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Biomedical subjects

N Nguyen

Publications and source records attributed to N Nguyen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Spatial patterning in nocturnal prosimians: a review of methods and relevance to studies of sociality.

Patterns of home range overlap between individuals are key parameters used in discussions of sociality in nocturnal prosimians. Despite the importance of space use variables in defining social structure in nocturnal prosimians, researchers have yet to reach a consensus concerning the most reliable techniques for measuring patterns of home range use. In this paper, we review the methods used in 27 studies of nocturnal prosimian ranging behavior published since 1977. We discuss the usefulness and limitations of the various methods of data collection (radio tracking, trap mark, and identification of sleeping site locations) and data analysis (minimum convex polygon method, minimum concave polygon method, and quadrat analysis) used in these studies. We conclude that the most effective method for gathering data on individual movements and social interactions is direct observation of individual radio tagged animals during all-night follows. In those cases where radio tracking and/or all-night follows are not possible, trap mark techniques can be used, although they tend to greatly underestimate home range size. We recommend that data collected on nocturnal prosimian ranging behavior be analyzed using the minimum convex polygon method, quadrat analysis, and, perhaps, one other of the more mathematically sophisticated techniques popular in studies of non-primate mammals. Finally, we urge researchers to employ standardized methods of data collection and data analysis in future studies of range use in nocturnal prosimians. Without standardization of methods, quantitative comparisons of the findings from different studies are biologically meaningless and prevent cross-species comparisons of space use and its relation to sociality.

Animals↗
PubMed2000

Fatty acid cytotoxicity to bovine lens epithelial cells: investigations on cell viability, ecto-ATPase, Na(+), K(+)-ATPase and intracellular sodium concentrations.

Unsaturated non-esterified fatty acids have been shown to be cytotoxic in micromolar concentrations to bovine lens epithelial cells, in the following order: arachidonic acid > linoleic acid > oleic acid = linolenic acid. As unsaturated free fatty acids are known to be Na(+), K(+)-ATPase inhibitors, the aim of the study was to investigate whether or not the fatty acid cytotoxicity is correlated with effects on Na(+), K(+)-ATPase activity and function in bovine lens epithelial cells. Furthermore, we also examined the effects of linoleic acid on an ecto-ATPase activity which could be demonstrated on the outside of primarily cultured bovine lens epithelial cells. It has already been shown that 10 micro mol l(-1)linoleic acid was cytotoxic but did not impair the ecto-ATPase activity of intact cells nor the Na(+), K(+)-ATPase in enriched membrane fractions. Na(+), K(+)-ATPase activity was slightly activated with 10 micro mol l(-1)linoleic acid and inhibited by about 50% with 100 micro mol l(-1). Using the sodium-binding benzofuran isophthalate, measurements of intracellular sodium concentrations were carried out. In serum-starved bovine lens epithelial cells the basal [Na(+)](in)was clearly lower than 5 mmol l(-1). When the function of the Na(+), K(+)-ATPase was interrupted by omitting K(+)-ions from the medium, [Na(+)](in)increased at a rate of 0.318 mmol l(-1)min(-1). Linoleic acid intensified that increase strongly in a concentration dependent manner. However, in K(+)-containing medium the linoleic acid-induced increase of [Na(+)](in)was completely prevented. Therefore, the high linoleioc acid cytotoxicity cannot be mediated by linoleic acid effects on Na(+), K(+)-ATPase activity and function in bovine lens epithelial cells.

Adenosine Triphosphatases↗
PubMed2000

Stability-indicating LC assay of and impurity identification in homoharringtonine samples.

Homoharringtonine (HHT) is a potent myelosuppressive agent and has antitumor activity. Recent studies suggest that it inhibits tumor growth by inducing apoptosis. HHT is an ester of the alkaloid cephalotaxine. It is isolated from genus Cephalotaxus. At least ten HHT analogs have been identified from cephalotaxus extracts. High performance liquid chromatography (HPLC) separations of the cephalotaxine alkaloids in plant extracts have been reported, they have not been validated as specific and stability-indicating for HHT. Due to the complexity of the alkaloid extracts, it is conceivable that additional analogs may still be unresolved from HHT. This paper presents an improved and validated HPLC assay for HHT. The assay is stability-indicating, precise (R.S.D. < 1%), linear (r2 = 0.9999), and accurate (error < 1%). The assay reveals three congeners present as impurities in HHT samples. Two are new and have not been previously reported. Identities of the impurities and forced decomposition products, elucidated with their HPLC retention and spectral data, are also presented.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Kangaroo care compared to incubators in maintaining body warmth in preterm infants.

