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1.
Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30-45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5-6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76-80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro-propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.  相似文献   

2.
Garenoxacin, a novel des-F(6)-quinolone, was tested against 40423 pathogenic isolates associated with community-acquired respiratory tract infections (CA-RTIs). The strains included Streptococcus pneumoniae (18887), Haemophilus influenzae (15555), and Moraxella catarrhalis (5981), each isolated from a significant infection monitored by the SENTRY Antimicrobial Surveillance Program (1999-2005; North America, Latin America, and Europe). All tests were performed by reference broth microdilution methods for garenoxacin and 19 comparison agents. The garenoxacin MIC(90) and percentage (%) of strains inhibited at < or =1 microg/mL (proposed susceptible breakpoint) were S. pneumoniae (0.06 microg/mL, >99.9% susceptible), H. influenzae (< or =0.03 microg/mL, >99.9%), and M. catarrhalis (< or =0.03 microg/mL, 100.0%). The garenoxacin potency versus the pneumococci was 16- to 32-fold greater than levofloxacin or ciprofloxacin and 2-fold superior to moxifloxacin (MIC(90), 0.12 microg/mL). Resistances to other classes of antimicrobials did not adversely influence garenoxacin MIC results. Ciprofloxacin- or levofloxacin-resistant (MIC, > or =4 microg/mL) S. pneumoniae had higher garenoxacin MIC(90) values (1 microg/mL), but 90.6% to 97.5% of strains remained susceptible. Strains of all 3 monitored pathogens with mutations in the quinolone resistance determining region (QRDR) had higher garenoxacin MIC results, with > or =3 to 4 QRDR mutations required to elevate garenoxacin MIC values to > or =2 microg/mL. In conclusion, garenoxacin possesses a potent activity against pneumococci, H. influenzae, and M. catarrhalis strains worldwide, at a level significantly greater than the available tested agents in the fluoroquinolone class (ciprofloxacin, levofloxacin, and moxifloxacin). Only 13 and 4 isolates (0.07% and 0.03%) of S. pneumoniae and H. influenzae, respectively, had a garenoxacin MIC at > or =2 microg/mL, thus, making this new "respiratory antipneumococcal" quinolone an attractive candidate for the therapy of contemporary CA-RTI (bronchitis, pneumonia, and sinusitis).  相似文献   

3.
Ki (in Japanese) or Qi (in Chinese) is the key concept in Eastern medicine, Eastern philosophy, as well as in martial arts. We explain the philosophical and psychological background of Ki. We emphasize that the unique aspects of Eastern philosophy are 'non-linearity' and 'holistic' approach. We then present physics aspect of Ki. Our experiments demonstrated that a 'Ki-beam' carries 'entropy' (or information), which is different from 'energy'. We introduce our experience of having taught Ki to 37 beginners in the United States through the Nishino Breathing Method. If beginners had martial arts training or a strong background in music or dance, about half of them could sense Ki within 10 weeks (1 h class per week) of practice.  相似文献   

4.
Genetic factors importantly contribute to migraine. However, unlike for rare monogenic forms of migraine, approaches to identify genes for common forms of migraine have been of limited success. Candidate gene association studies were often negative and positive results were often not replicated or replication failed. Further, the significance of positive results from linkage studies remains unclear owing to the inability to pinpoint the genes under the peaks that may be involved in migraine. Problems hampering these studies include limited sample sizes, methods of migraine ascertainment, and the heterogeneous clinical phenotype. Three genome-wide association studies are available now and have successfully identified four new genetic variants associated with migraine. One new variant (rs1835740) modulates glutamate homeostasis, thus integrates well with current concepts of neurotransmitter disturbances. This variant may be more specific for severe forms of migraine such as migraine with aura than migraine without aura. Another variant (rs11172113) implicates the lipoprotein receptor LRP1, which may interact with neuronal glutamate receptors, thus also providing a link to the glutamate pathway. In contrast, rs10166942 is in close proximity to TRPM8, which codes for a cold and pain sensor. For the first time this links a gene explicitly implicated in pain related pathways to migraine. The potential function of the fourth variant rs2651899 (PRDM16) in migraine is unclear. All these variants only confer a small to moderate change in risk for migraine, which concurs with migraine being a heterogeneous disorder. Ongoing large international collaborations will likely identify additional gene variants for migraine.  相似文献   

