Retraining motor control of abdominal muscles among elite cricketers with low back pain.

The purpose of this study was to document the effect of a staged stabilization training program on the motor control of the anterolateral abdominal muscles in elite cricketers with and without low back pain (LBP). Changes in the cross-sectional area of the trunk, the thickness of the internal oblique and transversus abdominis (TrA) muscles and the shortening of the TrA muscle in response to an abdominal drawing-in task were measured at the start and completion of a 13-week cricket training camp. Measures were performed using ultrasound imaging and magnetic resonance imaging. Participants from the group with LBP underwent a stabilization training program that involved performing voluntary contractions of the multifidus, TrA and pelvic floor muscles, while receiving feedback from ultrasound imaging. By the end of the training camp, the motor control of cricketers with LBP who received the stabilization training improved and was similar to that of the cricketers without LBP.

MRI study of the size, symmetry and function of the trunk muscles among elite cricketers with and without low back pain.

OBJECTIVES: To determine if asymmetry of trunk muscles and deficits of motor control exist among elite cricketers with and without low back pain (LBP). DESIGN: Single-blinded observational quasi-experimental design study SETTING: Assessments were conducted in a hospital setting. PARTICIPANTS: Among a total eligible sample of 26 male elite cricketers (mean age 21.2 (SD 2.0) years), selected to attend a national training camp, 21 participated in the study. RISK FACTORS: The independent variables were 'group' (LBP or asymptomatic) and 'cricket position' (fast bowler versus the rest of the squad). MAIN OUTCOME MEASUREMENTS: The dependent variables were the cross-sectional areas (CSA) of the quadratus lumborum (QL), lumbar erector spinae plus multifidus (LES + M) and psoas muscles, the thickness of the internal oblique (IO) and transversus abdominis (TrA) muscles, and the amount of lateral slide of the anterior abdominal fascia. RESULTS: The QL and LES + M muscles were larger ipsilateral to the dominant arm. In the subgroup of fast bowlers with LBP, the asymmetry in the QL muscle was the greatest. The IO muscle was larger on the side contralateral to the dominant arm. No difference between sides was found for the psoas and TrA muscles. Cricketers with LBP showed a reduced ability to draw in the abdominal wall and contract the TrA muscle independently of the other abdominal muscles. CONCLUSIONS: This study provides new insights into trunk muscle size and function in elite cricketers, and evidence of impaired motor control in elite cricketers with LBP. Rehabilitation using a motor control approach has been shown to be effective for subjects with LBP, and this may also benefit elite cricketers.

Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene.

Minor histocompatibility antigens (mHags) play an important role in both graft-versus-tumor effects and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. We applied biochemical techniques and mass spectrometry to identify the peptide recognized by a dominant tumor-reactive donor T-cell reactivity isolated from a patient with relapsed multiple myeloma who underwent transplantation and entered complete remission after donor lymphocyte infusion. A frequently occurring single nucleotide polymorphism in the human ATP-dependent interferon-responsive (ADIR) gene was found to encode the epitope we designated LB-ADIR-1F. Although gene expression could be found in cells from hematopoietic as well as nonhematopoietic tissues, the patient suffered from only mild acute GVHD despite high percentages of circulating LB-ADIR-1F-specific T cells. Differential recognition of nonhematopoietic cell types and resting hematopoietic cells as compared with activated B cells, T cells, and tumor cells was demonstrated, illustrating variable LB-ADIR-1F expression depending on the cellular activation state. In conclusion, the novel mHag LB-ADIR-1F may be a suitable target for cellular immunotherapy when applied under controlled circumstances.

Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer.

Characterization of the antigens recognized by tumor-reactive T cells isolated from patients successfully treated with allogeneic HLA-matched hematopoietic stem cell transplantation (SCT) can lead to the identification of clinically relevant target molecules. We isolated tumor-reactive cytotoxic CD8(+) T-cell (CTL) clones from a patient successfully treated with donor lymphocyte infusion for relapsed multiple myeloma after allogeneic HLA-matched SCT. Using cDNA expression cloning, the target molecule of an HLA-B7-restricted CTL clone was identified. The CTL clone recognized a minor histocompatibility antigen produced by a single nucleotide polymorphism (SNP) in the angiogenic endothelial-cell growth factor-1 (ECGF1) gene also known as thymidine phosphorylase. The SNP leads to an Arg-to-His substitution in an alternatively translated peptide that is recognized by the CTL. The ECGF1 gene is predominantly expressed in hematopoietic cells, although low expression can also be detected in other tissues. The patient from whom this CTL clone was isolated had mild graft-versus-host disease despite high numbers of circulating ECGF-1-specific T cells as detected by tetramer staining. Because solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematologic and solid tumors.

Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor histocompatibility antigens in response to inflammatory cytokines: relevance for allogeneic immunotherapy of leukemia.

T cells directed against hematopoietic-restricted minor histocompatibility antigens (mHags) may mediate graft-versus-leukemia (GVL) reactivity without graft-versus-host disease (GVHD). Recently, the HLA-A24-restricted mHag ACC-1 and the HLA-B44-restricted mHag ACC-2 encoded by separate polymorphisms within the BCL2A1 gene were characterized. Hematopoietic-restricted expression was suggested for these mHags. We demonstrate BCL2-related protein A1 (BCL2A1) mRNA expression in mesenchymal stromal cells (MSCs) that was up-regulated by the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and/or interferon gamma (IFN-gamma). Analysis of cytotoxicity and IFN-gamma production illustrated that ACC-2-specific T cells did not recognize untreated MSCs or IFN-gamma-treated MSCs but showed specific recognition and killing of MSCs treated with TNF-alpha plus IFN-gamma. We hypothesize that under steady-state circumstances BCL2A1-specific T cells may exhibit relative specificity for hematopoietic tissue, but reactivity against nonhematopoietic cells may occur when inflammatory infiltrates are present. Thus, the role of BCL2A1-specific T cells in differential induction of GVL reactivity and GVHD may depend on the presence of inflammatory responses that may occur during GVHD.

Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia.

Donor lymphocyte infusion (DLI) into patients with a relapse of their leukemia or multiple myeloma after allogeneic stem cell transplantation (alloSCT) has been shown to be a successful treatment approach. The hematopoiesis-restricted minor histocompatibility antigens (mHAgs) HA-1 or HA-2 expressed on malignant cells of the recipient may serve as target antigens for alloreactive donor T cells. Recently we treated three mHAg HA-1- and/or HA-2-positive patients with a relapse of their disease after alloSCT with DLI from their mHAg HA-1- and/or HA-2-negative donors. Using HLA-A2HA-1 and HA-2 peptide tetrameric complexes we showed the emergence of HA-1- and HA-2-specific CD8(+) T cells in the blood of the recipients 5-7 weeks after DLI. The appearance of these tetramer-positive cells was followed immediately by a complete remission of the disease and restoration of 100% donor chimerism in each of the patients. Furthermore, cloned tetramer-positive T cells isolated during the clinical response specifically recognized HA-1 and HA-2 expressing malignant progenitor cells of the recipient and inhibited the growth of leukemic precursor cells in vitro. Thus, HA-1- and HA-2-specific cytotoxic T lymphocytes emerging in the blood of patients after DLI demonstrate graft-versus-leukemia or myeloma reactivity resulting in a durable remission. This finding implies that in vitro generated HA-1- and HA-2-specific cytotoxic T lymphocytes could be used as adoptive immunotherapy to treat hematological malignancies relapsing after alloSCT.