Biomedical subjects

C Gaudin

Publications and source records attributed to C Gaudin.

At least 37 records · Page 2Linked to original sources

PubMed1996

TCR alpha/beta and TCR gamma/delta CD4-/CD8- HLA-DR alloreactive CTL clones do not use Fas/Fas ligand pathway to lyse their specific target cells.

The expression of Fas Ligand (FasL) on human TCRalpha/beta and TCRgamma/delta CD4-/CD8- MHC class II-alloreactive clones and Fas/FasL-mediated cytotoxicity were investigated. These clones mediated a HLA-DR2-restricted cytotoxicity toward E418 B cell line (Fas+). Northern blot analysis demonstrated that all the clones expressed FasL mRNA upon stimulation with E418 specific target. FasL surface expression was detected by immunofluorescence analysis using Fas-Fc soluble protein as well as anti-FasL polyclonal antibodies. Cytotoxicity experiments performed in the presence of anti-Fas, anti-FasL and Fas-Fc molecule indicated that these reagents were unable to inhibit T cell clone mediated lysis toward E418. In addition, when emetine, known to inhibit the induction of Fas-mediated killing, was added during the cytolysis effector phase, no inhibition was observed. These data strongly suggest that Fas/FasL pathway is not involved in this particular T-cell clone-mediated lysis. This cytotoxicity is extracellular Ca(2+)-dependent and is abolished in the presence of EGTA suggesting that it is mainly perforin/granzyme-based.

CD4 Antigens↗

PubMed1996

Interaction between the endoglucanase CelA and the scaffolding protein CipC of the Clostridium cellulolyticum cellulosome.

The 5' end of the cipC gene, coding for the N-terminal part of CipC, the scaffolding protein of Clostridium cellulolyticum ATCC 35319, was cloned and sequenced. It encodes a 586-amino-acid peptide, including several domains: a cellulose-binding domain, a hydrophilic domain, and two hydrophobic domains (cohesin domains). Sequence alignments showed that the N terminus of CipC and CbpA of C. cellulovorans ATCC 35296 have the same organization. The mini-CipC polypeptide, containing a cellulose-binding domain, hydrophilic domain 1, and cohesin domain 1, was overexpressed in Escherichia coli and purified. The interaction between endoglucanase CelA, with (CelA2) and without (CelA3) the characteristic clostridial C-terminal domain called the duplicated-segment or dockerin domain, and the mini-CipC polypeptide was monitored by two different methods: the interaction Western blotting (immunoblotting) method and binding assays with biotin-labeled protein. Among the various forms of CelA (CelA2, CelA3, and an intermediary form containing only part of the duplicated segment), only CelA2 was found to interact with cohesin domain 1 of CipC. The apparent equilibrium dissociation constant of the CelA2-mini-CipC complex was 7 x 10(-9)M, which indicates that there exists a high affinity between these two proteins.

Amino Acid Sequence↗

PubMed1996

Survival and regeneration of adult human and other mammalian photoreceptors in culture.

PURPOSE: Fully mature neurons of central nervous system origin generally are considered unable to survive for extended periods of time in simple culture conditions. The authors report that adult and aged human, porcine, and rodent retinal neurons, including rod and cone photoreceptors, constitute an exception to this idea. METHODS: Cells were dissociated from human postmortem retinas, adult mammalian retinas, and selected brain regions and were seeded into tissue culture plates and left to develop as monolayer cultures for up to 2 months. A battery of antibody markers was used to identify the nature and morphology of the cells in vitro. RESULTS: Photoreceptor cell survival of rods and cones was observed routinely when the delay between the time of death until culture preparation was 50 hours or less, compatible with current eye bank practice. Two-week-old cultures were formed of rod photoreceptors, representing approximately 50% of neuronal cell types; cone photoreceptors, representing 5% to 30% of neuronal cell types; other retinal neurons (especially amacrine cells approximately 20%); and retinal glial cells, present in variable numbers. Glial cells were essential for long-term photoreceptor survival and neurite outgrowth. Adult mammalian brain neurons isolated under the same conditions did not survive. CONCLUSIONS: Fully adult human and other mammalian retinal neurons, including photoreceptors, exhibit remarkable plasticity in vitro, and such monolayer models may have applications in physiological, pharmacologic, and toxicologic studies of human and other mammalian retina.

Aged↗

PubMed1996

[Effects of chloroquine on the replication of a murine retrovirus].

