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Biomedical subjects

L Gagnon

Publications and source records attributed to L Gagnon.

At least 19 recordsLinked to original sources

D-LysAsnProTyr tetrapeptide: a novel B-cell stimulant and stabilized bursin mimetic.

The tetrapeptide I (D-lysine-L-asparaginyl-L-prolyl-L-tyrosine or D-LysAsnProTyr), and analogue sequences, were synthesized and evaluated for the ability to stimulate immune cell subsets. These sequences were selected based on their perceived ability to readily adopt a beta-turn structure. In vitro immunological assays revealed a robust stimulation of mitogen activated B-cell proliferation and a modest to significant stimulation of cytotoxic T lymphocytes (CTLs). Further, this in vitro stimulation of B-cells was accompanied by an in vivo expansion of B-cells in C57BL/6 mice, as demonstrated by immunophenotyping experiments. Interestingly, a conformational analysis of the low energy conformers of I and the endogenous B-cell stimulant bursin (LysHisGlyNH2) shows that these molecules can be superimposed. However, I displayed significantly enhanced physiological stability. For a number of reasons, I may be a particularly useful vaccine adjuvant.

Animals↗

Inactivation of the ampD gene in Pseudomonas aeruginosa leads to moderate-basal-level and hyperinducible AmpC beta-lactamase expression.

It has been shown in enterobacteria that mutations in ampD provoke hyperproduction of chromosomal beta-lactamase, which confers to these organisms high levels of resistance to beta-lactam antibiotics. In this study, we investigated whether this genetic locus was implicated in the altered AmpC beta-lactamase expression of selected clinical isolates and laboratory mutants of Pseudomonas aeruginosa. The sequences of the ampD genes and promoter regions from these strains were determined and compared to that of wild-type ampD from P. aeruginosa PAO1. Although we identified numerous nucleotide substitutions, they resulted in few amino acid changes. The phenotypes produced by these mutations were ascertained by complementation analysis. The data revealed that the ampD genes of the P. aeruginosa mutants transcomplemented Escherichia coli ampD mutants to the same levels of beta-lactam resistance and beta-lactamase expression as wild-type ampD. Furthermore, complementation of the P. aeruginosa mutants with wild-type ampD did not restore the inducibility of beta-lactamase to wild-type levels. This shows that the amino acid substitutions identified in AmpD do not cause the altered phenotype of AmpC beta-lactamase expression in the P. aeruginosa mutants. The effects of AmpD inactivation in P. aeruginosa PAO1 were further investigated by gene replacement. This resulted in moderate-basal-level and hyperinducible expression of beta-lactamase accompanied by high levels of beta-lactam resistance. This differs from the stably derepressed phenotype reported in AmpD-defective enterobacteria and suggests that further change at another unknown genetic locus may be causing total derepressed AmpC production. This genetic locus could also be altered in the P. aeruginosa mutants studied in this work.

Ampicillin↗

Thioamides: synthesis, stability, and immunological activities of thioanalogues of Imreg. Preparation of new thioacylating agents using fluorobenzimidazolone derivatives.

Imreg (Tyr1-Gly2-Gly3) is a well-known immunostimulant. However, it possesses a short half-life. Stabilized analogues of Imreg were prepared by a regioselective insertion in which peptide bonds at position 1,2 or 2,3 were replaced by thioamide linkages. This was achieved by using new thioacylating agents based on thioacyl-fluoro-N-benzimidazolone. The synthesis and properties of these reagents are described herein. This peptide modification enhanced significantly the half-life of the thioanalogues relative to Imreg in blood. The thioanalogues and Imreg were tested in vitro in T and B cell proliferation assays and for their ability to stimulate cytotoxic T-lymphocytes (CTLs). Only thiotyrosyl glycyl glycine 11 displayed some activity as evidenced by a weak stimulation of CTLs. On the basis of this activity and the increased stability, an in vivo immunological evaluation was undertaken. Immunophenotyping of 11 revealed a significant increase in activated CTL and NK cell populations in the spleen. This expansion was also accompanied by a significant stimulation of NK cells and the B cell proliferative response. Thioanalogues of Imreg were generally nontoxic, as exemplified by 11. The latter is a promising immunostimulant which may be targeted for cancer and viral infections, where CTLs and NK cells play an important role, or as a vaccine adjuvant where stimulation of antibody-producing B cells is important.

