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)

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 a retrospective case note review of all cases of Pneumocystis carinii (now Pneumocystis jirovecii) pneumonia (PJP) over the period 1997-2004 at North Manchester General Hospital with a previous audit covering the years 1986-1995. During 1986-1995, 777 patients were diagnosed with HIV. One hundred and eighty-one were also diagnosed with PJP. Of these, 11 patients required ventilation with a mortality rate of 100%. For the current review during 1997-2004, 210 patients were diagnosed with PJP, and 64 with severe PJP. Median age was 39 years (interquartile range [IQR] 22-61). Twenty-four patients had a prior diagnosis of HIV (median 43 months, IQR 6-72 months), and for 38 patients this was the presenting diagnosis of HIV. Median CD4 was 34 cells/L (IQR of 12-80 cells/L). Median viral load was 3.5 x 10(5) copies/mL (IQR 1-5.8 x 10(5) copies/mL). Eighteen patients required intubation during this period. Nine (50%) were alive at 30 days postextubation. We believe that the 50% reduction in mortality seen between 1997-2004 in intubated patients with severe PJP is due to the improvement in intensive care management of severe respiratory failure rather than changes in the specific management of PJP. The necessity of ventilation in HIV patients is no longer a mandatory death sentence.
Int J STD AIDS 2009 Mar
PMID:Retrospective review of Pneumocystis jirovecii pneumonia over two decades. 1945 39

Enfuvirtide is beneficial in patients with limited treatment options. We report this case to highlight the possibility of a delayed hypersensitivity reaction as an important potential side-effect of enfuvirtide treatment. A highly antiretroviral treatment-experienced man was commenced on a new regimen containing enfuvirtide. Prophylaxis for Pneumocystis jirovecii pneumonia was started using trimethoprim/sulphamethoxazole (TMP-STX) simultaneously. Ten days later, he developed a maculopapular rash on the chest and abdomen without any systemic features. Both enfuvirtide and TMP-STX were discontinued. Re-introduction of enfuvirtide occurred in a hospital setting. Before re-challenge, haemodynamic observations were stable. The rash re-appeared involving the whole body 5 hours post-dose and was associated with fever (temperature 38.4), nausea and a presyncopal episode. Hypersensitivity to this drug occurred immediately post-dose in phase III trials. Enfuvirtide is a useful drug in those with reduced drug options. The possibility of delayed hypersensitivity has not been reported previously.
Int J STD AIDS 2009 Apr
PMID:A delayed hypersensitivity reaction to enfuvirtide after rechallenge. 1930 81

Tigecycline belong to glycylcycline antibiotics. This new group of antibiotics was derived from lipophilic tetracyclines but differs from them by higher effectivity, lower affinity to bacterial resistance mechanisms, and very long half-time. Tigecycline is registered for treatment two groups of infections: skin and soft tissue infections and complicated intra-abdominal infections. Nevertheless, its therapeutic use probably can be enlarged to pneumonia, STD, infections caused by multi-resistant Helicobacter pylori, subacute and chronic infections associated with biofilm formation, and serious infections caused by intracellular pathogens (serious brucellosis, Q-fever, rickettsial infections). By contrast, tigecycline seems not appropriate for treatment sepsis and similar acute life-threatening bacterial diseases.
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PMID:[Tigecycline: Its position between other antibiotics, features, clinical usage]. 1939 24

Compared with the Toll-like receptor 4 (TLR4) ligand LPS restricted to gram-negative bacteria, few studies have addressed induction of lung inflammation and concomitant leukocyte recruitment in response to TLR2 ligands. This study is the first report showing that selective TLR2 stimulation by its ligand Pam(3)-Cys-Ser-Lys-Lys-Lys-Lys-OH (Pam(3)CSK(4)) within the alveolar compartment promoted lung inflammation in mice and induced the migration of circulatory immune cells including mononuclear phagocytes into the inflamed alveolar space. By using the transgenic CX(3)CR1(+/GFP) mouse strain for high-purity sorting of circulating and alveolar recruited mononuclear phagocytes together with SMART preamplification and whole genome oligonucleotide microarray techniques, we found that alveolar trafficking of mononuclear phagocytes was associated with profound changes of their gene expression profiles (approximately 900 differentially regulated genes postrecruitment). In particular, alveolar recruited mononuclear phagocytes showed upregulated transcripts of genes encoding cytokines/chemokines and pattern recognition receptor (PRR)-associated molecules. Notably, we observed a dynamic change of the genetic program of recruited mononuclear phagocytes obtained from bronchoalveolar lavage fluid at different time points (24 vs. 48 h) post-Pam(3)CSK(4) challenge. In early alveolar recruited mononuclear phagocytes, mRNA levels of both proinflammatory (e.g., TNF-alpha, CCL2, and IL-6) and central anti-inflammatory/ proresolution [e.g., IL-1-receptor antagonist (IL-1RN), CD200 receptor (CD200R), IL-1 receptor-associated kinase (IRAK-M), IL-10, and Bcl-2-associated X protein (Bax)] mediators were found to be highly upregulated simultaneously. In corresponding cells recruited until later time points, transcript levels of anti-inflammatory/proresolution molecules persisted at the same level, whereas mRNA levels of proinflammatory mediators were found to decline. Collectively, our in vivo study identifies genetic programs by which alveolar recruited mononuclear phagocytes may contribute to the development and termination of pneumonia caused by gram-positive bacteria.
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PMID:Genome-wide transcriptional profiling of mononuclear phagocytes recruited to mouse lungs in response to alveolar challenge with the TLR2 agonist Pam3CSK4. 1961 7