The wide use of chloroquine (Cq) for prophylaxis and chemotherapy of malaria in Africa, and the increased spread of AIDS in areas of this continent where malaria is endemic, raised the question of a possible interaction between chloroquine intake and HIV infection. Indeed, hydroxychloroquine and chloroquine itself have been shown to inhibit HIV-1 replication in vitro, hydroxychloroquine being proposed as a potential useful adjunctive therapy in the treatment of HIV-1 infection. On the other hand, chloroquine has been reported to enhance the replication of Semliki forest and encephalomyocarditis viruses in a mouse model. In an attempt to elucidate Cq effect on retroviral replication, we have studied the effect of various concentrations of chloroquine in vitro (0.1 nmol/l to 25 mumol/l) on Friend retrovirus (FV)-infected fibroblasts of mice and in vivo (2 to 30 mg/kg) on FV-infected mice. No reduction in the number of virus foci was found in chloroquine-treated fibroblasts cultures. In chloroquine treated-infected mice, no differences were observed in the spleen weights, except an increase at 10 mg/kg. A decrease in splenocyte virus titer was only observed at 10 and 30 mg/kg. No differences in the median survival time was observed up to 30 mg/kg. The authors concluded that chloroquine seemed to have variable effects on viral replication in vivo depending on the dosage, but has no influence on the course of FV-induced disease.

Animals↗

PubMed1995

Crystal structure of the catalytic domain of a bacterial cellulase belonging to family 5.

BACKGROUND: Cellulases are glycosyl hydrolases--enzymes that hydrolyze glycosidic bonds. They have been widely studied using biochemical and microbiological techniques and have attracted industrial interest because of their potential in biomass conversion and in the paper and textile industries. Glycosyl hydrolases have lately been assigned to specific families on the basis of similarities in their amino acid sequences. The cellulase endoglucanase A produced by Clostridium cellulolyticum (CelCCA) belongs to family 5. RESULTS: We have determined the crystal structure of the catalytic domain of CelCCA at a resolution of 2.4 A and refined it to 1.6 A. The structure was solved by the multiple isomorphous replacement method. The overall structural fold, (alpha/beta)8, belongs to the TIM barrel motif superfamily. The catalytic centre is located at the C-terminal ends of the beta strands; the aromatic residues, forming the substrate-binding site, are arranged along a long cleft on the surface of the globular enzyme. CONCLUSIONS: Strictly conserved residues within family 5 are described with respect to their catalytic function. The proton donor, Glu170, and the nucleophile, Glu307, are localized on beta strands IV and VII, respectively, and are separated by 5.5 A, as expected for enzymes which retain the configuration of the substrate's anomeric carbon. Structure determination of the catalytic domain of CelCCA allows a comparison with related enzymes belonging to glycosyl hydrolase families 2, 10 and 17, which also display an (alpha/beta)8 fold.

Binding Sites↗

PubMed1995

In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma.

Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infiltrated by a large mononuclear infiltrate mainly composed of T lymphocytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) alpha and beta chains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined V alpha and V beta gene segment usage by PCR using a panel of V specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). A highly diverse usage of TCR V alpha and V beta gene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed V beta specificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with V beta 4 transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed V beta transcripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in V beta 4) specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens.

Adult↗

PubMed1995

Effects of superior mesenteric artery stenosis on splanchnic and systemic hemodynamics in conscious rats with biliary cirrhosis.

BACKGROUND/AIMS: Since portal tributary blood flow is increased in portal hypertension due to cirrhosis, a reduction in mesenteric arterial blood flow should decrease portal pressure. METHODS: Calibrated stenosis of the superior mesenteric artery was performed in bile duct ligated rats, using a 22-gauge needle. Arterial stenosis was performed 4 weeks after bile duct ligation. Hemodynamic studies were performed in the 5th week following bile duct ligation in conscious rats. RESULTS: At that time, no digestive tract alterations were observed. In rats with mesenteric arterial stenosis, portal pressure was 12.2 +/- 2.0 mmHg; this value was lower than in rats with cirrhosis without arterial stenosis (14.5 +/- 1.1 mmHg) but higher than normal rats (5.8 +/- 0.7 mmHg). In rats with cirrhosis with mesenteric arterial stenosis, portal tributary and mesenteric blood flows were lower than in rats with cirrhosis without arterial stenosis and not significantly different from normal rats. In rats with mesenteric stenosis, cardiac index was significantly lower than in rats with cirrhosis and not significantly different from normal rats. CONCLUSION: This study shows that calibrated superior mesenteric arterial stenosis normalized portal tributary blood flow and reduced but did not normalize the degree of portal hypertension.