Adjuvants, Immunologic↗

Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.

PURPOSE: To compare the hemodynamic effects of sevoflurane when used for induction and maintenance of anesthesia with a total intravenous technique in patients with known coronary artery disease (CAD). METHODS: Thirty patients undergoing elective coronary artery bypass graft (CABG) were randomly allocated to receive either sevoflurane (S group, n = 15) at a minimal concentration of 4% in oxygen for induction and at 0.5-2 MAC end-tidal concentration for maintenance, or a total intravenous technique (T group, n = 15) consisting of midazolam for induction and propofol for maintenance. In both groups, anesthesia was supplemented with sufentanil and muscle relaxation with cis-atracurium. Hemodynamic measurements included systemic and pulmonary pressures, heart rate, mixed venous oxygen saturation and cardiac output at the following times: pre-induction, 7 and 25 min post-induction, chest closure, one hour after surgery and pre and post tracheal extubation. RESULTS: More patients in the S group (8/15) presented bradycardia in the induction period (T:2/15) (P = 0.05). During maintenance of anesthesia, treatment of hypertension was more frequent in the T group (12/15) than in the S group (6/15) (P = 0.025). All other parameters were comparable. CONCLUSION: Induction of anesthesia in patients with CAD, VCRII with sevoflurane supplemented by sufentanil provided hemodynamic responses comparable with those of TIVA although bradycardia was observed more often with sevoflurane. Intraoperative control of systemic blood pressure was achieved with fewer interventions with a sevoflurane/sufentanil maintenance than with a propofol/sufentanil technique in CABG surgery.

Aged↗

A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To determine the hemodynamic and pharmacodynamic effects of rapid bolus administration of cisatracurium compared with vecuronium. DESIGN: A randomized, prospective, double-blind study. SETTING: Tertiary-care university hospitals. PARTICIPANTS: Seventy-nine adult patients with diagnosed coronary artery disease (CAD). INTERVENTION: Elective coronary artery bypass graft surgery (CABG). MEASUREMENTS AND MAIN RESULTS: Patients were randomly divided into four groups. Patients received a rapid bolus of two or four times the 95% peak depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all patients received a rapid bolus administration of either study drug. Maintenance of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic. Patients were monitored with radial and pulmonary artery catheters and electromyography. End points of the study were hemodynamic stability at induction, after bolus administration of study drugs, and after intubation; the quality of intubating conditions; drug interventions to correct hemodynamic instability; the onset, duration, and recovery of neuromuscular function; and drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a similar proportion in all four groups after induction while, following study drug administration, MAP and HR did not change significantly. Both cisatracurium groups required more boluses to maintain neuromuscular block, but spontaneous recovery rates were faster. Both agents, but cisatracurium to a lesser degree, showed increased duration with repeated maintenance doses. Both agents afforded good to excellent intubating conditions, but the cost of cisatracurium was significantly less. CONCLUSION: The authors conclude there is no evidence of a hemodynamic difference between the two neuromuscular blocking drugs (NMBDs). There are some clinical and cost advantages in favor of cisatracurium.

Adolescent↗

Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss?

Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) or no or < 500 microgram/d (control group [Group C] mean: 309 microgram/d) for more than 5 yr were enrolled in this study. Each had, 3 yr ago and at this last evaluation, a clinical evaluation and measurements of expiratory flows and of bone density and bone metabolism markers. Lumbar spine bone density (last visit) was similar in the two groups with respective values of 0.94 +/- 0.03 (HD) and 0.96 +/- 0.03 g/cm2 (C) (p > 0.05). T and Z scores were -1.21 +/- 0.19 and -0.70 +/- 0.18 (HD), -0.95 +/- 0.25 and -0.47 +/- 0.21 (C) respectively (p > 0.05). A correlation was found between the decrease in bone density and the mean daily dose of corticosteroid in Group HD although these changes were quite small, mean bone density being unchanged over the 3-yr period. Serum and urinary parameters were similar in the two groups. Furthermore, neither initial bone density nor any of the biological parameters could predict changes in bone density over a period of 3 yr. In conclusion, bone density was similar in both study groups and not significantly different over a 3-yr period. Neither initial bone density nor biological markers of bone metabolism helped to predict changes in bone mass.

Administration, Inhalation↗

Synthesis and activity of dipeptides, linked to targeting ligands, as specific NK cell enhancers.

Water soluble analogues of the lipophilic immunostimulant, octadecyl D-alanyl-L-glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate natural killer (NK) cells. One of these compounds in which the octadecyl chain of BCH-527 was replaced with a shorter chain alcohol, 6-(D-alanyl-L-glutaminylamino)hexan-1-ol, 9, displayed an in vitro stimulation of NK cells comparable to that of interleukin 2 (IL 2). However, when the hydroxyl of 9 was linked to L-fucose to yield 1-beta-[6-(D-alanyl-L-glutaminylamino)hex-1-yl]-L- fucopyranose (BCH-2537, 1), the observed stimulation of NK cells was greater than that observed with IL 2. Further evaluation of these compounds revealed that the improved in vitro activity of BCH-2537 was more pronounced in vivo. That is, while both compounds significantly increased splenic NK cells, only BCH-2537 significantly increased the activity of these cells in vivo. In terms of a structure-activity relationship, NK cell activity was sensitive to minor structural modifications. It was influenced by conservative substitutions within the dipeptide, the length of the hydrocarbon chain, and the functionality at the end of the chain. No other compound enhanced NK cell activity to the extent exhibited by BCH-2537, although a few were equipotent to 9.

Adjuvants, Immunologic↗

Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization.

BACKGROUND: The efficacy of prophylactic epsilon-aminocaproic acid and tranexamic acid to reduce transfusions after primary myocardial revascularization was evaluated in a teaching hospital context. METHODS: Patients (n = 134) received either epsilon-aminocaproic acid (15-g bolus + infusion of 1 g/h), high-dose tranexamic acid (10-g bolus + placebo infusion), or normal saline solution in a double-blind fashion. Anticoagulation and conduct of cardiopulmonary bypass were standardized. RESULTS: Tranexamic acid and epsilon-aminocaproic acid produced a significant reduction in postoperative blood loss compared with placebo (median loss, 438 mL, 538 mL, and 700 mL, respectively). Transfusion of red cells was similar in all three groups. Nonetheless, the percentage of patients receiving hemostatic blood products was significantly decreased in the epsilon-aminocaproic acid group compared with the placebo group (20% versus 43%; p = 0.03). Both tranexamic acid and epsilon-aminocaproic acid significantly decreased total exposure to allogeneic blood products compared with placebo (p = 0.01 and p = 0.05, respectively), and this reduction was clinically important (median exposure, 2, 2, and 7.5 units, respectively). Fibrinolysis was inhibited significantly in both treatment groups. CONCLUSIONS: We conclude that either high-dose tranexamic acid or epsilon-aminocaproic acid effectively reduces transfusions in patients undergoing primary, elective myocardial revascularization.

Aminocaproic Acid↗

Music and emotion: perceptual determinants, immediacy, and isolation after brain damage.

