Specific Tolerance Research Articles

A new approach to predict the flexibility and precision of manufacturing systems using geometric constraints and small displacement torsors

Cost and quality of a product are prime drivers in manufacturing. It is important to optimize these variables for maximum benefit. It is to be noted that higher quality means a product which has fewer errors. The quality of product is associated with the precision of the manufacturing system but machines to produce such products are expensive. Therefore, a method of machine selection is devised based on tolerance range. In this study, mathematical formulation is developed for parallelism and perpendicularity constraints of a surface using the concept of torsors. Torsors represent any feature (plane, cylinder, point, etc.) only in terms of its degree of freedom. Torsors also have the advantage of being added during tolerance stack-up. Mathematical equations are developed for parallelism and perpendicularity as the function of surface parameters i.e. surface angles. Alternatively, the developed model can be used to control surface parameters to obtain the required tolerances. Maximum and minimum values of system parameters are calculated. Assuming that the parameters of the manufactured parts follow statistical distribution, random values of the surface parameters are generated and compared with the parallelism and perpendicularity constraints. It is concluded that the behavior of parallelism and perpendicularity tolerances is more precise if we control individual parameters. The results are in compliance with the proposed idea that a less precise machine can produce high quality product within a specific tolerance range as the machine need not control parallelism but only the dependent variables.

Multiscale dimensional tolerance specifications established on shrinkage assessment in ceramic micro injection molding

Taking advantage of a micro powder injection molding production of a critical functional component in a miniaturized mechanism, a method for the formulation of specification intervals was developed, based on the evaluation of the shrinkage.The synthesis allows to allocate tolerance intervals according to a desired risk of rejecting parts in future evaluations. Such specifications are formulated as a function of the shrinkage, optimizing its impact on different features of size independently of their shapes or dimensions.The method is of general validity for any molding process where the material undergoes a change in dimensions due to a phase transformation.

An Approach to the Sensitivity Analysis in Variation Simulations considering Form Deviations

In tolerance and variation simulations, sensitivity analyses are used to assess the influences of tolerance specifications and geometrical deviations on the assembly key characteristics and to support product and process developers in deriving more suitable tolerancing decisions and in optimizing manufacturing and assembly processes. However, established methods to the sensitivity analysis in the context of variation simulations disregard important statistical dependencies, which occur when considering form deviations. To overcome these shortcomings, an approach to the density-based sensitivity analysis in variation simulations considering form deviations based on Skin Model Shapes is presented. The method is highlighted and discussed employing a typical tolerance analysis case study.

Treatment of high-strength purified terephthalic acid (PTA) wastewater using a magnetic porous ceramic support in laboratory-scale anaerobic-aerobic fluidized bed reactors

Laboratory-scale anaerobic-aerobic fluidized-bed bioreactors (FBR) with porous magnetic ceramics as support were successfully applied to treat purified terephthalic acid (PTA) wastewater. After a short 14-day start-up period, the system was stably operating. During the 40 d stable period, the system organic loading rate (OLR) increased from 6.68 to 23.87 kg chemical oxygen demand (COD)/(m3d), the effluent COD and PTA were below 90 and 30 mg/L, respectively. The FBR presented excellent COD and PTA removal efficiency with a low hydraulic retention time (HRT) value of six hours. The growth kinetic parameters suggested that the biomass in FBR possess high maximum specific growth rate (μmax = 2.22 d−1) and good tolerance to varied OLR (Ks = 258.67 mg COD/L).

Developments in research on abiotic stress responsive microRNAs of Hevea brasiliensis

Abiotic stresses such as drought and low temperature are the major environmental factors that restrict the expansion of Hevea brasiliensis (rubber tree) cultivation to non-traditional regions of India. The H. brasiliensis cultivars, which are proven superior in traditional regions, do not perform well in such regions and hence it is imperative to find/develop stress tolerant cultivars specifically for these regions. Marker assisted selection for stress tolerance is widely employed to minimize time required to develop such cultivars with desired traits. In this review, developments in abiotic stress responsive gene expression studies in Hevea with special reference to miRNA research are discussed. The recent researches in this field have revealed the nature of abiotic stress responsive miRNAs and their possible role on their corresponding target genes. These attempts indicate the possibility of employing specific stress tolerance associated miRNAs in the crop improvement programmes by the breeders to identify or develop drought/cold-tolerant cultivars of H. brasiliensis.

Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials.

Tolerogenic dendritic cells (tolDCs) have reached patients with autoimmune and inflammatory disease, at least in clinical trials. The safety of tolDCs as intervention therapy has been established, but the capacity to modulate autoimmune response in vivo remains to be demonstrated. Studies have revealed a diversity of regulatory mechanisms that tolDCs may employ in vivo. These mechanisms differ between various types of modulated tolDC. The most often foreseen action of tolDCs is through regulatory polarization of naïve T cells or activation of existing regulatory T cells, which should ultimately diminish autoimmune inflammation. Yet, selection of a target autoantigen remains critical to expedite tissue specific tolerance induction, while measuring immune modulation incited by tolDCs in vivo provides a great challenge. We will discuss the regulatory action of different types of tolDCs and the possible methods to monitor immunological efficacy endpoints for the next generation clinical trials.

Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.

Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide- co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen (Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that codelivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction. TGF-β was coupled to the surface of Ag-NPs such that the loadings of Ag and TGF-β were independently tunable. The particles demonstrated bioactive delivery of Ag and TGF-β in vitro by reducing the inflammatory phenotype of bone marrow-derived dendritic cells and inducing regulatory T cells in a coculture system. Using an in vivo mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis, TGF-β codelivery on Ag-NPs resulted in improved efficacy at lower doses by i.v. administration and significantly reduced disease severity by s.c. administration. This study demonstrates that the codelivery of immunomodulatory cytokines on Ag-NPs may enhance the efficacy of Ag-specific tolerance therapies by programming Ag presenting cells for more efficient tolerance induction.

Genome resequencing and transcriptome profiling reveal structural diversity and expression patterns of constitutive disease resistance genes in Huanglongbing-tolerant Poncirus trifoliata and its hybrids

Huanglongbing (HLB) is the most destructive bacterial disease of citrus worldwide. While most citrus varieties are susceptible to HLB, Poncirus trifoliata, a close relative of Citrus, and some of its hybrids with Citrus are tolerant to HLB. No specific HLB tolerance genes have been identified in P. trifoliata but recent studies have shown that constitutive disease resistance (CDR) genes were expressed at much higher levels in HLB-tolerant Poncirus hybrids and the expression of CDR genes was modulated by Candidatus Liberibacter asiaticus (CLas), the pathogen of HLB. The current study was undertaken to mine and characterize the CDR gene family in Citrus and Poncirus and to understand its association with HLB tolerance in Poncirus. We identified 17 CDR genes in two citrus genomes, deduced their structures, and investigated their phylogenetic relationships. We revealed that the expansion of the CDR family in Citrus seems to be due to segmental and tandem duplication events. Through genome resequencing and transcriptome sequencing, we identified eight CDR genes in the Poncirus genome (PtCDR1-PtCDR8). The number of SNPs was the highest in PtCDR2 and the lowest in PtCDR7. Most of the deletion and insertion events were observed in the UTR regions of Citrus and Poncirus CDR genes. PtCDR2 and PtCDR8 were in abundance in the leaf transcriptomes of two HLB-tolerant Poncirus genotypes and were also upregulated in HLB-tolerant, Poncirus hybrids as revealed by real-time PCR analysis. These two CDR genes seem to be good candidate genes for future studies of their role in citrus-CLas interactions.

