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Biomedical subjects

B L Bennett

Publications and source records attributed to B L Bennett.

At least 37 records · Page 2Linked to original sources

Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB.

Interleukin-4 (IL-4), an immunoregulatory cytokine secreted from activated T-helper 2 lymphocytes, eosinophils, and mast cells, stimulates the expression of a number of immune system genes via activation of the transcription factor, STAT6. However, IL-4 can concomitantly suppress the expression of other immune-related gene products, including kappa light chain, FcgammaRI, IL-8, and E-selectin. We demonstrate that IL-4 activates STAT6 in human vascular endothelial cells and that two STAT6 binding sites are present in the promoter of the E-selectin gene. IL-4-induced STAT6 binding does not activate E-selectin transcription but instead suppresses tumor necrosis factor alpha-induced expression of the E-selectin gene. STAT6 was found to compete for binding to a region in the E-selectin gene promoter containing overlapping STAT6 and NF-kappaB binding sites, effectively acting as an antagonist of NF-kappaB binding and transcriptional activation. This novel mechanism for IL-4-mediated inhibition of inflammatory gene expression provides an example of a STAT factor acting as a transcriptional repressor rather than an activator.

DNA↗

Glucose transport in a murine mammary epithelial cell line.

The glucose transport systems of the COMMA-D cell line (a murine mammary epithelial cell line) were examined using 2-deoxyglucose as substrate. The kinetics and inhibition studies with other sugars including xylose suggested that the transport system had properties of both GLUT-1 and Glut-3. Subsequent analysis of mRNA transcripts using cDNAs for GLUT-1 to 4 showed that only GLUT-1 was expressed in the COMMA-D cells. The results highlight the fact that kinetic and substrate specificity are not sufficient, by themselves, for the identification and characterisation of GLUT isoforms in cultured cells.

Animals↗

Persistence of supercompensated muscle glycogen in trained subjects after carbohydrate loading.

Several carbohydrate (CHO)-loading protocols have been used to achieve muscle glycogen supercompensation and prolong endurance performance. This study assessed the persistence of muscle glycogen supercompensation over the 3 days after the supercompensation protocol. Trained male athletes completed a 6-day CHO-loading protocol that included cycle ergometer exercise and dietary manipulations. The 3-day depletion phase began with 115 min of cycling at 75% peak oxygen uptake followed by 3 x 60-s sprints and included the subjects consuming a low-CHO/high-protein/high-fat (10:41:49%) diet. Subjects cycled 40 min at the same intensity for the next 2 days. During the 3-day repletion phase, subjects rested and consumed a high-CHO/low-protein/low-fat (85:08:07%) diet, including a glucose-polymer beverage. A 3-day postloading phase followed, which involved a moderately high CHO diet (60%) and no exercise. Glycogen values for vastus lateralis biopsies at baseline and postloading days 1-3 were 408 +/- 168 (SD), 729 +/- 222, 648 +/- 186, and 714 +/- 196 mmol/kg dry wt, respectively. The CHO-loading protocol increased muscle glycogen by 1.79 times baseline, and muscle glycogen remained near this level during the 3-day postloading period. Results indicate that supercompensated muscle glycogen levels can be maintained for at least 3 days in a resting athlete when a moderate-CHO diet is consumed.

Adult↗

A model lightning safety policy for athletics.

OBJECTIVE: The purpose of this paper is to present a model policy on lightning safety for athletic trainers. BACKGROUND: Among college athletic programs in the United States there is a serious lack of written policy on lightning safety. Available evidence shows that most National Collegiate Athletic Association (NCAA) Division I institutions, even though they are located in high lightning activity areas of the country, do not have formal, written lightning safety policies. CLINICAL ADVANTAGES/ RECOMMENDATIONS: The policy presented herein, which is at the forefront of such policies, is the lightning safety policy written as part of a policies and procedures manual for the division of sports medicine at a public NCAA Division I university. This is a policy based on practicality that utilizes the "flash-to- bang" method for determining the distance of lightning activity from the observer. The policy begins with the importance of prevention, including the daily monitoring of weather reports. The policy defines a "safe shelter" and specifies the chain of command for determining who removes a team or individuals from an athletic site in the event of dangerous lightning activity.

Journal Article↗

Identification of signal-induced IkappaB-alpha kinases in human endothelial cells.

