Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical assays have been employed to study the expression of ER, PgR, EGFR and Ki67 immunostaining in normal breast tissue (n = 76). The expression of ER and PgR was highly variable in both pre and postmenopausal women and was characterised by large numbers of apparently negative cells. This was most evident for ER-ICA staining in tissues removed from premenopausal women. PgR levels were highest in the ducts of premenopausal women, while EGFR expression was elevated in both ducts and lobules. Ki67 expression was observed in less than 10% of all normal cells and was suppressed by the menopause in lobular tissue. Tamoxifen therapy (40 mg d-1) did not influence the expression of PgR, EGFR or Ki67 immunostaining in cancer associated normal tissue (n = 17). A significant increase, however, was observed in the mean percentage ER positivity in ductal tissue. No effect of duration of tamoxifen therapy was observed on the expression of the antigens studied.
...
PMID:Influence of the antioestrogen tamoxifen on normal breast tissue. 191 Dec 27

The effect of psychosocial stress produced by aggregation in a special cage designed by Henry was investigated in three separate experiments using Wistar-Kyoto (WKY), Sprague-Dawley (SD) and F1 hybrids of the Japanese spontaneously hypertensive and Wistar-Kyoto (SHR-WKY F1) rats. Each aggregated group displayed typical 'stressed' behavioural disturbances. Adrenal hypertrophy, elevation of plasma renin activity and gastric erosions were noted in male aggregated SD rats; while adrenal enlargement, elevation of plasma noradrenaline and gastric erosions were found in male aggregated SHR-WKY F1 rats. Sustained hypertension, however, did not develop in any strain nor in any subgroup within each strain. Gastric erosions were also noted in isolated SD and SHR-SKY F1 rats suggesting that long term isolation of rats also induces stress. Isolated rats also remained normotensive throughout. Reduced haematocrit was found in both aggregated and isolated male SHR-WKY F1 rats suggesting increased plasma volume. We conclude that neither stress due to psychosocial disturbances nor that due to isolation produces chronic hypertension in the three strains of rat studied.
...
PMID:Failure of psychosocial stress to induce chronic hypertension in the rat. 654 22

Since the Chernobyl nuclear reactor accident, a striking increase of thyroid carcinoma has been reported in children exposed to radiation in Belarus. Because of its unprecedented scale and its emotional implications, this finding has raised concern and called the attention of the scientific community to this major health problem. Although epidemiologically documented, a direct correlation between thyroid cancer and radiation exposure has not been definitely proven at the molecular level. On the assumption that ionizing radiation could cause specific and common cancer-associated genetic lesions, an analysis of oncogene activation and/or tumor suppressor gene inactivation would help to define radiation-induced thyroid carcinomas. Therefore, we have analyzed by different molecular approaches, including Southern blotting, DNA transfection assay on NIH-3T3 cells, and reverse transcription-PCR analysis, six papillary carcinomas from children living in the region of Belarus at the time of the Chernobyl nuclear accident to identify tumor-specific gene rearrangements of the proto-oncogenes RET and TRK, previously found activated in a tumor type-specific manner in papillary thyroid carcinoma. Using Southern blot analysis in four cases, we could detect specific rearranged bands indicating an oncogenic activation of RET that in three cases resulted in rearranged sequences provided by the same activating gene. Moreover, the DNA of the last three cases showed a biological activity in transforming NIH-3T3 cells after the DNA-mediated transfection assay, and the respective NIH-3T3 transfectants were found to express the oncogenic fusion transcripts. These results support the possibility that RET oncogenic activation could represent a major genetic lesion associated with thyroid carcinoma in children exposed to the Chernobyl nuclear accident.
...
PMID:Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. 758 43

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.
...
PMID:Screening for pregnancy risk-drinking. 784 99

