Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A validation study was performed on the MESAM 4, a digital recording device developed to monitor oxygen saturation, heart rate (HR), snoring, and body position in order to screen subjects for obstructive sleep apnea syndrome (OSAS). MESAM 4 recordings were scored with the computer-based automatic scoring system provided with the equipment. Nocturnal polysomnography (PSG) and MESAM 4 recordings were run simultaneously on 56 subjects presenting with any type of sleep complaint, including those secondary to OSAS. Patients were assigned to one room by hospital administration and were monitored consecutively. The polygraphic equipment and MESAM 4 equipment were placed on the subjects by separate teams. Records of PSG and MESAM 4 were analyzed in double-blind fashion. With the MESAM 4 computerized analysis, three indices based on SaO2 (ODI), on heart rate (HVI), and on snoring (ISI) were obtained, and the number of abnormal respiratory events occurring during the time selected for analysis (TAT) were determined. Polysomnographic records were scored by 30-s epochs following the American Sleep Disorders Association standards for sleep states and stages and for sleep-related events, including sleep apneas, hypopneas, and periodic leg movements. Following independent scoring, 26 subjects were identified with OSAS by PSG, while MESAM 4 identified 25 subjects with OSAS using oxygen algorithm; all had a respiratory disturbance index greater than or equal to 10 with PSG. Results of each polysomnogram and each MESAM 4 analysis were compared. With the polysomnogram used as a standard, the degree of error for each variable with the MESAM 4 was calculated. Specificity and sensitivity of the most accurate index of the MESAM 4, the ODI, were 97 percent and 92 percent, respectively. The other two indices, HVI and ISI, were less accurate: specificity and sensitivity were 32 percent and 58 percent for HVI and 27 percent and 96 percent for ISI. Nevertheless, a combination of all three indices (ODI, HVI, ISI) would have prevented the two false-positive cases we observed. The results of this validation study show that MESAM 4 can be helpful to general practitioners, clinicians, and epidemiologists as a low-cost screening device for subjects with OSAS and habitual snoring.
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PMID:MESAM 4: an ambulatory device for the detection of patients at risk for obstructive sleep apnea syndrome (OSAS). 158 75

Copper in the presence of excess 1,10-phenanthroline, a reducing agent, and molecular oxygen causes cleavage of DNA with a preference for T-3',5'-A-steps, particularly in TAT triplets. The active molecular species is commonly thought to be the bis-(1,10-phenanthroline)Cu(I) complex, (Phen)2Cu(I), regardless of the reducing agent type. We have found that (Phen)2Cu(I) is not the predominant copper complex when 3-mercaptopropionic acid (MPA) or 2-mercaptoethanol are used as the reducing agents, but (Phen)2Cu(I) predominates when ascorbate is used as the reducing agent. Substitution of ascorbate for thiol significantly enhances the rate of DNA cleavage by 1,10-phenanthroline + copper, without altering the sequence selectivity. We show that (Phen)2Cu(I) is the complex responsible for DNA cleavage, regardless of reducing agent, and that 1,10-phenanthroline and MPA compete for copper coordination sites. DNA cleavage in the presence of ascorbate also occurs under conditions where the mono-(1,10-phenanthroline)Cu(I) complex predominates (1:1 phenanthroline:copper ratio), but preferential cleavage was observed at a CCGG sequence and not at TAT sequences. The second phenanthroline ring of the (Phen)2Cu(I) complex appears essential for determining the T-3',5'-A sequence preferences of phenanthroline + copper when phenanthroline is in excess.
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PMID:The influence of reducing agent and 1,10-phenanthroline concentration on DNA cleavage by phenanthroline + copper. 206 55

