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C J Brown

Publications and source records attributed to C J Brown.

At least 73 records · Page 4Linked to original sources
PubMed1998

Preliminary experience with neural response telemetry in the nucleus CI24M cochlear implant.

OBJECTIVE: This study aimed to compare recordings of the electrically evoked whole nerve action potential (EAP) made using the reverse telemetry system of the Nucleus CI24M device with those recorded from individuals who use the Ineraid cochlear implant system. STUDY DESIGN: Data were collected in a prospective fashion from Nucleus CI24M cochlear implant users and compared with retrospective data collected from patients who use the Ineraid device. SETTING: All data were collected at the Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics. PATIENTS: Data are reported from 8 patients who use the Nucleus CI24M cochlear implant and 20 patients who use the Ineraid cochlear implant system. INTERVENTIONS: The interventions described in this study were diagnostic in nature. MAIN OUTCOME MEASURES: EAP growth and refractory recovery data are reported. EAP thresholds recorded from patients who use the Nucleus CI24M device also are compared with behavioral thresholds for the stimulus used to evoke the EAP as well as the stimulation levels needed to program the speech processor. RESULTS: EAP morphology, growth, and refractory recovery functions recorded using the Nucleus CI24M reverse telemetry system compared favorably with similar measures recorded from Ineraid cochlear implant users. CONCLUSIONS: Reasonable EAP responses can be recorded using the Nucleus CI24M device. More data are needed to determine whether the information about neural responsiveness available with this device will be clinically useful.

Cochlear Implantation↗
PubMed1997

Proteoglycan breakdown from bovine nasal cartilage is increased, and from articular cartilage is decreased, by extracellular ATP.

The addition of ATP, but not ADP or AMP, to the culture media of bovine nasal cartilage explants caused an acceleration in the rate of proteoglycan loss from the tissue. The ATP-stimulated loss of proteoglycan was not inhibited by the IL1-receptor antagonist protein, but was partially inhibited by the presence of ADP or AMP. The proteolytic events resulting from the presence of ATP were found to be similar to those following treatment with IL1, in that inhibitors of the cysteine-peptidase cathepsin B, serine-proteinases with trypsin-like specificity, and of some of the matrixins, could all prevent proteoglycan loss, which was mediated, at least in part, by the action of 'aggrecanase'. In contrast to its effects on nasal cartilage, ATP inhibited basal and stimulated proteoglycan release from articular cartilage. Both ADP and AMP had no effect on proteoglycan release in articular cartilage but enhanced the response to ATP when added concurrently. We conclude that extracellular ATP, probably acting via P2-purinoceptors, stimulates proteoglycan breakdown from bovine nasal cartilage and thus, may have a role in diseases which primarily involve destruction of non-articular cartilage. Extracellular ATP has, in contrast, a chondroprotective effect on bovine articular cartilage.

Adenosine Diphosphate↗
PubMed1997

Skewed X-chromosome inactivation is common in fetuses or newborns associated with confined placental mosaicism.

The inactivation of one X chromosome in females is normally random with regard to which X is inactivated. However, exclusive or almost-exclusive inactivation of one X may be observed in association with some X-autosomal rearrangements, mutations of the XIST gene, certain X-linked diseases, and MZ twinning. In the present study, a methylation difference near a polymorphism in the X-linked androgen-receptor gene was used to investigate the possibility that nonrandom X inactivation is increases in fetuses and newborns that are associated with confined placental mosaicism (CPM) involving an autosomal trisomy. Extreme skewing was observed in 7 (58%) of 12 cases with a meiotic origin of the trisomy, but in none of 10 cases examined with a somatic origin of the trisomy, and in only 1 (4%) of 27 control adult females. In addition, an extremely skewed X-inactivation pattern was observed in 3 of 10 informative cases of female uniparental disomy (UPD) of chromosome 15. This may reflect the fact that a proportion of UPD cases arise by "rescue" of a chromosomally abnormal conceptus and are therefore associated with CPM. A skewed pattern of X inactivation in CPM cases is hypothesized to result from a reduction in the size of the early-embryonic cell pool, because of either poor early growth or subsequent selection against the trisomic cells. Since approximately 2% of pregnancies detected by chorionic villus sampling are associated with CPM, this is likely a significant contributor to both skewed X inactivation observed in the newborn population and the expression of recessive X-linked diseases in females.