We examined the ability of intravenous (i.v.) challenge with pentagastrin to induce behavioural and cardiovascular effects consistent with panic attack in conscious rhesus monkeys. For behavioural evaluation, 4 naive male rhesus monkeys familiar with minimal manual restraint necessary for drug administration received a rapid i.v. bolus of pentagastrin (4, 8 or 16 micrograms/kg) or water on four separate occasions according to a randomised cross-over design. Behaviour was rated by a blind observer continuously during, and for the first 5 min immediately following i.v. injections while the monkey sat on the handler's lap, and then for a further 25 min in an individual observation cage. In separate experiments, the ability of pentagastrin to alter cardiovascular parameters which may accompany panic or anxiety (elevated heart rate and blood pressure) was explored. For cardiovascular studies, 8 male or female rhesus monkeys with femoral artery catheters were chair restrained and received a bolus injection of pentagastrin (4, 8 or 16 micrograms/kg) or saline into the saphenous vein at 30 min intervals. Blood pressure and heart rate were monitored continuously using a Statham Gould pressure transducer. Pentagastrin induced no consistent behavioural or cardiovascular changes. Similar pilot studies using CCK4 also failed to reveal such effects. We conclude that CCK-induced panic-like effects may not be demonstrable following challenge with pentagastrin under laboratory conditions in rhesus monkeys.
...
PMID:Failure of intravenous pentagastrin challenge to induce panic-like effects in rhesus monkeys. 841 56

Acetylcholine often affects cardiac action potential repolarization only during augmented adrenergic tone, i.e., the phenomenon of accentuated antagonism. Since chronic exercise involves repeated changes in autonomic outflow, we determined whether it also influenced adrenergic/cholinergic interactions in isolated canine cardiac tissue. Using standard micro-electrode techniques in thin ventricular subendocardial slices isolated from exercised (EX: 8-10 wk daily exercise) and sedentary (SED): 8-10 wk cage rest) dogs, we examined transmembrane potential responses to isoproterenol (ISO: 10(-8), 10(-7), 10(-6) M) and to ISO in the presence of ACH (10(-5) M). Control transmembrane characteristics at BCL = 500 ms were similar for EX (N = 8 dogs) and SED (N = 9 dogs). ISO (10(-6) M) decreased action potential duration at 50% repolarization (APD50): EX = -29 +/- 15 ms; SED = 11 ms and at 90% repolarization (APD90): EX = -37 +/- 17 ms; and SED = -24 +/- 14 ms (P > 0.05, EX vs SED). ACH alone did not alter APD. With ACH (10(-5) M), delta APD50 with ISO (10(-6) M) was -5 +/- ms and 0 +/- 5 ms for EX and SED, respectively; delta APD90 was -8 +/- 4 ms and -8 +/- 7 ms for EX and SED, respectively (P > 0.05, EX vs SED). Thus, ACH antagonized ISO-mediated acceleration of repolarization equally in both groups. Chronic daily exercise does not influence adrenergic/cholinergic interactions at the cellular level.
...
PMID:Accentuated antagonism in canine subendocardium is not altered by chronic exercise. 926 57

Anti-HER2/neu therapy of human HER2/neu-expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu IgG3 fusion protein containing GM-CSF. Anti-HER2/neu IgG3-(GM-CSF) expressed in myeloma cells was correctly assembled and secreted. It was able to target HER2/neu-expressing cells and to support growth of a GM-CSF-dependent murine myeloid cell line, FDC-P1. The Ab fusion protein activated J774.2 macrophage cells so that they exhibit an enhanced cytotoxic activity and was comparable to the parental Ab in its ability to effect Ab-dependent cellular cytotoxicity-mediated tumor cell lysis. Pharmacokinetic studies showed that anti-HER2/neu IgG3-(GM-CSF) is stable in the blood. Interestingly, the half-life of anti-HER2/neu IgG3-(GM-CSF) depended on the injected dose with longer in vivo persistence observed at higher doses. Biodistribution studies showed that anti-HER2/neu IgG3-(GM-CSF) is mainly localized in the spleen. In addition, anti-HER2/neu IgG3-(GM-CSF) was able to target the HER2/neu-expressing murine tumor CT26-HER2/neu and enhance the immune response against the targeted Ag HER2/neu. Anti-HER2/neu IgG3-(GM-CSF) is able to enhance both Th1- and Th2-mediated immune responses and treatment with this Ab fusion protein resulted in significant retardation in the growth of s.c. CT26-HER2/neu tumors. Our results suggest that anti-HER2/neu IgG3-(GM-CSF) fusion protein is useful in the treatment of HER2/neu-expressing tumors.
...
PMID:Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity. 1104 42

