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Biomedical subjects

S Wientroub

Publications and source records attributed to S Wientroub.

At least 55 records · Page 3Linked to original sources

Hemimetatarsal transfer: a unique solution for postaxial metatarsal duplication.

Many operations have been described for the reconstructive treatment of foot congenital anomalies involving multiplication of toes and metatarsi. We describe a surgical procedure designed to solve the problem of postaxial polydactily with complete duplication of metatarsi. We successfully performed hemimetatarsal transposition of the hypoplastic metatarsal bone with its intact metatarso-phalangial joint to the base of the extra metatarsus. We achieved good alignment of the lateral ray with restoration of the metatarsal weight-bearing touch points. Functional and cosmetic results of the procedure were excellent.

Child, Preschool↗

PTH and 1,25(OH)2 vitamin D priming to growth factors differentially regulates the osteoblastic markers in MBA-15 clonal subpopulations.

The functional modulation of enzymatic activities of alkaline phosphatase (ALK-P) and neutral endopeptidase (CD10/NEP) in MBA-15.4 and MBA-15.6 marrow stromal osteoblastic cells was studied. The hormonal effects of parathyroid hormone (PTH) and 1,25 (OH)2D3 combined with various growth factors (bone morphogenic protein [BMP-2 and BMP-3], TGF beta and IGF-I) on these cells were monitored. The cell responses of MBA-15.4, a preosteoblastic cell, and MBA-15.6, a more mature osteoblastic cell, to the growth factors and the hormonal challenge were measured by changes of the enzymatic activities (ALK-P and CD10/NEP). The cellular response was not uniform and revealed a differential pattern.

Alkaline Phosphatase↗

Monoclonal antibodies recognize antigen expressed by osteoblasts.

A marrow stromal osteogenic cell line (MBA-15) was used to create monoclonal antibodies (MoAbs). In this study, we describe a series of MoAbs for mouse marrow stroma (MMS) (MMS-25/17, MMS-85/12, MMS-302/40, and MMS-319/4) that recognized antigens expressed by stromal cells including osteoblastic cells. The MoAbs were screened against various cell and tissue types. MMS-85/12 was positive in detecting an antigen that was highly abundant in osteoblastic cells and primary adherent bone marrow cultures (BMC) but was negative for the marrow adipocytes copartner. The MMS-85/12 MoAb is an IgGl immunoglobulin. The immunohistochemical staining pattern is suggestive of the antigen being associated with the osteoblasts' plasma membrane and with the extracellular matrix constituent secreted by these cells. Western blotting and immunoprecipitation indicated that the antigen that was recognized by MMS-85/12 apparently had a molecular weight of 84 dD.

Animals↗

Bone marrow interface: preferential attachment of an osteoblastic marrow stromal cell line.

In this study, we report on the cell adhesion properties of marrow stromal cells to extracellular matrix components such as collagen and noncollagenous proteins. The osteoblastic cells and their non-osteoblastic counter-parts (MBA series) from the marrow stroma differentially recognized a spectrum of extracellular matrix proteins. The osteoblastic cells, MBA-15, preferentially attached to bone matrix proteins, whereas fibroendothelial MBA-2.1 and adipocytic 14F1.1 cells did not. The MBA-15 cells demonstrated a preference in their attachment to fibronectin > mixture of collagens > bone matrix extracts > collagen type I > noncollagenous proteins. Clonal subpopulations derived from the MBA-15 cell line representing various stages along the osteogenic lineage expressed differential attachment preference. MBA-15.4, a less differentiated clonal line, was compared to MBA-15.6, a mature cell line.

Animals↗

Localized fibromyalgia in a child.

A 14-year-old male was investigated because of a limp and a localized sharp pain in the right lumber paravertebral region radiating to the lower abdomen and the medial aspect of the thigh, which started following forced physical activity. With the diagnosis of fibromyalgia the patient received two perifacetal injections of local anaesthetics with steroids followed by transcutaneous electrical nerve stimulation (TENS). Following the injections, pain intensity dropped dramatically, disability was reduced and muscle swelling resolved. The possible association of symptoms to sport activity raises the question of sport-induced fibromyalgia, and the excellent response to treatment may suggest a facet joint irritation as possible aetiology.

Adolescent↗

Muscle imbalance in the aetiology of idiopathic club foot. An electromyographic study.

