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J A Spector

Publications and source records attributed to J A Spector.

26 records · Page 2Linked to original sources
PubMed2000

Immature versus mature dura mater: II. Differential expression of genes important to calvarial reossification.

The ability of immature animals and newborns to orchestrate successful calvarial reossification is well described. This capacity is markedly attenuated in mature animals and in humans greater than 2 years of age. Previous studies have implicated the dura mater as critical to successful calvarial reossification. The authors have previously reported that immature, but not mature, dural tissues are capable of elaborating a high expression of osteogenic growth factors and extracellular matrix molecules. These findings led to the hypothesis that a differential expression of osteogenic growth factors and extracellular matrix molecules by immature and mature dural tissues may be responsible for the clinically observed phenotypes (i.e., immature animals reossify calvarial defects; mature animals do not). This study continues to explore the hypothesis through an analysis of transforming growth factor (TGF)-beta3, collagen type III, and alkaline phosphatase mRNA expression. Northern blot analysis of total RNA isolated from freshly harvested immature (n = 60) and mature (n = 10) dural tissues demonstrated a greater than three-fold, 18-fold, and nine-fold increase in TGF-beta3, collagen type III, and alkaline phosphatase mRNA expression, respectively, in immature dural tissues as compared with mature dural tissues. Additionally, dural cell cultures derived from immature (n = 60) and mature dura mater (n = 10) were stained for alkaline phosphatase activity to identify the presence of osteoblast-like cells. Alkaline phosphatase staining of immature dural cells revealed a significant increase in the number of alkaline phosphatase-positive cells as compared with mature dural tissues (p < 0.001). In addition to providing osteogenic humoral factors (i.e., growth factors and extracellular matrix molecules), this finding suggests that immature, but not mature, dura mater may provide cellular elements (i.e., osteoblasts) that augment successful calvarial reossification. These studies support the hypothesis that elaboration of osteogenic growth factors (i.e., TGF-beta33) and extracellular matrix molecules (i.e., collagen type III and alkaline phosphatase) by immature, but not mature, dural tissues may be critical for successful calvarial reossification. In addition, these studies suggest for the first time that immature dural tissues may provide cellular elements (i.e., osteoblasts) to augment this process.

Aging↗
PubMed2000

A molecular analysis of the isolated rat posterior frontal and sagittal sutures: differences in gene expression.

Although it is one of the most commonly occurring craniofacial congenital disabilities, craniosynostosis (the premature fusion of cranial sutures) is nearly impossible to prevent because the molecular mechanisms that regulate the process of cranial suture fusion remain largely unknown. Recent studies have implicated the dura mater in determining the fate of the overlying cranial suture; however, the molecular biology within the suture itself has not been sufficiently investigated. In the murine model of cranial suture fusion, the posterior frontal suture is programmed to begin fusing by postnatal day 12 in rats (day 25 in mice), reliably completing bony union by postnatal day 22 (day 45 in mice). In contrast, the sagittal suture remains patent throughout the life of the animal. Using this model, this study sought to examine for the first time what differences in gene expression--if any--exist between the two sutures with opposite fates. For each series of experiments, 35 to 40 posterior frontal and sagittal suture complexes were isolated from 6-day-old Sprague-Dawley rat pups. Suture-derived cell cultures were established, and ribonuicleic acid was derived from snap-frozen, isolated suture tissue. Results demonstrated that molecular differences between the posterior frontal and sagittal suture complexes were readily identified in vivo, although these distinctions were lost once the cells comprising the suture complex were cultured in vitro. Hypothetically, this change in gene expression resulted from the loss of the influence of the underlying dura mater. Significant differences in the expression of genes encoding extracellular matrix proteins existed in vivo between the posterior frontal and sagittal sutures. However, the production of the critical, regulatory cytokine transforming growth factor beta-1 was equal between the two suture complexes, lending further support to the hypothesis that dura mater regulates the fate of the overlying cranial suture.

Animals↗
PubMed1999

Transforming growth factor-beta1 modulates the expression of vascular endothelial growth factor by osteoblasts.

