[The mechanism and regulation of Fas-mediated apoptosis].
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Animals↗
Biomedical subjects
H Kazama
Publications and source records attributed to H Kazama.
Oncogenic K-Ras and basic fibroblast growth factor prevent Fas-mediated apoptosis in fibroblasts through activation of mitogen-activated protein kinase.
By an expression cloning method using Fas-transgenic Balb3T3 cells, we tried to obtain inhibitory genes against Fas-mediated apoptosis and identified proto-oncogene c-K-ras. Transient expression of K-Ras mutants revealed that oncogenic mutant K-Ras (RasV12) strongly inhibited, whereas dominant-inhibitory mutant K-Ras (RasN17) enhanced, Fas-mediated apoptosis by inhibiting Fas-triggered activation of caspases without affecting an expression level of Fas. Among the target molecules of Ras, including Raf (mitogen-activated protein kinase kinase kinase [MAPKKK]), phosphatidylinositol 3 (PI-3) kinase, and Ral guanine nucleotide exchange factor (RalGDS), only the constitutively active form of Raf (Raf-CAAX) could inhibit Fas-mediated apoptosis. In addition, the constitutively active form of MAPKK (SDSE-MAPKK) suppressed Fas-mediated apoptosis, and MKP-1, a phosphatase specific for classical MAPK, canceled the protective activity of oncogenic K-Ras (K-RasV12), Raf-CAAX, and SDSE-MAPKK. Furthermore, physiological activation of Ras by basic fibroblast growth factor (bFGF) protected Fas-transgenic Balb3T3 cells from Fas-mediated apoptosis. bFGF protection was also dependent on the activation of the MAPK pathway through Ras. All the results indicate that the activation of MAPK through Ras inhibits Fas-mediated apoptosis in Balb3T3 cells, which may play a role in oncogenesis.
3T3 Cells↗
Characterization of the antiseptic-resistance gene qacE delta 1 isolated from clinical and environmental isolates of Vibrio parahaemolyticus and Vibrio cholerae non-O1.
The nucleotide sequence and mechanism of action were examined on the antiseptic-resistance gene qacE delta 1 that had been isolated from Pseudomonas aeruginosa, Vibrio parahaemolyticus and Vibrio cholerae non-O1. The nucleotide sequences of qacE delta 1 genes isolated from environmental isolates of V. cholerae non-O1 and V. parahaemolyticus differed by one base from that of the gene from P. aeruginosa. Escherichia coli C600 that harbored qacE delta 1 genes from several strains of Vibrio spp. exhibited low-level resistance to intercalating dyes. The resistance of E. coli cells with these genes to intercalating dyes, such as ethidium bromide, was mediated by an efflux system. Moreover, the activity of QacE delta 1 was inhibited in the presence of calcium channel blockers but not of calmodulin inhibitors. These results indicate that the qacE delta 1 gene can be function in E. coli and that the gene mediates resistance in a similar manner to the antiseptic-resistance gene smr.
Amino Acid Sequence↗
Incomplete Sjögren-Larsson syndrome in two Japanese siblings.
Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder characterized by ichthyosis, spastic diplegia and mental retardation. Biochemical studies have pinpointed the pathogenesis resulting in the deficiency of the fatty aldehyde dehydrogenase (FALDH) component of the fatty alcohol NAD+ oxidoreductase complex. Histochemical analysis revealed a reduction in alcohol dehydrogenase (AD) activity in the skin. SLS patients have been categorized biochemically into two groups: complete and incomplete reduction according to the degree of FALDH deficiency. Our patients demonstrated incomplete clinical features, including a 1/3 reduction in FALDH activity, and decreased AD activity in the ichthyotic lesion. The phenotypical differences between our cases and classic SLS are probably due to the partial FALDH deficiency.
Aldehyde Oxidoreductases↗
Ecotropic viral integration site-1 is activated during, and is sufficient for, neuroectodermal P19 cell differentiation.
Expression of the ecotropic viral integration site-1 (Evi1) proto-oncogene during murine embryonal development is observed by in situ hybridization in primary head folds and neural crest-derived cells associated with the peripheral nervous system and embryonic mesoderm. To elucidate whether expression of Evi1 is involved in early neuroectodermal or mesodermal differentiation, we used murine embryonal carcinoma P19 cells as a model for the study of early embryonic differentiation. After retinoic acid (RA) treatment with aggregation, expression of Evi1 was detected during neural differentiation in P19 cells. However, Evi1 was not expressed in P19 cells during mesodermal differentiation after DMSO treatment with aggregation. Enforced expression of Evi1 in P19 cells induced neuron-specific microtubule-associated protein-2 microtubule-associated protein-2 and TrkA expression in the absence of RA under monolayer culture. After incubation with RA with aggregation, the Evi1 clones expressed microtubule-associated protein-2 continuously but did not express glial fibrillary acidic protein as an astrocyte marker protein until 12 days of culture. Thus, the overexpression of Evi1 leads to neural differentiation of P19 cells and blocks further differentiation into astrocytes by RA treatment, suggesting that Evi1 might be an important transcription factor for regulation of early neuroectodermal differentiation.
