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Motor skill acquisition utilizes a wide array of neural structures; however, few articles evaluate how the relative contributions of these structures shift over the course of learning. Recent evidence from rodents and songbirds suggests there is a transfer from cortical to subcortical structures following intense, repetitive training. Evidence from humans indicate that the reticulospinal system is modulated over the course of skill acquisition and may be a subcortical facilitator of learning. The objective of this study was to evaluate how reticulospinal contributions are modulated by task expertise. Reticulospinal contributions were assessed using StartReact (SR). We hypothesized that expert typists would show SR during an individuated, keystroke task but SR would be absent in novices. Expert (75.2 ± 9.8 WPM) and novice typists (41.6 ± 8.2 WPM) were evaluated during an individuated, keystroke movements. In experts, SR was present but was absent in novices. Together, these results suggest that experts use reticulospinal contributions more for movement than novices indicating that the reticular formation becomes increasingly important for movement execution in highly trained, skilled tasks even those that require individuated movement of the fingers.

Background: Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM., Methods: Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients., Results: We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90)., Conclusions: We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

Background: Multiple myeloma (MM) and its therapies may induce a severely compromised humoral immunity. We have performed a longitudinal analysis of IgG-antibody responses against influenza virus (FLU) and tetanus toxoid (TT) as surrogate markers for the B cell-mediated immunity in MM patients., Methods: 1094 serum samples of 190 MM patients and samples from 100 healthy donors were analyzed by ELISA for FLU- and TT-specific antibodies., Results: MM patients evidenced lower levels of FLU- and TT-specific antibodies than healthy controls (P < 0.001). Immunoreactivity decreased with progressing disease and worsening clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6 months) after alloSCT (P < 0.001), a time-period during which intravenous immunoglobulin (IVIG) is routinely applied. Thereafter, antibody concentrations declined and remained suppressed for 3 years in the case of FLU-specific and for more than 5 years in the case of TT-specific antibodies., Conclusions: We found that MM is associated with a profound disease- and therapy-related immunosuppression, which is compensated for a few months after alloSCT, most likely by application of IVIG. This and the differences regarding the recovery of anti-FLU and anti-TT antibody titers during the following years need to be taken into account for optimizing IVIG application and immunization after alloSCT.

The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS). However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM). Screening 1094 peripheral blood (PB) sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2(211-230) as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients' BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT). Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n = 74). Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

Objective: Cancer-testis (CT) antigens represent attractive targets for tumor immunotherapy based on their tumor-restricted expression and immunogenicity. However, a broad picture of the expression of CT antigens and associated humoral immune responses in chronic myeloid leukemia (CML) is still missing., Methods: We screened CML cell lines and bone marrow (BM) samples from healthy donors by RT-PCR for the expression of 31 CT antigens before and after treatment with epigenetic agents. Expression of tumor-restricted antigens was further examined in 60 CML patients and humoral immune responses against 15 CT antigens were screened by ELISA., Results: In untreated cell lines we detected the expression of 17 CT antigens that were absent from normal BM. Expression of most antigens increased following demethylating treatment with 5'-Aza-2'-Deoxycytidine. In these samples, only PRAME was repeatedly detected and expression correlated with several clinicopathological parameters and decreased overall survival. We further show that a lower frequency of PRAME-positive samples during imatinib treatment was not caused by gene-specific downregulation. Analyzing the patients' antibody responses we found that the vast majority of patients lacked spontaneous immunity against CT antigens including PRAME., Conclusions: CT antigen expression can be increased by the application of epigenetic agents and the expression of PRAME correlates with clinicopathological parameters and overall survival in patients with CML, but does not lead to humoral immune responses. PRAME-specific immunotherapy might represent a promising approach for the eradication of residual therapy-resistant leukemic cells due to its frequent expression and stability under imatinib treatment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Pressures influencing the size and composition of medical staffs are increasing as hospitals and physicians respond to competition, market priorities, increasing numbers of physicians, and quality-of-care concerns. This article examines whether the quality of care provided by an applicant may be the primary criterion for admission to a hospital's medical staff. Methodological, legal, and organizational concerns that arise from this approach are reviewed. A quality criteria approach can assist in responding to increasing numbers of physicians, the transition to management care, and the marketing interests of a hospital.