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Biomedical subjects

J W Taylor

Publications and source records attributed to J W Taylor.

At least 73 records · Page 4Linked to original sources

Exposure to hair-coloring products and the risk of multiple myeloma.

An interview study of persons diagnosed with multiple myeloma between 1977 and 1981 and suitable control subjects was conducted to test the hypothesis that exposure to hair dyes increases the risk of multiple myeloma. Among women, there was little evidence that prior regular use of hair dyes (odds ratio [OR] = 1.0; 95% confidence interval [CI] = 0.70, 1.4) or prior employment as a hairdresser (OR = 1.1; 95% CI = 0.43, 2.7) increased risk; however, the former comparison was limited by the lack of detailed information concerning the exposure. Among men, there was a modest association of regular use of hair dyes (OR = 1.5; 95% CI = 0.75, 2.9) with myeloma, but this was based on a small number of exposed persons.

Beauty Culture↗

Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography.

OBJECTIVE: To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period. DESIGN: Randomized double-blind, placebo-controlled trial. SETTING: Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic). INTERVENTION: Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days. MAIN OUTCOME MEASURES: Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale. RESULTS: Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole. CONCLUSIONS: Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution.

Aged↗

Epidemiology of the M-component immunoglobulin types of multiple myeloma.

The purpose of this population-based case-control study was to learn whether risk factors differ for the individual immunoglobulin types of multiple myeloma. In particular, we sought to determine whether IgA and IgG myeloma were related to a history of exposure to reported IgA- and IgG-stimulating conditions, respectively, or to a history of selected occupational and physicochemical exposures. The M-component immunoglobulin type was determined from immunoelectrophoresis as reported in medical records, and exposure status was obtained through in-person interviews. IgG (56 percent) and IgA (22 percent) M-components predominated. For 17 percent of cases, no peak was found on immunoelectrophoresis; they were presumed to have light-chain myeloma. Persons with these three types of myeloma did not differ with respect to distributions of age or race, but a somewhat higher proportion of light-chain cases were women (58 percent cf 45 percent of all other cases). Detailed analysis of the IgA and IgG subtypes provided little evidence that they differ with respect to prior immune stimulation or employment in several specific jobs. IgA myeloma, but not IgG myeloma, was associated modestly with a history of exposure to chest and dental X-rays. Our study provides little evidence that IgA and IgG myeloma differ with respect to the risk factors examined.

Benzene↗

Uniparental inheritance and replacement of mitochondrial DNA in Neurospora tetrasperma.

This study tested mechanisms proposed for maternal uniparental mitochondrial inheritance in Neurospora: (1) exclusion of conidial mitochondria by the specialized female reproductive structure, trichogyne, due to mating locus heterokaryon incompatibility and (2) mitochondrial input bias favoring the larger trichogyne over the smaller conidium. These mechanisms were tested by determining the modes of mitochondrial DNA (mtDNA) inheritance and transmission in the absence of mating locus heterokaryon incompatibility following crosses of uninucleate strains of Neurospora tetrasperma with trichogyne (trichogyne inoculated by conidia) and without trichogyne (hyphal fusion). Maternal uniparental mitochondrial inheritance was observed in 136 single ascospore progeny following both mating with and without trichogyne using mtDNA restriction fragment length polymorphisms to distinguish parental types. This suggests that maternal mitochondrial inheritance following hyphal fusions is due to some mechanism other than those that implicate the trichogyne. Following hyphal fusion, mutually exclusive nuclear migration permitted investigation of reciprocal interactions. Regardless of which strain accepted nuclei following seven replicate hyphal fusion matings, acceptor mtDNA was the only type detected in 34 hyphal plug and tip samples taken from the contact and acceptor zones. No intracellular mtDNA mixtures were detected. Surprisingly, 3 days following hyphal fusion, acceptor mtDNA replaced donor mtDNA throughout the entire colony. To our knowledge, this is the first report of complete mitochondrial replacement during mating in a filamentous fungus.

Cell Nucleus↗

Surface-induced conformational switching in amphiphilic peptide segments of apolipoproteins B and E and model peptides.

