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Unlabelled: Combined fractures of the greater and the lesser tuberosity are very rare injuries. This is a case report on arthroscopic treatment using suture anchors and one distal fixation screw. Clinical and radiographic follow-up showed recovery of active motion and consolidation of the fragments in anatomic positions., Level of Evidence: V.

Background: The macroscopic pathomorphology in recurrent shoulder instability has been described. However, less is known regarding the histopathologic details of the affected structures. This study evaluates different histopathologic stages of shoulder instability by assessing biopsy specimens of static stabilizers for possible correlations with clinical parameters. Our hypothesis was that clinical parameters of shoulder instability correlate with histopathologic findings., Materials and Methods: Passive shoulder stabilizers (labrum, anterior bundle of the inferior glenohumeral ligament) were biopsied during arthroscopic shoulder stabilization. Samples were submitted to immunohistochemistry, in situ hybridization, and blinded evaluation. Clinical data, comprising age (<30 years or ≥30 years), total number of dislocations (1, 2-3, or >3), and period since initial dislocation (<6 months, 6 months to 6 years, or >6 years), were tested for statistical correlation with the following histopathologic parameters: inflammation, lipomatous changes, vascular proliferation, tissue fragmentation, and cellularity., Results: Standardized biopsies were performed in 30 consecutive patients (4 women and 26 men; mean age, 32.6 years) with anterior shoulder instability. Microscopic evaluation showed only small variations in histologic changes among all samples. Only limited variations in cell density, matrix swelling, and collagen fiber disruptions were found. Immunohistochemical analysis showed a similar expression of decorin in all samples. Clinical parameters (age, total number of dislocations, and period since initial dislocation) were statistically independent from histopathologic parameters (inflammation, lipomatous changes, vascular proliferation, tissue fragmentation, and cellularity). No correlation was found in patients with 1 dislocation versus those with more than 1 dislocation., Conclusions: In contrast to macroscopic findings among different grades of shoulder instability, this study detected no correlation between clinical items (age, total number of dislocations, and period since initial dislocation) and histopathologic parameters. These clinical items seem to be independent from the tissue status of static stabilizers of the shoulder., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: The aim of this study was to evaluate the clinical and radiological results of 37 consecutive patients (Ø age 37.9; 4♀, 33♂) following arthroscopically assisted and image intensifier-controlled AC joint reconstruction using the double TightRope™ technique for acute AC joint separations grade V according to Rockwood., Material and Methods: After 12 months 30 patients with a mean age of 38.8 years (range 18.6-65.8 years) could be included. The postoperative assessment included the Subjective Shoulder Value (SSV), Constant Score (CS), and Taft Score (TF) as well as radiological evaluation using bilateral stress views and bilateral Alexander views for determining vertical and horizontal AC joint instability., Results: The clinical scores reached 91.4±9.8% for SSV, 87.8±5.2 for CS, and 10.1±2.1 points for TF. The initial coracoclavicular distance (CCD) was 22.1±5.6 mm and could be reduced to 8.6±2.8 mm postoperatively (p<0.05). The CCD increased at final follow-up to 12.8±2.4 mm. The difference of the CCD compared to the contralateral side was initially 13.7±4.8 mm; postoperatively it was 0.3±3.0 mm with an increase at final follow-up to 3.6±3.5 mm. A posterior instability on the Alexander view occurred in 53.3% of patients. A correlation between inferior clinical results and horizontal instability could be detected. Only one patient was slightly tender to palpation at the AC joint., Conclusion: Following arthroscopic AC joint stabilization using the double TightRope™ technique, despite partial recurrent instability, favorable clinical results can be expected.

