Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies

The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts 相似文献   

Neonatal lupus erythematosus: 4 cases and clinical review

Neonatal lupus erythematosus (NLE) is an infrequent disease in newborns caused by the transplacental passage of maternal Anti-Ro/SSA, Anti-La/SSB and/or Anti-U1 RNP antibodies. The most common manifestations are cutaneous and cardiac. We carried out a retrospective study of cases of NLE diagnosed in the last 10 years at the Hospital Universitario Insular in Gran Canaria. Complete data was obtained for 4 patients. Three cases had circulating Anti-Ro antibodies in the mother and in the newborns, while in the fourth case they were Anti-RNP. Two mothers were diagnosed with systemic lupus, one with mixed connective tissue disease and the other with leucocytoclastic vasculitis. The skin lesions consisted of urticaria-like and desquamative lesions. One patient presented with ulceration. The histological study of the urticaria-like lesions showed a non-specific perivascular infiltrate; the desquamative lesions were consistent with subacute lupus erythematosus.     

Development of Junctions During Differentiation of Lens Fibers

Throughout the differentiation of eye lens epithelium into fibers, an extensive system of intercellular junctions develops. The junctional assembly is initially characterized by the accumulation of 9.0-nm intramembranous particles, forming linear rows in the matching plasma membranes of adjoining fibers. At the final stage of the fiber differentiation, the junctional particles are assembled in geometrically packed arrays. The formation of linear rows and bidimensional lattices of intramembranous particles probably favors reciprocal recognition of cell surfaces and specific cell-to-cell interlocking. Moreover, the existence of a rather rigid lipid core of the plasma membrane of eye lens fiber may promote the clustered distribution of intramembranous particles and facilitate the junctional assembly.     

New Approach for Using of Mentha longifolia L. and Citrus reticulata L. Essential Oils as Wood-Biofungicides: GC-MS,SEM, and MNDO Quantum Chemical Studies

Background: Fungi growing on wood cause deterioration of stored food materials or discoloration of the wood itself, and the search for new and safe bioagents is recently needed. Methods: Essential oils (EOs) from aerial parts from Mentha longifolia L. and Citrus reticulata L., analyzed by gas chromatography-mass spectrometry (GC-MS), were tested for their antifungal activity by the vapor method against four common fungi, Aspergillus flavus, A. niger, A. fumigatus, and Fusarium culmorum, and confirmed by SEM examination as the oils applied on wood samples. Results: The most abundant compounds identified in the EO from M. longifolia were menthone and eucalyptol; in C. reticulata EO, they were β-caryophyllene, β-caryophyllene oxide, and β-elemene. EOs from M. longifolia and C. reticulata, at 500 and 250 µL/mL, showed potent antifungal activity against A. flavus and A. fumigatus, with 100% fungal mycelial inhibition growth (FMIG). C. reticulata and M. longifolia EOs, at 125 µL/mL, observed FMIG values of 98% and 95%, respectively, against A. fumigatus. M. longifolia EO, at 500 and 250 µL/mL, showed potent activity against A. niger, with 100% FMIG. F. culmorum completely inhibited (100% FMIG) EOs from M. longifolia and C. reticulata applied at 500 µL/mL. Pinus roxburghii Sarg. Wood, treated with M. longifolia at 125 µL/mL, showed inhibition zone values of 7.33 and 21.33 mm against A. flavus and A. niger, respectively. Conclusions: Both oils possessed good wood-biofungicide activity with the vapor method, as clearly shown by the SEM examination. These activities suggest their possible use as natural wood preservatives.     

Dilemmas of the structural and biochemical organization of lens membranes during differentiation and aging

This review deals with the biogenesis of MP26 and with the problem of the structural pattern which may be formed by MP26 during differentiation and aging of the lens fibers and as a consequence of the extraction or degradation of other membrane components. The data reported here imply that the MP26 biosynthesis is one of the key steps of cell surface domain formation during terminal differentiation of lens fibers. One striking observation involves the bidimensional long and short range distribution of MP26 copies within the lipid matrix. The protein oligomers may form, in the plane of the membrane, either a geometrical lattice or randomly distributed particle arrays. However, the mechanism controlling the assembly of either one of these patterns and eventually the transition of one into the other, is still unknown. We speculate that the formation of various membrane domains can be depicted as a self-assembly of repeating identical or quasi equivalently related protein subunits, but this process appears to be dependent both on the lipid environment and on interaction of the transmembrane protein oligomers with other membrane or cytoskeletal components, in particular crystalline polypeptides and cytoskeleton constituents. Finally, during the aging process, the post translational modification of MP26 and eventually the variation of the spatial arrangement and composition of the lipids may implicate the predominant lattice arrangement of the lipid and protein phases.     