5.
Track-density imaging (TDI) was recently introduced as a method to achieve super-resolution imaging using whole-brain fibre-tracking data (the so called tractogram). A similar approach to achieve super-resolution was later applied for average pathlength mapping (APM). These two methods have in common that the tractogram information is used to create an image with novel contrast and super-resolution properties. In this study, we present a generalised framework for creating super-resolution track-weighted imaging (TWI), where the intensity of the map can be made dependent on any specific property of the streamlines or their set of spatial coordinates. Furthermore, each contrast can be determined by a number of characteristics that are under user control. It is shown that TDI and APM represent specific cases of this generalised framework, and that this framework opens up the possibility of generating a large range of images with novel image contrasts. Finally, it is shown that the same super-resolution principles as those introduced in the original TDI method are also applicable to any of these new images.  相似文献   

6.
Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD.Methods: The effect of gene/gene and gene/environment interaction related to late onset Alzheimer Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched controls enrolled in the Personalized Medicine Research Project, a population-based bio-repository. Genetic risk factors examined included APOE, ACE, OLR1,and CYP46 genes, and environmental factors included smoking, total cholesterol, LDL, HDL, triglycerides, C-reactive protein, blood pressure, statin use, and body mass index.Results: The mean age of the cases was 78.2 years and the mean age of the controls was 87.2 years. APOE4 was significantly associated with LOAD (OR=3.55, 95%CL=1.70, 7.45). Cases were significantly more likely to have ever smoked cigarettes during their life (49.3% versus 38.4%, p=0.03). The highest recorded blood pressure and pulse pressure measurements were significantly higher in the controls than the cases (all P<0.005). Although not statistically significant in this pilot study, the relationship of the following factors was associated in opposite directions with LOAD based on the presence of an APOE4 allele: obesity at the age of 50, ACE, OLR1, and CYP46.Conclusions: These pilot data suggest that gene/gene and gene/environment interactions may be important in LOAD, with APOE, a known risk factor for LOAD, affecting the relationship of ACE and OLR1 to LOAD. Replication with a larger sample size and in other racial/ethnic groups is warranted and the allele and risk factor frequencies will assist in choosing an appropriate sample size for a definitive study.  相似文献   

7.
OBJECTIVES: To examine the relationship between genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumour protein p53 (TP53) genes, and gallbladder cancer (GBC) risk, a case-control study was conducted. DESIGN AND METHODS: Genotypes of CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1, and TP53 Arg72Pro were determined in 54 cases of GBC and 178 controls. RESULTS: The age-adjusted odds ratios (ORs) for the Ile/Val genotype of CYP1A1 Ile462Val polymorphism in women and the Arg/Pro genotype of TP53 Arg72Pro polymorphism in men were observed to be 2.70 (95% CI: 1.14-6.40) and 4.32 (95% CI: 1.08-17.2), respectively. No significant differences in the genotypic frequencies of CYP1A1 T3801C and GSTM1 polymorphisms were observed between controls and cases in both men and women. CONCLUSION: These results suggest that the Val allele of CYP1A1 Ile462Val polymorphism and the Pro allele of TP53 Arg72Pro polymorphism contribute to an increased risk of GBC among Japanese women and men, respectively.  相似文献   

8.
The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine.  相似文献   

9.
The bifidogenic effect of an infant formula supplemented with inulin and fructooligosaccharides (4.0 g/l) was examined clinically and in vitro, and compared that of mature breast milk. In a 28-day clinical study, fecal samples of 21 infants, divided into two groups: one receiving the infant formula and the other breast milk, were microbiologically and biochemically examined. In the in vitro investigation, microbiological and biochemical changes in the infant formula and breast milk induced by the action of bifidobacteria isolated from infant feces were examined. There were no significant differences in the fecal numbers of lactobacilli, total aerobes, anaerobes or yeasts and fungi. In contrast, the bifidobacteria numbers in the stools increased significantly during the study in the infants receiving the supplemented formula. The comparative in vitro test showed that the bifidogenic effect was similar for infant formula and breast milk in terms of the number of bifidobacteria. Consumption of infant formula with added inulin and fructooligosaccharides stimulated the bifidogenic effect, both clinically and in vitro. The in vitro test can quickly and objectively determine the bifidogenic effect of infant formula and indicate their quality. However, a clinical test is necessary to determine the acceptance and biological value of infant formula.  相似文献   