We performed electrophysiological studies on both legs of 52 children, aged from 3 months to 15 years, with idiopathic club foot. In only nine (17%) was no abnormality found. Isolated peroneal nerve damage was seen in 14 (27%). Abnormality of both peroneal and posterior tibial nerves was found in five (10%). Four patients (8%) had evidence of isolated spinal-cord dysfunction, whereas combined spinal-cord and peripheral-nerve lesions were seen in 14 (27%). Six patients (11%) had variable neurogenic electrophysiological patterns. In 13 patients in whom the studies were repeated neither progression nor improvement of the electrophysiological parameters was observed. Pathological electrophysiological findings were found in 66% of conservatively-treated patients. In the 43 patients treated surgically, all 16 with fair and poor results had pathological electrophysiological findings and 12 required further operations. Multiplicity of the pathological findings was related to the severity of the deformity of the foot; normal studies represent a good prognostic sign. Electrophysiological studies are useful in idiopathic club foot with residual deformities after conservative or operative treatment. Our findings support the theory that muscle imbalance is an aetiological factor in idiopathic club foot.

Adolescent↗

Serrated (W/M) osteotomy: a new technique for simultaneous correction of angular and torsional deformity of the lower limb in children.

The serrated (W/M) osteotomy allows for simultaneous correction of angular and/or torsional deformities of the lower limb in the growing child. This osteotomy provides an attractive alternative to various types of upper tibial or distal femoral osteotomies. It eases the translations of the preoperative clinical and radiological evaluation to accurate angles during surgery. This type of osteotomy is stable, with large contact surfaces that provide excellent healing. Although no length is sacrificed, neither bone graft nor internal or external fixation is required.

Adolescent↗

Bone formation by marrow osteogenic cells (MBA-15) is not accompanied by osteoclastogenesis and generation of hematopoietic supportive microenvironment.

This study was aimed at elucidating the relationship between osteogenic activity of marrow stromal cells and their ability to support hematopoiesis followed by the bone-remodeling process. We used the MBA-15 cell line, which expresses osteoblastic phenotype in vitro and forms bone in diffusion chamber. We have compared bone formation and hematopoietic responses elicited in vivo by these cells with the implantation of freshly isolated bone marrow cells (BMC) or demineralized tooth matrix (DTM). Both MBA-15 cells and BMC, implanted under the kidney capsule, yielded intramembraneous bone, but DTM, implanted subcutaneously, elicited endochondral bone. MBA-15 formed primary bone, mimicking only the initial sequential stages of the ossification process. Neither histologic signs of bone resorption and remodeling nor tartrate-resistant acid phosphatase (TRAP)-positive cells and marrow formation were observed. Bone formation was monitored biochemically. Functions for hematopoietic stem and committed cell content were measured by GM-CFU and BFU-E assays that confirmed the morphologic observations. In both BMC and DTM implantation, bone formation was followed by hematopoietic activity, osteoclastogenesis, and remodeling. We conclude that MBA-15 osteoprogenitor cells, despite their extensive bone formation ability, are unable to form a microenvironment supportive for hematopoiesis and osteoclastogenesis or to initiate bone remodeling.

Animals↗

Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts.

The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH and PGE2, but no significant effects could be observed in other clonal lines.

1-Methyl-3-isobutylxanthine↗

Mineralization of marrow-stromal osteoblasts MBA-15 on three-dimensional carriers.

The present study describes a new three-dimensional (3-D) culture system that enables the maintenance and phenotypic expression of bone marrow stromal osteoblasts. This culture substratum is advantageous in that it provides suitable conditions for attachment, growth, and differentiation of cells forming 3-D layers. The MBA-15 cell line was grown in unlimited quantities on 3-D Fibro-Cel carriers. These cells mineralized when exposed to ascorbic acid and beta-glycerophosphate (beta GP). Under these mineralization conditions, mRNA expressions of procollagen alpha 2(I) and [3H]-proline-labeled protein were increased. The expression of mRNA for osteonectin and to a lesser extent, for osteopontin was increased, whereas alkaline phosphatase and biglycan remained unaffected under similar conditions. Exposure of mineralizing cultures to dexamethasone reduced mRNA of procollagen alpha 2 (I) and osteonectin to control level. Scanning electron microscopy revealed that cells were grown along the fabric's fibers and produced collagen fibrils. Under appropriate conditions, extensive mineralization had taken place. The mineralization process involves the formation of calcospherites, and correlates with an increase in calcium content. The Fibro-Cel carriers enable formation of 3-D architecture and mineralized tissue in vitro.

Animals↗

Marrow adipocytes regulate growth and differentiation of osteoblasts.

