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)

The authors measured plasmatic beta 2-microglobulin in 42 type II diabetes patients, whose 23 microalbuminuria (group A) and 19 normal albuminuria (group B), and in 20 healthy control subjects (group C) comparable for sex and age. Beforehand, everybody was subject to diagnostic verification to exclude other simultaneous diseases. The glomerular filtration rate, measured by creatinine clearance did not show statistical significance between three groups as well as duration of diabetes and levels of glycosylated hemoglobin between group A and B. Plasmatic beta 2-microglobulin was 3.16 +/- 0.9, 2.1 +/- 0.6, 2.0 +/- 0.9 mg/L respectively in the groups A, B and C (p < 0.001 A vs B and A vs C). The authors think in type II diabetic subjects with microalbuminuria can be an early and mild decrease of FGR. The measurement of plasmatic beta 2-microglobulin rather than creatinine clearance could be a suitable method to show it.
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PMID:[Plasma beta 2-microglobulin in patients with non-insulin-dependent diabetes mellitus]. 775 32

A subset of adult acute lymphoblastic leukemia (ALL) patients have blast cells which co-express myeloid-associated antigens (MY+ ALL). We have analyzed 113 adult ALL cases for expression of MY-associated antigens (MAA). ALL was diagnosed by standard morphology, cytochemistry, and immunophenotype in central review. MY+ ALL was diagnosed when > or = 20% of lymphoblasts co-expressed CD13 and/or CD33. Overall incidence of MY+ was 31/113 (27%). MAA expression was not significantly correlated with WBC, blast count, hemoglobin, or hematocrit. MY+ cases were more likely to express B-associated antigens, especially CALLA, and to be FAB L2, Ph+, or to have the BCR-ABL translocation by PCR, but these differences were not statistically significant. All patients were induced with a L10M regimen, and 67 (59%) achieved CR: 43/66 (65%) of B MY neg; 14/29 (48%) of B MY+; 10/16 (63%) T MY neg; and 0/2 T MY+. In age-adjusted analyses CR rate did not differ significantly between MY+ and MY neg patients or between B- and T-cell patients. Of the 113 patients, 84 have died and the remaining 29 patients have been followed for a median of 49 months. In proportional hazards regression analyses adjusting for age and WBC, heterogeneity of survival among the four groups was statistically significant (p = 0.021), largely due to MY status. The mortality rate was 85% greater for MY+ patients compared to MY neg patients (two-tailed p = 0.013). By contrast, survival did not vary significantly between B- and T-cell patients. The data indicate that MAA expression is useful for predicting overall survival of adult patients with ALL treated in a L10M protocol. As a predictive factor MAA expression is comparable to the WBC and superior to the more standard stratification by B- or T-cell markers for this group of patients.
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PMID:Expression of myeloid antigens by blast cells in acute lymphoblastic leukemia of adults. The Southwest Oncology Group experience. 780 99

The hemoglobin-oxygen dissociation curve and the relationships between the parameters of tension, saturation, capacity, affinity and concentration of oxygen in the course of respiratory failure in chronic obstructive lung diseases (COLD) were studied. The study included 141 patients divided into four basic groups according to the value of pO2 (a): patients with normoxia, mild, moderate and severe arterial hypoxia. The blood-gas status was determined using the ABL-330 and OSM-3 analyzers (Radiometer A/S, Denmark). It is concluded that: 1. Presence of normoxia (pO2 and sO2 in norm) in COLD patients does not exclude abnormalities in their arterial blood oxygen transport and increased risk of tissue hypoxia. 2. Total oxygen concentration in respiratory failure is relatively stable and "independent" from the stepwise decrease of the arterial pO2, which results from the compensatory increase of the total and effective hemoglobin. 3. There are phase fluctuations of the ctO2/pO2 dissociation curve in the reference interval, expressed in the "lowering" of P50 and p90 in mild hypoxia and the "centering" or "raising" of their values in severe hypoxia. Such fluctuations are more pronounced in the p90 than in the p50. 4. The oxygen extraction tension lowers progressively (without reaching the anaerobic threshold) and the oxygen compensation factor elevates with the pO2 (a) reduction and the arising of hypercapnia and acidemia. 5. The calculated 2,3-diphosphoglycerate (2,3-DPG) concentration values are significantly higher in hypercapnics with COHb > 1% than in those with COHb < 1%. The relationships between hypoxia, oxygen affinity, hemoglobinemia and oxygen affinity as well as the dissociation curve properties in chronic respiratory failure are discussed.
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PMID:Relationships between blood oxygen parameters in patients with chronic obstructive lung disease. 819 1

