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Biomedical subjects

C Bell

Publications and source records attributed to C Bell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor.

Reiterative in vitro selection-amplification from random oligonucleotide libraries allows the identification of molecules with specific functions such as binding to specific proteins. The therapeutic usefulness of such molecules depends on their high affinity and nuclease resistance. Libraries of RNA molecules containing 2'amino-(2'NH2)- or 2'fluoro-(2'F)-2'-deoxypyrimidines could yield ligands with similar nuclease resistance but not necessarily with similar affinities. This is because the intramolecular helices containing 2'NH2 have lower melting temperatures (Tm) compared with helices containing 2'F, giving them thermodynamically less stable structures and possibly weaker affinities. We tested these ideas by isolating high-affinity ligands to human keratinocyte growth factor from libraries containing modified RNA molecules with either 2'NH2 or 2'F pyrimidines. We demonstrated that 2'F RNA ligands have affinities (Kd approximately 0.3-3 pM) and bioactivities (Ki approximately 34 pM) superior to 2'NH2 ligands (Kd approximately 400 pM and Ki approximately 10 nM). In addition, 2'F ligands have extreme thermo-stabilities (Tm approximately 78 degrees C in low salt, and specificities).

3T3 Cells↗
PubMed1997

Premedication in the United States: a status report.

We undertook a mailing survey study to assess the current practice of sedative premedication in anesthesia. A total of 5396 questionnaires were mailed to randomly selected physician members of the American Society of Anesthesiologists. Forty-six percent (n = 2421) of those sampled returned the questionnaire after two mailings. The reported rate of sedative premedication in the United States varied widely among age groups and geographical locations. Premedicant sedative drugs were least often used with children younger than age 3 years and most often used with adults less than 65 years of age (25% vs 75%, P = 0.001). Midazolam was the most frequently used premedicant both in adults and children (> 75%). When analyzed based on geographical locations, use of sedative premedicants among adults was least frequent in the Northeast region and most frequent in the Southeast region (50% vs 90%, P = 0.001). When the frequency of premedication was examined against health maintenance organization (HMO) penetration (i.e., HMO enrollment by total population) in the various geographical regions, correlation coefficients (r) ranged from -0.96 to -0.54. Multivariable analysis revealed that HMO penetration is an independent predictor for the use of premedication in adults and children. The marked variation among geographical areas in premedicant usage patterns underscores the lack of consensus among anesthesiologists about the need for premedication. The data suggest that HMO participation may affect delivery of this component of anesthetic care.

Adolescent↗
PubMed1997

Colonic structural and ion transport abnormalities in suckling rabbits infected with Escherichia coli K12.

BACKGROUND: Escherichia coli K12 is a laboratory strain considered nonpathogenic. The purpose of this study was to examine the effect of E. coli K12 infection on colonic structure and function. METHODS: Suckling rabbits were infected at 10 days of age with 6 x 10(9) CFU E. coli by intragastric inoculation and were examined 4 to 5 days later. Segments of ileum and proximal and distal colon were removed for light and electron microscopy, and NaCl transport was examined in vitro under short-circuited conditions in Ussing chambers. RESULTS: Infection did not cause weight loss or diarrhea. Colonic mucosa was inflamed with infiltration by polymorphonuclear neutrophils mainly in the lamina propria. The proximal and distal colon exhibited reduced Na+ absorption. The proximal colon also showed increased Cl- secretion; the ileum was unaffected. CONCLUSIONS: Infection with E. coli K12 disrupts the epithelium and alters ion transport in the colon, probably as a result of mucosal inflammation. The changes indicate that nonpathogenic E. coli have the potential to cause intestinal disease.

Animals↗
PubMed1997

The generation and subtraction of sensory expectations within cerebellum-like structures.

The generation of expectations about sensory input and the subtraction of such expectations from actual input appear to be important features of sensory processing. This paper describes the generation of sensory expectations within cerebellum-like structures of four distinct groups of fishes: Mormyridae; Rajidae; Scorpaenidae; and Apteronotidae. These structures consist of a sheet-like array of principal cells. Apical dendrites of the principal cells extend out into a molecular layer where they are contacted by parallel fibers. The basilar regions of the arrays receive primary afferent input from octavolateral endorgans, i.e., electroreceptors, mechanical lateral line neuromasts, or eighth nerve endorgans. The parallel fibers in the molecular layer convey various types of information, including corollary discharge signals associated with motor commands, sensory information from other modalities such as proprioception, and descending input from higher stages of the sensory modality that is processed by the structure. Associations between the signals conveyed by the parallel fibers and particular patterns of sensory input to the basal layers lead to the generation of a negative image of expected sensory input within the principal cell array. Addition of this negative image to actual sensory input results in the subtraction of expected from actual input, allowing the unexpected or novel input to stand out more clearly. Intracellular recording indicates that the negative image is probably generated by means of anti-Hebbian synaptic plasticity at the parallel fiber to principal cell synapse. The results are remarkably similar in the different fishes and may generalize to cerebellum-like structures in other sensory systems and taxa.

