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)

Translocation t(9;22) or Philadelphia chromosome (Ph)/BCR-ABL rearrangement positive acute lymphoblastic leukemia (Ph/BCR+ ALL) is associated with a very short survival of about one year in most patients. We analyzed long-term outcome of 76 adults with Ph/BCR+ ALL, in order to detect which factors were associated with longer survival. Modifiable prognostic factors included type of treatment, allogeneic marrow transplant (allo-BMT), and early anthracycline dose intensity (high = H/A, low = L/A); unmodifiable factors were age, gender, FAB morphology, phenotype, blast count, P190/210 transcript, hepatospleno-lymphadenopathy, LDH level. Median patient age was 43 years (range 15-71). Four favorable prognostic factors (FPF) were found associated with greater likelihood of complete remission (blast count < 50 x 10(9)/l, p = 0.08), longer remission duration (age < 50 years, p < 0.001; H/A, p < 0.05), and lower relapse rate (allo-BMT, p = 0.017). Age and anthracycline dose intensity exerted a synergistic prognostic effect. According to the cumulative incidence of FPF in each patient (FPF 0-1 = 29, 2-3 = 42, 4 = 5), the probability of survival increased from nil to 0.22 to 0.60 at 5 years (p < 0.005). Adult Ph/BCR+ ALL is relatively sensitive to anthracyclines, which therefore should be prescribed at full dosage to patients not eligible to allo-BMT or in the waiting list for unrelated donor transplantation.
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PMID:Clinical sensitivity to anthracyclines in PH/BCR+ acute lymphoblastic leukemia. 1050 Aug 26

During the 1990s, no studies of various clinical presentations of syphilis have been published in the indexed literature. However, a change in the clinical profile of secondary syphilis was expected during the last decade with the rapid spread of the HIV epidemic. The objective was to study the mucocutaneous manifestations of secondary syphilis in patients attending the STD clinic at the Postgraduate Institute of Medical Education & Research Chandigarh, India, during the last decade and to compare them with other similar studies published during the 1980s. All patients who were diagnosed with secondary syphilis in our STD clinic from 1990 to 1999 were examined and investigated. Serological response was measured at 3, 6, 9, 12, and 24 months post-treatment or until serological negativity was reached. Fifty-three patients (males = 34, female = 19) during this period were found to have secondary syphilis. The most common symptoms were as follows-skin rash 38 (71.7%), lymphadenopathy 26 (49%), persistent chancre 4 (7.5%), nodular syphilides 2 (3.8%), lues maligna 2 (3.8%), patches in the oral mucosa 6 (11.3%), condylomata lata 14 (26.4%), split papules 2 (3.8%). Five patients had a thin and conspicuous genital scar of the healed primary chancre. Three patients were HIV seropositive (1 patient each with lues maligna, lichenoid, and nodular syphilides). With the spread of the HIV epidemic, atypical muco-cutaneous manifestations of secondary syphilis may be seen more frequently than before and may pose problems in diagnosis. In the present study, six patients had atypical manifestations, and three of them were HIV seropositive.
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PMID:Mucocutaneous manifestations of secondary syphilis in north Indian patients: a changing scenario? 1134 64

Our objective was to determine the prevalence of HIV and the distribution of HIV-related diseases among adult, medical inpatients. Consecutive admissions were recruited and a single ELISA assay was used to determine HIV infection. Demographic and clinical details were extracted from clinical records. Of 507 patients, 54% were infected with HIV of which 84% had AIDS. HIV-infected patients were significantly younger (34.9 years) than uninfected patients (47.1 years) and had significantly higher risks for oral/oesophageal candidiasis (risk ratio [RR] 18.6), generalized lymphadenopathy (RR 7.1), unexplained fever (RR 7.0), chronic diarrhoea (RR 6.2) and pulmonary tuberculosis (RR 3.1). Pulmonary tuberculosis was present in 56% of HIV cases. Mortality was 22% for HIV cases and 9% (P=0.016) for others. The mean length of hospital stay was the same for HIV-infected and uninfected patients. AIDS is the most common reason for admission to adult medical wards and will increasingly limit the number of beds available for non-AIDS patients.
Int J STD AIDS 2001 Jun
PMID:Prevalence of HIV and HIV-related diseases in the adult medical wards of a tertiary hospital in Durban, South Africa. 1136 20