The conformational and surface-binding properties of a synthetic peptide corresponding to Tyr-apolipoprotein B-100(1000-1016) amide, SP-4, which was previously shown to mimic the focal accumulation pattern of LDL on the healing de-endothelialized rabbit aorta [Shih et al. (1990) Proc. Natl. Acad. Sci. USA 87, 1436-1440], have been investigated. SP-4 behaves as an amphiphilic alpha-helical peptide at the air-water interface and bound to siliconized quartz slides. However, its N alpha-acetylated analogue formed beta-sheet structures at the air-water interface. Nonhomologous peptide models of SP-4 also exhibited mixed alpha-helical and beta-sheet surface-binding behavior. Peptides corresponding to the cationic apolipoprotein (apo) B/E receptor binding regions of apoE (SP-2) and apoB (SP-11) were also studied. SP-2 behaved as an amphiphilic alpha helix, but, surprisingly, SP-11 formed surface-induced beta-sheets. These results demonstrate that all of the peptides studied have surface-binding properties, and suggest further that either alpha-helical or beta-sheet peptide structures may determine the binding of LDL to the arterial wall or the apoB/E receptor.

Amino Acid Sequence↗

Lithium-induced parathyroid dysfunction: a case report and review of the literature.

OBJECTIVE: Twenty-six cases of lithium-induced hyperparathyroidism have been reported in the literature. This article describes an additional case that illustrates current management recommendations. DESIGN: Case report. Clinical presentation and proposed mechanisms of the suspected drug-induced effect are discussed. CONCLUSIONS: Serum calcium concentrations should be determined before and periodically during long-term lithium carbonate therapy. Discontinuation of therapy in patients who develop lithium-induced parathyroid dysfunction generally corrects calcium and parathyroid hormone concentrations. Surgery is indicated in patients with complications of hyperparathyroidism.

Adult↗

Yeast biology.

Explore the source record for details and available documents.

History, 19th Century↗

Dimeric structure and conformational stability of brain-derived neurotrophic factor and neurotrophin-3.

We have examined the molecular structure of the related neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) by physical methods, including gel filtration, velocity sedimentation, sedimentation equilibrium, urea gel electrophoresis, fluorescence spectroscopy, and far-ultraviolet circular dichroism. The results of these studies indicate that at physiologically relevant concentrations both recombinant proteins exist as tightly associated dimers. The dimers are stable even in 8 M solutions of urea. In solutions of guanidine hydrochloride, BDNF and NT-3 undergo slow unfolding between 3 and 5 M concentration of denaturant. Circular dichroism spectroscopy revealed approximately 70% beta-sheet and 20% beta-turn content in the native structure of both neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.

Animals↗

Probing the functional conformation of neuropeptide Y through the design and study of cyclic analogues.

The functional importance of the PP-fold conformation in neuropeptide Y (NPY) was investigated. NPY and N alpha-Ac-NPY(10-36), and corresponding cyclic analogues cyclo18,22-[Lys18,Asp22]-NPY and N alpha-Ac-cyclo18,22-[Lys18,Asp22]-NPY(10-36), were synthesized. Strategies for synthesis of the cyclic analogues included the use of the Kaiser oxime resin and a segment condensation approach. Circular dichroism studies in phosphate buffer, pH 5.0, indicated self-association of all four peptides at low micromolar concentrations. Monomeric N alpha-Ac-NPY(10-36) showed only 13% alpha-helix, compared to 32% alpha-helix for monomeric NPY, demonstrating a helix-stabilizing effect of residues 1-9 that is consistent with the PP fold. The [Lys18,Lys22] lactam bridge stabilized the helical conformation in N alpha-Ac-NPY(10-36)(51% alpha-helix), but was helix destabilizing in NPY (21% alpha-helix). In rat brain receptor binding assays, the cyclic and linear N alpha-Ac-NPY(10-36) analogues were equipotent (IC50 = 13 nM for 125I-BH-NPY displacement), although the cyclic analogue was twice as potent in rat vas deferens assays. NPY was more potent than its cyclic analogue in the brain receptor binding assays (IC50 = 0.07 and 0.25 nM, respectively), but these peptides were equipotent in the vas deferens assays. These results support a functional role for the PP fold in NPY and correlate with the solution conformations of the monomeric peptides.

