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C Bell

Publications and source records attributed to C Bell.

At least 19 recordsLinked to original sources
PubMed1997

Does this patient have an abnormal systolic murmur?

Our objective was to review the available evidence of the precision and accuracy of the clinical examination for abnormal systolic murmurs. We conducted a MEDLINE search, manually reviewed all reference lists, and contacted authors of published studies. Each study was independently reviewed by 2 observers and graded for methodologic quality. We found that most studies were conducted using cardiologist examiners. In the clinical setting, the reliability of detecting systolic murmurs was fair (kappa, 0.30-0.48). The most useful findings for ruling in aortic stenosis are a slow rate of rise of the carotid pulse (positive likelihood ratio, 2.8-130), mid to late peak intensity of the murmur (positive likelihood ratio, 8.0-101), and decreased intensity of the second heart sound (positive likelihood ratio, 3.1-50). The most useful finding for ruling out aortic stenosis is the absence of murmur radiation to the right carotid artery (negative likelihood ratio, 0.05-0.10). Smaller, lower-quality studies indicate that cardiologists can accurately rule in and rule out mitral regurgitation, tricuspid regurgitation, hypertrophic cardiomyopathy, and echocardiographic mitral valve prolapse. We conclude that the clinical examination by cardiologists is accurate for detecting various causes of abnormal systolic murmurs. Studies of the clinical examination by noncardiologists are needed.

Cardiology↗
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↗
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↗
PubMed1995

Potent 2'-amino-2'-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor.

Screening of random oligonucleotide libraries with SELEX [systematic evolution of ligands by exponential enrichment; Tuerk, C., & Gold, L. (1990) Science 249, 505-510] has emerged as a powerful method for identifying high-affinity nucleic acid ligands for a wide range of molecular targets. Nuclease sensitivity of unmodified RNA and DNA, however, imposes considerable restrictions on their use as therapeutics or diagnostics. Modified RNA in which pyrimidine 2'-hydroxy groups have been substituted with 2'-amino groups (2'-aminopyrimidine RNA) is known to be substantially more resistant to serum nucleases. We report here on the use of SELEX to identify high-affinity 2'-aminopyrimidine RNA ligands to a potent angiogenic factor, basic fibroblast growth factor (bFGF). High-affinity ligands with the same consensus primary structure have been isolated from two independent libraries of approximately 6 x 10(14) molecules containing 30 or 50 randomized positions. Compared to unmodified RNA with the same sequence, 2'-aminopyrimidine ligands are at least 1000-fold more stable in 90% human serum. The sequence information required for high-affinity binding to bFGF is contained within 24-26 nucleotides. The minimal ligand m21A (5'-GGUGUGUGGAAGACAGCGGGUGGUUC-3'; G = guanosine, A = adenosine, C = 2'-amino-2'-deoxycytidine, U = 2'-amino-2'-deoxyuridine, and C = 2'-amino-2'-deoxycytidine or deoxycytidine) binds to bFGF with an apparent dissociation constant (Kd) of 3.5 +/- 0.3) x 10(-10) M at 37 degrees C in phosphate-buffered saline (pH 7.4). Disassociation of m21A from bFGF is adequately described with a first-order rate constant of (1.96 +/- 0.08) x 10(-3) s-1 (t1/2 = 5.9 min). The calculated value for the association rate constant (kon = k(off)/Kd) was 5.6 x 10(6) M-1 s-1. Highly specific binding of m21A to bFGF was observed: binding to denatured bFGF, five proteins from the FGF family (acidic FGF, FGF-4, FGF-5, FGF-6, and FGF-7), and four other heparin binding proteins is substantially weaker under the same conditions with KdbFGF/Kdprotein values ranging from (4.1 +/- 1.4) x 10(-2) to > 10(-6). Heparin but not chondroitin sulfate competed for binding of m21A to bFGF. In cell culture, m21A inhibited [125I]bFGF binding to both low-affinity sites (ED50 approximately 1 nM) and high-affinity sites (ED50 approximately 3 nM) on CHO cells expressing transfected FGF receptor-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Worthy journals.

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Periodicals as Topic↗
PubMed1995

Cat health care.

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Animals↗