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Biomedical subjects

M A Ignelzi

Publications and source records attributed to M A Ignelzi.

10 recordsLinked to original sources

Mechanical environment alters tissue formation patterns during fracture repair.

Fracture repair has previously been shown to be sensitive to mechanical environment, yet the specific relationship between strain character, magnitude and frequency, as well as other mechanical parameters, and tissue formation is not well understood. This study aimed to correlate strain distribution within the healing fracture gap with patterns of tissue formation using a rat model of a healing osteotomy subject to mechanical stimulation in bending. Finite element models based on realistic tissue distributions were used to estimate both the magnitude and spatial distribution of strains within the fracture gap. The spatial distribution of regenerating tissue was determined by microcomputed tomography and histology, and was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Results suggest that tensile strains suppress chondrogenesis during the mechanical stimulation period. After stimulation ends, however, tensile strains increased chondrogenesis followed by rapid bone formation. In contrast, in compressive environments, bone is formed primarily via intramembranous ossification. Taken together, these results suggest that intermittent tensile strains during fracture repair stimulate endochondral ossification and promote eventual bone healing compared to intermittent compressive strains and unstimulated fractures. Further understanding of these relationships may allow proposal of optimal therapeutic strategies for improvement of the fracture repair process.

Animals↗

Compatibility of staining protocols for bone tissue with Raman imaging.

We report the use of Raman microscopy to image mouse calvaria stained with hematoxylin, eosin and toluidine blue. Raman imaging of stained specimens allows for direct correlation of histological and spectral information. A line-focus 785 nm laser imaging system with specialized near-infrared (NIR) microscope objectives and CCD detector were used to collect approximately 100 x 450 micro m Raman images. Principal components analysis, a multivariate analysis technique, was used to determine whether the histological stains cause spectral interference (band shifts or intensity changes) or result in thermal damage to the examined tissue. Image analysis revealed factors for tissue components and the embedding medium, glycol methacrylate, only. Thus, Raman imaging proved to be compatible with histological stains such as hematoxylin, eosin and toluidine blue.

Animals↗

Premature suture closure and ectopic cranial bone in mice expressing Msx2 transgenes in the developing skull.

The coordinate growth of the brain and skull is achieved through a series of interactions between the developing brain, the growing bones of the skull, and the fibrous joints, or sutures, that unite the bones. These interactions couple the expansion of the brain to the growth of the bony plates at the sutures. Craniosynostosis, the premature fusion of the bones of the skull, is a common birth defect (1 in 3000 live births) that disrupts coordinate growth and often results in profoundly abnormal skull shape. Individuals affected with Boston-type craniosynostosis, an autosomal dominant disorder, bear a mutated copy of MSX2, a homeobox gene thought to function in tissue interactions. Here we show that expression of the mouse counterpart of this mutant gene in the developing skulls of transgenic mice causes craniosynostosis and ectopic cranial bone. These mice provide a transgenic model of craniosynostosis as well as a point of entry into the molecular mechanisms that coordinate the growth of the brain and skull.

Animals↗

Genetically engineered mice: tools to understand craniofacial development.

In this review, we provide a survey of the experimental approaches used to generate genetically engineered mice. Two specific examples are presented that demonstrate the applicability of these approaches to craniofacial development. In the first, a promoter analysis of the Msx2 gene is presented which illustrates the cis regulatory interactions that defined cell-specific gene expression. In the second, a mouse model of the human disease craniosynostosis, Boston type, has been created by misregulation of the Msx2 gene product. Finally. we present a formulary of spontaneously occurring and genetically engineered mice that exhibit defects in developmental processes affecting the craniofacial complex. The purpose of this review is to provide insight into the experimental approaches that are used to create genetically engineered mice and to impress upon the reader that genetically engineered mice are well-suited to address fundamental questions pertaining to the development maintenance, and regeneration of tissues and organs.

Animals↗

Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.

The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-, and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.

Animals↗

Altered expression of pp60c-src induced by peripheral nerve injury.