Angiogenesis is essential to both normal and pathological bone physiology. Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis, whereas transforming growth factor-beta1 (TGF-beta1) modulates bone differentiation, matrix formation, and cytokine expression. The purpose of this study was to investigate the relationship between TGF-beta1 and VEGF expression in osteoblasts and osteoblast-like cells. Northern blot analysis revealed an early peak of VEGF mRNA (6-fold at 3 h) in fetal rat calvarial cells and MC3T3-E1 osteoblast-like cells after stimulation with TGF-beta1 (2.5 ng/ml). The stability of VEGF mRNA in MC3T3-E1 cells was not increased after TGF-beta1 treatment. Actinomycin D inhibited the TGF-beta1-induced peak in VEGF mRNA, whereas cycloheximide did not. Blockade of TGF-beta1 signal transduction via a dominant-negative receptor II adenovirus significantly decreased TGF-beta1 induction of VEGF mRNA. Additionally, TGF-beta1 induced a dose-dependent increase in VEGF protein expression by MC3T3-E1 cells (P < 0.01). Dexamethasone similarly inhibited VEGF protein expression. Both TGF-beta1 mRNA and VEGF mRNA were concurrently present in rat membranous bone, and both followed similar patterns of expression during rat mandibular fracture healing (mRNA and protein). In summary, TGF-beta1-induced VEGF expression by osteoblasts and osteoblast-like cells is a dose-dependent event that may be intimately related to bone development and fracture healing.

Animals↗
PubMed1999

Adenovirus-mediated gene therapy of osteoblasts in vitro and in vivo.

Modulation of biological pathways governing osteogenesis may accelerate osseous regeneration and reduce the incidence of complications associated with fracture healing. Transforming growth factor beta1 (TGF-beta1) is a potent growth factor implicated in the regulation of osteogenesis and fracture repair. The use of recombinant proteins, however, has significant disadvantages and has limited the clinical utility of these molecules. Targeted gene therapy using adenovirus vectors is a technique that may circumvent difficulties associated with growth factor delivery. In this study, we investigate the efficacy of replication-deficient adenoviruses containing the human TGF-beta1 and the bacterial lacZ genes in transfecting osteoblasts in vitro and osseous tissues in vivo. We demonstrate that adenovirus-mediated gene therapy efficiently transfects osteoblasts in vitro with the TGF-beta1 virus causing a marked up-regulation in TGF-beta1 mRNA expression even 7 days after transfection. Increased TGF-beta1 mRNA expression was efficiently translated into protein production and resulted in approximately a 46-fold increase in TGF-beta1 synthesis as compared with control cells (vehicle- or B-galactosidase-transfected). Moreover, virally produced TGF-beta1 was functionally active and regulated the expression of collagen IalphaI (5-fold increase) and the vascular endothelial growth factor (2.5-fold increase). Using an adenovirus vector encoding the Escherichia coli LacZ gene, we demonstrated that adenovirus-mediated gene transfer efficiently transfects osteoblasts and osteocytes in vivo and that transfection can be performed by a simple percutaneous injection. Finally, we show that delivery of the hTGF-beta1 gene to osseous tissues in vivo results in significant changes in the epiphyseal plate primarily as a result of increased thickness of the provisional calcification zone.

Adenoviridae↗
PubMed1998

Periorbital melanocytic lesions: excision and reconstruction in 40 patients.

The treatment of melanoma arising in the periorbital region is a difficult reconstructive problem. The abundance of vital structures in close proximity to one another makes the resection and subsequent reconstructive procedures extremely challenging. Reported here is experience with periorbital melanocytic lesions in 40 patients with the emphasis on the types of reconstruction performed. Forty patients with periorbital melanocytic lesions were treated between 1984 and 1995. The periorbital region was subdivided into five zones. These zones are the following: zone I, upper eyelid; zone II, lower eyelid; zone III, medial canthus; zone IV, lateral canthus; and zone V, contiguous structures. Ocular melanomas were not included in this study. The distribution of the lesions in our 40 patients was zone I (n = 1), zone II (n = 14), zone III (n = 1), zone IV (n = 9), and zone V (n = 31). The ages of the patients ranged from 3 to 84 years at the time of reconstruction, with an average age of 57 years. Resection and reconstruction were performed simultaneously in all patients. Thirty-six of the patients were reconstructed with one procedure, three patients required two procedures, and one patient required five procedures. The tumor type was superficial spreading melanoma in 15 patients, melanoma in situ in 17 patients, malignant spindle cell neoplasm in 2 patients, desmoplastic melanoma in 2 patients, amelanocytic melanoma in 1 patient, epithelioid melanoma in 1 patient, and atypical melanocytic nevus in 2 patients in which an early, evolving melanoma could not be excluded. Elective lymph node dissection was performed in four patients for intermediate thickness lesions (1.5 to 4.0 mm). The types of reconstructions performed included full-thickness skin grafts, upper lid myocutaneous flaps, cheek advancement flaps, cervicofacial flaps, inferiorly based nasolabial flaps, tarsoconjunctival flaps, frontalis muscle flaps, medial transposition Z-plasty, and primary closure. The resection of periorbital melanomas can be difficult because of the number of important anatomic structures in the region. The challenge to the surgeon in handling head and neck melanomas in general lies in the need to provide the best functional and aesthetic result while still resecting the primary lesion with the intent of effecting a cure. We present our series to demonstrate that the adequacy of margins of resection need not be compromised to facilitate reconstruction and that excellent results are obtainable with reconstructive procedures performed after adequate resections. Several different types of flaps and grafts can be used, with the indications varying depending on the location of the lesion and the extent of resection. The major reconstructive options will be reviewed in detail.

