Some observations on the Inb antigen and evidence that anti-Inb causes accelerated destruction of radiolabeled red cells

This report describes an example of anti-Inb, a red cell alloantibody directed against a high-frequency antigen, detected in a prenatal sample obtained from a Canadian woman of Asian Indian extraction. Although the antibody is IgG1, it could not be detected in the serum or on the red cells (RBCs) of her In(b+) infant. Evidence is provided that the Inb antigen is denatured by papain, ficin, trypsin, bromelin, cystein-activated papain/dithiothreitol, 6 percent aminoethylisothiouronium, and 50 mM dithiothreitol, but not by neuraminidase. Inb antigen strength appears reduced on the In(Lu) type but not on the LuLu type of Lu(a-b-) RBCs. RBCs from a patient with paroxysmal nocturnal hemoglobinuria showed normal Inb antigen strength as did Ko, Ge:-2,3, Ge:-2,-3, and Yt(a-) RBCs. A RBC survival study using 51Cr-labeled In(b+) RBCs showed 97 percent survival 90 minutes after injection but reduced survivals of 62 and 14 percent at 24 and 96 hours, respectively. These results indicate that this example of anti-Inb is unlikely to be implicated in an immediate hemolytic transfusion reaction, but that delayed extravascular hemolysis might occur.     

Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts [see comments]

Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.     

Prefrontal cortex white matter tracts in prodromal Huntington disease

Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large‐scale analysis using multisite diffusion‐weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT‐HD study collected imaging and neuropsychological data on gene‐positive HD participants without a clinical diagnosis (i.e., prodromal) and gene‐negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto‐occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG‐age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long‐range tracts essential for cross‐region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717–3732, 2015. © 2015 Wiley Periodicals, Inc.     

Tracking motor impairments in the progression of Huntington's disease

The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene‐expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT‐HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed. © 2013 International Parkinson and Movement Disorder Society     

苦绳的甾体成分

从苦绳(Dregea sinensis Hemsl.)中分离到两个新化合物∶苦绳甙元乙(dresigeninB,1)和苦绳甙I(dresiosideI,2)。经光谱和化学反应确定其结构为∶20-O-(2-甲基丁酰基) 托曼托甙元[20-O-(2-methylbutyryl)-tomentogenin]和二氢肉珊瑚甙元3-O-β-D-吡喃黄夹糖基(1-4)-β-D-吡喃夹竹桃糖基(1-4)-β-D-吡喃磁麻糖甙[dihydrosarcostin 3-O-β-D-thevetopyranosyl(1-4)-β-D-oleandropyranosyl(1-4)-β-D-cymaropyranoside]。