Towards an ontology-supported case-based reasoning approach for computer-aided tolerance specification

In this paper, an ontology-supported case-based reasoning approach for computer-aided tolerance specification is proposed. This approach firstly considers the past tolerance specification problems and their schemes as previous cases and the new tolerance specification problems as target cases and uses an ontology to represent previous and target cases. Then certain ontology-based similarity measure is used to assess the similarity between the toleranced features of target and previous cases, the similarity between the part features of target and previous cases, and the similarity between the topological relations of target and previous cases. Based on these similarities, an ontology-based similarity measure for computing the similarity between target and previous cases is designed, and an algorithm for establishing such similarity measure with high accuracy and retrieving similar previous cases for a target case with this similarity measure is presented. This algorithm shows how to linearly combine the similarity of toleranced features, the similarity of part features, and the similarity of topological relations to assess the similarity between target and previous cases to implement retrieval of previous cases under the prerequisite of ensuring the highest accuracy of the similarity measure. The paper also reports a prototype implementation of the proposed approach, provides an example to illustrate how the approach works, and evaluates the approach via theoretical and experimental comparisons.

Rainbow trout adaptation to a warmer Patagonia and its potential to increase temperature tolerance in cultured stocks

The viability of rainbow trout Oncorhynchus mykiss (Walbaum, 1792) culture is being challenged progressively by global warming. Previous trials with Australian and Japanese rainbow trout lines suggested that improvements in thermal performance may be possible. Here, we hypothesized that strain-related differences in physiological response to temperature exist between a north Patagonian hatchery stock (CENSALBA), a Neotropical one (Criadero Boca de Río), and a thermal stream (Valcheta) population of wild introduced rainbow trout. This was tested by comparing, at 20°C, the thermal preference, specific metabolic rate, thermal tolerance, growth, and condition on juveniles of the three strains, and on a Valcheta stream male x CENSALBA female F1 cross. Preferred temperature (PT) and loss of equilibrium temperature (LET, a measure of thermal tolerance) of Valcheta stream and F1 were significantly higher than those of CENSALBA, and the average PTs of Valcheta stream and F1 were higher than the 95% confidence interval of available reference data for rainbow trout. These results suggest that the F1, reared under standard hatchery conditions and selected by growth and thermal preference, presents higher thermal preference and higher thermal tolerance than the current CENSALBA hatchery stock. Introduction of this naturally adapted strain to hatchery stocks would likely result in the improvement of their temperature resistance to warmer waters. Current studies on adults of this F1 generation are underway.

Cyclophosphamide-induced tolerance in kidney transplantation avoids long-term immunosuppressive therapy.

There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of Tcells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation. Various factors induce tolerance that involves establishment of hematopoietic chimerism and various cell subsets. In particular, we have carried out various studies regarding the cyclophosphamide-induced tolerance system. Tolerance is induced after establishment of hematopoietic chimerism after donor bone marrow transplantation. At the clinical stage, kidney transplantation before administration of cyclophosphamide after transfusion of bone marrow to create hematopoietic chimera is considered to be one of the most successful protocols. Furthermore, recent studies have shown the involvement of multiple populations of immune cells in preserving immunological tolerance and promoting long-term renal grafts. The present review focuses on how cyclophosphamide and other immune factors induce tolerance in kidney transplantation.

Generalized trigonometric Fourier-series method with automatic time step control for non-linear point kinetics equations

The trigonometric Fourier-series method (TFS) is generalized to provide approximate solutions for non-linear point kinetics equations with feedback using varying step sizes. This method can provide a very stable solution against the size of the discrete time step allowing much larger step sizes to be used. Systems of the point kinetics equations are solved using Fourier-series expansion over a partition of the total time interval. The approximate solution requires determining the series coefficients over each time step in that partition. These coefficients are determined using the high-order derivatives of the solution vector at the beginning of the time step introducing a system of linear algebraic equations to be solved at each step. This system is similar to the Vandermonde system. Two successive orders of the partial sums are used to estimate the local truncation error. This error and some other constrains are used to produce the largest step size allowable at each step while keeping the error within a specific tolerance. The process of calculating suitable step sizes should be automatic and inexpensive. Convergence and stability of the proposed method are discussed and a new formula is introduced to maintain stability. The proposed method solves the general linear and non-linear kinetics problems. The method has been applied to five different types of reactivities including step/ramp insertions with temperature feedback. The method is seemed to be valid for larger time intervals than those used in the conventional numerical integration, and is thus useful in reducing computing time. Computational results are found to be consistent with the analysis, they demonstrate that the convergence of the iteration scheme can be accelerated and the resulting computing times can be greatly reduced while maintain computational accuracy.

