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71.
Deatly AM Coleman JW McMullen G McAuliffe JM Jayarama V Cupo A Crowley JC McWilliams T Taffs RE 《Virology》1999,255(2):221-227
Mice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice. 相似文献
72.
In a case of familial early onset Alzheimer's disease, a mutation was detected in exon 7 of the presenilin 1 gene at codon 226 with a resultant amino acid change from leucine (CTC) to arginine (CGC) (L226R). This is a novel finding, yet is consistent with the previously reported mutations at codons 222, 229, 233 and 237 in transmembrane domain 5 which show a helical alignment of mutations in this domain. We conclude that the cause of Alzheimer's disease in this patient is an authentic PS1 gene abnormality responsible for the patient's early onset Alzheimer's disease. 相似文献
73.
74.
Differential regulation of mast cell cytokines by both dexamethasone and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 下载免费PDF全文
Koranteng RD Swindle EJ Davis BJ Dearman RJ Kimber I Flanagan BF Coleman JW 《Clinical and experimental immunology》2004,137(1):81-87
Activated mast cells generate multiple cytokines but it is not known if these can be differentially regulated by pharmacological agents. We report here that the glucocorticoid dexamethasone (DEX) preferentially inhibited Ag-induced expression of IL-4 and IL-6 mRNA relative to TNF-alpha mRNA in RBL-2H3 cells. Likewise, the drug more readily inhibited release of IL-4 than TNF-alpha protein. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), enhanced Ag-induced TNF-alpha mRNA expression without affecting IL-4 or IL-6 mRNA. At the protein level, SB203580 exerted little effect on TNF-alpha release but inhibited IL-4 release; notably, the ratio of TNF-alpha : IL-4 increased markedly with the concentration of SB203580, confirming the differential regulation of these cytokines. PD98059, an inhibitor of MAPK kinase (MEK), a component of the p44/42 MAPK pathway, partially inhibited Ag-induced expression of mRNA for all three cytokines while cyclosporin A inhibited Ag-induced IL-4 and IL-6 mRNA more readily than TNF-alpha mRNA. Ag activation of the cells led to phosphorylation of p38 and p44/42 MAPK but this was not influenced by DEX. In conclusion, mast cell cytokines can be differentially regulated pre- and post-translationally by DEX and SB203580 but there does not appear to be a direct mechanistic link between the actions of these two drugs. 相似文献
75.
Coleman SL Buckland PR Hoogendoorn B Guy C Smith K O'Donovan MC 《Human molecular genetics》2002,11(16):1817-1821
The ability to identify and examine promoter elements is important to researchers who wish to understand how gene expression is regulated in normal and pathological states. Unfortunately, the number of human promoters that have been directly experimentally defined is small. In order to determine if promoter sequences can be identified by simply aligning mRNA and genomic sequences, we have used a reporter gene assay to assess the promoter activity of the immediate 5' region flanking 38 mRNAs mapping to chromosome 21. For comparison, we have measured the activities of 19 sequences not thought to be promoters and 39 sequences taken from the Eukaryotic Promoter Database. Our results suggest that alignment of reference mRNAs to genomic sequence allows promoters to be identified for at least 75% of genes. These data provide the first empirical evidence that the current state of annotation of the genome is sufficient to allow molecular geneticists to correctly identify promoter sequences for most genes for which reference mRNA and genomic sequences are available. 相似文献
76.
