Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of pathological situations to fetal lung maturation during the last 9 weeks of pregnancy was studied. Lung maturity was determined by four different methods, analyzing the concentration of surfactant in amniotic fluid L/S ratio was measured planimetrically and densitometrically, foam test and surface tension of the liquor amnii were used on this purpose. 89 normal pregnancies for obtaining normal values served as a basis for comparison with pathological events. A general retardation of fetal lung maturity showed 26 patients with rhesus isoimmunization so as 26 patients with diabetes classes A, B and C (White). In three pregnancies complicated by diabetes class D a remarkable acceleration of fetal lung maturity was obvious. 30 patients with placental insufficiency sui generis presented a very inhomogenous development of the fetal lung, whereas in 35 patients with EPH-gestosis a minute acceleration between 33th and 37th week of gestation was found. A good correlation between all of the used methods for measuring the concentration of surfactant was noted. Best reliability in correct prediction of lung maturity showed the method of measuring the surface-tension of the amniotic fluid.
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PMID:[Fetal lung maturity in differen abnormal pregnancies (author's transl)]. 58 Jul 2

Preservation of peripheral nerves may, in the near future, play an important role in reconstructive surgery, especially if recent advances in immunosuppressive therapy are taken into account. Therefore, it has to be investigated whether peripheral nerves can be stored for some time after harvesting without diminishing their regenerative potential. Previous experiments of our group could demonstrate only little benefit of organ storage solution (HTK) or normal saline (NaCl 0.9%) to peripheral nerves when kept at cold ischaemia of 4 degrees C for 32 and 72 hours. In this presentation, we are reporting the results of peripheral nerve storage in Dulbecco's Modified Eagle Medium which has been used for Schwann cell culture. In 30 adult Sprague-Dawley rats, a 2.5 cm segment of the right sciatic nerve was harvested and kept at 4 degrees C for 14, 32, 72, and 120 hours. It was then reimplanted into the donor animal; regeneration quality was assessed clinically, histologically and morphometrically after 6 weeks. Best regeneration results were obtained in the 32 and 72 hour groups; regeneration here was comparable to the normal controls. These results are explained with the positive effect of nerve predegeneration.
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PMID:Preservation of peripheral nerve grafts with Schwann cell culture medium. 826 79

Elucidation of the molecular genetic basis of leukaemias has relied on the cloning and characterization of recurring chromosomal translocations. A common theme in acute myeloid leukaemia (AML) associated with balanced reciprocal translocations is the involvement of transcription factors as one or both of the fusion partners. Transcription factors commonly involved in chromosomal translocations include core binding factor (CBF), retinoic acid receptor alpha (RARalpha), ETS family of transcription factors and homeobox gene (HOX) family members. In addition, the recruitment of transcriptional co-activators and co-repressors by these transcription factors suggests that these proteins also may play a critical role in leukaemogenesis. In support of this hypothesis' at least three fusions associated with leukaemias and involving transcriptional co-activators CBP and p300 have been recently cloned. However expression of transcription factor fusion proteins is not sufficient to induce a leukaemic phenotype, as evidenced in part by the long latencies required for disease development in the murine models of the disease. An emerging paradigm is the co-operation between constitutively activated tyrosine kinase molecules, such as FLT3, and transcription factor fusions in the pathogenesis of AML. In such a model, the activated tyrosine kinase confers proliferation and/or anti-apoptotic activity to the hematopoietic cells, while the transcription factor fusion impairs normal differentiation pathways with limited effect on cellular proliferation.
Best Pract Res Clin Haematol 2001 Mar
PMID:Molecular genetics of acute myeloid leukaemia. 1135 23

