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K D Patel

Publications and source records attributed to K D Patel.

34 records · Page 2Linked to original sources
PubMed1994

The necrotic venom of the brown recluse spider induces dysregulated endothelial cell-dependent neutrophil activation. Differential induction of GM-CSF, IL-8, and E-selectin expression.

Brown recluse spider (Loxosceles reclusa) venom induces severe dermonecrotic lesions. The mechanism for this is unknown but presents an interesting paradox: necrosis is completely dependent on the victim's neutrophils, yet neutrophils are not activated by the venom. We show Loxosceles venom is a potent, but disjointed, endothelial cell agonist. It weakly induced E-selectin expression, but not intercellular adhesion molecule-1 or IL-6 expression, yet significantly stimulated release of IL-8 and large amounts of GM-CSF by 4 h. In contrast, TNF strongly induced all of these, except for GM-CSF. PMN bound to E-selectin on venom-activated endothelial cells, apparently via counterreceptors different from those that bind E-selectin on TNF alpha-activated monolayers. Notably, PMN bound venom-activated monolayers only at intercellular junctions, did not polarize, and completely failed to migrate beneath the monolayer. Despite this, bound PMN demonstrated increased intracellular Ca2+ levels and secreted primary and secondary granule markers. The latter event was suppressed by sulfones used to treat envenomation. We have defined a new endothelial cell agonist, Loxosceles venom, that differentially stimulates the inflammatory response of endothelial cells. This, in turn, leads to a dysregulated PMN response where adhesion and degranulation are completely dissociated from shape change and transmigration.

Animals↗
PubMed1993

Juxtacrine interactions of endothelial cells with leukocytes: tethering and signaling molecules.

The interaction of blood leukocytes with the endothelium of post-capillary venules and other vessels involves regulated expression of molecules on both the endothelial cell (EC) and the leukocyte. This is true for each of the major classes of leukocytes, including lymphocytes, monocytes, and granulocytes. Interaction of polymorphonuclear leukocytes (PMNs), a particular subset of granulocytes, with cultured human endothelium illustrates this concept and also illustrates the diversity of structure, mechanisms of expression, and mechanisms of action of the molecules involved. One group of molecules binds, or "tethers", the PMN to the EC without requiring PMN activation; P-selectin and E-selectin, which are glycoproteins that are expressed by translocation from subcellular granules or synthesis under transcriptional regulation, respectively, are examples. A second group of molecules activates the PMN by binding to signal-transducing receptors. Platelet-activating Factor (PAF), a biologically-active phospholipid, is an example of this class. Its production is controlled by regulation of synthetic enzymes and is induced rapidly (minutes) when EC are appropriately stimulated. PAF is translocated to the EC surface, where it mediates juxtacrine activation of PMNs by binding to a "7 membrane-spanning" receptor. One consequence of juxtacrine activation of PMNs by PAF is functional upregulation of CD11/CD18 integrins on the PMN. These integrins bind to counterreceptors on the EC, enhancing the avidity of adhesion over that provided by P-selectin alone. Thus, combinations of tethering and signaling molecules regulate PMN adhesive interactions with EC. Combinations of such molecules also regulate other functional responses of the PMNs that are important in inflammation. The time-dependent expression of different patterns of tethering and signaling molecules by EC provides a general mechanism for differential adhesion and activation of different classes leukocytes in acute and subacute inflammation.

Animals↗
PubMed1992

Novel leukocyte agonists are released by endothelial cells exposed to peroxide.

Reactive oxygen species do not activate isolated neutrophils, yet in vivo, such oxidants promote their adhesion to, and subsequent migration through, the vascular wall. We show human endothelial cells exposed to t-butylhydroperoxide shed large, sealed membrane vesicles that contained potent neutrophil agonists. This activity migrated on TLC like platelet-activating factor (PAF). Since neutrophils have a receptor for this phospholipid, which recognizes its unique characteristics including the short sn-2 acetyl residue, we examined the effect of PAF receptor antagonists and PAF acetylhydrolase on this activity. Structurally unrelated PAF receptor antagonists blocked neutrophil stimulation by vesicular phospholipids, and digestion with PAF acetylhydrolase, which is specific for short sn-2 residues, destroyed this activity. However, metabolic labeling, inhibition of synthesis, phospholipase A1 digestion, and high performance liquid chromatographic studies demonstrated that the vesicles did not contain PAF. Instead, the bioactivity migrated on high performance liquid chromatography like the phospholipids generated by oxidative fragmentation of synthetic arachidonoyl phosphatidylcholine that we have shown previously (Smiley, P. L., Stremler, K. E., Prescott, S. M., Zimmerman, G. A., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11104-11110) to stimulate neutrophils through their receptor for PAF. Thus, peroxide treatment of endothelial cells fragments cellular phosphatidylcholines, forming novel PAF-like phospholipids, and induces the shedding of membrane vesicles that contain these bioactive phospholipids.

