[Juvenile rheumatoid arthritis associated with aortitis syndrome].
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Adult↗
Biomedical subjects
A Sato
Publications and source records attributed to A Sato.
Mhc class I genes of swordtail fishes, Xiphophorus: variation in the number of loci and existence of ancient gene families.
Swordtail fishes and platies in the genus Xiphophorus (order Cyprinodontiformes, Teleostei) encompass 22 closely related species which are the products of a recent adaptive radiation in the streams of Central America. To investigate the evolution of the major histocompatibility complex (Mhc) genes in the period immediately following speciation, the class I genes from 20 of the 22 species were cloned and characterized by sequencing. The analysis revealed the existence of multiple loci (at least seven in some individuals) whose numbers vary among the different species and probably also among individuals of the same species. The variation does not seem to bear any relationship to the taxonomy of the genus. Genes at the different loci are distinguished by their intron sequences and by the presence of characteristic motifs in exons 2 and 3. The variation in copy number of loci may have been effected in part by unequal crossing over occurring between introns of misaligned closely related genes. The sequences of the genes fall into two groups, A and B, which represent ancient lineages. The groups define two families of loci, which diverged from each other an estimated 85 million years ago, before the separation of the Acanthopterygii from the Paracanthopterygii of the advanced bony fishes. Evolution of the genes within each family can be explained by the birth-and-death process driven by gene duplications and mutational differentiation.
Amino Acid Sequence↗
Ca(2+) stabilizes the semiquinone radical of pyrroloquinoline quinone.
Spectroelectrochemical studies were performed on the interaction between Ca(2+) and pyrroloquinoline quinone (PQQ) in soluble glucose dehydrogenase (sGDH) and in the free state by applying a mediated continuous-flow column electrolytic spectroelectrochemical technique. The enzyme forms used were holo-sGDH (the holo-form of sGDH from Acinetobacter calcoaceticus) and an incompletely reconstituted form of this, holo-X, in which the PQQ-activating Ca(2+) is lacking. The spectroelectrochemical and ESR data clearly demonstrated the generation of the semiquinone radical of PQQ in holo-sGDH and in the free state in the presence of Ca(2+). In contrast, in the absence of Ca(2+) no semiquinone was observed, either for PQQ in the free state (at pH 7.0) or in the enzyme (holo-X). Incorporation of Ca(2+) into the active site of holo-X, yielding holo-sGDH, caused not only stabilization of the semiquinone form of PQQ but also a negative shift (of 26.5 mV) of the two-electron redox potential, indicating that the effect of Ca(2+) is stronger on the oxidized than on the reduced PQQ. Combining these data with the observations on the kinetic and chemical mechanisms, it was concluded that the strong stimulating effect of Ca(2+) on the activity of sGDH can be attributed to facilitation of certain kinetic steps, and not to improvement of the thermodynamics of substrate oxidation. The consequences of this conclusion are discussed for the oxidative as well as for the reductive part of the reaction of sGDH.
Acinetobacter calcoaceticus↗
Site-directed removal of N-glycosylation sites in BST-1/CD157: effects on molecular and functional heterogeneity.
Cyclic ADP ribose (cADPR) is a novel second messenger that releases calcium from intracellular calcium stores, but works independently of inositol 1,4,5-trisphosphate. In mammals ADP-ribosyl cyclase function is found in two membrane proteins, CD38 and bone marrow stromal cell antigen 1 (BST-1)/CD157. These enzymes are exposed extracellularly and also possess cADPR hydrolase activity, but an intracellular soluble ADP-ribosyl cyclase has been reported in human T-cells. Previously, a soluble form of BST-1/CD157 (sBST-1), which lacked the glycosylphosphatidylinositol-anchored portion, was expressed by a baculovirus-insect-cell system. In this study, we have purified the sBST-1, and it migrated as two major bands by SDS/PAGE, suggesting that it is post-translationally modified. BST-1 contains four putative N-glycosylation sites. Tunicamycin treatment reduced sBST-1 expression in the culture medium, indicating that N-glycosylation is essential for secretion. Site-directed mutagenesis was performed to generate sBST-1 mutants (N1-N4), each preserving a single N-glycosylation site. N1, N3 and N4 were well secreted into the medium, and were each detected as a single band. Although N3 and N4 retained the ADP-ribosyl cyclase activity, the cADPR-hydrolase activity was retained only in N4. We conclude that N-glycosylation of sBST-1 facilitates the folding of the nascent polypeptide chain into a conformation that is conductive for intracellular transport and enzymic activity. Furthermore a crystal has been obtained using the N4 mutant, but not the wild-type sBST-1. Thus the artificial engineering of N-glycosylation sites could be an effective method to generate homogeneous material for structural studies.
