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Biomedical subjects

M M Campbell

Publications and source records attributed to M M Campbell.

At least 19 recordsLinked to original sources
PubMed2004

Complete nucleotide sequence of the genomic RNA of poplar mosaic virus (Genus Carlavirus).

The complete nucleotide sequence of the Poplar mosaic virus (PopMV) genome was determined. The genomic RNA of PopMV is 8,742 nucleotides in length. Comparative sequence analysis supports earlier research suggesting that this virus is a member of the genus Carlavirus. For example, as is the case for all carlaviruses, there are 6 predicted ORFs in the PopMV genome. The first ORF, ORF1, encodes a predicted helicase/replicase, which corresponds to ORF1 from other carlaviruses, while ORF2, ORF3, ORF4, ORF5 and ORF6 encode the three triple block proteins, the coat protein, and a putative nucleic acid-binding protein respectively.

3' Untranslated Regions↗
PubMed2001

Pachyderms, primates, plants and population.

In the past, growth in human population has often been associated with species loss. Current rates of population growth, both globally (1 million more births than deaths every 103 hours) and regionally, pose a threat of additional ecological damage. There is a well-documented unmet demand for family planning in nearly all high-fertility countries. Improved family planning and safe abortion services will improve the health of women and their families, accelerate fertility decline, and help preserve the environment. Many ecologically vulnerable areas are especially poorly served by family planning services. Examples are given here of improving family planning services through private health providers near the Kakamega Forest in western Kenya, and of adding family planning choices to a reforestation project run by the Jane Goodall Institute near the Gombe National Park, Tanzania. Wildlife biologists can play a critical role in identifying local professionals and institutions with the potential to improve family planning.

Animals↗
PubMed2000

Aluminum toxicity in a molluscan neuron: effects of counterions.

Previous studies using the freshwater snail Lymnaea stagnalis have indicated significant accumulation of aluminum (Al) from simple salts (chloride or nitrate) or Al lactate [Al(lactate)3 preparations, but not from the Al maltol complex [Al(maltol)3]. This is in contrast to findings in mammalian systems, where uptake and neurotoxicity are greatest for the soluble and lipophilic Al(maltol)3 complex. This study was undertaken to investigate the direct effects of extracellular Al (100 microM) from three Al preparations [AlCl3, Al(lactate)3 and Al(maltol)3] on electrophysiological parameters of an identified neuron, the right parietal dorsal 1 (RPD1) neuron, of L. stagnalis in vitro. The effects of the corresponding counterion/ligand on the solubility and availability of Al in solution were also examined. Significant effects of Al on electrical properties, including membrane depolarization, increased firing activity, and abnormal firing patterns, were seen in the presence of AlCl3 and Al(lactate)3, which formed polyhydroxy and labile Al species in aqueous solution, but not with Al(maltol)3, which remained as the soluble monomeric complex. Qualitative differences were also observed between the response to AlCl3 and Al(lactate)3, despite their similar chemistry. The extent of action potential broadening was greater with Al(lactate)3, suggesting some interaction between Al and lactate in their cellular uptake and/or toxicity. It is suggested that polyhydroxy Al species are toxic to molluscan neurons, possibly via disruption of intracellular Ca2+ homeostasis.

Aluminum↗
PubMed2000

Bioaccumulation and toxicity of aluminium in the pond snail at neutral pH.

The low solubility of aluminium (Al) at neutral pH means that it largely exists as colloidal particulates in aquatic systems. However, the pond snail Lymnaea stagnalis accumulates significant amounts of Al following exposure to water containing added Al (up to 500 microg l(-1)) at pH 7. This is accompanied by depression of behavioural activity (locomotion, feeding) which subsequently recovers, suggesting tolerance to the metal. The presence of silica ameliorates behavioural toxicity of Al, but does not prevent uptake of the metal. In vitro studies using the isolated central nervous system demonstrate toxicity at the cellular level. Extracellular application of Al (100 microM) led to membrane depolarisation, bursts of action potentials and action potential broadening. The chemical form in which Al is applied influences the extent of bioaccumulation and toxicity. Detailed knowledge of its solution chemistry is therefore essential.

Action Potentials↗
PubMed1998

Analysis of xylem formation in pine by cDNA sequencing.

