Fulminant subacute sclerosing panencephalitis in association with pregnancy

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.     

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.     

Forms of dystonia in patients with Parkinson's disease

We studied various forms of dystonia associated with Parkinson's disease (PD) in 207 patients who were on levodopa therapy for more than 1 year. Dystonia, sometimes more than one type, occurred in 63 (30%). In five patients, dystonia preceded initiation of treatment. Fifteen patients had peak-dose dystonia, 33 had early-morning dystonia, and 20 had "off-period" dystonia. The different clinical features of the dystonias are presented and compared. Findings indicate that dystonia is a frequent feature of levodopa-treated PD patients.     

The Effect of Basic Fibroblast Growth Factor on the Reversion of Omental Adipocytes from Lean and Obese Patients

Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml^-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast, basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance may contribute to the intractability of massive obesity.     

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     

Challenges of Using In Vitro Data for Modeling P-Glycoprotein Efflux in the Blood-Brain Barrier

The efficacy of central nervous system (CNS) drugs may be limited by their poor ability to cross the blood-brain barrier (BBB). Transporters, such as p-glycoprotein, may affect the distribution of many drugs into the CNS in conjunction with the restricted paracellular pathway of the BBB. It is therefore important to gain information on unbound drug concentrations in the brain in drug development to ensure sufficient drug exposure from plasma at the target site in the CNS. In vitro methods are routinely used in drug development to study passive permeability and p-glycoprotein efflux of new drugs. This review discusses the challenges in the use of in vitro data as input parameters in physiologically based pharmacokinetic (PBPK) models of CNS drug disposition of p-glycoprotein substrates. Experience with quinidine demonstrates the variability in in vitro parameters of passive permeability and active p-glycoprotein efflux. Further work is needed to generate parameter values that are independent of the model and assay. This is a prerequisite for reliable predictions of drug concentrations in the brain in vivo.