ADP-ribosyl Cyclase↗
Non-invasive visualization of sperm mitochondria behavior in transgenic mice with introduced green fluorescent protein (GFP).
Using high sensitive polymerase chain reaction (PCR), we previously demonstrated that selective elimination of sperm mitochondrial DNA occurred during early embryogenesis in mouse. To analyze the process morphologically in more detail, a non-invasive, real-time observation of sperm mitochondria was used. Transgenic mice that express green fluorescent protein (GFP) exclusively in mitochondria (mtGFP-tg mice) were generated. The fluorescence in mtGFP-tg mice was strong and stable enough to carry out repeated observations under confocal laser scanning microscopy. In these mtGFP-tg mice it was revealed that the sperm mitochondria were selectively eliminated from egg cytoplasm during the two-cell stage of early embryogenesis. Therefore, mtGFP-tg mice should contribute to studies on sequential or repeated analysis of mitochondria.
Animals↗
The charge-transfer complex trans-STB-TCNQF4.
In the crystal structure of the title charge-transfer complex, namely trans-stilbene-2,2'-(2,3,5,6-tetrafluorobenzene-1,4-diylidene)propanedinitrile (1/1) (trans-STB-TCNQF(4)), C(14)H(12).C(12)F(4)N(4), the planar STB and TCNQF(4) molecules are stacked alternately. The structure is not isostructural with that of STB-TCNQ. No anomaly was found in the displacement parameters of any atoms, while the bond length of the central C=C moiety was shorter than the corresponding bond in ethylene. This suggests that the central C=C moiety of the STB molecule vibrates with a large amplitude, similar to the case in free STB and STB-TCNQ.
Journal Article↗
Spontaneous spinal cord herniation.
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Hernia↗
Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy.
Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 +/- 0.226 vs. 0.057 +/- 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 +/- 0.134 vs. 0.320 +/- 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104-5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer.
Age Factors↗
A novel amplification at 17q21-23 in ovarian cancer cell lines detected by comparative genomic hybridization.
OBJECTIVE: Little is known about the molecular mechanisms involved in the pathogenesis and/or progression of ovarian cancer (OC). To investigate the genomic imbalances and identify the cancer-related genes associated with this tumor, we applied comparative genomic hybridization (CGH) in OC cell lines. METHODS: Chromosomal aberrations among 17 OC cell lines were analyzed with CGH. Since novel chromosomal regions, including 17q21-23, were identified, we examined the involvement of two candidate genes, PS6K and ZNF147, mapped on this chromosomal region. We examined the status of amplification and expression by fluorescence in situ hybridization as well as by Southern blot analysis and by Northern blot analysis on two candidate genes, respectively. RESULTS: All lines displayed numerous chromosomal imbalances; the most frequent losses were observed on 18q22-23 (29.4%), 13q22-34 (23.5%), 9p (17.6%), 4p11-14 (17.6%), and 11p14-15 (17.6%). The most common gains were noted at 20q12-13 (47.1%), 8q23-24 (35.2%), 5p15 (23.5%), 7q32-36 (23.5%), and 20p (23.5%). High-level gains (HLGs) were detected at 20q12-13 (four cell lines), 8q24 (two cell lines), 12p11-12 (two cell lines), and 17q21-23 (two cell lines). PS6K and ZNF147 genes were amplified in two cell lines exhibiting HLGs at 17q21-23, but not overexpressed. CONCLUSIONS: Our CGH data indicate that OCs have various DNA copy number changes. Among these frequent changes, 17q21-23 may harbor another tumor-associated gene(s) responsible for OC carcinogenesis.
Chromosome Aberrations↗
Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer.
PURPOSE: Irinotecan hydrochloride shows a strong activity against gastric cancer and colorectal cancer, while combined therapy with irinotecan and cisplatin is useful for gastric cancer. However, myelosuppression and diarrhea are still dose-limiting factors. To reduce such toxicities to enable therapy to be performed on an outpatient basis, we tested the effect of divided administration of cisplatin. METHODS: Irinotecan (60 mg/m2) plus cisplatin (30 mg/m2) were administered on days 1 and 15 every 4 weeks to 13 patients with advanced gastric cancer and 13 with advanced colorectal cancer. Treatment was continued if a leukocyte count > or = 3000/mm3, a platelet count > or = 100,000/mm3, and grade 0 diarrhea were confirmed. Doses were reduced if grade 3-4 hematological toxicity and grade 2 or higher nonhematological toxicity occurred. RESULTS: The major toxicity was leukopenia (neutropenia), but grade 3-4 nonhematological toxicity was not observed. The response rate was 41.7% for gastric cancer (5/12 evaluable patients) and 36.7% for colorectal cancer (4/11 evaluable patients). The median survival time was 313 days (range 29-920 days) for gastric cancer patients and 490 days (range 83-1184 + days) for colorectal cancer patients. CONCLUSION: Fortnightly administration of irinotecan and cisplatin (with a divided cisplatin dose) seems to be a useful regimen for gastrointestinal cancer. It reduces toxicity while maintaining a good antitumor effect.
