of the P. aeruginosa lasR gene product. The LasR protein was overexpressed and purified as a glutathione S-transferase (GST) fusion protein. Using gel retardation and UV cross-linking analysis, we demonstrated that the GST-LasR could bind to a separate site in the lasB upstream operator regions 1 and 3 in the presence of the autoinducer. Regions 1 and 3 are located at 105 and 42 base pairs upstream, respectively, from the lasB transcriptional start site. Our present results clearly demonstrate that LasR is a specific DNA-binding protein that regulates the transcription of the lasB gene in the presence of an autoinducer.

4-Butyrolactone↗
PubMed1996

Neuron-specific alternative splicing of nonmuscle myosin II heavy chain-B pre-mRNA requires a cis-acting intron sequence.

In addition to the ubiquitously expressed form of nonmuscle myosin II heavy chain-B (MHC-B), the existence of a neuron-specific MHC-B isoform, which contains a 30-nucleotide inserted sequence near the ATP binding region, has been reported (Takahashi, M., Kawamoto, S., and Adelstein, R. S.(1992) J. Biol. Chem. 267, 17864-17871). In this study, the genomic location of the neuron-specific inserted 30-nucleotide sequence found in the cDNA is determined to be a single cassette type exon, N30, in the human nonmuscle MHC-B gene. Inclusion or exclusion of exon N30 is cell type-specific, with inclusion being restricted to neuronal cells and being regulated during cell differentiation. Expression of a minigene construct that contains the alternative exon N30 along with the flanking introns and exons was studied in human neuronal retinoblastoma Y79 cells. Inclusion of the N30 exon in the mRNA from the transfected minigene occurs in differentiated Y79 cells that have been treated with butyrate but not in the undifferentiated Y79 cells and non-neuronal cell lines. Systematic deletion and mutation analysis of the minigene construct established that neuron-specific N30 exon recognition requires a cis-acting RNA sequence located approximately 1.5 kilobases downstream of the N30 exon.

Alternative Splicing↗
PubMed1996

Genetic control of in vivo tumor necrosis factor production in mice.

We report on the genetic effect on in vivo production of tumor necrosis factor (TNF)-alpha induced by lipopolysaccharides (LPS) using various congenic mouse strains. B10.A, Bl0.A(3R), B10.AQR, B10.A(5R), and B10.S(7R) produced significantly high TNF-alpha compared with B10.BR, B10.S, C57BL/10, B10.A(2R), B10.A(4R), B10.G, B10.DA(80NS), and B10.RIII(71NS). This suggests that LPS-induced TNF-alpha production is genetically controlled by H-2. Mice with the same alleles on K, A, E, or S loci produced various (high or low) levels of TNF-alpha, thus indicating that regulatory genes are located outside these loci. All strains with H-2Dd produced significantly high levels of TNF-alpha, but strains with other alleles in the H-2D locus produced low levels. Thus, TNF-alpha production appears to be genetically linked to H-2D itself or H-2D linked genes and the allele d is linked to a high responder gene. This was the case with the A background. C3H/HeN (H-2k), however, showed a high TNF-alpha production, suggesting the presence of another controlling gene outside H-2. In addition, high TNF-alpha productivity was transmitted into F1 mice (B10.A X B10.BR) in a dominant fashion. Both LPS-stimulated and unstimulated TNF-alpha mRNA expression in splenic macrophages were enhanced in high responder strains. Thus, we conclude that TNF-alpha production is closely related to genes within or linked to the H-2D locus as well as others outside H-2.

Animals↗
PubMed1996

Resolution of cirrhosis-related pulmonary shunting in two children with a transplanted liver.

We treated two children with hypoxemia caused by intrapulmonary shunting associated with cirrhosis secondary to extrahepatic biliary atresia. Following orthotopic liver transplantation, digital clubbing and intrapulmonary shunting were resolved, as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction, and perfusion lung scanning with 99mTc-labeled macroaggregates of albumin. We recommend that early liver transplantation be considered for young subjects with a severe hepatopulmonary syndrome.

Biliary Atresia↗
PubMed1996

Primary cavernous sinus malignant lymphoma treated by gamma knife radiosurgery: case report and review of the literature.