Adult↗
PubMed1997

Expression of genes from the human active and inactive X chromosomes.

X-chromosome inactivation results in the cis-limited inactivation of many, but not all, of the genes on one of the pair of X chromosomes in mammalian females. In addition to the genes from the pseudoautosomal region, which have long been anticipated to escape inactivation, genes from several other regions of the human X chromosome have now been shown to escape inactivation and to be expressed from both the active and inactive X chromosomes. The growing number of genes escaping inactivation emphasizes the need for a reliable system for assessing the inactivation status of X-linked genes. Since many features of the active or inactive X chromosome, including transcriptional activity, are maintained in rodent/human somatic-cell hybrids, such hybrids have been used to study the inactivation process and to determine the inactivation status of human X-linked genes. In order to assess the fidelity of inactivation status in such hybrids, we have examined the expression of 33 X-linked genes in eight mouse/human somatic-cell hybrids that contain either the human active (three hybrids) or inactive X (five hybrids) chromosome. Inactivation of nine of these genes had previously been demonstrated biochemically in human cells, and the expression of these genes only in hybrids retaining an active X, but not in those retaining an inactive X, confirms that expression in hybrids reflects expression in human cells. Although the majority of genes tested showed consistent patterns of expression among the active X hybrids or inactive X hybrids, surprisingly, 5 of the 33 genes showed heterogeneous expression among the hybrids, demonstrating a significantly higher rate of variability than previously reported for other genes in either human somatic cells or mouse/human somatic-cell hybrids. These data suggest that at least some X-linked genes may be under additional levels of epigenetic regulation not previously recognized and that somatic-cell hybrids may provide a useful approach for studying these chromosomal phenomena.

Animals↗
PubMed1997

Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord.

The impetus for the enlargement of syringes is unknown. The authors hypothesize that there is a flow of cerebrospinal fluid (CSF) from perivascular spaces into the central canal and that the flow is driven by arterial pulsations. Using horseradish peroxidase as a tracer, the CSF flow was studied in normal sheep, in sheep with damped arterial pulsations, and in sheep with lowered spinal subarachnoid pressure. The CSF flow from perivascular spaces into the central canal was demonstrated in the normal sheep, and two patterns of flow were identified: 1) from perivascular spaces in the central gray matter; and 2) from perivascular spaces in the ventral white commissure. Flow into the central canal was also observed in the sheep with lowered spinal subarachnoid pressure, but not in those with reduced arterial pulse pressure. This study provides evidence that CSF flow from perivascular spaces into the central canal is dependent on arterial pulsations. Arterial pulsation-driven CSF flow may be the impetus for the expansion of syringes.

Animals↗
PubMed1997

A clinically significant anti-HLA-A2 detectable by extended incubation cytotoxicity and flow cytometric techniques but not by a standard NIH lymphocytotoxicity test.

A previously transfused female patient, known to have a platelet defect, was transfused with platelets prior to surgery. After the 18th unit she felt unwell, developed fever, rigor, became nauseous, and vomited. Her blood pressure decreased from 140/90 to 80/50 mm Hg. Passive transfer of donor granulocytes or red cell antibodies were excluded as a cause. Therefore, a serum sample from the patient was investigated for the presence of antibodies to human leukocyte antigens (HLA) using a standard National Institutes of Health (NIH) lymphocytotoxicity test, but antibodies were not detected. However, an extended incubation cytotoxicity test demonstrated the presence of an anti-HLA-A2, and indirect immunofluorescence flow cytometry showed the presence of an IgG1 antibody reacting with 50 percent of cells in a random pool of lymphocytes. One week later, multispecific HLA antibodies were detectable by both NIH and extended incubation cytotoxicity tests. Flow cytometry showed a 16-fold increase in the amount of IgG antibodies and the appearance of an IgM component. Such clinically important HLA antibodies can be detected by extended incubation cytotoxicity and flow cytometric assays prior to becoming reactive in a standard NIH cytotoxicity technique.

Journal Article↗
PubMed1996

Evidence for rapid fluid flow from the subarachnoid space into the spinal cord central canal in the rat.

