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Biomedical subjects

A Shteyer

Publications and source records attributed to A Shteyer.

At least 19 recordsLinked to original sources

[Maxillofacial gunshot injuries in hostility activities in 2000-2003].

The management of facial gunshot wounded patients requires the coordination of multiple surgical disciplines to optimize the functional and cosmetic outcome while minimizing overall morbidity and mortality. All reports indicate that early management of these patients must focus on the basis of resuscitation, with major attention given to the status of maintaining the airway, hemostasis and hemodynamic resuscitation. Subsequent management of these patients becomes more controversial in terms of surgical reconstruction: immediate or delayed. Involvement of the use of suicide bombers, the type of weapons used in the last 2 years were different than previously described. The injuries were inflicted by explosives mixed with nails bolts and stones, which caused different kinds of wounds ever described. Numerous series in the literature advocate early aggressive intervention of one-stage reconstruction of all involved structures. However, several series published in the literature favor a more conservative approach, some of them even advocating non-operative management of these injuries. We concluded that a delay in final reconstruction of facial fractures in the critically ill patient has an acceptably low complication rate and may be advantageous in decreasing operative risk. A carefully planned reconstruction schedule is required to achieve satisfactory function and appearance. It is our purpose in this report to indicate the difference of the gunshot wounds in the last 2 years of the hostilities in this part of the world and emphasize the function of the Oral & Maxillofacial Surgeons in treating these patients.

Explosions↗

[The overlooked chin trauma in children].

UNLABELLED: Children seldom experience major facial trauma. However, minor injuries such as facial lacerations, abrasions and dental trauma are more common and naturally get less attention. Children with TMJ trauma usually present with pain, limited jaw movement and even malocclusion. However, these findings are not always recognized and sometimes get overlooked when chin laceration is the only sign. Plain x-rays can contribute to the diagnosis but in many cases are inconclusive and are difficult to interpret. Often, there is a diagnostic dilemma, especially when the clinical findings are not clear and normal occlusion is hard to restore. We present 3 out of 12 children in whom we diagnosed condylar head fracture following minor facial trauma. All children had normal physiological occlusion. Most of them had mild clinical signs such as limited mouth opening, pain and tenderness upon palpation of the joint. Routine plain films were not conclusive. The diagnosis was made or confirmed with CT scan. Early diagnosis of TMJ fracture in children is mandatory for the prevention of long term functional and esthetically debilitating sequela. CONCLUSION: A thorough clinical examination and normal occlusion do not rule out condylar head fracture after chin trauma. Plain films are of limited value in the diagnosis of such fractures. CT should be considered for the evaluation of these children.

Child↗

Structure-bioactivity of C-terminal pentapeptide of osteogenic growth peptide [OGP(10-14)].

The amino acid sequence of osteogenic growth peptide (OGP) consists of 14 residues identical to the C-terminal tail of histone H4. Native and synthetic OGP are mitogenic to osteoblastic and fibroblastic cells and enhance osteogenesis and hematopoiesis in vivo. The C-terminal truncated pentapeptide of OGP, H-Tyr-Gly-Phe-Gly-Gly-OH [OGP(10-14)], is a naturally occurring osteoblastic mitogen, equipotent to OGP. The present study assesses the role of individual amino acid residues and side chains in the OGP(10-14) mitogenic activity which showed a very high correlation between osteoblastic and fibroblastic cell cultures. Truncation of either Tyr10 or its replacement by Ala or D-Ala resulted in substantial, but not complete, loss of activity. Nevertheless, only a small loss of activity was observed following removal of the Tyr10 amino group. No further loss occurred consequent to the monoiodination of desaminoTyr10 on meta-position. However, a marked decrease in proliferative activity followed removal of the Tyr10 phenolic or the Phe12 aromatic group. Loss of activity of a similar magnitude also occurred subsequent to replacing Gly11 with L- or D-Ala. Approximately 50% loss of mitogenic activity occurred subsequent to truncation of Gly14 or blocking the C-terminal group as the methyl ester. All other modifications of the C-terminus and L- or D-Ala substitution of Gly13 resulted in 70-97% decrease in activity. Collectively, these data suggest that the integrity of the pharmacophores presented by Tyr and Phe side chains, as well as the Gly residues at the C-terminus, are important for optimal bioactivity of OGP(10-14).