Theoretical computations are performed of the comparative binding affinities of five polymethylene carboxamide derivatives of 9-aminoacridine to a series of double-stranded hexanucleotides. The purpose of this investigation is to ascertain whether minor groove recognition of a guanine base adjacent to the intercalation site can occur, and be preferentially stabilized, for a given length of the polymethylene side chain, encompassing from n = 2 up to n = 6 methylene groups. For that purpose, several representative sequences were investigated, in which intercalation of the 9-aminoacridine chromophore occurred at a central d(CpG) or d(TpA) step. Investigated were the self-complementary sequences d(CGCGCG)2, d(GCCGGC)2, d(TATATA)2 and d(ATTAAT)2, as well as the 'mixed' sequences d(ACTAAT) .d(ATTAGT) and d(TGTATA). d(TATACA). For n = 3 up to n = 6, such a recognition was enabled only when the guanine base was located downstream of the intercalation site, i.e. with steps d(CGG) and d(TAG). It occurred by means of a bidentate interaction involving, on the one hand, H(N2) and N3 of the base, and, on the other hand, the carbonyl oxygen and the cis amino hydrogen of the terminal formamide moiety of the ligand. Because of the flexibility of the side chain, however, alternative binding modes were also found to occur competitively, involving backbone-only interactions of the side chain. On the basis of the present computations, upon binding to the sequence d(GCCGGC)2, an optimal value of n = 5 could be derived, with the corresponding acridine derivative eliciting both a significant prevalence of the bidentate over backbone only binding mode, and the most favourable energy balance within the investigated series. This privileged value of n = 5 is fully consistent with the experimental results of Markovits et al. and Gaugain et al. The very flexibility of the side chain, however, hampered any preferential recognition of a triplet sequence with a downstream guanine, such as d(CGG) or d(TAG), to be elicited over sequences such as d(TAA), d(TAT) or d(TAC).
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PMID:A theoretical investigation of the base sequence preferences of monointercalating polymethylene carboxamide derivatives 9-aminoacridine. 231 37

On reaching the respiratory compensation point (RCP) during rapidly increasing incremental exercise, the ratio of minute ventilation (VE) to CO2 output (VCO2) rises, which coincides with changes of arterial partial pressure of carbon dioxide (PaCO2). Since PaCO2 changes can be monitored by transcutaneous partial pressure of carbon dioxide (PCO2,tc) RCP may be estimated by PCO2,tc measurement. Few available studies, however, have dealt with comparisons between PCO2,tc threshold (TAT) and lactic, ventilatory or gas exchange threshold (VAT), and the results have been conflicting. This study was designed to examine whether this threshold represents RCP rather than VAT. A group of 11 male athletes performed incremental exercise (25 W.min-1) on a cycle ergometer. The PCO2,tc at (44 degrees C) was continuously measured. Gas exchange was computed breath-by-breath and hyperaemized capillary blood for lactate concentration ([la-]b) and PaCO2 measurements was sampled each 2 min. The TAT was determined at the deflection point of PCO2,tc curve where PCO2,tc began to decrease continuously. The VAT and RCP were evaluated with VCO2 compared with oxygen uptake (VO2) and VE compared with the VCO2 method, respectively. The PCO2,tc correlated with PaCO2 and end-tidal PCO2. At TAT, power output [P, 294 (SD 40) W], VO2 [4.18 (SD 0.57) l.min.1] and [la(-)] [4.40 (SD 0.64) mmol.l-1] were significantly higher than those at VAT[P 242 (SD 26) W, VO2 3.56 (SD 0.53) l.min-1 and [la(-)]b 3.52 (SD 0.75), mmol.l-1 respectively], but close to those at RCP [P 289 (SD 37) W; VO2 3.97 (SD 0.43) l.min-1 and [la(-)]b 4.19 (SD 0.62) mmol.l-1, respectively]. Accordingly, linear correlation and regression analyses showed that P, VO2 and [la(-)]b at TAT were closer to those at RCP than at VAT. In conclusion, the TAT reflected the RCP rather than VAT during rapidly increasing incremental exercise.
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PMID:Does the threshold of transcutaneous partial pressure of carbon dioxide represent the respiratory compensation point or anaerobic threshold? 854 75