Animals↗
Distribution of the antiseptic-resistance gene qacE delta 1 in gram-positive bacteria.
The distribution of the antiseptic-resistance genes qacE and qacE delta 1, originally isolated from Gram-negative bacteria, was studied in a large number of Gram-positive bacteria by a method that included the polymerase chain reaction. A total of 151 strains of Staphylococcus and Enterococcus, isolated from clinical sources and obtained from the Japanese Collection of Microorganisms, was used in this analysis. We found the qacE delta 1 gene in 36 of 103 strains of Staphylococcus and in nine of 48 strains of Enterococcus. All of the strains in which we detected the qacE delta 1 gene were clinical isolates. The qacE gene was not detected in any of the strains examined in this study. The nucleotide sequences of the qacE delta 1 genes from the strains of Staphylococcus and Enterococcus were identical to that of the gene located on integron InC in Pseudomonas aeruginosa. These results indicate that the antiseptic-resistance gene qacE delta 1 is present in Gram-positive, as well as Gram-negative, bacteria.
Anti-Infective Agents, Local↗
Distribution of the antiseptic-resistance genes qacE and qacE delta 1 in gram-negative bacteria.
The distribution of the antiseptic-resistance genes qacE and qacE delta 1 was studied in a large number of Gram-negative bacteria by a method that included the polymerase chain reaction (PCR). A total of 117 strains of Gram-negative bacteria, isolated from clinical or environmental sources, was used in this analysis. We demonstrated the presence of these genes in 48 of 78 strains of Pseudomonas, in 20 of 26 strains of Vibrio, and in four of 13 strains of other species. These results indicate that the antiseptic-resistance genes are present in a broad range of species of Gram-negative bacteria.
Anti-Infective Agents, Local↗
Isolation of an Escherichia coli mutant which permits the high-level expression of a streptomycin-resistance gene derived from Pseudomonas aeruginosa.
Pretreatment with streptomycin at a low concentration influenced the susceptibility to streptomycin of a strain of Escherichia coli carrying a streptomycin-resistance plasmid, pSA1700, derived from Pseudomonas aeruginosa. This phenomenon was due to a mutation that occurred at about 10(-8)-10(-10) of frequency in a regulatory gene involved in gene expression on the chromosome of E. coli. A product encoded by the regulatory gene on the chromosome of E. coli might normally repress gene expression by binding to part of the promoter region of the streptomycin-resistance gene derived from P. aeruginosa.
Cloning, Molecular↗
Acute myeloblastic leukemia associated with trisomy 8 and translocation 8;21 in a child with Down syndrome.
The present study examined an 11-year-old girl with Down syndrome who suffered from acute myeloblastic leukemia (AML) preceded by preleukemic pancytopenia. Chromosomal analysis of leukemic cells revealed a chromosome change at t(8;21) and trisomy 8 associated with constitutional trisomy 21. Treatment with antineoplastic agents led to complete remission.
Child↗
Hyperplastic (metaplastic) polyposis of the colorectum associated with adenomas and an adenocarcinoma.
Hyperplastic (metaplastic) polyposis associated with adenoma and adenocarcinoma of the colorectum is rare. We describe a 55-year-old man with hyperplastic polyposis associated with multiple adenomas and an adenocarcinoma who underwent total colectomy. We found at least 200 polyps in the surgical specimen. Nearly all of the polyps were hyperplastic, and some were adenomas. Furthermore, some hyperplastic polyps had adenomatous areas. This indicates the transformational sequence of a hyperplastic polyp to adenoma to adenocarcinoma.
Adenocarcinoma↗
Does selective intra-arterial injection of calcium stimulate insulin secretion in all insulinoma cases?
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Aged↗
Common acute lymphoblastic leukemia preceded by hypercalcemia in an infant.
A case of common acute lymphoblastic leukemia (ALL) preceded by hypercalcemia was observed in an infant. A high blood level of parathyroid hormone related protein (PTH-rP) was detected during the first examination at Ohashi Hospital. Treatment with antineoplastic agents led to complete remission. The blood PTH-rP level decreased as a result of treatment. PTH-rP produced by leukemic cells was though to be the cause of the hypercalcemia.
Antineoplastic Combined Chemotherapy Protocols↗
A new gene, aadA2b, encoding an aminoglycoside adenylyltransferase, AAD(3")(9), isolated from integron InC in Pseudomonas aeruginosa.
A gene, designated aadA2 and encoding an aminoglycoside-adenylyltransferase, was located on integron InC, isolated from the R-plasmid of Pseudomonas aeruginosa, as a gene cassette. The aadA2 gene of InC was identical to those of pSa and R1033 with the exception of one base in each case. This single-base substitution did not influence the expression of streptomycin resistance. It is proposed that the aadA2 genes isolated from pSa and from R1033, and the aadA2 gene from InC, be designated aadA2a and aadA2b, respectively.
