Speech perception in young children using nucleus or Clarion Cochlear Implants: effect of communication mode.
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Auditory Perception↗
Biomedical subjects
C J Brown
Publications and source records attributed to C J Brown.
Involvement of the X chromosome in non-Hodgkin lymphoma.
Gain of an X chromosome is observed as a secondary, acquired karyotypic alteration in a significant proportion of malignant lymphomas. To determine the potential involvement of X-linked genes in neoplastic development, we have analyzed the inactivation status of the supernumerary X chromosome in lymphomas in both male and female patients. In males, neither methylation of FMR1 nor expression of XIST was detected, demonstrating that the duplicated chromosome was not subject to inactivation. In females, both expressed polymorphisms and polymorphisms associated with methylation differences between the active and inactive X chromosome were analyzed to determine whether the duplicated chromosome was active or inactive. To facilitate this analysis, allele-specific PCR primers were designed for detection of previously described polymorphisms in the IDSX and G6PD genes. The female lymphomas were shown to be clonal in origin, and duplication of either the active (5 cases) or inactive (4 cases) X chromosome was observed. Correlations between clinical status and the inactivation status of the X chromosome involved in the duplication were not observed in our relatively small sample, although 4/4 informative cases with a t(14;18) showed duplication of the active X chromosome. In the course of these studies, we detected hypermethylation of the androgen receptor (AR) locus in an extremely high proportion of both male (7/9) and female (9/10) samples. These results are discussed with respect to whether sex chromosome aneuploidies in tumors are involved in, or simply the result of, the neoplastic process. Genes Chromosomes Cancer 28:246-257, 2000.
Adult↗
Intrinsic protein disorder in complete genomes.
Intrinsic protein disorder refers to segments or to whole proteins that fail to fold completely on their own. Here we predicted disorder on protein sequences from 34 genomes, including 22 bacteria, 7 archaea, and 5 eucaryotes. Predicted disordered segments > or = 50, > or = 40, and > or = 30 in length were determined as well as proteins estimated to be wholly disordered. The five eucaryotes were separated from bacteria and archaea by having the highest percentages of sequences predicted to have disordered segments > or = 50 in length: from 25% for Plasmodium to 41% for Drosophila. Estimates of wholly disordered proteins in the bacteria ranged from 1% to 8%, averaging to 3 +/- 2%, estimates in various archaea ranged from 2 to 11%, plus an apparently anomalous 18%, averaging to 7 +/- 5% that drops to 5 +/- 3% if the high value is discarded. Estimates in the 5 eucarya ranged from 3 to 17%. The putative wholly disordered proteins were often ribosomal proteins, but in addition about equal numbers were of known and unknown function. Overall, intrinsic disorder appears to be a common, with eucaryotes perhaps having a higher percentage of native disorder than archaea or bacteria.
Animals↗
Comparing predictors of disordered protein.
More than 6,000 amino acid sequence attributes were ranked by their conditional probabilities for indicating ordered or disordered protein structure. The top 10 each from several different groups of attributes were merged with still other attributes and then subjected to selection by logistic regression. Evidently, the determination of order or disorder results from the interplay among several attributes, such as average Coordination Number, aromatic content and the numbers of non-polar amino acids, all of which favor the ordered state, and others like Net Charge, Flexibility Index, and the presence of certain polar amino acids, all of which favor disorder. The top 12 selected attributes were used as inputs for artificial neural network (ANN) predictors. Five predictors were developed, compared with each other, and with previous work. The best of these shows substantially improved generalization compared to our previously published predictor.
Computational Biology↗
Skewed X-chromosome inactivation: cause or consequence?
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Age Factors↗
Parasitic infection with Trichuris trichiura influences plasma levels of soluble HLA class I.
High levels of sHLA-I (soluble HLA--class I) have been correlated with rejection episodes in solid organ transplant recipients and with graft versus host disease in bone marrow recipients. Studies of human infection with parasitic worms of the gut have suggested that certain individuals may be genetically predisposed to intense infection. In this study, the influence of parasitic helminth infection on levels of sHLA-I in plasma was investigated in 155 HLA typed individuals from St. Lucia, exposed to the gut parasite Trichuris trichiura. The results confirmed previous findings showing increased levels of sHLA-I in HLA-A9, and in this case HLA-A23 positive individuals. However, HLA-A9 positive individuals with high worm burden had significantly lower levels of sHLA-I in their plasma compared with HLA-A9 positive subjects with low worm burden. These results suggest that the intensity of T. trichiura infection influences the ability of HLA-A9 positive subjects to maintain high levels of sHLA-I.
