Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy.
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PMID:Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma. 1177 76

The prophylactic and therapeutic activities of two fluoroquinolones, levofloxacin and alatrofloxacin (the L-Ala-L-Ala prodrug of trovafloxacin), were compared to those of vancomycin in two different experimental models of foreign-body-associated infections caused by methicillin-resistant but quinolone-susceptible Staphylococcus aureus (MRSA) isolates. In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected with 10(3) CFU of MRSA, which was a 100% infectious dose in control animals. A single dose of 50 mg of levofloxacin per kg of body weight, administered intraperitoneally 3 h before bacterial challenge, was more efficient than vancomycin for the prevention of infections in tissue cages with MRSA inocula of 10(4) and 10(5) CFU. In a rat model used to evaluate therapy of chronic tissue cage infection caused by MRSA, the efficacies of 7-day high-dose regimens of levofloxacin (100 mg/kg once a day [q.d.] or 50 mg/kg twice a day [b.i.d.]) or alatrofloxacin (50 mg/kg q.d.) were compared to the efficacy of vancomycin (50 mg/kg b.i.d.). Active levels of levofloxacin, trovafloxacin, and vancomycin were continuously present in tissue cage fluid, with the levels exceeding the minimal bactericidal concentrations for MRSA during therapy. The q.d. and b.i.d. regimens of levofloxacin had equivalent activities and were significantly (P < 0.05) more active than alatrofloxacin or vancomycin in decreasing the viable counts of MRSA in tissue cage fluids. No quinolone-resistant mutants emerged during therapy with either fluoroquinolone. The mechanisms explaining the inferior activity of alatrofloxacin compared to the activity of levofloxacin against chronic foreign-body-associated infections by MRSA are unknown.
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PMID:Comparison of levofloxacin, alatrofloxacin, and vancomycin for prophylaxis and treatment of experimental foreign-body-associated infection by methicillin-resistant Staphylococcus aureus. 1195 88

Alcohol is the most commonly abused substance yet alcoholism is frequently undiagnosed. The misuse of alcohol is common and frequently an occult problem. More than 10% of current drinkers meet diagnostic criteria for alcohol abuse or dependence while the lifetime prevalence for these conditions in outpatient settings ranges from 16 to 36 percent. Long-term, heavy drinking is associated with significant morbidity, mortality, and economic costs. Clues to alcohol use can be discovered from a patient's history and physical stigmata. Validated screening instruments such as the Alcohol Use Disorders Identification Test (AUDIT), CAGE Questionnaire, and Brief Michigan Alcoholism Screening Tests help confirm the clinical suspicion of alcohol dependence. Laboratory abnormalities of mean corpuscular volume, gamma-glutamyl transferase, alkaline phosphatase, or alanine amino transferase levels are non-specific indicators of possible alcohol-induced liver impairment. Newer, less well-known FDA-approved biochemical markers such as the Carbohydrate Deficient Transferrin and the Early Detection of Alcohol Consumption test may also be used to detect heavy alcohol abuse and to monitor relapse episodes. Brief interventions are successful, making identification and diagnosis a vital role for the family physician. Improved awareness of alcohol misuse, increased use of screening tools, and the appropriate use of biochemical markers will facilitate early intervention and successful management of patients with alcohol use disorders.
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PMID:Use of contemporary biomarkers in the detection of chronic alcohol use. 1464 83

Employing chemical shift melts and hydrogen/deuterium exchange NMR techniques, we have determined the stabilization of the Trp-cage miniprotein due to multiple alanine insertions within the N-terminal alpha-helix. Alanine is shown to be uniquely helix-stabilizing and this stabilization is reflected in the global fold stability of the Trp-cage. The associated free energy change per alanine can be utilized to calculate the alanine propagation value. From the Lifson-Roig formulation, the calculated value (wAla = 1.6) is comparable to those obtained for short, solubilized, alanine-rich helices and is much larger than the values obtained by prior host-guest techniques or in N-terminally templated helices and peptides bearing long contiguous strings of alanines with no capping or solubilizing units present.
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PMID:The helical alanine controversy: an (Ala)6 insertion dramatically increases helicity. 1549 25

The single binding pocket of a self-assembled Pd6L4 coordination cage recognizes oligopeptides in a highly sequence-selective fashion. In particular, the Trp-Trp-Ala sequence is strongly bound by the cavity (Ka >/=106 M-1). Tripeptides possessing the same residues but in different sequences (i.e., Trp-Ala-Trp and Ala-Trp-Trp) show much poorer affinity. Even singly mutated tripeptides with aromatic-aromatic-aliphatic sequences of the residues (e.g., Trp-Trp-Gly and Trp-Tyr-Ala) are not recognized efficiently. X-ray analysis and NMR reveal that all residues of the Trp-Trp-Ala sequence cooperatively interact with the cage via CH-pi and pi-pi interactions.
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PMID:Sequence-selective recognition of peptides within the single binding pocket of a self-assembled coordination cage. 1579 99

The conformational preferences of peptides of the type, Ac-X-Y-NHMe, where X and Y = Ala, cage and Pro, were studied by means of computational techniques within the framework of a molecular mechanics approach. For each of the eight peptide analogues, extensive conformational searches were carried out using molecular dynamics (MD) and simulated annealing (SA) protocols in an iterative fashion. Both results are in good agreement and complement each other. The conformational search indicates that the cage residue restricts the conformational freedom of the dipeptide considerably in comparison with the other model residues used. This study revealed that proline exhibits a greater tendency in promoting reverse-turn characteristics in comparison to the cage peptides, which show promising beta-turn characteristics. It was also found that 300-500 K is not sufficient to overcome rotational barriers for cage peptides. In all cases, the low-energy conformers have a tendency to form bent structures.
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PMID:A theoretical study of pentacyclo-undecane cage peptides of the type [Ac-X-Y-NHMe]. 1595 37

