Platelet Transfusion Induces Alloimmunization to D and Non-D Rhesus Antigens.

BACKGROUND: Platelet concentrates (PC) contain residual contaminating red blood cells (RBC), being higher in pooled buffy coat PC (BC-PC) than in apheresis units (AP-PC). Data about PC-induced alloimmunization against non-D Rhesus (Rh) antigens are limited. METHODS: For all newly detected RhD and non-D alloantibodies between August 2015 and September /2017 we prospectively evaluated if they were triggered through PC by analyzing for incompatible RBC and/or PC transfusions. RESULTS: We found 5,799 positive results in 89,190 antibody screening tests. We identified 13 newly detectable Rh antibodies through incompatible PCs in 11 patients: 6× anti-D, 4× anti-E, 2× anti-c, 1× anti-f. They received a total of 156 PC (83 BC-PC; 73 AP-PC): 5 patients received incompatible BC-PC only, 1 patient received incompatible AP-PC only, 5 patients received incompatible BC-PC and AP-PC. Quality control showed a mean (range) of 0.304 (0.152-1.662) and 0.014 (0.003-0.080) × 109 RBC/l for BC-PC and AP-PC, respectively. Ten of the 11 patients received RBC transfusions, all of them being antigen-negative for the alloantibodies identified. CONCLUSIONS: PC transfusions may not only induce RhD alloimmunization, but also immunization against further Rh antigens such as c, E, and f. The risk seems higher for BC-PC than for AP-PC. The results may have impact on future recommendations of PC transfusion with respect to Rh compatibility and upper limits of RBC contamination.

Time-resolved X-ray diffraction reveals the hidden mechanism of high piezoelectric activity in a uniaxial ferroelectric.

High piezoelectric activity of many ferroelectrics has been the focus of numerous recent studies. The structural origin of this activity remains poorly understood due to a lack of appropriate experimental techniques and mixing of different mechanisms related to ferroelectricity and ferroelasticity. Our work reports on the study of a uniaxial Sr_{0.5}Ba_{0.5}Nb_{2}O_{6} ferroelectric where the formation of regions with different spontaneous strains is ruled out by the symmetry and where the interrelation between piezoelectricity and ferroelectricity can be inspected in an isolated fashion. We performed x-ray diffraction experiments on a single crystalline sample under alternating electric field and observed an unknown hidden-in-the-bulk mechanism, which suggests that the highest piezoelectric activity is realized in the volumes where nucleation of small ferroelectric domains takes place. This new mechanism creates a novel roadmap for designing materials with enhanced piezoelectric properties.

Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer.

BACKGROUND AND PURPOSE: Pancreatic cancer is a highly aggressive malignancy, and improvement in systemic therapy is necessary to treat this frequently encountered metastatic disease. The current targeted agents used in combination with gemcitabine improved objective response rates, but with little or no improvements in survival and also increased toxicities in pancreatic cancer patients. Recently, we showed that the triterpenoid cucurbitacin B inhibited tumour growth in pancreatic cancer cells by inhibition of the JAK/STAT pathway, and synergistically increased antiproliferative effects of gemcitabine in vitro. EXPERIMENTAL APPROACH: The anti-tumour effects and toxicities of cucurbitacin B in combination with gemcitabine were tested against human pancreatic cancer cells in a murine xenograft model. KEY RESULTS: Combined therapy with cucurbitacin B and gemcitabine at relatively low doses (0.5 mg x kg(-1) and 25 mg x kg(-1) respectively) resulted in highly significant tumour growth inhibition of pancreatic cancer xenografts (up to 79%). Remarkably, this therapy was well tolerated by the animals, as shown by histology of visceral organs, analysis of serum chemistry, full blood counts and bone marrow colony numbers. Western blot analysis of the tumour samples of mice who received both cucurbitacin B and gemcitabine, revealed stronger inhibition of Bcl-XL, Bcl-2 and c-myc, and higher activation of the caspase cascades, than mice treated with either agent alone. CONCLUSIONS AND IMPLICATIONS: Combination of cucurbitacin B and gemcitabine had profound anti-proliferative effects in vivo against xenografts of human pancreatic cancer cells, without any significant signs of toxicity. This promising combination should be examined in therapeutic trials of pancreatic cancer.

McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement.

BACKGROUND: The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with hematologic, neuromuscular, and central nervous system (CNS) manifestations. All carriers of the McLeod blood group phenotype examined so far had at least subclinical signs of systemic involvement. STUDY DESIGN AND METHODS: Evaluation of two brothers carrying the McLeod phenotype with neurologic examination, immunohematology, RBC membrane protein Western blotting, analysis of XK DNA sequence and RNA levels, muscle histology including XK/Kell immunohistochemistry, cerebral magnetic resonance imaging (MRI), and quantified positron emission tomography (PET). RESULTS: Immunohematology and Western blotting confirmed presence of the McLeod blood group phenotype. No acanthocytosis or other hematologic anomalies were found. XK gene sequence analysis revealed a missense mutation in exon 3 (E327K). WBC XK RNA levels were not decreased. There were no neuromuscular and CNS signs or symptoms. In addition, no subclinical involvement was discovered on the basis of normal muscle histology with a physiologic pattern of XK and Kell immunohistochemistry, normal cerebral MRI, and quantified PET. CONCLUSION: Known disease-causing XK gene mutations comprised deletions, nonsense, or splice-site mutations predicting absent or truncated XK protein devoid of the Kell-protein binding site. Although the E327K missense mutation was associated with the immunohematologic characteristics of McLeod syndrome, the mutated XK protein seemed to be largely functional. These findings contribute to the understanding of the physiology of XK and Kell proteins, and the pathogenetic mechanisms of acanthocytosis, myopathy, and striatal neurodegeneration in McLeod syndrome.