Measurement of molecular markers predictive of response to therapy should enable more selective and effective utilization of anticancer agents. The predictive value of HER2 remains a complex and inconclusive subject. In metastatic breast cancer, HER2-positive, ER-positive patients can show responses to endocrine treatment, but experience shorter time to progression and survival than HER2-negative patients. In the adjuvant setting, weak, retrospective evidence suggests that tamoxifen is potentially harmful in HER2-positive patients and that there is no benefit from prolonged tamoxifen therapy. It has not yet been demonstrated conclusively that HER2 positivity increases resistance to adjuvant cyclophosphamide, methotrexate, 5-FU (CMF), but there are indications that HER2-positive patients benefit more from adequately dosed anthracyclines than from CMF. The greatest value of HER2 as a predictive marker lies in the prediction of response to therapies that target HER2, such as Herceptin. Patients with strongly HER2-positive breast cancer derive significant clinical benefit from single-agent and combined Herceptin therapy. HER2 testing has become an integral part of the optimal management of the breast cancer patient. Best current practice in adjuvant breast cancer therapy based on the current knowledge of the potential predictive power of HER2 constitutes not denying tamoxifen to HER2-positive, ER-positive patients or CMF to HER2-positive patients. Outside of clinical trials, adequately dosed anthracycline-based chemotherapy is the current preferred adjuvant treatment option for HER2-positive patients.
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PMID:The predictive value of HER2 in breast cancer. 1169 91

Steroids can be administered in at least five different ways: injectables; hormone-releasing intra-uterine devices (IUDs); implants; vaginal rings; and pills. Progestogens which are synthetic steroids, are used as the main bioactive substances. Different progestogens are effective for different periods of time. Progestins in daily oral pills are effective for 24 hours. The effectiveness of a progestogen can be prolonged by incorporating it in a sustained-release system that gradually releases the hormone; therefore they can be effective up to 5 years or more. Two progestogen-only injectables are widely available in the family planning programmes, (DMPA and NET-EN) and two combined injectables, Cyclofem (DMPA + EC), and Mesigyna (NET-EN + EV). The ring is placed by the woman in her vagina, where it gradually releases hormone. Implantable contraceptives are placed just under the skin on the inside of the woman's arm. Implant capsules release the progestogen at a slow, steady rate. There are three implantables available in the market: Implanon; Norplant; and Jadelle. They are effective for 1-5 years, but then must be replaced. Natural and synthetic progestogens were first added to IUDs in the early 1970s. The main problem of long-acting progestogens is the disruption of the menstrual cycle.
Best Pract Res Clin Obstet Gynaecol 2002 Apr
PMID:Long-acting progestogens. 1204 60

Ovarian cancer is caused by genetic alterations that disrupt proliferation, apoptosis, senescence and DNA repair. Approximately 10% of ovarian cancers arise in women who have inherited mutations in cancer susceptibility genes (BRCA1 or BRCA2). The ability to perform genetic testing allows identification of women at increased risk who can be offered prophylactic oophorectomy or other interventions aimed at preventing ovarian cancer. The vast majority of ovarian cancers are sporadic, resulting from the accumulation of genetic damage over a lifetime. Several specific genes involved in ovarian carcinogenesis have been identified, including the p53 tumour suppressor gene and HER2/ neu andPIC3KA oncogenes. The recent availability of expression microarrays has facilitated the simultaneous examination of thousands of genes, and this promises to extend further our understanding of the molecular events involved in the development of ovarian cancers. Hopefully, this knowledge can be translated into effective screening, treatment, surveillance, and prevention strategies in the future.
Best Pract Res Clin Obstet Gynaecol 2002 Aug
PMID:Molecular aspects of ovarian cancer. 1241 30

An innovative control parameter for rate responsive (RR) pacing that uses a sensor to measure mechanical vibrations generated by the myocardium during the isovolumetric contraction phase (peak endocardial acceleration [PEA]), has been devised by SORIN Biomedica (BEST Living System). To assess the physiological sensitivity of the pacemaker sensor along with reliability of the algorithm to supply appropriate pacing rates three different relationships were examined (linear regression analysis): (1) recorded deltaPEA exercise steps against the calculated energy cost of exercise (MET), (2) exercise pacing rates against predicted values, and (3) deltaPEA against exercise pacing rates. Fifteen patients (mean age 68 +/- 12 years) in NYHA Class I-II, implanted with the BEST Living System (Living 1 DDDR pacemaker) for advanced AVB and/or SSS, underwent one of the following maximal exercise stress protocols: bicycle (25 W, 2-minute steps) or Bruce or Chronotropic Assessment Exercise Protocol (CAEP). Pacing rates for each step were matched against those predicted by a reliable and tested custom software called Pacing Rate Profile Software (PRPS). The PRPS is based on the oxygen pulse reserve (OPR) method (OPR = VO2 reserve divided by heart rate reserve), American College of Sports Medicine (ACSM) formulas for calculating workload/metabolic requirements, and data derived from the Weber functional classes. On the basis of certain patient, data the PRPS then supplies appropriate metabolic pacing rate profiles. In all 15 patients linear regression analysis of deltaPEA against MET, as evaluated during the exercise protocol steps, showed a high correlation (r = 0.97). Likewise, a high correlation was also obtained between PRPS predicted heart rates and exercise pacing rates (r = 0.96) and PEA against exercise pacing rates (r = 0.96). The results of this study show that, through PEA dynamic monitoring, the SORIN Best Living System produces physiological pacing rates that are significantly related to metabolic needs.
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PMID:Clinical evaluation of peak endocardial acceleration as a sensor for rate responsive pacing. 1271 40