Animals↗

Alkaline phosphatase-somatostatin hybrid proteins as probes for somatostatin-14 receptors.

By inserting appropriate peptide ligands into surface loops on globular proteins, we expect to develop probes for the location, accessibility, and steric and electrostatic environment of these ligand-binding sites on their membrane-bound receptors. Three residues in a loop on the surface of E. coli alkaline phosphatase were substituted by an 18-residue peptide containing the receptor-binding segment of somatostatin-14 without significantly affecting the catalytic properties of the enzyme. This hybrid protein was then used to investigate the ligand-binding site of somatostatin receptors. Tryptic cleavage of the hybrid protein within the inserted sequence, and binding of the hybrid protein to antisomatostatin antibodies demonstrated the surface accessibility of the guest peptide. Both the wild-type enzyme and the hormone-enzyme hybrid displaced 125I-labeled somatostatin from rat brain membrane receptors only at high concentrations. However, chemical cationization of the hybrid protein, which again did not disturb the phosphatase activity, enhanced its receptor-binding potency to a level only 23 times lower than that of somatostatin itself and 280 times higher than that of the cationized wild-type protein. This alkaline phosphatase/somatostatin hybrid protein appears, therefore, to be a suitable starting point for the development of probes for the steric and electrostatic environment of the ligand-binding site of somatostatin receptors.

Alkaline Phosphatase↗

Detecting morphological convergence in true fungi, using 18S rRNA gene sequence data.

For the true fungi, phylogenetic relationships inferred from 18S ribosomal DNA sequence data agree with morphology when (1) the fungi exhibit diagnostic morphological characters, (2) the sequence-based phylogenetic groups are statistically supported, and (3) the ribosomal DNA evolves at roughly the same rate in the lineages being compared. 18S ribosomal RNA gene sequence data and biochemical data provide a congruent definition of true fungi. Sequence data support the traditional fungal subdivisions Ascomycotina and Basidiomycotina. In conflict with morphology, some zygomycetes group with chytrid water molds rather than with other terrestrial fungi, possibly owing to unequal rates of nucleotide substitutions among zygomycete lineages. Within the ascomycetes, the taxonomic consequence of simple or reduced morphology has been a proliferation of mutually incongruent classification systems. Sequence data provide plausible resolution of relationships for some cases where reduced morphology has created confusion. For example, phylogenetic trees from rDNA indicate that those morphologically simple ascomycetes classified as yeasts are polyphyletic and that forcible spore discharge was lost convergently from three lineages of ascomycetes producing flask-like fruiting bodies.

DNA, Fungal↗

Convergence in ascospore discharge mechanism among pyrenomycete fungi based on 18S ribosomal RNA gene sequence.

Fungi of the class Pyrenomycetes (Ascomycotina) form a morphological series ranging from those that shoot ascospores (sexual spores) forcibly from the ascus (spore sac) to fungi that ooze ascospores or have no obvious mechanism for ascospore release. Did forcible ascospore discharge evolve within these pyrenomycetes, or has it been lost in the group? We determined the sequences of the 18S ribosomal RNA gene from three fungi and used these, along with six sequences from our previous work and three sequences from GenBank, to infer the phylogeny of 12 ascomycetes with various ascospore discharge mechanisms. The 1720 base pairs of sequence data per fungus yielded 361 variable sites, 198 phylogenetically informative sites, and a single most parsimonious tree requiring 562 nucleotide changes. The tree shows that the capacity to shoot ascospores into the air has been lost or, less probably, gained repeatedly and independently. Species lacking forcible ascospore discharge are intercalated among three lineages of species with forcible discharge. In this tree, seven of the nine internal branches appeared in 95% or more of 500 bootstrap replicates. A tree uniting the fungi with forcible ascospore discharge into a monophyletic group required 45 additional steps and fit significantly less well with the data than the most parsimonious tree, based on a maximum likelihood test. Two of the fungi whose sequence we determined, Pseudallescheria boydii and Sporothrix schenckii, are not closely related to one another, even though both are human pathogens and both are from pyrenomycete lineages lacking forcible ascospore discharge. Using the well-resolved, most parsimonious tree, we inferred base substitution patterns in the 18S rRNA. The transition-to-transversion ratio was 1.9. Of all 12 possible substitutions, 29% were from U to C. At sites corresponding to yeast stem positions, A to G transitions were frequent, perhaps compensating for some of the U to C changes, and maintaining secondary structure base pairing (A to G:U to C = 3:4). In loop or bulge positions without secondary structure base pairing, U to C transitions were still frequent, but A to G transitions were rare (A to G:U to C = 1:5).