Secondary xylem (wood) formation is likely to involve some genes expressed rarely or not at all in herbaceous plants. Moreover, environmental and developmental stimuli influence secondary xylem differentiation, producing morphological and chemical changes in wood. To increase our understanding of xylem formation, and to provide material for comparative analysis of gymnosperm and angiosperm sequences, ESTs were obtained from immature xylem of loblolly pine (Pinus taeda L.). A total of 1,097 single-pass sequences were obtained from 5' ends of cDNAs made from gravistimulated tissue from bent trees. Cluster analysis detected 107 groups of similar sequences, ranging in size from 2 to 20 sequences. A total of 361 sequences fell into these groups, whereas 736 sequences were unique. About 55% of the pine EST sequences show similarity to previously described sequences in public databases. About 10% of the recognized genes encode factors involved in cell wall formation. Sequences similar to cell wall proteins, most known lignin biosynthetic enzymes, and several enzymes of carbohydrate metabolism were found. A number of putative regulatory proteins also are represented. Expression patterns of several of these genes were studied in various tissues and organs of pine. Sequencing novel genes expressed during xylem formation will provide a powerful means of identifying mechanisms controlling this important differentiation pathway.

DNA, Complementary↗
PubMed1997

Inheritance, gene expression, and lignin characterization in a mutant pine deficient in cinnamyl alcohol dehydrogenase.

We have discovered a mutant loblolly pine (Pinus taeda L.) in which expression of the gene encoding cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) is severely reduced. The products of CAD, cinnamyl alcohols, are the precursors of lignin, a major cell wall polymer of plant vascular tissues. Lignin composition in this mutant shows dramatic modifications, including increased incorporation of the substrate of CAD (coniferaldehyde), indicating that CAD may modulate lignin composition in pine. The recessive cad-n1 allele, which causes this phenotype, was discovered in a tree heterozygous for this mutant allele. It is inherited as a simple Mendelian locus that maps to the same genomic region as the cad locus. In mutant plants, CAD activity and abundance of cad RNA transcript are low, and free CAD substrate accumulates to a high level. The wood of the mutant is brown, whereas the wood in wild types is nearly white. The wood phenotype resembles that of brown midrib (bm) mutants and some transgenic plants in which xylem is red-brown due to a reduction in CAD activity. However, unlike transgenics with reduced CAD, the pine mutant has decreased lignin content. Wood in which the composition of lignin varies beyond previous expectations still provides vascular function and mechanical support.

Alcohol Oxidoreductases↗
PubMed1996

Preparation of dipeptoid mimetics for the tetrapeptide cholecystokinin, CCK(30-33).

The diastereoselective synthesis of 2,3-methanophenylalanine methyl esters (5) has been achieved in 58% yield. The preparation of the dehydropeptides (1, R = Me; 2, R = H) and the cyclopropylpeptides (3, R = Me; 4, R = H) possessing good binding affinities for the CCK-A and CCK-B receptors is described. Conformational studies of the dipeptide esters 1 and 3 indicated the presence of a beta-turn within the peptide backbone, although there was no preference in type. The Phe and Trp moieties, however, did prefer to be situated on the same side of the peptide turn which is favourable for receptor binding.

Molecular Conformation↗
PubMed1994

Evaluation of universal hepatitis B immunization practices of Illinois pediatricians.

OBJECTIVE: To characterize universal hepatitis B immunization practices of pediatricians who routinely provide childhood immunizations in Illinois. DESIGN: Survey of 522 randomly chosen Illinois pediatricians. Student's t test, chi 2 analysis, and multivariate logistic regression were used to identify relationships between physician demographics and outcomes of interest. MAIN OUTCOME MEASURES: Physician agreement with the new Centers for Disease Control and Prevention Immunization Practices Advisory Committee and the American Academy of Pediatrics universal infant hepatitis B immunization guidelines, incorporation of the recommendations, routine hepatitis B immunization of older children (aged 6 months to 11 years), and routine hepatitis B immunization of adolescents. RESULTS: The survey response rate was 71.5%. Of those pediatricians routinely providing immunizations (N = 323), 72.8% agreed with and 90.1% have incorporated universal hepatitis B immunization; 36.5% and 53.0% routinely immunized older children and adolescents, respectively. Pediatricians practicing in medium-sized practices were half as likely to agree with the recommendations (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.31 to 0.84). Cost and a belief that universal immunization of infants is not medically necessary were the two most commonly listed reasons for not incorporating the new guidelines. Percent reimbursement from public aid was negatively related to the routine immunization of older children (OR, 0.34; 95% CI, 0.12 to 0.95). Both percent reimbursement from self-pay (OR, 5.62; 95% CI, 2.25 to 14.05) and a rural location (OR, 0.16; 95% CI, 0.04 to 0.56) were related to routine hepatitis B immunization of adolescents. Gender and number of years in practice were not associated with physician response. CONCLUSIONS: The majority of Illinois pediatricians who routinely provide pediatric immunizations have incorporated the new universal hepatitis B immunization guidelines into their practices. Continued efforts to address financial barriers and to educate physicians may hasten the time when the transmission of the hepatitis B virus will no longer occur.