Background: Red blood cells (RBC) possess a nitric oxide synthase (RBC-NOS) whose activation depends on the PI3-kinase/Akt kinase pathway. RBC-NOS-produced NO exhibits important biological functions like maintaining RBC deformability. Until now, the cellular target structure for NO, to exert its influence on RBC deformability, remains unknown. In the present study we analyzed the modification of RBC-NOS activity by pharmacological treatments, the resulting influence on RBC deformability and provide first evidence for possible target proteins of RBC-NOS-produced NO in the RBC cytoskeletal scaffold., Methods/findings: Blood from fifteen male subjects was incubated with the NOS substrate L-arginine to directly stimulate enzyme activity. Direct inhibition of enzyme activity was induced by L-N5-(1-Iminoethyl)-ornithin (L-NIO). Indirect stimulation and inhibition of RBC-NOS were achieved by applying insulin and wortmannin, respectively, substances known to affect PI3-kinase/Akt kinase pathway. The NO donor sodium nitroprusside (SNP) and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) were additionally applied as NO positive and negative controls, respectively. Immunohistochemical staining was used to determine phosphorylation and thus activation of RBC-NOS. As a marker for NO synthesis nitrite was measured in plasma and RBCs using chemiluminescence detection. S-nitrosylation of erythrocyte proteins was determined by biotin switch assay and modified proteins were identified using LC-MS. RBC deformability was determined by ektacytometry. The data reveal that activated RBC-NOS leads to increased NO production, S-nitrosylation of RBC proteins and RBC deformability, whereas RBC-NOS inhibition resulted in contrary effects., Conclusion/significance: This study first-time provides strong evidence that RBC-NOS-produced NO modifies RBC deformability through direct S-nitrosylation of cytoskeleton proteins, most likely α- and β-spectrins. Our data, therefore, gain novel insights into biological functions of RBC-NOS by connecting impaired RBC deformability abilities to specific posttranslational modifications of RBC proteins. By identifying likely NO-target proteins in RBC, our results will stimulate new therapeutic approaches for patients with microvascular disorders.

Background: Arthroscopic double-row fixation of supraspinatus tendon tears compared with single-row techniques is still a matter of debate., Hypothesis: Arthroscopic double-row rotator cuff repair using the suture bridge technique provides better clinical results and lower retear rates than does single-row repair using a modified Mason-Allen stitch technique., Study Design: Cohort study; Level of evidence 3., Methods: Forty patients underwent either an arthroscopic single-row modified Mason-Allen stitch (SR) (n = 20; mean age ± SD, 61.5 ± 7.4 y) or a modified suture bridge double-row repair (DR) (n = 20; age, 61.2 ± 7.5 y). The anteroposterior extension was classified as Bateman I in 10% and Bateman II in 90% of patients in the SR group and as Bateman II in 80% and Bateman III in 20% of patients in the DR group. Patients were matched for sex and age. The subjective shoulder value (SSV), Constant-Murley score (CS), and Western Ontario Rotator Cuff Index (WORC) were used for clinical follow-up. Furthermore, MRI scans were conducted for analysis of tendon integrity, muscle atrophy, and fatty infiltration via semiquantitative signal intensity analysis. In addition, re-defect patterns were evaluated., Results: The mean follow-up time in the SR group was 16.8 ± 4.6 months. The mean SSV was 91.0% ± 8.8%, mean CS was 82.2 ± 8.1 (contralateral side, 88.8 ± 5.3), and mean WORC score was 96.5% ± 3.2%. The mean follow-up time in the DR group was 23.4 ± 2.9 months, with patients achieving scores of 92.9% ± 9.6% for the SSV, 77.0 ± 8.6 for the CS (contralateral side, 76.7 ± 17.1), and 90.7% ± 12.6% for the WORC (P > .05). No significant differences were detected in the clinical outcome between groups. Tendon integrity was as follows. Type 1, none in either group; type 2, 4 SR and 5 DR; type 3, 9 SR and 10 DR; type 4, 3 SR and 3 DR; and type 5, 3 SR and 2 DR. The failure rate was 31.6% (n = 6) in the SR group and 25% (n = 5) in the DR group (P > .05). No significant differences were obtained for muscular atrophy or fatty degeneration (SR group, 0.94 ± 0.16; DR group, 1.15 ± 0.5) (P > .05). Re-defects revealed lateral cuff failure in 83.3% of SR patients in contrast to patients treated with DR techniques. The re-defect pattern was medial cuff failure in 80% of the patients., Conclusion: The clinical results after modified Mason-Allen single-row versus double-mattress suture bridge technique did not demonstrate significant differences in a matched patient cohort. Concerning the failure mode, single- and double-row techniques seem to demonstrate different re-defect patterns.

