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Biomedical subjects

C J Brown

Publications and source records attributed to C J Brown.

At least 91 records · Page 5Linked to original sources
PubMed1996

Case report: radical management of an adolescent with amelogenesis imperfecta.

Amelogenesis imperfecta is a rare developmental abnormality of enamel, the main clinical problems of which are extensive loss of tooth tissue, poor aesthetics and tooth sensitivity. Management often involves complex and long-term treatment but is usually successful if patients are well motivated. This case report outlines the management of a teenager with amelogenesis imperfecta (hypocalcified type) who had requested a dental clearance at an early age.

Adolescent↗
PubMed1995

24-hour service.

Explore the source record for details and available documents.

Career Choice↗
PubMed1995

Identification of a PIG-A related processed gene on chromosome 12.

PIG-A, the gene encoding the glycoinositol phospholipid anchor synthetic element that is defective in paroxysmal nocturnal hemoglobinuria (PNH), resides on the X chromosome. In the course of analyses of PIG-A genetic alterations in PNH patients, polymerase chain reaction (PCR) amplification of reverse-transcribed RNA from affected leukocytes of a patient with diminished PIG-A mRNA expression yielded a PIG-A related sequence with 126 nucleotide substitutions and five deletions. In the present study, the origin of this product was investigated. Selective reverse transcription (RT)/PCR amplifications with primers specific for PIG-A and this variant sequence, analyses of RNA from unaffected cells, and differential endonuclease digestions showed that mRNA with this sequence is coexpressed with PIG-A mRNA in a wide range of cell types. Mapping of genomic DNA from human/rodent hybrids showed that the sequence derives from a processed gene, designated PIG-A-II, that is encoded on chromosome 12.

Base Sequence↗
PubMed1995

The DXS423E gene in Xp11.21 escapes X chromosome inactivation.

The DXS423E gene has been localized to Xp11.21 and is expressed in somatic cell hybrids retaining either the human active or inactive X chromosome, demonstrating that DXS423E escapes X chromosome inactivation. The XE169 (DXS1272E or SMCX) gene that escapes X chromosome inactivation is also located in Xp11.21-11.22 and maps within the same YAC as DXS423E. Thus the DXS423E and XE169 genes define a new region in the proximal short arm of the X chromosome that is not subject to X chromosome inactivation, supporting a regional basis for escape from inactivation.

Base Sequence↗
PubMed1995

Longitudinal assessment of physiological and psychophysical measures in cochlear implant users.

OBJECTIVE: The purpose of this study was to evaluate the effects of long-term electrical stimulation on human cochlear implant users. DESIGN: Repeated measures of electrically evoked auditory brain steam response (EABR) threshold, slope of the EABR growth function, and behavioral measures of threshold and dynamic range were made for a group of 22 Ineraid cochlear implant users and 19 Nucleus cochlear implant users over a 3- to 5-yr period. RESULTS: Data from both Ineraid and Nucleus cochlear implant users suggest that EABR threshold, slope of the EABR growth function, and behavioral measures of threshold and dynamic range remain reasonably stable for periods up to 5 yr postimplant. CONCLUSIONS: The results of this study show little evidence that prolonged electrical stimulation through daily use of a cochlear implant has deleterious effects on the auditory system.

Cochlear Implants↗
PubMed1995

Direct detection of non-random X chromosome inactivation by use of a transcribed polymorphism in the XIST gene.

As a result of X chromosome inactivation, females are mosaic for cell lineages in which either the paternal or the maternal X chromosome is active, and, if inactivation were random, each lineage should be present at approximately the same frequency. Detection of instances of non-random X inactivation can be important both clinically and for the study of X chromosome inactivation. Identification of a single-base polymorphism in an expressed region of the human XIST gene has permitted the development of a direct PCR-based assay for randomness of X inactivation. Oligonucleotide primers were designed, incorporating the variant base, and conditions established that allowed allele-specific PCR amplification. As the XIST gene is expressed only from the inactive X chromosome, differential amplification of the alleles in cDNA from heterozygotes can be used as an indicator of non-random inactivation. Using this assay, non-random X chromosome inactivation has been demonstrated in chromosomally abnormal cell lines and in lymphocytes from heterozygous, normal females. Virtually complete non-random X inactivation was also shown in a mother and her daughter, suggesting the existence of some familial factor affecting X chromosome inactivation.

Base Sequence↗
PubMed1995

The Carolina Children's Communicative Disorders Program. An opportunity for North Carolina's children.

