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51.
52.
Cytopathogenicity of HIV and other enveloped viruses is reduced by membrane fluidizing agents and by dextran sulphate (DS). To investigate whether DS exerts its antiviral action via plasma membrane fluidization of host cells, we performed anisotropy measurements on human peripheral blood lymphocytes (PBL) using the fluorescent marker diphenylhexatriene. Anisotropy was decreased in DS-exposed PBL indicating increased fluidity in the hydrophobic membrane interior.  相似文献   
53.
54.
The purpose of this study was to document seizure events associated with the use of a computer-based assessment and to describe the contextual factors surrounding these seizure episodes. Study participants were adults with epilepsy who were enrolled at research sites in Atlanta and Boston. Subjects were asked to complete a computer-based assessment at 3 time points. Fourteen seizure events were documented; they occurred during 1.6% of all completed assessments (896) and affected 4.4% of the participants (320). The mean age of participants who experienced seizure events was 41.4 years; about 70% were female, and 70% were white. A variety of possible precipitating factors for seizure events included hunger, fatigue, stress, and medication changes. Participants indicated computer use could have triggered their seizures in 2 instances. These findings suggest use of computer-based assessments may pose minimal risks for adults with epilepsy, particularly those without a history of photosensitivity epilepsy.  相似文献   
55.
A sensitive method is described for the detection of beta 2-transferrin, a transferrin-variant found only in cerebrospinal fluid (CSF). The determination of beta 2-transferrin, whose presence is characteristic of CSF-admixtures in secretions, is performed in three steps. The proteins of the secretion are separated by polyacrylamide gel electrophoresis and then transferred electrophoretically onto a nitrocellulose sheet. Finally, the transferrins on the nitrocellulose sheet are specifically detected by an antibody reaction. The bands are visualized either by using antibodies conjugated with peroxidase or by protein A gold. With the exception of certain cases (Ritchie, R. F. & Smith, R. (1976) Clin. Chem. 22, 497-499; G?rg, A. et al. (1983) Human Genetics 64, 222-226) beta 2-transferrin is found only in cerebrospinal fluid, and not in other body fluids. Therefore the detection of beta 2-transferrin can be used for the diagnosis of rhino- and otoliquorrhea. The advantage of this method is that beta 2-transferrin can be unequivocally identified by the use of a relatively small amount of technical equipment. CSF can therefore be clearly identified in secretions. An additional advantage of the method is its high sensitivity.  相似文献   
56.
Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.  相似文献   
57.
Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.  相似文献   
58.
Background:  The association between cigarette smoke exposure and allergic airway disease is a matter for debate. We sought to investigate in an in vitro system whether active smoking reduces the integrity and barrier function of the respiratory epithelium and thus facilitates allergen penetration.
Methods:  We cultured the human bronchial epithelial cell line 16HBE14o− in a transwell culture system as a surrogate for the intact respiratory epithelium. The cell monolayer was exposed to standardized cigarette smoke extract (CSE). The extent and effects of trans-epithelial allergen penetration were measured using 125I-labelled purified major respiratory allergens (rBet v 1, rPhl p 5 and rDer p 2) and histamine release experiments.
Results:  Exposure of cells to concentrations of CSE similar to those found in smokers induced the development of para-cellular gaps and a decrease in trans-epithelial resistance. CSE exposure induced a more than threefold increase in allergen penetration. Increased subepithelial allergen concentrations provoked a substantial augmentation of histamine release from sensitized basophils.
Conclusions:  Our results indicate that cigarette smoke is a potent factor capable of reducing the barrier function of the respiratory epithelium for allergens and may contribute to increased allergic inflammation, exacerbation of allergic disease and boosting of IgE memory.  相似文献   
59.