10.
Total phenolic contents, antioxidant activity and chemical composition of propolis samples from three localities of Minas Gerais state (southeast Brazil) were determined. Total phenolic contents were determined by the Folin-Ciocalteau method, antioxidant activity was evaluated by DPPH, using BHT as reference, and chemical composition was analyzed by GC/MS. Propolis from Itapecerica and Paula Candido municipalities were found to have high phenolic contents and pronounced antioxidant activity. From these extracts, 40 substances were identified, among them were simple phenylpropanoids, prenylated phenylpropanoids, sesqui- and diterpenoids. Quantitatively, the main constituent of both samples was allyl-3-prenylcinnamic acid. A sample from Virginópolis municipality had no detectable phenolic substances and contained mainly triterpenoids, the main constituents being α- and β-amyrins. Methanolic extracts from Itapecerica and Paula Candido exhibited pronounced scavenging activity towards DPPH, indistinguishable from BHT activity. However, extracts from Virginópolis sample exhibited no antioxidant activity. Total phenolic substances, GC/MS analyses and antioxidant activity of samples from Itapecerica collected monthly over a period of 1 year revealed considerable variation. No correlation was observed between antioxidant activity and either total phenolic contents or contents of artepillin C and other phenolic substances, as assayed by CG/MS analysis.  相似文献   

11.
A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-alpha and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.  相似文献   

12.
Studies investigating the association between the BRCA1 rs799917 polymorphism and breast cancer risk have reported controversial results. In order to derive a more precise estimation of the relationship, we performed a comprehensive meta-analysis. A total of 8 articles comprising 19,878 subjects were included in this meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by Stata 11 software. Heterogeneity tests were conducted by Q test with I2 value, and publication bias assessment was performed by Begg's funnel plot and Egger's test. The pooled results did not show any sufficient evidence approving the association between the BRCA1 rs799917 polymorphism and breast cancer risk in total population (T vs C: OR = 1.01, 95% CI = 0.97–1.06; TT vs CC: OR = 1.03, 95% CI = 0.93–1.13; CT vs CC: OR = 1.04, 95% CI = 0.92–1.16; TT + CT vs CC: OR = 1.04, 95% CI = 0.94–1.15; TT vs CT + CC: OR = 1.03, 95% CI = 0.94–1.12). In the further subgroup analyses, no significant associations were found in any comparison models according to ethnicity and source of controls. No publication bias was observed in this meta-analysis. In summary, based on the overall results, this meta-analysis strongly suggests that the BRCA1 rs799917 polymorphism is not associated with breast cancer risk.  相似文献   

13.
Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins-haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury.  相似文献   

14.
Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological effects, such as anti-microbial, anti-inflammatory and anticancer. Shoot apices of Baccharis dracunculifolia (alecrim plant, Asteraceae) have been pointed out as sources of resin for green propolis. The present work aimed (i) to observe the collecting behavior of bees, (ii) to test the efficacy of histological analysis in studies of propolis botanical origin and (iii) to compare the chemistries of alecrim apices, resin masses and green propolis. Bee behavior was observed, and resin and propolis were microscopically analyzed by inclusion in methacrylate. Ethanol extracts of shoot apices, resin and propolis were analyzed by gas chromatography/mass spectroscopy. Bees cut small fragments from alecrim apices, manipulate and place the resulting mass in the corbiculae. Fragments were detected in propolis and identified as alecrim vestiges by detection of alecrim structures. Prenylated and non-prenylated phenylpropanoids, terpenoids and compounds from other classes were identified. Compounds so far unreported for propolis were identified, including anthracene derivatives. Some compounds were found in propolis and resin mass, but not in shoot apices. Differences were detected between male and female apices and, among apices, resin and propolis. Alecrim apices are resin sources for green propolis. Chemical composition of alecrim apices seems to vary independently of season and phenology. Probably, green propolis composition is more complex and unpredictable than previously assumed.  相似文献   

