Biomedical subjects

S Bresnick

Publications and source records attributed to S Bresnick.

9 recordsLinked to original sources

PubMed2000

In vitro characteristics of neonatal hemangioma endothelial cells: similarities and differences between normal neonatal and fetal endothelial cells.

BACKGROUND: Increased angiogenesis and eventual involution are major characteristics of neonatal hemangiomas. The mechanism to explain this transition is not completely understood. METHODS: To determine the nature of these changes, endothelial cells were isolated from eight hemangiomas and the growth characteristics and morphology of these cells were compared to cells isolated from normal fetal and neonatal skin. Three cells lines were further characterized by analyzing protein expression with immunohistochemistry and FACS analysis. RESULTS: Hemangioma endothelial cells converted to a spindle-shaped morphology similar to that of fetal endothelial cells whereas neonatal endothelial cells maintained their characteristic epithelioid morphology. While neonatal, hemangioma and fetal endothelial cells continued to express platelet-endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand factor (vWf), hemangioma and fetal cells expressed both proteins at a lower level and in a distribution distinct from normal neonatal endothelial cells. Neonatal endothelial cells continued to express epithelial specific Type IV collagen, while hemangioma and fetal endothelial cells produced interstitial Type I collagen. CONCLUSIONS: Both cell morphology and protein expression of neonatal hemangioma endothelial cells were more characteristic of embryonic microvascular endothelial cells than that of postembryonic cells demonstrating a similarity in these two cell types and suggesting a dysfunction in the normal growth and maturation of endothelial cells in this tumor.

Biomarkers, Tumor↗

PubMed1999

Proliferative hemangiomas: analysis of cytokine gene expression and angiogenesis.

Hemangiomas are benign vascular tumors of childhood that can lead to disfigurement and/or life-threatening consequences. The pathogenesis of hemangioma formation is likely to involve increased angiogenesis. Basic fibroblast growth factor and vascular endothelial growth factor are cytokines that stimulate angiogenesis in multiple in vivo and in vitro models. Proliferative hemangiomas have been found to have elevated levels of basic fibroblast growth factor and vascular endothelial growth factor protein, but the gene expression of these cytokines in human specimens has not been previously studied. We examined the gene expression and spatial distribution of basic fibroblast growth factor and vascular endothelial growth factor messenger RNA in proliferative versus involuted human hemangioma specimens using nonisotopic in situ hybridization techniques. Thirteen hemangioma specimens were harvested during initial surgical excision. In situ hybridization was performed on frozen sections of both proliferative and involuted hemangioma specimens using genetically engineered antisense probes specific for basic fibroblast growth factor and vascular endothelial growth factor messenger RNA. Controls were an interleukin-6 sense sequence and a transforming growth factor-beta 1 antisense sequence. A large number of cells within the specimens of proliferative hemangiomas revealed localized gene expression of basic fibroblast growth factor and vascular endothelial growth factor messenger RNA (626 +/- 129 and 1660 +/- 371 cells/mm2, respectively). The majority of the cells were endothelial in origin. In contrast, involuted hemangioma specimens revealed significantly lower numbers of cells staining positive for basic fibroblast growth factor and vascular endothelial growth factor messenger RNA (44 +/- 11 and 431 +/- 76 cells/mm2, respectively; p < 0.05). Transforming growth factor-beta 1 messenger RNA was slightly more expressed by involuted hemangiomas (117 +/- 30 cells/mm2). There were very low levels of transforming growth factor-beta 1 gene expression from proliferative hemangiomas (37 +/- 24 cells/mm2; p < 0.02). These data demonstrate that (1) in situ hybridization allows identification and relative quantitation of cells expressing messenger RNA for specific growth factors in human hemangioma specimens; (2) basic fibroblast growth factor and vascular endothelial growth factor messenger RNA are up-regulated in proliferative hemangiomas; and (3) transforming growth factor-beta 1 messenger RNA remains low in both proliferative and involuted hemangiomas. Because basic fibroblast growth factor and vascular endothelial growth factor messenger RNA have been implicated in the pathobiology of human hemangioma formation, biochemical modulation of these angiogenic cytokines may eventually help inhibit proliferation and promote regression of hemangiomas.

Child, Preschool↗

PubMed1999

Basic fibroblast growth factor and transforming growth factor beta-1 expression in the developing dura mater correlates with calvarial bone formation.