Animals↗

PubMed1995

Blunted natriuresis and abnormal systemic hemodynamic responses to C-type and brain natriuretic peptides in rats with cirrhosis.

BACKGROUND/AIMS: The effects of C-type and brain natriuretic peptides (CNP and BNP, respectively) on renal excretion of sodium and hemodynamics have not yet been studied in cirrhosis. METHODS: This study aimed to examine the effects of saline, CNP (300 ng.kg-1.min-1 i.v. for 30 min) and BNP (600 ng.kg-1.min-1 i.v. for 30 min) on natriuresis and diuresis in normal and rats with cirrhosis. Moreover, regional and systemic hemodynamics were measured prior to and following CNP and BNP administration in normal rats and rats with cirrhosis with ascites. RESULTS: In rats with cirrhosis, the effects of CNP or BNP or natriuresis and diuresis did not significantly differ from the effects of saline. CNP significantly decreased portal pressure and systemic vascular resistance and significantly increased the cardiac index. BNP significantly decreased portal tributary blood flow, portal pressure and cardiac index. In normal rats, natriuresis and diuresis were significantly higher with CNP and BNP than with saline. Systemic hemodynamics were not changed by CNP. A decrease in arterial pressure was the sole BNP-induced hemodynamic change. CONCLUSIONS: In conclusion, this study shows that the natriuretic response to pharmacological doses of CNP and BNP is blunted in rats with cirrhosis. This blunting may be related to an activation of the endogenous antinatriuretic systems secondary to systemic vasodilation (by CNP) or to a decreased cardiac index (by BNP). Finally, this study shows that CNP and BNP have a portal hypotensive action.

Animals↗

PubMed1995

Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis.

BACKGROUND/AIMS: In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, alpha 1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown. METHODS: Thus, pressor dose-response curves to vasoconstrictors [phenylephrine (an alpha 1-agonist, 0.1-500 micrograms/kg) angiotensin II (10-500 ng/kg), vasopressin (0.01-5 IU/kg), and Bay K 8644 (an L-type calcium channel activator, 0.5-50 micrograms/kg)] were obtained in normal rats and in rats with secondary biliary cirrhosis. All experiments were performed in ganglionic-blocked animals to limit the influence of cardiovascular reflexes. Doses of vasoconstrictor necessary to obtain a 40 mmHg increase in arterial pressure (D40) were calculated. RESULTS: Compared to normal animals, rats with cirrhosis had significantly higher D40 values for angiotensin II (171 +/- 57 vs. 344 +/- 41 ng/kg), phenylephrine (2.6 +/- 0.2 vs. 26.4 +/- 10.7 micrograms/kg) and vasopressin (73 +/- 19 vs. 401 +/- 150 mU/kg). Pressor responses to Bay K 8644 did not differ between normal rats and rats with cirrhosis (8.8 +/- 0.9 vs. 10.5 +/- 2.1 micrograms/kg). CONCLUSIONS: In conclusion, this study shows that cirrhosis produces vascular hyporeactivity to phenylephrine, vasopressin and angiotensin II but not to Bay K 8644. Therefore, cirrhosis impairs certain constrictor mechanisms which are shared by phenylephrine, angiotensin II and vasopressin but which do not contribute to the vascular response to Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1995

Short-term cardiovascular effects of somatostatin in patients with cirrhosis.

Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 micrograms) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 micrograms of somatostatin, followed by a 250 micrograms/h infusion for 65 min. A second bolus of 250 micrograms of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to 73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Biochemical properties of a beta-xylosidase from Clostridium cellulolyticum.

A 43-kDa beta-xylosidase from Clostridium cellulolyticum was purified to homogeneity. The enzyme releases xylose from p-nitrophenylxylose and xylodextrins with a degree of polymerization ranging between 2 and 5. The N-terminal amino acid sequence of the enzyme showed homologies with three other bacterial beta-xylosidases. By proton nuclear magnetic resonance spectroscopy, the enzyme was found to act by inverting the beta-anomeric configuration.

Amino Acid Sequence↗

PubMed1995

Validation of 1- and 2-mm transit-time ultrasound flow probes on mesenteric artery and aorta of rats.