Adolescent↗
PubMed1993

Bayesian forecasting of gentamicin pharmacokinetics in pediatric intensive care unit patients.

The predictive performance of a one compartment Bayesian forecasting program was evaluated in pediatric intensive care unit patients with normal renal function. Gentamicin pharmacokinetic parameters were determined in 44 PICU patients (0.8 month to 14 years old) from all available serum concentrations and doses by nonlinear least squares regression. Population pharmacokinetic parameter estimates were established from 27 of the PICU patients. Mean prediction error (ME) and mean absolute error (MAE) for 2 future sets of peak and trough gentamicin serum concentrations with the use of the population parameter estimates with and without feedback were evaluated in the remaining 17 patients. Mean clearance (+/- SD) and volume of distribution for all 44 patients were 0.123 +/- 0.041 liter/hour/kg and 0.424 +/- 0.116 liter/kg, respectively. Bayesian forecasting of the second set of peak and trough concentrations with feedback from the first set of peak and trough concentrations resulted in smaller bias (peak ME, -0.15 mg/liter; trough ME, 0.13 mg/liter) and better accuracy (peak MAE, 0.91 mg/liter; trough MAE, 0.28 mg/liter) compared with the population parameter estimates alone (peak ME, 0.4 mg/liter; trough ME, 0.28 mg/liter; peak MAE, 1.21 mg/liter; trough MAE, 0.57 mg/liter). This study indicates that gentamicin volume of distribution in PICU patients is larger than non-PICU literature values. The Bayesian program, with specific population parameter estimates for PICU patients, provides accurate initial and subsequent predictions of gentamicin serum concentrations.

Adolescent↗
PubMed1992

Conformational analysis of the melanin-concentrating hormone core by circular dichroic spectroscopy. Disulphide bridge and tyrosine contributions.

A detailed circular dichroic (CD) study of the conformational flexibility of the melanin-concentrating hormone core [MCH(5-14)] is reported. Variable pH (2-10) and temperature (-80 degrees to +80 degrees C) in aqueous media reveal that CD contributions from tyrosine, disulphide bridge and the amide backbone can be discriminated. Only below -10 degrees C does a preferred -S-S-conformation (P chirality, dihedral angle phi = 90 +/- 10 degrees) dominate. The amide backbone CD contribution varies over all temperatures (-80 degrees to +80 degrees C) providing evidence for a type-II beta-turn at low temperatures, with the emergence of a type-I beta-turn at higher temperatures. Tyrosine exhibits a special behaviour at pH 7. These conclusions are in broad agreement with published NMR studies. Nevertheless, the MCH(5-14) core is seen to be conformationally flexible in aqueous solution at ambient temperatures. Conformation differences are observed in a non-aqueous environment.

Amino Acid Sequence↗
PubMed1992

Modeling of substrate and inhibitor binding to phospholipase A2.

Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma.

Amino Acid Sequence↗
PubMed1992

Fungal Elicitor-Mediated Responses in Pine Cell Cultures : III. Purification and Characterization of Phenylalanine Ammonia-Lyase.

Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) is involved in the lignification of pine suspension cultures in response to an elicitor prepared from an ectomycorrhizal fungus. To elucidate the molecular basis of this response, PAL was purified to homogeneity from jack pine (Pinus banksiana) suspension cultures using anion-exchange and chromatofocussing fast protein liquid chromatography. Physical characterization of the enzyme revealed that pine PAL was similar to PAL from other plant sources. Pine PAL had a pH optimum of 8.8, an isoelectric point of 5.75, and a native molecular mass of 340 kilodaltons. The enzyme appears to be a tetramer composed of 77 kilodalton subunits. Chromatographic and western blot analyses were used to identify possible isoenzymic changes in pine PAL in response to elicitation and to determine the nature of the increase in PAL activity associated with inducible lignification in these cultures. Only one species of PAL was detected in P. banksiana cell cultures and increased quantities of this protein were correlated with the enhanced enzyme activity observed in elicited cultures. P. banksiana PAL was not feedback-inhibited by a wide range of phenolic compounds at micromolar concentrations, including the reaction product cinnamic acid. Our data suggest that a different set of metabolic and molecular controls must be in place for the regulation of PAL in pine.

