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J R Powell

Publications and source records attributed to J R Powell.

At least 73 records · Page 4Linked to original sources
PubMed1994

Higher level relationships of the arctoid Carnivora based on sequence data and "total evidence".

The relationships of the lesser or red panda, Ailurus, have remained elusive even as any doubts about the identity of the giant panda as a bear have been erased. While usually classified as a member of the Procyonidae (raccoons), recent anatomical studies have suggested that the red panda may not fall in any of the arctoid carnivore families but instead may reflect an early offshoot of the lineage leading to ursids (bears) and pinnipeds (seals, sea lions, and walruses). Sequence data from the cytochrome b and 12S genes for multiple representatives of all relevant families support this hypothesis. Such a systematic position makes this threatened species particularly worthy of conservation. Sequence data alone, as well as a combined analysis of the sequence and anatomical data, strongly support a single origin of pinnipeds and their aquatic adaptations, lending some resolution to the general disagreement about familial relationships in this group. These molecular data also support canids as the basal members of this caniform clade, but are unresolved with respect to whether mustelids or procyonids constitute the sister group to the (ursid, pinniped, Ailurus) clade. There is support for the notion that skunks are a genetically divergent and possibly nonmustelid lineage.

Animals↗
PubMed1994

Phylogeny of all major groups of cetaceans based on DNA sequences from three mitochondrial genes.

Traditionally, living cetaceans (order Cetacea) are classified into two highly distinct suborders: the echolocating toothed whales, Odontoceti, and the filter-feeding baleen whales, Mysticeti. A molecular phylogeny based on 1,352 base pairs of two mitochondrial ribosomal gene segments and the mitochondrial cytochrome b gene for all major groups of cetaceans contradicts this long-accepted taxonomic subdivision. One group of toothed whales, the sperm whales, is more closely related to the morphologically highly divergent baleen whales than to other odontocetes. This finding suggests that the suborder Odontoceti constitutes an unnatural grouping and challenges the conventional scenario of a long, independent evolutionary history of odontocetes and mysticetes. The superfamily Delphinoidea (dolphins, porpoises, and white whales) appears to be monophyletic; the Amazon River dolphin, Inia geoffrensis, is its sister species. This river dolphin is genetically more divergent from the morphologically similar marine dolphins than the sperm whales are from the morphologically dissimilar baleen whales. The phylogenetic relationships among the three families of Delphinoidea remain uncertain, and we suggest that the two cladogenetic events that generated these three clades occurred within a very short period of time. Among the baleen whales, the bowhead is basal, and the gray whale is the sister species to the rorquals (family Balaenopteridae). The phylogenetic position of beaked whales (Ziphioidea) remains weakly supported by molecular data. Based on molecular clock assumptions, the mitochondrial-DNA data suggest a more recent origin of baleen whales (approximately 25 mya) than has been previously assumed (> 40 mya). This revised phylogeny has important implications for the rate and mode of evolution of morphological and physiological innovations in cetaceans.

Animals↗
PubMed1994

BMS-180560, an insurmountable inhibitor of angiotensin II-stimulated responses: comparison with losartan and EXP3174.