Numerous studies have found dura mater-calvarial mesenchyme interactions during calvarial bone induction; however, the exact molecular mechanisms governing these inductive events remain unknown. Recent studies have implicated basic fibroblast growth factor (FGF-2) and transforming growth factor-beta1 (TGF-beta1) in regulating bone formation. The purpose of this study was, therefore, to investigate the expression of FGF-2 and TGF-beta1 during calvarial bone formation in rats. Eight rats were killed on embryonic days 14, 18, and 20 and neonatal day 1 (n = 32). Four animals at each time point were analyzed by in situ hybridization, and the remainder were analyzed by immunohistochemistry. The results indicated that the dura mater underlying the developing calvarial bone strongly expressed FGF-2 and TGF-beta1 mRNA at all time points examined. In contrast, minimal growth factor expression was noted in the overlying calvarial mesenchyme until embryonic day 18, but it increased significantly with increasing age. Importantly, FGF-2 and TGF-beta1 mRNA expression in the dura mater underlying the developing calvarium preceded and was significantly greater than expression in the calvarium mesenchyme (p < 0.05). Interestingly, minimal expression of FGF-2 and TGF-beta1 mRNA was noted for all time points in the dura mater underlying the posterior frontal suture and within the posterior frontal suture connective tissue (p < 0.01 when compared with the dura mater underlying the developing calvarium). Immunohistochemical findings closely paralleled mRNA expression, with intense staining for FGF-2 and TGF-beta1 in the dura mater underlying the developing calvarial mesenchyme. Increasing FGF-2 and TGF-beta1 staining was noted within calvarial osteoblasts with increasing age, particularly in cells located near the endocranial surface (i.e., in contact with the developing dura mater). These findings, together with the known biologic functions of FGF-2 and TGF-beta1, implicate these growth factors in the regulation of calvarial bone growth by the developing dura mater. The possible mechanisms of this interaction are discussed.

Animals↗

PubMed1998

Apert's syndrome correlates with low fibroblast growth factor receptor activity in stenosed cranial sutures.

Recent genetic studies have shown that Apert's syndrome results from mutations of the fibroblast growth factor (FGF) receptor 2 gene. We were interested in investigating the expression of FGF receptor 2 at the tissue level in children with Apert's syndrome. We studied FGF receptor activity in cranial sutures of children with Apert's syndrome and nonsyndromic, isolated craniosynostosis. Fourteen children between the ages of 6 months and 12 months were studied. Five of these children had Apert's syndrome with coronal suture stenosis. Nine children had an isolated, nonsyndromic coronal stenosis. Stenosed and nonstenosed cranial sutures were removed at the time of cranioplasty, fixed, decalcified, and paraffinized. Immunohistochemistry was performed with labeled, specific anti-FGR receptor 2 antibodies. We found lower levels of FGF receptor 2 staining in both stenosed and unstenosed sutures of children with Apert's syndrome compared with those from children with a nonsyndromic suture stenosis. Furthermore, fused sutures from children with Apert's syndrome demonstrated lower levels of FGF receptor 2 staining than unfused sutures from the same sample. The findings suggest that Apert's syndrome correlates with low FGF receptor 2 activity in cranial sutures. These results are consistent with and similar to our findings in Crouzon's syndrome, and support genetic studies showing localized mutational changes occurring at the FGF receptor 2 gene for both Apert's and Crouzon's syndromes. Furthermore, the findings suggest the possibility that variable expression of FGF receptor 2 occurs at the tissue level in patients with Apert's syndrome.

Acrocephalosyndactylia↗

PubMed1997

The development of multiple role-related selves during adolescence.

The organization of the adolescent self-portrait is discussed within a framework that focuses on the construction of multiple self-representations across different relational contexts. Contradictions between self-attributes in different contexts create conflict, beginning in midadolescence when cognitive-developmental structures allow one to detect but not resolve opposing attributes. Conflict is greater across roles than within roles. Moreover, for certain roles (e.g., self with mother vs. self with father) conflict is higher. Females, particularly those with a feminine gender orientation, report greater conflict involving attributes in more public contexts. Opposing self-attributes also raise concerns for adolescents about which attributes reflect true versus false self-behaviors. Conflict is more frequent for opposing attributes that pit true against false self-characteristics. False self-behavior is associated with liabilities including devaluation of false self-attributes, low self-esteem, and depressive reactions. Perceived support across relational contexts is highly predictive of favorable evaluations of attributes, high self-esteem, and true self-behavior within corresponding contexts. Strategies for resolving potential contradictions in self-attributes would appear to emerge as one moves into late adolescence and adulthood, when multiple self-representations are perceived as both appropriate and desirable, and the individual can achieve some degree of integration through higher level abstractions and the narrative construction of his or her life story.

