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)

Some of the HIV-1-infected patients who were given highly active anti-retroviral therapy (HAART) including efavirenz (EFV) presented adverse central nervous system (CNS) symptoms such as fatigue and insomnia. The incidence of adverse CNS symptoms is associated with hepatic cytochrome P450 isozymes (CYP2B6) polymorphisms. For example, CYP2B6 *6 (G516T and A785G) and *7 (G516T, A785G and C1459T) prolonged the EFV half-life despite discontinuation of EFV. CYP2B6 *2/*2 (C64T) is extremely rare and there have been no data describing the EFV plasma concentrations in C64T homozygous patients, who developed adverse CNS symptoms. C64T homozygous possibly has some catalytic defects.
Int J STD AIDS 2007 Aug
PMID:Efavirenz-induced neurological symptoms in rare homozygote CYP2B6 *2/*2 (C64T). 1768 25

The etiology of skeletal muscle fatigue is not well understood partly because techniques portraying muscle performance in vivo are limited by either their invasiveness (e.g., needle electrodes) or poor spatial resolution (e.g., surface EMG). To better characterize effects of FES and muscle fatigue, we captured real-time high resolution dynamics of the human forearm before and after a fatigue exercise using ultrasound strain imaging. A 10 MHz linear ultrasound probe aligned with the fiber axis of the 3rd flexor digitorum superficialis (FDS) provided scans at 3-msec intervals during isometric twitch and tetanic contractions evoked by low and high frequency electrical stimuli (ES). Ultrasound images synchronized with traditional force and EMG were obtained for 5 healthy adults before and after a fatiguing exercise, induced by sustained maximal exertion of the middle finger pressed against a restraint until the initial force decreased by 75%. Immediately after fatigue, twitch and tetanic stimuli generated 55.1% and 19.5% less force, respectively, implying that low frequency fatigue dominated. The force deficit was associated with a decrease in several mechanical properties of the fatigued muscle during twitch contractions, such as transverse peak strain (34 +/- 15%) and half peak strain duration (32.3 +/- 12.5 msec). Changes were not uniform across the imaged section of the muscle, suggesting that boundary conditions or fiber heterogeneity affected the strain profile. Indeed, high stress zones appeared closer to the muscle-tendon junction during isometric contractions. This study provided new insight on the elastic behavior of muscle and potential mechanisms of injury, especially directed at prolonged stimulation and control of a neuromuscular prosthesis.
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PMID:Effect of fatigue on muscle elasticity in the human forearm using ultrasound strain imaging. 1794 90

A 62-year-old man presented with fatigue, pallor and mild weight loss. Laboratory studies showed Hb 7.6 g/dl, Hct 21.8%, WBC 108x10(9)/1, PLT 143x10(9)/1. At morphological examination, circulating cells appeared as 60% blasts and 40% lymphocytes, with smudge cells. A bone marrow aspirate showed infiltration by blasts (50%) and lymphocytes (40%); alpha-naphtyl-acetate esterase was positive in 90% of blasts, while myeloperoxidase was positive in 10%. The immunologic phenotype of blasts was characterized by the co-expression of CD13, CD33, CD14, CD4, CD15, CD64, CD117, HLA-DR, CD11b. Lymphocytes were characterized by a B-CLL immunophenotype: CD19+, CD5+, CD23+, CD20+(dim), FMC7+(dim), K light chain+(dim). Karyotype was normal and PCR assays for AML-ETO, CBFbeta-MYH11, PML-RARalpha, BCR-ABL and bcl-1/JH translocation were negative. Coexistence of CLL and AML with monoblastic features was diagnosed. Simultaneous appearance of CLL and AML has rarely been described and represents a peculiar biological phenomenon.
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PMID:Association of B-chronic lymphocytic leukemia and acute myeloid leukemia. 1798 6

