Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Accuracy of ICD-9 codes to identify nonunion and malunion and developing algorithms to improve case-finding of nonunion and malunion

ObjectiveTo evaluate the accuracy of using ICD-9 codes to identify nonunions (NU) and malunions (MU) among adults with a prior fracture code and to explore case-finding algorithms.Study designMedical chart review of potential NU (N = 300) and MU (N = 288) cases. True NU cases had evidence of NU and no evidence of MU in the chart (and vice versa for MUs) or were confirmed by the study clinician. Positive predictive values (PPV) were calculated for ICD-9 codes. Case-finding algorithms were developed by a classification and regression tree analysis using additional automated data, and these algorithms were compared to true case status.SettingGroup Health Cooperative.ResultsCompared to true cases as determined from chart review, the PPV of ICD-9 codes for NU and MU were 89% (95% CI, 85–92%) and 47% (95% CI, 41–53%), respectively. A higher proportion of true cases (NU: 95%; 95% CI, 90–98%; MU: 56%; 95% CI, 47–66%) were found among subjects with 1 + additional codes occurring in the 12 months following the initial code. There was no case-finding algorithm for NU developed given the high PPV of ICD-9 codes. For MU, the best case-finding algorithm classified people as an MU case if they had a fracture in the forearm, hand, or skull and had no visit with an NU diagnosis code in the 12-month post MU diagnosis. PPV for this MU case-finding algorithm increased to 84%.ConclusionsIdentifying NUs with its ICD-9 code is reasonable. Identifying MUs with automated data can be improved by using a case-finding algorithm that uses additional information. Further validation of the MU algorithms in different populations is needed, as well as exploration of its performance in a larger sample.     

Views of teenage children about the effects of a Parent's mobility disability

Background

Few U.S. studies have explored how children experience a parent's mobility disability and its effects on their daily lives.

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.     

Primary Prevention of Falls: Effectiveness of a Statewide Program

Objectives. We examined a population-wide program, Pennsylvania’s Healthy Steps for Older Adults (HSOA), designed to reduce the incidence of falls among older adults. Older adults completing HSOA are screened and educated regarding fall risk, and those identified as being at high risk are referred to primary care providers and home safety resources.Methods. From 2010 to 2011, older adults who completed HSOA at various senior center sites (n = 814) and a comparison group of older adults from the same sites who did not complete the program (n = 1019) were recruited and followed monthly. Although participants were not randomly allocated to study conditions, the 2 groups did not differ in fall risk at baseline or attrition. We used a telephone interactive voice response system to ascertain the number of falls that occurred each month.Results. In multivariate models, adjusted fall incidence rate ratios (IRRs) were lower in the HSOA group than in the comparison group for both total (IRR = 0.83; 95% confidence interval [CI] = 0.72, 0.96) and activity-adjusted (IRR = 0.81; 95% CI = 0.70, 0.93) months of follow-up.Conclusions. Use of existing aging services in primary prevention of falls is feasible, resulting in a 17% reduction in our sample in the rate of falls over the follow-up period.The public health significance of falls among older adults is clear. As noted by the National Council on Aging,

falls are the leading cause of injury related deaths of older adults, the primary reason for older adult injury emergency department visits, and the most common cause of hospital admissions for trauma.1

In 2011, the rate of nonfatal fall injuries requiring emergency department care was 2301 per 100 000 among people aged 50 to 54 years but 14 159 per 100 000 among people 85 years or older.2Self-report measures from health surveys confirm that there is a high prevalence of falls (30%–40%) among people 65 years or older and that the prevalence increases with age (40%–50% among those 80 years or older), as does the inability to get up from falls.3,4 Even noninjurious falls are disabling in that they are associated with activity restriction, isolation, deconditioning, and depression.5–8 In 2005, medical care costs associated with falls in the United States among people 50 years or older totaled about $13.5 billion (including deaths, hospital care, and emergency department admissions).2 A challenge for public health is to decrease the risk of falls without encouraging reduced physical activity, which carries other risks.Risk factors for falls include sedative use, cognitive impairment, lower extremity weakness, poor reflexes, balance and gait abnormalities, foot problems, and environmental hazards.9,10 Community-level efforts have adapted clinical interventions in addressing such risk factors. A review of 5 prospective but nonrandomized community trials involving matched control communities suggested that fall-related fractures could potentially be reduced by 6% to 33%,11 and meta-analyses and systematic reviews provide support for the effectiveness of multifactorial assessments and management of fall risk.12 The Centers for Disease Control and Prevention (CDC) has compiled a compendium of successful interventions that can be used by public health practitioners and community-based organizations.13,14Recommendations for optimal means of preventing falls are still evolving.15,16 A Cochrane review reported that exercise and home safety programs reduce the rate of falls and risk of falling but did not reveal any benefits of interventions that increase knowledge regarding fall prevention without additional components.3Pennsylvania’s Department of Aging has opted for a hybrid program in which older adults can take advantage of an intervention that offers, within the current aging service infrastructure, risk screening for falls and education regarding prevention. This voluntary program, Healthy Steps for Older Adults (HSOA), is available to all adults 50 years or older. Those identified as having a high risk for falls are referred to primary care providers and encouraged to complete home safety assessments. Because it relies on referrals to physician care rather than direct clinical interventions, the program may be less effective among people at high risk for falls; however, it is scalable across the state and reaches large numbers of people. In the case of some public health challenges, such a strategy may be more effective than more intensive interventions targeting high-risk individuals.17There is a lack of evidence regarding the effectiveness of this short-term, low-cost, population-wide program in reducing the incidence of falls among its participants, however. Here we report the results of a statewide evaluation of HSOA, which uses the state’s network of providers of aging services in its primary prevention efforts.     

Preliminary characterization of ribosomes of Entamoeba invadens

The ribosomes of Entamoeba invadens trophozoites have sedimentation coefficients of 77, 53 and 36 S. Most of the ribosomal proteins are basic and their one- and two-dimensional electrophoretic patterns differ from the corresponding patterns of Escherichia coli and Saccharomyces cerevisiae. Two dozen bands were observed in the 10 000 to 100 000 molecular weight range following sodium dodecylsulfate-gel electrophoresis of amoebal ribosomal proteins. Long, thin pronase-sensitive structures were seen in electron micrographs of E. invadens ribosomal preparations.