[Molecular mechanisms of self-incompatibility in Brassica].
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Brassica↗
Biomedical subjects
S Takayama
Publications and source records attributed to S Takayama.
[The clinical utility of asbestos body counts in bronchoalveolar lavage fluid].
To assess the clinical utility of measuring the number of asbestos bodies (AB) present in bronchoalveolar lavage fluid (BALF), we counted the number of AB in BALF from 119 subjects using light microscopy. The results were analyzed according to occupational histories, radiological findings of asbestos-induced lung and pleural changes, and asbestos-related diseases. The 94 subjects in group 1 had a history of dust exposure, whereas group 2 subjects (n = 25) had no dust exposure. Group 1 was subdivided into subjects with obvious exposure to asbestos (group 1A, n = 61), and subjects with no known exposure to asbestos (group 1B, n = 33). The distribution of AB counts per ml of BALF (means +/- SEM) differed significantly between groups 1 and 2 (38.8 +/- 17.4 vs 0.06 +/- 0.04, p < 0.0001). The AB counts were significantly different between groups 1A and 1B (57.9 +/- 26.6 vs 3.4 +/- 1.2, p = 0.01). Subject, exposed to dust who had radiological evidence of pleural thickening had significantly higher AB counts than subjects in whom pleural thickening was absent (66.0 +/- 31.1 vs 5.1 +/- 4.2, p = 0.03). In group 1, the BALF was positive for AB in 7 of 14 patients with pulmonary fibrosis, 4 of 5 patients with lung cancer, all 6 patients with malignant mesothelioma, and all 4 patients with benign asbestos pleural effusion. We conclude that AB counts in BALF are useful for evaluating both the history of asbestos exposure in a population exposed to dust, as well as patients having asbestos-related diseases.
Adult↗
Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.
BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Mechanism and specificity of human alpha-1,3-fucosyltransferase V.
Human alpha-1,3-fucosyltransferase catalyzes the transfer of the L-fucose moiety from guanosine diphosphate-beta-L-fucose (GDP-Fuc) to acceptor sugars to form biologically important fucoglycoconjugates, including sialyl Lewis x (SLex). Evidence for a general base mechanism is supported by a pH-rate profile that revealed a catalytic residue with a pKa of 4.1. The characterized solvent kinetic isotope effect (Dv = 2.9, Dv/k = 2.1) in a proton inventory study indicates that only one-proton transfer is involved in the catalytic step leading to the formation of the transition state. Evidence for Mn2+ as an electrophilic catalyst was supported by the observation that the nonenzymatic transfer of L-fucose from GDP-Fuc to the hydroxyl group of water in the presence of 10 mM MnCl2 at 20 degrees C was accelerated from K(obs)= 3.5 x 10(-6) to 3.8 x 10(-5) min-1. Using the GDP-Fuc hydrolysis as the nonenzymatic rate, the enzymatic proficiency of FucT V, (Kcat/Ki,GDP-fuc. K(m),1.acNAc)/K(non), was estimated to be 1.2 x 10(10) M-1 with a transition-state affinity of 8.6 x 10(-11) M. The Km for Mn2+ was determined to be 6.1 mM, and alternative divalent metal cofactors were identified as Ca2+, Co2+, and Mg2+. Detailed kinetic characterization of the acceptor sugar specificity indicated that incorporation of hydrophobic functionality [e.g. -O-(CH2)5CO2CH3] to the reducing end of the acceptor sugar substantially decreased the K(m),acceptor by over 100-fold. The role of the nucleotide was investigated by studying the inhibition of nucleotides, including the guanosine series. The inhibitory potency trend (GTP approximately GDP > GMP > > guanosine) is consistent with bidentate chelation of Mn2+ by GDP-Fuc. The role of charge and distance in the synergistic inhibitory effect by the combination of GDP, an aza sugar, and the acceptor sugar was probed. A mechanism for fucosyl transfer incorporating these findings is proposed and discussed.
1-Deoxynojirimycin↗
Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12.
cDNAs encoding the human homolog of BAG1, a Bcl-2-binding protein with anti-apoptotic function, were cloned. DNA sequence analysis of human BAG1 cDNAs predicts a protein with an additional 55 amino acids at its NH2-terminus compared to the mouse protein. Immunoblot assays using monoclonal antibodies raised against bacterially produced h-BAG1 protein confirmed the larger size of the human protein (approximately 34 kDa) compared to mouse. PCR analysis of DNA from human x rodent somatic cell hybrids using human BAG1-specific primers localized the gene to human chromosome 9. Cosmid clones of h-BAG1 were obtained and used for fluorescence in situ hybridization analysis of normal metaphase chromosomes, thus localizing h-BAG1 to 9p12, a region associated with hereditary disorders that may involve developmental dysregulation of programmed cell death.