This study grew out of the observation of a remarkable sparing of emotional responses to music in the context of severe deficits in music processing after brain damage in a non-musician. Six experiments were designed to explore the perceptual basis of emotional judgments in music. In each experiment, the same set of 32 excerpts taken from the classical repertoire and intended to convey a happy or sad tone were presented under various transformations and with different task demands. In Expts. 1 to 3, subjects were required to judge on a 10-point scale whether the excerpts were happy or sad. Altogether the results show that emotional judgments are (a) highly consistent across subjects and resistant to brain damage; (b) determined by musical structure (mode and tempo); and (c) immediate. Experiments 4 to 6 were designed to asses whether emotional and non-emotional judgments reflect the operations of a single perceptual analysis system. To this aim, we searched for evidence of dissociation in our brain-damaged patient, I.R., by using tasks that do not require emotional interpretation. These non-emotional tasks were a 'same-different' classification task (Expt. 4), error detection tasks (Expt. 5A,B) and a change monitoring task (Expt. 6). I.R. was impaired in these non-emotional tasks except when the change affected the mode and the tempo of the excerpt, in which case I.R. performed close to normal. The results are discussed in relation to the possibility that emotional and non-emotional judgments are the products of distinct pathways.

Adult↗

Sequence of the ponA gene and characterization of the penicillin-binding protein 1A of Pseudomonas aeruginosa PAO1.

The nucleotide sequence of the ponA gene encoding the high molecular-mass penicillin-binding protein 1A (PBP1A) of Pseudomonas aeruginosa (Pa) PAO1 was determined and characterized. The predicted PBP1A protein of 822 amino acids (aa) has a calculated molecular mass of 91.2 kDa corresponding to the size of the protein expressed in vitro and in vivo. A penicillin-binding (PB) assay showed that the Pa ponA gene product covalently binds penicillin. The deduced PBP1A aa sequence has features typical of class-A high-molecular-mass PBPs: a highly hydrophobic N-terminus portion containing a potential transmembrane segment which might anchor the protein to the cytoplasmic membrane; an N-terminal module with the conserved boxes 1 (E86D(DN)F(AN)H(Y)G), 2 (G117GS(T)I(TM)Q), 3 (R139K(IN)E(ILL)AL) and 4 (R221R(NW)IL); a PB module with the conserved boxes 5 (S461SFK), (S520RN) and (K695TG); an internal extension at aa 297-407 between the N-terminal and PB modules; and a C-extension at the end of the PB module at aa 742 to 822. The highest percentage of similarity (62.8%) was found with the class A high-molecular-mass PBP1A of Escherichia coli (Ec) and Haemophilus influenzae. The observed extensive homology in the modular design of the Pa PBP1A with the bifunctional Ec PBP1A suggests structural and functional relationships between these proteins and refutes the proposed correspondence between Pa PBP1A and Ec PBP1B.

Amino Acid Sequence↗

Synthesis and activity of 6-substituted purine linker amino acid immunostimulants.

A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), displayed an in vitro stimulation of CTLs comparable to interleukin 2 (IL 2). BCH-1393 increased the CTL response between 10(-9) M and 10(-5) M. Further, this potent in vitro activity was reflected as a significant increase in CTL cell number in vivo. However, immunophenotyping of some of the other equipotent compounds did not reveal a parallel relative increase in CTLs in vivo. It was difficult to formulate a rigorous structure-activity relationship based on in vitro CTL activity. Nevertheless, the activity was dependent upon the nature of the 6-substituent on the purine, the type and stereochemistry of the amino acid, and the distance and spatial freedom between the purine and amino acid as defined by the length and rigidity of the linker. These compounds were generally nontoxic, as exemplified by BCH-1393. BCH-1393 is a promising immunostimulant which may be targeted for those disease states which require an increased CTL or TH1 type response.

Adjuvants, Immunologic↗

Propofol or midazolam for sedation and early extubation following cardiac surgery.

PURPOSE: The purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery. METHODS: ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesia. During cardiopulmonary bypass 100 micrograms.kg-1.min-1 propofol was substituted for isoflurane. Upon arrival in the Intensive Care Unit (ICU), patients were randomized to either 10 micrograms.kg-1.min-1 propofol (n = 21) or 0.25 microgram.kg-1.min-1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2-4). The infusion was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when Haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, arterial blood gas tensions and pulmonary function tests were recorded at specified times. RESULTS: There were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, arterial blood gas tensions and pulmonary function. CONCLUSION: We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.