Horseradish peroxidase (HRP) was used as a CSF tracer in Sprague-Dawley rats. One group of rats received an injection of HRP in the cisterna magna and a second group was injected in the thoracic spinal subarachnoid space. The animals were sacrificed 0, 10 or 30 min after HRP injection by rapid perfusion with paraformaldehyde and glutaraldehyde. In both groups, there was rapid HRP labeling of brain and spinal cord perivascular spaces. HRP was present in the central canal in a pattern that was not consistent with flow from the fourth ventricle: in both groups there were segments of unlabeled central canal between the fourth ventricle and central canal segments containing HRP. HRP-labeled perivascular spaces were seen in the central gray matter adjacent to the central canal. There was a distinctive pattern of interstitial HRP between perivascular spaces and the central canal. The results suggest that there is a normal flow of fluid from the subarachnoid space, into the perivascular spaces, across the interstitial space and into the central canal. The function of this flow may be to clear metabolites from the interstitial space. The existence of such a flow would add considerable support to the theory that non-communicating syringomyelia develops in segments of central canal isolated by occlusion or stenosis at each end.

Animals↗
PubMed1996

Evidence that heteronuclear proteins interact with XIST RNA in vitro.

The process of X chromosome inactivation results in the transcriptional silencing of one of the two X chromosomes in mammalian females. A large heterogeneous nuclear RNA that is expressed exclusively from the inactive X chromosome (XIST--X Inactive Specific Transcripts) has been implicated in the inactivation process. The XIST RNA colocalizes with the inactive X chromosome and therefore proteins that interact with the XIST RNA may be involved in the inactivation of the X chromosome. In order to identify such proteins we have used an in vitro UV light cross-linking technique to detect nuclear proteins associating with sections of the XIST RNA. The strongest interaction detected by this technique was between a pair of approximately 40 kDa proteins and a 5' region of the XIST RNA which contains a series of well-conserved tandem repeats. Immunoprecipitation suggested that these proteins may be the heteronuclear proteins hnRNPC1/C2.

Animals↗
PubMed1996

Electrically evoked whole nerve action potentials in Ineraid cochlear implant users: responses to different stimulating electrode configurations and comparison to psychophysical responses.

Electrically evoked whole nerve action potentials (EAP) have been recorded from 20 ineraid cochlear implant users in response to bipolar and/or monopolar electrical stimulation of the cochlea. EAP growth functions and refractory recovery functions were obtained for a variety of different stimulating conditions. Where possible, parallel psychophysical experiments were conducted that measured the just detectable increment in stimulus current level (JND), forward-masking functions, and detection thresholds for a range of different stimuli. Variations in EAP threshold, slope of the EAP growth function, and the rate of recovery of the EAP from the refractory state were observed both across subjects for a given place and by mode of stimulation (bipolar versus monopolar), as well as across electrodes within a subject. A poor correlation between slope of the EAP growth functions and current JNDs was obtained. However, good correlations were observed between EAP threshold and psychophysical detection threshold and between the EAP refractory recovery functions and the psychophysical forward-masking functions. Our interpretation of these findings is that these particular physiological measures are related to the excitability of the auditory nerve to electrical stimulation and further that these measures are related to performance of cochlear implant patients on listening tasks. Consequently, such information may prove to be useful in adjusting the stimulation parameters of the cochlear implant speech processor in order to maximize an individual's performance with the device.

Cochlear Implants↗
PubMed1996

Gene expression in a young multigene family: tissue-specific differences in the expression of the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3.

Three human alcohol dehydrogenase genes, ADH1, ADH2, and ADH3, were formed by tandem duplications and have diverged in their tissue-specific and developmental expression. Their proximal promoters remain 80-84% identical in sequence, approximately the same degree of identity as at synonymous sites in the coding regions of these three genes. To understand the evolution of tissue specificity, gene expression must be studied in many different cells and tissues. A systematic comparison of their promoters reveals the effects of subtle sequence differences on the binding of nuclear proteins to their cis-acting elements. There are differences in the affinity with which some proteins are bound to altered sites including C/EBP sites, USF/MLTF sites, and the G3T site (which binds Sp1). There are also differences in the sites that are occupied, e.g. CTF/NFI-related sites. These sequence differences are reflected in differences in gene expression in three cell lines. In H4IIE-C3 hepatoma cells, the ADH1 promoter was more active than the ADH2 promoter, and the ADH3 promoter was nearly nonfunctional. In HeLa cells, both ADH1 and ADH2 promoters directed expression; again the ADH3 promoter was extremely weak. None of the three promoters had much activity in CV-1 cells. Coexpression of C/EBP alpha greatly stimulated expression of the ADH1 promoter in HeLa cells and in CV-1 cells, but only weakly stimulated expression in H4IIE-C3 cells. The stimulation of the ADH1 promoter by C/EBP alpha was comparable to that of ADH2, despite the weaker binding to the C/EBP sites that flank the TATA box in ADH1. The ADH3 promoter was not greatly stimulated by C/EBP alpha, despite good binding of C/EBP alpha. These results demonstrate that small differences in the cis-acting elements affect affinity of binding by transcription factors and the pattern of gene expression.