The nuclear bile acid receptor, farnesoid X receptor (FXR), may play a pivotal role in liver fibrosis. We tested the impact of genetic FXR ablation in four different mouse models. Hepatic fibrosis was induced in wild-type and FXR knock-out mice (FXR−/−) by CCl4 intoxication, 3,5-diethoxycarbonyl-1,4-dihydrocollidine feeding, common bile duct ligation, or Schistosoma mansoni (S.m.)-infection. In addition, we determined nuclear receptor expression levels (FXR, pregnane X receptor (PXR), vitamin D receptor, constitutive androstane receptor (CAR), small heterodimer partner (SHP)) in mouse hepatic stellate cells (HSCs), portal myofibroblasts (MFBs), and human HSCs. Cell type-specific FXR protein expression was determined by immunohistochemistry in five mouse models and prototypic human fibrotic liver diseases. Expression of nuclear receptors was much lower in mouse and human HSCs/MFBs compared with total liver expression with the exception of vitamin D receptor. FXR protein was undetectable in mouse and human HSCs and MFBs. FXR loss had no effect in CCl4-intoxicated and S.m.-infected mice, but significantly decreased liver fibrosis of the biliary type (common bile duct ligation, 3,5-diethoxycarbonyl-1,4-dihydrocollidine). These data suggest that FXR loss significantly reduces fibrosis of the biliary type, but has no impact on non-cholestatic liver fibrosis. Since there is no FXR expression in HSCs and MFBs in liver fibrosis, our data indicate that these cells may not represent direct therapeutic targets for FXR ligands.The farnesoid X receptor (FXR;NR1H4) is a key regulator of hepatic bile acid homeostasis, lipoprotein and glucose metabolism, bacterial colonization of the small intestine, the inflammatory response, and liver regeneration.1,2,3 Hereditary and acquired FXR defects may contribute to cholestasis and gallstone formation in humans.4,5,6,7 Defects in its target genes (eg, bile salt export pump/ABCB11; multidrug resistance gene 3/ABCB4 (a phosphatidylcholine floppase); multidrug related protein 2/ABCC2) cause well-characterized clinical syndromes.8,9,10,11 Moreover, FXR knockout mice (FXR−/−) have impaired resistance to bile acid feeding,12,13 and show substantial differences in the cholestatic phenotype in response to common bile duct ligation,14,15,16 have increased susceptibility for diet-induced gallstone disease,17,18 and impaired liver regeneration following partial hepatectomy.19 FXR may also directly or indirectly (eg, by the interaction with other members of the nuclear receptor family such as PXR/NR1I2 and VDR/NR1I1) regulate the metabolism and hepatic clearance of xenobiotics.20,21,22Recent studies also reported mRNA expression of FXR in hepatic stellate cells and FXR protein in renal proximal tubules23,24,25 suggesting that FXR could represent a therapeutic target for the treatment of liver fibrosis and diabetic nephropathy.23,24,25,26 Moreover, FXR ligands were claimed to repress collagen expression in HSCs in vitro via a postulated FXR/SHP-dependent mechanism.23 It is also attractive to hypothesis that genetic FXR variants may predispose patients suffering from various forms of liver diseases to liver fibrosis as a kind of genetic disease modifier.7,27 Taken together its pleiotrophic functions (eg, central regulator of bile acid homoeostasis, glucose and lipid metabolism, inflammation) make FXR an extremely attractive candidate for therapeutic targeting in cholestatic liver diseases and nonalcoholic fatty liver disease including their major sequel liver fibrosis.28,30 However, little is known on hepatic cell-type FXR expression in human liver fibrosis.The aims of this study were threefold. First, we aimed to determine the impact of genetic FXR ablation on the degree of liver fibrosis in untreated mice and four different well established mouse models including CCl4-intoxicated mice, 3,5 -diethoxycarbonyl-1,4-dihydrocollidine (DDC)-intoxicated mice and common bile duct-ligated (CBDL) mice for biliary fibrosis, and infection with Schistosoma mansoni (S.m.), which has been shown to induce “pipe-stem” fibrosis and granuloma formation.31,32 Comparison of cholestatic (DDC, CBDL) and non-cholestatic (CCl4, S.m.) mouse models for liver fibrosis should provide differentiated knowledge on the role of FXR in various types and etiologies of liver fibrosis. Based on previous studies reporting that pharmacological activation of FXR is antifibrotic in liver but also kidney23,25 we hypothesized that FXR−/− mice spontaneously develop liver fibrosis and are more susceptible to experimentally induced liver fibrosis due to the lack of a postulated FXR/SHP-dependent down-regulation of collagen mRNA expression in profibrotic states.23,24 We therefore compared the extent of fibrosis in FXR−/− mice and wild-type controls in a longitudinal study under baseline conditions and in response to cholestatic and non-cholestatic fibrogenic injury. Second, we aimed to determine the expression of genes involved in bile acid transport/metabolism and their regulatory nuclear receptors (including FXR, PXR, CAR/NR1I3, VDR, and SHP/NR0B2) in isolated profibrogenic rodent cells [ie, periductal myofibroblasts (MFBs), and quiescent as well as activated hepatic stellate cells (HSCs)] and to test the effects of FXR ligands on FXR target genes in vitro. Cell type-specific FXR protein expression was determined in five different in vivo models for liver fibrosis. Finally, we cross-validated these findings in isolated human HSCs and histological sections from human prototypic fibrotic liver diseases [eg, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and alcoholic steatohepatitis (ASH)].  相似文献   
60.
People with epilepsy must adopt many self-management behaviors, especially regarding medication adherence, stress management, and sleep quality. In response to the need for theory-based self-management programs that people with epilepsy can easily access, the WebEase Web site was created and tested for feasibility, acceptability, and usability. This article discusses the theoretical background and developmental phases of WebEase and lessons learned throughout the development process. The WebEase research team developed content for the Web site on the basis of social cognitive theory, the transtheoretical model of behavior change, and motivational interviewing. Formative research and development of the WebEase program included a literature search, computer use survey, a focus group, and review by content experts and consumers. The program has 2 main components: 1) the modules, which provide a tailored opportunity for learning, reflection, and goal setting, and 2) MyLog, a place to enter daily information.  相似文献   
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