Genetically regulated human (T,G)-AL specific helper T cell replacing factors possess HLA-DR and Vh determinants

Human (T,G)-AL specific T cell helper factors secreted by in vitro activated peripheral blood lymphocytes of normal donors were characterized. Factors were passed through columns of Sepharose coupled either to antibodies against human immunoglobulin or antibodies against the variable region of the heavy (V_h) and light (V_l) chains of human immunoglobulin. In addition, the same factors were applied to columns of Sepharose coupled to anti-HLA-DR antibodies or to monoclonal antibodies against human Ia or β₂-microglobulin. The activity of the antigen specific factors was removed by the anti-V_h antibodies and not by anti-V_l or anti-human immunoglobulin antibodies. The factors passed through Sepharose coupled to anti-DR antibodies could be removed and eluted from columns of anti-DR antibodies relevant to the donors' DR antigens. The same factors were also removed by a monoclonal antibody (anti-Ia) which recognizes a monomorphic determinant on HLA-DR, but not by monoclonal anti-β₂-microglobulin. The results suggest that the genetically regulated (T,G)-AL specific helper factors possess HLA-DR as well as V_h determinants in their active moiety.     

Involvement of the Pta-AckA pathway in protein folding and aggregation

Acetyl phosphate is a central metabolite involved in a broad range of versatile cellular functions. Recently it was observed that in Escherichia coli the acetyl phosphate pathway is required for efficient ATP-dependent proteolysis. Deletion of the operon coding for acetyl phosphate metabolism (ΔackApta) results in a very low cytoplasmic level of acetyl phosphate and impaired proteolysis. Here we show that the ΔackApta mutation affects additional components of the protein quality control system. Thus, this deletion is accompanied by a decrease in protein refolding and rescue from aggregates. These results indicate the involvement of the acetyl phosphate pathway in chaperone capabilities, in addition to their effect on proteolysis.     

Polystyrene‐block‐Polyisoprene Diblock‐Copolymer Micelles: Coupled Pressure and Temperature Effects

The structural changes of diblock‐copolymer micelles under pressures from 200 to 16 000 psi are investigated using small‐angle neutron scattering (SANS). Asymmetric polystyrene‐block‐polyisoprene (PS–PI) diblock copolymers are dissolved in decane, a selective solvent for PI, to form spherical micelles with a core of PS and a corona of PI. The micellar solutions are put under pressure at temperatures of 25 to 60 °C. At room temperature, elevating the pressure from 200 to 16 000 psi has no effect on the size of the micelles. While the micellar solutions remain stable, instantaneous association of micelles is detected. In contrast to micelles at atmospheric pressure, increasing the temperature at elevated pressures does not lead to dissociation of micelles; instead, the micelles aggregate and evolve into sheet‐like structures, reminiscent of a macroscopic phase separation. Furthermore, higher pressures lead to a smaller temperature range in which shape transitions take place.

     

Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: Risk stratified approach with a long-term follow-up

The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post‐transplant graft‐versus‐host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1–134), 32 patients are alive. 97% engrafted. 5‐year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant‐related mortality (TRM) was 13%. Twenty‐four patients received DLI for residual disease. Acute GvHD, mostly Grades I‐II, occurred in 18% of patients post‐transplant and in 24% of patients receiving DLI. In conclusion, the risk‐adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long‐term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

Steroid‐responsive,progressive, focal measles virus brain infection

Chronic measles virus infection of the brain causes subacute sclerosing panencephalitis (SSPE), a progressive, relentless fatal disorder. We report a 52‐year‐old male who developed focal, chronic persistent measles virus infection of the brain following interferon and ribavirin therapy for hepatitis C, and who responded to steroid therapy. This case, diametrically different from SSPE, has 2 unique features, its focal nature and its permissive response to steroids, that may add to the understanding of the pathogenesis of SSPE and the mechanism enabling viruses to evade the immune response and establish persistent brain infection. Ann Neurol 2014;75:967–970     

Tc-99m sestamibi bone marrow scintigraphy in Gaucher disease

PURPOSE: No imaging technique has been found to be adequate to assess the severity and extent of bone involvement in patients with Gaucher disease. Marrow involvement, as determined by Tc-99m sulfur colloid, correlated well with the clinical and radiologic changes of the skeleton, but a normal pattern was found in the early stages of the disease. Subsequently, Tc-99m sestamibi (MIBI) has been suggested for direct visualization of glycolipid deposits in the bone marrow. This study was initiated as a pilot using MIBI to detect various forms of bone disease in patients with Gaucher disease of varying severity. MATERIALS AND METHODS: Eleven patients (9 men; median age, 39.9; age range, 21 to 61 years) were evaluated. The clinical severity of disease was scored at presentation, and four patients with moderate to severe disease were treated with enzyme replacement therapy. Each patient underwent a radiographic skeletal survey, bone densitometry, and MIBI scintigraphy. The scan included static images of the lower limbs, with a whole-body scan acquired between the early and late acquisition. Tracer uptake in the bone marrow was graded and correlated with clinical and objective variables. RESULTS: All but one patient had increased MIBI uptake in the bone marrow. No correlation was noted between MIBI uptake and severity score, radiographic changes, densitometry z score, or treatment status. CONCLUSIONS: MIBI scanning is a sensitive technique for detecting bone marrow deposits in Gaucher disease, but it is inadequate for early identification of patients at high risk for skeletal complications or for the follow-up of patients treated with enzyme replacement.     

Genome Scans for Q1 and Q2 on General Population Replicates Using Loki

The Markov Chain Monte Carlo linkage package Loki was used to perform a genome scan under realistic conditions (using a 10‐cM marker map without marker data on unsampled individuals, analyzing each chromosome separately, and without knowing the answers) for traits Q1 and Q2 on general population replicate 1. Using this approach we detected and correctly localized MG1 for Q1 and MG3 for Q2. We then repeated the analyses on replicate 1 and the “best replicate” (42) adding more information (using marker data on everyone, fitting a polygenic effect, and analyzing multiple chromosomes jointly) to see the effect on the detection of trait loci. We found that adding more data often improves the quality of the linkage signal, and reduces the false positive rate, but did not allow the detection of trait loci missed by the initial analysis. We also investigated the convergence of the sampler by repeating one multi‐chromosome analysis six times with different random number seeds. We concluded that a strategy of performing a single chromosome scan using a moderate number of sampling iterations, followed by a multi‐chromosome analysis of all chromosomes with linkage signals detected in the first scan using a longer sampling run, was an effective way of performing a genome scan on this data set. © 2001 Wiley‐Liss, Inc.