Background: Simvastatin increases the expression of bone morphogenetic protein 2 (BMP-2) in osteoblasts, therefore it is important to investigate the influence of statins on bone formation, fracture healing and implant integration. The aim of the present study was to investigate the effect of simvastatin, locally applied from intramedullary coated and bioactive implants, on bone integration using biomechanical and histomorphometrical analyses., Methods: Eighty rats received retrograde nailing of the femur with titanium implants: uncoated vs. polymer-only (poly(D,L-lactide)) vs. polymer plus drug coated (either simvastatin low- or high dosed; "SIM low/ high"). Femurs were harvested after 56 days for radiographic and histomorphometric or biomechanical analysis (push-out)., Results: Radiographic analysis revealed no pathological findings for animals of the control and SIM low dose group. However, n=2/10 animals of the SIM high group showed osteolysis next to the implant without evidence of bacterial infection determined by microbiological analysis. Biomechanical results showed a significant decrease in fixation strength for SIM high coated implants vs. the control groups (uncoated and PDLLA). Histomorphometry revealed a significantly reduced total as well as direct bone/implant contact for SIM high- implants vs. controls (uncoated and PDLLA-groups). Total contact was reduced for SIM low vs. uncoated controls. Significantly reduced new bone formation was measured around SIM high coated implants vs. both control groups., Conclusions: This animal study suggests impaired implant integration with local application of simvastatin from intramedullary titanium implants after 8 weeks when compared to uncoated or carrier-only coated controls.

The incidence of rotator cuff tears and recurrent defects positively correlate with patient age. However, this observation has never been analysed at the cellular level. The present study aims to better understand this correlation by investigating cellular characteristics of rotator cuff tenocytes of different age groups. Additionally, previous studies reported on stimulating effects of Bone Morphogenetic Protein (BMP) -2 and BMP-7 on tenocytes. Thus, the second aim was to investigate, whether the stimulation potential of tenocytes demonstrates age-related differences. Tenocyte-like cells from supraspinatus tendons of young and aged patients were analysed for the following cell biological characteristics: cell density, cell growth, marker expression, collagen-I protein synthesis, stem cell phenotype, potential for multipotent differentiation and self-renewal. To analyse the stimulation potential, cells were treated with BMP-2 and BMP-7 in 2D-/3D-cultures. Measured parameters included cell activity, marker expression and collagen-I protein synthesis. An effect of age was seen for cell growth and stem cell potential but not on extracellular matrix level. Cells from both groups responded to BMP-7 by increasing cell activity, collagen-I expression and protein synthesis. BMP-2 led to smaller increases in these parameters when compared to BMP-7. In general, 3D-cultivation improved the stimulation compared to 2D-culture. The cell biological characteristics of tenocyte-like cells, considered important for successful restoration of the tendon-bone unit, were inferior in elderly donors. This may help explain higher rates of recurrent defects seen in elderly patients. Regarding the stimulation potential, on a cellular level young and aged patients may benefit from biological augmentation with BMPs.