Activation of the nuclear transcription factor-kappaB is an early event in endothelial activation. NF-kappaB activation is regulated by the inducible phosphorylation and subsequent degradation of the inhibitory subunit IkappaB-alpha. We identified two discrete kinases of approximately 36 and 41 kDa in the cytoplasm of human umbilical vein endothelial cells that specifically bind to and phosphorylate the IkappaB-alpha subunit. IkappaB-alpha kinase activity is transiently elevated following treatment with either tumor necrosis factor alpha, interleukin-1beta, or bacterial lipopolysaccharides and precedes activation of either mitogen-activated kinase or Jun kinase. Furthermore, activation of the IkappaB-alpha kinases precedes both the appearance of hyperphosphorylated IkappaB-alpha and its subsequent degradation, as well as the translocation of NF-kappaB to the nucleus. Deletion mutagenesis of the IkappaB-alpha polypeptide revealed that these kinases bind in or around the ankyrin repeat domains and phosphorylate residues within the C terminus. These kinases, however, were not identical to casein kinase II and displayed a pharmacologic profile distinct from other known kinases. These kinases may represent components of a signal transduction pathway regulating IkappaB-alpha levels in vascular endothelium.

Ankyrins↗

Comparison of two cool vests on heat-strain reduction while wearing a firefighting ensemble.

This study evaluated the effectiveness of a six-pack versus a four-pack cool vest in reducing heat strain in men dressed in firefighting ensemble, while resting and exercising in a warm/humid environment [34.4 degrees C (day bulb), 28.9 degrees C (wet bulb)]. Male volunteers (n = 12) were monitored for rectal temperature (Tre), mean skin temperature (Tsk), heart rate, and energy expenditure during three test trials: control (no cool vest), four-pack vest, and six-pack vest. The cool vests were worn under the firefighting ensemble and over Navy dungarees. The protocol consisted of two cycles of 30 min seated rest and 30 min walking on a motorized treadmill (1.12 m.s-1, 0% grade). Tolerance time for the control trial (93 min) was significantly less than both vest trials (120 min). Throughout heat exposure, energy expenditure varied during rest and exercise, but no differences existed among all trials (P > 0.05). During the first 60 min of heat exposure, physiological responses were similar for the four-pack and six-pack vests. However, during the second 60 min of heat exposure the six-pack vest had a greater impact on reducing heat strain than the four-pack vest. Peak Tre and Tsk at the end of heat exposure for 6-pack vest [mean (SD) 38.0(0.3) degrees C and 36.8(0.7) degrees C] were significantly lower compared to four-pack [38.6(0.4) degrees C and 38.1(0.5) degrees C] and controls [38.9(0.5) degrees C and 38.4(0.5) degrees C].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidural analgesia and uterine function.

OBJECTIVE: To determine whether continuous epidural analgesia with bupivacaine and fentanyl affects the rate of cervical dilation and myometrial contractility. METHODS: In a 5-week period, 62 consecutive women who received standardized epidural analgesia were matched with the next two groups of 124 consecutive women of the same parity who did not receive epidural analgesia. The outcome variables were uterine activity, rate of cervical dilation, oxytocin therapy, and operative deliveries. RESULTS: Continuous epidural analgesia with bupivacaine and fentanyl did not result in a change in myometrial contractility in the first hour after the initiation of analgesia. However, despite more oxytocin therapy, the rate of cervical dilation was significantly lower in the epidural group than in the nonepidural group (1.9 versus 5.6 cm/hour, P < .001). Operative deliveries were more common in patients with epidural analgesia than in those without it (12 of 62 versus two of 124, P < .001). CONCLUSION: After epidural analgesia, myometrial contractility is maintained with oxytocin, but the ability of the uterus to dilate the cervix is reduced significantly.

Analgesia, Epidural↗

Interaction between adrenergic and peptide stimulation in the rat pineal: pituitary adenylate cyclase-activating peptide.

The 27 amino acid peptide, pituitary adenylate cyclase-activating polypeptide (PACAP-27), and its 38 amino acid analogue, PACAP-38, stimulate serotonin-N-acetyltransferase (NAT) activity and N-acetylserotonin (NAS) and melatonin content of pineal glands from adult rats. Maximal stimulation of rat pineal NAT by PACAP-38 is not increased further significantly by concurrent stimulation with the two related peptides, vasoactive intestinal polypeptide (VIP) and/or peptide N-terminal histidine C-terminal isoleucine (PHI). Isoproterenol was a more potent inducer of NAT activity than any of these peptides alone or in combination. PACAP-38 also stimulates melatonin production by chicken pineal cells in culture as does VIP. Stimulation by both was not greater than after either alone. Prior stimulation of rat pineal NAT activity with VIP, PHI, or PACAP-38 reduces the magnitude of subsequent stimulation with PACAP-38 or forskolin. Concurrent stimulation of alpha-receptors or treatment with active phorbol ester augments rat pineal response to PACAP-38 stimulation just as it increases the response to VIP, PHI, and beta-receptor stimulation. Pineals from newborn rats respond to PACAP-38 with an increase in NAT activity and the increase is augmented by concomitant alpha 1-adrenergic stimulation. The putative PACAP inhibitor PACAP (6-38) and the putative VIP inhibitor (Ac-Tyr,D-Phe)-GRF 1-29 amide, in 100-1,000-fold excess, did not affect the stimulatory activity of any of the peptides. Pineal melatonin concentration parallels changes in pineal NAT activity.

