Information retrieval and genomics--an introduction.
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Databases, Factual↗
Biomedical subjects
E A Fox
Publications and source records attributed to E A Fox.
Pulmonary embolism and deep venous thrombosis during pregnancy or oral contraceptive use: prevalence of factor V Leiden.
Activated protein C resistance caused by factor V Leiden mutation is the most common inherited cause of an underlying predisposition to pulmonary embolism (PE) and deep venous thrombosis (DVT). We studied the frequency of the factor V Leiden mutation in 50 women who had PE and/or DVT during or after pregnancy or during oral contraceptive use. Ten (20%; 95% CI 10% to 34%) of the 50 women were heterozygous for the mutation. First-trimester PE or DVT developed in 6 (60%; 95% CI, 26% to 88%) of the 10 women with the mutation compared with 3 (8%; 95% CI 2% to 20%) of 40 women without the mutation (p = 0.0009). These data indicate that the factor V Leiden mutation is an important risk factor for PE or DVT during pregnancy (especially the first trimester), after pregnancy, or during oral contraceptive use.
Adolescent↗
Ionotropic and metabotropic components of electrophysiological response of cerebellar Purkinje neurons to excitatory amino acids.
Cerebellar Purkinje neurons possess AMPA ((RS)-alpha-amino-3-hydroxyl-5- methyl-4-isoxazolepropionic acid)-sensitive ionotropic glutamate receptors (AMPA GluRs) and ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid)-sensitive metabotropic glutamate receptors (mGluRs). The contributions of these receptors to responses elicited by dual receptor activation in cultured cerebellar Purkinje neurons were delineated by quantitative analysis of agonist-induced single unit activity. Responses to co-activation using Quis or AMPA + ACPD were biphasic, consisting of a dramatic increase in firing rate (excitatory phase) followed by a temporary decrease (inhibitory phase). In half of the cells tested bursting was induced during both the excitatory and inhibitory phases and the duration of each phase was prolonged relative to responses observed in non-bursting cells. Quantitative comparisons of these responses and responses produced by selective activation of AMPA GluRs and mGluRs revealed that: (a) AMPA GluRs mediated the dramatic changes in firing rate, (b) mGluRs mediated the dramatic increases in bursting and the extended duration of each phase and (c) these AMPA GluR and mGluR mediated effects were largely additive when simultaneously activated. Nevertheless, interactions did occur with repeated co-activation of AMPA GluRs and mGluRs, as indicated by selective changes in the mGluR-mediated bursting component of the response. Such modulation may contribute to synaptic regulation of Purkinje neuron excitability, for example, that associated with long term depression.
Animals↗
Corticotropin-releasing factor suppresses the afterhyperpolarization in cerebellar Purkinje neurons.
Corticotropin-releasing factor (CRF) is present in climbing fibers and their terminations on Purkinje neurons. To determine whether CRF may have a postsynaptic action in this pathway, CRF effects on the electrophysiological properties of cultured cerebellar Purkinje neurons were studied. CRF produced a dose-dependent reduction of the amplitude of the afterhyperpolarization (AHP) which follows a current-induced spike train. The effect of CRF on the AHP was specific in that CRF did not significantly alter input resistance, membrane potential, amplitude of the depolarizing-off response produced at the termination of a hyperpolarizing current pulse, or the number of depolarization-induced simple spikes. Suppression of the AHP by CRF may be one mechanism by which CRF regulates the response of Purkinje neurons to other transmitters in the climbing fiber pathway or in other inputs to Purkinje neurons.
Animals↗
Personality-focused learning environments: learning preferences of students in dietetics and restaurant, hotel/institution management programs.
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Dietetics↗
Morphology of identified preganglionic neurons in the dorsal motor nucleus of the vagus.