A 73-year-old female of Dutch descent was referred for investigation of a high oxygen affinity hemoglobin variant. The beta-globin gene was amplified using the polymerase chain reaction. Direct nucleotide sequencing of the polymerase chain reaction amplified DNA revealed that she is heterozygous for a novel beta-globin gene mutation at codon 139, AAT-->TAT. The resulting hemoglobin variant has been designated Hb Aurora [beta 139 (H17) Asn-->Tyr].
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PMID:Identification of a new high oxygen affinity hemoglobin variant: Hb Aurora [beta 139(H17) Asn-->Tyr]. 871 92

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. The RCCs are characterized by 1) high incidence of pulmonary metastasis and peritoneal invasion, 2) high incidence of tumor-associated mortality and 3) possible involvement of reactive oxygen species in carcinogenesis. The present study investigated the possible role of Tsc2 and VHL tumor suppressor genes in this model. Thirty-four Fe-NTA-induced primary RCCs and 20 other primary or metastatic tumors of rats were searched for genetic alteration in all the coding exons of both genes by polymerase chain reaction-single-strand-conformation polymorphism analysis and sequencing in conjunction with morphological evaluation. In the Fe-NTA-induced RCCs, frequency of metastasis or invasion was proportionally associated with the nuclear grade of the tumor (grades 1-3). Only one Fe-NTA-induced RCC of grade 1 revealed missense mutations with loss of heterozygosity in exon 10 of the Tsc2 gene (codons 334, GTG (Val) to GCG (Ala), and 336, TAT (Tyr) to CAT (His). No mutation was found in the VHL gene. The results suggest that 1) high-grade RCCs can develop in the absence of mutations in the Tsc2 and VHL genes in rats, and that 2) Tsc2 gene somatic mutation can nonetheless be one of the causes of non-Eker rat RCCs.
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PMID:Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes. 976 16

In this study, an anaerobic fluidized bed reactor (AFBR) was used to treat a synthetically produced pink water waste stream containing trinitrotoluene (TNT). The synthesized waste consisted of 95 mg/l-TNT, the main contaminant in pink water, which was to be co-metabolized with 560-mg/l ethanol. Granular activated carbon was used as the attachment medium for biological growth. TNT was reduced to a variety of compounds, mainly 2,4,6-triaminotoluene (2,4,6-TAT), 2,4-diamino-6-nitrotoluene (2,4-DA-6-NT), 2,6-diamino-4-nitrotoluene (2,6-DA-4-NT), 2-amino-4,6-dinitrotoluene (2-A-4,6-DNT), and 4-amino-2,6-dinitrotoluene (4-A-2,6-DNT). These conversions resulted through the oxidation of ethanol to carbon dioxide under anoxic conditions, or reduction to methane under methanogenic conditions. The anaerobic reactor was charged with 1.0 kg of 16 x 20 U.S. Mesh Granular Activated Carbon (GAC) and was pre-loaded with 200 g of TNT prior to the addition of the mixed seed culture. During the first three weeks of operation, ethanol was completely degraded and no methane was produced. Effluent inorganic carbon revealed stoichiometric conversion of the feed ethanol to dissolved inorganic carbon with accumulation of carbon dioxide in the headspace of the reactor. GAC extraction showed incremental reduction of the nitro groups to amino groups, with 2,4,6-TAT as the final product. After three weeks, the oxygen from the nitro groups was depleted and methane production commenced. The reproducibility of this phenomenon was confirmed by repeating the experiment in the same manner using an identical AFBR. Furthermore, serum bottle tests were conducted using TNT loading ratios of 0.2, 0.4, 0.8, 1.0 g-TNT/g-GAC as well as experiments in the absence of GAC. Similar behavior to that of the columns was observed, with degradation rates varying according to the particular condition. GAC greatly enhanced the degradation rates and the higher TNT loading resulted in slower degradation rates of ethanol.
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PMID:Anaerobic degradation of 2,4,6-trinitrotoluene in granular activated carbon fluidized bed and batch reactors. 1137 14