Amino Acid Sequence↗

Isolation of mitogenically active C-terminal truncated pentapeptide of osteogenic growth peptide from human plasma and culture medium of murine osteoblastic cells.

The osteogenic growth peptide (OGP) is a 14-amino acid stromal cell mitogen that stimulates in vivo osteogenesis and hematopoiesis. In the blood circulation and cell culture conditioned medium immunoreactive OGP (irOGP), identified using antibodies raised against the OGP C-terminal region, presents free and bound forms. The bound form consists entirely of the full length peptide. The present study was designed to investigate the identity of free irOGP under nondenaturing conditions. Fresh human serum and culture medium conditioned with murine osteoblastic MC3T3 E1 cells were fractionated using ultrafiltration (3000 molecular weight cut-off). Hydrophobic chromatography of the ultrafiltrate, immunoscreening of chromatographic fractions with antibodies directed against the OGP C-terminal region and amino acid sequencing of immunoreactive peaks demonstrated the presence of two mitogens, the full length OGP and a C-terminal truncated form, OGP(10-14). The OGP(10-14) derived from both serum and conditioned medium, as well as the synthetic pentapeptide [sOGP(10-14)], shared the in vitro OGP proliferative activity. However, in a competitive binding assay, devised to assess the OGP-OGP binding protein (OGPBP) complex formation, sOGP(10-14) failed to compete out radiolabeled OGP from the complex. It is concluded that OGP(10-14) is a naturally occurring human and murine mitogen. In addition, the data suggests that the OGP(10-14) is generated from OGP by proteolytic cleavage upon dissociation of the OGP-OGPBP complexes.

Animals↗

Surgical management of temporomandibular joint ankylosis type III by retaining the displaced condyle and disc.

PURPOSE: This article proposes a hypothesis regarding the value of saving the fractured condyle and disc in their displaced position in ankylosis type III for optimal temporomandibular joint (TMJ) function and growth, and describes four cases treated in this manner. PATIENTS AND METHODS: Four patients (three females and one male, 9 to 48 years old) with TMJ ankylosis type III of 3 to 8 years' duration, a maximal mouth opening of 15 to 19 mm, and severely limited lateral and protrusive movements were treated. The ankylosed sites were resected, leaving the displaced condyle and disc in their medial position. RESULTS: Fifteen to 60 months after surgery, the patients had a maximal mouth opening of 44 to 50 mm, as well as better contralateral and protrusive movements. In addition, two young patients (9 and 11 years old) showed an improved facial symmetry. CONCLUSIONS: Treatment of patients with type III TMJ ankylosis should involve retention rather than removal of the displaced condyle and disc. The condyle and disc are left untouched in their precarious medial position so as to provide normal function and growth.

Adult↗

Isolation of osteogenic growth peptide from osteoblastic MC3T3 E1 cell cultures and demonstration of osteogenic growth peptide binding proteins.

The osteogenic growth peptide (OGP) was recently characterized in regenerating bone marrow. In experimental animals in increases osteogenesis and hemopoiesis. In stromal cell cultures OGP stimulates proliferation, alkaline phosphatase activity, and matrix mineralization. OGP in high abundance is present in normal human and animal serum mainly complexed to OGP binding protein (OGPBP) or proteins. Here we show the presence of two OGPBPs, OGPBP-1, and OGPBP-2, in cultures of osteoblastic MC3T3 E1 cells. Immunoreactive OGP (irOGP) also accumulates in the medium of these cultures and in cultures of NIH 3T3 fibroblasts. A large amount of irOGP was released by heat inactivation of OGPBP-2 and purified by ultrafiltration and hydrophobic HPLC. The purified irOGP was identical to OGP obtained previously from rat regenerating bone marrow and human serum in terms of its amino acid sequence, immunoreactivity, and mitogenicity. Osteoblastic and fibroblastic cell proliferation can be arrested by anti-OGP antibodies and rescued by exogenous OGP, indicating that in the absence of serum or other exogenous growth stimulators the endogenously produced OGP is both necessary and sufficient for baseline proliferation. The OGP production is up- and down-regulated, respectively, by low and high doses of exogenous OGP in a manner consistent with an autoregulated feedback mechanism. The most effective OGP dose in MC3T3 E1 cells is at least two orders of magnitude lower than that in non-osteoblastic cell systems. This differential sensitivity of the osteoblastic cells could result in a preferential anabolic effect of OGP in bone.