Adolescent↗

PubMed1997

Acute reconstruction of traumatic injuries of median and ulnar nerves by grafting with intercostal nerves from the rectus muscle: case reports.

In two cases of complicated hand and wrist injuries for which rectus flaps were used as soft-tissue coverage, intercostal nerves from the rectus muscles were harvested simultaneously to graft significant nerve defects. In one patient, a 7-cm ulnar-nerve defect was bridged with four intercostal nerves. The other patient had a 5-cm median-nerve defect repaired with three intercostal nerves. Both patients recovered either protective or normal sensation; and the patient with the median nerve injury recovered thenar muscle function. Intercostal nerves harvested with rectus muscle flaps can be the basis for acute grafting of nerve defects without using conventional nerve grafts at a traumatic site.

Abdominal Muscles↗

PubMed1997

Preliminary report: a ceramic containing crosslinked collagen as a new cranial onlay and inlay material.

Simple ceramic bone graft materials have demonstrated significant limitations for use in craniomaxillary reconstruction. We investigated a new, alloplastic composite bone grafting material containing particulate hydroxyapatite and crosslinked collagen in a time-sequence study. Five rabbits underwent surgical placement of high-loading and low-loading composite onlay and inlay grafts in the parietal region of the skull. Animals were sacrificed at either 1, 2, 4, or 6 months postoperatively. All rabbits demonstrated tissue continuity and healing of both onlay and inlay grafts to the outer table of the skull. Bony ingrowth was shown in both onlays and inlays with bone proliferation and vascularization. Bony ingrowth was seen as early as 1 month postoperatively. Inlay grafts healed flush to the outer table, while onlay grafts maintained at least 80% of graft volume at 6 months postoperatively. We conclude that a composite bone grafting material containing a ceramic and collagenous matrix may offer significant advantages to the reconstructive surgeon. The material appears to be easy to handle and carve, is biologically tolerated, and is able to maintain graft volume. Further studies of this new composite material are warranted.

Animals↗

PubMed1995

Crouzon's disease correlates with low fibroblastic growth factor receptor activity in stenosed cranial sutures.

Reports have demonstrated that Crouzon's disease is associated with a gene on chromosome 10 coding for the fibroblastic growth factor (FGF) receptor 2. The purpose of this investigation was to evaluate the FGF receptor 2 levels in cranial sutures of children with Crouzon's disease and nonsyndromic, isolated craniosynostosis. Twelve children between the ages of 6 and 24 months were studied. Four patients had Crouzon's disease with coronal suture stenosis. The 8 remaining had a nonsyndromic, isolated coronal stenosis. Stenosed and adjacent nonstenosed cranial sutures were removed at cranioplasty and promptly fixed, decalcified, and embedded in paraffin. Immunohistochemical analysis of cranial sutures was performed with labeled, specific anti-FGF receptor 2 antibodies. In children with Crouzon's disease, we found significantly lower levels of FGF receptor 2 staining in stenosed sutures compared with nonstenosed sutures. In addition, sutures from children with Crouzon's disease demonstrated lower levels of FGF receptor 2 activity in both stenosed and nonstenosed sutures compared with children with a nonsyndromic, isolated coronal stenosis. However, there were no significant differences in FGF receptor 2 staining between stenosed and nonstenosed sutures in children with a nonsyndromic, isolated coronal stenosis. These findings suggest that low FGF receptor 2 activity in cranial sutures correlates with Crouzon's disease. This work supports genetic studies and yet shows that patients with Crouzon's disease have low FGF receptor 2 activity in cranial sutures. The findings also suggest that there may be etiological differences between syndrome- and nonsyndrome-associated craniosynostoses in children.

Child, Preschool↗

PubMed1991

Improved healing of tympanic membrane perforations with basic fibroblast growth factor.

We have investigated the effects of basic fibroblast growth factor (FGF) on the healing of tympanic membrane (TM) perforations. In the first series of experiments, a simple, round 1-mm perforation was made in the membrane and the effects of basic FGF examined. In a second series of experiments, basic FGF was tested on 2-mm perforations in which the borders were folded inward in order to delay normal healing. Topical applications of saline or basic FGF were administered onto gelfoam overlays of the TM perforations in 51 guinea pigs by delivering 5 microliters aliquots of PBS or 5 microliters of PBS containing 1 microgram of basic FGF on the day of surgery and daily thereafter. Repair of the lesions was evaluated 3, 5 or 8 days after surgery. The results show that basic FGF mediates faster healing of TM perforations by inducing rapid proliferation of the subepithelial connective tissue layer.

Animals↗