Adenylyl Cyclases↗

Physiological responses during shipboard firefighting.

This study determined the level of heat strain experienced by U.S. Navy personnel while combating fires aboard a damage control research ship. Male volunteers (n = 9), wearing the standard Navy firefighting ensemble, were recorded for core temperature (Tre), skin temperatures (weighted mean, Tmsk), and heart rate (HR) during three fire test days. During the tests, air temperatures in the compartment containing the fire to be extinguished averaged 470 +/- 170 degrees C, while air temperatures in the compartment from which the fire was fought ranged from 40 to 125 degrees C. Dressing in the ensemble and execution of preliminary firefighting activities led to a gradual increase in Tre, Tmsk, and HR; while during active firefighting, Tre, Tmsk, and HR increased rapidly. For all tests, the rate of Tmsk rise (8.73 degrees C.h-1) exceeded the rate of Tre rise (2.95 degrees C.h-1), leading to convergence of these values. Average peak values for all tests were: Tre, 39.2 +/- 1.0 degrees C; Tmsk, 39.5 +/- 0.9 degrees C; body heat storage (HS), 2.02 +/- 0.77 kcal.kg-1; rate of HS during firefighting, 170 +/- 92 kcal.m-2.h-1; HR, 186 +/- 13 bpm. Our findings quantify the limits of tolerance of heat strain encountered during shipboard firefighting.

Adult↗

Isolation of cDNAs and tissue specific expression of ovine glucose transporters.

The facilitative glucose transporters are a family of proteins responsible for the transmembrane transport of glucose and other hexose sugars (1,2). In mammals, the seven glucose transporter isoforms display a characteristic tissue distribution reflecting the physiological requirement and metabolism of glucose. This report describes the isolation and sequencing of the full length ovine GLUT-3 cDNA and the tissue distribution of ovine GLUT-1 and GLUT-3 mRNA. The ovine GLUT-3 cDNA is 3854 base pairs and the coding nucleotides show 82% and 79% homology with the human and mouse GLUT-3 sequences respectively. In addition, a reverse transcriptase-polymerase chain reaction strategy is described for the rapid isolation of mammalian cDNA subclones for GLUT-1, GLUT-2 and GLUT-4. This method has been used to isolate the corresponding ovine subclones.

Amino Acid Sequence↗

Commonalities in vasoactive intestinal peptide and peptide N-terminal histidine C-terminal isoleucine stimulation of N-acetyltransferase activity in the rat pineal.

Exposure of adult rat pineal glands in organ culture to the polypeptides vasoactive intestinal polypeptide (VIP), and peptide N-terminal histidine C-terminal isoleucine (PHI) increases pineal serotonin N-acetyltransferase (NAT) activity and melatonin synthesis. The following research results are taken to indicate that VIP and PHI share common components of the NAT induction system: (1) The effects of the two peptides are additive at concentrations of 10 nM VIP and 100 nM PHI but not at higher peptide concentrations. (2) Pineals from newborns also respond to PHI with a dose dependent increase in NAT activity. NAT responses are additive at the same concentrations as seen with the adult pineals. (3) Light exposure affects the sensitivity of pineals to VIP and PHI stimulation in a similar manner; pineals taken after 3 hr of light are much less sensitive to PHI or VIP than those taken after 13 hr of light. (4) Pineals exposed for 48 hr to either PHI or VIP have a reduced NAT response to either agonist, which is reversible by culture in agonist-free media. (5) Neither VIP nor PHI stimulation of NAT activity is affected by concentrations of the VIP antagonists (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 (NAcTDGRF), L-8-K, VIP-Neurotensin Hybrid (VIPNET), or (4Cl-D-Phe6, Leu17)-VIP (4C1PLVIP), which affect VIP binding or function in other tissues.

Amino Acid Sequence↗

Whey proteins of the common brushtail possum (Trichosurus vulpecula): isolation, characterization and changes in concentration in milk during lactation of transferrin, alpha-lactalbumin and serum albumin.

1. Transferrin and serum albumin were purified from both whey and serum and alpha-lactalbumin was purified from whey from the common brushtail possum (Trichosurus vulpecula). 2. The N-terminal amino acid sequences for transferrin and serum albumin were identical for the proteins from both whey and serum and showed homologies with transferrin or serum albumin from other species. 3. N- and C-terminal regions of possum alpha-lactalbumin were also sequenced and have been compared with wallaby alpha-lactalbumin and several eutherian alpha-lactalbumins. 4. Antisera raised to each of the three proteins were species specific and Western blots further confirmed the identity of the serum and whey transferrins and serum and whey serum albumins. 5. The concentration of transferrin increased ten-fold between days 110 and 130 of lactation, whereas no significant changes in the concentration of alpha-lactalbumin could be detected after day 60.