HSCT is the optimal treatment for patients with SCID. In particular, HSCT from a HLA-identical donor gives rise to successful engraftment with long survival. We report a six-month-old girl with JAK3-deficient SCID who developed hemophagocytosis after BMT without conditioning from her HLA-identical father. She had suffered from pneumonia and hepatitis before BMT. Prophylaxis for GVHD was short-term methotrexate and tacrolimus. On day 18 after BMT, the patient developed hemophagocytosis in bone marrow when donor lymphocytes were increasing in peripheral blood. Analysis of chimerism confirmed host origin of macrophages and donor origin of lymphocytes. Thus, host macrophage activation was presumably induced in response to donor lymphocytes through immunoreaction to infections and/or alloantigens. HSCT for SCID necessitates caution with respect to hemophagocytosis.
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PMID:Hemophagocytosis after bone marrow transplantation for JAK3-deficient severe combined immunodeficiency. 1965 8

A retrospective case-notes audit of 359 HIV-1-infected adult patients with first-episode laboratory-confirmed Pneumocystis jirovecii pneumonia treated with co-trimoxazole (from 1987 adjuvant steroids were used if PaO(2) <9.3 kPa) showed that only 230/359 (64%) patients completed treatment; 104 (29%) patients had treatment-limiting toxicity; rash occurred in 4/60 (6.7%) patients in 1985-1988 and in 15/47 (31.9%) in 2005-2008. Twenty-five patients (7%) failed co-trimoxazole treatment. Overall mortality was 13.6% (49/359); mortality among patients who failed co-trimoxazole treatment was 48% (12/25) and by contrast mortality was 4.8% (5/104) among patients with treatment-limiting toxicity.
Int J STD AIDS 2009 Sep
PMID:Outcome from treatment of Pneumocystis jirovecii pneumonia with co-trimoxazole. 1971 Mar 43

This report describes the first case of vancomycin-resistant Enterococcus pneumonia complicated with empyema and lung abscess in an HIV patient and reviews previously published cases of Enterococcus pleuro-pulmonary infection. Our case highlights the rarity of this entity and reviews the risk factors for Enterococcus pleuro-pulmonary infections.
Int J STD AIDS 2009 Sep
PMID:Enterococcus pneumonia complicated with empyema and lung abscess in an HIV-positive patient. Case report and review of the literature. 1971 Mar 46

We describe a rare case of Pneumocystic jirovecii-associated organizing pneumonia (PJP) in an HIV-infected individual on highly active antiretroviral therapy (HAART) with a CD4(+) T-cell count of 835 x 10(3) cells/mL and a low viral load. PJP was confirmed using transbronchial biopsies and bronchoalveolar lavage. The presentation in this patient suggests immune reconstitution inflammatory syndrome (IRIS) after institution of antiretroviral therapy (ART). This case report, however, is the first documented presentation of PJP in a patient with CD4 count greater than 300 prior to the induction of HAART who developed PJP and organizing pneumonia as a manifestation of IRIS. This suggests that there is continuing immune dysfunction in the face of re-expansion of CD4(+) T-cells and low viral load in HIV patients despite ART.
Int J STD AIDS 2009 Sep
PMID:Pneumocystis-associated organizing pneumonia as a manifestation of immune reconstitution inflammatory syndrome in an HIV-infected individual with a normal CD4+ T-cell count following antiretroviral therapy. 1971 Mar 47

Pneumocystis jirovecii pneumonia (PCP) prophylaxis may be discontinued when CD4 is > or =200 cells/mm(3) for three months in response to highly active antiretroviral therapy (HAART). Unlike CD4, the total lymphocyte count (TLC) is inexpensive and widely available in resource-constrained countries. Paired TLC and CD4 values of HIV-infected patients attending an HIV clinic from 1998 to 2005 were analysed by Spearman's correlation. The sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristics (ROC) using TLC cut-off points between > or =1400 and > or =2000 cells/mm(3) to predict CD4 > or =200 cells/mm(3) were calculated. Next, a cohort of patients who had a TLC < or = 1200 cells/mm(3) and subsequently achieved various TLC cut-off points sustained over three months while receiving HAART was identified. Subjects with subsequent CD4 > or =200 cells/mm(3) in response to HAART were considered to have negligible risk for PCP. There was significant correlation between TLC and CD4 in 46,250 observations from 4307 individuals (r = 0.695, P < or = 0.001). The area under the ROC curve was 0.85 (95% CI = 0.85-0.86). In the historical cohort analysis, 85% and 70% of subjects who achieved TLC > or = 2000 cells/mm(3) and > or =1400, respectively, had a corresponding CD4 > or = 200 cells/mm(3). A sustained rise in TLC in response to HAART may potentially serve as a criterion for discontinuing PCP prophylaxis in resource-constrained countries.
Int J STD AIDS 2010 Jun
PMID:Pneumocystis jirovecii prophylaxis discontinuation based upon total lymphocyte count in HIV-infected adults treated with antiretroviral therapy. 2060 20


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