Amino Acid Sequence↗
Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.
The Bcl-2 protein blocks programmed cell death (apoptosis) through an unknown mechanism. Previously we identified a Bcl-2 interacting protein BAG-1 that enhances the anti-apoptotic effects of Bcl-2. Like BAG-1, the serine/threonine protein kinase Raf-1 also can functionally cooperate with Bcl-2 in suppressing apoptosis. Here we show that Raf-1 and BAG-1 specifically interact in vitro and in yeast two-hybrid assays. Raf-1 and BAG-1 can also be coimmunoprecipitated from mammalian cells and from insect cells infected with recombinant baculoviruses encoding these proteins. Furthermore, bacterially-produced BAG-1 protein can increase the kinase activity of Raf-1 in vitro. BAG-1 also activates this mammalian kinase in yeast. These observations suggest that the Bcl-2 binding protein BAG-1 joins Ras and 14-3-3 proteins as potential activators of the kinase Raf-1.
Animals↗
BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy.
The BCL-2 gene was first discovered because of its involvement in the t(14;18) chromosomal translocations commonly found in lymphomas, which result in deregulation of BCL-2 gene expression and cause inappropriately high levels of Bcl-2 protein production. Expression of the BCL-2 gene can also become altered in human cancers through other mechanisms, including loss of the p53 tumor suppressor which normally functions as a repressor of BCL-2 gene expression in some tissues. Bcl-2 is a blocker of programmed cell death and apoptosis that contributes to neoplastic cell expansion by preventing cell turnover caused by physiological cell death mechanisms, as opposed to accelerating rates of cell division. Overproduction of the Bcl-2 protein also prevents cell death induced by nearly all cytotoxic anticancer drugs and radiation, thus contributing to treatment failures in patients with some types of cancer. Several homologs of Bcl-2 have recently been discovered, some of which function as inhibitors of cell death and others as promoters of apoptosis that oppose the actions of the Bcl-2 protein. Many of these Bcl-2 family proteins can interact through formation of homo- and heterotypic dimers. In addition, several nonhomologous proteins have been identified that bind to Bcl-2 and that can modulate apoptosis. These protein-protein interactions may eventual serve as targets for pharmacologically manipulating the physiological cell death pathway for treatment of cancer and several other diseases.
Apoptosis↗
Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma.
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Apoptosis↗
Development of a quantitative sampling method for periapical exudates from human root canals.
A quantitative method for collection of periapical exudates on endodontic paper points is described. In a pilot study, it was revealed that the relationship between fluid volume and wetted length of paper points had a highly significant curvilinear relationship (p < 0.0001), and a highly significant positive linear relationship was found to describe eluted and absorbed interleukin (IL)-1 beta activities from paper points. Periapical exudates from 29 root canals with apical periodontitis were collected using this method, and IL-1 beta activities in clinical specimens were measured. Periapical exudates (0.15 to 26.7 microliters) were recovered, and the range of IL-1 beta concentration was 0.1 to 179.5 ng/ml. These results showed that this sampling method was useful to analyze immunological changes in periapical lesions.
Dental Pulp Cavity↗
Relationship between prostaglandin E2 concentrations in periapical exudates from root canals and clinical findings of periapical periodontitis.
In this study the relationship of prostaglandin E2 (PGE2) concentrations in periapical exudates with clinical findings of teeth with periapical periodontitis is discussed. Periapical exudate samples were obtained from root canals of 77 endodontically involved teeth during routine root canal treatment by the quantitative sampling method using paper points. PGE2 concentrations in periapical exudates (PE-PGE2) were determined by radioimmunoassay. Significantly higher levels of PGE2 were found in periapical exudates from teeth with radiolucent areas than from teeth without radiolucent areas (236.8 +/- 521.3 pg/microliter vs. 14.9 +/- 23.1 pg/microliter, respectively). The elevated PE-PGE2 levels were associated with the presence of clinical symptoms that reflected an acute inflammation in the periapical lesion. In contrast, a significantly negative association of decreased PE-PGE2 levels with increasing size of radiolucent areas was demonstrated. These results suggested that PGE2 was produced locally in periapical lesions and that the PGE2 concentration in periapical exudate could reflect the state of the disease activity in periapical periodontitis.
Chi-Square Distribution↗
The SLGs corresponding to the same S24-haplotype are perfectly conserved in three different self-incompatible Brassica campestris L.
