Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stereochemical course of the reaction catalyzed by the EcoRV restriction endonuclease has been determined. This endonuclease recognizes GATATC sequence and cuts between the central T and dA bases. The Rp isomer of d(GACGATsATCGTC) (this dodecamer contains a phosphorothioate rather than the usual phosphate group between the central T and dA residues, indicated by the s) was a substrate for the endonuclease. Performing this reaction in H2 18O gave [18O]dps(ATCGTC) (a pentamer containing an 18O-labeled 5'-phosphorothioate) which was converted to [18O]dAMPS with nuclease P1. This deoxynucleoside 5'-[18O]phosphorothioate was stereospecifically converted to [18O]dATP alpha S with adenylate kinase and pyruvate kinase [Brody, R. S., & Frey, P. A. (1981) Biochemistry 20, 1245-1251]. Analysis of the position of the 18O in this product by 31P NMR spectroscopy showed that it was in a bridging position between the alpha- and beta-phosphorus atoms. This indicates that the EcoRV hydrolysis proceeds with inversion of configuration at phosphorus. The simplest interpretation is that the mechanism of this endonuclease involves a direct in-line attack at phosphorus by H2O with a trigonal bipyramidal transition state. A covalent enzyme oligodeoxynucleotide species can be discounted as an intermediate. An identical result has been previously observed with the EcoR1 endonuclease [Connolly, B. A., Eckstein, F., & Pingoud, A. (1984) J. Biol. Chem. 259, 10760-10763]. X-ray crystallography has shown that both of these endonucleases contain a conserved array of amino acids at their active sites. Possible mechanistic roles for these conserved amino acids in the light of the stereochemical findings are discussed.
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PMID:Stereochemical outcome of the hydrolysis reaction catalyzed by the EcoRV restriction endonuclease. 151 Sep 72

This high-performance liquid-chromatographic (HPLC) method for simultaneous determination of prednisone and its metabolite, prednisolone, in plasma is a modification of the method of Frey et al. (Clin Chem 1979;25:1944-7). Heparinized plasma (1.0 mL) with 0.1 mL of internal standard solution (11-deoxy-17-hydroxycorticosterone, 2 mg/L) is extracted with 7.0 mL of dichloromethane, then washed sequentially with 0.1 mol/L HCl, 0.1 mol/L NaOH, and deionized water, 2.0 mL each. The extract is evaporated and the residue reconstituted with 75 microL of mobile phase, methanol/H2O (40/60 by vol). Thirty microliters of this is injected onto a reversed-phase C6 column, which is eluted at 1.4 mL/min. Analytical recoveries of prednisone and prednisolone were 94-98% and 102-106%, respectively. Day-to-day precision (CV) was 3.8% for prednisone, 6.1% for prednisolone. We encountered no interference from the 21 other steroids and 25 drugs tested. This method is simple, accurate, and precise.
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PMID:Simultaneous liquid-chromatographic determination of prednisone and prednisolone in plasma. 341 42

Recent reports in the literature of solid-state 13C nuclear magnetic resonance (NMR) spectra of crystalline L-alanine [Naito, A., Ganapathy, S., Akasaka, K., and McDonnell, C. A. (1981) J. Chem. Phys. 74, 3190-3197] and L-leucine [Frey, M. H. and Opella, S. J. (1980) J. Chem. Soc. Chem. Commun., 474-475], recorded with cross-polarization and magic-angle spinning (CP-MAS), show downfield resonance shifts of several parts per million in their side-chain methyl groups, relative to their resonance positions in aqueous solution. Similar findings are reported here for crystalline aliphatic amino acids and L-alanine peptides, including tetra(L-alanine), which show similar, specific downfield shifts in their side-chain methyl resonances. Coupled with X-ray crystallographic data of these compounds, and previous gas and solution-phase 13C NMR studies, the CP-MAS 13C NMR data indicate that these downfield shifts are a result of van der Waals' interactions. This group have reported similar van der Waals' induced shifts of the same magnitude for 13C resonances of the side-chain methyl groups of 13C-enriched tetra(L-alanine) upon binding to high-affinity Fab' fragments of heterogeneous sheep anti-[poly(L-alanine)] antibodies in aqueous solution [Geller, S., Wei, S. C., Shkuda, G. K., Marcus, D. M., and Brewer, C. F. (1980) Biochemistry 19, 3614-3623]. The above findings show that van der Waals' induced 13C NMR shifts of similar magnitudes can be detected in specific antibody-hapten complexes and the side chains of crystalline aliphatic amino acids and peptides. The results also indicate that water possesses relatively little attractive van der Waals' interactions with aliphatic molecules.
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PMID:van der Waals' induced 13C NMR shifts in crystalline amino acids and peptides. 646 99