3T3 Cells↗

Cleidocranial dysplasia: Part 2--Treatment protocol for the orthodontic and surgical modality.

The principles on which the present approach to the treatment of cleidocranial dysplasia are based were stated in part 1 of this article. Comparison was made with two other methods and the advantages of the present method were described in terms of (a) how this method is adapted to the clinical features of the condition, (b) when surgical intervention is appropriate, (c) how the dynamic appliance system may be adapted to the changing environment as more teeth erupt, and (d) the importance of rapidly bringing about the eruption of the anterior teeth. The practical aspects of the treatment are now described step-by-step with illustrations taken from the treatment of several different patients.

Adolescent↗

Cleidocranial dysplasia: Part 1--General principles of the orthodontic and surgical treatment modality.

Over several decades, occasional reports of dental treatment provided by an individual practitioner to patients suffering with cleidocranial dysplasia have appeared in the literature. In the past, the main treatment was prosthetic replacement. Orthodontic treatment has only recently been considered as a serious treatment option, with success being described in several aspects of this treatment modality, in published individual case reports. Given the rarity of the condition, guidelines for the treatment of cleidocranial dysplasia are difficult to find in the literature, because few practitioners have treated enough cases to be in a position to make such recommendations. Two different approaches have been proposed in the past and are discussed here. The relative advantages of a third approach are expounded in detail.

Child↗

Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice.

The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.

Animals↗

Attachment bonding to impacted teeth at the time of surgical exposure.

This study examines the relative success of bonding an attachment to an impacted tooth at the time of surgical exposure, compared with placing it on a subsequent occasion. In addition, the relative merits of various attachments, the choice of bonding site and whether or not pumice prophylaxis is necessary, were tested. The results showed that bonding at the time of exposure is superior to its performance at a later date, that the use of an eyelet attachment has a lower failure rate than the use of a conventional bracket, that the palatal aspect offers the poorest bonding surface and that pumicing the exposed tooth offers no advantage over immediate etching of the exposed enamel. The results of this study refute the view that the circumstances prevalent at the time of surgical exposure are not conducive to the reliable bonding of an attachment to an impacted tooth.

Acid Etching, Dental↗

Structural and functional characterization of osteogenic growth peptide from human serum: identity with rat and mouse homologs.

The osteogenic growth peptide (OGP) was recently characterized in regenerating bone marrow. In experimental animals, OGP increases osteogenesis. Immunoreactive OGP (irOGP) in high abundance was demonstrated in normal animal serum mainly as an OGP-OGP-binding protein (OGPBP) complex. Here we show the presence of an OGP-OGPBP system in normal human serum. The total irOGP content, of which the bound peptide comprises at least 80-90%, ranged from 480-4460 mumol/L, several orders of magnitude higher than that of other regulatory polypeptides. The steady state/total irOGP ratio declined between 23 and 49 yr of age. The bound irOGP, purified by boiling, ultrafiltration, and hydrophobic high pressure liquid chromatography, was identical to OGP obtained previously from rat regenerating marrow and mouse stromal cell cultures in terms of its amino acid sequence, immunoreactivity, and mitogenicity. These data demonstrate the usefulness of our immunoassay to measure circulating OGP. More importantly, the identity of the human OGP with that of other species indicates the peptide's evolutionary conservation and, thus, its biological importance. The natural occurrence of OGP in man signifies its potential role in the prevention of bone loss and rescue of bone mass, especially in osteoporosis.

3T3 Cells↗

Mitogenic action of osteogenic growth peptide (OGP): role of amino and carboxy-terminal regions and charge.