Regulation of hepatocyte activator inhibitor-1 expression by androgen and oncogenic transformation in the prostate 下载免费PDF全文
Knudsen BS Lucas JM Fazli L Hawley S Falcon S Coleman IM Martin DB Xu C True LD Gleave ME Nelson PS Ayala GE 《The American journal of pathology》2005,167(1):255-266
Hepatocyte activator inhibitor-1 (HAI-1) is a transmembrane serine protease inhibitor that regulates the conversion of latent to active hepatocyte growth factor (HGF). Studies supporting a role for the HGF pathway in prostate carcinogenesis prompted an analysis of HAI-1 expression in the prostate. Here we analyze the regulation of HAI-1 expression by androgen, oncogenic transformation, and cancer progression. Immunohistochemical analysis revealed that HAI-1 expression was restricted to prostate epithelium, where staining occurred primarily in basal and atrophic luminal epithelial cells. Compared to normal glands, HAI-1 expression was significantly increased in localized prostate cancer and was present in most prostate cancer metastases. HAI-1 protein expression levels were sensitive to androgen in normal epithelium but not in cancer. Although androgen did not increase HAI-1 protein expression levels in LNCaP cells, it decreased HAI-1 surface expression, consistent with previous data from our group (Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR, Aebersold R, Nelson PS: Quantitative proteomic analysis of proteins released by neoplastic prostate epithelium. Cancer Res 2004, 64:347-355). HAI-1 overexpression in cancer was predictive of prostate-specific antigen recurrence (relative risk, 1.24). These results suggest that HAI-1 regulates the HGF Met axis on prostate epithelial cells and influences HGF mediated tumor invasion and metastasis. 相似文献
77.
Construction and characterization of a live, attenuated aroA deletion mutant of Pseudomonas aeruginosa as a candidate intranasal vaccine 下载免费PDF全文
Priebe GP Brinig MM Hatano K Grout M Coleman FT Pier GB Goldberg JB 《Infection and immunity》2002,70(3):1507-1517
Antibodies to the lipopolysaccharide O antigen of Pseudomonas aeruginosa mediate high-level immunity, but protective epitopes have proven to be poorly immunogenic, while nonprotective or minimally protective O-antigen epitopes often elicit the best immune responses. With the goal of developing a broadly protective P. aeruginosa vaccine, we used a gene replacement system based on the Flp recombinase to construct an unmarked aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1. The resultant aroA deletion mutant of PAO1 is designated PAO1 Delta aroA. The aroA deletion was confirmed by both PCR and failure of the mutant to grow on minimal media lacking aromatic amino acids. When evaluated for safety and immunogenicity in mice, PAO1 Delta aroA could be applied either intranasally or intraperitoneally at doses up to 5 x 10(9) CFU per mouse without adverse effects. No dissemination of PAO1 Delta aroA to blood, liver, or spleen was detected after intranasal application, and histological evidence of pneumonia was minimal. Intranasal immunization of mice and rabbits elicited high titers of immunoglobulin G to whole bacterial cells and to heat-stable bacterial antigens of all seven prototypic P. aeruginosa serogroup O2/O5 strains. The mouse antisera mediated potent phagocytic killing of most of the prototypic serogroup O2/O5 strains, while the rabbit antisera mediated phagocytic killing of several serogroup-heterologous strains in addition to killing all O2/O5 strains. This live, attenuated P. aeruginosa strain PAO1 Delta aroA appears to be safe for potential use as an intranasal vaccine and elicits high titers of opsonic antibodies against multiple strains of the P. aeruginosa O2/O5 serogroup. 相似文献
78.