Journal Article↗
PubMed1991

Conformational analysis of peptide surrogates. Reduced and retro-amide links in blocked alanine and in secondary structures.

We have investigated the conformational effects of modifying the amide link of peptides. We studied a reverse amide bond psi [NHCO], a reduced amide bond psi [CH2NH] and a retro-reduced bond psi [NHCH2] as surrogates for the amide link [CONH] in native peptides. A complete search of the conformational space available to residues with these modified links was carried out. The local minima and the rotational barriers were described and compared to the minima of the native residue. The results are compatible with the available observed structural data. These modified links have been incorporated in secondary structure units such as beta turns, alpha helices, and parallel and anti-parallel beta sheets. It was found that a reduced amide link can lead to stabilised beta turns, while the retro modification can be incorporated in stable beta sheets. A significant reduction in the stability of alpha helices is caused by the retro links, while a reduced amide link results in only a small destabilisation.

Alanine↗
PubMed1990

Melanin-concentrating hormone: a structural and conformational study based on synthesis, biological activity, high-field NMR, and molecular modeling techniques.

A series of Melanin-concentrating hormone (MCH) fragments have been synthesized and their biological activities compared with the parent peptide. The substructural units, 5-14 linear and 5-14 cyclic, have been used as models for MCH-- H-Asp1-Thr-Met-Arg-Cys-Met-Val-Gly-Arg HO-Val17-Glu-Trp-Cys-Pro-Arg-Tyr-Val in 1H-nmr conformational studies. Conformational features predicted by molecular dynamics analyses find support in the nmr experiments.

Amino Acid Sequence↗
PubMed1990

Accessible conformations of melanin-concentrating hormone: a molecular dynamics approach.

Molecular dynamics simulations have been used to search for the accessible conformations of the melanin-concentrating hormone (MCH). The studies have been performed on native MCH and two of its peptide fragments, a cyclic MCH(5-14) fragment and a linear MCH(5-14) fragment. An analysis of the molecular dynamics trajectories of the three peptides indicates that two regions of the peptide have characteristic conformational properties that may be important for the biological activity. One is a region around Gly8, which is conformationally mobile, and the other is around Pro13, which shows unusual rigidity. The molecular dynamics simulation results are discussed in terms of backbone structural features like beta turns, side-chain interactions, and orientations of the disulfide bridge. The results of this analysis are used to suggest new analogues that will modify the conformational features of the peptide and further define the conformational requirements for activity. Finally, the results are related to nmr studies of the peptide and reveal agreements between the experimental nuclear Overhauser effect constraints and some of the accessible conformations obtained from the simulation.

Amino Acid Sequence↗
PubMed1990

The conformational preferences of gamma-lactam and its role in constraining peptide structure.

The conformational constraints imposed by gamma-lactams in peptides have been studied using valence force field energy calculations and flexible geometry maps. It has been found that while cyclisation restrains the psi of the lactam, non-bonded interactions contribute to the constraints on psi of the lactam. The gamma-lactam also affects the (psi, psi) of the residue after it in a peptide sequence. For an L-lactam, the ring geometry restricts psi to about -120 degrees, and psi has two minima, the lowest energy around -140 degrees and a higher minimum (5 kcal/mol higher) at 60 degrees, making an L-gamma-lactam more favourably accommodated in a near extended conformation than in position 2 of a type II' beta-turn. The energy of the psi approximately +60 degrees minimum can be lowered substantially until it is more favoured than the -140 degrees minimum by progressive substitution of bulkier groups on the amide N of the L-gamma-lactam. The (psi, psi) maps of the residue succeeding a gamma-lactam show subtle differences from those of standard N-methylated residues. The dependence of the constraints on the chirality of gamma-lactams and N-substituted gamma-lactams, in terms of the formation of secondary structures like beta-turns is discussed and the comparison of the theoretical conformations with experimental results is highlighted.

Computer Simulation↗