Background: Rotator cuff repair is prone to incomplete regeneration. To explore biological improvements of tendon-bone healing, it was the aim of this study to investigate the influence of growth factors bone morphogenetic protein (BMP)-2 and BMP-7 on tenocyte cell activity and matrix gene expression and production. A beneficial effect of these factors would be promising to improve tendon-bone healing in vivo., Methods: Tenocyte-like cells were isolated from human rotator cuff tissue samples (supraspinatus and long head of biceps tendon) and incubated with BMP-2 (100-1000 ng/mL) and BMP-7 (100-2000 ng/mL), both alone and in combination. At days 0, 3, and 6, cell activity was assessed. At day 6, collagen type I production and the expression of several tendon-, bone-, and cartilage-related markers (collagen types I-III, osteocalcin, scleraxis) were evaluated., Results: Dose-dependent effects of both investigated growth factors on tenocyte-like cells were observed. Application of BMP-2 increased collagen type I production significantly but its expression only slightly. Cell activity was decreased in higher doses over time. For BMP-7, a significant increase in collagen type I production and expression, as well as increased cell activity, was observed. The addition of both factors resulted in decreased parameters when compared with BMP-7 alone. The expression of collagen types II and III, osteocalcin, and scleraxis was not significantly affected by application of BMPs., Conclusion: Besides the well-known effects of BMP-2 and BMP-7 on osteoblasts, this study describes further effects on rotator cuff tendon cell biology. Both tissue types potentially need to be addressed to improve tendon-bone healing of the rotator cuff., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: An implant coating with poly(D, L-lactide) (PDLLA) releasing incorporated zoledronic acid (ZOL) has already proven to positively effect osteoblasts, to inhibit osteoclasts and to accelerate fracture healing. Aim of this study was to investigate the release kinetics of the chosen coating and the effect of different concentrations of ZOL locally released from this coating on the osseointegration of implants., Methods: For release kinetics the release of C14-labled ZOL out of the coating was monitored over a period of six weeks in vitro. For testing the osseointegration, titanium Kirschner wires were implanted into the medullary canal of right femurs of 100 Sprague Dawley rats. The animals were divided into five groups receiving implants either uncoated or coated with PDLLA, PDLLA/ZOL low (1.2% w/w) or PDLLA/ZOL high (2% w/w). Additionally, a group with uncoated implants received ZOL intravenously (i.v.). After 56 days animals were sacrificed, femurs dissected and either strength of fixation or histological bone/implant contacts and newly formed bone around the implants were determined., Results: Release kinetics revealed an initial peak in the release of C14-ZOL with a slight further progression over the following weeks. There was no significant enhancement of osseointegration for both groups who received ZOL-coated implants or ZOL i.v. compared to the controls in biomechanical or histological analyses, except for a significant raise in strength of fixation of ZOL i.v. versus PDLLA., Conclusions: Even though the investigated local ZOL application did not enhance the osseointegration of the implant, the findings might support its application in fracture treatment, since fracture stabilization devices are often explanted after consolidation.

Background: Biomechanical comparison of four different Speed-Bridge configurations with or without medial or lateral row reinforcement. Reinforcement of the knotless Speed-Bridge double-row repair technique with additional medial mattress- or lateral single-stitches was hypothesized to improve biomechanical repair stability at time zero., Methods: Controlled laboratory study: In 36 porcine fresh-frozen shoulders, the infraspinatus tendons were dissected and shoulders were randomized to four groups: (1) Speed-Bridge technique with single tendon perforation per anchor (STP); (2) Speed-Bridge technique with double tendon perforation per anchor (DTP); (3) Speed-Bridge technique with medial mattress-stitch reinforcement (MMS); (4) Speed-Bridge technique with lateral single-stitch reinforcement (LSS). All repairs were cyclically loaded from 10-60 N up to 10-200 N (20 N stepwise increase) using a material testing device. Forces at 3 and 5 mm gap formation, mode of failure and maximum load to failure were recorded., Results: The MMS-technique with double tendon perforation showed significantly higher ultimate tensile strength (338.9 ± 90.0 N) than DTP (228.3 ± 99.9 N), LSS (188.9 ± 62.5 N) and STP-technique (122.2 ± 33.8 N). Furthermore, the MMS-technique provided increased maximal force resistance until 3 and 5 mm gap formation (3 mm: 77.8 ± 18.6 N; 5 mm: 113.3 ± 36.1 N) compared with LSS, DTP and STP (P < 0.05 for each 3 and 5 mm gap formation). Failure mode was medial row defect by tendon sawing first, then laterally. No anchor pullout occurred., Conclusion: Double tendon perforation per anchor and additional medial mattress stitches significantly enhance biomechanical construct stability at time zero in this ex vivo model when compared with the all-knotless Speed-Bridge rotator cuff repair.

