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The importance of accessory signaling pathways amplifying endotoxin responses has recently been highlighted by genetic studies describing LPS-hyporesponsive individuals despite carrying the common allele for TLR4. The nucleotide receptor P2X7 modulates the production of numerous LPS-stimulated inflammatory mediators. We have recently described the largest phenotypic screen known for genetic polymorphisms associated with the nucleotide receptor P2X7, a global regulator of leukocyte function. This required the development of a novel monocyte pore assay with numerous advantages over previous methods and with the potential to facilitate rapid (< 3 h), multiplex analysis of clinical samples. This paper addresses aspects pertinent to the development of the monocyte pore assay, briefly summarizes our results suggesting that P2X7 alleles modulate LPS-stimulated cytokine production, and discusses a model wherein P2X7 may serve as an amplification loop of innate immunity.  相似文献   
64.
We examined the effect of a previous deep breath on both inert gas mixing and the single breath diffusing capacity (DLCOSB) during submaximal single breath maneuvers in normal subjects. Single breath washouts were performed either immediately after a deep breath or after breathing tidally for 10 min. Maneuvers consisted of inhaling test gas from functional residual capacity to 50% inspiratory capacity and, after either 0 or 6 s of breath holding, exhaling slowly back to residual volume. We measured the Fowler dead space, the Phase III slope of the alveolar plateau of the He washout (delta He/L), the amplitude of the cardiogenic oscillations (Oc), closing capacity, mixing efficiency (Emix) and DLCOSB using the three equation method. For maneuvers immediately after a deep breath we found that delta He/L was steeper and the Oc were larger for washouts with 6 s but not 0 s of breath holding, while Emix was significantly lower and DLCOSB significantly higher for both the 0 s and the 6 s breath holding maneuvers. We conclude that a deep breath increases DLCOSB but simultaneously also increases convective-dependent inhomogeneity in the lung.  相似文献   
65.
Few studies have evaluated population-level risk factors for having a bedbug infestation. We describe characteristics associated with bedbug complaints among New York City Housing Authority (NYCHA) residents. Unique households receiving bedbug extermination services in response to a complaint during January 1, 2010 to December 31, 2011 were identified from NYCHA’s central facilities work order database. We examined associations between household characteristics and having a bedbug complaint using a generalized estimating equation Poisson regression model, accounting for clustering by housing development. Of the 176,327 NYCHA households, 11,660 (6.6 %) registered a bedbug complaint during 2010–2011. Bedbug complaints were independently associated with households having five or more children versus no children (prevalence ratio [PR] = 2.0), five or more adults versus one adult (PR = 1.6), a head of household (HOH) with impaired mobility (PR = 1.3), a household member receiving public assistance (PR = 1.2), a household income below poverty level (PR = 1.1), and a female HOH (PR = 1.1). Infestations were less likely to be reported by households with employed members (PR = 0.9), and an HOH aged 30–44 years (PR = 0.9) or 45–61 years (PR = 0.9), compared with an HOH aged 18–29 years. These results indicate that bedbug control efforts in public housing should be targeted toward households with low income and high occupancy.  相似文献   
66.

Background

Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear.

Methods

Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined.

Results

COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort.

Conclusions

COX-2 expression has predictive utility for management of rectal but not colon cancer.  相似文献   
67.
Myoclonus is a brief, rapid, involuntary muscle jerk originating in the central nervous system that can be physiological or a symptom of disease. We report a group of five children with excessive myoclonic jerks, only during sleep, and abnormal EEG during the events. Although only one third of the events had EEG epileptiform correlate, the presence of myoclonus without epileptiform EEG correlate has been described in patients with benign myoclonic epilepsy of infancy. We hypothesize that these findings may represent a variant of benign myoclonic epilepsy of infancy.  相似文献   
68.
Surgery alters the body’s homeostatic balance and defense mechanisms. In adults transient postoperative cellular and humoral immunosuppression after different degrees of operative stress has been reported. In children the immunologic consequences of operations are not elaborated. This study investigates the effect of minor and major surgery on early nonspecific immune response in terms of neutrophil counts and function. Forty-three children undergoing minor and major elective procedures were studied. Blood samples were collected before, immediately after, and 72 h after surgery. Total white cell count, differential neutrophil count, and neutrophil phagocytic function were studied using nitroblue tetrazolium test. Children were divided into two groups—group 1 underwent minor surgery and group 2 major surgery. In group 1 there was a significant drop in total counts after surgery, but in group 2 total counts were not affected. In both groups, the percentage of neutrophils increased immediately after surgery but fell to near or less than preoperative levels 72 h after surgery. However, the assessment of neutrophil functions by nitroblue tetrazolium test in both unstimulated and stimulated forms revealed it to be unchanged in group 1. In group 2 the unstimulated neutrophil function was elevated 72 h after surgery, whereas stimulated function was elevated immediately after surgery. Minor surgery does not alter the early nonspecific immune response. However, major surgery seems to induce a transient increase in neutrophil phagocytic activity.  相似文献   
69.
The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8?mL/kg body weight of 50% glycerol, glycerol?+?ferulic acid at the dose of 5, 10, 15, 20 and 25?mg/kg body weight. After 24?h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.  相似文献   
70.
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