Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF.
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PMID:Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF). 128 75

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothesize new possible therapeutic implications for these tumors.
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PMID:Pulmonary blastomas of childhood: histologic, immunohistochemical, ultrastructural aspects and therapeutic considerations. 1631 50

The term "mastocytosis" denotes a heterogeneous group of disorders characterised by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem to contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently encountered, especially in systemic disease. We present a literature review of mastocytosis and a rare case report of an 18 month-old-girl with a bullous dermatosis, respiratory distress and anaphylaxis, as clinical manifestations of mastocytosis. The developments of accepted classification systems and novel useful markers allowed a re-evaluation and updating of the classification of mastocytosis. In paediatric age cutaneous forms of disease prevail and may regress spontaneously. SM is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow. The clinical course in these patients is variable. Today diagnostic criteria for each disease variant are reasonably well defined. There are, however, peculiarities, namely in paediatric age, that makes the diagnostic approach difficult. Systemic disease may pose differential diagnostic problems resulting from multiple organ systems involvement. Conversely, the "unexplained" appearance of those symptoms with no skin lesions should raise the suspicion of MC disease. This case is reported in order to stress the clinical severity and difficult diagnostic approach that paediatric mastocytosis may assume.
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PMID:Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review. 1868 Jul 4

A 13-year-old male neutered British blue cat presented with uveitis, hyphema, and dyscoria in the right eye. Light microscopic examination revealed that the ciliary body, iris root, drainage angle, and adjacent choroid were infiltrated by sheets of large neoplastic mononuclear and multinucleate round to polygonal cells. Neoplastic cells stained immunopositive for CD18 and HLA-DR (MHC class II) and were immunonegative for CD3, CD79a, MUM-1, CD117 (c-Kit), and S100. These findings were consistent with a histiocytic sarcoma. The cat later developed multiple cutaneous masses composed of a similar neoplastic cell population to that seen in the eye. Eight months following enucleation, the cat developed respiratory distress and was euthanized. Postmortem examination revealed multiple pulmonary tumors associated with a pleural effusion.
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PMID:Ocular histiocytic sarcoma in a cat. 2368 65

Vascular disruption is one of the pathological hallmarks in acute respiratory distress syndrome. Bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) and lung tissue-resident EPCs have been considered to play a pivotal role in pulmonary vascular repair; however, which population is predominant in local pulmonary vasculogenesis remains to be clarified. We therefore examined the origin of EPCs participating in the regenerative process of pulmonary vascular endothelial cells (PVECs) in experimental acute respiratory distress syndrome. Lung samples from mice administered LPS intratracheally were investigated for cell dynamics and EPC functions. Quantitative flow cytometric analysis demonstrated that the number of PVECs decreased by roughly 20% on Day 1 and then recovered on Day 7 of LPS challenge. Bromodeoxyuridine-incorporation assays and immunofluorescence microscopy demonstrated that proliferating PVECs preferentially located in the capillary vessels. Experiments using BM chimera mice revealed that most of the regenerating PVECs were tissue-resident cells, and BM-derived cells hardly engrafted as PVECs. The population of circulating putative phenotypical EPCs decreased during the first week after LPS challenge. The regenerating PVECs were characterized by high colony-forming and vasculogenic capacities, intracellular reactive oxygen species scavenging and aldehyde dehydrogenase activites, and enhanced gene expression of Abcb1b (a drug-resistant gene), suggesting that the population of PVECs included tissue-resident EPCs activated during regenerative process of PVECs. The proliferating PVECs expressed CD34, Flk-1/KDR, and c-kit more strongly and Prom1/CD133 less strongly on the surface than nonproliferating PVECs. Our findings indicated that lung tissue-resident EPCs predominantly contribute to pulmonary vascular repair after endotoxin-induced injury.
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PMID:Vascular Repair by Tissue-Resident Endothelial Progenitor Cells in Endotoxin-Induced Lung Injury. 2571 75