The incidence of syphilis has increased substantially over the past years, particularly in men who have sex with men. The clinical manifestations of syphilis are variable and liver involvement is uncommon, but may occur at any stage of the disease. We report a case of early syphilitic hepatitis (ESH) in an immunocompetent patient referring multiple bisexual exposures, who presented at admission with jaundice, tiredness, an ulcerated genital lesion and an increase of liver aminotransferases. During his hospital stay, he developed a skin rash, and serology for syphilis was found positive. Our case report strengthens the need to take into consideration the diagnosis of ESH in all patients with unexplained liver enzyme increase and epidemiological data of unsafe sexual exposures. Indeed, an early recognition of the clinical manifestations of syphilis can lead to a prompt treatment, and allows the prevention of the transmission of this disease to other individuals.
Int J STD AIDS 2008 Jan
PMID:Early syphilitic hepatitis in an immunocompetent patient: really so uncommon? 1827 54

Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
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PMID:Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. 1840 16

Arginine supplementation has been shown to alleviate endothelial dysfunction and improve exercise performance through increasing nitric oxide production in patients with cardiopulmonary diseases. In addition, arginine supplementation could decrease accumulations of lactate and ammonia, metabolites involved in development of muscular fatigue. The aim of this study was to investigate the effect of short-term arginine supplementation on performance in intermittent anaerobic exercise and the underlying mechanism in well-trained male athletes. Ten elite male college judo athletes participated with a randomized crossover, placebo-controlled design. The subjects consumed 6 g/day arginine (ARG trial) or placebo (CON trial) for 3 days then performed an intermittent anaerobic exercise test on a cycle ergometer. Blood samples were collected before supplementation, before and during exercise and 0, 3, 6, 10, 30 and 60 min after exercise. ARG trial had significantly higher arginine concentrations than CON trial at the same time point before, during and after exercise. In both trials, nitrate and nitrite concentration was significantly higher during and 6 min after exercise comparing to the basal concentration. The increase in nitrate and nitrite concentration during exercise in both trials was parallel to the increase in plasma citrulline concentrations. There was no significant difference between the 2 trials in plasma nitrate and nitrite, lactate and ammonia concentrations and peak and average power in the exercise. The results of this study suggested that short-term arginine supplementation had no effect on nitric oxide production, lactate and ammonia metabolism and performance in intermittent anaerobic exercise in well-trained male athletes.
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PMID:No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. 1870 87

The objective of this study was to examine the effect of sodium bicarbonate (NaHCO3-) ingestion on performance and perceptual responses in a laboratory-simulated bicycle motocross (BMX) qualification series. Nine elite BMX riders volunteered to participate in this study. After familiarization, subjects undertook two trials involving repeated sprints (3 x Wingate tests [WTs] separated by 30 minutes of recovery; WT1, WT2, WT3). Ninety minutes before each trial, subjects ingested either NaHCO3- or placebo in a counterbalanced, randomly assigned, double-blind manner. Each trial was separated by 4 days. Performance variables of peak power, mean power, time to peak power, and fatigue index were calculated for each sprint. Ratings of perceived exertion were obtained after each sprint, and ratings of perceived readiness were obtained before each sprint. No significant differences were observed in performance variables between successive sprints or between trials. For the NaHCO3- trial, peak blood lactate during recovery was greater after WT2 (p < 0.05) and tended to be greater after WT3 (p = 0.07), and ratings of perceived exertion were not influenced. However, improved ratings of perceived readiness were observed before WT2 and WT3 (p < 0.05). In conclusion, NaHCO3- ingestion had no effect on performance and RPE during a series of three WT simulating a BMX qualification series, possibly because of the short duration of each effort and the long recovery time used between the three WTs. On the contrary, NaHCO3- ingestion improved perceived readiness before each WT.
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PMID:Effects of sodium bicarbonate ingestion on performance and perceptual responses in a laboratory-simulated BMX cycling qualification series. 1871 19