1. This study compares the activity of BMS-180560 (2-butyl-1-chloro-1-[[1-[2-(2H-tetrazol-5-yl)phenyl]-1H-indol-4- yl]methyl]-1H-imidazole-5-carboxylic acid), an insurmountable angiotensin II (AII) receptor antagonist, with that of losartan and EXP3174 in functional and biochemical models of AII-receptor activation. 2. BMS-180560 selectively inhibited [125I]-Sar1Ile8AII ([125I]SI-AII) binding to rat aortic smooth muscle (RASM) cell and rat adrenal cortical AT1 receptors (Ki = 7.6 +/- 1.2 and 18.4 +/- 3.9 nM respectively) compared to adrenal cortical AT2 receptors (Ki = 37.6 +/- 1.3 microM). The Ki values of BMS-180560 and EXP3174, but not losartan, varied as a function of the BSA concentration used in the assays, indicating that the diacid drugs bound to albumin. 3. BMS-180560 (3-300 nM) increased the KD of SI-AII for RASM cell AT1 receptors. Only at high concentrations of BMS-180560 (300 nM) were Bmax values decreased. 4. BMS-180560 inhibited AII-stimulated contraction of rabbit aorta with a calculated KB = 0.068 +/- 0.048 nM and decreased maximal AII-stimulated contraction at 1 nM BMS-180560 by 75%. In the presence of 0.1% BSA, a higher KB value (5.2 +/- 0.92 nM) was obtained. Losartan behaved as a competitive antagonist with a KB = 2.6 +/- 0.13 nM. Contraction stimulated by endothelin-1, noradrenaline, KCl, or the TXA2 receptor agonist U-46619 were unaffected by BMS-180560 (1 nM). 5. AII stimulated the acidification rates of RASM cells as measured by a Cytosensor microphysiometer with an EC50 of 18 nM. Losartan (30 nM) shifted the AII concentration-effect curves in a competitive manner whereas BMS-180560 (0.01 and 0.1 nM) decreased the maximum responses by 60 and 75% respectively. Inhibition by losartan and BMS-180560 could be reversed following washout although recovery took longer for BMS-180560. 6. In [3H]-myoinositol-labelled RASM cells, losartan (30 and 200 nM), shifted the EC50 for AII-stimulated [3H]-inositol monophosphaste formation to higher values, with no change in the maximal response. By contrast, EXP3174 (0.1 to 1 nM) decreased the maximal response in a concentration-dependent manner (17-55%). BMS-180560 (3 and 10 nM) increased the EC50 for AII and decreased the maximum response by 30 and 80% respectively. The inhibition by EXP3174 and BMS-180560 could be reversed by inclusion of losartan (200 nM) indicating that the inhibition was not irreversible. 7. In conclusion, BMS-180560 is a potent, specific, predominantly competitive, reversible All receptor antagonist, which displays insurmountable receptor antagonism. At concentrations of BMS-180560 which have no effect on receptor number, BMS-180560 produced insurmountable antagonism of AII-stimulated second messenger formation, extracellular acidification, and smooth muscle contraction.

Adrenal Cortex↗
PubMed1994

Immunological characteristics of a synthetic peptide associated with a catalytic domain of mutans streptococcal glucosyltransferase.

The immunogenicity of a multiple antigenic peptide construct consisting of four copies of the synthetic 21-mer peptide DANFDSIRVDAVDNVDADLLQ was measured. The composition of this peptide was derived from a sequence in the N-terminal region of mutans streptococcal glucosyltransferases (GTFs) containing an aspartic acid implicated in catalysis. The peptide (CAT) construct was synthesized as a tetramer on a lysine backbone and subcutaneously injected into Sprague-Dawley rats for polyclonal antibody formation or intraperitoneally injected into BALB/c mice, and then spleen cell fused with Sp2/0Ag14 murine myeloma cells for monoclonal antibody formation. The resulting rat antisera and mouse monoclonal antibodies reacted with CAT and with native GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (in enzyme-linked immunosorbent assay and Western blot [immunoblot] analyses). Functional inhibition of the water-insoluble glucan synthetic activity of S. sobrinus GTF-I was demonstrated with an immunoglobulin M anti-CAT monoclonal antibody (> 80% inhibited) and with rat sera (approximately 17% inhibited). The monoclonal antibody preparation also modestly inhibited the water-soluble glucan synthetic activity of an S. mutans GTF mixture. These results suggest that the CAT peptide contains B-cell epitopes that are similar to those of intact mutans streptococcal GTFs and has the potential to elicit antibody that can inhibit GTF function. Thus, sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine.

Amino Acid Sequence↗
PubMed1993

Computer simulation of lipid diffusion in a two-component bilayer. The effect of adsorbing macromolecules.

We have modelled the effects of macromolecular adsorption upon lipid lateral diffusion in a two-component lipid bilayer or monolayer, which is at a temperature above both of the main transition temperatures. One set of lipids (binders, b) can bind to the macromolecules with a free energy of binding, FB, while the other set does not bind (non-binders, nb). We assumed that no phase separation of the lipids occurs in the absence of adsorbed macromolecules. We represented the lipid bilayer/monolayer by a triangular lattice, each site of which is occupied by a lipid molecule. Adsorbed macromolecules were represented by hexagons covering nH sites, and we defined a probability per unit of time, p, that a hexagon attempts to adsorb onto the lattice. We considered two sizes of hexagons, nH = 7 (Size-1) and nH = 19 (Size-2) and disallowed or permitted adsorbed hexagons to move laterally on the lattice. We calculate the lipid relative diffusion coefficients, Dnb, and Db, for three characteristic time-regimes, (i) tau c << tau a, (ii) tau c approximately tau a and (iii) tau c >> tau a, where tau c and tau a are the times for proteins to adsorb/desorb or for lipids to move from site to site, respectively. We obtain analytical expressions for Dnb and Db in the first case and calculate them using computer simulation in the other two cases. We found that (i) D alpha (iii) < or = D alpha (ii) < or = D alpha (i) (alpha = nb, b); (ii) D alpha could display a shoulder as a function of FB for low values of p; (iii) compared to cases in which lateral diffusion was disallowed, the lateral diffusion of absorbed hexagons appeared to have little effect on Dnb, but could cause Db to increase by 50%. (iv) Scatter in the calculated values of D via simulation appeared to be largest for Size-1 hexagons, and could be understood as a consequence of the large interfacial region between areas free of hexagons and areas 'covered' by hexagons. Our results suggest that it is advisable to measure Db, since Dnb might show little change from 1.0 for the values of F and p appropriate to the system being studied.