Ascomycota↗

Two ascomycete classes based on fruiting-body characters and ribosomal DNA sequence.

Traditional fruiting body-based classification of ascomycetes has been under attack for 2 decades. Fruiting-body types can converge, and few researchers now assume that either the closed fruiting bodies (cleistothecia) characterizing the class Plectomycetes or the flask-shaped fruiting bodies (perithecia) characterizing the class Pyrenomycetes are stable, unifying characters. Unless we identify characters uniting major ascomycete groups, orders of ascomycetes remain narrowly defined, and supraordinal classification is impossible. We sequenced both strands of 18s rDNA from nine ascomycete fungi, adding three sequences from GenBank into our analysis. The phylogeny, inferred from 162 informative sites in 1,700 bp of DNA sequence data and using yeast as an outgroup, divided the fungi into two groups correlating well both with fruiting-body type and with the traditional classes Plectomycetes and Pyrenomycetes. Each group received strong statistical support. Genera producing cleistothecia, such as Talaromyces (with a Penicillium asexual state) and the human pathogen Ajellomyces capsulatus (causing histoplasmosis), fall within the plectomycete group. Plectomycetes also includes Eremascus albus and the bee pathogen Ascosphaera apis, although both lack typical fruiting bodies. The Dutch elm disease fungus groups with pyrenomycetes such as Neurospora, in spite of its confusing mixture of class-level characters.

Ascomycota↗

Molecular evolution of the fungi: relationship of the Basidiomycetes, Ascomycetes, and Chytridiomycetes.

Establishing the phylogeny of fungi and protists often has proved difficult owing to the simple morphologies and convergent characters in these organisms. We used DNA sequences of nuclear small-subunit ribosomal RNA genes to determine phylogenetic relationships among three major classes of organisms considered to be fungi--Basidiomycetes, Ascomycetes and Chytridiomycetes--and to assess the taxonomic position of Neocallimastix, an economically important anaerobic rumen microorganism whose classification is controversial. The Basidiomycetes and Ascomycetes, two classes of nonflagellated fungi, are the most closely related taxa. Chytridiomycetes, though bearing flagella, group with these higher fungi rather than with the protists. Neocallimastix, a eukaryote lacking mitochondria and variously classified as a protist or as a fungus, shows closest molecular affinities with the Chytridiomycete fungi in the order Spizellomycetales.

Ascomycota↗

Phylogeny of five fungus-like protoctistan Phytophthora species, inferred from the internal transcribed spacers of ribosomal DNA.

Ribosomal DNA variation was used to study evolutionary relationships among five fungal-like protoctistan Phytophthora species. On the basis of morphological and ecological characteristics, four of these species--P. palmivora, P. megakarya, P. capsici, and P. citrophthora--were once thought to be related. Variation within a species was extensively studied in a fifth, outgroup species--P. cinnamomi--known, on the basis of ecological, isozyme, and mitochondrial DNA studies, to be variable. Internal transcribed spacer regions (ITS I, between the 18S and 5.8S rDNAs; and ITS II, between the 5.8S and 25S rDNAs) from 27 isolates of these five species were analyzed by polymerase chain reaction amplification and direct sequencing. Intraspecific variability was undetected or low. Interspecific nucleotide difference was 0.3%-14.6%, and comparisons of variable regions permitted the evaluation of phylogenetic relationships among species. Both neighbor-joining and parsimony analysis of ITS variability support a close relationship between cacao isolates of P. capsici and P. citrophthora and a common lineage for P. palmivora and P. megakarya. Large distance values were estimated between P. cinnamomi and the other species. Inferred relationships based on ITS variability were compared with those based on other characters. The catalog of sequences provides the information necessary to design taxon-specific probes potentially useful in taxonomic, ecological, and population-level studies.

Base Sequence↗

Molecular evolution of the fungi: human pathogens.

The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.

Base Sequence↗