We have identified three strains of the same S24-haplotype in self-incompatible B. campestris L. Two of them, S-12j and 1-1j, have been derived from Japanese populations and one, 27-1t, from Turkish one. The cDNA clones of SLG24 (S24-locus glycoprotein), which linked to the S-locus, were isolated from each strain, and sequenced. Each clone isolated from S-12j, 1-1j and 27-1t, was designated as SLG24 (S-12j), SLG24 (1-1j) and SLG24 (27-1t), respectively. Their nucleotide sequences were completely identical in coding region, 5' non-coding region, and 3' non-coding region, though the position of the polyadenylation site was slightly different among the cDNA clones. This result suggests that the origin of S24-haplotype in these three strains might be common, and that the nucleotide sequences of SLG24 of the same S24-haplotype are completely conserved among different populations. The high conservation of the SLG24 nucleotide sequences is probably essential for the recognition of self or non-self of self-incompatibility in this S24-haplotype.
Amino Acid Sequence↗
Hyperglycemia decreases dehydroepiandrosterone in Japanese male with impaired glucose tolerance and low insulin response.
Recent studies indicate that experimentally induced hyperinsulinemia may reduce serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S). Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We selected 30 male IGT patients receiving diet therapy only, whose insulinogenic Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P = 0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at 60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min, respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c, the sum of insulin values (sigma IRI) or the area under the curve of plasma glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S 60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(-S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is attributable to hyperglycemia in male Japanese IGT with low insulin response.
Dehydroepiandrosterone↗
Depression of dehydroepiandrosterone in Japanese diabetic men--comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance.
Hyperglycemia is known to reduce dehydroepiandrosterone (DHEA) circulating levels; however, the mechanism by which hyperglycemia decreases DHEA is not elucidated. In this study, serum DHEA and DHEA sulfate (DHEA-S) levels were compared in 50 men with non-insulin-dependent diabetes mellitus (NIDDM) and 50 age-matched men with impaired glucose tolerance (IGT) receiving only diet therapy. Serum concentrations of DHEA and DHEA-S in the NIDDM group were significantly lower than in the IGT group (7.8 and 9.7 nmol/l vs 3.4 and 4.9 mumol/l, respectively; p < 0.01) but there was no significant difference in immunoreactive insulin between the two groups. When the results from both groups were combined, HbA1C was significantly inversely related to DHEA (r = -0.243, p < 0.01) and DHEA-S (r = -0.305, p < 0.01). Immunoreactive insulin showed no correlation with DHEA and DHEA-S. Multiple regression analysis showed that HbA1C was independently negatively related to both DHEA and DHEA-S. We conclude that hyperglycemia may decrease serum DHEA and DHEA-S in Japanese men with NIDDM, but the depression of DHEA(-S) is independent of serum insulin level.
Dehydroepiandrosterone↗
Scanning electron microscopy of C-banding.
The mechanism of C-banding was analyzed on the basis of the structural changes of the 30 nm chromatin fibre using scanning electron microscopy (SEM). SEM of non-banded metaphase spreads of L-cells revealed chromosomes consisting of 30 nm chromatin fibre loops along the entire length. No marked difference in both the dimension and appearance of such looped structures was discernible between the centromeric region and the rest of the chromosome. In contrast, C-banded chromosomes exhibited a conspicuous alteration of the fibre conformation in the centromeric region. The looped, fibrous structures were almost completely lost from this region, while the non-centromeric region still exhibited fibrous structures with slightly different appearances compared with those observed in the control chromosomes. On the other hand, results obtained using fluorescence microscopy showed that more DNA retained in the centromeric region than in the non-centromeric region. Since the analytical experiments exhibited that the characteristic collapsed state of the centromeric region occurred only with the alkali treatment but neither with the 2 x SSC nor acid treatments, the centromeric heterochromatin seemed to contain some specific protein which should be sensitive to alkali. The structurally collapsed but subsequently compact centromeric region may become more, or still, resistant to the DNA extraction due to the 2 x SSC treatment and the centromeric chromatin thus retained may be visualized as the C-band.
Animals↗
Cytologic assessment of metastatic ovarian carcinoma.