In this review, we focus on new data from basic, translational and clinical research relating to the Epstein-Barr virus (EBV). Beside its well-known tropism for B lymphocytes and epithelial cells, EBV also infects T lymphocytes, monocytes and granulocytes. After primary infection, EBV persists throughout the life span in resting memory B cells, from where it is reactivated upon breakdown of cellular immunity. In the process of neoplastic transformation, the EBV-encoded latent membrane protein 1 (LMP1) oncogene represents the major driving force. LMP1 acts like a constitutively activated receptor of the tumor necrosis factor receptor family and allows the amplification or bypassing of physiological regulatory signals through direct and indirect interactions with proteins of the tumor necrosis factor receptor-associated factor (TRAF) family. TRAF2-mediated NF-kappaB activation, AP-1 induction and JAK3/STAT activation may result in sustained proliferation leading to lymphoma. The ability of LMP1 to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light on the pathogenesis of EBV-associated latency type II lymphoproliferations like Hodgkin's disease and angioimmunoblastic lymphadenopathy. The carboxy terminus of LMP1 is also a reliable marker for individual EBV strain identification and thus offers new possibilities in tracing the molecular events leading to posttransplant lymphoproliferative disorders (PTLDs). Cytotoxic T lymphocytes directed against well-characterized epitopes of EBV latency genes represent an already successful and promising therapeutic approach to EBV-associated lymphomas, in particular PTLDs.
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PMID:The role of Epstein-Barr virus in neoplastic transformation. 1140 95

Primary HIV can be asymptomatic or result in a severe symptomatic illness. Common symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mucous membrane ulceration, lymphadenopathy and headache. It can be reliably diagnosed by a positive virologic test in the absence of HIV-specific antibodies. Progression to late-stage disease is influenced by the severity of the symptoms in primary HIV infection, the duration of the illness, the presence of neurological symptoms and the presence of oral candidiasis. This stage is characterized by a very high viral load and infectiousness. Currently the experimental data are insufficient to recommend whether or not those diagnosed with primary HIV infection should routinely receive antiretroviral therapy.
Int J STD AIDS 2002 Feb
PMID:Primary HIV infection. 1183 60

This article provides clinical profiles for HIV seropositive patients discovered at an STD clinic in Tirupati, India. Considering that sexual contact is the most common mode of transmission of HIV, researchers from the SV Medical College at Tirupati conducted a surveillance for HIV infection among patients attending an STD clinic. From January 1988 to April 1989, the researchers collected serum samples from 2320 patients. 11 people were found to be infected with HIV, 1 of whom exhibited the AIDS Related Complex (ARC). 9 out the HIV-infected patients were 20-30 year-old males categorized as heterosexually promiscuous; the remaining 2 seropositive patients were female prostitutes. The seropositivity rate among heterosexually promiscuous males was 0.58%, and 6.7% among female prostitutes (the total seropositivity rate was 0.47%). Among the HIV-infected patients, the most commonly associated STD was syphilis. 5 of the patients had syphilis alone, and 2 others had syphilis and another STD. One of the HIV-infected patients, a 50 year-old heterosexual male with a history of multiple partners, suffered from a nonhealing genital ulcer and inguinal buboes of 1 month duration. A biopsy of the genital ulcer revealed a pattern consistent with that of granuloma venereum. He also developed angular stomatitis which did not respond to B complex therapy. Furthermore, suffering from persistent lymphadenopathy, weight loss, slight thrombo-cytopenia, an opportunistic infection in the form of oral candidosis and persistent seropositivity for HIV antibodies, the patient was deemed to have the AIDS Related Complex. Tirupati's seropositivity rate of .47% was higher that noticed in other parts of the country, leading the authors call for a plan to investigate the problems of HIV-infected people.
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PMID:Clinical profile of STD clinic patients seropositive for HIV antibodies. 1228 35

This report examines the case of a 45 year-old married man suffering from primary syphilis with seventh nerve palsy and generalized lymphadenopathy -- a rare clinical expression in the present antibiotic era. On March 3, 1988, the individual sought assistance a month after first noticing an ulcer genitalia. He also complained of headaches, watering, and the inability to close his right eye. Though previously free of any STD, the man was promiscuous, having exposures to prostitutes off and on. Upon a genital examination, physicians discovered over the coronal sulcus a large, solitary, nontender, nonbleeding, indurated, pinkish ulcer oozing serum. Besides excessive lacrimation and the inability to close the right eye, the examiners noticed a deviation of the angle of the mouth towards the left side and Bell's sign. A series of tests indicated that the man was suffering from syphilis. Following the diagnosis, he received injections of procaine penicillin for a period of 21 days. Although she did not show any clinical or serological evidence of syphilis, the individual's wife also received treatment for syphilis. 45 days after the beginning of specific therapy, the man's ulcer had healed completely. The facial palsy had recovered completely after 2 weeks.
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PMID:Early syphilis with seventh nerve palsy: a case report. 1228 36