Many preterm infants cared for in incubators do not experience Kangaroo Care (KC), skin-to-skin contact with their mothers, due to fear of body heat loss when being held outside the incubator. A randomized clinical trial of 16 KC and 13 control infants using a pretest-test-posttest design of three consecutive interfeeding intervals of 2.5 to 3.0 h duration each was conducted over 1 day. Infant abdominal and toe temperatures were measured in and out of the incubator; maternal breast temperature was measured during KC. Repeated measures ANOVA showed no change in abdominal temperature across all periods and between groups. Toe temperatures were significantly higher during KC than incubator periods, and maternal breast temperature met each infant's neutral thermal zone requirements within 5 min of onset of KC. Preterm infants similar to those studied here will maintain body warmth with up to 3 h of KC.

Abdomen↗
PubMed2000

Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180) define a canine homologue of linear IgA disease of humans.

Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering dermatosis that affects human children and adults. In contrast to bullous pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA autoantibodies that target LAD-1, the processed extracellular form of type XVII collagen. An immunologic homologue of LAD in humans was identified in two dogs according to the following criteria: 1) erosive, ulcerative, and crusted lesions seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal clefting present in the basement membrane lamina lucida without inflammation or with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd soluble protein LAD-1. The present study establishes unequivocally the existence of a naturally occurring canine model of LAD of humans.

Animals↗
PubMed2000

A MATLAB toolbox for the analysis of articulatory data in the production of speech.

The goal of this paper is to present EMATOOLS, a set of scripts for displaying and annotating acoustic and articulatory data simultaneously in studies on speech production. These scripts were developed with the use of MATLAB, a multiplatform computing environment for numeric computation and visualization. The system is equipped with a mouse-driven graphical interface made up of a number of displays. This interface can be easily customized to speed up routine tasks. The scripts can also be used in a noninteractive way, as stand-alone MATLAB commands. Output data can be imported into any standard spreadsheet. EMATOOLS is freely available from www.lpl.univ-aix.fr/nguyen/ematools.html.

Computer Graphics↗
PubMed1999

Contribution of alpha-adrenergic and beta-adrenergic stimulation to ischemia-induced glucose transporter (GLUT) 4 and GLUT1 translocation in the isolated perfused rat heart.

The intracellular signaling mechanism of the ischemia-stimulated glucose transporter (GLUT) translocation in the heart is not yet characterized. It has been suggested that catecholamines released during ischemia may be involved in this pathway. The purpose of this study was to evaluate the contribution of alpha-adrenoceptors and beta-adrenoceptors to ischemia-mediated GLUT4 and GLUT1 translocation in the isolated, Langendorff-perfused rat heart. Additionally, GLUT translocation was studied in response to catecholamine stimulation with phenylephrine (Phy) and isoproterenol (Iso). The results were compared with myocardial uptake of glucose analogue [18F]fluorodeoxyglucose (FDG). Subcellular analysis of GLUT4 and GLUT1 protein on plasma membrane vesicles (PM) and intracellular membrane vesicles (IM) using membrane preparation and immunoblotting revealed that alpha- and beta-receptor agonists stimulated GLUT4 translocation from IM to PM (2.5-fold for Phy and 2.1-fold for Iso, P<0.05 versus control), which was completely inhibited by phentolamine (Phe) and propranolol (Pro), respectively. Plasmalemmal GLUT1 moderately rose after Iso exposure, and this was prevented by Pro. In contrast, ischemia-stimulated GLUT4 translocation (2.2-fold, P<0.05 versus control) was only inhibited by alpha-adrenergic antagonist Phe but not by beta-adrenergic antagonist Pro. Similarly, Phe but not Pro inhibited ischemia-stimulated GLUT1 translocation. GLUT data were confirmed by FDG uptake monitored using bismuth germanate detectors. The catecholamine-stimulated FDG uptake (6.9-fold for Phy and 8.9-fold for Iso) was significantly inhibited by Phe and Pro; however, only Phe but not Pro significantly reduced the ischemia-induced 2.5-fold increase in FDG uptake (P<0.05 versus ischemia). This study suggests that alpha-adrenoceptor stimulation may play a role in the ischemia-mediated increase in glucose transporter trafficking leading to the stimulation of FDG uptake in the isolated, perfused rat heart, whereas beta-adrenergic activation does not participate in this signaling pathway.