Background: The value of arthroscopic revision shoulder stabilization after failed instability repair is still a matter of debate., Hypothesis: Arthroscopic revision shoulder stabilization using suture anchors provides equivalent subjective and objective results compared with initial arthroscopic instability repair., Study Design: Cohort study; Level of evidence, 3., Methods: Twenty consecutive patients who underwent arthroscopic revision shoulder stabilization using suture anchors (group 2) were matched for age, gender, and handedness (dominant or nondominant) with 20 patients who had initial arthroscopic instability repair using the same technique (group 1). At the time of follow-up, a complete physical examination of both shoulders and evaluation with the Rowe score, Walch-Duplay score, Melbourne Instability Shoulder Score, Western Ontario Shoulder Instability Index, and the Subjective Shoulder Value were performed. In addition, standard radiographs (true AP and axillary views) were taken to evaluate signs of osteoarthritis., Results: After a minimum follow-up of 24 months, no recurrent dislocations were observed in either group. The apprehension sign was positive in 2 cases of revision surgery (0 vs 2; P > .05). No significant differences in the Rowe score (89 vs 81.8 points) were found between groups 1 and 2 (P > .05). However, group 2 revealed significantly lower scores in the Walch-Duplay score (85.3 vs 75.5 points), Melbourne Instability Shoulder Score (90.2 vs 73.7 points), Western Ontario Shoulder Instability Index (89.8% vs 68.9%), and Subjective Shoulder Value (91.8% vs 69.2%) (P < .05). Signs of instability arthropathy were found more often in patients with arthroscopic revision surgery (2 vs 5; P > .05)., Conclusion: Arthroscopic revision shoulder stabilization is associated with a lower subjective outcome compared with initial arthroscopic stabilization. The objective results found in this study may overestimate the clinical outcome in this patient population.

Purpose: Biomechanical comparison of different suture-bridge configurations of the medial row with respect to initial construct stability (time 0, porcine model)., Methods: In 40 porcine fresh-frozen shoulders, the infraspinatus tendons were dissected from their insertions. All specimens were operated on by use of the suture-bridge technique, only differing in terms of the medial-row suture-grasping configuration, and randomized into 4 groups: (1) single-mattress (SM) technique, (2) double-mattress (DM) technique, (3) cross-stitch (CS) technique, and (4) double-pulley (DP) technique. Identical suture anchors were used for all specimens (medial: Bio-Corkscrew FT 5.5 [Arthrex, Naples, FL]; lateral: Bio-PushLock 3.5 [Arthrex]). All repairs were cyclically loaded from 10 to 60 N until 10 to 200 N (20-N stepwise increase after 50 cycles each) with a material testing machine. Forces at 3 and 5 mm of gap formation, mode of failure, and maximum load to failure were recorded., Results: The DM technique had the highest ultimate tensile strength (368.6 ± 99.5 N) compared with the DP (248.4 ± 122.7 N), SM (204.3 ± 90 N), and CS (184.9 ± 63.8 N) techniques (P = .004). The DM technique provided maximal force resistance until 3 and 5 mm of gap formation (90.0 ± 18.1 N and 128.0 ± 32.3 N, respectively) compared with the CS (72 ± 8.9 N and 108 ± 20.2 N, respectively), SM (66.0 ± 8.9 N and 90.0 ± 26.9 N, respectively), and DP (62.2 ± 6.2 N and 71 ± 13.2 N, respectively) techniques (P < .05 for each 3 and 5 mm of gap formation). The main failure mode was suture cutting through the tendon., Conclusions: Comparing the 4 different suture-bridge techniques, we found that modified application of suture-bridge repair with double medial mattress stitches significantly enhanced biomechanical construct stability at time 0 in this porcine ex vivo model., Clinical Relevance: This technique increases initial stability and resistance to suture cutting through the rotator cuff tendon after arthroscopic suture-bridge repair., (Copyright © 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Rotator cuff tears are common soft tissue injuries of the musculoskeletal system that heal by formation of repair tissue and may lead to high retear rates and joint dysfunction. In particular, tissue from chronic, large tendon tears is of such degenerative nature that it may be prone to retear after surgical repair. Besides several biomechanical approaches, biologically based strategies such as application of growth factors may be promising for increasing cell activity and production of extracellular tendon matrix at the tendon-to-bone unit. As a precondition for subsequent experimental growth factor application, the aim of the present study was to establish and characterize a human rotator cuff tendon cell culture. Long head biceps (LHB)- and supraspinatus muscle (SSP)- tendon samples from donor patients undergoing shoulder surgery were cultivated and examined at the RNA level for expression of collagen type-I, -II and -III, biglycan, decorin, tenascin-C, aggrecan, osteocalcin, tenomodulin and scleraxis (by Real-time PCR). Finally, results were compared to chondrocytes and osteoblasts as control cells. An expression pattern was found which may reflect a human rotator cuff tenocyte-like cell culture. Both SSP and LHB tenocyte-like cells differed from chondrocyte cell cultures in terms of reduced expression of collagen type-II (p