We have recently reported the discovery of a 14-amino-acid osteogenic growth peptide (OGP). In vivo OGP increases bone formation and trabecular bone density. Physiologically it is found in serum complexed to an OGP binding protein (OGPBP). In vitro OGP has a biphasic effect on osteoblastic MC 3T3 E1 and fibroblastic NIH 3T3 cell proliferation; at low concentrations (0.01-1.0 and 1.0-100.0 pM, respectively) it is highly stimulatory with an inhibition at higher doses. To assess possibilities of labeling synthetic OGP to obtain radio- or fluorescent ligands, OGP analogues were extended at the N- or C-termini with Cys or Cys(S-NEtSucc) or the OGP Tyr-10 replaced by 3-I(Tyr). All analogues with N-terminal modifications, as well as the [Cys15]OGP-NH2 retained the OGP-like dose-dependent effect on proliferation of the MC 3T3 E1 and NIH 3T3 cells, although the magnitude of stimulation was lower, approx. 2/3 that of the native-like synthetic OGP. The [Cys15(S-NEtSucc)]OGP-NH2 and [3-I(Tyr10)]OGP shared only the inhibitory activity of OGP. This suppression is further shared by a number of other positively and negatively net charged, but not net neutral, peptides. Both N-terminal-modified analogues displayed a decreased binding activity to the OGPBP. All analogues except reverse OGP, [3-I(Tyr10)]OGP and [Cys15(S-NEtSucc)]OGP-NH2 reacted with anti-OGP antibodies. These data are not only important for labeling purposes but suggest a respective role for the OGP N-and C-terminal regions in binding to the OGPBP and putative OGP receptor. It appears that the OGP proliferative activity represents the net effect of stimulation specific to the OGP structure and nonspecific inhibition associated with the peptide's high positive net charge.

3T3 Cells↗

Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity.

It has been established that regenerating marrow induces an osteogenic response in distant skeletal sites and that this activity is mediated by factors released into the circulation by the healing tissue. In the present study we have characterized one of these factors, a 14 amino acid peptide named osteogenic growth peptide (OGP). Synthetic OGP, identical in structure to the native molecule, stimulates the proliferation and alkaline phosphatase activity of osteoblastic cells in vitro and increases bone mass in rats when injected in vivo. Immunoreactive OGP in high abundance is present physiologically in the serum, mainly in the form of an OGP-OGP binding protein complex. A marked increase in serum bound and unbound OGP accompanies the osteogenic phase of post-ablation marrow regeneration and associated systemic osteogenic response. Authentic OGP is identical to the C-terminus of histone H4 and shares a five residue motif with a T-cell receptor beta-chain V-region and the Bacillus subtilis outB locus. Since these latter proteins have not been implicated previously in the control of cell proliferation or differentiation, OGP may belong to a novel, heretofore unrecognized family of regulatory peptides. Perhaps more importantly, OGP appears to represent a new class of molecules involved in the systemic control of osteoblast proliferation and differentiation.

Amino Acid Sequence↗

Effect of demineralized bone powder on osteoblast-like cells in culture. A potential rapid quality control assay.

Demineralized bone powder (DBP) has been shown to induce osteogenesis in a variety of bone defects and extra-osseous sites. Previous investigations have been carried out in animal models which are time-consuming and expensive. We studied the effect of DBP on well-established populations of osteoblast and non-osteoblast-like cells in culture to establish an inexpensive, efficient and reliable assay for bone induction. DBP and BP (non-demineralized powder), of particle size 38-53 microns, were prepared from rat long bones. ROS (rat osteosarcoma) 17/2.8 and ROS 24/1 cell lines were subcultured weekly. For both 17/2.8 (well differentiated) and 24/1 (poorly differentiated) cells, proliferation, i.e. cell count, was significantly greater in DBP enriched medium when compared with control or medium with BP. Cell counts for wells with BP were no different from controls. The increased cell count in DBP-enriched medium was significant on days 2-5 (peak effect 2-3 days). Alkaline phosphatase production reached peak levels after day 3 when proliferation was beginning to taper off. In this study a consistent increase in osteoblast proliferation and alkaline phosphatase production under the influence of DBP was demonstrated. The tissue culture assay for proliferation must now be correlated with bone induction in vivo. In future, the method may be useful for investigating the mechanism of bone induction.