Afferent Pathways↗
PubMed1997

Amplitude modulation following response in children as a clinical audiometric tool.

The current study was designed to investigate the clinical application of amplitude modulation following response (AMFR) in cochlear implant candidates. A new digital signal processor (DSP)-assisted PC-based hardware and software was developed to perform both simultaneous generation of amplitude-modulated stimuli and the recording, and synchronized signal processing of the electrode signals. Our first results show that AMFR can be recorded in adults as well as in children without any contamination by response-like stimulus artifacts. Very high sound pressure levels can be applied, allowing frequency-specific assessment of residual hearing. Response threshold detection, using spectral analysis, proved to be superior compared to visual evaluation of average time waveforms.

Adult↗
PubMed1996

Detection of jun but not fos protein during developmental cell death in sympathetic neurons.

A large proportion of neurons die during normal development of the nervous system via an active process known as apoptosis. We counted the total number of neurons and apoptotic neurons in the superior cervical ganglion of the GH Wistar rat strain, which possesses a neurotrophic deficit leading to excessive perinatal cell death, and in its normal counterpart (N) by using the optical disector method to quantify the extent of apoptosis during postnatal development. Total neuron numbers fell between postnatal days 3 and 14 by 10 and 40% in N and GH, respectively. In GH ganglia, 1.5% of neurons were apoptotic at any given time, as determined by the presence of condensed chromatin clumps. Some types of cell death have been associated with expression of the immediate-early genes c-fos and c-jun. Therefore, we used histological and immunocytochemical techniques to characterise individual neurons and to detect the products of these immediate-early genes during developmental cell death. All apoptotic cells were immunopositive for c-jun protein, whereas no c-jun protein was detected in nonapoptotic cells. Conversely, members of the fos family of transcription factors were detected in the nucleus of 60% of nonapoptotic cells but in only a minor proportion of cells undergoing apoptosis. These results indicate that c-jun occurs in neurons that are committed to die. This is the first situation in which the presence of jun protein has been correlated with normal programmed cell death in individual apoptotic neurons.

Aging↗
PubMed1996

Interaction of cytochrome c with flavocytochrome b2.

Flavocytochrome b2 from Saccharomyces cerevisiae couples L-lactate dehydrogenation to cytochrome c reduction. At 25 degrees C, 0.10 M ionic strength, and saturating L-lactate concentration, the turnover rate is 207 s-1 [per cytochrome c reduced; Miles, C. S., Rouviere, N., Lederer, F., Mathews, F. S., Reid, G. A., Black, M. T., & Chapman, S. K. (1992) Biochem. J. 285, 187-192]. The second-order rate constant for cytochrome c reduction in the pre-steady-state has been determined by stopped-flow spectrophotometry to be 34.8 (+/- 0.9) muM-1 s-1 in the presence of 10 mM L-lactate. This rate constant has been found to be dependent entirely on the rate of complex formation, the electron-transfer rate in the pre-formed complex being in excess of 1000 s-1. Inhibition of the pre-steady-state reduction of cytochrome c by either zinc-substituted cytochrome c or ferrocytochrome c has led to the estimation of a Kd for the catalytically competent complex of 8 microM, and from this the dissociation rate constant of 280 s-1, a value much less than the actual electron-transfer rate. The inhibition observed is only partial which indicates that electron transfer from the 1:1 complex to another cytochrome c can occur and that alternative electron transfer sites exist. The cytochrome c binding site proposed by Tegoni et al. [Tegoni, M., White, S. A., Roussel, A., Mathews, F. S. & Cambillau, C. (1993) Proteins 16, 408-422] has been tested using site-directed mutagenesis. Mutations designed to affect the complex stability and putative electron-transfer pathway had little effect, suggesting that the primary cytochrome c binding site on flavocytochrome b2 lies elsewhere. The combination of tight binding and multiple electron-transfer sites gives flavocytochrome b2 a low K(m) and a high kcat, maximizing its catalytic efficiency. In the steady-state, the turnover rate is therefore largely limited by other steps in the catalytic cycle, a conclusion which is discussed in the preceding paper in this issue [Daff, S., Ingledew, W. J., Reid, G. A., & Chapman, S. K. (1996) Biochemistry 35, 6345-6350].

Base Sequence↗
PubMed1996

Ethnic differences and recent trends in coronary heart disease incidence in New Zealand.

