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Biomedical subjects

Nir Cohen

Publications and source records attributed to Nir Cohen.

8 recordsLinked to original sources

The generation and regulation of functional diversity of malignant plasma cells.

Cellular diversity, which is a hallmark of malignancy, can be generated by both genetic and nongenetic mechanisms. We describe here variability in the adhesive and migratory behavior of malignant plasma cell populations, including multiple myeloma-derived lines and primary patient samples. Examination of the plasma cell lines ARH-77, CAG, and AKR revealed two distinct subpopulations of cells, one displaying highly adhesive properties (type A) and the other consisting of poorly adhesive, floating cells (type F). In the ARH-77 cell line, type A cells attach better to fibronectin and to human bone fragments and form paxillin-rich focal adhesions, whereas type F cells are highly motile and exert integrin-dependent bone marrow homing capacity in nonobese diabetic/severe combined immunodeficient mice. Flow cytometry indicated that type A cells express significantly higher levels of CD45 and CD56 and lower levels of CD138 compared with type F cells. Interestingly, culturing of either type A or type F cells under nonselective conditions resulted in the development of mixed cell population similar to the parental ARH-77 cells. Analysis of bone marrow aspirates of multiple myeloma patients revealed that spicules within the aspirates are enriched with type A-like cells. Nonadherent cells within the aspirate fluids express a marker profile similar to type F cells. This study indicates that multiple myeloma patients contain heterogeneous populations of malignant plasma cells that display distinct properties. Diverse subpopulations of malignant plasma cells may play distinct roles in the different biological and clinical manifestations of plasma cell dyscrasias, including bone dissemination and selective adhesion to bone marrow compartments.

Cell Adhesion↗

Free fibula flap elbow-joint hemiarthroplasty reconstruction for chronic osteomyelitis of the distal humerus.

The vascularized fibula flap has become a major tool in upper limb reconstruction. Free fibula flap reconstructions of the humeral part of the shoulder and the radial part of the wrist joints are well-documented, but reports of elbow joint reconstruction are rare. The authors report a 53-year-old patient with chronic osteomyelitis of the distal humerus that was unsuccessfully treated by many local surgical debridements and long-term systemic antibiotics. The patient underwent a wide debridement of the distal two-thirds of the humerus, and a spacer was inserted to fill the bony humeral gap. At a second stage, the distal humerus was reconstructed with a free fibula flap that included the proximal fibular head. The fibular shaft was used to bridge the bony gap and the fibular head created an elbow joint with the olecranon process. At an 18-month follow-up after surgery, the patient has stable and sufficient function of his elbow joint with no signs of infection. The free fibula flap has an important role for distal humerus reconstruction, both for bridging the bony gap with a vascularized bone, and for restoring elbow joint function.

Arthroplasty↗

Vacuum-assisted wound closure after resection of musculoskeletal tumors.

UNLABELLED: Resection of musculoskeletal tumors may result in large soft tissue defects that cannot be closed primarily and require prolonged dressing changes and complex surgical interventions for wound coverage. We retrospectively reviewed 23 patients with such defects treated with a vacuum-assisted wound closure system and compared the outcome of these patients with a control group. The study group included 15 women and eight men who had their wounds located at the back (two), pelvic girdle (11), thigh (eight), and leg (two). Treatment included sealed wound coverage with polyurethane foam and overlying tape connected to a vacuum pump. This system was disconnected and changed every 48 hours for 7 to 19 days, after which all defects were reduced in size by an average of 25% and covered with a viable granulation tissue. This allowed primary closure in seven patients, primary closure with skin grafting in 14 patients, and healing by secondary intention in two patients. Compared with the control group, patients in the study group had shorter hospital stays and number of surgical interventions and greater rates of primary wound closure. The use of vacuum-assisted wound closure facilitates wound healing and primary wound closure in patients who have a large soft tissue defect after resection of a musculoskeletal tumor. LEVEL OF EVIDENCE: Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

Resolving and classifying haematopoietic bone-marrow cell populations by multi-dimensional analysis of flow-cytometry data.

The study of normal or malignant haematopoiesis requires the analysis of heterogeneous cell populations using multiple morphological and molecular criteria. Flow cytometry has the capacity to acquire multi-parameter information of large haematopoietic cell populations, utilizing various combinations of >200 molecular markers (clusters of differentiation, CD). However, current flow cytometry analyses are based on serial gating of two-parametric scatter plots--a process that is inherently incapable to discriminate all subgroups of cells in the data. Here we studied the cellular diversity of normal bone marrows (BM) using multi-dimensional cluster analysis of six-parametric flow cytometry data (four CD, forward scatter and side scatter), focusing mainly on the myeloid lineage. Twenty-three subclasses of cells were resolved, many of them inseparable even when examined in all possible two-parametric scatter plots. The multi-dimensional analysis could distinguish the haematopoietic progenitors according to International Society of Haematotherapy and Graft Engineering criteria from other types of immature cells. Based on the defined clusters, we designed a classifier that assigns BM cells in samples to subclasses based on robust six-dimensional position and extended shape. The analysis presented here can manage successfully both the increasing numbers of haematopoietic cellular markers and sample heterogeneity. This should enhance the ability to study normal haematopoiesis, and to identify and monitor haematopoietic disorders.

Antigens, CD↗

Targeted delivery of progenitor cells for cartilage repair.

An approach for promoting the adherence of chondrogenic progenitor cells to specific matrix molecules has been tested in a cartilage defect model. Culture-expanded pre-chondrocytes fluorescently labeled with a vital dye were coated by a two-step method wherein lipidated protein G was first allowed to intercalate into cell membranes, and a second incubation in a solution of antibodies to cartilage matrix antigens allowed the binding of the antibodies to the protein G, on the external surface of the cell. The coating technique (termed "cell painting") does not effect cell viability or inhibit growth and chondrogenic potential. Painted cells were then added to rabbit cartilage explants that had a partial-thickness defect, washed, and prepared for histological examination and for confocal microscopy. The histological observations and the confocal observations and fluorescent intensity quantification consistently demonstrated that progenitor cells painted with multiple antibodies were capable of preferential binding to the exposed cartilage matrix within the defect. These results demonstrate that painting cell membranes with antibodies to matrix molecules is an effective method for promoting the adherence of stem or progenitor cells to a cartilage injury site.

Animals↗

Primary subacute epiphyseal osteomyelitis: role of conservative treatment.

Primary subacute epiphyseal osteomyelitis is a rare disease. Owing to its insidious onset, mild symptoms, and inconsistent supportive laboratory data, diagnosis and treatment are usually delayed. The authors report a retrospective review of 16 patients with hematogenous osteomyelitis primarily affecting the epiphysis. In all of these patients an osteolytic lesion developed. In eight patients it was confined to the epiphysis or apophysis alone; in the other patients there was contiguous involvement of the adjacent metaphysis. Complete clinical and radiologic healing was observed in all patients after antibiotic therapy alone. Based on this experience, in view of the controversy in the literature, the authors recommend a conservative treatment policy in the management of both epiphyseal and epiphyseal-metaphyseal subacute osteomyelitis as the treatment of choice. Surgery should be reserved for persistent infection that does not respond to appropriate antibiotic therapy or when bone lesions cannot be distinguished from bone tumors by use of all available imaging modalities.

Anti-Bacterial Agents↗