Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical protocol to treat infants with severe combined immuno deficiency due to adenosine deaminase (ADA) deficiency by means of gene thereapy has been approved recently. The Human Gene Therapy Subcommittee and the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) concluded the review on July 30th and opened the door for the first federally approved somatic Human Gene Therapy.
Diskussionsforum Med Ethik 1990 Sep
PMID:[First somatic human gene therapy in the USA approved]. 209 67

To assess the yield of adenosine deaminase (ADA) measurement in the diagnosis of tuberculous pleuritis and to afford parameters applicable to different populations and risk groups, a meta-analysis was performed in this study. National and anglo-saxon studies included in the Index Medicus from 1980 to march of 1990 were reviewed. The estimated incidence of tuberculous pleuritis in our medium was about 0.18 (confidence intervals for 95%-95% CI: 15-0.21). The diagnostic yield of ADA was as follows: sensitivity of 0.99 (95% CI: 0.98-0.99) and specificity of 0.93 (95% CI: 0.91-0.94). The quotients of probability (parameters that measure the predictive values of the tests at any given prevalence) were 14.31 and 0.004 for the positive and negative tests, respectively. In or medium the positive and negative predictive values were 0.74 (95% CI: 0.68-0.81) and 0.99 (95% CI: 0.98-0.99), respectively. An ADA value below the discriminative level nearly rules out the existence of tuberculous pleuritis, whereas at the contrary, and ADA value above the discriminative point offers a limited information about the etiology of the pleural effusion.
Med Clin (Barc) 1990 Sep 22
PMID:[The usefulness and limitations of adenosine deaminase in the diagnosis of tubercular pleurisy. A meta-analytical study]. 214 57

Incubation of rat adipocytes with 1 microM glucagon plus adenosine deaminase (5 micrograms/ml) inhibited maximally insulin-stimulated 3-O-methyl-D-glucose (MeGlc) transport by approximately 70%, concomitant with 30% and 55% decreases in insulin binding and cellular ATP, respectively. In contrast, under conditions where cellular ATP levels are well preserved (i.e. high albumin concentration in the medium), the inhibition of transport was reduced to about 30%, but that of insulin binding was not. Because depletion of the cellular ATP level by more than 60% by metabolic inhibitors induced 40% or more inhibition of insulin-stimulated MeGlc transport, the greater inhibition of the transport with the low albumin concentration appears to be caused in part by the secondary effect of ATP loss. The relationship between the amount of cell-bound insulin and hormone-stimulated transport activity showed that glucagon does not modulate insulin action at the step of insulin binding to its receptors. Furthermore, glucagon suppressed insulin-stimulated MeGlc transport, mainly through an attenuation of the hormone-induced increase in maximum velocity. The data show that glucagon modulates the process of signal transduction of insulin action. However, the possibility that glucagon directly modulates the process of translocation or the intrinsic activity of the glucose transporters cannot be eliminated.
Endocrinology 1990 Sep
PMID:Glucagon inhibits insulin activation of glucose transport in rat adipocytes mainly through a postbinding process. 220 31

The age-related declines in the antilipolytic and lipogenic actions of insulin were studied in adipocytes from rats aged 2, 6, 12, and 24 months. Since adenosine modulates insulin action, its concentration was controlled by treatment of adipocytes with adenosine deaminase and addition of the non-metabolizable adenosine analog, N6-[(R)-(-)1-methyl-2-phenethyl] adenosine (PIA). Inhibition of isoproterenol-stimulated lipolysis by PIA increased significantly by 6 months of age. Decreasing the concentration of PIA rendered the adipocytes from the 6-, 12-, and 24-mo-old rats less sensitive to the antilipolytic effect of insulin. Basal and insulin-stimulated lipogenesis decreased with aging. PIA increased insulin-stimulated lipogenesis at 0.2 ng/ml insulin only in the 2-month-old rats. PIA reduced insulin-stimulated lipogenesis at higher insulin doses in the oldest rats. These results suggest that aging causes quantitative declines in maximal lipolysis and basal and maximal lipogenesis. Maturation may cause a decline in sensitivity to insulin, but adenosine in sufficient concentration reverses the acquired resistance to the antilipolytic effect of insulin.
J Gerontol 1990 Sep
PMID:Effects of age and adenosine in the modulation of insulin action on rat adipocyte metabolism. 220 45

