Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of spatial folding of peptides is a very difficult task needing time-consuming elaborations. The complexity of the problem demands tools that predict in a simple manner basic properties such as the secondary structure starting from the amino acid sequence, which contains all the information necessary for the determination fo the folding of a protein. The study of secondary structure is of considerable interest, in particular the prediction of regular structures, because these regions, like alpha-helices and beta-sheets, may form nucleation sites (M.J.E. Sternberg and J.M. Thornton, Nature 2H (1978) 15-20; B. Robson and R.H. Pain, Biochem. J. 155 (1976) 331-344). The aim of this paper is to propose a procedure for the secondary structure prediction, based on statistics (B. Robson and J. Garnier, Introduction to Proteins and Protein Engineering (Elsevier, Amsterdam, 1986); J. Garnier, D.J. Osguthorpe and B. Robson, J. Mol. Biol. 120 (1977) 97-120) and heuristic rules, also taking into account experimental data.
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PMID:A secondary structure evaluation of peptides based on statistics and heuristic rules. 203 92

Bradykinin is the prime initiator of pain and the key initial activator of the inflammatory response at the site of tissue injury. The subsequent transfer of nociceptive information (pain sensation) into the central nervous system is then mediated via afferent type C dorsal root ganglion neurons. A recently developed hybrid cell line, F-11, shows many qualities characteristic of these pain-sensitive cells. In these neuronal hybrids, we have found that bradykinin induces sequential elevation in the concentrations of several second messengers involved in neuronal activation, including inositol trisphosphate (6.5-fold), intracellular calcium (2.7-fold), and cyclic GMP (20.5-fold). Importantly, the production of these second messengers is potently inhibited by several novel bradykinin antagonists that possess no intrinsic agonist activity. The same relative rank order of potency of inhibition of bradykinin-induced second messenger production was achieved in the inositol trisphosphate, calcium, and cyclic GMP assay systems, suggesting strongly that all three messenger systems are being activated by the same bradykinin receptor. The most potent antagonist was D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin, which inhibited in a competitive manner, with pA2 values, upon Schild plot analysis, in the nanomolar range. These potent bradykinin antagonists may be useful in the characterization of bradykinin receptors and in the clinical management of pain and inflammation.
Mol Pharmacol 1989 Jan
PMID:Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line. 253 66

Electrical stimulation of trigeminal afferents increases expression of preproenkephalin mRNA in neurons of laminae I and II of the trigeminal nucleus caudalis in animals sacrificed 6 hours after the end of stimulation. More neurons express, and positive cells express at higher levels. These neurons thus express the mRNA corresponding to a major pain-modulating neurotransmitter gene with significant input-related plasticity.
Brain Res Mol Brain Res 1989 Nov
PMID:Preproenkephalin mRNA expression in nucleus caudalis neurons is enhanced by trigeminal stimulation. 261 96

For the diagnosis of acute myocardial infarction (AMI) in patients circulating constituents of the contractile apparatus may be measured instead of cytosolic cardiac enzymes. The potential advantages of the use of myofibrillar cardiac proteins as marker proteins for AMI results from their expression as cardio-specific isoforms, their high intracellular concentration, and their continuous release from infarcting myocardium. While analyzing the specificity of polyclonal goat anti-human cardiac myosin light chains antisera a cardio-specific antibody fraction was identified which is directed against cardiac troponin T contaminations of the myosin light chains antigen. Using this antibody fraction a standardized enzyme immuno-assay for circulating troponin T was developed to detect AMI in patients. In this assay troponin T is bound on different epitopes by affinity purified goat anti-cardiac troponin T antibodies immobilized on polyvinyl chloride test tubes as well as horse raddish peroxidase labeled monoclonal anti-troponin T antibody in liquid phase. The assay procedure can be completed semiautomatically in 90 min with a detection limit of the assay of 0.5 ng/ml human or bovine cardiac troponin T. There is 1% crossreactivity with skeletal troponin T. In 26 healthy volunteers no cardiac troponin T was detectable in serum of 25 persons, while in 1 further volunteer 1 ng/ml troponin T was found. In the sera of all 50 patients with transmural AMI troponin T was elevated ranging from 7.2 to 110 ng/ml. In the mean troponin T remained elevated from three until 300 hours after onset of ischemic pain showing a biphasic serum concentration curve.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1989 Dec
PMID:Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. 263 16