BACKGROUND: Malignant lymphomas originating primarily in the cavernous sinus have not been histologically verified by any authors. The first reported case to our knowledge of primary cavernous sinus malignant lymphoma, initially diagnosed as benign meningioma and treated by gamma knife radiosurgery, is presented. CASE DESCRIPTION: The patient was a 77-year-old man whose initial symptoms were left facial hypesthesia and diplopia on left gaze. During the 21-month follow-up period after gamma knife radiosurgery, no evidence of tumor regrowth was seen in the irradiated area, but an unirradiated mass expanded with invasion of the brain stem. Subsequent surgery provided histologic verification of the diagnosis. Despite successful local tumor control, the patient died due to sepsis 31 months after the onset of symptoms. Autopsy failed to disclose any remaining lymphoma cells either in the primary lesion or anywhere throughout the entire body. CONCLUSION: Primary cavernous sinus malignant lymphoma is an extremely rare brain tumor, but it must be considered in the differential diagnosis of an enhanced mass in the cavernous sinus. Stereotactic radiosurgery using the gamma knife technique for intracranial brain tumors, especially in the cavernous sinus, is associated with risk, as was seen in our patient. Our experience points out the pitfalls of gamma knife radiosurgery; it should be performed only after histologic confirmation has been obtained.

Aged↗
PubMed1996

Detection of low-level expression of P-glycoprotein in ACHN renal adenocarcinoma cells.

A highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay and a flow cytometric assay were used to examine ACHN cells for the expression of P-glycoprotein. The expression of P-glycoprotein was detected at the RNA and protein levels in ACHN cells by RT-PCR and flow cytometry, respectively. However, it was below the limit of detection by immunoblotting. The intracellular accumulation of adriamycin in ACHN cells was enhanced by verapamil, cyclosporin A and medroxyprogesterone acetate. Therefore, this study has demonstrated that low-level expression of P-glycoprotein detectable only by RT-PCR and flow cytometry plays a significant role in reducing the intracellular concentration of antitumor agents and thus contributes to the multidrug-resistant phenotype of ACHN cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Significance of IL-1beta and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB).

We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The number of neutrophils in BALF obtained from DPB patients was significantly higher than that of healthy volunteers. Treatment with erythromycin (600 mg/day for 12.9+/-9.5 months (mean +/- s.d.)) significantly reduced the total number of cells and neutrophils in the airway, and significantly improved pulmonary function tests. The levels of IL-1beta and IL-8 were significantly higher in DPB compared with healthy volunteers (P<0.05, P<0.05, respectively). IL-1Ra in patients is considered to have a weak inhibitory activity for IL-1beta, with approximately five-fold concentration of IL-1beta compared with that in healthy volunteers (approx. nine-fold concentration of IL-1beta). Erythromycin therapy significantly reduced these cytokines to levels comparable to those of healthy volunteers, and produced a trend toward reduction in the level of IL-1Ra in BALF. The level of IL-1beta correlated significantly with the concentration of neutrophils in BALF (r=0.72, P<0.01), as well as with the level of IL-1Ra (r=0.688, P<0.05) and IL-8 (r=0.653, P<0.05). A nearly significant or significant correlation was observed between the concentration of neutrophils and levels of IL-1Ra or IL-8 in BALF (r=0.526, P=0.053 or r=0.776, P<0.01, respectively). There was also a significant relationship between FEV(1) and the concentration of neutrophils in BALF (r=0.524, P<0.05). Our results suggest that the relative amounts of IL-1beta and IL-1Ra or IL-8 may contribute, at least in part, to the neutrophil-mediated chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cycle between the cytokine network and neutrophil accumulation, with resultant reduction of neutrophil-mediated inflammatory response.

Adult↗
PubMed1996

Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25-dihydroxyvitamin D3-stimulated THP-1 cells.

We have recently reported that long-term administration of erythromycin at a low dose reduced the number of neutrophils and concentrations of interleukin 8 (IL-8) in bronchoalveolar lavage fluid in patients with chronic lower respiratory tract disease. To investigate the mechanism of action of erythromycin, we evaluated its effect on IL-8 production in the 1 alpha,25-dihydroxyvitamin D3-stimulated human monocytic cell line THP-1. Erythromycin at a concentration of 10 micrograms/ml significantly reduced IL-8 production by THP-1 cells stimulated with lipopolysaccharide (10 ng/ml) and 1% normal human serum compared with the amount produced by untreated cells (untreated cells, 2,448 pg/ml; erythromycin-treated cells, 872 pg/ml). Our results suggest that erythromycin may impair IL-8 production by alveolar macrophages, ultimately reducing neutrophil accumulation in the airspace.

Anti-Bacterial Agents↗
PubMed1996

Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2).