Anti-Bacterial Agents↗
[Acute myelogenous leukemia with ins(21;8) expressing AML-1-MTG8 fusion transcript].
Here we report a case of acute myelogenous leukemia (M2, FAB classification) presenting with cytogenetic abnormalities of ins(21;8), +del(8) without t(8;21). A 8;21 chromosome translocation is frequently found in acute myelogenous leukemia, especially in the M2 subtype. The translocation results in a fusion transcript between AML1 and MTG8 (ETO), assigned on chromosomes 21 and 8, respectively. Among patients with a t(8;21) abnormality, solid leukemic tumor deposits outside the marrow or good response to chemotherapy are observed frequently. Decrease in neutrophil alkaline phosphatase score and positive rate, and eosinophilia in bone marrow or the blast cells with Auer rods expressing CD19, CD56 antigens occur at a relatively high rate. Although our case lacked these clinical, cytological and cytochemical features, expression of chimeric AML1-MTG8 mRNA was detected. AML1-MTG8 fusion transcript may play a critical role in leukemogenesis of AML M2. Studies on this case may help to reveal the oncogenic function of the AML1-MTG8 fusion gene in AML M2.
Adult↗
Isolation and structure of a new integron that includes a streptomycin resistance gene from the R plasmid of Pseudomonas aeruginosa.
A new integron, located on the R plasmid of Pseudomonas aeruginosa, was isolated in Japan. This integron was made up of two conserved segments (5'-and 3'-conserved segments) and a single streptomycin resistance gene as a gene cassette. The structure of this integron resembles that of integron InC, the existence of which was postulated by Bissonnette and Roy (J. Bacteriol. 174, 1248-1257, 1992).
Biological Evolution↗
Changes in the arrangement of actin filaments in myoid cells and Sertoli cells of rat testes during postnatal development and after experimental cryptorchidism.
BACKGROUND: Abundant actin filaments are present in myoid cells and Sertoli cells in the testis. In the adult rat, the filaments form a lattice arrangement within the myoid cell, and show a hexagonal pattern in the basal junctional regions of Sertoli cells. METHODS: Isolated seminiferous tubules and frozen sections were prepared from juvenile to adult Wistar rat testes, stained with FITC-conjugated phalloidin, and observed by confocal microscopy. Unilateral cryptorchidism was induced in adult rats, and seven days later, their testes were also examined. RESULTS: In the myoid cell, parallel actin filaments running circularly around the seminiferous tubules were observed at 15 and 20 days of age. Then, at 30 days, actin filaments arranged longitudinally along the tubular long axis appeared in addition to the circular bundles. A lattice arrangement of actin-filament bundles in myoid cells became obvious at 40 days, when elongated spermatids are found in the tubule. Actin filaments in the basal junctional regions of Sertoli cells did not acquire the hexagonal pattern seen in the adult testis until 30 days of age. In the cryptorchid testes, the arrangement of actin filaments in the both cells showed a remarkable change compared to the control testis; the filaments became thinner and disrupted. CONCLUSIONS: A lattice arrangement of the actin filaments in the myoid cell appear at around 30 days, before the completion of spermatogenesis. A hexagonal pattern of the filaments in the junctional regions of Sertoli cells has already developed at this age. Cryptorchidism affects the actin filaments of the both cells.
Actins↗
Minimizing the drainage period for continuous ambulatory peritoneal dialysis.
OBJECTIVES: To examine features of drainage flow and to determine whether the drainage period could be safely reduced in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Open nonrandomized prospective study in CAPD patients. SETTING: The kidney center in a tertiary care university hospital. PATIENTS: Fourteen CAPD patients with good catheter function. INTERVENTIONS: Drainage flow pattern was studied using a 2-L dialysate. The drainage period was reduced from 28 minutes (mean) to 10 minutes throughout a short-term, 2-month study period and a long-term, 6-month study period for 10 patients. MAIN OUTCOME MEASURES: Ultrafiltration volume, body weight, and peritoneal clearance. RESULTS: A kinetics analysis of the drainage period and volume indicated a positive linear correlation with two different slopes: one for rapid drainage for the first 5-7 minutes and one for subsequent slow drainage. The effluent exceeded 80% in the former period. Ultrafiltration volume and body weight showed no change due to the reduction. Improved peritoneal clearance of small molecular substances could not be confirmed despite a 5% increase in the effective dialysis period. Nearly all patients were satisfied with the reduction and desired its continuation. CONCLUSIONS: Ten minutes is a sufficient drainage period for most CAPD patients with a 2-L dialysate volume. This may possibly allow an increase in daily activities and an effective peritoneal membrane dialysate contact period.
Adult↗