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A August

Publications and source records attributed to A August.

31 records · Page 2Linked to original sources
PubMed1994

Activation of src family kinase lck following CD28 crosslinking in the Jurkat leukemic cell line.

T lymphocytes require a signal via their antigen specific receptors (the T cell receptors) and an antigen independent costimulatory signal. Signals through CD28 can costimulate T cells in the presence of limiting amounts of T cell receptor signal, or in the presence of PMA, providing this second signal. CD28 signaling is known to involve the activation of protein tyrosine kinases. Using the Jurkat leukemic cell line as a model, we have tested CD28 crosslinking for its effects on the protein tyrosine kinases p56lck. We report that following crosslinking of CD28, p56lck kinase activity is increased. Crosslinking CD28 causes a shift in the relative mobility of p56lck from 56 to 60 kD similar to that seen after crosslinking of CD2 and CD4, cell surface receptors known to be associate with and activate p56lck. Finally, lck could be found in anti-CD28 immunoprecipitates in exponentially growing Jurkat and in "activated" CD28 (i.e., cross linked), but not in CD28 in resting Jurkat cells. These findings suggest an important role for p56lck in CD28 signal transduction.

Animals↗
PubMed1994

CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase.

T lymphocyte activation requires recognition of antigen by the antigen specific TCR as well as second co-stimulatory signals. This recognition event results in the activation of non-TCR linked protein tyrosine kinases (PTKs). The mechanism of co-stimulation of T cells is unknown except for the involvement of PTKs. The T cell surface molecule CD28 is effective in delivering co-stimulatory signals and prevents T cell anergy by inducing T cell proliferation in TCR stimulated T cells, primarily due to an increase in IL-2 production. The mechanism by which CD28 mediates this effect is currently unknown. Some conventional receptor molecules possess intrinsic tyrosine kinase and as a consequence of cross-linking or ligand binding, phosphorylate numerous tyrosines within their cytoplasmic tail, leading these tyrosines to become 'activated' and bind cytoplasmic effector molecules possessing Src homology 2 domains which specifically recognize phosphorylated tyrosines. One such cytoplasmic effector molecule is the phosphatidylinositol-3-phosphate kinase (PI3 kinase) which recognizes the motif phosphotyrosine-methione/valine-X-methionine (X being any amino acid) within the cytoplasmic tails of numerous receptor tyrosine kinases. As CD28 contains a copy of the PI3 kinase binding motif within its cytoplasmic tail, we investigated CD28 signaling and PI3 kinase activation. Here we demonstrate using the Jurkat cell line that CD28 becomes tyrosine phosphorylated following CD28 cross-linking and associates with PI3 kinase. Furthermore, a synthetic peptide representing the YM/VXM motif within the cytoplasmic tail of CD28 also interacts with PI3 kinase only when the tyrosine is phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Cross-competition for binding of alpha 1-antitrypsin (alpha 1 AT)-elastase complexes to the serpin-enzyme complex receptor by other serpin-enzyme complexes and by proteolytically modified alpha 1 AT.

The serpin-enzyme complex (SEC) receptor recognizes a pentapeptide neo-domain of alpha 1-antitrypsin (alpha 1 AT)-elastase complexes and, in so doing, mediates internalization and intracellular catabolism of the macromolecular complex, mediates an increase in synthesis of alpha 1 AT, and elicits neutrophil chemotactic activity. In previous studies we have shown that this pentapeptide domain is highly conserved among members of the serpin family and that binding of a synthetic peptide corresponding to this region (125I-peptide 105Y, SIP-PEVKFNKPFVYLI, based on alpha 1 AT sequence 359-374) to HepG2 cells is blocked by several serpin-enzyme complexes. To determine whether the SEC receptor is the primary HepG2 cell surface binding site for these serpin-enzyme complexes, we examined the capacity for serpin-enzyme complexes to compete with each other for binding to the SEC receptor. The results indicate that binding of 125I-elastase-alpha 1 AT complexes is blocked by thrombin-antithrombin III (ATIII), thrombin-heparin cofactor II, and cathepsin G-alpha 1-antichymotrypsin (alpha 1 ACT) complexes. Moreover, unlabeled elastase-alpha 1 AT complexes compete for binding of 125I-thrombin-ATIII, 125I-thrombin-heparin cofactor II, and 125I-cathepsin G-alpha 1 ACT complexes. Preformed soluble tissue plasminogen activator-plasminogen activator inhibitor 1 complexes also compete for binding of elastase-alpha 1 AT complexes to the SEC receptor but do so to a less effective extent, probably because of a less favorable pentapeptide sequence for binding to the SEC receptor. Under conditions in which these serpin-enzyme complexes would be expected to bind to the SEC receptor there is an increase in synthesis of alpha 1 AT but not in synthesis of ATIII or alpha 1 ACT. Proteolytically modified alpha 1 AT also competes for binding of 125I-elastase-alpha 1 AT complexes to the SEC receptor and vice versa. The purified 51-kDa amino-terminal fragment of alpha 1 AT does not compete for binding of 125I-elastase-alpha 1 AT complexes, indicating that the pentapeptide neodomain in the 4-kDa carboxyl-terminal fragment is sufficient for binding to the SEC receptor.

Amino Acid Sequence↗
PubMed1991

Intracellular signaling events associated with the induction of proliferation of normal human B lymphocytes by two different antigenically related human B cell growth factors (high molecular weight B cell growth factor (HMW-BCGF) and the complement factor Bb).