The CCCDP provides devices and services to underprivileged children with communication disorders. Since its organization, the program has helped 197 children, including 21 given cochlear implants, and has disbursed 258 hearing aids or devices. It is cost-efficient program that has potential to help many of our state's needful children. We solicit referrals from all NC physicians, audiologists, speech pathologists, educators, and other professionals. Applications and financial forms will be furnished on request.

Adolescent↗
PubMed1994

The human X-inactivation centre is not required for maintenance of X-chromosome inactivation.

X-chromosome inactivation occurs early in mammalian female development to achieve dosage compensation with males. Although it is widely accepted that this inactivation requires the presence in cis of the X-inactivation centre (XIC), it is not known whether the XIC is required for the initiation, promulgation or maintenance of X inactivation. The XIST gene, which is localized within the XIC interval on both the human and mouse X chromosomes, is constitutively expressed from inactive X chromosomes, suggesting a possible role in the maintenance of X inactivation. To address whether the presence of the XIC, including the XIST gene, is continuously required for the maintenance of X-chromosome inactivation, we have analysed the transcriptional activity of a number of X-linked genes in mouse/human somatic cell hybrids retaining an intact human inactive X chromosome or derivatives of the inactive X chromosome lacking the XIC. Genes subject to X inactivation remain transcriptionally silent despite the loss of the XIC, demonstrating that the presence of the XIC is not required for the maintenance of X inactivation in somatic cells.

Animals↗
PubMed1994

Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter.

The human alcohol dehydrogenase gene ADH2 is expressed at high levels in liver, at lower levels in kidney and several other tissues, and is not expressed in other tissues such as spleen. This pattern of expression suggests a complex regulatory region that responds to a variety of transcription factors in different cellular contexts. Seven cis-acting sequences in the proximal 271 bp of the ADH2 promoter were mapped. The occupancy of these sites differed markedly among extracts from liver, kidney, spleen, H4IIE-C3 cells, HeLa cells, and CV-1 cells. These differences in occupancy were accompanied by differences in gene expression in the three cell lines. The ADH2 promoter directed substantial CAT expression in H4IIE-C3 cells (rat hepatoma) and in HeLa cells, but only minimal expression in CV-1 cells (monkey kidney fibroblasts). The three cell lines differed in the effects of deletions within the promoter. An ADH2 promoter that contained both the USF/MLTF site and the G3T site gave four- to eight-fold higher expression in both H4IIE-C3 and HeLa cells than a smaller promoter that lacked these sites; in contrast, these sequences did not significantly stimulate transcription in CV-1 cells. A CTF/NF-I-related site acted as a negative element in all three cell lines. Coexpression of C/EBP alpha altered the cell specificity. The ADH2 promoter was moderately stimulated (two-fold) by coexpression of C/EBP alpha in H4IIE-C3 cells, but markedly stimulated in HeLa cells and in CV-1 cells (11- and 20-fold, respectively). These results demonstrate the differential importance of cis-acting sequences and of specific transcription factors in different cells, which allows regulated expression of ADH2 in multiple tissues.

Alcohol Dehydrogenase↗
PubMed1994

Intraoperative and postoperative electrically evoked auditory brain stem responses in nucleus cochlear implant users: implications for the fitting process.

Electrically evoked auditory brain stem responses (EABR) were measured in 12 adults and 14 children with the Nucleus cochlear implant. Measures were made both intraoperatively and several months following surgery. EABR thresholds were consistently greater than clinically determined measures of behavioral threshold (T-level) but less than maximum comfort levels (C-level). When the data were pooled across subjects and different stimulating electrodes, EABR thresholds were strongly correlated with both T- and C-levels. In subjects where both intraoperative and postimplant EABR measures were obtained, intraoperative EABR thresholds were consistently higher than postimplant thresholds. The electrophysiologic data have been incorporated into a practical procedure for programming the implant in young children.

Acoustic Stimulation↗
PubMed1994

Small marker X chromosomes lack the X inactivation center: implications for karyotype/phenotype correlations.

The abnormal phenotype and/or mental retardation seen in persons with small marker X (mar(X)) chromosomes has been hypothesized to be due to the loss of the X inactivation center (XIC) at Xq13.2, resulting in two active copies of genes in the pericentromeric region. In order to define precisely the DNA content of mar(X) chromosomes and to correlate phenotype with karyotype, we studied small mar(X) chromosomes, using FISH with probes in the juxtacentromeric region. One of the probes was a 40-kb genomic cosmid for the XIST gene, which maps to the smallest interval known to contain the XIC and is thought to be involved in X inactivation. Our findings reveal that small mar(X) chromosomes do not include the XIC and therefore cannot be subject to X inactivation, supporting the premise that abnormal dosage of expressed genes in the pericentromeric region of the X generates the aberrant phenotype seen in patients with small mar(X) chromosomes.