To determine the degree of variation of neuronal morphology both within and between the subnuclei of the dorsal motor nucleus of the vagus (dmnX), structural features of the preganglionic neurons of each of the five primary subnuclei in the rat dmnX were characterized quantitatively. Each of the columnar subnuclei was separately labeled by application of the retrograde tracer fast blue to its corresponding subdiaphragmatic vagal branch. Fixed brain slices of 100 microns thickness were then prepared in coronal, sagittal, and horizontal orientations. Next, randomly selected fast blue labeled neurons (n = 1,256) were injected with Lucifer yellow, drawn with camera lucida, and digitized. For each cell, three features of the perikaryon and twelve of the dendritic tree were measured. Dorsal motor nucleus neurons with up to eight primary dendrites, 30 dendritic segments, and seventh order dendritic branches were observed. Throughout the dmnX, the dendrites of preganglionic neurons were preferentially oriented in the horizontal plane. Consistent with an organizing role for the columnar subnuclei, most dendrites remained within their column of origin. However, between 5 and 30% of the neurons in each of the columns projected dendrites into adjacent dmnX subnuclei or other brainstem nuclei, including the nucleus of the solitary tract (NTS). The cyto- and dendroarchitectural analyses revealed systematic gradations in morphology, although they did not support the idea that the dmnX was composed of multiple distinct preganglionic types. The most parsimonious interpretation of the data is that dmnX motorneurons are variants of a single prototype, with dendrites varying widely in length and degree of ramification. The extent of an individual preganglionic neuron's dendritic field was predicted by three factors: the cell's rostrocaudal position within the dmnX, its location within a transverse plane (i.e., its coronal position within or ectopic to the dmnX), and its subnucleus of origin. Neurons at rostral and midlongitudinal levels of each column had more extensive dendritic arbors than those at caudal levels. Ectopic neurons had more extensive dendritic fields than similar cells in the corresponding columns; in fact, of all vagal preganglionic neurons, ectopics had the most extensive dendritic fields. Somata and dendrites of celiac column neurons were more extensive than those of hepatic and gastric column cells. These differential regional distributions of vagal preganglionics suggest that their structure and function are correlated.
Amidines↗
Colorectal intussusception in a young cat.
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Animals↗
Abdominal pathways and central origin of rat vagal fibers that stimulate gastric acid.
The brainstem location and peripheral course of the vagal preganglionic fibers that stimulate gastric acid secretion were identified using electrical stimulation combined with retrograde (True Blue; Dr. K. G. Illing, Gross Umstadt, Germany) and anterograde (Dil; Molecular Probes) fluorescent neural tracers in rats with various selective vagotomies. Animals with only one or both gastric branch(es) spared had normal, large gastric acid responses to electrical stimulation of the ipsilateral cervical vagus and showed an abundance of Dil-labeled vagal fibers and terminals in the gastric myenteric plexus. Rats with only the unpaired hepatic branch spared had a much smaller but significant gastric acid response and a few labeled vagal profiles in the antral region of the stomach. In contrast, rats with only one or both celiac branch(es) intact had neither a gastric acid response, nor evidence for Dil transport to the stomach. Retrograde transport of True Blue through the spared vagal axons to the brainstem indicated that the cell bodies of the preganglionics that send their axons through the acid-positive gastric and hepatic branches occupy the medial longitudinal columnar subnuclei of the dorsal motor nucleus. It is concluded that besides the long-recognized gastric branches, which are the major access route to the parietal cells, the hepatic branch contains a small number of fibers that most likely reach the antrum through the right gastroepiploic artery along the greater curvature and/or the right gastric artery.
Animals↗
Avian alcohol dehydrogenase: the chicken liver enzyme. Primary structure, cDNA-cloning, and relationships to other alcohol dehydrogenases.
The major ethanol-active form of chicken liver alcohol dehydrogenase was characterized. The primary structure was determined by peptide analysis and, to a large part, was also deduced by cDNA analysis of a near full-length cDNA clone. The latter was detected by screening of a chicken liver cDNA library with antibodies raised against the purified dehydrogenase. The structure shows that the avian enzyme exhibits characteristics of the complex mammalian alcohol dehydrogenase system, tracing its origin and divergence, and allowing functional correlations. The chicken protein analyzed proves to be a class I alcohol dehydrogenase, with 74% residue identity to gamma chains of the human enzyme, a Km for ethanol of 0.5 mM and a Ki for 4-methyl pyrazole of 2.5 microM. Relationships to the other two classes are non-identical; residue exchanges towards the human classes increase in the order I less than III less than II, and human/chicken differences are less than inter-class differences. Consequently, the origins of the classes are more distant than the avian/mammalian separation. They reflect duplicatory events separated in time, and the lines that lead to present-day classes I and II deviate early. Integrated with the data for the quail enzyme, the structure of the chicken protein shows that within the avian enzymes the degree of variation is comparable to that within the mammalian class I enzymes, which are more variable than the class III forms. The coenzyme-binding and substrate-binding residues of this chicken alcohol dehydrogenase are largely identical to those in the mammalian class I counterparts. However, the subunit-interacting areas are more variable and suggest some relationships of the avian enzyme with both class I and III mammalian forms. One of the residues, Gly260 (mammalian class I numbering system), previously considered characteristic of all alcohol dehydrogenases, is replaced by Gln.
