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

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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)

Detailed parasitologic, serologic, clinical and histopathologic studies were conducted in owl monkeys (Aotus nancymai) exposed to varying numbers of cercariae of Schistosoma mansoni. All the experimental animals had clinical symptoms suggestive of infection (weight loss diarrhoea, mucus in stools, etc.) which were not seen in uninfected individuals. The only A. vociferans included in this study passed S. mansoni eggs 8 weeks after infection. None of the A. nancymai passed eggs in their faeces. No adult worms were recovered following perfusion of the sacrificed experimental monkeys, suggesting that they were early eliminated. Serological techniques (ELISA-SEA and COPT) allowed diagnosis of infection, starting 9 weeks post challenge, in all but one A. nancymai exposed to 100 cercariae. Granulomas containing eggs were observed predominantly in liver and less extensively in intestine, suggesting that adult worms were mainly lodged in the intrahepatic portal system. We conclude that A. nancymai is susceptible to infection with S. mansoi, with the worms reaching sexual maturity, but being eliminated shortly after oviposition.
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PMID:Schistosoma mansoni infection in owl monkeys (Aontus nancymai): evidence for the early elimination of adult worms. 977 12

Acute infectious disease presentations among many at-risk patient groups (eg, uninsured, homeless, and recent immigrants) are frequently seen in emergency departments. Therefore EDs may be useful sentinel sites for infectious disease surveillance. This article describes the background, development, and implementation of EMERGE ncy ID NET, an interdisciplinary, multicenter, ED-based network for research of emerging infectious diseases. EMERGE ncy ID NET was established in cooperation with the National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) as part of the CDC's strategy to expand and complement existing disease detection and control activities. The network is based at 11 university-affiliated, urban hospital EDs with a combined annual patient visit census of more than 900,000. Data are collected during ED evaluation of patients with specific clinical syndromes, and are electronically stored, transferred, and analyzed at a central receiving site. Current projects include investigation of bloody diarrhea and the prevalence of Shiga toxin-producing Escherichia coli, animal exposures and rabies postexposure prophylaxis practices, seizures and prevalence of neurocysticercosis, nosocomial ED Mycobacterium tuberculosis transmission, and hospital isolation bed use for adults admitted for pneumonia or suspected tuberculosis. EMERGE ncy ID NET also was developed to be a mechanism for rapidly responding to new diseases or epidemics. Future plans include study of antimicrobial use, meningitis, and encephalitis, and consideration of other public health concerns such as injury and national and international network expansion.
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PMID:EMERGEncy ID NET: an emergency department-based emerging infections sentinel network. The EMERGEncy ID NET Study Group. 983 68

The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers. A randomized field trial was conducted in 52 day care centers in Quebec, Canada, between September 1, 1996 and November 30, 1997. Absences for any reasons and the daily occurrence of colds and/or diarrhea in toddlers were recorded on calendars by the educators. The number of fecal coliforms on children's hands and on educators' hands was measured during three unannounced visits. Overall, 1,729 children were followed in 47 day care centers for a total of 153,643 child-days. The incidence rate of diarrhea was considerably reduced by the effect of monitoring (IRR = 0.73, 95% CI = 0.54,0.97), and the intervention reduced the incidence rate of upper respiratory tract infections (IRR = 0.80, 95% CI = 0.68,0.93). Monitoring alone also had an important effect in reducing the level of bacterial contamination on children's and educators' hands. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers.
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PMID:Effectiveness of a training program in reducing infections in toddlers attending day care centers. 1023 Aug 25

A phase I study of escalating doses of humanized bispecific antibody (bsAb) MDX-H210 with granulocyte-colony-stimulating factor (G-CSF) was conducted in patients with metastatic breast cancer that overexpressed HER2/neu. The main objectives of the study were to define the maximal tolerated dose (MTD) of MDX-H210 when combined with G-CSF, to measure the pharmacokinetics of MDX-H210 when administered with G-CSF, and to determine the toxicity, biological effects and possible therapeutic effect of MDX-H210 with G-CSF. MDX-H210 is a F(ab)' x F(ab)' humanized bispecific murine antibody that binds to both HER2/neu and the FcgammaR1 receptor (CD64), and was administered intravenously weekly for three doses followed by a 2-week break and then three more weekly doses. A total of 23 patients were treated, and doses were escalated from 1 mg/m2 to 40 mg/m2 with no MTD reached. The toxicity of the bsAb + G-CSF combination was modest, with no dose-limiting toxicity noted: 19 patients had fevers, 7 patients had diarrhea, and 3 patients had allergic reactions that did not limit therapy. The beta-elimination half-life varied from 4 h to 8 h at doses up to 20 mg/m2. Significant release of cytokines interleukin-6, G-CSF, and tumor necrosis factor alpha was observed after administration of bsAb. Circulating monocytes disappeared within 1 h of bsAb infusion, which correlated with binding of bsAb, noted by flow-cytometric analysis. Significant levels of human anti-(bispecific antibody) were measured in the plasma of most patients by the third infusion. No objective clinical responses were seen in this group of heavily pre-treated patients.
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PMID:A phase I study of a HER2/neu bispecific antibody with granulocyte-colony-stimulating factor in patients with metastatic breast cancer that overexpresses HER2/neu. 1023 84

