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Biomedical subjects

C Bell

Publications and source records attributed to C Bell.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1995

Neurokinin A and substance P vary independently in different regions of rat sensory neurons.

Neurokinin A (NKA) and substance P (SP) are often co-localized in small sensory neurons and have been suggested to subserve similar roles. We have now compared tissue levels of NKA and SP in rat cervical dorsal root ganglia with those in the central and peripheral terminations of the same neurons. We found that NKA content was less than that of SP in dorsal root neuron perikarya and in two peripheral tissues (superior cervical ganglion and ear skin) containing SP axon terminals from cervical spinal ganglia; in a third peripheral tissue, trachea, equal amounts of NKA and SP were present. By contrast, in the spinal cord containing the central terminals of these sensory neurons there was almost twice as much NKA as SP. Our results indicate that, although NKA and SP are co-localized in sensory neurons, their levels vary independently, suggesting distinct functional roles.

Animals↗
PubMed1995

Infant apnea detection after herniorrhaphy.

STUDY OBJECTIVE: To elucidate risk factors for apnea in preterm infants discharged from the hospital and in full-term healthy infants. To determine the efficacy of real-time cardiopulmonary monitoring versus computerized storage and retrieval for infants at risk. STUDY DESIGN: Prospective study. SETTING: Operating rooms and pediatric patient care units of university medical center. PATIENTS: 27 preterm infants and 20 full-term infants no more than 60 weeks' post-conceptional age, who were admitted for elective herniorrhaphy. INTERVENTIONS: Infants were monitored before and after herniorrhaphy with general anesthesia using an infant apnea impedance monitor, pulse oximetry, and nursing observation. MEASUREMENTS AND MAIN RESULTS: Demographic information and medical history were correlated with postoperative apnea. The sensitivity and specificity of nursing observation and oximetry were compared with computerized apnea monitors. Five patients (11%, four preterm, one full-term) were apneic postoperatively as recorded by computerized pneumocardiography. Previous apnea history, gestational age at birth, and postconceptional age at operation positively correlated with postoperative apnea. Nursing observation failed to detect 4 of 5 patients with documented apnea (sensitivity 20%, positive predictive value 50%). Pulse oximetry failed to detect 3 of 5 patients with apnea (sensitivity 40%, positive predictive value 66%). CONCLUSIONS: Although it is easier to predict postoperative respiratory dysfunction in previously sick or very young infants, absolute predictability for all neonates remains elusive. Clinical monitors with both storage and retrieval capabilities and real-time monitoring increase our ability to detect significant events in children at risk for apnea after herniorrhaphy.

Apnea↗
PubMed1995

Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor.

BACKGROUND: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a potent inducer of new blood vessel growth (angiogenesis) that contributes to the pathology of many angiogenesis-associated disease states such as psoriasis, rheumatoid arthritis and cancer. Few molecular entities capable of binding to VPF/VEGF with high affinity and specificity have been described to date. RESULTS: Nuclease-resistant 2'-amino-2'-deoxypyrimidine nucleotide RNA (2'-aminopyrimidine RNA) ligands that bind to VPF/VEGF with high affinity have been identified by iterative rounds of affinity-selection/amplification from two independent random libraries. The sequence information that confers high affinity binding to VPF/VEGF is contained in a contiguous stretch of 24 nucleotides, 5'-CCCUGAUGGUAGACGCCGGGGUG-3' (2'-aminopyrimidine nucleotides are designated with italic letters). Of the 14 ribopurines in this minimal ligand, 10 can be substituted with the corresponding 2'-O-methylpurine nucleotides without a reduction in binding affinity to VPF/VEGF. In fact, the 2'-O-methyl substitution at permissive positions leads to a approximately 17-fold improvement in the binding affinity to VPF/VEGF. The higher affinity results from the reduction in the dissociation rate constant of the 2'-O-methyl-substituted RNA ligand from the protein compared to the unsubstituted ligand. The 2'-O-methyl-substituted minimal ligand, which folds into a bulged hairpin motif, is also more thermally stable than the unsubstituted ligand. Nuclease resistance of the ligand is further improved by the 2'-O-methyl substitutions and the addition of short phosphorothioate caps to the 3'- and 5'-ends. CONCLUSIONS: We have used the SELEX (systematic evolution of ligands by exponential enrichment) process in conjunction with post-SELEX modifications to define a highly nuclease-resistant oligonucleotide that binds to VPF/VEGF with high affinity and specificity.

Animals↗
PubMed1995

A comparison of techniques used to estimate the amount of resuspended soil on plant surfaces.

The objectives of this study were to compare four common techniques used to estimate soil mass loadings on plant surfaces and to assess the need to account for particle-size distributions of both the soil tracer and contaminant of concern within the soil. Soil loadings (g soil kg-1 dried plant) from split samples collected in a pasture near Chernobyl were estimated using soil tracers of plutonium analyzed via alpha spectroscopy (mean +/- standard error; 1.0 +/- 0.2), titanium analyzed with an inductive coupled plasma spectrometer; (3.6 +/- 0.6), and neutron activation analysis for scandium (8.1 +/- 1.6), as well as simply washing the soil off the vegetation (34.1 +/- 5.6) Differences were significant at p < 0.001. We also found that soil loading estimates from any one technique varied by a factor of 10 depending on the soil particle size used in the calculations. This was because soil loadings decreased when smaller-sized soil fractions dominated the resuspension process. However, the percent of the plant's total contamination attributable to soil loading increased with smaller soil particles. Smaller soil particles apparently contribute less to the mass of soil loading (g soil kg-1 dry plant), but more to the total plant contamination (Bq) because of the higher concentration of contaminant found in the smaller-sized soil fractions. Differences in mass loading estimates due to the technique chosen (a factor of 10), or due to differences in elemental concentration as a result of the soil particle size used in the calculation (also a factor of 10), were greater than the natural variability observed in the field (2.5).

Alpha Particles↗