Adrenergic alpha-Agonists↗
PubMed1999

Role of multiple CytR binding sites on cooperativity, competition, and induction at the Escherichia coli udp promoter.

The CytR repressor fulfills dual roles as both a repressor of transcription from promoters of the Escherichia coli CytR regulon and a co-activator in some circumstances. Transcription is repressed by a three-protein complex (cAMP receptor protein (CRP)-CytR-CRP) that is stabilized by cooperative interactions between CRP and CytR. However, cooperativity also means that CytR can recruit CRP and, by doing so, can act as a co-activator. The central role of cooperativity in regulation is highlighted by the fact that binding of the inducer, cytidine, to CytR is coupled to CytR-CRP cooperativity; this underlies the mechanism for induction. Similar interactions at the different promoters of the CytR regulon coordinate expression of the transport proteins and enzymes required for nucleoside catabolism but also provide differential expression of these genes. A fundamental question in both prokaryotic and eukaryotic gene regulation is how combinatorial mechanisms of this sort regulate differential expression. Recently, we showed that CytR binds specifically to multiple sites in the E. coli deoP promoter, thereby providing competition for CRP binding to CRP operator site 1 (CRP1) and CRP2 as well as cooperativity. The effect of the competition at this promoter is to negate the role of CytR in recruiting CRP. Here, we have used quantitative footprint and mobility shift analysis to investigate CRP and CytR binding to the E. coli udp promoter. Here too, we find that CytR both cooperates and competes for CRP binding. However, consistent with both the distribution of CytR recognition motifs in the sequence of the promoter and the regulation of the promoter, the competition is limited to CRP2. When cytidine binds to CytR, the effect on cooperativity is very different at the udp promoter than at the deoP2 promoter. Cooperativity with CRP at CRP1 is nearly eliminated, but the effect on CytR-CRP2 cooperativity is negligible. These results are discussed in relation to the current structural model of CytR in which the core, inducer-binding domain is tethered to the helix-turn-helix, DNA-binding domain via flexible peptide linkers.

Animals↗
PubMed1999

Regulation and function of family 1 and family 2 UDP-glucuronosyltransferase genes (UGT1A, UGT2B) in human oesophagus.

Human UDP-glucuronosyltransferases (UGTs) are expressed in a tissue-specific fashion in hepatic and extrahepatic tissues [Strassburg, Manns and Tukey (1998) J. Biol. Chem. 273, 8719-8726]. Previous work suggests that these enzymes play a protective role in chemical carcinogenesis [Strassburg, Manns and Tukey (1997) Cancer Res. 57, 2979-2985]. In this study, UGT1 and UGT2 gene expression was investigated in human oesophageal epithelium and squamous-cell carcinoma in addition to the characterization of individual UGT isoforms using recombinant protein. UGT mRNA expression was characterized by duplex reverse transcriptase-PCR analysis and revealed the expression of UGT1A7, UGT1A8, UGT1A9 and UGT1A10 mRNAs. UGT1A1, UGT1A3, UGT1A4, UGT1A5 and UGT1A6 transcripts were not detected. UGT2 expression included UGT2B7, UGT2B10 and UGT2B15, but UGT2B4 mRNA was absent. UGT2 mRNA was present at significantly lower levels than UGT1 transcripts. This observation was in agreement with the analysis of catalytic activities in oesophageal microsomal protein, which was characterized by high glucuronidation rates for phenolic xenobiotics, all of which are classical UGT1 substrates. Whereas UGT1A9 was not regulated, differential regulation of UGT1A7 and UGT1A10 mRNA was observed between normal oesophageal epithelium and squamous-cell carcinoma. Expression and analysis in vitro of recombinant UGT1A7, UGT1A9, UGT1A10, UGT2B7 and UGT2B15 demonstrated that UGT1A7, UGT1A9 and UGT1A10 catalysed the glucuronidation of 7-hydroxybenzo(alpha)pyrene, as well as other environmental carcinogens, such as 2-hydroxyamino-1-methyl-6-phenylimidazo-(4, 5-beta)-pyridine. Although UGT1A9 was not regulated in the carcinoma tissue, the five-fold reduction in 7-hydroxybenzo(alpha)pyrene glucuronidation could be attributed to regulation of UGT1A7 and UGT1A10. These data elucidate an individual regulation of human UGT1A and UGT2B genes in human oesophagus and provide evidence for specific catalytic activities of individual human UGT isoforms towards environmental carcinogens that have been implicated in cellular carcinogenesis.