Chemical elements as fingerprints of geographical origin in cultivars of Vitis vinifera L. raised on the same SO4 rootstock.

The uptake of major and trace elements in grapevine (Vitis vinifera L.) can be influenced by soil, climate, geographic origin, and rootstock type. Rootstocks were mainly selected to resist phylloxera and for specific tolerance to lime, mineral uptake, drought, and salinity. The relationship among concentrations of major, trace, and rare earth elements was studied in soil and leaves from two Italian grapevine cultivars, "Cabernet Sauvignon" and "Corvina," employed to produce renowned controlled designation of origin (DOC) wines. The cultivars were raised on the same rootstock SO4 in two different areas of the Veneto Region (Northern Italy). The elements were studied by X-ray fluorescence and inductively coupled plasma mass spectrometry, and data were elaborated by non-parametric tests and multivariate linear discrimination analysis. The related index of bioaccumulation was calculated to define the specific assimilation of the elements from soil to leaves. A statistically significant correspondence between soil and leaf samples was observed for Mg, Sm, V, and Zr. The results allowed to discriminate soil and leaf samples of the two cultivars according to geographical provenance, possibly providing geochemical markers (fingerprints) useful against fraudulent use of DOC wine labels.

In vivo antitumor activity evaluation of cancer vaccines prepared by various antigen forms in a murine hepatocellular carcinoma model.

Cancer cell vaccines with strong specificity and low tolerance have been revealed to be a promising option for oncology treatment. Various antigen forms, including tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively used in cancer vaccine preparation. However, the most effective antigen form has not yet been identified. In the present study, the antitumor efficiency of vaccines prepared by these two antigen forms was systematically investigated. Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22 hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL were administrated by subcutaneous immunization in prophylactic and therapeutic strategies. The results of the present study revealed that H22-TCL immunization induced more significant inhibition on tumor growth and metastasis compared with Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated that H22-TCL vaccine induced larger areas of continuous necrosis within tumors compared to the Fixed-H22-CELL vaccine, which was associated with the extent of tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more evident antigen-specific antibody responses compared with the Fixed-H22-CELL injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more significant T lymphocytes proliferation compared with that from Fixed-H22-CELL-treated mice. All the results indicated that whole tumor cell lysate may be a more effective antigen form in cancer vaccine preparation compared with glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific humoral and cellular immune responses resulted with a superior antitumor efficiency. This would have important clinical signification for cancer vaccine preparation and serve a role in prompting this to other researchers.

CD28 Blockade Ex Vivo Induces Alloantigen-Specific Immune Tolerance but Preserves T-Cell Pathogen Reactivity.

Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling. Treatment of human allogeneic dendritic cell/T-cell co-cultures with a human CD28 blocking antibody fragment (α-huCD28) significantly abrogated subsequent allospecific immune responses, seen by decreased T-cell proliferation and of type 1 cytokine (IFN-γ and IL-2) expression. Allo-tolerization persisted after discontinuation of CD28 blockade and secondary alloantigen stimulation, as confirmed by enhanced CTLA-4 and PD-1 immune checkpoint signaling. However, T-cells retained reactivity to pathogens, supported by clonotyping of neo-primed and cross-reactive T-cells specific for Candida albicans or third-party antigens using deep sequencing analysis. In an MHC-mismatched murine model, we tolerized C57BL/6 T-cells by ex vivo exposure to a murine single chain Fv specific for CD28 (α-muCD28). Infusion of these cells, after α-muCD28 washout, into bone marrow-transplanted BALB/c mice caused allo-tolerance and did not induce GvHD-associated hepatic pathology. We conclude that selective CD28 blockade ex vivo can allow the generation of stably allo-tolerized T-cells that in turn do not induce graft-versus-host reactions while maintaining pathogen reactivity. Hence, CD28 co-stimulation blockade of donor T-cells may be a useful therapeutic approach to support the immune system after HSCT.