Animals↗
Influence of sodium oxide content on bioactive glass properties.
The rate of in vivo degradation and level of bioactivity of bioactive glasses are composition dependent [1]. By altering bioactive glass composition, the rate of resorption can be controlled. The network connectivity of a glass can be used to predict various physical properties of the glass including its solubility and, hence, its bioactivity [2]. Glass solubility increases as network connectivity is reduced. Glasses in the soda-lime phosphosilicate system were studied. The initial choice of composition was based on phosphate content and low network connectivity. A systematic substitution of calcium oxide for sodium oxide on a molar basis was made in order to examine the influence of sodium oxide content on the glass properties while keeping the network connectivity constant. The glass transition temperature and the peak crystallization temperature were seen to decrease linearly with increasing sodium oxide content. Thermal expansion coefficient and glass density were also seen to be related to sodium oxide content. Preliminary in vitro biocompatibility studies revealed that the glasses of higher sodium oxide content were associated with a cytotoxic response. The measurement of media pH indicated that this cytotoxic effect was due to ion exchange reactions at the glass surface.
Journal Article↗
Extremely skewed X-chromosome inactivation is increased in women with recurrent spontaneous abortion.
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Abortion, Habitual↗
Polymorphic X-chromosome inactivation of the human TIMP1 gene.
X inactivation silences most but not all of the genes on one of the two X chromosomes in mammalian females. The human X chromosome preserves its activation status when isolated in rodent/human somatic-cell hybrids, and hybrids retaining either the active or inactive X chromosome have been used to assess the inactivation status of many X-linked genes. Surprisingly, the X-linked gene for human tissue inhibitor of metalloproteinases (TIMP1) is expressed in some but not all inactive X-containing somatic-cell hybrids, suggesting that this gene is either prone to reactivation or variable in its inactivation. Since many genes that escape X inactivation are clustered, we examined the expression of four genes (ARAF1, ELK1, ZNF41, and ZNF157) within approximately 100 kb of TIMP1. All four genes were expressed only from the active X chromosome, demonstrating that the factors allowing TIMP1 expression from the inactive X chromosome are specific to the TIMP1 gene. To determine if this variable inactivation of TIMP1 is a function of the hybrid-cell environment or also is observed in human cells, we developed an allele-specific assay to assess TIMP1 expression in human females. Expression of two alleles was detected in some female cells with previously demonstrated extreme skewing of X inactivation, indicating TIMP1 expression from the inactive chromosome. However, in other cells, no expression of TIMP1 was observed from the inactive X chromosome, suggesting that TIMP1 inactivation is polymorphic in human females.
Alleles↗
Summary of results using the nucleus CI24M implant to record the electrically evoked compound action potential.
OBJECTIVE: This study outlines a series of experiments using the neural response telemetry (NRT) system of the Nucleus CI24M cochlear implant to measure the electrically evoked compound action potential (EAP). The goal of this investigation was to develop a protocol that allows successful recording of the EAP in a majority of CI24M cochlear implant users. DESIGN: Twenty-six postlingually deafened adults participated in this study. A series of experiments were conducted that allowed us to examine how manipulation of stimulation and recording parameters may affect the morphology of the EAP recorded using the Nucleus NRT system. RESULTS: Results of this study show consistent responses on at least some electrodes from all subjects. Cross-subject and cross electrode variations in both the growth of the response and the temporal refractory properties of the response were observed. The range of stimulus and recording parameters that can be used to record the EAP with the Nucleus NRT system is described. CONCLUSIONS: Using the protocol outlined in this study, it is possible to reliably record EAP responses from most subjects and for most electrodes in Nucleus CI24M cochlear implant users. These responses are robust and recording these responses does not require that the subject sleep or remain still. Based on these results, a specific protocol is proposed for measurement of the EAP using the NRT system of the CI24M cochlear implant. Potential clinical implications of these results are discussed.
Adult↗
Relationship between EABR thresholds and levels used to program the CLARION speech processor.