Adsorption↗
PubMed1993

Conservation and change of the developmentally crucial fushi tarazu gene in Drosophila.

We have studied the evolutionary changes occurring in the noncoding regions around the developmentally important fushi tarazu (ftz) gene in a total of 11 species in the genus Drosophila. Previous molecular developmental studies have identified DNA elements both 3' and 5' to the coding region which are important in proper regulation of expression of the Drosophila melanogaster ftz gene. We show here that these same elements are the most evolutionarily conserved regions in the vicinity of the gene homologs. Parts of some control elements are more conserved than exonic sequences. Not only is there sequence conservation, but the relative position, orientation, and distances among the control elements remain conserved. One quite significant difference does exist between the two major subgenera studied, Sophophora and Drosophila: namely, an inversion of the ftz unit with respect to other genes in the Antennapedia complex, ANT-C. As a comparison, we applied similar analysis to a "housekeeping" gene-rosy (ry), or Xdh. In contrast, DNA sequences 5' to the ry coding region revealed little evolutionary conservation. These studies bear out the proposition that functionally important DNA sequences remain more conserved through evolutionary time than do less functionally important sequences. This proposition could be tested in the present case because we could predict a priori from the developmental studies which DNA regions should be most conserved.

Animals↗
PubMed1993

Interleukin-1 beta and IgG subclass concentrations in gingival crevicular fluid from patients with adult periodontitis.

Interleukin-1 beta (IL-1 beta) and the four IgG subclasses were measured in gingival crevicular fluid (GCF) at 35 sites in 19 patients with adult periodontitis. Serum concentrations of the IgG subclasses were assayed in 16 patients. IL-1 beta was detected in GCF at 88.6% of sites at concentrations ranging from 12.38-420.90 pg/microliters (mean 138.35 +/- 112.61 pg/microliters). IgG1 was detected at 81.2% sites, IgG2 at 93.6%, IgG3 at 71% and IgG4 at 71%. Absolute concentrations in GCF were: IgG1--2.419 g/l +/- (SD) 3.389; IgG2--2.945 +/- 6.434; IgG3--0.118 +/- 0.144; IgG4 0.864 +/- 1.336. There were no significant correlations between IL-1 beta concentrations, GCF volume or the clinical status of the sample site. IL-1 beta was not correlated with any of the IgG subclasses. The absolute concentrations of all subclasses in GCF were significantly negatively correlated with GCF volume and positively correlated with the Bleeding Index. Only IgG4 was significantly negatively correlated with the probeable crevice depth index. The concentration of each IgG subclass was positively correlated with the other three IgG subclasses. Subclass concentrations in GCF, relative to serum concentrations, were not correlated with GCF volume or clinical status. Relative concentrations of IgG1, IgG2 and IgG3 showed significant positive correlation with each absolute concentration of the other subclasses but IgG4 did not show this relation. It was concluded that IL-1 beta is not related to clinical measurements of inflammation or previous attachment loss. The data suggest that IgG in GCF is largely derived from plasma but that some IgG4 may be locally synthesized.

Adult↗
PubMed1993

Effect of sodium acid pyrophosphate on ranitidine bioavailability and gastrointestinal transit time.