There is now considerable evidence that nitric oxide (NO) is an important neuroregulatory agent, but there has been very little investigation of the possible role of NO in neuroendocrine mechanisms. We have previously shown that acute rat hypothalamic explants can be used to study the regulation of hypothalamic neuropeptide release, and we have now utilised this experimental approach to investigate the putative involvement of NO in the control of the principal corticotropin-releasing hormone, CRH. We studied the direct effects of the NO precursor L-arginine (L-ARG), as well as the NO donors molsidomine and sodium nitroprusside, on both the basal and stimulated release of CRH; the stimuli used were non-specific depolarisation with potassium chloride (KCl) and the specific cytokine, interleukin-1 beta (IL-1 beta; 100 U/ml). L-ARG was tested in each experimental condition with and without contemporaneous addition of its competitive antagonist NG-monomethyl-L-arginine (L-NMMA). IL-1 beta-induced CRH release was also investigated in the presence of D-arginine (D-ARG), which is not active as a precursor to NO, and ferrous hemoglobin (Hb), a substance which is a potent inactivator of NO. None of the NO precursors (L-ARG, molsidomine, sodium nitroprusside) or antagonists (L-NMMA or Hb) was able to affect basal CRH release. However, L-ARG 10 and 100 microM were found to significantly inhibit the release of CRH induced by 40 mM KCl; CRH fell to 45% of its stimulated level at the higher dose of L-ARG. This effect was attenuated in the presence of L-NMMA at a ten-fold higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro. 848 68

The acute phase proteins (APPs) have been empirically defined as those whose plasma concentration changes following inflammatory reaction. Those proteins whose concentrations increase are referred to as positive APP, while those whose levels decline are termed negative APP. In man, positive APP are: alpha 1 acid glycoprotein, alpha 1 protease inhibitor, alpha 1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A. Great variability in the APP response between different species is observed. The principal functions of APP, result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The drop of the plasma concentration of negative APP during an inflammatory reaction carries a rise of free ligands (fatty acids, hormones, vitamins, trace elements). IL6 has been recognized as the principal regulator of most APP genes. The response of the hepatic cell to IL6 is characterized by the enhanced production of type 2 or IL6 specific APPs. The biochemical process of signal transduction is IL6--JAK2--APRF The set of APP genes regulated by IL1 type cytokines (type 1 APPs) is distinct from that regulated by IL6 type cytokine. IL1 and TNF alpha mediated stimulation of type 1 APP genes is synergistically enhanced by IL6 type cytokines. The biochemical process of signal transduction is IL1, IL6--Ras--MAP kinase--NFIL6 The targeted inflammatory proteic profile including the assay of C-reactive protein, haptoglobin and alpha 1 acid glycoprotein produces a "biological tool" to the clinician in order to manage an inflammatory response. IL6, a proteic marker for the future, connected with CRP, will be assayed during early inflammatory reaction.
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PMID:[Acute-phase proteins in inflammation]. 856 70

In response to erythropoietin, J2E cells proliferate and differentiate into mature hemoglobin-producing erythroid cells. Here we show that following hormonal stimulation, between 10 and 17 proteins, including the erythropoietin receptor and JAK2, were tyrosine phosphorylated immediately after exposure to the hormone. Although the receptor was only phosphorylated to 15% of its maximum with 0.1 unit/ml erythropoietin, this was sufficient to induce peak hemoglobin synthesis. The importance of JAK2 to J2E cell maturation was demonstrated by inhibiting JAK2 protein synthesis with antisense oligonucleotides; not only was erythropoietin-stimulated mitogenesis inhibited by this procedure, but differentiation was also suppressed. In addition, the activation of STAT5 paralleled the kinetics of receptor phosphorylation. During differentiation, 94% decrease in surface erythropoietin receptors was detected 48 h after ligand binding, but transcription of the receptor gene, mRNA steady-state levels, protein content, and translation rates did not alter with hormonal stimulation. We concluded from these experiments that (a) sub-maximal receptor phosphorylation is sufficient for differentiation to proceed; (b) JAK2 is required for erythropoietin-induced cell division and maturation; and (c) post-translational processing, or translocation, play important roles in controlling surface erythropoietin receptor numbers.
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PMID:Regulation of the erythropoietin receptor and involvement of JAK2 in differentiation of J2E erythroid cells. 905 92

In some situations such as a sudden bleeding during surgery, rapid testing of blood hemoglobin concentration is necessary. The HemoCue Blood Hemoglobin Test uses a lightweight photometer, which is easily movable anywhere. The HemoCue needs only 10 microliters of blood and it takes only about 45 seconds to produce the result. Therefore, the device might be useful in the operating suite and the emergency unit. To evaluate the accuracy of the HemoCue, we compared the blood hemoglobin concentrations measured by the HemoCue with those measured by the ABL 300. A positive correlation was found between the variables by the HemoCue (Y) and those by the ABL 300 (X); Y = 0.944X - 0.208, r = 0.97, P < 0.001. It is concluded that the HemoCue is a reliable device for measurement of blood hemoglobin concentration.
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PMID:[A simple, lightweight device for measurement of hemoglobin; the HemoCue Blood Hemoglobin Test]. 907 Nov 18