15.
Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. Both diabetes and depression negatively interact, in that depression leads to poor metabolic control and hyperglycemia exacerbates depression. We hypothesize one novel vanadium complex of vanadium-enriched Cordyceps sinensis (VECS), which is beneficial in preventing depression in diabetes, and influences the long-term course of glycemic control. Vanadium compounds have the ability to imitate the action of insulin, and this mimicry may have further favorable effects on the level of treatment satisfaction and mood. C. sinensis has an antidepressant-like activity, and attenuates the diabetes-induced increase in blood glucose concentrations. We suggest that the VECS may be a potential strategy for contemporary treatment of depression and diabetes through the co-effect of C. sinensis and vanadium. The validity of the hypothesis can most simply be tested by examining blood glucose levels, and swimming and climbing behavior in streptozotocin-induced hyperglycemic rats.  相似文献   

16.
Background: A standardized rose-hip powder produced from the seeds and husks of fruit from a subtype of Rosa canina has been reported to inhibit leukocyte functions that cause cell injury in osteoarthritis.Objective: The aim of this study was to assess the impact of standardized rose-hip powder on mobility of the hip and knee joints, activities of daily living, quality of life, and pain in patients with osteoarthritis.Methods: Patients with a diagnosis of osteoarthritis of either the hip or knee, verified on radiography, participated in this randomized, placebo-controlled, double-blind study. Half of the patients were given five 0.5-g capsules of standardized rose-hip powder twice daily for 4 months, and the other half received identical placebo capsules twice daily for the same period. Mobility of the hip or knee was measured in both groups after the initial screening and again after 4 months of therapy.Results: One hundred patients (65 women, 35 men; mean [SD] age, 65.2 [11.1] years) were divided into 2 treatment groups of 50 patients each. Hip joint mobility improved significantly in the treatment group compared with the placebo group (P = 0.033). Similarly, pain decreased significantly in the treatment group compared with the placebo group (P = 0.035). Two patients (4%) from each group withdrew during the early stages of the trial for reasons not related to treatment.Conclusions: In this study population, standardized rose-hip powder reduced symptoms of osteoarthritis, as 64.6% of patients reported at least some reduction of pain while receiving treatment. Standardized rose-hip powder may improve hip flexion and reduce pain in patients with osteoarthritis.  相似文献   

17.
18.
To elucidate the role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lacking A1-a, a subtype of the A1 gene in mice (A1-a−/− mice). Spontaneous apoptosis of peripheral blood neutrophils of A1-a−/− mice was enhanced compared with that of either wild-type mice or heterozygous mutants (A1-a+/− mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatment in vitro or transendothelial migration in vivo observed in wild-type mice was abolished in both A1-a−/− and A1-a+/− animals. On the other hand, the extent of tumor necrosis factor α–induced acceleration of neutrophil apoptosis did not differ among A1-a−/−, A1-a+/−, and wild-type mice. The descending order of A1 mRNA expression was wild-type, A1-a+/−, and A1-a−/−. Taken together, these results suggest that A1 is involved in inhibition of certain types of neutrophil apoptosis.  相似文献   

19.
Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce and exhibit widespread fear and panic than the actual potential of physical damage. Bacillus anthracis(B. anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non-motile bacterium. This is supposed to be one of the most potent BW agents because its spores are extremely resistant to natural conditions and can survive for several decades in the environment. B.anthracis spores enter the body through skin lesion(cutaneous anthrax), lungs(pulmonary anthrax), or gastrointestinal route(gastrointestinal anthrax) and germinate, giving rise to the vegetative form. Anthrax is a concern of public health also in many countries where agriculture is the main source of income including India. Anthrax has been associated with human history for a very long time and regained its popularity after Sept 2001 incidence in United States. The present review article describes the history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon.  相似文献   

20.
Helicobacter pylori infection is associated with gastric epithelial damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as “bait” to capture receptor proteins in solubilized membranes of gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-γ, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-γ. IFN-γ increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II–negative cell lines, H. pylori induced apoptosis in cells expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.  相似文献   

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