Seven genetic marker systems were analyzed from liquid blood and dried bloodstain specimens submitted to the Nebraska State Patrol Crime Laboratory from various law enforcement agencies throughout Nebraska. The phenotypic and genotypic frequencies for the ABO, Lewis, esterase D (ESD), phosphoglucomutase (PGM), adenylate kinase (AK), adenosine deaminase (ADA), and haptoglobin (HP) systems were calculated. The results indicate that the phenotypic frequencies are generally in agreement with frequencies reported in other populations in the United States.
J Forensic Sci 1990 Sep
PMID:Distributions of genetic markers in a Nebraska population. 223 Jun 94

(R)- and (S)-2'-deoxycoformycin, (R)-coformycin, and the corresponding 5'-monophosphates were compared as inhibitors of yeast AMP deaminase. The overall inhibition constants ranged from 4.2 mM for (S)-2'-deoxycoformycin to 10 pM for (R)-coformycin 5'-monophosphate, a difference of 3.8 x 10(8) in affinities. (R)-Coformycin, (R)-2'-deoxycoformycin 5'-monophosphate, and (R)-coformycin 5'-monophosphate exhibited both rapid and slow-onset inhibition. The S inhibitors and (R)-2'-deoxycoformycin exhibited classical competitive inhibition but no time-dependent onset of inhibition. The results indicate that the presence of the 2'-hydroxyl and 5'-phosphate and the R stereochemistry at the C-8 position of the diazepine ring are necessary for the optimum interaction of inhibitors with yeast AMP deaminase. This differs from the results for rabbit muscle AMP deaminase [Frieden C., Kurz, L. C., & Gilbert, H. R. (1980) Biochemistry 19, 5303-5309] and calf intestinal adenosine deaminase [Schramm, V. L., & Baker, D. C. (1985) Biochemistry 24, 641-646], in which a tetrahedral hydroxyl at C-8 in the R stereochemistry is sufficient for slow-onset inhibition with the coformycins. The results suggest that the transition state contains a tetrahedral carbon with the R configuration as a result of the direct attack of an oxygen nucleophile at C-6 of AMP. Slow-onset inhibition of yeast AMP deaminase is consistent with the mechanism [formula: see text] in which the combination of E and I is rapidly reversible. For these inhibitors, Ki varied by a factor of 3 x 10(3), and the overall inhibition constant (Ki*) varied by a factor of 2 x 10(5).(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemistry 1990 Sep 11
PMID:The rate constant describing slow-onset inhibition of yeast AMP deaminase by coformycin analogues is independent of inhibitor structure. 225 96

Neurons in the tuberomammillary nucleus (TM) of the rat hypothalamus were immunolabelled for the enzyme adenosine deaminase (ADA) and investigated by electron microscopic immunohistochemical techniques. ADA-immunoreactivity was distributed throughout the somal and dendritic cytoplasm of TM neurons and in the karyoplasm of most, but not all of these neurons. Immunoreactive axons were rarely observed within the tightly packed cell clusters of the TM subdivisions examined. Dense deposition of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreactive profiles and allowed characterization of the ultrastructural features of labelled neurons and the relationships of these with each other and with surrounding unlabelled neuronal and glial elements. Immunolocalization of ADA therefore represents a reliable and convenient method for the identification of TM neurons in EM studies of their ultrastructure and synaptic interactions.
Brain Res 1990 Sep 17
PMID:Ultrastructural immunolocalization of adenosine deaminase in histaminergic neurons of the tuberomammillary nucleus of rat. 225 38