During extracorporeal circulation (ECC) a continuous monitoring of venous oxygen saturation yields a quantitative impression of the equilibrium of oxygen supply and oxygen consumption in steady state conditions. The aim of the investigation was to study whether the measurements of venous oxygen saturation and haemoglobin of a continuous on-line monitor (CDI-100) agree with those of the ABL-4 bloodgasmonitor or the haemoglobincyanid method in hospital laboratory. The study group consisted of 21 patients, with comparable conditions of anesthesia and ECC set-up. Measurements of saturation and haemoglobin were compared at three moments, resulting in a total of 189 measurements. Analysis was based on the Bland Altman method, using the differences between correspondent measurements, which contain all the information needed to decide whether the methods agree. Bias of saturation measurement (CDI-100 versus ABL-4) is -3.4, 3.0 and -3.5% at times 1,2 and 3. All values are situated within the limits of agreement. Bias of haemoglobin measurement (CDI-100 versus ABL-4) is 0.3, 0.3, and 0.2 gr/dl at times 1, 2 and 3. All values (except one value) are situated within the limits of agreement. Bias of hemoglobin measurement (CDI-100 versus hospital laboratory) is 0.2, 0.0 and 0.1 gr/dl, and all values are situated within the limits of agreement. The results confirm that the CDI-100, in the set-up as described, can be used as a reliable instrument to monitor venous oxygen saturation and haemoglobin during ECC.
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PMID:Comparison between CDI-100 continuous SO2, Hb, and Hct monitoring, intermittent ABL-4 saturation and Hb monitoring, and lab Hb and Hct monitoring. 909 48

Eight healthy males performed four rides to exhaustion at approximately 70% of their VO2max obtained in a neutral environment. Subjects cycled at ambient temperatures (Ta) of 3.6 +/- 0.3 (SD), 10.5 +/- 0.5, 20.6 +/- 0.2, and 30.5 +/- 0.2 degrees C with a relative humidity of 70 +/- 2% and an air velocity of approximately 0.7 m.s-1. Weighted mean skin temperature (Tsk), rectal temperature (Tre), and heart rate (HR) were recorded at rest, during exercise and at exhaustion. Venous samples were drawn before and during exercise and at exhaustion for determination of hemoglobin, hematocrit, blood metabolites, and serum electrolytes and osmolality. Expired air was collected for calculation of VO2 and R which were used to estimate rates of fuel oxidation. Ratings of perceived exertion (RPE) were also obtained. Time to exhaustion was significantly influenced by Ta (P = 0.001): exercise duration was shortest at 30.5 degrees C (51.6 +/- 3.7 min) and longest at 10.5 degrees C (93.5 +/- 6.2 min). Significant effects of Ta were also observed on VE, VO2, R, estimated fuel oxidation, HR, Tre, Tsk, sweat rate, and RPE. This study demonstrates that there is a clear effect of temperature on exercise capacity which appears to follow an inverted U relationship.
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PMID:Effects of ambient temperature on the capacity to perform prolonged cycle exercise in man. 930 37

Interactions of mesangial cells (MCs) with components of the extracellular matrix (ECM) profoundly influence the MC phenotype, such as attachment, contraction, migration, survival and proliferation. Here, we investigated the effects of exogenous nitric oxide (NO) on the process of MC adhesion to ECM molecules. Incubation of rat MCs with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) dose- and time-dependently inhibited MC adhesion and spreading on various ECM substrata, being more pronounced on collagen type I than on collagen type IV, laminin or fibronectin. In contrast, SNAP did not inhibit MC adhesion to L-polylysine-coated plates. The inhibitory effects of SNAP were reduced by hemoglobin and enhanced by superoxide dismutase. The anti-adhesive action of SNAP was mimicked not only by other NO donors but also by 8-bromo-cGMP, and significantly reversed by the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ). Moreover, SNAP and 8-bromo-cGMP decreased the adhesion-induced phosphorylation of focal adhesion kinase (pp125FAK). In the presence of SNAP or 8-bromo-cGMP, adherent MCs exhibited disturbed organization of alpha-actin filaments and reduced numbers of focal adhesions, as shown by immunocytochemistry. In additional experiments with adherent MCs, it was found that exposure to SNAP or 8-bromo-cGMP for 12 and 24 hours induced detachment of MCs. The results indicate that exogenous NO interferes with the establishment and maintenance of MC adhesion to ECM components. This inhibitory NO effect is mediated predominantly by cGMP-signaling. Disturbance of MC attachment to ECM molecules could represent an important mechanism by which NO affects MC behavior in vitro and in vivo.
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PMID:Exogenous nitric oxide inhibits mesangial cell adhesion to extracellular matrix components. 950 4


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