Adolescent↗
PubMed1996

A classification of plagiocephaly utilizing a three-dimensional computer analysis of cranial base landmarks.

Plagiocephaly is a term commonly used to describe congenital forehead asymmetry. Previous classification systems based on the various etiologies of dysmorphic crania have been used in an effort to categorize the patients into groups and to assist in treatment planning. The system most commonly used today was described by Bruneteau and Mulliken in 1992. The authors separated frontal plagiocephaly into three types: synostotic, compensational, and deformational. The present study was undertaken in order to define a simple system for classifying plagiocephaly based on Bruneteau and Mulliken's system using the patients' preoperative craniofacial computed tomography scans. The involvement of the entire coronal ring in synostotic plagiocephaly led to the choice of 20 skull base landmarks as the basis of the analysis. Nine lateral landmarks (the superior orbital fissure, the optic foramen, the zygomatic arch, the greater palatine foramen, the foramen ovale, the mastoid tip, the hypoglossal canal, the external auditory canal, and the internal auditory canal) and two midline landmarks (the crista galli and the internal occipital protuberance) were used. The changes that occurred in these landmarks were analyzed in 30 patients. The results demonstrated that Bruneteau and Mulliken's classification system underestimated the number of different subtypes of plagiocephaly. As a result, three major types of frontal plagiocephaly and several different subtypes based on the different etiologies were described. Type I plagiocephaly includes plagiocephaly resulting from cranial suture synostosis. Type II includes those with a nonsynostotic etiology. Type III describes patients with craniofacial microsomia-associated plagiocephaly. Statistical analysis was unavailable because of the small number of patients in each subtype. With a larger number of patients, we hope to refine this system for use by the surgeon in preoperative diagnosis and surgical planning. The analysis is unique in its ability to quantitate changes from normal on the x-, y-, and z-coordinates, and therefore allows for identification of both horizontal (frontal bone deviation) and vertical (ear shear) growth disturbances.

Facial Asymmetry↗
PubMed1996

The management of pigmented lesions of the nail bed.

Pigmented lesions of the nail bed, especially without a history of trauma, represent a diagnostic challenge to the clinician. These lesions are often categorized as melanonychia striata (MS), which refers to any linear tan-brown-black pigmentation of the nail bed. The differential diagnosis of MS includes subungual hematomas, onchomycosis nigricans, junctional nevi, melanoma in situ (MIS), and malignant melanoma (MM). Our algorithm at the New York University (NYU) Medical Center for the treatment of pigmented lesions of the nail bed is presented. A histopathologic diagnosis with any evidence of melanocytic atypia, however subtle, requires absolute confirmation by complete excision. The absence of a clear margin or recurrence requires total nail bed excision and reconstruction using a full-thickness graft. The diagnosis of MIS is similarly treated. The surgical management of subungual MM is discussed. All cases of MM of the hand treated at NYU were reviewed. In all, 30 patients were treated from 1982 to 1995. Follow-up ranged from 6 months to 13 years. In our series, there were 8 cutaneous and 22 subungual melanomas. There was a marked delay in treatment of both groups, with subungual melanomas more often erroneously treated as other pathology prior to correct diagnosis. The 5-year survival rate was 100% for patients with cutaneous lesions, but only 80% for those with the subungual variety. There was a statistical difference in the depths of the lesions (subungual, 3.68 mm; cutaneous, 1.36 mm) with a p-value of 0.008. The role of elective lymph node dissection in the absence of clinical metastases as well as intraoperative sentinel lymphatic mapping remains controversial and is discussed.

Adolescent↗