The WD40 repeat protein WDR5 specifically associates with the K4-methylated histone H3 in human cells. To investigate the structural basis for this specific recognition, we have determined the structure of WDR5 in complex with a dimethylated H3-K4 peptide at 1.9 A resolution. Unlike the chromodomain that recognizes the methylated H3-K4 through a hydrophobic cage, the specificity of WDR5 for methylated H3-K4 is conferred by the nonconventional hydrogen bonds between the two zeta-methyl groups of the dimethylated Lys4 and the carboxylate oxygen of Glu322 in WDR5. The three amino acids Ala-Arg-Thr preceding Lys4 form most of the specific contacts with WDR5, with Ala1 forming intermolecular hydrogen bonds and salt bridges, and the side chain of Arg2 inserting into the central channel of WDR5. Both structural and biochemical studies presented here suggest another mode of recognition for the methylated histone tail.
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PMID:Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. 1660 Aug 77

Although mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferases (ALT), and the AST/ALT ratio are sometimes used as markers of alcohol disorders, their utility has not been established in older persons. We determined the tests' performance characteristics for (1) at-risk drinking, (2) CAGE positivity, (3) at-risk drinking and CAGE positivity, and (4) a clinician-recorded diagnosis of alcohol abuse/dependence in a study of older male veterans receiving primary care. Participants (n = 587) included patients who had MCV, AST, and/or ALT data collected as part of routine care no more than 12 weeks before or after enrollment. MCV, AST, and ALT test results were obtained from the VA's database. At enrollment, the Timeline Followback and Alcohol Use Disorders Identification Test (AUDIT) were used to identify at-risk drinkers (> or = 15 drinks per week or AUDIT score > or = 8), and the CAGE questionnaire was administered to identify participants with a history abuse/dependent drinking (CAGE score > or = 2). Participants' medical records were reviewed to identify subjects with a clinician-recorded diagnosis of alcohol abuse/dependence. The prevalence of abnormal test results for MCV (threshold value = > 98), AST (> 41), ALT (> 41), and the AST/ALT ratio (> 2) was 11%, 4%, 4%, and 5%, respectively. The occurrence of at-risk drinking, CAGE positivity, at-risk drinking and CAGE positivity, and a clinician-recorded diagnosis of alcohol abuse/dependence was 11%, 25%, 5%, and 9%, respectively. Test sensitivity ranged from 3.9% to 25.4% and specificity from 88.5% to 97.1%, whereas positive likelihood ratios varied from 0.72 to 4.01 and negative likelihood ratios from 0.82 to 1.04. Areas under the receiver operating characteristic curve were similar (range = 0.50-0.58) across tests. In conclusion, MCV, AST, ALT, and the AST/ALT ratio are not useful markers of alcohol disorders in older male veterans.
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PMID:Are commonly ordered lab tests useful screens for alcohol disorders in older male veterans receiving primary care&#63. 1668 67

An Ac-Ala-Ala-Ala-NH2 tripeptide was folded into a beta-turn structure even in water through hydrophobic binding by a self-assembled porphyrin cage. The turn conformation of the bound peptide was fully assigned from NOESY measurements and was strongly supported by molecular dynamics simulation. Single mutation experiments and molecular modeling also suggested that CH-pi interactions between methyl groups of Ala residues and porphyrin ligands were important for the stabilization of the turn conformation. Furthermore, we observed the induction of a beta-hairpin structure by encapsulation of a heptapeptide, Ac-Gly-Gly-Ala-Ala-Ala-Gly-Gly-NH2, possessing Ala-Ala-Ala sequence at the middle.
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PMID:Folding of an Ala-Ala-Ala tripeptide into a beta-turn via hydrophobic encapsulation. 1684 33

In this study, the effects of breeding systems and stocking density on some blood parameters of rock partridges [total protein, total cholesterol, triglyceride, urea, glucose, calcium, phosphorus, alkaline phosphatase (ALP), sodium, chlorine, potassium, aspartate amino transferase (AST), and alanine amino transferase (ALT)] were investigated. For this purpose, blood samples of 18-wk-old male rock partridges, which were bred on the ground and in cages with 3 different stocking densities (group I: 15 partridges/m(2); group II: 20 partridges/m(2); and group III: 25 partridges/m(2)) were examined. Breeding method of rock partridges was found to have significant effects on blood total protein, (P < 0.05), total cholesterol (P < 0.05), triglyceride (P < 0.01), urea (P < 0.01), glucose (P < 0.05), calcium (P < 0.05), phosphorus (P < 0.01), ALP (P < 0.05), sodium (P < 0.01), chlorine (P < 0.05), and potassium (P < 0.01) levels, whereas it was found to have no significant effect on blood AST and ALT levels (P > 0.05). Stocking density of rock partridges was also found to affect significantly the levels of blood total protein, total cholesterol, triglyceride, urea, glucose, calcium, phosphorus, ALP, sodium, chlorine, and potassium (P < 0.05), whereas it did not have a significant effect on blood AST and ALT levels (P > 0.05). When the breeding method of the partridges was changed from the ground to the cages and the stocking density was increased, it was observed that the levels of blood total cholesterol, triglyceride, urea, glucose, sodium, and chlorine increased, whereas total protein, calcium, phosphorus, ALP, and potassium levels decreased. It was understood that the reactions of partridges toward breeding systems and stocking density were different and passing from ground system to cage system, and the increase in stocking density caused significant changes in blood parameters.
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PMID:The effects of breeding systems and stocking density on some blood parameters of rock partridges (Alectoris graeca). 1723 60


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