Adult↗
Molecular cloning, sequence analysis and expression of a novel gene induced by near-UV light in Bipolaris oryzae.
A cDNA clone derived from a novel gene (uvi-1) that is inducible by near-UV light was isolated by a differential screening procedure from a cDNA library of the fungus Bipolaris oryzae and characterized further. Sequence analysis of the clone revealed that uvi-1 encodes a protein with a putative molecular mass of 17 kDa; the UVI-1 protein shows significant similarity to a putative protein encoded by a cDNA which is expressed during appressorium formation in the rice blast fungus, Magnaporthe grisea. The corresponding genomic clone was also isolated, and Southern analysis of genomic DNA indicated the presence of a single copy of the uvi-1 gene in B. oryzae. Northern analysis showed that the uvi-1 transcripts are induced by exposure to near-UV light, but not by blue or red light. Furthermore, accumulation of uvi-1 transcripts is observed during differentiation of the appressorium.
Amino Acid Sequence↗
A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are selective for human immunodeficiency virus type 1 (HIV-1) and generally not effective on HIV-2 or simian immunodeficiency virus (SIV). Only SIVagm was found to be sensitive to NNRTIs. When the amino acid differences in RT between SIVmac and SIVagm were compared with the known amino acid substitutions of NNRTI-resistance variants of HIV-1, we came to consider that the amino acid residue Leu-188 of HIV-2 and SIVmac might be related to their resistance to NNRTIs. To test this hypothesis, we substituted Leu-188 to Cys or Tyr in HIV-2 and SIVmac, and examined sensitivity of the mutant molecular clones to NNRTIs. The L188Y mutant of HIV-2 became completely sensitive to delavirdine and efavirenz, while that of SIVmac was also significantly sensitive to these NNRTIs. We further isolated NNRTI-resistant variants from these mutant viruses and determined amino acid substitutions in RT. The roles of the observed substitutions in NNRTI-resistance were further confirmed by site-directed mutagenesis. Our study reveals the crucial role of L188 in the natural resistance of HIV-2 and SIVmac to NNRTIs. Furthermore, the observed substitutions in RT of HIV-2 and SIVmac support the common mechanism of action of NNRTIs against HIV-1, HIV-2 and SIV.
Alkynes↗
Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis.
The diversity of biological effects resulting from exposure to dioxin may reflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes. AHR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR target molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase. Analysis of the genomic organization of AHRR revealed an open reading frame consisting of a 2094-bp mRNA encoded by ten exons. We found one novel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), in exon 5 of the AHRR gene; among 108 healthy unrelated Japanese women, genotypes Ala/Ala, Ala/Pro, and Pro/Pro were represented, respectively, by 20 (18.5%), 49 (45.4%), and 39 (36.1%) individuals. We did not detect previously published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A and C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population. No association was found between uterine endometriosis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.
Aryl Hydrocarbon Receptor Nuclear Translocator↗
Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis.
Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. Several studies have demonstrated that mutations in the cationic trypsinogen (PRSS1) gene and the cystic fibrosis transmembrane conductance regulator (CFTR) gene are causative of the pathogenesis in a subset of hereditary and/or idiopathic CP cases. Recently, the N34S alteration of the pancreatic secretory trypsin inhibitor (PSTI) gene has been suggested to be closely associated with the pathogenesis of hereditary and/or idiopathic CP. Herein we analyzed genetic alterations of the PSTI gene in 32 unrelated Japanese CP patients who developed juvenile-onset CP or had a family history of CP; 5 patients were found to harbor alterations in this gene. In 3 of these 5 patients, heterozygous N34S alterations were found; this frequency is significantly lower than that in Caucasian patients reported previously. Moreover, a novel homozygous G-to-A transition in the promoter region of PSTI at 215bp upstream from the translation initiation site (-215G>A) was observed in 2 patients. We further surveyed the -215G>A alteration in 117 normal individuals; none of these individuals harbored this alteration. Our results suggested that the -215G>A alteration, as well as the N34S alteration, is a predisposing factor for CP.
Adolescent↗
Use of omentum for mediastinal tracheostomy after total laryngoesophagectomy.
