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Biomedical subjects

J M Green

Publications and source records attributed to J M Green.

At least 37 records · Page 2Linked to original sources

The effects of creatine supplementation on repeated upper- and lower-body Wingate performance.

Nineteen physically active men supplemented their diet with 20 g per day creatine monohydrate (Cr group) or placebo (PI group) for 6 days. Before and after supplementation, subjects performed 3 arm Wingates (AW1, AW2, and AW3) and 3 leg Wingates (LW1, LW2, and LW3) on consecutive days. Wingates were separated by 2 minutes each. Mean power (MP), peak power (PP), and percent decrease (%D) were compared between and within groups. MP did not change significantly for arms or legs. PP did not change significantly for legs. PP increased significantly in the Cr group (AW1) and for the P1 group (AW1 and AW3). MP and PP were not significantly different between groups. The %D increased significantly in the P1 group (AW1, AW3, and LW3). For the Cr group, %D decreased significantly (pre vs. post) and was significantly lower than for the P1 group (LW2-post). Results suggest that short-term Cr supplementation does not enhance MP and PP during repeated upper- and lower-body Wingate tests when not accompanied by an increase in body weight. However, changes in %D suggest possible ergogenic effects.

Adult↗

Membrane raft association of CD47 is necessary for actin polymerization and protein kinase C theta translocation in its synergistic activation of T cells.

CD47 is a ubiquitously expressed membrane protein with an extracellular Ig domain and a multiple membrane-spanning domain that can synergize with antigen to induce interleukin (IL)-2 secretion by T lymphocytes. Ligation of CD47 induced actin polymerization and increased protein kinase Ctheta (PKCtheta) association with the cytoskeleton independent of antigen receptor ligation, but ligation of mutant forms of the molecule missing either the Ig domain or the multiple membrane-spanning domain did not. Simultaneous ligation of CD47 and CD3 led to additive effects on F-actin and synergistic effects on PKCtheta cytoskeletal association. Disruption of membrane rafts by removal of cholesterol with cyclodextrin blocked CD47-induced actin polymerization, and mutant forms of CD47 that localized poorly to rafts failed to effect cytoskeletal rearrangement. However, raft association alone was not sufficient, because a raft-localized CD47 Ig domain bound to the membrane by a glycan phosphoinositol anchor was unable to induce actin polymerization. A mutant form of CD47 without its Ig domain that did not induce actin polymerization or localize to rafts still enhanced T cell receptor (TCR)-dependent tyrosine phosphorylation of PLCgamma and associated Ca(2+) signaling but did not augment IL-2 secretion. Thus, CD47 synergy with TCR to increase [Ca(2+)](i) is independent of actin and rafts but is insufficient to explain CD47 cooperation with TCR in IL-2 synthesis. Full synergy with TCR requires CD47 localization to membrane rafts where ligation leads to TCR-independent signals causing actin polymerization and PKCtheta translocation.

Actins↗

Identification and cloning of a CD43-associated serine/threonine kinase.

CD43 is expressed on most hematopoetic cells and has been shown to regulate the activation and adhesion of T cells. We have cloned a serine/threonine kinase that can interact with the cytoplasmic domain of CD43. This protein is expressed in multiple tissues, including lymphoid cells. Analysis of the subcellular localization reveals it to be present in both the nucleus and the cytoplasm of the cell. The identification of this protein suggests that CD43 may mediate its biologic effects through activation of a kinase cascade, resulting in the regulation of cell growth.

Amino Acid Sequence↗

Coordinate regulation of T cell activation by CD2 and CD28.

T cell activation requires co-engagement of the TCR with accessory and costimulatory molecules. However, the exact mechanism of costimulatory function is unknown. Mice lacking CD2 or CD28 show only mild deficits, demonstrating that neither protein is essential for T cell activation. In this paper we have generated mice lacking both CD2 and CD28. T cells from the double-deficient mice have a profound defect in activation by soluble anti-CD3 Ab and Ag, yet remain responsive to immobilized anti-CD3. This suggests that CD2 and CD28 may function together to facilitate interactions of the T cell and APC, allowing for efficient signal transduction through the TCR.

Animals↗

Gender differences in sweat lactate.