Aged↗
PubMed1999

Reuse of catheters for percutaneous transluminal coronary angioplasty: effects on procedure time and clinical outcomes.

In July 1996, because of concern regarding the possible transmission of Creutzfeldt-Jakob disease, the province of Quebec stopped the reuse of percutaneous transluminal coronary angioplasty (PTCA) catheters. Prior to this time, PTCA balloon catheters were used a maximum of four times and guide catheters a maximum of two times in the cardiac catheterization laboratory at our institution. After this time, only new catheters were used. In order to examine the effects of catheter reuse on duration of PTCA procedures and clinical outcomes, we compared 53 consecutive patients undergoing PTCA prior to 21 July 1996 with 54 consecutive patients undergoing PTCA after that time. A total of 81 men and 26 women underwent PTCA (average age, 64 +/- 12 years). There were no significant differences between the single-use and reuse groups with respect to baseline characteristics. There were also no significant differences in the numbers of PTCA catheters used (97 vs. 103, P = NS) or angiographic success rates (88% vs. 83%, P = NS). There was a trend for total procedure time and fluoroscopy time to be slightly longer for single-use compared with reuse cases (49.2 vs. 45.7 min and 19.7 vs. 16.8 min, respectively; P = NS for both comparisons). However, after controlling for case severity and the use of stents, there were no significant differences in total procedure time or fluoroscopy time between the two groups. We found little evidence to suggest that the reuse of PTCA catheters is associated with longer total procedure time or fluoroscopy time. We conclude that if catheter reuse is not found to be associated with infectious disease transmission, its widespread use should be considered. Cathet. Cardiovasc. Intervent. 48:54-60, 1999.

Aged↗
PubMed1999

Myocardial glucose transporter GLUT1: translocation induced by insulin and ischemia.

Myocardial glucose transport is not only facilitated by the insulin sensitive glucose transporter (GLUT) 4 but also by GLUT1. It was recently demonstrated that ischemia induces GLUT4 translocation by a mechanism distinct from the insulin-induced signaling pathway. However, the role of ischemia-mediated GLUT1 translocation and the signaling pathway involved is not yet defined. This study investigated the effects of wortmannin, a phosphatidylinositol-3 kinase (PI3kinase) inhibitor, on basal, ischemia- and insulin-stimulated GLUT1 redistribution. PI3kinase is known to participate in insulin-mediated GLUT4 translocation. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mmol/l glucose according to Langendorff and treated with/without 1 micromol/l wortmannin, 100 nmol/l insulin and 15 min no-flow ischemia. Relative subcellular distribution of GLUT1 protein was analysed using membrane fractionation and subsequent Western blotting. Both ischemia and insulin significantly increased the relative amount of GLUT1 in the plasma membrane (PM) compared to controls (41.6+/-2.8% in controls v 46.0+/-2.3% in ischemic and 51.4+/-3.9% in insulin hearts, both P<0.05) with a concomitant decrease of GLUT1 in intracellular membranes. However, the increases were moderate in view of the more than 2-fold stimulated GLUT4 translocation shown for ischemia and insulin. Although wortmannin completely inhibited insulin-induced GLUT1 translocation (42.0+/-2.0% GLUT1 on PM), it had no effect on the ischemia-induced translocation of GLUT1 (45. 4+/-1% GLUT1 on PM). Treatment with the inhibitor alone did not influence basal GLUT1 distribution. Results show that in the perfused rat heart, PI3 kinase is involved in the insulin-induced signaling leading to GLUT1 translocation but not in the ischemia-mediated signaling and basal GLUT1 trafficking. This suggests two different pathways for ischemia- and insulin-induced GLUT1 translocation as recently shown for GLUT4.

Androstadienes↗
PubMed1999

UDP-glucuronosyltransferase activity in human liver and colon.