High molecular weight B cell growth factor (HMW-BCGF) and the complement component, Factor B, are antigenically related. HMW-BCGF and the physiologic Factor B activation fragment Bb, are both mitogenic for B lymphocytes and compete for binding to the B cell plasma membrane (Peters, M., Ambrus, J. L., Jr., Fauci, A., and Brown, E. (1988) J. Exp. Med. 168, 1225-1235). To understand which second messengers that occur after ligand-receptor interaction are associated with mitogenesis, we have examined the early signaling events after stimulation of activated B cells with these related growth factors. HMW-BCGF but not Bb increased [cAMP]i with a maximum between 45 and 60 min after stimulation. The increase in [cAMP]i was inhibited by indomethacin, suggesting that prostaglandin synthesis is involved in this response. Increase in [cAMP]i induced by HMW-BCGF, cholera toxin, or dibutyryl cAMP was associated with increased expression of the HMW-BCGF receptor, but there was no increase in proliferation of activated B cells when they were stimulated with cAMP agonists other than HMW-BCGF. These data suggest that cAMP is associated with regulation of receptor expression but is neither necessary nor sufficient for induction of proliferation. Both HMW-BCGF and Bb increased cellular levels of diacylglycerol and a water-soluble molecule which could be labeled with both [3H]myoinositol and [14C] glucosamine. However, only HMW-BCGF induced increases in intracellular calcium. Thus, two antigenically related B cell growth factors, HMW-BCGF and Bb, produce overlapping but distinct sets of second messengers after incubation with Sac-activated B cells. Since both induced increases in diacylglycerol and water-soluble inositol, one or both of these molecules may be involved in the proliferative signal generated by the related growth factors. In contrast, the increase in [cAMP]i caused by HMW-BCGF but not Bb is involved in the signal to increase HMW-BCGF receptor expression, but is unrelated to proliferation.

B-Lymphocytes↗
PubMed1991

Induction of proliferation by high molecular weight B cell growth factor or low molecular weight B cell growth factor is associated with increases in intracellular calcium in different subpopulations of human B lymphocytes.

The activation of resting B cells with anti-surface Ig is associated with transient increases in intracellular calcium. In the present study, we demonstrate that stimulation of B cells which have already been activated by Staphylococcus aureus Cowan I (Sac), with high molecular weight B cell growth factor (HMW-BCGF) or low molecular weight B cell growth factor (LMW-BCGF), but not IL-2, IL-4, or interferon-gamma, is associated with an increase in intracellular calcium, which is modest compared to that seen with anti-Ig (approximately 100 nM vs approximately 400 nM). The increases in intracellular calcium induced by HMW-BCGF or LMW-BCGF occur in distinct but overlapping subpopulations of B cells. Thus, increases in intracellular calcium in human B cells occur not only upon activation but also upon the induction of proliferation by certain (but not all) B cell growth factors. Presumably, the effect of increasing intracellular calcium during the induction of proliferation is to modify a different group of intracellular molecules than those induced during activation.

B-Lymphocyte Subsets↗
PubMed1990

T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease.

Crohn's disease represents part of a spectrum of inflammatory bowel diseases characterized by immune regulatory defects and genetic predisposition. T cell antigen receptor V gene usage by T lymphocytes was investigated using four MAbs specific for various V gene products. One MAb (Ti3a), reactive with V beta 8 gene products, detected increased numbers of T cells in a subset of Crohn's disease patients as compared with normal controls and ulcerative colitis patients. In family studies there was no apparent inherited predisposition to the use of V beta 8 genes, and there was no association between a restriction fragment length polymorphism of the V beta 8.1 gene and Crohn's disease. The V beta 8+ T cells were concentrated in the mesenteric lymph nodes draining the inflammatory lesions and belonged to both the CD4+ and CD8+ T cell subsets. In contrast, lamina propria and intraepithelial T cells were not enriched in V beta 8+ T cells, suggesting that these cells were participating in the afferent limb of a gut-associated immune response. The expanded V beta 8+ T cells in Crohn's disease appear to result from an immune response to an as yet unknown antigen.

Antibodies, Monoclonal↗
PubMed1990

Excision arthroplasty for infected constrained total knee replacements.

We have reviewed 15 patients with infected total knee replacements after removal of the prosthesis, rigorous debridement, antibiotic irrigation, and prolonged systemic antibiotics. Infection was permanently eradicated in all patients; they were left with a functioning limb, on which they could walk with either a caliper (8 patients), a simple splint (3), crutches, or sticks. Three were disappointed because of residual pain. We believe that, if exchange arthroplasty is inappropriate, this procedure is preferable to arthrodesis or amputation for persistent and disabling infection, particularly where constrained artificial joints have been used.

Aged↗
PubMed1986

Biomechanical performance of locked intramedullary nail systems in comminuted femoral shaft fractures.

The biomechanical properties of commercially available locked nail systems designed for use in comminuted femoral shaft fractures were compared and evaluated. Ender nails as well as three forms of interlocking nails, Brooker-Wills (B-W), Klenm-Schellman (K-S), and Grosse-Kempf (G-K), were implanted in cadaver femora. The femora were tested in torsion, bending, and axial loading to failure. Two fracture models were tested--a 3 cm subtrochanteric defect and an 8 cm midshaft defect. Results of the testing revealed the three interlocking nails to be comparable to each other and superior to Ender nails in bending and torsion. However, the distally bolted locked nails (K-S, G-K) resisted significantly higher loads than either the distally bladed locked nail (B-W) or Ender nails when tested to failure by axial loading.

Adult↗
PubMedDate not supplied

Late vascular complication after blunt trauma.

The left clavicle of a 52-year-old patient was fractured at a road traffic accident in 1991. Three months after uneventful recovery axillary vein thrombosis developed on the side of the trauma, which was treated conservatively. One year after the trauma embolization of the left hand developed. The cause was an intimal tear with application thrombus, which were successfully excised. The case proves the importance of awareness of late vascular complications after blunt traumas.

Accidents, Traffic↗