A strain of Streptomyces lividans, TK24, was found to produce a pigmented antibiotic, actinorhodin, although S. lividans normally does not produce this antibiotic. Genetic analyses revealed that a streptomycin-resistant mutation str-6 in strain TK24 is responsible for induction of antibiotic synthesis. DNA sequencing showed that str-6 is a point mutation in the rpsL gene encoding ribosomal protein S12, changing Lys-88 to Glu. Gene replacement experiments with the Lys88-->Glu str allele demonstrated unambiguously that the str mutation is alone responsible for the activation of actinorhodin production observed. In contrast, the strA1 mutation, a genetic marker frequently used for crosses, did not restore actinorhodin production and was found to result in an amino acid alteration of Lys-43 to Asn. Induction of actinorhodin production was also detected in strain TK21, which does not harbor the str-6 mutation, when cells were incubated with sufficient streptomycin or tetracycline to reduce the cell's growth rate, and 40 and 3% of streptomycin- or tetracycline-resistant mutants, respectively, derived from strain TK21 produced actinorhodin. Streptomycin-resistant mutations also blocked the inhibitory effects of relA and brgA mutations on antibiotic production, aerial mycelium formation or both. These str mutations changed Lys-88 to Glu or Arg and Arg-86 to His in ribosomal protein S12. The decrease in streptomycin production in relC mutants in Streptomyces griseus could also be abolished completely by introducing streptomycin-resistant mutations, although the impairment in antibiotic production due to bldA (in Streptomyces coelicolor) or afs mutations (in S. griseus) was not eliminated. These results indicate that the onset and extent of secondary metabolism in Streptomyces spp. is significantly controlled by the translational machinery.

Alleles↗
PubMed1996

Gamma Knife radiosurgery for brain stem metastases: two autopsy cases.

Early neuropathological findings were obtained at autopsy in two cases of brain stem metastasis treated with the Gamma Knife. In both cases, light microscopy radiation changes were strictly localized. Residual tumor tissue in the irradiation field showed marked degenerative changes including multinuclear cells, atypical nuclei and vacuolar degeneration. A characteristic finding in the irradiation field was fibrosis associated with hyalinized and thickened vessels. In more peripheral regions, demyelination and vacuolar degeneration were seen. This is the first report demonstrating extravascular fibrosis in the irradiated field following radiosurgery.

Aged↗
PubMed1996

Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium.

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.

Animals↗
PubMed1996

Chronic encapsulated expanding hematoma in association with gamma knife stereotactic radiosurgery for a cerebral arteriovenous malformation. Case report.

The authors report a rare case of a patient with a chronic encapsulated expanding hematoma and progressive neurological deterioration who presented 2 years after gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A tough capsule containing multiple layers of organized hematoma resulting from previous bleeding was confirmed surgically. Histological examination revealed that the capsule consisted of a dense collagenous outer layer and a granulomatous newly vascularized inner layer with marked fibrosis. Hemosiderin deposits were frequently observed in the inner layer, which suggested recurrent minor bleeding from fragile vessels in this layer. An AVM was found in the hematoma, which had degenerated as the result of radiosurgery. A cross-section of the abnormal vessels showed various stages of obliteration due to intimal hypertrophy. The clinical course, radiological features, and histological findings in this case were compatible with those of previously reported chronic encapsulated hematomas. A possible mechanism of hematoma formation and its expansion are discussed.

Adult↗
PubMed1996

[Enhancement of cytotoxic effect of anticancer agents of renal cell carcinoma].

BACKGROUND: Human renal adenocarcinomas do not adequately respond to cancer chemotherapy. Their multidrug resistance is mainly conferred by the P-glycoprotein (P-gp). In this study, we analyzed effects of P-gp modulators on enhancement of anticancer activities against human renal cell carcinomas. METHODS: ACHN/ADM human renal adenocarcinoma cells with a high level expression of P-gp and 28 surgical specimens of renal cell adenocarcinomas were recruited. Adriamycin (ADM) and vinblastin (VLB) were used as anticancer drugs, and verapamil (Ver) and cyclosporin A (CsA) were as P-gp modulators. The chemosensitivity was determined by the ATP-assay. RESULTS: Ver and CsA exhibited 1.5-fold and 6-fold increase, respectively, in the anticancer activities of ADM against ACHN/ADM cells. The anticancer activities of VLB were also enhanced by the modulators; 7-fold for Ver and 11-fold for CsA. In the chemosensitivity test of clinical specimens, the cancer for which the viability of the cells assessed by the ATP-assay was 50% or less than 50% after exposure to the anticancer drug with or without a P-gp modulator was defined as sensitive to the drug. Of the 14 clinical specimens exposed to anticancer drugs without Ver, only 3 tumors and 1 tumor were sensitive to ADM and VLB, respectively, whereas with Ver, 6 tumors and 4 tumors were sensitive to ADM and VLB, respectively. Of the other 14 clinical specimens exposed to anticancer drugs without CsA, only 3 tumors and no tumor were sensitive to ADM and VLB, respectively, whereas, with CsA, 9 tumors and 6 tumors were sensitive to ADM and VLB, respectively. CONCLUSION: This study indicate that Ver and CsA have effects on enhancement of the anticancer activities of ADM and VLB against human renal adenocarcinomas. The addition of Ver or CsA to chemotherapy will be a potential circumvention of P-gp-mediated multidrug resistance of renal cell adenocarcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