Fully developed eccrine glands distributed over the entire integument are found only in man. The secretory mechanism is based on the active transport of sodium ions; water diffuses passively following the osmotic gradient. The thermoregulatory center in the hypothalamic region receives impulses from external and internal thermoreceptors and is modified by levels of hormones, by emotions, physical activity and pyrogens. Heat loss is controlled by the blood flow through the skin and by activity of eccrine glands. Thermoregulatory sweating occurs mainly on head and trunk. Emotions trigger eccrine sweating predominantly in the axillae, on palms, and soles. Generalized hyperhidrosis is mostly due to metabolic or endocrinologic disorders; in the state of acclimatization or following menopause hyperhidrosis is conceived to be physiologic. In underlying neurologic disorders hyperhidrosis follows a segmental or irregular pattern. Functional or anatomic eccrine nevi have been described. Gustatory sweating elicited by certain foods is found to be idiopathic and occurs symmetrically on the face. Subsequent to neurologic lesions (e.g., Frey's syndrome) gustatory sweating in segmental distribution may be associated with salivation and can be triggered by any foodstuff. The idiopathic localized hyperhidrosis of axillae, palms, and soles poses a frequent therapeutic problem in the dermatologist's office. Frequently, a familial predisposition is found. To what extent the disorder may be part of a general imbalance of psychovegetative functions is not yet fully understood.
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PMID:[Physiopathologic aspects and clinical pictures in hyperhidrosis]. 666 23

We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia.
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PMID:Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail. 779 Sep

We attempted to develop an experimental animal model using rat's tail for understanding the mechanisms involving peripheral neuropathic pain. Under sodium pentobarbital anesthesia, the left inferior caudal trunk of the rat was resected between the S3 and S4 spinal nerves. Latencies of tail-flick induced by the stimulus such as warm (40 degrees C) and cold (4 degrees C) water to the tail were measured for the following 30 weeks. In addition, sensitivity of the tail to mechanical stimulation was tested with von Frey hairs on these rats. Operated rats showed abnormal sensitivity of the tail to normally innocuous mechanical and thermal (warm and cold) stimuli. We interpreted these results as signs of neuropathic pain following nerve injury. The present model offers several advantages in performing behavioral tests; (1) it is easy to apply thermal stimulation to the rat's tail using a water bottle; (2) it is easy to apply the mechanical stimulation with von Frey hairs and to localize sensitive areas in the tail; and (3) blind behavioral studies are possible due to the lack of deformity in the tail after surgery.
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PMID:A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury. 782 81

A goal of the present study was to document the behavioral changes observed in a model of painful neuropathy in the primate (Macaca fascicularis). A neuropathic state was induced by tight ligation of the L7 spinal nerve, just distal to the L7 dorsal root ganglion. Sensory testing was done on the ventral surface of the foot, a region that includes the L7 dermatome. Within 1 week following surgery, all monkeys (n = 3) developed a marked sensitivity to mechanical stimulation (with a camel hair brush and von Frey hairs), indicating the presence of mechanical allodynia. In 2 animals, the increased sensitivity to mechanical stimulation was also observed on the contralateral side. The threshold for withdrawal to a heat stimulus decreased, indicating the presence of heat hyperalgesia. Presentation of various cooling stimuli, such as acetone and cold water baths, suggested that cold allodynia had also developed. These behavioral phenomena are similar to those seen in humans diagnosed with peripheral neuropathic pain. The behavioral abnormalities are discussed in relation to the responses of spinothalamic tract cells recorded from primates with the same peripheral nerve injury (Palecek et al. 1992).
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PMID:Behavioral manifestations of an experimental model for peripheral neuropathy produced by spinal nerve ligation in the primate. 800 6

Nerve ligation injury in rats may represent a useful model of some clinical neuropathic pains. Activation of N-methyl-D-aspartate (NMDA) receptors may maintain central sensitivity and contribute to neuropathic pain. Here, nerve injury was produced by unilateral ligation of the L5 and L6 spinal roots of the sciatic nerve of rats. Catheters were inserted for intrathecal (i.th.) or local delivery of drugs at the site of nerve ligation. Acute nociception was measured by the 55 degrees C water tail flick test in sham-operated and nerve-injured rats, and allodynia was determined by measuring response to von Frey filaments. In sham-operated rats, morphine (30 micrograms, i.th.) produced a 60 +/- 14.4% MPE (maximal possible effect). MK-801 pretreatment did not alter tail-flick latency or morphine antinociception in sham-operated rats. In nerve-injured rats, morphine (30 micrograms, i.th.) produced a significantly lower antinociceptive effect than in controls (34 +/- 6.3% MPE). While MK-801 alone did not alter tail-flick latency in nerve-injured rats, it significantly enhanced the antinociceptive effect of morphine to 84 +/- 16.0% MPE. Bupivacaine (0.2 ml, 0.75% w/v) at the site of injury also significantly increased the efficacy of morphine (100 +/- 0% MPE) without affecting tail flick latency alone. Bupivacaine administered at the site of injury also produced a significant antiallodynic effect of 94 +/- 7.4% MPE. The reduction in antinociceptive efficacy of i.th. morphine in nerve injured rats may be due, in part, to an ongoing spontaneous activity initiated by ectopic foci at the site of injury, and possible NMDA receptor-mediated activity of spinal neurons.
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PMID:The loss of antinociceptive efficacy of spinal morphine in rats with nerve ligation injury is prevented by reducing spinal afferent drive. 858 50