Sweat rate may affect sweat lactate concentration. The current study examined potential gender differences in sweat lactate concentrations because of varying sweat rates. Males (n = 6) and females (n = 6) of similar age, percentage body fat, and maximal oxygen consumption (VO2max) completed constant load (CON) cycling (30 min--approximately 40% VO2max) and interval cycling (INT) (15 1-min intervals each separated by 1 min of rest) trials at 32 (1) degrees C wet bulb globe temperature (WBGT). Trials were preceded by 15 min of warm-up (0.5 kp, 60 rpms) and followed by 15 min of rest. Blood and sweat samples were collected at 15, 25, 35, 45, and 60 min during each trial. Total body water loss was used to calculate sweat rate. Blood lactate concentrations (CON approximately equal to 2 mmol.l-1, INT approximately equal to 6 mmol.l-1) and sweat lactate concentrations (CON and INT approximately equal to 12 mmol.l-1) were not significantly different (P > 0.05) at any time between genders for CON or INT. Overall sweat rates (ml.h-1) were not significantly different (P > 0.05) between trials but were significantly greater (P < or = 0.05) for males than for females for CON [779.7 (292.6) versus 450.3 (84.6) ml.h-1] and INT [798.0 (268.3) versus 503.0 (41.4) ml.h-1]. However, correcting for surface area diminished the difference [CON: 390.7 (134.4) versus 277.7 (44.4) ml.h-1, INT: 401.5 (124.1) versus 310.6 (23.4) ml.h-1 (P < or = 0.07)]. Estimated total lactate secretion was significantly greater (P < or = 0.05) in males for CON and INT. Results suggest that sweat rate differences do not affect sweat lactate concentrations between genders.

Adult↗

Regulation of T cell apoptosis.

Proliferative expansion of lymphoid cells is required for effective immune responses against invading microorganisms, but after the infection is controlled, the expanded effector cells must be eliminated to prevent non-adaptive accumulation of cells. Higher vertebrates have developed extensive networks of signal transduction pathways to ensure controlled activation and expansion of cells during immune responses and apoptotic deletion of lymphoid cells that are no longer needed at the end of immune responses. Extracellular signals received by cell surface receptors that trigger intracellular signaling cascades are essential elements that control both processes. These signal transduction pathways converge to regulate cell fate at both transcriptional and post-transcriptional levels. Here we review the role of pathways, especially those triggered by TNF receptor-related molecules, that determine the fate of T cells during development and activation. In addition, we introduce the possibility that these same pathways may be abnormally programmed and so lead to immune cell accumulation during inflammatory diseases such as asthma.

Animals↗

Continuity of carer: what matters to women? A review of the evidence.

OBJECTIVES: To consider how 'continuity of carer' has been defined in the literature and to review the literature on what aspects of continuity matter to women. DESIGN: Structured literature review. SETTING: The first objective was addressed within the context of a review of the organisation of midwifery services in the UK; for the second objective a wider literature was drawn on. MEASUREMENTS AND FINDINGS: Data were systematically extracted from the identified 'core' studies on the methods used for assessing continuity of carer and on women's satisfaction with periods of care. Continuity of carer was found to be defined in these studies as fewer caregivers, either overall or during pregnancy, or as a known caregiver in labour. Little attention was paid to other possible interpretations of continuity of carer. The literature on what is important to women was found to have used four distinct methods and findings were consistent within methods. Studies comparing women who had and had not had a known carer in labour found no significant differences in satisfaction; those using rankings or ratings found that a known intrapartum carer was a relatively low priority and most of those using open-ended questions found that few women mentioned continuity. In contrast, all studies which asked postnatal women whether a known intrapartum carer was important reported that those who had experienced it said 'yes', while those who had not, generally thought it unimportant. KEY CONCLUSIONS: There has been an emphasis in existing literature on continuity of carer but little attempt to assess continuity or quality of care. Limited definitions of continuity of carer have been used. There is no evidence that women who were cared for in labour by a midwife that they had already met were more satisfied than those who were not. Other aspects of woman-centred care were likely to be more important. Women wanted consistent care from caregivers that they trust, but most did not value continuity of carer for its own sake. IMPLICATIONS FOR PRACTICE: Limited definitions of continuity of carer seem to be becoming ends in themselves. This has particularly been the case with defining continuity as 'having a known carer in labour'. The available evidence does not justify prioritising this definition of continuity--rather the reverse. This is important for both women and midwives since it opens up other possibilities for organising services that put less strain on midwives' lives and may be equally satisfying for both women and midwives.

Continuity of Patient Care↗

Effects of high and low blood lactate concentrations on sweat lactate response.

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.

Adult↗

Role of cholesterol in formation and function of a signaling complex involving alphavbeta3, integrin-associated protein (CD47), and heterotrimeric G proteins.

Integrin-associated protein (CD47) is a multiply membrane spanning member of the immunoglobulin superfamily that regulates some adhesion-dependent cell functions through formation of a complex with alphavbeta3 integrin and trimeric G proteins. Cholesterol is critical for the association of the three protein components of the supramolecular complex and for its signaling. The multiply membrane spanning domain of IAP is required for complex formation because it binds cholesterol. The supramolecular complex forms preferentially in glycosphingolipid-enriched membrane domains. Binding of mAb 10G2 to the IAP Ig domain, previously shown to be required for association with alphavbeta3, is affected by both the multiply membrane spanning domain and cholesterol. These data demonstrate that cholesterol is an essential component of the alphavbeta3/IAP/G protein signaling complex, presumably acting through an effect on IAP conformation.