Our understanding of the genetic basis of acute myeloid leukaemias has been enhanced through cloning of recurring chromosomal translocation breakpoints. However, the remarkable observation, more than a decade ago, that all-trans retinoic acid (ATRA) induced remission in patients with t(15;17) acute promyelocytic leukaemia (APL) was a driving force in the subsequent cloning and characterization of the PML-RARalpha fusion that is causally implicated in the pathogenesis of this disease. Major improvements in treatment and outcome of APL patients have been made since that time by incorporating ATRA in conventional chemotherapy but 30% of APL patients still succumb to complications of their disease or their therapy. Recent information that the haematopoietic receptor tyrosine kinase FLT3 is mutated in about 30% of APL patients suggests strategies for further improving treatment and outcome in this subset of APL patients using small-molecule inhibitors of FLT3. The role of FLT3 mutations in APL and other AML will be discussed.
Best Pract Res Clin Haematol 2003 Sep
PMID:FLT3-activating mutations in acute promyelocytic leukaemia: a rationale for risk-adapted therapy with FLT3 inhibitors. 1293 59

The vitamin A derivative, all-trans retinoic acid (ATRA), induces differentiation of leukaemic promyelocytes in patients with acute promyelocytic leukaemia (APL). As a result, the majority of patients achieve complete remission either with ATRA alone or with combined ATRA and chemotherapy. The most important complication is the retinoic acid syndrome, which is usually successfully treated with the early administration of dexamethasone. Prospective randomized trials have shown that ATRA is better than conventional chemotherapy in newly diagnosed patients, that ATRA combined with chemotherapy confers an advantage with respect to relapse rate, compared to ATRA alone for induction followed by chemotherapy for consolidation, and that maintenance therapy with ATRA or ATRA plus low-dose chemotherapy is beneficial. The presence of adverse prognostic factors, including older age, presenting white blood cell count and platelet count, expression of CD56 and presence of mutations in the FLT3 gene, identify patients at risk for relapse for whom new strategies are needed.
Best Pract Res Clin Haematol 2003 Sep
PMID:All-trans retinoic acid in acute promyelocytic leukaemia. 1293 60

Hematological malignancies are phenotypically organized into lymphoid and myeloid disorders, although such a distinction might not be precise from the standpoint of lineage clonality. In turn, myeloid malignancies are broadly categorized into either acute myeloid leukemia (AML) or chronic myeloid disorder (CMD), depending on the presence or absence, respectively, of AML-defining cytomorphologic and cytogenetic features. The CMD are traditionally classified by their morphologic appearances into discrete clinicopathologic entities based primarily on subjective technologies. It has now become evident that most CMD represent clonal stem cell processes where the primary oncogenic event has been characterized in certain instances; Bcr/Abl in chronic myeloid leukemia, FIP1L1-PDGFRA or c-kit(D816V) in systemic mastocytosis, rearrangements of PDGFRB in chronic eosinophilic leukemia, and rearrangements of FGFR1 in stem cell leukemia/lymphoma syndrome. In addition, Bcr/Abl-negative classic myeloproliferative disorders are characterized by recurrent JAK2(V617F) mutations, whereas other mutations affecting the RAS signaling pathway molecules have been associated with juvenile myelomonocytic leukemia. Such progress is paving the way for a transition from a histologic to a semi-molecular classification system that preserves conventional terminology, while incorporating new information on molecular pathogenesis.
Best Pract Res Clin Haematol 2006
PMID:Classification of chronic myeloid disorders: from Dameshek towards a semi-molecular system. 1678 78


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