The aim of this investigation was to validate and calibrate the 1- and 2-mm transit-time ultrasound, perivascular flow probes on the superior mesenteric artery and aorta of the rat by using an in vivo and in situ calibration system. The baseline blood flows measured by the flowmeter zero-flow function and the true-zero flow measurement, after complete occlusion of the vessels, were not different. The probes were then calibrated, in situ, by timed-volume measurements with a blood/saline pump-perfused circuit. The relationship between measured flow and true flow was linear for both probes. The slope of the 1-mm probe data was not significantly different from the line of identity, whereas the 2-mm probe data slightly overestimated the true flow (slope = 1.2, y-intercept = -3.2 ml/min). The slope of the middle region of the 2-mm probe data, however, was not significantly different from the line of identity, suggesting that the 2-mm probe has a window of accuracy over this range of flows. Progressive elimination of the low and high data points varying the most from the line of identity and reanalysis of the data revealed that the window of accuracy for the 2-mm probe, under our experimental conditions, was between 10.4 and 45.1 ml/min.

Animals↗

PubMed1995

Overexpression of Gs alpha protein in the hearts of transgenic mice.

Alterations in beta-adrenergic receptor-Gs-adenylyl cyclase coupling underlie the reduced catecholamine responsiveness that is a hallmark of human and animal models of heart failure. To study the effect of altered expression of Gs alpha, we overexpressed the short isoform of Gs alpha in the hearts of transgenic mice, using a rat alpha-myosin heavy chain promoter. Gs alpha mRNA levels were increased selectively in the hearts of transgenic mice, with a level 38 times the control. Despite this marked increase in mRNA, Western blotting identified only a 2.8-fold increase in the content of the Gs alpha short isoform, whereas Gs activity was increased by 88%. The discrepancy between Gs alpha mRNA and Gs alpha protein levels suggests that the membrane content of Gs alpha is posttranscriptionally regulated. The steady-state adenylyl cyclase catalytic activity was not altered under either basal or stimulated conditions (GTP + isoproterenol, GTP gamma S, NaF, or forskolin). However, progress curve studies did show a significant decrease in the lag period necessary for GppNHp to stimulate adenylyl cyclase activity. Furthermore, the relative number of beta-adrenergic receptors binding agonist with high affinity was significantly increased. Our data demonstrate that a relatively small increase in the amount of the coupling protein Gs alpha can modify the rate of catalyst activation and the formation of agonist high affinity receptors.

Adenylyl Cyclases↗

PubMed1994

T cell repertoire in patients with B chronic lymphocytic leukemia. Evidence for multiple in vivo T cell clonal expansions.

To characterize circulating T cell subpopulations in B chronic lymphocytic leukemia patients, TCR V alpha and V beta gene-segment use was analyzed by PCR using a panel of V gene-segment subfamily-specific oligonucleotide primers (V alpha 1-29/V beta 1-24). Virtually all V alpha and V beta subfamily specificities were expressed in these patients (nine stage A and four stage C), and the mean values obtained for each specificity were similar to those of a group of 13 healthy donors. Nonetheless, individual analysis revealed that unique V alpha or V beta gene-segment transcripts were overrepresented in patients compared with the control group. Overrepresentation of some TCR V beta chains was also detected by cytofluorometric analysis using a panel of 18 anti-V beta-specific mAbs. To further characterize these T cell subpopulations, we sequenced five different V beta-C beta PCR products in two selected stage A patients and found highly predominant recurrent transcripts in each of the five V beta specificities (50% to 100% of the analyzed sequences with identical V(D)J regions). These results were confirmed on bulk cDNA (i.e., without cloning) and extended to other V beta specificities (up to nine clonal expansions of 24 V beta specificities in one patient) and two other patients using a PCR-based method that determines V(D)J junction size patterns. Finally, it was observed that a V beta 19+ T cell subpopulation was clonally expanded in one patient to up to 30% of circulating T cells. This V beta 19+ CD8+ T cell clone was shown to specifically recognize the autologous tumor cells in vitro, as determined in cytokine release assays. Together, these results support the view that multiple expansions of unique T cell clones may derive in vivo from B chronic lymphocytic leukemia tumor-associated Ag stimulation.

Aged↗

PubMed1994

Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis.