Antibodies, Monoclonal↗

Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.

The Src family tyrosine kinases Lck and Fyn are critical for signaling via the T cell receptor. However, the exact mechanism of their activation is unknown. Recent crystal structures of Src kinases suggest that an important mechanism of kinase activation is via engagement of the Src homology (SH)3 domain by proline-containing sequences. To test this hypothesis, we identified several T cell membrane proteins that contain potential SH3 ligands. Here we demonstrate that Lck and Fyn can be activated by proline motifs in the CD28 and CD2 proteins, respectively. Supporting a role for Lck in CD28 signaling, we demonstrate that CD28 signaling in both transformed and primary T cells requires Lck as well as proline residues in CD28. These data suggest that Lck plays an essential role in CD28 costimulation.

Alanine↗

Structural requirements for CD43 function.

The regulation of T cell activation and adhesion by CD43 (leukosialin, sialophorin) has been thought to be mainly a function of the large size and negative charge of the extracellular domain of the protein. In this work, we demonstrate that the cytoplasmic tail is both necessary and sufficient for the negative regulatory effect of CD43 on cell-cell adhesion. Expression of mutant CD43 proteins in primary T cells from CD43-deficient mice demonstrated that the antiproliferative effect of CD43 is also dependent upon the cytoplasmic tail. In contrast, Ab-mediated costimulation through CD43 does not require the intracellular domain of CD43. These data demonstrate that CD43 primarily serves as a negative regulator of T cell activation and adhesion, and that this is mediated not exclusively by passive effects of the extracellular domain, but requires participation of the cytoplasmic tail, perhaps through interactions with the cytoskeleton, or alternatively, active regulation of intracellular signaling pathways.

Animals↗

Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28.

Integrin-associated protein (IAP/CD47) is a 50 kDa transmembrane protein initially defined as a regulator of beta3 integrin-mediated functions in neutrophils. IAP also can synergize with the TCR in T cell activation independent of beta3 integrins. To analyze the mechanism for IAP synergy with TCR, we expressed in Jurkat cells a chimeric molecule, consisting of the CD16 extracellular domain, the CD7 transmembrane domain and the TCR zeta chain cytoplasmic tail (CD16-7-zeta), which on its own is unable to induce IL-2 production. Ligation of IAP acted in synergy with TCR to induce IL-2 transcription and synthesis, but failed to synergize with the signal generated by CD16-7-zeta, while CD28 was a potent co-stimulator with both TCR and CD16-7-zeta. The failure of IAP to activate Jurkat together with CD16-7-zeta correlated with a lack of c-Jun N-terminal kinase, but not extracellular-signal-regulated kinase activation. Jurkat adhesion to anti-IAP, but not anti-CD28, induced cell spreading and the same domains of IAP required for augmentation of T cell activation were required to induce cell spreading. IAP synergy with TCR signaling likely results from its ability to stimulate adhesion to a ligand-expressing surface or antigen-presenting cell (APC), rather than from initiation of a novel signaling cascade. We conclude that a major role for ligation of IAP in T cell activation is to enhance the efficiency of TCR signaling by causing T cells to spread on an APC or surface.

Antigens, CD↗

The validity of ratings of perceived exertion for cross-modal regulation of swimming intensity.

BACKGROUND: This study examined the use of Borg's category Ratings of Perceived Exertion (RPE) scale for prescribing and self-regulating swimming intensity. Subjects were males and females (n = 19) ages nineteen to fifty-eight who regularly swam for fitness. EXPERIMENTAL DESIGNS: Subjects completed six trials. Each trial was separated by a minimum of forty-eight hours. Mean cycle ergometry heart rates at estimated RPE-overall 12 and 16 were compared to mean swimming heart rates at produced RPE-overall 12 and 16. Also, mean arm ergometry heart rates at estimated RPE-arms 12 and 16 were compared to mean swimming heart rates at produced RPE-arms 12 and 16. Cycling and arm ergometry anchor trials familiarized subjects with testing protocol and Borg's scale prior to estimation and production trials. Comparisons were made using a one-way ANOVA (alpha 0.05). RESULTS: Mean cycling heart rate at RPE-overall 16 was not significantly different from mean swimming heart rate at RPE-overall 16. Mean swimming heart rate was significantly greater than cycling heart rate at RPE-overall 12. Mean swimming heart rates at RPE-arms 12 and 16 were significantly greater than arm ergometry heart rates at RPE-arms 12 and 16. CONCLUSIONS: Results suggest that RPE-overall 16 may be useful in prescribing a higher exercise intensity for swimmers. However, adjustments from RPE-overall 12 are needed for establishing a lower intensity. Additionally, arm ergometry-based RPEs may require adjustments to be effective in prescribing and regulating swimming intensity. Results suggest that cycling and arm ergometry anchored RPE responses should be used with discretion when prescribing and regulating swimming intensity.

Adult↗