Human solid tumors contain hypoxic regions that have considerably lower oxygen tension than normal tissues. These impart resistance to radiotherapy and anticancer chemotherapy, as well as predisposing to increased tumor metastases. To develop a potentially therapeutic protein drug highly specific for solid tumors, we constructed fusion proteins selectively stabilized in hypoxic tumor cells. A model fusion protein, oxygen-dependent degradation (ODD)-beta-galactosidase (beta-Gal), composed of a part of the ODD domain of hypoxia-inducible factor-1alpha fused to beta-Gal, showed increased stability in cultured cells under a hypoxia-mimic condition. When ODD-beta-Gal was further fused to the HIV-TAT protein transduction domain (TAT(47-57)) and i.p. injected to a tumor-bearing mouse, the biologically active fusion protein was specifically stabilized in solid tumors but was hardly detected in the normal tissue. Furthermore, when wild-type (WT) caspase-3 (Casp3(WT)) or its catalytically inactive mutant was fused to TAT-ODD and i.p. injected to a tumor-bearing mouse, the size of tumors was reduced by the administration of TAT-ODD-Casp3(WT) but not by TAT-ODD-mutant Casp3. TAT-ODD-Casp3(WT) did not cause any obvious side effects on tumor-bearing mice, suggesting specific stabilization and activation of the fusion protein in the hypoxic tumor cells. These results suggest that the combination of protein therapy using a cytotoxic TAT-ODD fusion protein with radiotherapy and chemotherapy may provide a new strategy for annihilating solid tumors.
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PMID:Antitumor effect of TAT-oxygen-dependent degradation-caspase-3 fusion protein specifically stabilized and activated in hypoxic tumor cells. 1192 18

Tumor hypoxia in a solid tumor mass has long been recognized as a cause of resistance to current cancer therapies, and has also been suggested to be a potent driving force towards malignancy. Recent progress in the understanding of the molecular mechanism of the tumor response to hypoxia has increased attention on targeting hypoxia for cancer therapy. We have generated a hypoxia-targeting fusion protein, TOP3, which is composed of a protein transduction domain (PTD) of HIV TAT, an oxygen-dependent degradation domain (ODD) of HIF-1 alpha, and procaspase-3. Here, we examine the effects of TOP3 in a rat ascites model. First, we clarified that the fluid in ascites from MM1 cells, which are derivatives of AH130 rat ascites hepatoma cells, was highly hypoxic. In vitro, MM1 cells retained protein degradation machinery through the ODD domain, and TOP3 effectively impaired MM1 cell growth in culture under hypoxic conditions by inducing apoptosis. Intraperitoneal administration of TOP3 prolonged the life span of rats bearing a significant amount of malignant ascites, and 60% of the treated animals were cured without recurrence of ascites. Thus, TOP3 had a dramatic effect on malignant ascites and, hence, we propose that rodent malignant ascites is an appropriate platform for testing hypoxia-targeted drugs.
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PMID:Targeting hypoxic cancer cells with a protein prodrug is effective in experimental malignant ascites. 1528 74

Islet transplantation has become an accepted method to treat type 1 diabetes. To succeed and achieve normal levels of glucose in transplant recipients, the quality of the transplanted islets is of the utmost importance. Lack of oxygen during organ procurement, islet isolation, and subsequent culture triggers apoptosis or necrosis and loss of islet function, causing the yield and quality to diminish. A promising candidate for cytoprotection against oxygen deprivation is neuroglobin (Ngb). Ngb is a recently described member of globin family and is expressed in neurons, retina, and pancreatic islets. To overexpress this protein in the islets and study its ability to protect them, we utilized protein transduction. Protein transduction is achieved by fusing Ngb to the TAT/PTD transduction domain, a peptide originated from the HIV transcriptional transactivator protein. Our study proved that TAT-Ngb is an efficient fusion protein capable of protecting the human islets in culture from loss of cell mass and function, thus increasing the quality of transplantable islets. If the islets could be cultured for a longer period of time without suffering harmful effects, it would be possible to precondition the recipient and there would be more time to assess their quality and function before transplantation.
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PMID:Protection of islets in culture by delivery of oxygen binding neuroglobin via protein transduction. 1580 6


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