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41.
Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans 总被引:9,自引:0,他引:9
Advanced age has repeatedly been identified as an independent correlate of adverse outcome and a predictor of mortality in cases of severe acute respiratory syndrome (SARS). SARS-associated mortality may exceed 50% for persons aged 60 years or older. Heightened susceptibility of the elderly to severe SARS and the ability of SARS coronavirus to replicate in mice led us to examine whether aged mice might be susceptible to disease. We report here that viral replication in aged mice was associated with clinical illness and pneumonia, demonstrating an age-related susceptibility to SARS disease in animals that parallels the human experience. 相似文献
42.
Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals 总被引:23,自引:0,他引:23 下载免费PDF全文
Maines TR Lu XH Erb SM Edwards L Guarner J Greer PW Nguyen DC Szretter KJ Chen LM Thawatsupha P Chittaganpitch M Waicharoen S Nguyen DT Nguyen T Nguyen HH Kim JH Hoang LT Kang C Phuong LS Lim W Zaki S Donis RO Cox NJ Katz JM Tumpey TM 《Journal of virology》2005,79(18):11788-11800
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret. 相似文献
43.
Haider MZ Habeeb Y Al-Nakkas E Al-Anzi H Zaki M Al-Tawari A Al-Bloushi M 《Journal of biomedical science》2005,12(5):815-818
Summary Idiopathic generalized epilepsies (IGEs) are the most common types of epilepsy in childhood and adolescence. A variety of
data suggest that IGEs have a predominant genetic etiology. Recently, a number of gene mutations have been found to be associated
with various types of epilepsy in mainly the Caucasian populations. The objective of this study was to investigate the association
of three different candidate genes with IGE in Kuwaiti Arab children. This study includes 123 Kuwaiti patients with a confirmed
diagnosis of epilepsy. Most of the patients have had a diagnostic EEG with generalized spike-wave discharges (GSWs). All patients
were evaluated by using a validated seizure questionnaire. The clinical type of epilepsy was determined by a trained neurologist/pediatrician.
The study also include 100 controls, the control subjects were children which did not have any history of neurological disorders.
Blood samples were collected from all patients and control subjects after taking informed consent. DNA was isolated and analyzed
by molecular methods. A FokI polymorphism in neuronal nicotinic acetylcholine receptor alpha-4 subunit (CHRNA4) gene was detected by PCR-RFLP method.
A missense mutation (Ser248Phe) in CHRNA4 gene was analyzed by PCR-RFLP using HpaII. A C121W mutation in sodium-channel beta-1 subunit (SCN1B) gene was screened by a PCR-RFLP method using HinPI. A 2-bp deletion in Cystatin B gene was detected by PCR-RFLP using XcmI. The incidence of three FokI polymorphism genotypes in Kuwaiti IGE patients was 1,1 (85%), 1,2 (14%) and 2,2 (1%) respectively. The missense mutation
Ser248Phe of CHRNA4 gene was not detected at all in Kuwaiti IGE patients. The C387G transversion resulting in C121W change
in third exon of the SCN1B gene was detected in 3/123 patients (2%). The patients carrying this mutation also exhibited febrile
seizures. The incidence of 2 bp deletion in the cystatin B gene was found to be 4% (5/123 IGE patients). The data obtained
from molecular analysis show a lack of association between three candidate genes and clinical expression of IGE in Kuwaiti
Arab children. This is completely different from the findings reported from Caucasian populations of France, Australia and
USA in which case a strong association has been reported between IGE and these genes.
To whom corresspondence should be addressed. Tel: +965-5319486; Fax: +965-5338940; E-mail: haider@hsc.edu.kw 相似文献
44.
Gupta M Greer P Mahanty S Shieh WJ Zaki SR Ahmed R Rollin PE 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(7):4198-4202
CD8 T cells have been shown to play an important role in the clearance and protection against fatal Ebola virus infection. In this study, we examined the mechanisms by which CD8 T cells mediate this protection. Our data demonstrate that all normal mice infected s.c. with a mouse-adapted Ebola virus survived the infection, as did 100% of mice deficient in Fas and 90% of those deficient in IFN-gamma. In contrast, perforin-deficient mice uniformly died after s.c. challenge. Perforin-deficient mice failed to clear viral infection even though they developed normal levels of neutralizing anti-Ebola Abs and 5- to 10-fold higher levels of IFN-gamma than control mice. Using MHC class I tetramers, we have also shown that perforin-deficient mice have 2- to 4-fold higher numbers of Ebola-specific CD8s than control mice. These findings suggest that the clearance of Ebola virus is perforin-dependent and provide an additional example showing that this basic immunologic mechanism is not limited to the clearance of noncytopathic viruses. 相似文献
45.
Background
Extracting motifs from sequences is a mainstay of bioinformatics. We look at the problem of mining structured motifs, which allow variable length gaps between simple motif components. We propose an efficient algorithm, called EXMOTIF, that given some sequence(s), and a structured motif template, extracts all frequent structured motifs that have quorum q. Potential applications of our method include the extraction of single/composite regulatory binding sites in DNA sequences. 相似文献46.