BACKGROUND & AIMS: The contribution of glucuronidation toward human drug metabolism is carried out by the Super gene family of UDP-glucuronosyltransferases (UGTs). Regulation of the human UGT1A locus is tissue specific, resulting in the unique expression of multiple hepatic and extrahepatic gene products. Studies were undertaken to examine UGT1A expression in human hepatic and colonic tissues. METHODS: UGT1A messenger RNA, protein, catalytic activity, and substrate kinetics were studied in 5 samples of normal hepatic and sigmoid colon tissue using duplex reverse-transcription polymerase chain reaction (RT-PCR), enzymatic and Western blot analysis, and indirect immunofluorescence analysis. RESULTS: Specific patterns of UGT1A gene expression occur in the liver and colon, which were consistent with different banding patterns as detected by Western blot analysis using a UGT1A-specific antibody. However, microsomal UGT activities in colon were up to 96-fold lower for many phenolic substrates, a finding that was not concordant with RT-PCR and Western blot analysis. Interestingly, UGT activity toward tertiary amines and some steroid hormones was equal. CONCLUSIONS: Differences of glucuronidation activity between human liver and colon suggest that UGT1A activity may be regulated as a result of the relative presence of individual isoforms with differing catalytic activities or by tissue-specific modulators after gene expression.

Adolescent↗
PubMed1999

Pharmacology of G-1-64, a new nondepolarizing neuromuscular blocking agent with rapid onset and short duration of action.

BACKGROUND: Chances are slim that a clinically useful ultra-short-acting neuromuscular blocking agent of rapid onset will emerge from the benzylisoquinolinium or the aminosteroid series to which all currently popular relaxants belong. G-1-64 is a promising prototype of a new series of bis-quaternary ammonium salt of bistropinyl diester derivatives we have synthesized and studied in the laboratory. METHODS: Neuromuscular block (NMB) and autonomic and cardiovascular side effects were studied on appropriate preparations of anesthetized rats, rabbits, cats, ferrets, pigs and monkeys. Neuromuscular blocking characteristics, cumulativeness, and pharmacological reversibility were determined. Cardiac vagal block was evaluated by the inhibition of the bradycardic response to stimulation of the vagus in the cat, rat, ferret, and pig. Sympathetic ganglion block was evaluated on the cat's superior cervical ganglion/nictitating membrane preparation. Arterial blood pressure and heart rate were determined in all species. RESULTS: G-1-64 produced nondepolarizing NMB with train-of-four (TOF) and tetanic fades, and reversible with anticholinesterases. Its ED50 ranged between 60 and 800 microg/kg in these species. It showed a significantly faster onset (0.9-2.1 min) and/or shorter duration of action (5-12 min) than either atracurium or mivacurium. It did not show cumulativeness on repeated doses or infusion. A varying degree of cardiac vagal block was present, dependent on the species at doses exceeding the ED80 for NMB. Cardiovascular changes, ganglion block or signs suggesting histamine release were absent. CONCLUSION: With favorable neuromuscular blocking characteristics and modest side effects, G-1-64 and similar derivatives may have clinical potential.

Androstanols↗
PubMed1999

Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects.

Using a bipolar rating scale, human subjects rated the intensity of irritation sensation evoked by repeated application of piperine (75 p.p.m.) or nicotine (0.12%) to one side of the dorsal surface of the tongue. The intensity of irritation elicited by repeated application of piperine significantly increased, while irritation elicited by repeated nicotine significantly decreased. We additionally tested if nicotine or piperine desensitized the tongue. After either piperine or nicotine was repeatedly applied to one side of the tongue, a 5 or 10 min rest period ensued, followed by re-application of piperine or nicotine to both sides of the tongue. Subjects were asked to choose which side of the tongue gave rise to a stronger irritation in a two-alternative forced choice (2-AFC) paradigm. In addition, they gave separate ratings of the intensity of irritation on the two sides of the tongue. When piperine was applied bilaterally after unilateral pretreatment with piperine and a 10 min rest period, subjects consistently chose the non-pretreated side to yield stronger irritation and assigned significantly higher ratings to that side, indicative of piperine self-desensitization. A similar self-desensitization effect was found when bilateral application of nicotine followed unilateral treatment with nicotine and a 5 min rest period. Unilateral treatment with piperine also reduced nicotine-evoked irritation on the pretreated side (cross-desensitization), but treatment with nicotine did not affect piperine-evoked irritation. This asymmetrical cross-desensitization pattern is similar to that observed between capsaicin and nicotine and constitutes an additional similarity between piperine and capsaicin.

Adult↗
PubMed1999

Nerve-mediated motility of ileal segments isolated from NK(1) receptor knockout mice.