Cell Adhesion↗
PubMed1991

Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils.

The initial step in extravasation of neutrophils (polymorphonuclear leukocytes [PMNs]) to the extravascular space is adherence to the endothelium. We examined the effect of oxidants on this process by treating human endothelial cells with H2O2, t-butylhydroperoxide, or menadione. This resulted in a surface adhesive for PMN between 1 and 4 h after exposure. The oxidants needed to be present only for a brief period at the initiation of the assay. Adhesion was an endothelial cell-dependent process that did not require an active response from the PMN. The adhesive molecule was not platelet-activating factor, which mediates PMN adherence when endothelial cells are briefly exposed to higher concentrations of H2O2 (Lewis, M. S., R. E. Whatley, P. Cain, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman. 1988. J. Clin. Invest. 82:2045-2055), nor was it ELAM-1, an adhesive glycoprotein induced by cytokines. Oxidant-induced adhesion did not require protein synthesis, was inhibited by antioxidants, and, when peroxides were the oxidants, was inhibited by intracellular iron chelators. Granule membrane protein-140 (GMP-140) is a membrane-associated glycoprotein that can be translocated from its intracellular storage pool to the surface of endothelial cells where it acts as a ligand for PMN adhesion (Geng, J.-G., M. P. Bevilacqua, K. L. Moore, T. M. McIntyre, S. M. Prescott, J. M. Kim, G. A. Bliss, G. A. Zimmerman, and R. P. McEver. 1990. Nature (Lond). 343:757-760). We found that endothelial cells exposed to oxidants expressed GMP-140 on their surface, and that an mAb against GMP-140 or solubilized GMP-140 completely blocked PMN adherence to oxidant-treated endothelial cells. Thus, exposure of endothelial cells to oxygen radicals induces the prolonged expression of GMP-140 on the cell surface, which results in enhanced PMN adherence.

Cell Adhesion↗
PubMed1991

Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils.

The adhesion of polymorphonuclear leukocytes (PMNs) to vascular endothelial cells (EC) is an early and fundamental event in acute inflammation. This process requires the regulated expression of molecules on both the EC and PMN. EC stimulated with histamine or thrombin coexpress two proadhesive molecules within minutes: granule membrane protein 140 (GMP-140), a member of the selectin family, and platelet-activating factor (PAF), a biologically active phospholipid. Coexpression of GMP-140 and PAF is required for maximal PMN adhesion and the two molecules act in a cooperative fashion. The component of adhesion mediated by EC-associated PAF requires activation of CD11/CD18 integrins on the PMN and binding of these heterodimers to counterreceptors on the EC. GMP-140 also binds to a receptor on the PMN; however, it tethers the PMN to the EC without requiring activation of CD11/CD18 integrins. This component of the adhesive interaction is blocked by antibodies to GMP-140 or by GMP-140 in the fluid phase. Experiments with purified GMP-140 indicate that binding to its receptor on the PMN does not directly induce PMN adhesiveness but that it potentiates the CD11/CD18-dependent adhesive response to PAF by a mechanism that involves events distal to the PAF receptor. Tethering of the PMN to the EC by GMP-140 may also be required for efficient interaction of PAF with its receptor on the PMN. These observations define a complex cell recognition system in which tethering of PMNs by a selectin, GMP-140, facilitates juxtacrine activation of the leukocytes by a signaling molecule, PAF. The latter event recruits the third component of the adhesive interaction, the CD11/CD18 integrins.

Antibodies, Monoclonal↗
PubMed1980

Anaesthetic management of a patient with carcinoid tumor undergoing myocardial revascularization.