BACKGROUND: Carcinomas of the cervicothoracic esophagus frequently invade the trachea and complete removal of the tumor often requires mediastinal tracheostomy. Traditionally, this surgical management was associated with high morbidity and mortality. Several types of myoctaneous flaps have been used for mediastinal tracheostomy to reduce the complication. We present our experience with a new technique for construction of mediastinal tracheotomy after total laryngoesophagectomy and reconstruction with the stomach. METHODS: The anterior chest wall was amply resected and the distal end of the trachea was placed low between the superior vena cava and aortic arch. We mobilized the entire omentum with the stomach and brought them up to the neck through the posterior mediastinum. The omentum was put around the trachea, main arteries, and the anastomosis. RESULTS: Seven mediastinal tracheostomies were performed using this method. There was no hospital death. Complications included respiratory failure (2 patients) and pyothorax (1 patient). Anastomotic leakage and inominate artery rupture were not experienced. Postoperative survival was disease dependent. All patients were discharged with satisfactory oral food intake, good airway condition, and excellent cosmetic appearance. CONCLUSIONS: We suggest the use of the omentum as a simple and reliable technique in constructing mediastinal tracheostomy following total laryngoesophagectomy for cervicothoracic esophageal cancer.
Esophageal Neoplasms↗
Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells.
Vascular smooth muscle cells play a key role in the development of atherosclerosis. Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. Since a long period of high glucose incubation was required for the effect, and it was inhibited by co-incubation with azaserine, the role of hexosamine biosynthesis in the development of atherosclerosis in diabetes was studied in A10 cells. Addition of glucosamine to the culture media enhanced PDGF-stimulated BrdU incorporation, and PDGF-induced tyrosine phosphorylation of the PDGF beta-receptor was increased by glucosamine treatment. Of the subsequent intracellular signaling pathways, PDGF-induced PDGF beta-receptor association with PLC gamma was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. In contrast, PDGF-induced PDGF beta-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% (P<0.01) and 36% (P<0.01), respectively. The intracellular signaling molecules responsible for the glucosamine effect were further examined using pharmacological inhibitors. Pretreatment with PLC inhibitor (U73122) had negligible effects, and MEK1 inhibitor (PD98059) showed only a slight inhibitory effect on the PDGF-induced BrdU incorporation. In contrast, pretreatment with PI3-kinase inhibitor (LY294002) significantly inhibited glucosamine enhancement of PDGF-induced BrdU incorporation. These findings suggest that glucosamine is involved in the development of atherosclerosis by enhancing PDGF-induced mitogenesis specifically via the PI3-kinase pathway.
Adaptor Proteins, Signal Transducing↗
Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain.
The intracranial neural vasodilative system of cholinergic fibers projecting from the basal forebrain to the cortex was discovered by Biesold, Inanami, Sato and Sato (Biesold, D., Inanami, O., Sato, A., Sato, Y., 1989. Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci. Lett. 98, 39-44) using laser Doppler flowmetry in anesthetized rats. This cholinergic vasodilative system, which operates by increasing extracellular ACh release, relies upon activation of both muscarinic and nicotinic cholinergic receptors in the parenchyma of the cortex. Further, the involvement of nitric oxide in this cholinergic vasodilation, indicates the necessity to this system of neurons, which contain nitric oxide synthase. The increase in cortical blood flow elicited by this cholinergic vasodilative system is independent of systemic blood pressure and is not coupled to cortical metabolic rates. This cholinergic vasodilative system may be activated by somatic afferent stimulation. Most of the data presented here were obtained in anesthetized animals.
Animals↗
Effect of dietary oils enriched with n-3 fatty acids on survival of mice.
Female mice were fed a conventional diet, shifted at 119 days of age to a diet supplemented with 10 wt % lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed oil (low-erucic, Rap), high-alpha-linolenic (n-3) perilla oil (Per) or a mixture (1:9) of ethyl docosahexaenoate (n-3) and soybean oil (DHA/Soy). Weight gain was less in the Per group than in the other groups at 497 days of age. In the Rap group, proteinuria was more severe than in the Saf, Per and DHA/Soy group, and hepatic triacylglycerol accumulation was greater than in the other groups. The mean survival time of the DHA/Soy group (753 days) was significantly longer than in the Lar group (672 days) and Saf group (689 days); the differences among other groups (e.g., 701 days in the Per group and 712 days in the Rap group) were not statistically significant. Although DHA is more susceptible to auto-oxidation than other major fatty acids in the air, an oil containing DHA was found to increase the survival of mice. Rapeseed oil that decreases the survival time of SHRSP rats was found to be safe in the mouse strain used in this study when survival was an end point.
Journal Article↗