The effects of a novel kappa-opioid receptor agonist, TRK-820, on the development of physical dependence on morphine were investigated in mice in comparison with those of U-50,488H. A marked body weight loss and several withdrawal signs were observed following naloxone challenge in morphine-dependent mice. Co-injection of TRK-820 (0.003-0.03 mg/kg, s.c.) but not U-50,488H (1-10 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the naloxone-precipitated body weight loss, jumping, wet dog shakes and diarrhea. These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may play a significant role in modulating the development of physical dependence on morphine.
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PMID:A novel kappa-opioid receptor agonist, TRK-820, blocks the development of physical dependence on morphine in mice. 1089 94

An outbreak of staphylococcal food poisoning due to an egg yolk (EY) reaction-negative strain occurred in Japan. Twenty-one of 53 dam construction workers who ate boxed lunches prepared at their company cafeteria became ill, and eight required hospital treatment. The outbreak showed a typical incubation time (1.5-4 h with a median time of 2.7 h) and symptoms (vomiting and diarrhea) of staphylococcal food poisoning. Staphylococcus aureus, which produces staphylococcal enterotoxin (SE) A, was isolated from four fecal specimens of eight patients tested. Scrambled egg in the boxed lunches contained 20-40 ng/g of SEA, and 3.0 x 10(9)/g of viable S. aureus cells that produced this toxin. All isolates from patients and the food were EY reaction-negative, coagulase type II, and showed the same restriction fragment length polymorphism (RFLP) pattern. We concluded that the outbreak was caused by scrambled egg contaminated with EY reaction-negative S. aureus. In Japan, outbreaks of staphylococcal food poisoning are mainly caused by EY reaction-positive S. aureus, and EY reaction-negative colonies grown on agar plates containing EY are usually not analyzed further for detection of S. aureus. The present outbreak suggested that EY reaction-negative isolates should be subjected to further analysis to detect the causative agents of staphylococcal food poisoning.
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PMID:An outbreak of food poisoning due to egg yolk reaction-negative Staphylococcus aureus. 1129 58

A significant number of women with advanced breast cancer fail to respond to standard-dose chemotherapy. From the beginning of 1999, 17 women with HER2 positive advanced breast cancer received Herceptin as monotherapy or in combination with paclitaxel or other non-anthracyclines. Eight (47%) women previously received high-dose chemotherapy followed by haematopoiesis stem cell rescue. Three women received Herceptin alone, eleven Herceptin plus paclitaxel and three Herceptin and some of the other non-anthracyclines (CCNU, cisplatin and gemcitabine). In the group of patients who received Herceptin monotherapy, one has partial response (PR), one stable disease (SD) and in the third patient the disease progressed. Out of three patients who received Herceptin in combination with other non-anthracyclines, two have SD and one progressed. In the group of 11 women who received Herceptin + Taxol, 7 (64%) patients achieved PR, 2 (18%) SD, and 2 (18%) had disease progression. Grade 3-4 neutropenia has been observed in four (23%) women. Febrile neutropenia was observed in two cases and resolved completely when antibiotics were introduced. Other grade 3 toxicity that has been noted is peripheral neuropathy in three (18%) patients, diarrhoea in four (23%) and onycholysis in one (6%). Serial heart ultrasound showed no significant decline in left ventricular ejection fraction. According to our preliminary experience, Herceptin therapy showed promising results in women with metastatic breast cancer.
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PMID:Trastuzumab in the treatment of advanced breast cancer: single-center experience. 1152 30

Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) is a gastrointestinal pathogen that is generally non-invasive for intestinal epithelial cells, yet causes acute intestinal inflammation, diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome. To study signal transduction pathways activated in human intestinal epithelial cells by EHEC, we took advantage of EHEC O157:H7 and isogenic mutants deficient in the major EHEC virulence factors, intimin (eae-) and Shiga toxin (stx-). Infection with wild-type EHEC activated p38 and ERK MAP kinases and the nuclear translocation of the transcription factor NF-kappaB. Downstream, this was accompanied by increased expression of mRNA and protein for the neutrophil chemoattractant IL-8. Isogenic eae- and stx- mutants also activated p38 and ERK MAP kinases, and NF-kappaB and stimulated increases in IL-8 protein secretion similar to those of wild-type EHEC. Further, inhibition of either p38, ERK or NF-kappaB activation abrogated the IL-8 response induced by wild-type EHEC and the mutants. Epithelial cell MAP kinase and NF-kappaB pathways leading to IL-8 secretion were also activated by isolated EHEC H7 flagellin, which was active when added to either the apical or basolateral surface of polarized human intestinal epithelial cells. We conclude that EHEC interacting with intestinal epithelial cells activates intracellular signalling pathways and an epithelial cell proinflammatory response independent of either Shiga toxin or intimin, two of the major known virulence factors of EHEC. The activation of proinflammatory signals in human colon epithelial cells in response to this non-invasive pathogen appears to depend to a significant extent on H7 flagellin.
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PMID:Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-kappaB and MAP kinase pathways and the upregulated expression of interleukin 8. 1236 1

Natural infection of humans with human T-cell lymphotropic virus type I (HTLV-I) and of old world nonhuman primates with the simian counterpart, STLV-I, is associated with development of neoplastic disease in a small percentage of individuals after long latent periods. HTLV-I is also the etiologic agent of a more rapidly progressive neurologic disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Macaques have been used experimentally in studies to evaluate HTLV-I candidate vaccines for efficacy, but no evidence of disease was observed. Here we report experimental infection of pig-tailed macaques with STLV-I(sm) and HTLV-I(ACH), both of which were associated with a disease syndrome characterized by rapid onset, hypothermia, lethargy, and death within hours to days. Other pathologic sequelae included diarrhea, rash, bladder dysfunction, weight loss, and, in one animal, arthropathy. Both retroviruses were detected in the central nervous systems of some animals, either by culture or by direct antigen capture for p19 Gag in cerebrospinal fluid. Although virus was recovered throughout infection from peripheral blood mononuclear cells (PBMC), all infected macaques maintained low antiviral antibody titers and stable proviral burdens, which generally ranged between 10 and 100 copies per 10(6) PBMC. However, of 13 macaques infected with HTLV-I(ACH) or STLV-I(sm), seven animals (54%) died between 35 weeks and 412 years after infection. This unexpected high mortality within a relatively short time suggests that infection of pig-tailed macaques might be a useful model for studying immune responses to and pathologic events resulting from HTLV-I infection.
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PMID:Association of primate T-cell lymphotropic virus infection of pig-tailed macaques with high mortality. 1250 76

Despite the widespread use of trastuzumab in the management of patients with HER2-overexpressing metastatic breast cancer, its optimal duration of administration is unknown. We retrospectively reviewed the medical records of 80 such patients who received trastuzumab monotherapy or combination chemotherapy beyond disease progression in order to register their clinical course. Median age of the patients was 54 years. Ninety-one percent had 3+ HER2 overexpression and 9% had 2+ HER2 overexpression. Fifty-six percent of patients had previously been treated with chemotherapy for advanced disease. The most commonly used combinations in first- and second-line treatments were trastuzumab with paclitaxel and trastuzumab with vinorelbine, respectively. In total, 32 responses were observed, most of them during the second or third line of treatment. Severe toxicities frequently seen (in = 5% of patients) were neutropenia (25%), thrombocytopenia (11.5%), infection (10%), peripheral neuropathy (9%), nausea/vomiting (6%), stomatitis (6%), diarrhea (6%), constipation (6%), edema (6%), and myalgias/arthralgias (5%). Median survival from diagnosis of advanced disease was 43.4 months (range, 6.4-91.7+), whereas median survival from disease progression after trastuzumab administration was 22.2 months (range, 0.01-32.9+). In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic breast cancer is feasible and safe. Randomized studies are warranted.
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PMID:Continuation of trastuzumab beyond disease progression is feasible and safe in patients with metastatic breast cancer: a retrospective analysis of 80 cases by the hellenic cooperative oncology group. 1286 40


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