Alcohol Dehydrogenase↗
PubMed1996

The effects of selection for size in cattle on horn fly population density.

Statistically significant differences were observed in the population density of the horn fly, Haematobia irritans irritans L., on Angus cows having significantly different frame sizes. Angus cows, averaging < 112.5 cm in height at the hip, had significantly lower numbers of horn flies than Angus cows that measured 112.5-117.5 cm, 117.5-120 cm, 120-126 cm and > 126 cm in height at the hip. The Angus I cows ( < 112.5 cm in height at the hip) were significantly shorter in length (mean distance from the withers to the hip bone) and were smaller in girth than the Angus II (112.5-126 cm) and Booneville Angus cows ( > 126 cm). The estimated heritability (h2) of horn fly resistance was 0.43 +/- 0.07 and 0.95 +/- 0.31 for 1989 and 1990, respectively. Horn fly counts on the Angus I herd ( < 112.5 cm in height) was 118.1 (probable breeding value, PBV = -20.69) to 165 horn flies per cow (PBV = 26.9 flies per cow in 1989) and from 75.9 (PBV = -29.1) to 134.5 (PBV = 29.5) flies per cow in 1990. Angus I bulls had PBV = -23.7 to 13.4 and from -26.5 to 14.75 in 1989 and 1990, respectively. The Angus II cows had horn fly counts that ranged from 159.6 (PBV of -23.5) to 208.1 (PBV of 25) per cow in 1989 and from 232.3 (PBV of -56.2) to 378.7 (PBV of 90) per cow in 1990. Angus II bulls had PBVs that ranged from -17.1 to 18.9 in 1989 and from -28.1 to 48.8 in 1990. The Angus I cows had significantly (P < 0.0001) lower numbers of horn flies (mean of 63.8 horn flies per m2) than the small, medium or large Angus II cows (mean of 129.4, 149.6 and 145.5 horn flies per m2, respectively). The data indicated that some specific factor(s) associated with cow size contribute(s) to innate resistance of cattle to the horn fly.

Animals↗
PubMed1996

Inhibitors of collagenase but not of gelatinase reduce cartilage explant proteoglycan breakdown despite only low levels of matrix metalloproteinase activity.

Aims-To investigate the level of matrix metalloproteinase activity during the time-course of cartilage explant proteoglycan breakdown; to determine the effects of selective small-molecule inhibitors of matrix metalloproteinases on proteoglycan degradation.Methods-The levels of matrix metalloproteinase activity in cartilage explant cultures and conditioned media were monitored by use of a quenched fluorescent substrate. The constants for inhibition of certain matrix metalloproteinases by a series of synthetic inhibitors were determined. Bovine and human cartilage explant cultures were treated with interleukin-1, tumor necrosis factor or retinoic acid and the amount of proteoglycan released into the culture medium in the absence and presence of the inhibitors was quantified. Control experiments, examining the inhibition of other proteinases, and investigating possible toxic or non-specific effects of the inhibitors, were carried out.Results-The profile of inhibition of proteoglycan release suggested the involvement of interstitial collagenase-like, rather than gelatinase- or possibly stromelysin-like, proteinases. No evidence was found for toxic or non-specific mechanisms of inhibition. Very low levels of activity of the known matrix metalloproteinases were present during the time-course of aggrecan breakdown.Conclusions-A novel collagenase-like proteinase(s) may be involved in cartilage proteoglycan breakdown. Gelatinase-type matrix metalloproteinases do not seem to be involved in this process. Specific collagenase inhibitors may be therapeutically efficacious in the treatment of arthritis.

Journal Article↗