Alkaline Phosphatase↗

Further characterization of osteogenic-cell growth promoting activity derived from healing bone marrow.

During its osteogenic phase, post-ablation regenerating bone marrow produces bone promoting activity to osteogenic cells. In the experiments reported, activity derived from (rat) healing bone marrow conditioned medium (HBMCM) after boiling was analyzed using chromatography on heparin-Sepharose. The activity in HBMCM was shown to be divided among at least six independent activities that stimulated DNA synthesis rates is osteogenic rat osteosarcoma (ROS) cells. Three activities resolved when heparin-Sepharose was washed isocratically with phosphate buffered saline. Two of these were resistant to reduction and acidification and their effect was considerably more potent in osteogenic than non-osteogenic ROS cells. Three additional activity peaks recovered when the heparin-Sepharose column was pumped with an NaCl gradient. Two of them eluted at 0.3 and 0.65 M NaCl, affected osteogenic and non-osteogenic ROS cells to a similar extent and may be attributed to platelet-derived growth factor. A third peak, resolved at 1.2 M NaCl, implies the residual activity of acidic fibroblast growth factor that persisted after boiling of the conditioned medium. It is concluded that the activity profile of HBMCM reflects the in vivo situation where the osteogenic phase of marrow regeneration is probably regulated by multiple growth factor species.

Alkaline Phosphatase↗

Mitogenic response of cells in culture to demineralized bone matrix.

In this study the mitogenic effect of demineralized bone powder (DBP) on cells in tissue culture was evaluated. The cells studied have osteoblastic properties. At a DBP concentration of 100 micrograms/well, rat osteosarcoma cells (ROS) 17/2.8 cells, ROS 24/1 cells, and periosteal fibroblasts (POF) all showed a significant increase in proliferation in comparison to controls. The peak effect was on day two for ROS 17/2.8 (125% of control), on day three for ROS 24/1 (139% of control), and on day four for POF (145% of control). The results indicate that this in vitro system may be useful for evaluating the osteoinductive activity of DBP preparations.

Animals↗

Regenerating bone marrow produces a potent growth-promoting activity to osteogenic cells.

It is well documented that injury to bone marrow is followed by an osteogenic phase that precedes the complete tissue regeneration. We have recently shown that postablation healing of bone marrow in rat tibiae is associated with a systemic increase in osteogenesis. It was hypothesized that a growth factor(s) with an effect on osteogenic cells is produced in the healing limb, is transferred to the blood circulation, and enhances osteogenesis systemically. To test growth factor production, healing bone marrow-conditioned medium was prepared with tissue separated from rat tibias during the osteogenic phase and assayed for enhancement of mitogenic activity in culture of osteogenic rat osteosarcoma cells (ROS 17/2). Partial purification of healing bone marrow-conditioned medium-derived growth factor(s) consisted of gel filtration on Sephadex G-25, boiling, chromatography on heparin-Sepharose, and gel filtration on Sephadex G-75. Mitogenic activity eluted in the void volume of the Sephadex G-25 column (mol wt greater than 5,000). Potent activity resolved from heparin-Sepharose with PBS, and on filtration by Sephadex G-75 this activity recovered in 3 peaks with mol wt estimates of 35,000, 19,000, and less than 10,000. The partially purified factor also showed considerable stimulatory effect on DNA synthesis in osteoblastic fetal rat calvarial cells and on in vitro elongation of fetal long bone; it had only a small effect on nonosteoblastic ROS and fetal rat calvarial cells. These data indicate that healing bone marrow produces growth factor activity with a preferential effect on osteogenic cells. It is suggested that local growth factors have a role as mediators in the sequence of events whereby bone marrow expresses its osteogenic potential. During postablation healing of bone marrow these factors may also function as systemic promoters to osteogenic cells.

Animals↗