We designed a closed-system cage with vent ports that would allow continuous airflow in the occupied cage to ensure adequate ventilation and gas exchange. In this system, the metabolic heat loads of mice generate upward thermal air currents. Heat exits via the exhaust port, and room air enters via the intake port, providing adequate ventilation. Simulations based on computational fluid dynamics (CFD) helped us to optimize the cage's design. CFD simulations and smoke visualizations with a feeder-trough assembly illustrated the one-pass air circulation pattern and the lack of air recirculation, turbulence, and dead air space in our system. We used hot-film anemometry and smoke-test methodologies to show that adequate ventilation was provided. In a room with still air (0 air changes per hour [ACH]), a cage fitted with double wire-cloth filters (40 mesh size) and occupied by five mice has at least 12 ACH, whereas the same cage occupied by one mouse has 6 ACH. After five mice had occupied the cage for a week, its average temperature was 0.58C, relative humidity was 34%, and ammonia concentration was 3 ppm higher than that of the room. Our novel vented microisolation cage provides adequate intracage ACH, isolates mice from environmental contaminants, and contains allergenic particles within the cage in an environment appropriate for the species.
...
PMID:A novel vented microisolation container for caging animals: microenvironmental comfort in a closed-system filter cage. 1117 11

Anti-HER2/neu therapy of human HER2/neu expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu human IgG3 fusion protein containing interleukin-2 (IL-2) fused at its carboxyl terminus. Anti-Her2/neu IgG3-(IL-2) retained antibody and cytokine related activity. Treatment of immunocompentent mice with this antibody fusion protein resulted in significant retardation in the subcutaneous (s.c.) growth of CT26-HER2/neu tumors suggesting that anti-HER2/neu IgG3-(IL-2) fusion protein will be useful in the treatment of HER2/neu expressing tumors. We also found that fusing IL-2 to human IgG3 results in a significant enhancement of the murine anti-human antibody (MAHA) response.
...
PMID:A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors. 1145 61

Despite advances in treatment, long-term outcome of patients with diffuse large B cell lymphoma (DLBCL) is no better today than reported in 1975. A recent study applying DNA microarray technology revealed that patients whose cancer related to patterns of genes expressed in germinal center lymphocytes responded more favorably to chemotherapy than patients whose cancer related to patterns of genes expressed in activated lymphocytes. cDNA and oligonucleotide microarrays are described, and their applications in cancer research are reviewed. In addition to DLBCL, microarray technology has been used to study several types of cancer. The applications of microarray technology are numerous and include profiling gene expression patterns in order to facilitate diagnosis and predict response to therapy; correlating patterns of gene expression with prognosis; and identifying genes and gene products that are associated with tumorigenic phenotype or with drug resistance, among other applications. Microarraytechnology has also been used in cell lines to correlate gene expression and chemotherapy response. Furthermore, microarray technology may provide a useful tool to examine the development of drug resistance in cancer and has recently been used to study changes in gene expression caused by activated c-Myc in primary human fibroblasts. Tissue microarrays are described. In addition to the amplification of limited tissue re sources, tissue microarrays have the advantages of limiting the variability associated with tissue processing and limiting the necessary amount of reagent. Tissue microarrays have been used to determine the frequencies of amplication of 3 major breast cancer genes and identify overexpression of ERBB2 mRNA; assess and compare gene amplification in benign prostatic hyperplasia, primary prostate carcinoma, recurrent prostate tumors, and metastatic tumors; compare aggressiveness of prostate carcinoma in 2 patient populations; and study gene amplification across various tumor types. Furthermore, DNA microarray and tissue microarray techniques can be combined to provide convergent evidence of findings and to examine different aspects of gene expression. DNA array technology may also be used to identify critical molecular targets or to identify the critical rate-limiting step in a cascade of genes under the influence of a mutated gene. The historical progression of goals of the National Cancer Institute is reviewed, as well as the economic impact of reduction in cancer-associated mortality. Future efforts should continue the investment in basic research and more effectively integrate it with clinical trials and with approaches to prevention and treatment.
...
PMID:National Oncology Forum: perspectives for the year 2000. 1150 81


1 2 3 4 5 6 7 8 9 10 Next >>

---