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.     

A radioreceptor assay for quantitating plasma factor VIII/von Willebrand's protein

A sensitive and precise radioreceptor assay for determining plasma levels of human factor VIII/von Willebrand's factor (FVIII/vWF) has been developed by taking advantage of the FVIII/vWF receptor sites on human platelets. Paraformaldehyde-fixed platelets, which were processed and then stored, retained FVIII/vWF binding activity and therefore could be used as a convenient source of receptors. The human plasma samples to be tested were initially filtered on 4% agarose columns to concentrate the FVIII/vWF protein in the void volume and to remove the factor(s) that interferes with the assay. The percent recovery of FVIII/vWF in the pooled eluent was measured by the recovery of added trace 125I-FVIII/vWF. The coefficients of intra- and interassay variation were 6% and 10%, respectively. The plasma FVIII/vWF concentrations determined by the assay for pooled normal plasma, hemophilia A plasma, and plasmas from two patients with von Willebrand's disease were 16.3 +/- 0.5, 52.6 +/- 1.5, 6.8 +/- 0.8, and 3.2 +/- 0.2 microgram/ml, respectively. The range of plasma FVIII/vWF concentrations varied between 8.3 microgram/ml and 24.9 microgram/ml for 10 normal adults. The plasma FVIII/vWF concentrations determined by the radioreceptor assay correlated well with levels measured by the ristocetin-induced platelet aggregation method, thus demonstrating the functional relevancy of the radioreceptor assay for plasma FVIII/vWF.     

Separate impact of metabolic syndrome and altered glucose tolerance on early markers of vascular injuries

ObjectiveWe investigated the separate impact of metabolic syndrome (MS) and altered glucose tolerance on early markers of vascular injuries.MethodsIntima-media thickness (IMT) and Pulse Wave Analysis (PWA), were evaluated in 132 overweight or obese subjects, with (MS⁺) or without (MS^?) MS; subjects were further classified as normotolerant (NT) or with altered glucose tolerance (AGT) according to a 2 h oral glucose tolerance test (OGTT).ResultsIn MS⁺ patients, IMT was higher than in the MS^? group, and PWA revealed higher Augmentation Pressure (Aug, the contribution that wave reflection makes to systolic arterial pressure) and lower subendocardial viability ratio (SEVR, an estimate of myocardial perfusion). When analyzed according to glucose tolerance, IMT was higher in MS⁺NT subjects and AGT patients with and without MS, vs. MS^?NT subjects. Logistic regression modeling showed that both AGT and MS were independently associated with increased IMT. However, only MS remained associated with IMT after adjustment for age. SEVR was reduced only in MS⁺ patients, independently of glucose tolerance. In both groups, Aug and AugI were higher in the AGT group, but the correlation with 2 h-plasma glucose disappeared when corrected for age.ConclusionBoth MS and AGT altered IMT, but the effect of AGT disappears when age is added to the multiple regression model. In contrast, arterial stiffness was affected differently in the two categories: in subjects with MS, the subendocardial viability ratio (an estimate of myocardial perfusion) was impaired, while in subjects with AGT, both Aug and AugI were increased. These data suggest that applying the definition of MS might help to better characterize cardiovascular risk in subjects with altered glucose tolerance or obesity.     

Cystic echinococcosis in sheep in Sardinia. Changing pattern and present status

The epidemiological status of cystic echinococcosis (CE) in sheep in Sardinia over the 20 years since the last control attempt at the end of the 1980s has been assessed, comparing the results of two surveys carried out in abattoirs in southern Sardinia. In the first, conducted in 1995-1997 (5-7 years after the last control effort), CE prevalence of about 75% was observed in the 1375 sheep sampled, with intensity of 10.0 and mean abundance of 7.5. The most affected organ was the liver, whereas a large percentage of infected animals presented cysts in both the liver and lung. Overall, about 26% of parasitized sheep were found to be heavily infected and 12.15% of infected animals harboured fertile cysts. In the second survey, carried out ten years after the first, during the period 2005-2010 in absence of specific control measures, a total of 1414 sheep were examined. CE prevalence was 65%, 78% in the most rural Oristano province and 58% in the most "urbanised" province of Cagliari. Frequency of sheep infected in both the liver and lung had decreased slightly compared to the first survey, particularly in the Cagliari province, as had intensity and mean abundance, though to a lesser extent in the Oristano province. 14.6% of parasitized sheep were heavily infected, showing a general decline over the 10 years between the two surveys, particularly in the Cagliari area where the figure had more than halved. Conversely, about 14% of infected sheep hosted at least 1 fertile cyst, a slight increase compared to the 1st survey. Finally, the trend of CE transmission in Sardinian sheep according to surveys carried out from 1952 to 2010 has been analysed and the results are discussed in the light of the significant socio-economic and structural transformations that have actually modified the zoonosis scenario on the island.