The trans-synaptically activated biosynthesis of the preproenkephalin (PPE) mRNA in the dorsal horn of the rat lumbar spinal cord was examined by an in situ hybridization histochemical technique. As a nociceptive stimulus, a small amount of formalin was injected into the right hindpaw, and quantitative and qualitative changes of PPE-mRNA expression were determined by emulsion autoradiography. Formalin injection was found to result in a significant increase in the number and signal intensity of neurons expressing PPE-mRNAs in the superficial and deep layers of the ipsilateral spinal dorsal horn. Expression of PPE-mRNA increased within 1 h after formalin injection in neurons of deep layers, but gradually for at least 24 h in neurons in the superficial layers. These results at the level of the spinal cord showed that differential responses of PPE neurons related to the pain sensation occurred trans-synaptically after nociceptive stimulation applied to the periphery.
Brain Res Mol Brain Res 1989 May
PMID:Preproenkephalin gene expression in the rat spinal cord after noxious stimuli. 272 96

Conditions have been established where the deactivation of the beta-lactamase from Staphylococcus aureus PC1 by the penicillin substrate, quinacillin, is close to complete but fully reversible. The temperature-dependence of the rate of re-activation indicated a half-life of about 170 min for the deactivated state at 0 degrees C. Measurement of the relative viscosity of mixtures of enzyme and quinacillin at 8.4 degrees C ruled out any significant difference in shape or solvation between the deactivated and the normal enzyme. C.d. measurements of the deactivated protein, separated from excess quinacillin, showed that the quinacillin side-chain chromophore was bound in an asymmetric environment. The ellipticity associated with the bound quinacillin chromophore decreased with the same first-order rate constant as that for reappearance of enzyme activity. These findings support the accumulation of a deactivated state that contains bound quinacillin or a derivative. Quinacillin caused a 3-fold increase in the rate of 3H exchange-out (at a rate that was low compared with that for the substantially unfolded or expanded protein). However, there was rapid exchange-out of about 50 3H atoms on addition of 1 M-urea to the deactivated enzyme, whereas the same concentration had no effect on the exchange-out of 3H from native enzyme. The interpretation that quinacillin increases the susceptibility of the native state to unfolding in the presence of urea is supported by the demonstration that SO4(2)- ions decreased the rate and extent of deactivation but had no effect on the rate of re-activation, as predicted from the observation that SO4(2)- ions, in competition with urea, stabilize the native state relative to the partially unfolded state H [Mitchinson & Pain (1985) J. Mol. Biol. 184, 331-342].
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PMID:Reversible deactivation of beta-lactamase by quinacillin. Extent of the conformational change in the isolated transitory complex. 349 97

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.
Mol Aspects Med 1994
PMID:Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. 775 35

Venous malformation is the most common type of vascular anomaly. Depending upon size and location, these slow-flow anomalies may cause pain, anatomic distortion, or threaten life. Most venous malformations occur sporadically and present as solitary lesions. They also occur in several syndromes, some of which demonstrate Mendelian inheritance. We have mapped the locus for an autosomal dominant disorder in a three generation family that manifests as multiple cutaneous and mucosal venous malformations. This locus lies within a 24 cM interval on chromosome 9p, defined by the markers D9S157 and D9S163. The alpha and beta interferon gene cluster and the putative tumor suppressor genes MTS1 and MTS2 are also in this region. Characterization of the gene responsible for this disorder should yield insights into the precise pathogenic mechanisms for venous malformations.
Hum Mol Genet 1994 Sep
PMID:Assignment of a locus for dominantly inherited venous malformations to chromosome 9p. 783 15

Increased pain sensitivity (hyperalgesia) and persistent nociception following peripheral tissue injury depends both on an increase in the sensitivity of primary afferent nociceptors at the site of injury (peripheral sensitization), and on an increase in the excitability of neurons in the central nervous system (central sensitization). We will review evidence that central sensitization, and the persistent nociception it leads to, are dependent on an action of glutamate and aspartate at excitatory amino acid (EAA) receptors. Additional evidence will be presented implicating a role of various intracellular second messengers that are coupled to EAA receptors (nitric oxide, arachidonic acid, and protein kinase C) to central sensitization and persistent nociception following tissue injury. Finally, we will examine the evidence for a contribution of molecular events, including noxious stimulus-induced expression of immediate-early genes such as c-fos to persistent nociception.
Mol Neurobiol
PMID:The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. 791 27

Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions among macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia, or monocytes), after interacting with astrocytes, secrete eicosanoids, i.e., arachidonic acid and its metabolites, including platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. In addition, interferon-gamma (IFN-gamma) stimulation of macrophages induces release of the glutamate-like agonist, quinolinate. Furthermore, HIV-infected macrophage production of cytokines, including TNF-alpha and IL1-beta, contributes to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA) receptor-operated channels, and, therefore, offers hope for future pharmacological intervention. This article focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
Mol Neurobiol
PMID:HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists. 799 15


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