The normal src protein (pp60c-src) is localized principally in the nerve growth cone of developing neurons and declines to low levels with synaptic maturation. To determine whether pp60c-src is reexpressed in regenerating axons, its expression was studied by immunoblotting and immunocytochemical analyses in adult chicken sciatic nerve following nerve crush injury. pp60c-src expression was found to increase during nerve repair with a temporal and spatial pattern consistent with a localization in regenerating axons. At the crush site, pp60c-src increased to maximal levels 7 days postinjury, increasing fivefold relative to 0 day nerve. In the nerve segment distal to the injury, the maximal increase in pp60c-src was sevenfold and occurred between 11 and 21 days postinjury. Immunoperoxidase staining revealed pp60c-src in regenerating axons and certain nonneuronal cells at the site of nerve repair. pp60c-src was induced in both motor and sensory neurons, as shown by increased pp60c-src immunoreactivity in their cell bodies located in the spinal cord and dorsal root ganglion. Phosphotyrosine-modified proteins that were potential targets of pp60c-src increased following nerve crush, and were localized to outgrowing neurites as well as to nonneuronal cells. These results suggest that pp60c-src is a common component of cellular mechanisms regulating growth cone migration in both regenerating and developing axons.

Animals↗

Intracoronal radiolucencies within unerupted teeth. Case report and review of literature.

A panoramic radiograph obtained during orthodontic treatment revealed an intracoronal radiolucency within an unerupted permanent second molar. This unusual entity was successfully treated by surgical and endodontic intervention, followed by restorative and orthodontic treatment. These treatments enabled the tooth to maintain pulpal vitality, erupt, complete root formation, and function. This report will review the proposed etiologies for this condition, discuss the need for surgical intervention, and present the details of the case.

Calcium Hydroxide↗

Screening panoramic radiographs in children: prevalence data and implications.

The purpose of this paper was to review the rationale for the radiographic screening of asymptomatic pediatric patients and to report the prevalence of selected pathologic and developmental conditions using panoramic radiographs. Three observers participated in this retrospective study that utilized panoramic radiographs from 849 subjects, aged 3-9 years, chosen randomly from the School of Dentistry treatment records of the University of North Carolina at Chapel Hill. Findings indicated that 2.4% of the subjects had supernumerary teeth, 7.8% were missing permanent teeth, 9.1% had ectopic eruption, 0.1% had radiolucencies of the jaws, and 0.1% had radiopacities of the jaws. These prevalences are discussed in light of recent evidence concerning the risk/benefit ratio of the panoramic radiograph. We conclude that the panoramic radiograph is a poor projection for screening the dental needs of asymptomatic healthy children; alternative screening protocols should be examined.

Child↗

Comparing the safety, efficacy and recovery of intranasal midazolam vs. oral chloral hydrate and promethazine.

PURPOSE: The purpose of this study was to compare the safety, efficacy and recovery time of intranasal midazolam spray administered using an atomizer to orally administered chloral hydrate and promethazine for the sedation of pediatric dental patients. METHODS: A randomized double-blind crossover study design was utilized in which 31 patients (mean age 41.8 months, range 26-58 months) underwent two restorative dental appointments. At one appointment, subjects received 0.2 mg/kg intranasal midazolam; at the other appointment subjects received 62.5 mg/kg chloral hydrate with 12.5 mg promethazine. Administered at each appointment was 25%-50% N(2)0/0(2). Physiologic parameters (heart rate, blood pressure, respiratory rate, oxygen saturation) and behavior assessments (crying, movement, sleep) using the Houpt Sedation Rating Scale were recorded at baseline and every five minutes during treatment. Overall behavior was assessed at baseline and at the end of treatment. Following treatment, a modified Vancouver Recovery Scale was used to determine the length of time it took each subject to meet established discharge criteria. RESULTS: There were no clinically significant differences in physiologic parameters, however a statistically significant decrease in systolic and diastolic blood pressure was observed in patients sedated with chloral hydrate/promethazine. There were no significant differences in behavior between groups. Patients sedated with intranasal midazolam slept less and recovered quicker than patients sedated with oral chloral hydrate/promethazine. CONCLUSIONS: Intranasal midazolam administered using an atomizer is as safe (as assessed by physiologic parameters) and effective (as assessed by behavior ratings) as oral chloral hydrate/promethazine for conscious sedation of pediatric dental patients.

Administration, Inhalation↗