Carcinoid tumors with hepatic involvement can produce intense flushing, tachycardia, hypotension or hypertension and diarrhoea. Patients with limited cardiac reserve may not tolerate these effects under anaesthesia. Valvular heart disease associated with carcinoid tumors has been reported, but there is no record in the literature of such an association with coronary artery disease. This report presents the anaesthetic management of a patient with coronary artery disease and carcinoid tumor undergoing myocardial revascularization. Emphasis is placed on the rational use of anaesthetic and adjunctive agents which will minimize the incidence of carcinoid symptons. The salient features of the management are prevention of release of vasoactive substances by the use of promethazine hydrochloride during operation, the avoidance of stropine, prophylactic administration of corticosteroids and smooth induction of anaesthesia by the use of diazepam and dimethyl-tubocurarine iodide (Metocurine).

Aged↗
PubMedDate not supplied

Cardiovascular and neuromuscular effects of esmolol during induction of anesthesia.

Sixteen subjects scheduled for surgical procedures under general anesthesia participated in an investigation of the effects of esmolol on the transient hypertension and tachycardia that was observed during endotracheal intubation and on the duration of succinylcholine-induced neuromuscular blockade. In eight subjects, infusion of esmolol was begun five minutes before induction of anesthesia and continued for 12 minutes after induction. In the remaining subjects, an equivalent volume of solvent (D5W) was infused for 12 minutes. Infusion of esmolol significantly attenuated the cardioacceleration observed during intubation without any significant effect on the pressor effects of the procedure. Esmolol delayed the recovery from succinylcholine-induced neuromuscular blockade by less than three minutes. The mechanism of this delay remains to be investigated, although such a delay does not have clinical significance. Esmolol-induced attenuation of the tachycardia seen during intubation may offer a protective effect on the myocardium, especially in elderly subjects and patients with coronary artery disease.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Identification of new Fas mutations in a patient with autoimmune lymphoproliferative syndrome (ALPS) and eosinophilia.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare, newly recognized, chronic lymphoproliferative disorder in children and is characterized by lymphadenopathy, splenomegaly, pancytopenia, autoimmune phenomena and expansion of double-negative (DN) T lymphocytes (TCR alpha beta+, CD4-, CD8-). Defective lymphocyte apoptosis caused by mutations of the Fas (CD95) gene has been linked in the pathogenesis of ALPS, as binding of Fas-ligand to Fas can trigger apoptosis. Of the ALPS cases reported to date, point mutations, frameshifts and silent mutations in Fas all have been identified. We report two new point mutations in Fas in a child with ALPS and eosinophilia; studies on other family members established the pattern of inheritance for these mutations. Flow cytometric analysis of blood and tissues (spleen, lymph node, bone marrow) revealed abnormally expanded populations of DN T lymphocytes. Furthermore, activated lymphocytes and IFN gamma-activated eosinophils were resistant to Fas-mediated apoptosis. Eosinophil resistance to Fas-mediated apoptosis has not been previously described in ALPS. Sequencing of Fas revealed two separate mutations not previously reported. One mutation, a C to T change at base 836, was a silent mutation inherited from the mother, while the second mutation, a C to A change at base 916, caused a non-conservative amino acid substitution in the death domain of Fas, changing a threonine to a lysine. This mutation is associated with a predicted change in the structure of a part of the death domain from a beta-pleated sheet to an alpha-helix. We speculate that the mutation in the death domain prevents the interaction of Fas with intracellular mediators of apoptosis and is responsible for the autoimmune manifestations of ALPS and the abnormal lymphocytosis and eosinophilia in this patient.

Adult↗
PubMedDate not supplied

Papillary cystadenocarcinoma arising in a paratubal mesothelial cyst of the mesosalpinx--a case report.

Primary carcinoma arising from a paratubal cyst in the mesosalpinx in uncommon. Serous tumors of low malignant potential outnumber invasive carcinomas, which are often of endometrioid type. Only five cases of serous papillary cystadenocarcinoma with capsular invasion have been documented. We report a case of invasive papillary cystadenocarcinoma arising in a large paratubal cyst of the mesosalpinx, in an infertile woman. Possible hormonal basis, its link to serous borderline and malignant tumors of the peritoneum, and value of pre/intra operative cyst fluid cytology are discussed. Lack of definitive management protocols, prognostic indicators and possible consequences are briefly reviewed.

Adnexal Diseases↗