Adolescent↗

Influence of inhaled corticosteroids and dietary intake on bone density and metabolism in patients with moderate to severe asthma.

OBJECTIVES: Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. DESIGN: A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hôpital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition rate = 15%). MAIN OUTCOME MEASURES: In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and gamma-glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density. SUBJECTS: Thirty-one patients with moderate to severe asthma who had been taking more than 1,000 micrograms beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 micrograms beclomethasone per day or the equivalent. STATISTICAL ANALYSES PERFORMED: Four-factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients. RESULTS: Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P < .05). Significant correlations (P < .02) were observed between bone density and calcium intake (r = .40), phosphorus intake (r = .35), protein intake (r = .30), and serum alkaline phosphatase level (r = -.30). Bone density was not significantly different between the two groups of patients with asthma. APPLICATIONS: A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained.

Absorptiometry, Photon↗

Enhancement of human neutrophil survival and activation by TGF-beta 1.

Transforming growth factor beta (TGF-beta) is a multifunctional growth factor which promotes the inflammatory process. We have investigated the effect of TGF-beta 1 on neutrophil survival, recruitment and activation. These last steps are essential for their participation in the inflammatory response. Our results demonstrate that TGF-beta 1 at a concentration of 20-40 ng/ml is a potent neutrophil chemotactic factor. The chemotactic activity induced by TGF-beta 1 is greater than that induced by fMLP (10(-8) M). Furthermore, TGF-beta 1 (20-30 ng/ml) induces neutrophil activation demonstrated by an increase of respiratory burst and phagocytosis. Finally, TGF-beta 1 also enhances human neutrophil survival (43 to 93%) at concentrations as low as 2 to 20 ng/ml. This study provides evidence that TGF-beta 1 is capable of recruiting and activating neutrophils at inflammatory sites and enhances their survival.

Cell Survival↗

Measurement of heparin concentration in whole blood with the Hepcon/HMS device does not agree with laboratory determination of plasma heparin concentration using a chromogenic substrate for activated factor X.

UNLABELLED: Measurement of circulating heparin concentration has been suggested to optimize anticoagulation during cardiopulmonary bypass. The Hepcon/HMS device (Medtronic HemoTec, Inc., Parker, Colo.) uses heparin/protamine titration to quantitatively determine heparin concentration. Extensive validation of this instrument is still lacking. METHODS: Agreement between heparin concentrations measured by the Hepcon/HMS system and by laboratory determination was evaluated in 16 patients undergoing cardiac operations. For laboratory determinations, plasma heparin concentration was derived from the measure of anti-Xa activity by means of chromogenic substrate technique. The Hepcon/HMS instrument and cartridges measured whole blood heparin concentration. Samples were analyzed 5 minutes after administration of heparin, 15 and 30 minutes after the start of cardiopulmonary bypass, 5 minutes after aortic unclamping, at the end of cardiopulmonary bypass, and after administration of protamine. Data were plotted and interpreted according to the method of Bland and Altman: First, a difference less than 1.4 U/ml (i.e., +/- 0.7 U/ml) was chosen as acceptable, because it would not cause major difficulties in clinical interpretation; second, the difference between the two measurement techniques was plotted against the mean of the two measures. RESULTS: The mean difference (bias) between heparin concentrations derived by the Hepcon/HMS device and those obtained by laboratory determination was as expected for measures performed on whole blood versus plasma (1.45 U/ml). Nevertheless, heparin concentrations derived by the Hepcon/HMS device may be as much as 2.76 U/ml above or 6.17 U/ml below the concentrations measured in the laboratory, differences well outside the predetermined limits of agreement and clearly unacceptable for clinical purposes. CONCLUSION: We conclude that heparin concentrations determined with the Hepcon/HMS instrument do not agree with laboratory determination of heparin concentration. Monitoring of heparin concentrations during bypass with the Hepcon/HMS device cannot be recommended.

