Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive method for the quantitation of IgG on platelets had not been demonstrated until 1975, when Dixon, Rosse, and Ebbert described a quantitative antiglobulin consumption test useful in detecting platelet associated IgG (N Engl J Med 292:230, 1975). A modification of that technique has rendered the assay reproducible and removed the need for daily repetition of a standard IgG titration curve for quantitation. This modification utilizes 1-ethyl-3-3(dimethylaminopropyl)carbodiimide HCl (ECDI) (Sigma, E-7750), in place of chromic chloride, as a coupling agent for attaching IgG (Miles 64-145) to sheep cells (SRC), used as indicator cells. The ECDI consistently couples IgG to SRC and does not subject the SRC to sporadic spontaneous lysis, as does chromic chloride. This modification permits the detection of IgG on platelets (Direct Test), or in sera (Indirect Test) by incubation of a washed platelet pool with sera in vitro, and testing as in the Direct Test. Normal values of 0.01-1.56 and 0.14-1.6 femtograms (F) per platelet have been obtained for the Direct and Indirect Tests, respectively. In six cases of suspected ITP, values ranged 12.0-221.0 F and 2.9-37.6 F for the Direct and Indirect Tests, respectively. In conclusion, in disease states or other abnormal situations, quantities of IgG can be detected that are not usually present on the platelets of normal subjects.
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PMID:A quantitative determination for the detection of immunoglobulin (IgG) on the surface of platelets. 617 61

IgG-SRK (identical with Sandoglobulin) is a polyvalent IgG concentrate obtained by modified alcohol cryoprecipitation, including mild acidification at pH 4. This product was given in high doses intravenously for the treatment of six children with acute ITP, four children with intermittent ITP, and three children with severe chronic idiopathic thrombocytopenic purpura (ITP). An impressive initial response was observed in all patients, the extent of which may be of prognostic significance in acute ITP. Maintenance therapy was required in two of six patients with acute ITP, in three out of four patients with intermittent ITP, and in all of the patients with severe chronic ITP. In the cases of severe chronic ITP, the disease could not be adequately controlled over long periods of time, but bleeding episodes subsided or became considerably less frequent. Although little is known of the effects of IgG-SRK, possible mechanisms were discussed. It is emphasized that a new model has been discovered to study the interrelations between structure and function of human immunoglobulin molecules.
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PMID:Intravenous immunoglobulin for idiopathic thrombocytopenic purpura (ITP) in childhood. 643 40

Skrljevo disease, also called Rijeka (Fiume) or Grobnik disease, by some physicians was first identified in the village of Skrljevo in Croatia in 1790. From texts dating back to the beginning of the 19th century it is clear that it was a non-venereal (endemic) form of syphilis and represented a great calamity for the local people and a problem for the physicians. The disease was considered by some to be lepra, scurvy, scabies or others. The occurrence of the disease in the region around Rijeka was closely associated with the poor socioeconomic conditions present at that time in the region. It is interesting to note that many of the greatest physicians of the time such as Alibert, Frank, Hebra, Sigmund were acquainted with the disease and dealt with it in their writings. This paper gives a brief chronology of the major political events in the region since that time, underlying the measures used in fighting the disease.
Int J STD AIDS 2000 Apr
PMID:Skrljevo disease--two centuries of history. 1077 82

Growth hormone (GH) is secreted in a pulsatile pattern to promote body growth and metabolism. GH exerts its function by activating several signaling pathways, including JAK2/STAT and MEK/ERK. ERK1/2 activation by GH plays important roles in gene expression, cell proliferation, and growth. We previously reported that in rat H4IIE hepatoma cells after an initial GH exposure, a second GH exposure induces STAT5 phosphorylation but not ERK1/2 phosphorylation (Ji, S., Frank, S. J., and Messina, J. L. (2002) J. Biol. Chem. 277, 28384-28393). In this study the mechanisms underlying GH-induced homologous desensitization were investigated. A second GH exposure activated the signaling intermediates upstream of MEK/ERK, including JAK2, Ras, and Raf-1. This correlated with recovery of GH receptor levels, but was insufficient for GH-induced phosphorylation of MEK1/2 and ERK1/2. Insulin restored the ability of a second GH exposure to induce phosphorylation of MEK1/2 and ERK1/2 without altering GH receptor levels or GH-induced phosphorylation/activation of JAK2 and Raf-1. GH and insulin synergized in promoting cell proliferation. Further investigation suggested that insulin increased the amount of MEK bound to KSR (kinase suppressor of Ras) and restored GH-induced tyrosine phosphorylation of KSR. Previous GH exposure also induced desensitization of STAT1 and STAT3 phosphorylation, but this desensitization was not reversed by insulin. Thus, insulin-regulated resensitization of GH signaling may be necessary to reset the complete response to GH after a normal, physiologic pulse of GH.
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PMID:Insulin reverses growth hormone-induced homologous desensitization. 1671 97