Chronic lymphocytic leukemia follows an extremely variable clinical course with survival range from months to decades. Some patients present minimal symptoms and others organomegaly requiring rapidly therapy. Therapeutic options take into account efficacy, toxicity and prognostic factors. One of the well known prognosis factor is the clinical staging developed either by Rai et al. or by Binet et al. However, there is an important heterogeneity concerning the course of the disease among patients within a single stage group. Recently, several important observations related to the biologic significance of VH gene mutational status, expression of CD38, over-expression of ZAP-70 and chromosomal aberrations have led to the ability to identify high risk patients with rapid disease progression and lower survival. It has been demonstrated that the VH mutation status is clinically highly relevant. CLL patients with unmutated VH gene show an unfavourable course with a very rapid progression. Specific genomic aberrations have been associated with disease characteristics such as lymphadenopathy related to 11q deletion and resistance to treatment related to 17p deletion. VH gene mutation status and genomic aberrations appear separate parameters when considering their prognostic relevance but nevertheless they are correlated: unfavourable aberrations (11q- and 17p-) occur more frequently in VH unmutated CLL patients. According to these prognostic factors, several treatments including purine analogues and/or monoclonal antibodies have been tested with different schedules and doses of monoclonal antibodies (rituximab and alemtuzumab) considering safety to determine the better efficacy. Infections and haemolytic anemia remain the most frequent complications during conventional chemotherapy. In autologous transplant setting, the transplant related mortality is less than 10%, but survival curve do not show a plateau with about 50% of patients relapsing at 4 years. Conventional allogeneic transplantation could achieve durable remission and probably cure the disease but at the price of a too high transplant related mortality related to depressive immune status and old age of CLL population. In order to minimize the toxicity and to improve graft-versus-leukemia effect, development of reduced intensity conditioning (RIC) regimens appear particularly important for CLL patients. Recent studies, although a still short follow-up show very promising results and use of monoclonal antibodies in the conditioning or just after transplant could improve the results of allogeneic stem cell transplantation and cure a larger number of CLL patients. Recent advances to categorize CLL patients according to risk stratification regarding new prognostic factors (FISH, CD38, ZAP70, Ig mutational status) should allow to define better the best therapeutic strategy. In parallel, age, co morbidities and the notion of the risk-adapted strategy have also an important impact adding.
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PMID:[News in therapeutic management of chronic lymphoid leukemia]. 1582 Sep 19

Aberrant or deregulated activity of certain cellular kinases has been shown to cause certain malignancies and other disorders. The tyrphostin molecule AG490 inhibits the action of the janus kinases JAK2 and JAK3. JAK2 is an indispensable molecule for transducing the signals conveyed by a large number of cytokines including IL-3 while JAK3 is essential for signaling by a smaller number of cytokines including IL-7. A synthetic combinatorial chemical library containing 599 compounds was created and screened for the ability to inhibit proliferation of IL3- and IL7-dependent cell lines to focus on molecules that interrupt those signaling pathways. This screen identified a meta-trifluoromethyl derivative of AG490, 5H4, that is approximately twice as potent as AG490 in cell-based assays. 5H4 blocked the factor-dependent proliferation of both of these cell lines, actively promoted cell death, and diminished the JAK kinase activity. Administration of 5H4 to lymphoma-prone IL-7 transgenic mice reduced their spontaneous lymphadenopathy. The improved characteristics of this novel compound bring this class of molecules closer to therapeutic utility.
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PMID:Combinatorial approach to identification of tyrphostin inhibitors of cytokine signaling. 1586 81

We describe a case of coexisting BCR-ABL negative myeloproliferative disorder and precursor T-cell lymphoblastic lymphoma associated with t(8;13) involving FGFR1 at 8p11 in a 14-year-old boy who presented with generalized lymphadenopathy and an abdominal mass. JAK2 mutation and FIP1L1-PDGFRalpha were not detected. RT-PCR revealed the ZNF198-FGFR1 fusion transcript in both the bone marrow (BM) and lymph node (LN) of the patient at diagnosis. Of interest, reciprocal FGFR1-ZNF198 fusion transcript was demonstrated in the BM but not LN. Also differential clonal TcRgamma gene rearrangements in the BM and LN samples were observed. These findings provide novel insights into the genetic pathogenesis.
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PMID:Clonal evolution of 8p11 stem cell syndrome in a 14-year-old Chinese boy: a review of literature of t(8;13) associated myeloproliferative diseases. 1677 24


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