Adult↗
PubMed1994

Intraoperative measures of electrically evoked auditory nerve compound action potential.

A method for recording the electrically evoked whole-nerve action potential (EAP) at the time of cochlear implant surgery is described. Measures of EAP growth with stimulus level and functions describing the rate of recovery of the auditory nerve from the refractory state are reported for patients tested intraoperatively and for a group of patients using the ineraid implant, from whom recordings were made following implantation. Subjects tested intraoperatively were separated into three categories: congenitally deaf children (n = 14), prelingual meningitic children (n = 5), and postingual adults (n = 13). A fourth group consisted of postlingual adults (n = 14) tested postoperatively. Results from all groups showed a similar range of EAP growth and recovery rates across patients. Data from congenitally deaf children formed the exception showing steeper EAP growth functions than other subject groups. Electrically evoked whole-nerve action potential growth and recovery functions of the postoperative group of subjects showed modest correlations to speech perception scores measured after at least 18 months of implant use. The possible use of these measures in fitting an implant to an individual is discussed.

Adolescent↗
PubMed1994

Alcohol dehydrogenases: molecular biology and gene regulation.

The mammalian alcohol dehydrogenase genes are a closely related gene family, and show complex patterns of expression. The promoters contain multiple cis-acting elements that are binding sites for transcription factors. Both positive and negative cis-acting elements have been found. The binding of transcription factors to these sites differs among tissues. The complexity of the promoters allows different amounts of expression of the ADHs in many tissues.

Alcohol Dehydrogenase↗
PubMed1993

Characterization of a small supernumerary ring X chromosome by fluorescence in situ hybridization.

We report on a male with mild learning disabilities who has a supernumerary marker chromosome. The marker chromosome was defined by fluorescence in situ hybridization as a ring X chromosome with breakpoints in the juxacentromeric region. Replication studies suggest that the ring X is late-replicating. However XIST, a gene in the X inactivation centre interval which is expressed exclusively from the inactive X chromosome, is not present on the marker, nor is it expressed in the patient's cells. These results are discussed with respect to karyotype-phenotype correlations and X inactivation.

Base Sequence↗
PubMed1993

Electrically evoked auditory brainstem response to stimulation of different sites in the cochlea.

It is often assumed that stimulation of the eighth nerve with brief current pulses results in a highly synchronous discharge of action potentials from the ensemble of excited nerve fibers. Latency data derived from the electrically evoked auditory brainstem response (EABR) of the guinea pig and human indicate that there is a baso-apical gradient of response latencies in both species. Place-specific stimulation of different regions of the guinea pig cochlea was achieved by positioning a narrowly spaced bipolar electrode into each of the four spiral turns. Peak latencies of EABR waves I and III both revealed longer latencies with increasing distance from the base. Different amplitude growth functions were obtained from each turn. Place-specific stimulation in humans implanted with the Nucleus 22-electrode device was achieved by presenting current pulses across electrodes spaced 1.5 mm apart. A gradient of wave V latencies was observed in all subjects studied. The presence of a latency gradient would influence results obtained in efforts to correlate evoked potential amplitude measures with nerve survival. It may also provide information useful in characterizing the surviving fiber population in human implant subjects.

Animals↗
PubMed1993

Evolutionary conservation of possible functional domains of the human and murine XIST genes.

The human XIST gene, a candidate for a role in X chromosome inactivation, has recently been cloned and sequenced, yielding a 17 kb cDNA with no apparent significant, conserved open reading frame. In addition, the XIST transcript has been localized within the nucleus to the Barr body by RNA in situ hybridization. This subnuclear localization and lack of any significant protein-coding potential suggest that XIST may act as a functional RNA within the nucleus. In the absence of a conserved open reading frame, we have turned to evolutionary studies as a first step toward elucidating a function for XIST in the process of X inactivation. While probes for XIST detect homologues in numerous eutherians, sequence comparisons require significant gapping and reveal identity levels intermediate between those seen for coding and non-coding regions in other genes. Further, sequence comparison of the most likely candidate open reading frame among several primate species reveals sequence changes not normally associated with protein-coding regions. Other features of XIST are conserved in different species, however, including the position of a major transcription start site and active X chromosome-specific DNA methylation patterns at the gene's 5' end. Finally, a possible molecular basis for differing propensity toward X inactivation between Xce alleles in mouse is investigated by comparing the sequence of the Xist conserved 5' repeats in mouse strains carrying different Xce alleles.

Alleles↗