Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion

The CD11b/CD18 integrin plays a crucial role in cell-cell adhesion processes. Recently, we described a case of severe neonatal alloimmune neutropenia (NAIN) caused by an alloantibody against a variant of the CD11b subunit (Mart alloantigen). Allele-specific transfected cells allowed us to demonstrate that an H61R point mutation is directly responsible for the formation of Mart epitopes. No difference in the adhesion capability between H61 and R61 homozygous neutrophils was observed. Functional analysis showed that anti-Mart inhibited Mac-1-dependent adhesion of neutrophils and monocytic U937 cells to fibrinogen, intercellular adhesion molecule-1 (ICAM-1), receptor for advanced glycation end product (RAGE), and glycoprotein Ibalpha but not to junctional adhesion molecule-C or urokinase plasminogen activator receptor (uPAR). Accordingly, anti-Mart blocked neutrophil and U937 cell adhesion to endothelial cells and platelet-leukocyte aggregate formation in whole blood under high shear. Other sera of anti-Mart from mothers of infants without NAIN did not show inhibitory properties. We conclude that anti-Mart antibodies with different functional properties exist. This is supported by our findings that anti-Mart antibodies have different abilities to inhibit cell-cell adhesion, to enhance the respiratory burst of neutrophils, and to recognize different epitopes at the N-terminal region of CD11b. In conclusion, some anti-Mart alloantibodies interfere with Mac-1-dependent cellular functions of neutrophils, cause NAIN, and may be used as tools for studying Mac-1-dependent functions.     

Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells

Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. beta1 and beta2 integrins play a crucial role for progenitor cell homing to ischemic tissues. Integrin activity is regulated by chemokines and their respective G protein-coupled receptors. The phosphatidylinositol-3-kinase catalytic subunit gamma (PI3Kgamma) is the PI3K isoform that selectively transduces signals from G protein-coupled receptors. Here, we investigated the role of PI3Kgamma as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3Kgamma inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell-derived factor (SDF)1alpha-induced transmigration of human EPCs. Moreover, the PI3Kgamma inhibitor significantly reduced SDF1alpha-induced adhesion of EPCs to intercellular adhesion molecule-1 and human umbilical vein endothelial cell monolayers. These findings were corroborated with Lin(-) bone marrow-derived progenitor cells from PI3Kgamma-deficient mice that displayed reduced SDF1alpha-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kgamma reduced SDF1alpha-induced integrin activation in human EPCs and in murine Lin(-) BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kgamma-deficient Lin(-) progenitor cells to ischemic muscles after intravenous infusion in the model of hindlimb ischemia and their neovascularization-promoting capacity was reduced as compared with wild-type cells. In conclusion, PI3Kgamma is integral to the integrin-dependent homing of progenitor cells.     

Self-Care Behaviors of Adults with Type 2 Diabetes Mellitus in Greece

The purpose of this study was to examine self-care behaviors of adults with type 2 diabetes mellitus living in the Metropolitan Area of Thessaloniki in Northern Greece. The Summary of Diabetes Self-Care behaviors measurement was administered to 215 patients, out of which 177 were eligible to participate (87 males). Patients, aged 30 years or more, were recruited through a university hospital day-clinic. Older patients (>65 years), as well as those with “higher educational level” did not distribute their daily carbohydrate intake equally. Nevertheless, they were more likely to adapt to their physician’s recommendations regarding medication and to regularly perform suggested blood glucose checking. Exercise patterns were more often found for higher educated, earlier diagnosed males. Younger patients were less likely to follow their healthcare professional’s recommendations, regarding diet, medication intake, blood glucose checking, foot care and exercise compared to older patients. These results pose a higher risk for complications and morbidity in younger patients with type 2 diabetes mellitus, who most possibly will require intensive treatment in the future.     

The Christian Orthodox Church Fasting Diet Is Associated with Lower Levels of Depression and Anxiety and a Better Cognitive Performance in Middle Life

Lifestyle choices significantly influence mental health in later life. In this study we investigated the effects of the Christian Orthodox Church (COC) fasting diet, which includes long-term regular abstinence from animal-based products for half the calendar year, on cognitive function and emotional wellbeing of healthy adults. Two groups of fasting and non-fasting individuals were evaluated regarding their cognitive performance and the presence of anxiety and depression using the Mini Mental Examination Scale, the Hamilton Anxiety Scale, and the Geriatric Depression Scale (GDS), respectively. Data on physical activity, smoking, and vitamin levels were collected and correlated with mental health scoring. Negative binomial regression was performed to examine differences in the GDS scores between the two groups. Significantly lower levels of anxiety (7.48 ± 4.98 vs. 9.71 ± 5.25; p < 0.001) and depression (2.24 ± 1.77 vs. 3.5 ± 2.52; p < 0.001), along with better cognitive function (29.15 ± 0.79 vs. 28.64 ± 1.27; p < 0.001), were noticed in fasting compared to non-fasting individuals. GDS score was 31% lower (Incidence Rate Ratio: 0.69, 95% Confidence Interval: 0.56–0.85) in the fasting group compared to the control, while vitamin and ferrum levels did not differ. The COC fasting diet was found to have an independent positive impact on cognition and mood in middle-aged and elderly individuals.     

Invasive pneumococcal disease among children in Victoria.

This study analysed notification data from the first year of enhanced surveillance of invasive pneumococcal disease (IPD) in Victoria (1 July 2001 - 30 June 2002), with a focus on risk factors for infection and vaccination status among children under five years of age. Overall, there were 397 notifications (8.2 per 100,000 population), 131 (33%) were children under five years of age. The highest notification rates were among those aged less than two years (72.6 per 100,000 population). Among children aged less than five years: bacteraemia without a primary focus of infection was the most common clinical presentation (64%); 89 per cent were hospitalised with the median length of stay being three days; four children (3%) died. There were 107 cases of a known serotype, 92% (n = 98) were either in or closely related to those included in the 7-valent conjugate pneumococcal vaccine (7vPCV). Most cases (98%) were not eligible for free 7vPCV under the currently funded program in Victoria. Only one child had been vaccinated. The results from the first year of enhanced IPD surveillance in Victoria suggest consideration should be given to extending the publicly funded program to include all children under two years of age.