Many clinical and experimental investigations address the influence of statins on bone formation and fracture healing. Simvastatin was shown to increase the expression of Bone morphogenetic protein (BMP-2), which is one of the most potent growth factors targeting bone formation. In this study, the effect of simvastatin locally applied from a bioactive polymer coating of implants on fracture healing was investigated. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats was performed. Intramedullary stabilization was achieved with uncoated vs. polymer-only coated vs. polymer plus drug coated titanium Kirschner wires. Test substances (either simvastatin low- or high dosed or BMP-2) were incorporated into a biodegradable layer of poly(d,l-lactide). Tibiae were harvested after 28 or 42 days, respectively and underwent biomechanical testing (torsional stiffness and maximum load) and histomorphometric analysis. Radiographic results demonstrated progressed callus consolidation in the BMP-2- and simvastatin-treated groups compared to the uncoated group at both timepoints. The simvastatin-high-dosed group revealed an increased torsional stiffness and significantly elevated maximum load (d 28) compared to control group as well as a significant increase in both parameters at d 42. BMP-2-treated animals showed significantly elevated maximum load and stiffness at the early timepoint and elevated torsional stiffness after d 42. The histomorphometric analysis revealed a significantly decreased cartilage area for BMP-2 treated animals at d 28. Even though an increase of mineralized areas among periosteal callus was found at d 42 for simvastatin-high as well as BMP-2 treated animals, no significant difference could be detected at both timepoints compared to the uncoated group. However, simvastatin-high treated animals revealed significantly reduced cartilage areas within the periosteal callus at d 42. The present study revealed a dose-dependent effect and improved fracture healing under local application of simvastatin. Biomechanical, radiographic and histomorphometric properties showed comparable results to BMP-2- treated animals in this study.

Immobilization of the shoulder following dislocation and reduction is traditionally carried out using internal rotation braces. However, high recurrence rates of up to 96% may result depending on several concomitant intrinsic and extrinsic prognostic factors, such as age and level of physical activity. Recently, different cadaveric and radiologic studies have suggested an improved tissue apposition of the affected labroligamentous structures in a better anatomic position during external rotation of the humeral head. Recent clinical outcome studies have supported the hypothetical benefit of this immobilization technique. Significantly lower recurrent dislocation rates and a better anatomic positioning of the affected structures were observed after immobilization in external rotation compared to immobilization in internal rotation.However, the number of available studies in this respect is still limited. Further prospective evidence is therefore desirable to evaluate the contribution of exact positioning of the immobilization, influence of hemarthros and specific capsulolabral lesions to the long-term clinical and radiological outcome of this new concept of immobilization.