The purpose of this study was 1) to describe the relationship between electrically evoked auditory brain stem response (EABR) thresholds and the behavioral measures needed to program the speech processor of the CLARION Multi-Strategy Cochlear Implant, and 2) to determine whether the relationship between EABR threshold and the behavioral levels used to program the Clarion device was correlated with the temporal integration abilities of these subjects. The EABR thresholds, psychophysical thresholds, and the Clarion speech processor programming levels were recorded from 29 postlingually deafened adults. The mean EABR thresholds approximated most comfortable levels (M levels) for the programming stimulus. However, intrasubject variability was substantial. Significant intrasubject variability in temporal integration also was observed. Correlations were found between the ability of a cochlear implant user to perform temporal integration and the relationship between his or her EABR threshold and the threshold for the programming stimulus.
Adult↗
Effects of growth type on carcass traits of pasture- or feedlot-developed steers.
Carcasses of 342 steers of known genetic backgrounds from four fundamentally different growth types were developed either on pasture or feedlot regimens to study differences in carcass traits. Growth types were large framed-late maturing (LL), intermediate framed-intermediate maturing (II), intermediate framed-early maturing (IE), and small framed-early maturing (SE). Five calves from each growth type were assigned to each regimen in each year of a 9-yr study. Eighteen steers were removed from the study because of accident or illness. Data collected were preslaughter shrunk BW (SBW); hot carcass weight (HCW); chilled carcass weight (CCW); dressing percentage (DRESS); fat thickness at the 12th and 13th-rib interface (FAT); percentage kidney, pelvic, and heart fat (KPH); longissimus muscle area (LMA); marbling score (MARB); quality grade (QG); and yield grade (YG). Differences in carcass traits reflected genetic differences among growth types. The LL steers had heavier BW, HCW, and CCW and larger LMA (P < .05) than steers of other growth types, regardless of development regimen. Among pasture-developed steer carcasses, IE and SE steers had higher (P < .05) MARB and QG than either LL or II steers. Carcasses of large framed-late maturing steers had the lowest (P < .05) MARB and QG of the growth types. Carcasses of the II, IE, and SE steers had a higher (P < .05) numerical value for YG than carcasses of the LL steers. Among the carcasses of the feedlot-developed steers, IE and SE steers had the highest (P < .05) MARB and QG. Carcasses from the IE and SE steers were fatter (P < .05) than those from LL or II steers. Carcasses of the LL steers had the lowest percentage of KPH of growth types developed in the feedlot. No difference was observed in KPH for carcasses of II, IE, and SE steers. The LL steer carcasses had the lowest numerical value for YG of all growth types. These data indicate that variation existed among carcass traits for the four growth types and that carcass traits influenced by fatness were greater and more attainable in the feedlot-developed steers using current methods of evaluation.
Animal Feed↗
Stabilization and localization of Xist RNA are controlled by separate mechanisms and are not sufficient for X inactivation.
These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935-2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome, demonstrating for the first time that the active X chromosome in somatic cells is competent to associate with Xist RNA. These results imply that species-specific factors, present even in mature, somatic cells that do not normally express Xist, are necessary for localization. When Xist RNA is properly localized to an active mouse X chromosome, X inactivation does not result. Therefore, there is not a strict correlation between Xist localization and chromatin inactivation. Moreover, expression, stabilization, and localization of Xist RNA are not sufficient for X inactivation. We hypothesize that chromosomal association of XIST RNA may initiate subsequent developmental events required to enact transcriptional silencing.
Animals↗
Induction of XIST expression from the human active X chromosome in mouse/human somatic cell hybrids by DNA demethylation.
X chromosome inactivation occurs early in mammalian development to transcriptionally silence one of the pair of X chromosomes in females. The XIST RNA, a large untranslated RNA that is expressed solely from the inactive X chromosome, is implicated in the process of inactivation. As previous studies have shown that the XIST gene is methylated on the active X chromosome, we have treated a mouse/human somatic cell hybrid retaining an active human X chromosome with demethylating agents to determine whether expression of the human XIST gene could be induced. Stable expression of XIST was observed after several rounds of demethylation and stability of XIST expression correlated with the loss of methylation at the three sites analysed. We conclude that methylation is sufficient to inhibit expression of the XIST gene in somatic cell hybrids. No loss of expression was detected for eight other X-linked genes from the active X chromosome that was expressing XIST , suggesting that additional developmental or species-specific factors are required for the inactivation process.
Animals↗
A technique for in vivo vascular perfusion fixation of the sheep central nervous system.
A method for perfusion fixation of the sheep central nervous system is described. The technique utilises the vascular anatomy of the spinal cord and brain to provide fixation that is comparable to transcardiac perfusion of the small animal. It can be applied with relative ease, cost effectiveness and without risking premature death of the animal due to complications of a major procedure such as thoracotomy.