AIMS: This study compares recent coronary heart disease morbidity and mortality rates and ten year trends for Maori, Pacific Islands people and Europeans living in New Zealand. METHODS: Fatal coronary heart disease rates (mortality) and nonfatal hospitalisation rates for myocardial infarctions (morbidity) from 1983-92 were assessed and compared for males and females in each ethnic group, aged 35 to 64 years, using data from the Auckland Region Coronary or Stroke Study (ARCOS), a community-based coronary heart disease surveillance programme. RESULTS: The recent 1990-2 mean coronary heart disease mortality rate for Maori men (232/100 000) was almost double the rate for Pacific Islands men (135/100 000 p=0.008) and more than double the rate for European men (103/100 000 p=0.001). Maori women had a three-fold higher mean mortality rate (85/100 000) than European women (25/100 000 p=0.02). The morality rate for Pacific Islands women (42/100 000) was midway between the other ethnic groups. Over the decade 1983-92 coronary heart disease mortality rates have decreased significantly by approximately 5% per year for European men and women. Rates for Maori and Pacific Islands people also appear to have fallen although the precision of these estimates are low. Morbidity rates in 1990-2 were similar among men in all three ethnic groups. Among women, morbidity was approximately half the male rates and there were no clear differences between the ethnic groups. Between 1983 and 1992 morbidity rates declined significantly for European men (p=0.008) and women (p=0.02) by approximately 5% per year. Among Maori and Pacific Islands people the trends were variable. CONCLUSION: Maori men and women continue to experience more than double the coronary heart disease mortality rates than Europeans. Mortality rates for Pacific Islands people are intermediate between Maori and European. Both coronary heart disease mortality and morbidity rates are declining in Europeans; there appears to have been a decline in coronary heart disease mortality for Maori and Pacific Islands groups but not in morbidity rates which may have increased. Given the trend towards a decline in coronary heart disease mortality for Maori and Pacific Islands people, the most likely explanation for the apparent increase in morbidity is improved access to secondary health care services and greater awareness of coronary health disease symptoms.

Adult↗
PubMed1996

Sensory expectations and anti-Hebbian synaptic plasticity in cerebellum-like structures.

Cerebellum-like sensory structures in different groups of first have been shown to generate a negative image of predictable features of the sensory input. We show here that anti-Hebbian plasticity is present at the synapse between parallel fibers and Purkinje-like cells which could mediate the generation of these negative images. We also show that this synapse is capable of bidirectional changes in synaptic efficacy with the direction of change depending on the precise temporal relation of presynaptic input and postsynaptic spike during pairing. Parallel fiber-evoked EPSPs are depressed after pairings in which the EPSP begins between 0 and 60 ms before the postsynaptic spike but are enhanced at other delays, including those in which the postsysnaptic spike occurs just before the EPSP.

Animals↗
PubMed1996

Decreased developmental cell death in sympathetic and spinal sensory nervous systems of the Kyoto spontaneously hypertensive rat.

OBJECTIVE: To investigate the hypotheses that Kyoto spontaneously hypertensive rats (SHR) possess more sympathetic neurons than do normotensive Wistar-Kyoto (WKY) animals due to reduced perinatal cell death and that this is due to increased availability of the sympathetic survival neurotrophin, nerve growth factor. METHODS: Total cell counts of neuron numbers were performed in neonatal and adult SHR and WKY rat superior cervical ganglia and correlated with counts of apoptotic cells. The values for sympathetic neuron numbers were compared with those for a spinal sensory ganglion. Immunocytochemistry was used to obtain more information about the phenotypes of neurons counted. RESULTS: Adult SHR sympathetic ganglia contained about 25% more sympathetic neurons than did those of WKY animals. Similar elevation of numbers was found both for neurons containing and for those devoid of neuropeptide Y. In neonatal animals, in contrast, there was no strain difference in sympathetic cell numbers but the number of apoptotic cells was reduced in SHR. Spinal sensory neuron numbers in adult SHR were elevated to a similar extent as were sympathetic neurons, but biochemical and morphometric data suggested that this change does not involve cells that are sensitive to nerve growth factor. CONCLUSIONS: Although our results support the view that there is reduced developmental cell death both in sympathetic and in sensory systems, they also suggest that this is unlikely to be due to a simple excess of nerve growth factor during development.

Age Factors↗
PubMed1996

Cyclic AMP-dependent anion secretion in human small and large intestine.

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.

Adolescent↗
PubMed1996

Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family to chromosome 7q.

Retinitis pigmentosa is a group of hereditary retinopathies which is both clinically and genetically heterogeneous. Autosomal dominant (ADRP), autosomal recessive (ARRP), and X linked recessive (XLRP), as well as digenic forms of inheritance have been reported. ADRP has been linked to 3q, 6p, 7p, 7q, 8cen, 17p, 17q, and 19q. Three unrelated ADRP families have been reported to show linkage to 7q. We tested a Scottish ADRP family with microsatellite markers mapping within the 7q31-q35 region, and found three markers (D7S487, D7S514, D7S530) showing statistically significant evidence of linkage. A maximum two point lod score of 3.311 at 0% recombination was obtained for D7S514.

Adolescent↗