During development of a ranitidine effervescent oral solution dosage form, a marked decrease was observed in the extent of ranitidine absorption relative to the conventional oral tablet. Two studies were conducted in healthy volunteers to confirm the involvement of an excipient, SAPP (sodium acid pyrophosphate), and the mechanism of interaction, altered gastrointestinal transit. The first study (n = 12) involved single-dose crossover comparisons of (A) 150 mg ranitidine with 1132 mg SAPP versus (B) 150 mg ranitidine and (C) 150 mg ranitidine with all the effervescent tablet excipients except SAPP versus (D) a 150-mg ranitidine effervescent tablet, all administered as oral solutions. Serum ranitidine AUC, Cmax, and tmax were compared using two one-sided t test 90% confidence intervals (CI). Comparing treatments A to B and D to C, all 90% CI were below the 80-120% range, indicating significantly less extensive ranitidine absorption (54% based on AUC) from the oral solutions containing SAPP. The second study (n = 12) was a single-dose crossover comparing 50 microCi 111 InCl solutions with and without 1132 mg SAPP. Gastrointestinal transit times, determined by scintigraphic imaging, were compared between treatments. Gastric emptying time was unchanged, but small intestinal transit time was decreased to 56% in the presence of SAPP. More rapid small intestinal transit associated with an excipient of a solution dosage form apparently resulted in a decreased extent of ranitidine absorption. This observation contradicts the conventional wisdom that oral solutions are unlikely to fall short of bioequivalence relative to solid oral formulations.

Adult↗
PubMed1993

Rates of DNA evolution in Drosophila depend on function and developmental stage of expression.

DNA-sequence divergence of genes expressed in the embryonic stage was compared with the divergence of genes expressed in adults for 13 species of Drosophila representing various degrees of relatedness. DNA-DNA hybridization experiments were conducted using as tracers complementary DNA (cDNA) reversed transcribed from poly(A)+ mRNA isolated from different developmental stages. The results indicate: (1) cDNA is less diverged than total single-copy DNA; (2) cDNA sequences are not in the rapidly evolving fraction of the single-copy genome of Drosophila; (3) early in evolutionary divergence embryonic messages are about half as diverged as adult messages; sequence data from some of the species compared indicate this is likely due to differences in rates of silent substitutions in genes expressed at different stages of development; and (4) at greater evolutionary distance, the differences in embryonic and adult messages disappear; this could be due to lineage-specific shifts in codon usage.

Animals↗
PubMed1993

Evolution of the Adh locus in the Drosophila willistoni group: the loss of an intron, and shift in codon usage.

We report here the DNA sequence of the alcohol dehydrogenase gene (Adh) cloned from Drosophila willistoni. The three major findings are as follows: (1) Relative to all other Adh genes known from Drosophila, D. willistoni Adh has the last intron precisely deleted; PCR directly from total genomic DNA indicates that the deletion exists in all members of the willistoni group but not in any other group, including the closely related saltans group. Otherwise the structure and predicted protein are very similar to those of other species. (2) There is a significant shift in codon usage, especially compared with that in D. melanogaster Adh. The most striking shift is from C to U in the wobble position (both third and first position). Unlike the codon-usage-bias pattern typical of highly biased genes in D. melanogaster, including Adh, D. willistoni has nearly 50% G + C in the third position. (3) The phylogenetic information provided by this new sequence is in agreement with almost all other molecular and morphological data, in placing the obscura group closer to the melanogaster group, with the willistoni group farther distant but still clearly within the subgenus Sophophora.

Alcohol Dehydrogenase↗
PubMed1992

Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine.

Twelve healthy male subjects completed this randomized, placebo controlled, four-period crossover trial to determine the effect of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. Subjects received a 7-day course of one of four treatments; verapamil (120 mg every 8 hr), diltiazem (90 mg every 8 hr), labetalol (200 mg every 12 hr), or placebo (every 12 hr) during each study period. Imipramine (100 mg) was administered orally on the morning of day 4 of each study period. Plasma and urine samples were collected periodically over the ensuing 96 hours. Samples were assayed by HPLC for imipramine, desipramine, 2-hydroxyimipramine, and 2-hydroxydesipramine. Verapamil, diltiazem, and labetalol increased imipramine area under the plasma concentration time curve (relative bioavailability) as compared with placebo by 15%, 30%, and 53%, respectively. Verapamil and diltiazem did not demonstrate consistent changes in the formation of the measured metabolites. Labetalol caused a significant decrease in the amount of imipramine metabolized to 2-hydroxyimipramine (mean decrease: 22%) and from desipramine to 2-hydroxydesipramine (mean decrease: 8%). The molar ratios of plasma AUC of 2-hydroxyimipramine and 2-hydroxydesipramine to the parent compounds were significantly decreased. Since these metabolic processes are dependent on the cytochrome P450IID6 isozyme, these data suggest that labetalol decreases the oral clearance of imipramine by inhibiting this system. All three of these commonly used agents decreased the oral clearance of imipramine. These drug interactions could lead to elevated imipramine concentrations and have the potential for clinically important adverse events.