Intake of completely purine-free foods of low sodium content increased the plasma concentrations of both hypoxanthine and inosine and the urinary excretion of hypoxanthine, while it decreased the urinary excretion of uric acid and the fractional clearance of uric acid. However, this diet affects neither nucleotides (inosine monophosphate, adenosine monophosphate, adenosine diphosphate and adenosine triphosphate) in red blood cells, enzymes (purine nucleoside phosphorylase, adenosine deaminase and hypoxanthine guanine phosphoribosyl transferase) in red blood cells nor the fractional clearance of oxypurines. These results suggest that the salvage of purines becomes more effective by limiting the conversion of hypoxanthine to xanthine and limiting the loss of uric acid during intake of completely purine-free foods of low sodium content; also that a decrease in the fractional clearance of uric acid due to completely purine-free foods of low sodium content may be an additional mechanism associated with the conservation of purines but is more likely to be a response to the low sodium diet on the renal handling of uric acid.
Eur J Clin Nutr 1990 Sep
PMID:The effect of completely purine-free diet of low sodium content on purine intermediates and end-product. 226 97

Adenosine deaminase was estimated in ascitic fluids of 49 patients with ascites (19 tuberculous, 20 cirrhotic, and 10 malignant). The adenosine deaminase concentration in tuberculous ascitic fluid was 98.8 +/- 20.1 U/L (mean +/- SD), which was significantly more than that noted in cirrhotic (14 +/- 10.6 U/L) or malignant (14.6 +/- 6.7 U/L) ascitic fluids (p less than 0.001 for each). At a cut-off value of greater than 33 U/L, the sensitivity, specificity, positive and negative predictive value, and the overall diagnostic accuracy for diagnosing tuberculous ascites were 100%, 96.6%, 95%, 100%, and 98%, respectively. We conclude that estimation of adenosine deaminase in ascitic fluid is an easy and reliable method for diagnosing tuberculous ascites.
Am J Gastroenterol 1990 Sep
PMID:Value of adenosine deaminase estimation in the diagnosis of tuberculous ascites. 238 24

In summary, this study characterized the biphasic inhibition of fat cell glucose transport by the lipolytic agents caffeine and theophylline. Like the lipolytic drug forskolin, both methylxanthines produced an immediate inhibition of glucose transport that was not seen with 8-phenyltheophylline, a pure adenosine receptor antagonist. The immediate inhibition was therefore not mediated by the adenosine receptor antagonism but seems to be due to a direct interaction with the hexose transporter. This conclusion is supported by the immediate onset of the inhibition and additionally by the interference of theophylline and caffeine with the binding of cytochalasin B, a ligand of the glucose transporter that binds to an intracellular site of the transporter molecule. In addition, a second, delayed inhibitory effect of theophylline and caffeine on glucose transport was observed. This portion shared many aspects of the inhibitory effect of lipolytic hormones. It developed over a period of about 5 min and was antagonized by the simultaneous addition of the antilipolytic hormone PGE2. This component of transport inhibition could be attributed to the antagonistic effect of methylxanthines at the fat cell A1-adenosine receptor since it was also seen with 8-phenyltheophylline. This conclusion is further supported by data showing that the removal of endogenous adenosine with adenosine deaminase resulted in a comparable 25-30% inhibition of insulin-stimulated glucose transport. In addition, the time course of glucose transport inhibition by the subsequent addition of adenosine deaminase is similar to that of the delayed portion of the inhibition seen with theophylline and caffeine. Both treatments produced their maximal inhibition after 5 min. In conclusion, the methylxanthines theophylline and caffeine inhibit glucose transport by a combination of two different modes of action. The immediate major component is mediated via a direct interaction with the hexose transporter whereas the delayed component involves adenosine receptor antagonism and thereby the interaction with G-proteins.
Biochem Pharmacol 1990 Sep 01
PMID:Methylxanthines inhibit glucose transport in rat adipocytes by two independent mechanisms. 239 Jan 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>