The Country Walk case in Dade County, Florida was long considered a model for how to prosecute a multi-victim child sexual abuse case involving young children. In the past 10 years, however, a contrary view has emerged that the case was tainted by improper interviewing and was likely a false conviction. This is the first scholarly effort to assess the competing views of this case. Critics of this case advance three primary claims: (1) the positive STD test result from Frank Fuster's son was unreliable; (2) highly suggestive interviewing produced the children's claims; and (3) Frank Fuster's wife, Ileana, was coerced into testifying against her husband. On close examination, all three claims prove to be false. This article documents the reasons why these claims constitute myths and why those findings are significant in the larger debate on children as witnesses.
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PMID:Myths about the Country Walk case. 1803 42

In hematological disorders, thrombocytopenia is frequently observed, and it is sometimes difficult to diagnose the underlying disease. In this symposium, laboratory tests for platelet abnormality were reviewed. Tests for platelet aggregation were reported to be important for the diagnosis of platelet dysfunction. Thrombocytopenia is caused by disseminated intravascular coagulation (DIC), thrombotic microangiopathy (TMA), heparin-induced thrombocytopenia (HIT), antiphospholipid syndrome (APS), idiopathic thrombocytopenic purpura (ITP), etc. As DIC is classified according to the degree of fibrinolysis, it was stated that the measurement of hemostatic molecular markers was further required. TMA is caused by abnormality of ADAMTS13, verotoxin, DIC, etc. HIT is diagnosed by anti-PF4 antibody, but its specificity is not high. Further investigation of TMA and HIT is required. APS is one of the most important diseases which cause thrombosis or abortion, suggesting that a differential diagnosis of APS is important. It was reported that diagnostic criteria of ITP have been established using a new antibody assay for platelets, immature platelet fractions, thrombopoietin, etc. In myeloproliferative disorders such as polycythemia vera and essential thrombocythemia, the mutation of JAK2 V617F was reported to be an important risk factor for thrombosis.
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PMID:[Summary of pathophysiology and diagnosis of patients with platelet abnormality]. 1952 56

Since the phase-out of pentaBDE in the early 2000s, replacement flame-retardant mixtures including Firemaster 550 (FM 550), Firemaster 600 (FM 600), and organophosphate aryl ester technical mixtures have been increasingly used to treat polyurethane foam in residential upholstered furniture. These mixtures contain isomers of isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs), which have similar or greater neuro- and developmental toxicity compared to BDE 47 in high-throughput assays. Additionally, human exposure to ITPs and TBPPs has been demonstrated to be widespread in several recent studies; however, the relative composition of these mixtures has remained largely uncharacterized. Using available authentic standards, the present study quantified the contribution of individual ITP and TBPP isomers in four commercial flame retardant mixtures: FM 550, FM 600, an ITP mixture, and a TBPP mixture. Findings suggest similarities between FM 550 and the ITP mixture, with 2-isopropylphenyl diphenyl phosphate (2IPPDPP), 2,4-diisopropylphenyl diphenyl phosphate (24DIPPDPP), and bis(2-isopropylphenyl) phenyl phosphate (B2IPPPP) being the most prevalent ITP isomers in both mixtures. FM 600 differed from FM 550 in that it contained TBPP isomers instead of ITP isomers. These analytes were also detected and quantified in a house dust standard reference material, SRM 2585, demonstrating their environmental relevance.
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PMID:Characterization of Individual Isopropylated and tert-Butylated Triarylphosphate (ITP and TBPP) Isomers in Several Commercial Flame Retardant Mixtures and House Dust Standard Reference Material SRM 2585. 2907 39