Administration, Oral↗
PubMed1992

Complementary DNA-DNA hybridization in Drosophila.

We have performed DNA-DNA hybridization experiments among several species of Drosophila using the evolutionarily conserved portion of the genome representing sequences coding for amino acids of proteins. This was done by using as tracer, radioactively labeled complementary DNA that was reverse transcribed from adult mRNA. We show that this procedure extends phylogenetically the distance over which the technique can be applied to fast-evolving groups such as Drosophila. The major phylogenetic conclusions are (1) the subgenus Sophophora is a monophyletic lineage; (2) within Sophophora the melanogaster subgroup is closer to the obscura group than either group is to the willistoni group; (3) the subgenus Drosophila is complex with most major lineages originating deep in the phylogeny; the subgenus may not be monophyletic; (4) as with most groups classically placed in Drosophila, the Hawaiian Drosophila originate early, supporting the notion that this lineage is older than the extant islands; and (5) the virilis/repleta lineage is monophyletic within Drosophila.

Animals↗
PubMed1992

The production of equine monoclonal immunoglobulins by horse-mouse heterohybridomas.

Studies were carried out to determine the optimum conditions for the production of equine monoclonal antibodies (MAbs). Lymphocytes from ponies immunised with influenza A equine 2 virus, isolate A/Equine/Newmarket/79 (H3N8) were fused with mouse myeloma (NSO) cells and with horse-mouse heterohybridomas made aminopterin-sensitive by selective growth in 8-azaguanine. Although all fusions initially resulted in heterohybridoma colonies that secreted equine immunoglobulin, many of these were unable to maintain secretion for longer than a few weeks. Increasing the time between immunisation and the booster injection of Newmarket/79 virus, the inclusion of Freund's incomplete adjuvant and the use of an aminopterin-sensitive primary heterohybridoma as the fusion partner, improved the production of HIg-secreting heterohybridomas. After two clonings eight cell lines were established which maintained anti-Newmarket/79 antibody secretion for over a year. FACS analysis of the cell lines provided a useful means of predicting breakdown of MAb secretion by the cell lines, thus enabling re-cloning to be carried out in time.

Animals↗
PubMed1992

Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers.

Modest differences in the clearance of the 5HT3 antagonist, ondansetron, among different age groups were detected in two groups of healthy elderly volunteers, one group aged 61 to 74 years ("elderly") and the other 75 to 82 ("aged") years, in addition to young healthy subjects. Both a single 0.15 mg/kg intravenous dose and a single 8 mg oral dose were administered according to a randomized crossover design with a minimum 3-day washout period between treatments. Mean plasma clearance decreased (young, 0.349 L/hr/kg; elderly, 0.279 L/hr/kg; aged, 0.214 L/hr/kg; p less than 0.05) with increasing age. Volume of distribution at steady state was unaffected by age (young, 1.81 L/kg; elderly, 1.94 L/kg; aged, 1.71 L/kg), resulting in increases in mean plasma half-life (young, 3.4 hours; elderly, 4.5 hours; aged, 5.4 hours) and mean absolute bioavailability (young, 57%; elderly, 61%; aged, 69%) with increasing age. Female subjects cleared ondansetron more slowly than males (p less than 0.05), resulting in higher absolute bioavailability. Ondansetron was well tolerated by all age groups with no increase in the number of adverse events observed in older volunteers.

Administration, Oral↗
PubMed1992

Reassociation kinetics of Anopheles gambiae (Diptera: Culicidae) DNA.

The renaturation kinetics of nuclear DNA from the G3 colony of Anopheles gambiae Giles was studied to estimate the genome size and to determine the proportion of repeated sequences. An. gambiae has a haploid DNA content of 0.27 picograms or 2.6 x 10(8) basepairs. Analysis of reassociation kinetics indicated that the genome is composed of 61% single-copy and 33% repetitive sequences, with 6% foldback sequences.

Animals↗
PubMed1992

Elevated levels of the IgG2 subclass in serum from patients with a history of destructive periodontal disease. A case-control study.

The levels of the 4 subclasses of IgG were estimated in the serum from 35 patients with a history of chronic periodontitis and 35 matched controls. The levels of IgG2 were significantly (P less than 0.019) elevated in the patients (3.756 g l-1) compared to the controls (2.882 g l-1). The data suggest that the predominant antibody response to periodontal pathogens in periodontitis may be directed against carbohydrate or glycolipid antigens.

Adult↗