Serotoninergic mechanisms are thought to play a role in portal hypertension. Because this biomine is metabolized by the liver, peripheral blood and plasma levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid (the main metabolite of 5-hydroxytryptamine) were measured in 30 patients with cirrhosis. Whole-blood 5-hydroxytryptamine levels were significantly lower in patients with cirrhosis (158 +/- 28 nM) than in age-matched controls (332 +/- 19 nM), and no correlation was found between these levels and the severity of cirrhosis. Unconjugated plasma 5-hydroxytryptamine levels, an indication of the active form of 5-hydroxytryptamine, were significantly higher in patients with cirrhosis than in controls (6.8 +/- 1.7 nM and 3.4 +/- 0.5 nM, respectively), and in patients with cirrhosis these levels were higher in Pugh grade A than in Pugh grade C patients. Conjugated-plasma 5-hydroxytryptamine levels were not significantly different between patients with cirrhosis (32.2 +/- 8.1 nmol/L) and controls (16.4 +/- 1.4 nmol/L). Plasma 5-hydroxyindole acetic acid was significantly lower in patients with cirrhosis than in controls (1.5 +/- 0.1 nmol/L and 2.3 +/- 0.1 nmol/L, respectively). In conclusion, this study shows that serotoninergic mechanisms are altered in patients with cirrhosis.

Hepatic Veins↗

PubMed1994

Mammalian adenylyl cyclase family members are randomly located on different chromosomes.

Molecular cloning studies have elucidated the presence of multiple isoforms of mammalian adenylyl cyclase. So far, six different isoforms (I to VI) have been fully characterized. Comparison of their structural and biochemical characteristics suggests that the mammalian adenylyl cyclase family can be classified into four subfamilies: type I, type III, type II/IV, and type V/VI. We have determined the chromosomal localization of these genes. Type I gene was assigned to chromosome 7, type III to chromosome 2, types II and IV to chromosomes 5 and 14, and types V and VI to chromosomes 3 and 12. Our results indicate that the different adenylyl cyclase isoforms, even within the same subfamily, are distributed randomly in the genome, in contrast to the chromosomal organization of other components within the same signaling pathway, such as catecholamine receptors and G proteins.

Adenylyl Cyclases↗

PubMed1994

Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis.

BACKGROUND/AIMS: Because the vasodilator nitric oxide is overproduced in cirrhosis, this substance may decrease pressor responses to the vasoconstrictor endothelin 1. This study aimed to examine the effects of a NO synthesis inhibitor (NG-nitro-L-arginine methyl ester; L-NAME) on vascular responsiveness to endothelin 1 in normal and cirrhotic rats. METHODS: Pressor dose-response curves to endothelin 1 (0.5, 1, 3, 6, and 10 micrograms/kg intravenously) were obtained in animals with or without pretreatment with L-NAME. RESULTS: Pressor responses to endothelin 1 alone were significantly lower in cirrhotic than in normal rats. In cirrhotic animals, pressor responses to 3, 6, and 10 micrograms/kg of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. The responses to the other doses of endothelin 1 were not affected by L-NAME. In normal rats, pressor responses to all doses of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. In animals pretreated with L-NAME, pressor responses to 6 and 10 micrograms/kg of endothelin 1 did not differ between cirrhotic and normal rats, whereas responses to other doses remained lower in cirrhotic than in normal rats. CONCLUSIONS: In rats with cirrhosis, NO seems to contribute to vascular hyporeactivity to high doses but not to low doses of endothelin 1.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Effect of clonidine on liver oxygen extraction during alcohol withdrawal in man.

Since catecholamines can alter splanchnic oxygen transport and extraction, the suppression of sympathetic overactivity during alcohol withdrawal might improve hepatic oxygen extraction. Therefore, this study investigated the effects of clonidine, a centrally-acting alpha 2-agonist which reduces sympathetic nervous outflow, on splanchnic oxygen transport and extraction in 13 patients with chronic alcoholism during alcohol withdrawal. All patients had elevated transaminases and steatosis at liver biopsy and were withdrawn from alcohol 51 +/- 15 h (mean +/- SD) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of clonidine, 150 micrograms. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r = -0.63, p < 0.025). After clonidine administration, the decrease in plasma norepinephrine correlated with the norepinephrine basal value (r = 0.889, p < 0.001), and splanchnic oxygen extraction increased (from 40 +/- 15 to 49 +/- 17%, p < 0.025). After clonidine administration, splanchnic oxygen extraction was correlated with the decrease in plasma norepinephrine (r = 0.72, p < 0.01). Arterial lactate concentration decreased (from 0.74 +/- 0.20 to 0.64 +/- 0.23 mmol/l, p < 0.01). These results suggest that defective liver oxygen extraction might occur during alcohol withdrawal as a result of sympathetic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be controlled by pharmacological manipulation.

Adult↗