Animals↗
Physician awareness of alcohol use disorders among older patients.
OBJECTIVES: To determine primary care physicians' awareness of, and screening practices for, alcohol use disorders (AUDs) among older patients. DESIGN: Cross-sectional telephone survey of a national sample of primary care physicians. PARTICIPANTS: Physicians randomly sampled from the Masterfile database of the American Medical Association and stratified by specialty as family practice physicians, internal medicine physicians, and either family practice or internal medicine physicians with geriatric certification. MAIN RESULTS: A total of 171 physicians were contacted: 155 (91%) agreed to participate, and responses were analyzed from 150 (50 family practice, 50 internal medicine, 50 with geriatric certification). The median prevalence estimate of AUDs among older patients was 5% for each group of physicians. In contrast to published prevalence rates of AUDs ranging from 5% to 23%, 38% of physicians reported prevalence estimates of less than 5%, and 5% cited estimates of at least 25%. Compared with the other groups, the physicians with geriatric certification were more likely to report no regular screening (42% vs 20% for family practice vs 18% for internal medicine, p = .01), while younger (<40 years) and middle-aged physicians (40-55 years) reported higher annual screening rates relative to older physicians (>55 years) (77% vs 60% vs 44% respectively, p = .03). Among physicians who regularly screened (n = 110), 100% asked quantity-frequency questions, 39% also used the CAGE questions, and 15% also cited use of biochemical markers. CONCLUSIONS: Primary care physicians may "underdetect" AUDs among older patients. The development of age-specific screening methods and physician education may facilitate detection of older patients with (or at risk for) these disorders.
Aged↗
Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment.
When microbes evolve in a continuous, nutrient-limited environment, natural selection can be predicted to favor genetic changes that give cells greater access to limiting substrate. We analyzed a population of baker's yeast that underwent 450 generations of glucose-limited growth. Relative to the strain used as the inoculum, the predominant cell type at the end of this experiment sustains growth at significantly lower steady-state glucose concentrations and demonstrates markedly enhanced cell yield per mole glucose, significantly enhanced high-affinity glucose transport, and greater relative fitness in pairwise competition. These changes are correlated with increased levels of mRNA hybridizing to probe generated from the hexose transport locus HXT6. Further analysis of the evolved strain reveals the existence of multiple tandem duplications involving two highly similar, high-affinity hexose transport loci, HXT6 and HXT7. Selection appears to have favored changes that result in the formation of more than three chimeric genes derived from the upstream promoter of the HXT7 gene and the coding sequence of HXT6. We propose a genetic mechanism to account for these changes and speculate as to their adaptive significance in the context of gene duplication as a common response of microorganisms to nutrient limitation.
Adaptation, Physiological↗
Stromelysin 1, neutrophil collagenase, and collagenase 3 do not play major roles in a model of chondrocyte mediated cartilage breakdown.
AIMS: To determine the collective roles of stromelysin 1, neutrophil collagenase, and collagenase 3 in chondrocyte mediated cartilage proteoglycan and type II collagen degradation in tissue culture model systems. METHODS: Bovine nasal cartilage explants were cultured with and without recombinant human interleukin 1 alpha (IL-1 alpha), recombinant human tumour necrosis factor alpha, or retinoic acid. Proteoglycan and type II collagen release were determined by colorimetric assay and immunoassay, respectively, in the absence and presence of matrixin inhibitors. Potential toxic effects of the inhibitors were assessed by measuring rates of glycolysis. RESULTS: Loss of proteoglycan and type II collagen from nasal cartilage was inhibited by batimastat, a broad spectrum matrixin inhibitor. BB-3437, a selective inhibitor of stromelysin, neutrophil collagenase, and collagenase 3, at the concentrations used in this study, showed a weak but dose dependent inhibitory effect on the IL-1 stimulated degradation of type II collagen, but had virtually no effect on proteoglycan breakdown. Neither inhibitor affected rates of glycolysis. CONCLUSIONS: Stromelysin 1, neutrophil collagenase, and collagenase 3 are unlikely to contribute to chondrocyte mediated proteoglycan degradation in our model system. The modest effect of a selective inhibitor of these enzymes on IL-1 stimulated collagen breakdown suggests a minor role for one or more of these proteinases; potent inhibition by an inhibitor of interstitial collagenase and the gelatinases suggests that these enzymes play a major role in IL-1 stimulated, chondrocyte mediated type II collagen breakdown from nasal cartilage.
Amides↗