Significance of routine cytologic examination in the diagnosis of metastatic ovarian carcinoma was assessed. Twenty-one cases of metastatic carcinoma of the ovary were examined both pathologically and cytologically. Primary sites of the carcinoma were the stomach, breast, large bowel and uterine corpus. Cytology specimens were taken from the portio, endocervix and endometrium of the uterus, ascites and vaginal surgical stump. Malignant cells were detected in the samples from the portio, endocervix and endometrium in two, three and eight cases, respectively. One of the portio and endocervix and two of the endometrial specimens indicated the cases to be from endometrial primary sites. Primary sites of the remaining cases were the stomach and breast. Preoperative and intraoperative cytology of ascites were done in 16 cases and positive results were obtained in 11 cases. Postoperative recurrence was found cytologically in the surgical stump and ascites in two cases. Preoperative routine cytology of the uterus is considered to have diagnostic potential and ascite cytology to be an accurate index of intra-peritoneal spread in the case of metastatic ovarian carcinoma.
Adult↗
[Therapy for the gastric cancer in the near future].
Through the review of recent Japanese literatures, anticipated ways of the treatments for the gastric cancer in the near future were discussed. Most hopefully, no surgical intervention with the prevention and early diagnosis of initiation or promotions of the cancer development by genom analyses in individuals who may have high risk gene mutations will be expected. In the near future periods, however, vigorous molecular biological investigations for purpose will be required to clarify the mechanisms and each biological characteristics of the cancer developments. Further improvements of endoscopic ultrasonography and electron endoscopy will be needed for "early" detection of the lesions in the high risk group patients. More finely defined minimally invasive or extended operative procedures will still be challenged for molecular-biologically identified malignancies of the disease. Immuno-chemotherapy and chemotherapy aided by gene therapy will be the greatest hoperfull ways to conquer the disease. Direct concerns at the moment, however, cancer developments in the stomach with benign "ulcer" infected with Helicobacter Pylori must be urgently integrated for the prevention of the disease. Post-operative disorders after any type of surgery will still be one of the great issue in this until the complete achievements of above mentioned future tasks.
Antineoplastic Agents↗
Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death.
The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. To gain better understanding of how this protein functions, we have undertaken a structure-function analysis of this protein, focusing on domains within Bcl-2 that are required for function and for interactions with other proteins. Four conserved domains are present in Bcl-2 and several of its homologs: BH1 (residues 136-155), BH2 (187-202), BH3 (93-107) and BH4 (10-30). Deletion of the BH1, BH2, or BH4 domains of Bcl-2 abolishes its ability to suppress cell death in mammalian cells and prevents homodimerization of these mutant proteins, though these mutants can still bind to the wild-type Bcl-2 protein. These mutants also fail to bind to BAG-1 and Raf-1, two proteins that we have shown can associate with protein complexes containing Bcl-2 and which cooperate with Bcl-2 to suppress cell death. Deletion of either BH1 or BH2 nullifies the ability of Bcl-2 to: (a) suppress death in mammalian cells: (b) block Bax-induced lethality in yeast; and (c) heterodimerize with Bax. In contrast, deletion of the BH4 domain of Bcl-2 nullifies anti-apoptotic function and homodimerization, but does not impair binding to the pro-apoptotic protein Bax. Taken together, the data suggest the possibility that both Bcl-2/Bcl-2 homodimerization and Bcl-2/Bax heterodimerization are necessary but insufficient for the anti-apoptotic function of the Bcl-2 protein. Homodimerization of Bcl-2 with itself involves a head-to-tail interaction, in which an N-terminal domain where BH4 resides interacts with the more distal region of Bcl-2 where BH1, BH2, and BH3 are located. In contrast, Bcl-2/Bax heterodimerization involves a tail-to-tail interaction, that requires the portion of Bcl-2 where BH1, BH2, and BH3 reside and a central region in Bax where the BH3 domain is located. The BH3 domain of Bax is also required for Bax/Bax homodimerization and pro-apoptotic function in both yeast and mammalian cells. Thus, Bcl-2 may suppress cell death at least in part by binding to Bax via the BH3 domain and thereby preventing formation of Bax/Bax homodimers. Further studies however are required to delineate the full significance of Bcl-2/Bcl-2, Bcl-2/Bax, and Bax/Bax dimers and the biochemical mechanisms by which Bcl-2 family proteins ultimately control cell life and death.
Animals↗
[Usefulness of contrast-enhanced CT of the peritoneum to evaluate efficacy of neoadjuvant chemotherapy for peritoneal dissemination in an advanced gastric cancer case].
We performed contrast-enhanced CT before and after chemotherapy in a patient with advanced gastric cancer to assess the efficacy of neoadjuvant chemotherapy for peritoneal dissemination. The patient was preoperatively given combined chemotherapy with UFT and CDDP. Hepatic metastatic and peritoneal disseminated foci were markedly reduced on CT. Thus CT proved to be useful for assessing peritoneal dissemination and the efficacy of neoadjuvant chemotherapy.
Aged↗