Turell MJ Jones JW Sardelis MR Dohm DJ Coleman RE Watts DM Fernandez R Calampa C Klein TA 《Journal of medical entomology》2000,37(6):835-839
Mosquitoes collected in the Amazon Basin, near Iquitos, Peru, were evaluated for their susceptibility to epizootic (IAB and IC) and enzootic (ID and IE) strains of Venezuelan equine encephalomyelitis (VEE) virus. After feeding on hamsters with a viremia of approximately 10(8) plaque-forming units of virus per milliliter, Culex (Melanoconion) gnomatus Sallum, Huchings, & Ferreira, Culex (Melanoconion) vomerifer Komp, and Aedes fulvus (Wiedemann) were highly susceptible to infection with all four subtypes of VEE virus (infection rates > or = 87%). Likewise, Psorophora albigenu (Peryassu) and a combination of Mansonia indubitans Dyar & Shannon and Mansonia titillans (Walker) were moderately susceptible to all four strains of VEE virus (infection rates > or = 50%). Although Psorophora cingulata (Fabricius) and Coquillettidia venezuelensis (Theobald) were susceptible to infection with each of the VEE strains, these two species were not efficient transmitters of any of the VEE strains, even after intrathoracic inoculation, indicating the presence of a salivary gland barrier in these species. In contrast to the other species tested, both Culex (Melanoconion) pedroi Sirivanakarn & Belkin and Culex (Culex) coronator Dyar & Knab were nearly refractory to each of the strains of VEE virus tested. Although many of the mosquito species found in this region were competent laboratory vectors of VEE virus, additional studies on biting behavior, mosquito population densities, and vertebrate reservoir hosts of VEE virus are needed to incriminate the principal vector species. 相似文献
79.
A kinetic analysis of the in vitro sensitization of murine peritoneal mast cells with monoclonal IgE anti-DNP antibody. 总被引:1,自引:0,他引:1 下载免费PDF全文
J W Coleman 《Immunology》1988,64(3):527-531
Incubation of murine peritoneal cells with monoclonal IgE anti-DNP antibody in vitro led to sensitization of mast cells, measured as release of 5-HT upon challenge with DNP-HSA antigen. Sensitization was maximal at 0.3-3.0 micrograms/ml of IgE anti-DNP and declined above and below this concentration range. In kinetic studies, the time-course of sensitization was clearly divisible into an early slow phase of approximately 4 hr, followed by a more rapid linear phase from 4 to 48 hr. The early slow phase was more pronounced at lower concentrations of IgE anti-DNP (within the range 0.05-5.0 micrograms/ml). The degree of sensitization obtained after incubation of peritoneal cells with IgE anti-DNP for fixed periods (2, 4 and 8 hr) was markedly increased when the cells were washed and recultured in IgE-free medium, thus demonstrating that sensitization proceeds subsequent to an early stage of binding of IgE to receptors. Sensitization with IgE anti-DNP was blocked by addition of excess rat myeloma IgE, but only to a marked extent (greater than 50%) when the blocking immunoglobulin was added during the first 2 hr, thus providing further evidence that the major part of binding of the IgE antibody took place during this early stage, that is, prior to the phase of greatest sensitization. These findings indicate a period of delay between binding of IgE to receptors and functional sensitization, measured as mediator release in response to antigen. 相似文献
80.
Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina 总被引:4,自引:0,他引:4
1. Whole-cell recordings have been obtained from intact, photoactive retinal neurons using patch-clamp electrodes in the amphibian superfused retina eyecup preparation. 2. After removal of the vitreous humor from the surface of the retina, using a collagenase with low tryptic activity, high-resistance seals (1-10 G omega) could be formed between the patch pipette and the cell membrane by applying mild suction to the pipette. Additional suction broke the membrane patch and provided continuity between the low-resistance pipette and the interior of the neuron. 3. Measurements of input resistance and time constant were obtained from bipolar, amacrine, and ganglion cells. Assuming the membrane capacitance was 1 microF/cm2, time constant data were used to derive the specific membrane resistance. The average specific membrane resistance for the inner retinal neurons in our sample was 68,000 omega.cm2. 4. Analysis of the charging curve induced by a brief current pulse applied to the soma was used to analyze the average electrotonic length of dendrites. The charging curves of some ganglion cells were well represented by a single exponential, suggesting that they were essentially isopotential. 5. The voltage decay along an equivalent cylinder model of a ganglion cell was calculated, using the experimentally obtained values of membrane resistance to compute decay of steady-state voltages along the dendritic tree. The calculations indicate that with the high membrane resistance values implied by this study, the electrotonic length of dendritic cables were short, and there may be relatively little attenuation of the synaptic potentials irrespective of their location along the dendritic tree. 相似文献