Blood Chemical Analysis↗

Gastrojejunal kinetics and the digestion of [15N]beta-lactoglobulin and casein in humans: the influence of the nature and quantity of the protein.

The evolution and luminal effects of different quantities of casein and beta-lactoglobulin were investigated in the upper jejunum of 35 volunteers who ingested 400 mL water with either beta-lactoglobulin or casein in either low or high doses (72.6 mmol N, Lbetalg; 71.7 mmol N, LCas; 368.2 mmol N, Hbetalg; 386.8 mmol N, HCas). The flow rate of the liquid effluents as well as the nitrogen movements were measured and the exogenous ([15N]) and endogenous nitrogen fractions analyzed in the upper jejunum after milk protein ingestion. The basal jejunal liquid flow rate (mL/min) was 3.88+/-1.84 and peaked in the 0-20 min period for water (9.92+/-3.72) and Lbetalg (7.27+/-3.08) and during the 20-40 min period for LCas (5.69+/-2.49), HCas (6.32+/-1.85), and Hbetalg (6.11+/-2.31). One hour after water, LCas, Lbetalg, Hbetalg, and HCas ingestion, 100%, 95%, 85%, 71%, but only 38% of the liquid phase of the meal were passed through the jejunum, respectively. The flow rate of the endogenous nitrogen was 12.93+/-5.22 mmol N/h before meal ingestion; remained unchanged after water, LCas or Hbetalg ingestion; but increased significantly (P<0.05) after Lbetalg and HCas ingestion. The net disappearance of exogenous nitrogen in the upper jejunum 240 min after HCas, Lbetalg, LCas and Hbetalg ingestion was 82.6+/-9.5%, 61.6+/-9.6%, 58.4+/-14.7%, and 44.7%+/-24.4%, respectively. The exogenous fraction of protein nitrogen recovered in the upper intestinal lumen represented 43.3% of the ingested Hbetalg nitrogen, but only 4.9% of the ingested HCas nitrogen. In conclusion, casein and beta-lactoglobulin present differences in both the intestinal kinetics of amino acid delivery and in the nature of the products in the intestinal lumen. These differences have to be taken into account from both nutritional and physiologic points of view for the utilization of these proteins in humans.

Adult↗

Perceiving the tonal ending of tune excerpts: the roles of pre-existing representation and musical expertise.

In this study, sensitivity to tonal relations was assessed by using real melodies instead of traditional scales or chords. Two groups of listeners-one trained, one untrained-rated the goodness of fit of each of the 12 tones of the chromatic scale as the final note of familiar and unfamiliar tune excerpts. The unfamiliar excerpts were the mirror forms in pitch and time of the familiar tunes. The results showed that musicians and nonmusicians exhibited responses that were governed by tonal relations with both familiar and unfamiliar tunes. These findings were corroborated by multiple-regression analysis, which revealed that the pattern of ratings reflected knowledge of the musical structure, beyond the contribution of surface features such as note frequency or pitch proximity between the two last tones.

Adolescent↗

Immunomodulatory and antiviral activities of 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-fluorocytidine.

Two dideoxynucleosides, 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-flurocytidine, containing unnatural L-configuration in their sugar moieties, were synthesized and assayed for antiviral activities. Both compounds were shown to possess potent anti-human immunodeficiency virus type 1 and antihepatitis B virus activities, while demonstrating no anti-herpes simplex viruses 1 and 2 activity. These two compounds exhibited in vitro cellular toxicities for several leukocytic cell lines and were shown to inhibit phytohemagglutinin-stimulated human peripheral blood mononuclear leukocyte proliferations. At inhibitory concentrations, both compounds caused accumulations of cells in the S phase. While demonstrating no obvious morphological toxicity in vivo in mice at concentrations of 75 and 150 mg/kg, 2',3'-dideoxy-beta-L-5-fluorocytidine- treated animals were shown to have considerable increases in CD4/CD8 double positive T lymphocyte population in their blood circulation.

Animals↗