Amino Acid Sequence↗

Physical fitness in a submarine community as determined by the U.S. Navy Health and Physical Readiness Test.

This study was conducted to test the hypothesis that personnel assigned to submarine duty would display less physical fitness as compared to shore-based personnel. A message was submitted to all naval activities at a Naval Submarine Base requesting individual test scores from the annual Health and Physical Readiness (H&PR) Test. The results from the statistical analysis showed that the majority of personnel in both populations were classified as "good," which is an average level of physical fitness as determined by the Navy's fitness classification table. In both populations, 1% were classified as "outstanding," while approximately 10% failed to meet the minimum physical fitness requirements. A body fat value greater than 22% was the cause for the majority of test failures. In conclusion, the results of the analysis of H&PR data do not support the widely held belief that submarine personnel are less physically fit than their shore-based counterparts.

Adolescent↗

Cardiorespiratory fitness and cognitive performance before and after confinement in a nuclear submarine.

The aim of this study was to further document physiological deconditioning from occupational exposure to submarines as described in a small number of reports and determine whether cognitive performance parallels the physiological changes associated with physical training and deconditioning. We examined cardiorespiratory fitness and cognitive performance in 14 male subjects during 70 d of confinement in a nuclear submarine. Maximal oxygen consumption (VO2max) and anaerobic threshold (AT) were assessed before and after confinement. Six exercising subjects (ES) cycled 4-7 times per week for 20 min at 75% max heart rate for 8 weeks. Eight control subjects (CS) did no exercise. Every 14 d of the patrol, cognitive performance was evaluated in both groups by administering a mental arithmetic and choice reaction time tests before cycling, during cycling, and post cycling. The cycle bout consisted of exercising at 75% VO2max for 15 min. After confinement, VO2max remained constant for ES but declined 7% statistically nonsignificant for the CS. AT expressed as a percentage of VO2max increased 15% (p less than 0.05) in the ES and decreased 20% (p less than 0.05) in the CS. The only significant effect in the cognitive tests was that both groups responded faster in the choice reaction time test during the exercise session. In conclusion, these data demonstrate a training effect for AT in the ES and a deconditioning response for AT and a statistically nonsignificant reduction in VO2max in the CS. Under the conditions of this experiment we could find no effects of physical training and deconditioning on the cognitive performance test employed here, although some trends suggest that exercisers out-performed the control group.

Adult↗

Glucocorticoid induction of tryptophan oxygenase. Attenuation by intragastrically administered carbohydrates and metabolites.

In vivo tryptophan 2,3-dioxygenase (TPO) activity in male rats was estimated from the rate of production of 14CO2 after intragastric administration of [14C-2]tryptophan. The synthetic glucocorticoids hydrocortisone-21-sodium succinate or Triamcinolone acetonide were injected to elevate hepatic TPO activity on an acute (1-6 hr) or chronic (24 hr) basis. Glucose, fructose, or glycerol was intragastrically intubated in doses ranging from 4 to 16 mmoles to assess their abilities to attenuate acute or chronic increases of TPO activity by these glucocorticoids. Hydrocortisone-21-sodium succinate at doses of 0, 25, and 50 mg/kg produced dose-dependent elevations of TPO. A 50 mg/kg dose produced a 3-fold elevation of enzyme activity when measured in vitro as product produced by liver homogenates and a 2-fold elevation when assessed from expired radioactive carbon dioxide from radiolabeled tryptophan in vivo. Enzyme activity measured by 14CO2 production reached peak values in 2-3 hr and returned to baseline in 5 hr. Glucose, fructose or glycerol completely prevented the rise in conversion of [14C-2]tryptophan produced by hydrocortisone hemisuccinate when administered at doses of 12 or 16 mmoles 0.5 hr before the steroid. Lower doses had less effect. The potencies of the compounds in inhibiting acute increases in TPO activity produced by hydrocortisone hemisuccinate were in the order glycerol greater than fructose greater than glucose. Chronic Triamcinolone treatment elevated in vivo TPO activity by 2.5-fold and in vitro TPO activity by 5-fold. The chronic elevation of in vivo TPO by Triamcinolone could be arrested within 1 hr by an intragastric fructose load. The present finding, that acute or chronic glucocorticoid-induced increases in in vivo TPO activity were rapidly blocked by intragastric carbohydrate loads, is consistent with the view that dietary carbohydrates modulate hepatic TPO activity via feedback repression and not by a cessation of TPO enzyme synthesis.

Animals↗