The purpose of this study was to evaluate the immune status of women with stage I-III breast cancer after receiving external beam radiotherapy (RT). Fourteen stage I-III, estrogen or progesterone receptor-positive or-negative (FER/PR +\-), postsurgical breast cancer patients undergoing a standard course of chemotherapy and radiation were studied. Complete blood counts (CBC) with differential, phagocytic activity, natural killer (NK) cell functional activity, and tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma cytokine activity were measured immediately before and for the six weeks following the completion of radiation therapy. Fatigue levels after completion of RT were measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale. Nonparametric statistical methods (Wilcoxon rank and Spearman correlations) were used to analyze the data. Compared with postchemotherapy, following the completion of RT, these breast cancer patients showed lymphopenia, low functional activity of natural killer lymphocytes, decreased monocyte phagocytic activity, and decreased TNF-alpha production but no neutropenia, no anemia, and no change in interferon-gamma production. Lymphocyte count did not return to normal by the end of the 6-week post-RT observation period. The severity of lymphopenia and low natural killer cell activity was related to RT area but not radiation dose. Patients did not report significant fatigue levels for the 6 weeks after completing RT. Significant decreases in the numbers and functions of cells from both the innate and adaptive immune system were detected following a standard course of radiation therapy for the treatment of breast cancer. Immune deficits in lymphocyte populations and TNF-alpha production, should they persist, may have consequences for immune response to residual or recurrent malignancy following completion of conventional treatment. The use of adjunctive immune therapies which target these specific defects may be warranted in the post-treatment period.
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PMID:Immune defects in breast cancer patients after radiotherapy. 1908 68

We report a clinical case of chronic myelogenous leukaemia (CML) with regional B-lymphoblastic transformation. Peripheral leukocytosis of 160 x 10(9)/L, splenomegaly and fatigue suggested CML. In peripheral blood and bone marrow smears, white blood cells in all maturation stages and only few blasts were seen and therefore the diagnosis of chronic phase CML was proposed. Cytogenetics performed on peripheral blood cells revealed the characteristic t(9;22)(q34;q11) translocation as solitary abnormality. Analyzing the bone marrow biopsy a focal nodular B-lymphoid blast component was additionally seen. BCR-ABL FISH analysis demonstrated 31% atypical split signals in the B-lymphoid blasts and in the maturing myeloid cells, furthermore, BCR-ABL fusion transcripts were seen in the RT-PCR assay. Imatinib-based therapy led to temporary regression of peripheral leukocytosis. Bone marrow examination 3 weeks after therapy induction demonstrated considerably reduced cellularity and the proportion of B-lymphoid blasts had decreased to 20% of the nuclear cells. BCR-ABL FISH analysis still presented 21% atypical split signals but levels of BCR-ABL transcripts had significantly fallen indicating a rather favourable prognosis. However, 3 months after diagnosis the patient relapsed and developed an immunodeficiency with soor esophagitis and aspergillus pneumonia. A therapy with dasatinib was not successful and the patient died in consequence of immunodeficiency. This report demonstrates the high diagnostic value of bone marrow biopsy in the evaluation of CML. Besides morphology investigation of diverse methods including RT-PCR and FISH performed on diagnostic bone marrow biopsies are obligatory for ideal monitoring of drug response.
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PMID:High diagnostic value of morphologic examination and molecular analysis of bone marrow biopsies in a case of BCR-ABL+ CML with clusters of blasts. 1922 89

The aim of the study was to compare the clinical performance, quantitative and qualitative wear patterns of conventional hybrid (Tetric Ceram), micro-filled hybrid (Gradia Direct Posterior) and nano-hybrid (Tetric EvoCeram, TEC) posterior composite restorations in a 3-year randomised clinical trial. Sixteen Tetric Ceram, 17 TEC and 16 Gradia Direct Posterior restorations were placed in human molars and evaluated at baseline, 6, 12, 24 and 36 months of clinical service according to US Public Health Service criteria. The gypsum replicas at each recall were used for 3D laser scanning to quantify wear, and the epoxy resin replicas were observed under scanning electron microscope to study the qualitative wear patterns. After 3 years of clinical service, the three hybrid restorative materials performed clinically well in posterior cavities. Within the observation period, the nano-hybrid and micro-hybrid restorations evolved better in polishability with improved surface gloss retention than the conventional hybrid counterpart. The three hybrid composites showed enamel-like vertical wear and cavity-size dependant volume loss magnitude. Qualitatively, while the micro-filled and nano-hybrid composite restorations exhibited signs of fatigue similar to the conventional hybrid composite restorations at heavy occlusal contact area, their light occlusal contact areas showed less surface pitting after 3 years of clinical service.
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PMID:Three-year randomised clinical trial to evaluate the clinical performance, quantitative and qualitative wear patterns of hybrid composite restorations. 1966 76


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