Agha S El-Mashad N El-Malky M El-Shony H El-Sherif MZ El-Hasan MA Tanaka Y Mizokami M 《Microbiology and immunology》2006,50(6):447-452
Patients infected with schistosoma frequently show a high seroprevalence of anti-hepatitis C virus (anti-HCV) antibodies. The aim of this study was to find the underlying reason for this phenomenon, and to examine a possible involvement of autoantibodies. Out of 2,400 Egyptian blood donors, 192 (8%) were anti-HCV positive by ELISA. They were 133 males and 59 females with age ranging from 27 to 48 years. According to optical density ratio (ODR) of anti-HCV antibodies, 96 cases were low positive (LP) with ODR (1-2) designated as group I, and 96 were high positive (HP) with ODR (> or =2) (group II). Both groups were examined for quantitative HCV core antigen (HCVcAg), liver function (Albumin, ALT, AST) and anti-Schistosoma mansoni(anti-Sm) IgG. Group I cases were HCVcAg negative with normal liver function tests, and 44 of them were anti-Sm positive. Ninety cases (93.75%) of group II were HCVcAg positive with markedly affected liver function tests and 72 cases were anti-Sm positive. All group I cases were examined for autoimmune markers (ANA, AMA, SMA and LKM). In group I, 33 (75%) of anti-Sm positive cases were positive for one or more of the autoimmune markers examined, while none of anti-Sm negative was positive for any marker with significant difference between the two groups (P < 0.0001). Our results primarily on blood donors indicate that LP anti-HCV frequently represents false-positive reactivity with a possible role of Sm-induced autoantibodies in this phenomenon. 相似文献
47.
48.
Kersh GJ Lambourn DM Raverty SA Fitzpatrick KA Self JS Akmajian AM Jeffries SJ Huggins J Drew CP Zaki SR Massung RF 《Journal of wildlife diseases》2012,48(1):201-206
Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Humans are commonly exposed via inhalation of aerosolized bacteria derived from the waste products of domesticated sheep and goats, and particularly from products generated during parturition. However, many other species can be infected with C. burnetii, and the host range and full zoonotic potential of C. burnetii is unknown. Two cases of C. burnetii infection in marine mammal placenta have been reported, but it is not known if this infection is common in marine mammals. To address this issue, placenta samples were collected from Pacific harbor seals (Phoca vitulina richardsi), harbor porpoises (Phocoena phocoena), and Steller sea lions (Eumetopias jubatus). Coxiella burnetii was detected by polymerase chain reaction (PCR) in the placentas of Pacific harbor seals (17/27), harbor porpoises (2/6), and Steller sea lions (1/2) collected in the Pacific Northwest. A serosurvey of 215 Pacific harbor seals sampled in inland and outer coastal areas of the Pacific Northwest showed that 34.0% (73/215) had antibodies against either Phase 1 or Phase 2 C. burnetii. These results suggest that C. burnetii infection is common among marine mammals in this region. 相似文献
49.
Kataoka R Siddiqui ZA Kikuchi J Ando M Sriwati R Nozaki A Futai K 《Journal of microbiology (Seoul, Korea)》2012,50(2):199-206
The fungus Tricholoma matsutake forms an ectomycorrhizal relationship with pine trees. Its sporocarps often develop in a circle, which is commonly known
as a fairy ring. The fungus produces a solid, compact, white aggregate of mycelia and mycorrhizae beneath the fairy ring,
which in Japanese is called a ’shiro’. In the present study, we used soil dilution plating and molecular techniques to analyze
the bacterial communities within, beneath, and outside the T. matsutake fairy ring. Soil dilution plating confirmed previous reports that bacteria and actinomycetes are seldom present in the soil
of the active mycorrhizal zone of the T. matsutake shiro. In addition, the results showed that the absence of bacteria was strongly correlated with the presence of T. matsutake mycorrhizae. The results demonstrate that bacteria, especially aerobic and heterotrophic forms, and actinomycetes, are strongly
inhibited by T. matsutake. Indeed, neither bacteria nor actinomycetes were detected in 11.3% of 213 soil samples from the entire shiro area by culture-dependent
methods. However, molecular techniques demonstrated that some bacteria, such as individual genera of Sphingomonas and Acidobacterium, were present in the active mycorrhizal zone, even though they were not detected in soil assays using the dilution plating
technique. 相似文献
50.
NF Gallardo-Romero CP Drew SL Weiss MG Metcalfe YJ Nakazawa SK Smith GL Emerson CL Hutson JS Salzer JH Bartlett VA Olson CJ Clemmons WB Davidson SR Zaki KL Karem IK Damon DS Carroll 《PloS one》2012,7(8):e43881
Volepox virus (VPXV) was first isolated in 1985 from a hind foot scab of an otherwise healthy California vole (Microtus californicus). Subsequent surveys in San Mateo County, CA, revealed serological evidence suggesting that VPXV is endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus truei) was collected in 1988. Since then, few studies have been conducted regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence and role as a potential zoonotic agent remain unknown. To increase our understanding of VPXV disease progression, we challenged 24 California mice (Peromyscus californicus) intranasally with 1.6×10(3) PFU of purified VPXV. By day five post infection (pi) we observed decreased activity level, conjunctivitis, ruffled hair, skin lesions, facial edema, and crusty noses. A mortality rate of 54% was noted by day eight pi. In addition, internal organ necrosis and hemorrhages were observed during necropsy of deceased or euthanized animals. Viral loads in tissues (brain, gonad, kidney, liver, lung, spleen, submandibular lymph node, and adrenal gland), bodily secretions (saliva, and tears), and excretions (urine, and/or feces) were evaluated and compared using real time-PCR and tissue culture. Viral loads measured as high as 2×10(9) PFU/mL in some organs. Our results suggest that VPXV can cause extreme morbidity and mortality within rodent populations sympatric with the known VPXV reservoirs. 相似文献