Tachykinins such as substance P (SP) and neurokinin A (NKA) acting on neurokinin (NK) receptors modulate the nonadrenergic noncholinergic (NANC) neurotransmission in the gastrointestinal tract of several species, but the information about the mouse small intestine is scanty. Both SP and NKA induced concentration-dependent contractions of ileal segments isolated from wild-type mice that were blocked by NK(1) and NK(2) antagonists, respectively. In contrast, segments isolated from NK(1) receptor (NK(1)-R) knockout mice responded only to elevated concentrations of SP. To reveal the inhibitory NANC (iNANC) responses, tissues were pretreated with atropine and guanethidine. Under these conditions, a tetrodotoxin-sensitive relaxation in response to electrical field stimulation (EFS) was observed. NK(1)-R knockout mice presented a trend toward an increase in iNANC responses, whereas the NK(1)-R antagonist significantly potentiated iNANC relaxation in tissues isolated from wild-type mice. N(G)-nitro-L-arginine methyl ester (100 microM) transformed the relaxant response to EFS into a tetrodotoxin-sensitive, frequency-dependent contraction characteristic of an excitatory NANC (eNANC) system. A NK(1)-R antagonist abolished the contractile responses of the mouse ileum to EFS, whereas a NK(2) receptor antagonist had a trend toward reducing EFS-induced contraction. The eNANC component was absent in NK(1)-R knockout mice. Measurement of SP-like immunoreactivity indicated similar amounts of SP per gram of tissue isolated from wild-type and NK(1)-R knockout mice, indicating that the observed differences in response to EFS were not due to a differential peptide content. It is concluded that, in the mouse ileum, both NK(1) and NK(2) receptors modulated the responses to exogenous tachykinins, whereas NK(1) is the primary tachykinin receptor involved in both iNANC and eNANC transmission.

Animals↗
PubMed1999

Retigabine N-glucuronidation and its potential role in enterohepatic circulation.

The metabolism of retigabine in humans and dogs is dominated by N-glucuronidation (), whereas in rats, a multitude of metabolites of this new anticonvulsant is observed (). The comparison of the in vivo and in vitro kinetics of retigabine N-glucuronidation in these species identified a constant ratio between retigabine and retigabine N-glucuronide in vivo in humans and dog. An enterohepatic circulation of retigabine in these species is likely to be the result of reversible glucuronidation-deglucuronidation reactions. Rats did not show such a phenomenon, indicating that enterohepatic circulation of retigabine via retigabine N-glucuronide does not occur in this species. In the rat, 90% of retigabine N-glucuronidation is catalyzed by UDP-glucuronosyltransferase (UGT)1A1 and UGT1A2, whereas family 2 UGT enzymes contribute also. Of ten recombinant human UGTs, only UGTs 1A1, 1A3, 1A4, and 1A9 catalyzed the N-glucuronidation of retigabine. From the known substrate specificities of UGT1A4 toward lamotrigine and bilirubin and our activity and inhibition data, we conclude that UGT1A4 is a major retigabine N-glucuronosyl transferase in vivo and significantly contributes to the enterohepatic cycling of the drug.

Animals↗
PubMed1998

Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis.

The tyrosine kinase Jak3 plays a key role in transducing signals from the IL-2, -4, -7, -9, and -15 receptors. Mice lacking Jak3 exhibit a profound, early block in both B and T cell development. To examine the mechanisms whereby Jak3 influences T cell function, we have reconstituted thymic development in Jak3-/- animals by introducing a Jak3 transgene in which expression was driven by the lck proximal promoter. Thymic reconstitution required Jak3 kinase activity, as catalytically inactive Jak3 did not restore early thymic development. Furthermore, the thymus-restricted expression pattern of the transgene allowed us to assess the requirement for Jak3 in peripheral T cells. In these mice, loss of Jak3 expression was associated with a failure to proliferate in response to antigen receptor crosslinking, the accumulation of T cells manifesting an activated cell surface phenotype, and an increased CD4/CD8 ratio among peripheral T cells, all of which are characteristics that were observed in Jak3-/- animals. Finally, we present data which suggest that peripheral T cells proliferate more rapidly in vivo and also undergo apoptosis more rapidly, upon loss of Jak3. Hence Jak3 exerts effects on mature peripheral T lymphocytes, as well as on thymocytes, resulting in the proper maintenance of circulating, quiescent cells.

Animals↗