Curcumin converts Foxp3+ regulatory T cells to T helper 1 cells in patients with lung cancer.

The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.

Change in the Content of Immunoproteasomes and Macrophages in Rat Liver At the Induction of DonorSpecific Tolerance

Induction of donor specific tolerance (DST) by the introduction of donor cells into a recipient's portal vein is one of the approaches used to solve the problem of transplant engraftment. However, the mechanism of DST development remains unclear to this moment. In the present work, we first studied the change in the content of immunoproteasomes and macrophages of the liver at early stages of the development of allospecific portal tolerance in rats by Western blotting and flow cytofluorimetry. On the basis of the data obtained, we can conclude that the induction of DST is an active process characterized by two phases during which the level of the proteasome immune subunits LMP2 and LMP7 in liver mononuclear cells, including Kupffer cells, and the number of Kupffer cells change. The first phase lasts up to 5 days after the beginning of DST induction; the second phase - from 5 to 14 days. In both phases, the level of the subunits LMP2 and LMP7 in the total pool of mononuclear cells and Kupffer cells increases, with maximum values on days 1 and 7. In addition, the total number of Kupffer cells increases in both phases with a shift in several days. The most noticeable changes take place in the second phase. The third day is characterized by a lower content of mononuclear cells expressing immunoproteasomes compared to the control value in native animals. Presumably, at this time point a "window of opportunity" appears for subsequent filling of an empty niche with cells of different subpopulations and, depending on this fact, the development of tolerance or rejection. The results obtained raise the new tasks of finding ways to influence the cellular composition in the liver and the expression of immunoproteasomes on the third day after the beginning of DST induction to block the development of rejection.

Synthesis and Applications of Boronate Affinity Materials: From Class Selectivity to Biomimetic Specificity.

Due to the complexity of biological systems and samples, specific capture and targeting of certain biomolecules is critical in much biological research and many applications. cis-Diol-containing biomolecules, a large family of important compounds including glycoproteins, saccharides, nucleosides, nucleotides, and so on, play essential roles in biological systems. As boronic acids can reversibly bind with cis-diols, boronate affinity materials (BAMs) have gained increasing attention in recent years. However, real-world applications of BAMs are often severely hampered by three bottleneck issues, including nonbiocompatible binding pH, weak affinity, and difficulty in selectivity manipulation. Therefore, solutions to these issues and knowledge about the factors that influence the binding properties are of significant importance. These issues have been well solved by our group in past years. Our solutions started from the synthesis and screening of boronic acid ligands with chemical moieties favorable for binding at neutral and acidic pH. To avoid tedious synthesis routes, we proposed a straightforward strategy called teamed boronate affinity, which permitted facile preparation of BAMs with strong binding at neutral pH. To enhance the affinity, we confirmed that multivalent binding could significantly enhance the affinity toward glycoproteins. More interestingly, we observed that molecular interactions could be significantly enhanced by confinement within nanoscale spaces. To improve the selectivity, we investigated interactions that govern the selectivity and their interplays. We then proposed a set of strategies for selectivity manipulation, which proved to be useful guidelines for not only the design of new BAMs but also the selection of binding conditions. Applications in metabolomic analysis, glycoproteomic analysis, and aptamer selection well demonstrated the great potential of the prepared BAMs. Molecular imprinting is an important methodology for creating affinity materials with antibody-like binding properties. Boronate affinity-based covalent imprinting is a pioneering approach in molecular imprinting, but only a few cases of successful imprinting of glycoproteins by this method were reported. With sound understanding of boronate affinity, we developed two facile and generally applicable boronate affinity-based molecular imprinting approaches. The resulting boronate affinity molecularly imprinted polymers (MIPs) exhibited dramatically improved binding properties, including biocompatible binding pH range, enhanced affinity, improved specificity, and superb tolerance to interference. In terms of nanoconfinement effect, we explained why the binding pH range was widened and why the affinity was enhanced. The excellent binding properties made boronate affinity MIPs appealing alternatives to antibodies in promising applications such as disease diagnosis, cancer-cell targeting, and single-cell analysis. In this Account, we survey the key aspects of BAMs, the efforts we made to solve these issues, and the connections between imprinted and nonimprinted BAMs. Through this survey, we wish to pave a sound fundamental basis of the dependence of binding properties of BAMs on the nature and structure of the ligands and the supporting materials, which can facilitate the development and applications of BAMs. We also briefly sketch remaining challenges and directions for future development.

