We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic ...antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (T(H)1) rather than type 2 (T(H)2). B7-H3 expression was consistently enhanced by interferon-gamma but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Edge habitats may be considered ‘ecological traps’ for breeding birds if they attract many birds because of apparently favorable nesting conditions but have higher nest predation levels than interior ...habitats. Four alternative, nonexclusive hypotheses have been suggested to explain why edges might have higher predation levels than interior habitats: (1) predator activity is higher in areas with higher prey density (density-dependent predation); (2) predators are more abundant on edges than in forest interior; (3) the predator community is richer in species on edges than in forest interior; and (4) predators forage along travel lanes (linear geographical features) such as edges. Here we evaluated whether forest-farm edges in southern Illinois are ecological traps, and examined the relevance of these four hypotheses at our study site with several different experiments during May–July 1992 using artificial nests (
n = 605) baited with quail eggs and placed on the ground, in shrubs, or in saplings.
Our results showed that, in general, the forest-farm edges of southwestern Illinois did not attract significantly more individuals or species of nesting songbirds, but they did have higher nest predation levels than forest interior sites, primarily as a result of higher predation levels on sapling nests. We did not find evidence strongly supporting any of the four hypotheses suggested as explanations for higher nest predation levels near edges. Two data sets showed that predation levels on artificial nests were density-independent. Forest-farm edges had neither more total species of potential nest predators nor more individual predators. However, there were more species of avian predators on edges than in interior sites. Correlations between predator abundance and nest predation levels on individual transects were weak. The travel lane hypothesis was not supported because nest predation levels were either not affected by distance from linear geographical features (roads and ravines) or were significantly less when close to than when far from presumptive travel lanes.
High spatial heterogeneity in predation levels, numbers of singing birds, and potential nest predators may have obscured general patterns and suggest a need for larger sample sizes. Edges may be detrimental to some species of singing birds but not to others, and for different reasons.
As the prevalence of obesity and obesity-related disease among adolescents in the United States continues to increase, physicians are increasingly faced with the dilemma of determining the best ...treatment strategies for affected patients. This report offers an approach for the evaluation of adolescent patients' candidacy for bariatric surgery. In addition to anthropometric measurements and comorbidity assessments, a number of unique factors must be critically assessed among overweight youths. In an effort to reduce the risk of adverse medical and psychosocial outcomes and increase compliance and follow-up monitoring after bariatric surgery, principles of adolescent growth and development, the decisional capacity of the patient, family structure, and barriers to adherence must be considered. Consideration for bariatric surgery is generally warranted only when adolescents have experienced failure of 6 months of organized weight loss attempts and have met certain anthropometric, medical, and psychologic criteria. Adolescent candidates for bariatric surgery should be very severely obese (defined by the World Health Organization as a body mass index of > or =40), have attained a majority of skeletal maturity (generally > or =13 years of age for girls and > or =15 years of age for boys), and have comorbidities related to obesity that might be remedied with durable weight loss. Potential candidates for bariatric surgery should be referred to centers with multidisciplinary weight management teams that have expertise in meeting the unique needs of overweight adolescents. Surgery should be performed in institutions that are equipped to meet the tertiary care needs of severely obese patients and to collect long-term data on the clinical outcomes of these patients.
Recent studies have suggested a short-term impairment in the regulation of food intake in older adults, but further studies are needed to determine if a longer-term impairment exists and to identify ...underlying causes. Changes in body weight and composition were measured over a 6-week underfeeding study and a 6-month follow-up period in healthy young (n = 23) and older (OLD, n = 18) men and women. The young adults were either normal weight (YNW, n = 12) or overweight (YOW, n = 11). Energy intakes during underfeeding were 896 +/- 18 (SEM) kcal less than weight-maintenance energy requirements determined prior to underfeeding. In addition, changes in perceived hunger during underfeeding were monitored in a subgroup (n = 19). OLD and YOW subjects lost significantly more weight during underfeeding than did YNW subjects (p = .025 and .000, respectively), and they did not gain back significant weight in the 6-month follow-up. In addition, OLD subjects reported a significantly lower frequency of hunger during underfeeding (p = .05). There was no significant difference among groups in the relationship between weight lost and fat-free mass lost. Healthy OLD adults have an impaired ability to regulate food intake over at least 6 months following underfeeding compared with YNW adults, and a reduction in their perceived frequency of hunger may be a contributing factor.