In the absence of other substrates, L-Ser reacts rapidly with the tryptophan synthase alpha 2 beta 2 bienzyme from Salmonella typhimurium at pH 7.8 and 25 degrees C to give an equilibrating mixture of species dominated by comparable amounts of the L-Ser external aldimine Schiff base, E(Aex1), and the alpha-aminoacrylate Schiff base, E(A-A). The D-isomer of Ser is unreactive toward alpha 2 beta 2, and therefore, D,L-Ser can be used in place of L-Ser for investigations of catalytic mechanism. Due to the equilibrium isotope effect, when alpha-2H-D,L-Ser is substituted for alpha-1H-D,L-Ser, the position of equilibrium is shifted in favor of E(Aex1). On a much slower time scale, the 2H sample undergoes the exchange of enzyme bound 2H for the 1H of solvent water and is converted to a distribution of E(Aex1) and E(A-A) identical to that obtained with the 1H sample. This slow exchange indicates that the proton abstracted from the alpha-carbon of E(Aex1) is sequestered within a solvent-excluded site in E(A-A). Analysis of the UV/vis spectra gave an isotope effect on the equilibrium distribution of E(Aex1) and E(A-A) of KH/KD = 1.80 +/- 0.18. This large equilibrium isotope effect is the consequence of an unusual isotope fractionation factor of 0.62 for the residue which functions as the base to deprotonate and protonate the alpha-carbon proton in E(Aex1). A fractionation factor of 0.62 qualifies as evidence for the involvement of a low-barrier H-bond (LBHB) in this equilibration. Since this effect arises from abstraction of the alpha-proton from E(Aex1), the LBHB must be associated with the E(A-A) species. In contrast to weak H-bonds with energies of 3-12 kcal/mol, LBHBs are proposed to exhibit energies in the 12-24 kcal/mol range [Frey, P.A., Whitt, S.A., & Tobin, J. B. (1994) Science 264, 1927-1930]. Possible roles for this LBHB both in the chemical mechanism and in the stabilization of the closed conformation of E(A-A) are discussed.
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PMID:Evidence of a low-barrier hydrogen bond in the tryptophan synthase catalytic mechanism. 865 14

Behavioral studies have shown that mechanical hyperalgesia induced by intradermal injection of prostaglandin E2 is blocked by inhibitors of the cAMP second messenger system. Similarly, injection of prostaglandin E2 also induces a decrease in mechanical threshold and an increase in the number of action potentials elicited by test stimuli in most C-fibre nociceptors. This change is called sensitization. To further evaluate the degree of correlation between primary afferent sensitization and mechanical hyperalgesia, we conducted a study to evaluate the effect of agents known to block the cAMP second messenger system and behavioral manifestations of mechanical hyperalgesia following injection of prostaglandin E2. The agents tested were guanosine 5'-O-(2-thiodiphosphate), an inhibitor of stimulatory guanine nucleotide-binding regulatory proteins; 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase; and Walsh Inhibitor Peptide, an inhibitor of cAMP-dependent protein kinase. Single fibre electrophysiologic studies of 138 C-fibres, innervating the dorsum of the hind paw, was done in male Sprague-Dawley rats. The number of spikes evoked by a 10 s application of a threshold von Frey hair were determined before and after intradermal injection of test agents administered alone and in combination with prostaglandin E2. Injection of prostaglandin E2 with the test agent vehicle (saline or distilled water) resulted in a significant decrease in von Frey hair threshold and an increase in the number of spikes generated in response to threshold von Frey hairs. In contrast, co-injection of prostaglandin E2 with guanosine-5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine or Walsh inhibitor peptide did not result in a significant decrease in von Frey hair mechanical threshold or increase in the number of spikes generated to the threshold stimuli, compared with vehicle/prostaglandin E2. It is suggested that guanosine 5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine and Walsh inhibitor protein inhibited prostaglandin E2 sensitization of primary afferent C-fibres by inhibiting a stimulatory guanine nucleotide-binding regulatory protein, adenylyl cyclase, and protein kinase A, respectively. These results support the hypothesis that primary afferent sensitization by prostaglandin E2 underlies prostaglandin E2-induced hyperalgesia.
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PMID:Sensitization of C-fibres by prostaglandin E2 in the rat is inhibited by guanosine 5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine and Walsh inhibitor peptide. 883 7


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