The treatment of symptomatic chronic acromioclavicular joint dislocations can be challenging. Different surgical procedures have been described in the literature. We present an arthroscopically assisted stabilization using a gracilis tendon transclavicular-transcoracoid loop technique augmented with a Tight-Rope (Arthrex, Naples, FL, USA). In contrast to the classic Weaver-Dunn procedures this technique is designed to stabilize the acromioclavicular joint by recreating the anatomy of the coracoclavicular ligaments via a minimal invasive approach.

CD137 (ILA, 4-1BB), a member of the tumor necrosis factor receptor family, and its ligand CD137-L were assayed by RT-PCR and immunocytochemistry in cultured human brain cells. Results demonstrated that both neurons and astrocytes expressed specific RNA for CD137 and its protein, which was found both on the plasma membrane and in the cytoplasm. Surprisingly, microglia, which also expressed CD137 mRNA, showed negative immunostaining. CD137-L-specific RNA was detected only in astrocytes and neurons. When brain cells were treated with fibroblast growth factor-2 (FGF-2), upregulation of CD137 but not of its ligand was observed in neurons and astrocytes. Protein localization was also affected. In microglia, an inhibition of RNA expression was induced by treatment, whereas CD137-L remained negative. Our data are the first demonstration that human brain cells express a protein found thus far in activated immunocompetent cells and epithelia. Moreover, they suggest not only that CD137 and CD137-L might play a role in interaction among human brain cells, but also that FGF-2 might have an immunoregulatory function in brain, modulating interaction of the central nervous system with peripheral immunocompetent cells., (Copyright 2003 Wiley-Liss, Inc.)

CD137, a member of the TNF receptor family, and its ligand are expressed on T lymphocytes and antigen-presenting cells (APC), respectively. During interaction with APC, T lymphocytes receive a potent, costimulatory signal through CD137. Reverse signaling has been demonstrated for the CD137 ligand, which causes activation in monocytes. Here we show that B lymphocytes also receive costimulatory signals through the CD137 ligand. Immobilized CD137 augmented proliferation of preactivated B lymphocytes up to fivefold and immunoglobulin synthesis, up to threefold. CD137 had no effect on resting cells. Further, we show that CD137 is expressed in vivo by follicular dendritic cells (FDC) in germinal centers. Germinal centers form during humoral immune responses and are essential for B lymphocyte affinity maturation. These data imply that, similar to the CD40 receptor/ligand system, which mediates T lymphocyte help to B lymphocytes after the first antigen encounter, the CD137 receptor/ligand system may mediate costimulation of B lymphocytes by FDC during affinity maturation.

The molecular biological characteristics of Burkitt lymphoma (BL), in addition to the presence of the Epstein-Barr virus (EBV) in some forms, relies on well-characterized alterations, such as MYC translocations and TP53 inactivations. To ascertain the number and location of other genome alterations, we used 191 polymorphic markers in a genome-wide search for loss of heterozygosity (LOH) in 31 Burkitt lymphoma cell lines and their normal counterparts. We were able to distinguish two types of altered allelic patterns: a bona fide LOH profile, indicative of deletion (LOH), and a profile indicative of increased dosage (ID). The former type was most frequent at chromosome arm 17p, most likely indicating TP53 gene inactivation. Increased dosage at 1q was found almost exclusively in non-EBV cell lines (P < 0.00004) and correlated well with karyotypic abnormalities affecting region 1q21-25. Our results suggest that a gene important for BL pathogenesis is located in region 1q21-25 and that the activation of this gene mimics the effects of EBV., (Copyright 2002 Wiley-Liss, Inc.)

We have localized several markers in the Xq24-25 region containing DXS12, DXS42 and DXS37 which are closely linked to the X-linked lymphoproliferative syndrome (XLP) locus. A 850-kb restriction map has been established by mapping overlapping YACs and showed that DXS12 and DXS42 are physically linked within about 50 kb. DXS37 is separated from these two loci at a maximum distance of 3,700 kb. Several new probes have been generated which will contribute to further physical mapping of this region.