Manufacturing of retroviral vectors for gene therapy is complicated by the sensitivity of these viruses to stress forces during purification and concentration. To isolate viruses that are resistant ...to these manufacturing processes, we performed breeding of six ecotropic murine leukemia virus (MLV) strains by DNA shuffling. The envelope regions were shuffled to generate a recombinant library of 5 x 106 replication-competent retroviruses. This library was subjected to the concentration process three consecutive times, with amplification of the surviving viruses after each cycle. Several viral clones with greatly improved stabilities were isolated, with the best clone exhibiting no loss in titer under conditions that reduced the titers of the parental viruses by 30- to 100-fold. The envelopes of these resistant viruses differed in DNA and protein sequence, and all were complex chimeras derived from multiple parents. These studies demonstrate the utility of DNA shuffling in breeding viral strains with improved characteristics for gene therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Conflicting results have been reported regarding employment status and work ability in adults with congenital heart disease (CHD). Since this is an important determinant for quality of ...life, we assessed this in a large international adult CHD cohort.
Methods
Data from 4028 adults with CHD (53% women) from 15 different countries were collected by a uniform survey in the cross‐sectional APPROACH International Study. Predictors for employment and work limitations were studied using general linear mixed models.
Results
Median age was 32 years (IQR 25‐42) and 94% of patients had at least a high school degree. Overall employment rate was 69%, but varied substantially among countries. Higher education (OR 1.99‐3.69) and having a partner (OR 1.72) were associated with more employment; female sex (OR 0.66, worse NYHA functional class (OR 0.67‐0.13), and a history of congestive heart failure (OR 0.74) were associated with less employment. Limitations at work were reported in 34% and were associated with female sex (OR 1.36), increasing age (OR 1.03 per year), more severe CHD (OR 1.31‐2.10), and a history of congestive heart failure (OR 1.57) or mental disorders (OR 2.26). Only a university degree was associated with fewer limitations at work (OR 0.62).
Conclusions
There are genuine differences in the impact of CHD on employment status in different countries. Although the majority of adult CHD patients are employed, limitations at work are common. Education appears to be the main predictor for successful employment and should therefore be encouraged in patients with CHD.
The effect of aging on energy regulation remains controversial. We compared the effects of underfeeding on changes in energy expenditure and respiratory quotient in young normal weight men and women ...YNW, age 25.7 ± 3.2 y(sd), body mass index (BMI) 23.1 ± 1.6 kg/m2, young overweight men and women (YOW, age 26.1 ± 3.5 y, BMI 27.7 ± 2.1 kg/m2) and older (OLD) men and women (age 68.4 ± 3.3 y, BMI 27.4 ± 3.4 kg/m2). The thermic effect of feeding (TEF) during weight maintenance, and changes in resting energy expenditure (REE) and respiratory quotient were determined in response to undereating by an average 3.75 MJ/d for 6 wk. In addition, body composition was measured. No significant differences among the groups were observed in TEF, fasting and postprandial respiratory quotient, or the change in fasting respiratory quotient with underfeeding. However, REE adjusted for fat-free mass and fat mass was significantly lower in OLD subjects compared with YNW and YOW subjects (P < 0.05). In addition, the REE response to weight change was significantly attenuated in the OLD subjects (P = 0.023). These data suggest that the responsiveness of energy expenditure to negative energy balance is attenuated in old age, and provide further support for the hypothesis that mechanisms of energy regulation are broadly disregulated in old age.
Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, ...metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18h after ingestion. At 2h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0·5 and 0·15nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18% after 2h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1·2% only 18h post-gavage, with the urine and faecal content constituting almost 90% of the total recovered pelargonidin.
Synovial fluid proteins from microliter volumes of synovial fluid were resolved by two-dimensional polyacrylamide gel electrophoresis and detected by silver staining to investigate the feasibility of ...using two-dimensional (2D) electrophoresis in the clinical research setting and provide global disease information of disease progression. Several hundred proteins could be resolved as spots, many of which displayed the characteristic pattern of plasma-derived glycoproteins. The lowest level of detection was approximately 0.2 ng from a total of 50 microg of protein loaded. Most of the proteins could be identified on the basis of pI and molecular weight when compared with plasma protein maps on the World Wide Web. Unknown proteins were characterized by mass spectrometry of tryptic digests and by comparison with peptide databases. Synovial fluids from patients with rheumatoid arthritis were analyzed using this technique. Each subject received a fixed dose of antibody to CD4 as part of a phase II clinical trial to determine the efficacy of this immunosuppressive treatment in modifying disease activity. Synovial fluid was removed at day 0, followed by administration of antibody. Subsequent removal of synovial fluid and additional administration of antibody were carried out at different times thereafter. Changes in levels of acute-phase proteins were quantified by densitometry of silver-stained 2D polyacrylamide gels. Other parameters of disease progression such as serum C-reactive protein and physician's global assessment of clinical condition were used for comparison. In this way, changes in acute-phase proteins towards normal levels, as measured by 2D polyacrylamide gel electrophoresis, could be correlated with clinical improvement and conventional clinical chemistry measurements. Thus, the system can be used for quantitative analysis of protein expression in sites of autoimmune disease activity such as the synovial fluid of rheumatoid arthritis patients.
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