Conditioned media (CM) from various marrow subpopulations (MBA series) were examined for their effects on growth and maturation of marrow-derived osteoblastic cells, MBA-15. CM harvested from a stromal adipocytes, 14F1.1, stimulated cell growth, collagen but not non-collagenous proteins synthesized by MBA-15 cells. Alkaline phosphatase activity was inhibited under the same culture conditions. These results were associated with morphological changes, i.e., the large cuboidal MBA-15 cells acquired a fibroblast-like appearance. Exposure of MBA-15 cells to known growth factors: BMP-2, TGF beta, IGF-I and PDGF or combined with 14F1.1 CM resulted in a dominant effect of the latter. This may imply that marrow adipocytes produce factor/s that participate in the stromal regulation of osteoblastic functions.

Adipocytes↗

Osteoblasts release a soluble factor that modulates immunoglobulin secretion by mature B cells.

An osteogenic member, MBA-15 cell line, from marrow stroma compartment, was examined for its ability to regulate mature lymphoma B cell line functions. The effect of MBA-15 cell secreting factor/s on cell proliferation, immunoglobulin secretion and isotype switch of 29M4.1 IgM+ mature B cell line was examined. The factor causes temporal arrest in cell proliferation, augments immunoglobulin secretion and has no effect on isotype switching. The results revealed a direct effect of the MBA-15 factors on the B cell functions. Factors secreted by other osteoblastic cells (ROS 17/2.8 and MC-3T3-E1) possess the same biological activities. In contrast, factors secreted by an endothelial adipocyte stromal cell line 14F1.1 lack these properties.

Analysis of Variance↗

Marrow stroma-derived osteogenic clonal cell lines: putative stages in osteoblastic differentiation.

This report documents characterization of five osteogenic cell subpopulations of bone marrow stroma. The clonally derived cell lines were isolated from the parental line MBA-15 known to express osteoblastic-associated features in vitro and to form bone in vivo. The latter, presumably "arrested" at a particular stage along the osteogenic lineage, are useful models to study the processes involved in the differentiation of bone forming cells. The clones differ in their morphology, proliferation rate, quantities and distribution of extracellular matrix proteins, levels of alkaline phosphatase activity and activation of adenylate cyclase by parathyroid hormone and/or prostaglandin E. These properties have been retained during prolonged growth and subculturing through many passages. MBA-15.4 is a presumptive preosteoblast with a fibroblast-like appearance; it proliferates rapidly, synthesizes equal amounts of collagen and noncollagenous proteins, and produces constitutively low levels of alkaline phosphatase. This clone has PGE2-stimulated adenylate cyclase activity and a very low constitutive response to PTH. On the other hand, MBA-15.6 has a large polygonal morphology with limited proliferative potential, synthesizes twice as much noncollagenous proteins as collagen, has high alkaline phosphatase activity, and responds strongly to PTH. The characteristics of the other clones place them between these two categories. The effects of 10(-7) M dexamethasone or 10(-12)-10(-8) M 1,25 dihydroxyvitamin D3 on growth and differentiation further strengthen the variance between these clones. The different in vitro characteristics of the various clones were directly reflected in their bone formation ability in vivo. When transplanted under the renal capsule, MBA-15.33 formed a thick fibrous tissue, MBA-15.4 formed small foci of bone, and MBA-15.6 formed massive woven bone at the same period of time.

Adenylyl Cyclases↗

Hemopoietic functions of marrow-derived osteogenic cells.

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.

Alkaline Phosphatase↗

Subpopulations of marrow stromal cells share a variety of osteoblastic markers.

A series of stromal cell lines derived from mouse bone marrow, representing subpopulations of putative stromal cell types, were examined for the expression of osteoblastic properties. The effects of dexamethasone and specific inhibitors on alkaline phosphatase activity, cAMP response to bone-seeking hormones, and the ability to mineralize extracellular matrix in vitro as well as collagen typing were used as osteoblastic markers. We found that all stromal cell types examined possess some osteoblastic features but differ in the degree of expression. The data provide support to the hypothesis of a common stem cell for marrow stromal cells.

Alkaline Phosphatase↗

Dysplasia epiphysealis capitis femoris. Meyer's dysplasia.

We made a prospective longitudinal clinical and radiological study of 18 children diagnosed as having dysplasia epiphysealis capitis femoris. Half the cases were bilateral. Boys were affected five times more often than girls. There were no symptoms or clinical signs in most but some of the bilateral cases had an inconsistent waddling gait. The imaging studies suggest that the cartilaginous proximal femoral epiphysis is hypoplastic, with delayed appearance of single or multiple ossification centres. Progressive improvement occurred and at an average age of five years and six months, there was complete fusion of all the ossific nuclei and normal density and texture of the epiphyseal bone. The end result was a round epiphysis with a slightly diminished height. The dysplasia is attributed to focal hypoplasia of the proximal femoral epiphysis.

Arthrography↗