排序方式: 共有45条查询结果,搜索用时 15 毫秒
1.
Shevin T. Jacob Patricia B. Pavlinac Lydia Nakiyingi Patrick Banura Jared M. Baeten Karen Morgan Amalia Magaret Yuka Manabe Steven J. Reynolds W. Conrad Liles Anna Wald Moses L. Joloba Harriet Mayanja-Kizza W. Michael Scheld 《PloS one》2013,8(8)
Background
When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.Methods
We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.Results
Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].Conclusions
Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection. 相似文献2.
3.
Caroline Schmutz Alison Cartwright Helen Williams Oliver Haworth John HH Williams Andrew Filer Mike Salmon Christopher D Buckley Jim Middleton 《Arthritis research & therapy》2010,12(4):R161
Introduction
Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers. 相似文献4.
Jan Rossaint Christian Berger Hugo Van Aken Hans H. Scheld Peter K. Zahn Andreas Rukosujew Alexander Zarbock 《PloS one》2012,7(9)
Background
It is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB.Methods
We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis.Results
CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils.Conclusion
These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches. 相似文献5.
6.
Jamil M Neto Marina GM Viturino Galina Ananina Flvia F Bajano Sueli M da S Costa Alicia B Roque Gessica FS Borges Raissa Franchi Priscila HH Rim Flvio M Medina Fernando F Costa Mnica B de Melo Jos PC de Vasconcellos 《Experimental biology and medicine (Maywood, N.J.)》2021,246(21):2290
This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P = 5.47e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P = 0.0046) and CG genotypes (OR = 2.2249; P = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant. 相似文献
7.
Blood-brain barrier alterations in bacterial meningitis: Development of an in vitro model and observations on the effects of lipopolysaccharide 总被引:3,自引:0,他引:3
Allan R. Tunkel Susan W. Rosser Eric J. Hansen W. Michael Scheld 《In vitro cellular & developmental biology. Animal》1991,27(2):113-120
Summary To further examine the effects of purifiedHaemophilus influenzae type b lipopolysaccharide (LPS) on blood-brain barrier permeability, we have developed an in vitro model of the BBB. Microvascular
endothelial cells were isolated from rat cerebral cortices by enzymatic digestion, dextran centrifugation, and separation
on percoll gradients. The cells were determined to be endothelial in origin by positive fluorescent staining for Factor VIII-related
antigen and the ability to take up acetylated low density lipoproteins, and their cerebral origin by the formation of junctional
complexes in vitro. Cells were seeded onto semipermeable polycarbonate filters and permeability assessed by measuring traversal
of radioactive albumin across the monolayer. Treatment of the cells with LPS at concentrations of 1.0μg/ml and 0.1μg/ml for 4 h led to statistically significant increases in albumin permeability of 4.6% (P=0.001) and 5.6% (P<0.001), respectively, without evidence of cell death as assessed by release of lactate dehydrogenase into the media. These
results indicate that LPS significantly increases albumin permeability across a monolayer of cerebral microvascular endothelial
cells in the absence of host inflammatory cells. Future studies on the effects of LPS on intracellular regulation will determine
the mechanisms responsible for these alterations.
Supported by a research grant (RO1-AI17904) and a training grant (T32-AI07046) from the National Institute of Allergy and
Infectious Diseases, Bethesda, MD. W. Michael Scheld is an established investigator of the American Heart Association. 相似文献
8.
9.
Current estimates of the mortality associated with brain abscesses range from 0-24%, with neurological sequellae in 30-55% of survivors. Although the incidence of brain abscess appears to be increasing, likely due to an increase in the population of immunosuppressed patients, the condition is still sufficiently uncommon to make human clinical trials of therapy problematic. An animal model to study the efficacy of new treatment regimens, specifically, new antimicrobial agents is therefore necessary. This study uses a well-defined experimental paradigm as an inexpensive method of inducing and studying the efficacy of antibiotics in brain abscess. The rat model of brain abscess/cerebritis developed at this institution was used to determine the relative efficacy of trovafloxacin as compared to ceftriaxone in animals infected with Staphylococcus aureus. S. aureus ( approximately 10(5) CFU in 1 microliter) was injected with a Hamilton syringe, very slowly, over the course of 70 minutes after a two mm burr hole was created with a spherical carbide drill just posterior to the coronal suture and four mm lateral to the midline. Eighteen hours later treatment was begun; every 8 hours the rats were dosed with subcutaneous ceftriaxone (n = 10), trovafloxacin (n = 11) or 0.9% sterile pyogen-free saline (n = 10). After four days of treatment the brains were removed and sectioned with a scalpel. The entire injected hemisphere was homogenized and quantitative cultures performed. The mean +/- SEM log(10) colony forming units/ml S. aureus recovered from homogenized brain were as follows: controls 6.10 +/- 0.28; ceftriaxone 3.43 +/- 0.33; trovafloxacin 3.65 +/- 0.3. There was no significant difference in bacterial clearance between ceftriaxone versus trovafloxacin (p = 0.39). Trovafloxacin or other quinolones may provide a viable alternative to intravenous antibiotics in patients with brain abscess/cerebritis. 相似文献
10.
Three antibodies that recognize distinct fucose epitopes were used to study
fucosylation during growth and development of Dictyostelium discoideum.
mAb83.5 is known to recognize an undefined "fucose epitope" on several
proteins with serine-rich domains, while mAb CAB4, and a component of
anti-horse-radish peroxidase, specifically recognize Fucalpha1,6GlcNAc and
Fucalpha1,3GlcNAc residues respectively in the core of N-linked
oligosaccharides. We show that mAb 83.5 defines a new type of
O-glycosylation. Serine-containing peptides incubated with GDPbeta[3H]Fuc
and microsomes formed two fucosylated products. A neutral product
accounting for 30% of the label did not react with the antibody, while the
rest of the label was incorporated into a charged product which contained
all the mAb83.5 reactive material. beta- Elimination of the labeled peptide
or endogenous products produced [3H]Fuc-1-P, indicating phosphodiester
linkage to serine. Fucbeta-1-P and GDP-betaFuc at 100 microM blocked
mAb83.5 binding to endogenous and peptide products, but their alpha-linked
anomers did not. Electrospray ionization mass spectra of the neutral and
anionic labeled products showed major peaks of mass units corresponding to
O-Fuc-Ser peptide and O-Fuc-phospho-Ser peptide, respectively. The activity
of Fuc- phosphotransferase exactly paralleled the accumulation of reactive
glycans during growth and development. The expressions of N-glycan core
Fucalpha1,6GlcNAc and Fucalpha1,3GlcNAc and their respective fucosyl
transferase activities were also synchronous, but their developmental
regulation differed from one another. Fucalpha1, 6GlcNAc was expressed
maximally during growth but declined during development. In contrast core
Fucalpha1,3GlcNAc epitopes were expressed almost exclusively during
development. These findings provide direct evidence for a novel type of
O-phosphofucosylation, demonstrate the existence of an O- fucosyl
transferase, and identify two different types of core fucosylation in the
N-glycans of Dictyostelium.
相似文献