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David G McLone

Publications and source records attributed to David G McLone.

11 recordsLinked to original sources
PubMed2006

Regulation of murine TGFbeta2 by Pax3 during early embryonic development.

Previously our laboratory identified TGFbeta2 as a potential downstream target of Pax3 by utilizing microarray analysis and promoter data base mining (Mayanil, C. S. K., George, D., Freilich, L., Miljan, E. J., Mania-Farnell, B. J., McLone, D. G., and Bremer, E. G. (2001) J. Biol. Chem. 276, 49299-49309). Here we report that Pax3 directly regulates TGFbeta2 transcription by binding to cis-regulatory elements within its promoter. Chromatin immunoprecipitation revealed that Pax3 bound to the cis-regulatory elements on the TGFbeta2 promoter (GenBanktrade mark accession number AF118263). Both TGFbeta2 promoter-luciferase activity measurements in transient cotransfection experiments and electromobility shift assays supported the idea that Pax3 regulates TGFbeta2 by directly binding to its cis-regulatory regions. Additionally, by using a combination of co-immunoprecipitation and chromatin immunoprecipitation, we show that the TGFbeta2 cis-regulatory elements between bp 741-940 and bp 1012-1212 bind acetylated Pax3 and are associated with p300/CBP and histone deacetylases. The cis-regulatory elements between bp 741 and 940 in addition to associating with acetylated Pax3 and HDAC1 also associated with SIRT1. Whole mount in situ hybridization and quantitative real time reverse transcription-PCR showed diminished levels of TGFbeta2 transcripts in Pax3(-/-) mouse embryos (whose phenotype is characterized by neural tube defects) as compared with Pax3(+/+) littermates (embryonic day 10.0; 30 somite stage), suggesting that Pax3 regulation of TGFbeta2 may play a pivotal role during early embryonic development.

Animals↗
PubMed2005

Jack Walker.

Explore the source record for details and available documents.

History, 21st Century↗
PubMed2004

Surgical results of posterior fossa decompression for patients with Chiari I malformation.

INTRODUCTION: An increasing number of children with Chiari I malformations are coming to the attention of neurosurgeons today, although a consensus on the surgical approach to these lesions has yet to be found. METHODS: We present a retrospective analysis of posterior fossa decompression (PFD) performed at our institution on 96 patients from 1989 to 2001. Statistical analyses based on clinical and radiographic presentation and the types of surgical procedures used formed the basis for our review. RESULTS: Most of the patients with hydromyelia underwent duraplasty procedures with or without tonsillar manipulation. In contrast, most patients without hydromyelia underwent bony decompression with dural scoring and intraoperative ultrasound. PFD with bony decompression and dural scoring showed a 72% success rate, compared with 68% for duraplasty. Dural opening was not more likely to improve or arrest hydromyelia. The group subjected to duraplasty, however, had a significantly higher complication rate. Patients under the age of 8 fared better than their older counterparts. CONCLUSIONS: Overall, we favor a tailored posterior fossa craniectomy with dural scoring as the initial surgical procedure in children with Chiari I malformation with or without a syrinx. This less invasive approach minimizes complications associated with dural opening and offers comparable success rates.

Adolescent↗
PubMed2004

The anatomy of the ventricular system.

The embryology of the ventricular development of the brain assists in understanding the final relations between structures forming these cavities. An accurate concept of this anatomy allows the endoscopist to maneuver within the ventricular system.

Cerebral Ventricles↗
PubMed2003

The Chiari II malformation: cause and impact.

INTRODUCTION: It is the Chiari II malformation and its effects that determine the quality of life of the individual born with spina bifida. DISCUSSION: The cause of this malformation has been a source of debate for many years. Understanding the cause enables strategies for the management of problems created by this malformation to be developed. An open neural tube defect allows fluid to escape from the cranial vesicles, altering the intracranial environment and leads to all of the brain changes seen in the Chiari II malformation. Decompression of the intracranial vesicles causes overcrowding, decrease in the size of the third ventricle, and changes in the fetal skull. It also permanently links the intracranial ventricular system to the spinal cord central canal.

Animals↗
PubMed2003

The etiology of neural tube defects: the role of folic acid.

DISCUSSION: While the cause of neural tube defects in humans is considered to be multifactorial, it is apparent that folic acid can prevent 70% of open neural tube defects. Even in laboratory animals with known genetic defects, folic acid can prevent the genetic expression. CONCLUSION: While some of the metabolic pathways for folic acid are known, the true effects of folic acid on closure of the neural tube have yet to be discovered.

Female↗
PubMed2002

Measurement of cerebrospinal fluid output through external ventricular drainage in one hundred infants and children: correlation with cerebrospinal fluid production.

OBJECTIVE: Cerebrospinal fluid (CSF) production rates influence shunt design and the care of children with hydrocephalus. Measurement of hourly CSF output through external ventricular drainage (EVD) reflects the CSF production. In the present study, hourly CSF outputs in children with hydrocephalus were measured while they were treated with EVD and correlated with the age, sex and body weight of the patients as well as other clinical parameters. METHODS: One hundred children with hydrocephalus due to various causes had EVD treatment. Twenty-six had EVD on two or three separate occasions; thus, the CSF output measurements were observed and analyzed on the basis of 130 EVDs. The most common reason for EVD treatment was shunt infection (n = 75). The duration of EVDs ranged from 25 to 774 h (mean 269 h). The height of the drip chamber from the mid-head position ranged from 0 to 23 cm (mean 9.8 cm). The hourly CSF output was analyzed according to the patient's age, sex and body weight as well as the presence of CSF infection. RESULTS: The hourly CSF output rapidly increases during the first year of life. By the second year, it reaches 64% of the hourly CSF output of 15-year-old children. The mean hourly output ranged from 0.1 to 26.5 ml/h (mean 8.1 ml/h), with the standard deviation ranging from 0.4 to 10.8 ml/h (mean 5.2 ml/h). A regression analysis indicated that the age and body weight appeared to correlate with the hourly CSF output. Using the natural logarithm of age, body weight and sex, these predictors accounted for 50.9% of the variability in hourly CSF output. The regression equation is as follows: hourly CSF output = 2.78 - 2.23(male = 0, female = 1) + 0.97 log(age in years) + 2.26 log(body weight in kg). R sd = 3.36, R(2) = 0.509. The type of infecting organism and the height of EVD did not influence the overall CSF output. CONCLUSION: The hourly CSF output fluctuates, but the CSF output increases logarithmically with age and body weight. The gender also influences the CSF output, with males having a greater output than females. The data produced by the present study will help us to understand CSF production rates in developing children. They will also help us in the care of children receiving EVD treatment, as well as in selecting and designing shunt systems.

Adolescent↗