Leukofiltration plus pathogen reduction prevents alloimmune platelet refractoriness in a dog transfusion model

AbstractHuman lymphocyte antigen alloimmunization to filter leukoreduced (F-LR) platelets occurs in about 18% of immunosuppressed thrombocytopenic hematology/oncology patients and represents a significant challenge for effective chemotherapy. In a dog platelet transfusion model, we have evaluated other methods of preventing alloimmune platelet refractoriness and demonstrated that successful methods in our dog model are transferable to man. In the present study, donor/recipient pairs were dog lymphocyte antigen DR-B incompatible (88% of the pairs), and recipient dogs received up to 8 weekly treated transfusions from a single donor (a highly immunogenic stimulus), or until platelet refractoriness. Continued acceptance of F-LR platelets occurred in 6 of 13 recipients (46%), but neither γ-irradiation (γ-I; 0 of 5) nor Mirasol pathogen reduction (MPR; 1 of 7) treatment of donor platelets prevented alloimmune platelet refractoriness. Combining γ-I with F-LR was associated with only 2 of 10 (20%) recipients accepting the transfused platelets. Surprisingly, F-LR platelets that then underwent MPR were accepted by 21 of 22 (95%) recipients (P < .001 vs F-LR + γ-I recipients). Furthermore, 7 of 21 (33%) of these accepting recipients demonstrated specific tolerance to 8 more weekly donor transfusions that had not been treated. In addition, platelet concentrates prepared from F-LR + MPR whole blood were also nonimmunogenic; that is, 10 of 10 (100%) recipients accepted donor platelets. Overall, 31 of 32 (97%) recipients accepted F-LR + MPR platelets; none developed antibodies to donor lymphocytes. These data are the highest rate of acceptance for platelet transfusions reported in either animals or man. This approach to platelet transfusion may be particularly important when supporting patients with intact immune systems, such as in myelodysplastic syndromes.

O164 Different patterns of dysautonomia in relapsing and progressive multiple sclerosis

Objectives To determine differences in autonomic dysfunction in patients with relapsing remitting multiple sclerosis (RMMS) and progressive forms of MS (PMS). Methods Forty RRMS (33 females,35.45 ± 9.15, median EDSS 1.25, median disease duration 923 days) and 30 PPMS (17 females, 48.03 ± 10.58, median EDSS 6.5, median disease duration 4538 days) patients were enrolled. The following autonomic tests were performed: heart rate and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing (RSA), blood pressure response to passive tilt and Quantitative Sudomotor Axon Reflex Test (QSART). All tests were interpreted in the form of the composite autonomic scoring scale (CASS). Results Median CASS was 1 (range 0 to 5) and 3 (range 0 to 6) for RRMS and PMS patients, respectively. Patients with PMS had significantly higher adrenergic, cardiovagal, sudomotor indices and total CASS compared to patients with RRMS (p = 0.029, p = 0.018, p 0.001 and p 0.001 , respectively). Disease duration positively correlated with adrenergic, cardiovagal, sudomotor indices and total CASS (rs = 0.294, p = 0.02; rs = rs = 0.275, p = 0.027; rs = 0.409, p 0.001 and rs = 0.472, p 0.001 , respectively). EDSS positively correlated with cardiovagal and sudomotor indices and total CASS (rs = 0.264, p = 0.033; rs = 0.411, p 0.001 and rs = 0.402, p = 0.001, respectively). Discussion Autonomic function is rarely investigated in MS, although it may have an impact on several important aspects like fatigue, exercise capacity and MS specific medication tolerance. Conclusion Autonomic dysfunction is more prevalent in progressive MS compared to RRMS. Significance Autonomic dysfunction in MS correlates well with the EDSS and disease duration.