Modulation of the specific allergic response by mite allergens encapsulated into liposomes

Liposomes are non toxic and biodegradable lipid vesicles, which are safe and effective adjuvants to induce Th1-skewed immune response. Therefore, the encapsulation of allergens into liposomes could be an attractive alternative for specific allergy immunotherapy. Previously, we obtained DPPC iposomes encapsulating purified allergens from Dermatophagoides siboney, with suitable stability and extremely reduced allergenicity. In this study, Balb/c mice were immunized with allergens ncapsulated into liposomes (LP) and the induced immune response was evaluated in comparison with allergens dissolved in PBS (PBSA) or adsorbed in Alum (AL). The use of Alum or Liposomes induced a strong allergen specific IgG response. However, total IgE serum levels in the AL group were very high, while levels found in LP group were not significantly different from the control group receiving only PBS. The IgG2a/IgG1 subclass ratio was raised in the LP group. Allergen specific IgE, as measured by PCA assay, was similar for LP and PBSA groups, and approximately the half of the reaction size found in AL group. After allergen challenge by inhalation route, peripheral blood and airway eosinophil counts increased significantly in AL, but not in LP group. Additionally, histopathological analysis of lung tissue sections obtained from challenged mice indicated a reduced cellular infiltration in mice immunized with liposomes. These results support the potential use of liposomal formulations for allergen vaccines.     

Is serum amyloid A an endogenous TLR4 agonist?

Serum amyloid A (SAA), a classical acute-phase protein, is produced predominantly by hepatocytes in response to injury, infection, and inflammation. It has been shown that SAA primes leukocytes and induces the expression and release of proinflammatory cytokines. Here, we report that SAA induces NO production by murine peritoneal macrophages. Using specific inhibitors, we showed that NO production was dependent on inducible NO synthase thorough the activation of ERK1/2 and p38 MAPKs. Moreover, SAA activity was decreased after proteolysis but not with polymyxin B, a lipid A antagonist. Finally, we found that NO production was dependent on functional TLR4, a receptor complex associated with innate immunity. Macrophages from C3H/HeJ and C57BL/10ScCr mice lacking a functional TLR4 did not respond to SAA stimulation. In conclusion, our study makes a novel observation that SAA might be an endogenous agonist for the TLR4 complex on macrophages. The contribution of this finding in amplifying innate immunity during the inflammatory process is discussed.     

Diastolic Function in Paced Children with Cardiac Defects: Septum vs Apex

In children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial.The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects.Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow‑up of 4.9 years.Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 ± 9.19 vs 83 ± 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E´ wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R²= 0.9849, p ≤ 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function.Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function.     

Differentiation of mesenchymal stem cells in chitosan scaffolds with double micro and macroporosity

Bone Marrow mesenchymal stem cells can be induced to differentiate into osteoblasts to regenerate damaged bone tissue using tissue engineering techniques. In this study, we examine the use of chitosan scaffolds with double pore structure prepared by an innovative method that combines freeze gelation (that produces micropores) and particle leaching out technique (that produces interconnected spherical macropores) seeking to enhance the osteogenic differentiation of goat bone marrow stromal cells (GBMSCs). The double pore architecture of the scaffold was characterized by scanning electron microscopy (SEM), microcomputed tomography and confocal laser scanning microscopy. The obtained hierarchical pore structure allowed very efficient seeding of GBMSCs that are able to occupy the whole volume of the scaffold, showing good adhesion and proliferation. GBMSCs were differentiated into osteoblasts as indicated by alkaline phosphatase activity and osteocalcin expression. The results of this study demonstrate that chitosan scaffold may be promising biomaterial for bone regeneration.