Alcohol Dehydrogenase↗
Mutagenesis of residues flanking Lys-40 enhances the enzymatic activity and reduces the angiogenic potency of angiogenin.
The primary structure of the blood vessel inducing protein angiogenin is 35% identical with that of pancreatic ribonuclease (RNase) and contains counterparts for the critical RNase active-site residues His-12, Lys-41, and His-119. Although angiogenin is a ribonucleolytic enzyme, its activity toward conventional substrates is lower than that of pancreatic RNase by several orders of magnitude. Comparison of the amino acid sequences of RNase and angiogenin reveals several striking differences in the region flanking the active-site lysine, including a deletion and a transposition of aspartic acid and proline residues. In order to examine how these sequence changes alter the functional properties of angiogenin, an angiogenin/RNase hybrid protein (ARH-II), in which residues 38-41 of angiogenin (Pro-Cys-Lys-Asp) have been replaced by the corresponding segment of bovine pancreatic RNase (Asp-Arg-Cys-Lys-Pro), was prepared by regional mutagenesis. Compared to angiogenin, ARH-II has markedly diminished angiogenic activity on the chick embryo chorioallantoic membrane but 5-75-fold greater enzymatic activity toward a variety of polynucleotide and dinucleotide substrates. In addition, the specificity of ARH-II toward dinucleotide substrates differs from that of angiogenin and is qualitatively similar to that of pancreatic RNase. Thus, non-active-site residues near Lys-40 in angiogenin appear to play a significant role in determining enzymatic specificity and reactivity as well as angiogenic potency. An additional angiogenin/RNase hybrid protein (ARH-IV), in which residues 59-71 of ARH-II have been replaced by the corresponding segment of pancreatic RNase, was also prepared.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
The placental ribonuclease inhibitor (RNH) gene is located on chromosome subband 11p15.5.
The ribonuclease inhibitor from human placenta is a tight-binding inhibitor of alkaline and neutral ribonucleases, including the blood vessel-inducing protein, angiogenin. The location of the inhibitor gene within the human genome has now been determined. Utilizing human-rodent hybrid cell lines, it was found on chromosome 11. The localization was refined to chromosome band 11p15 by in situ hybridization of the ribonuclease inhibitor cDNA to normal metaphase chromosomes. A further refinement was obtained by in situ hybridization of the probe to metaphase chromosomes from RPMI 8402 cells, a line containing a well-characterized translocation t(11;14)(p15;q11) with a chromosome 11 breakpoint between the insulin-like growth factor 2 (IGF2) and Harvey rat sarcoma viral oncogene homolog genes. This analysis has localized the ribonuclease inhibitor gene to chromosome subband 11p15.5, distal to the IGF2 gene.
Animals↗
Localization of vagal preganglionics that stimulate insulin and glucagon secretion.
Although it is generally acknowledged that pancreatic islets are under powerful vagal control, specifics of vagal pathways and their central representation in the brain stem are unclear. To define this circuitry, we combined a protocol measuring electrical vagal stimulation-induced insulin and glucagon secretion with a retrograde tracer strategy that delineated the pool of spared motoneurons in the dorsal motor nucleus of the vagus (dmnX) following selective abdominal branch vagotomies. Three of the five branches mediated both insulin and glucagon release: posterior gastric (+198 and +117% increase from basal for insulin and glucagon, respectively), anterior gastric (+177 and +104%), and hepatic branch (+103 and +60%). In contrast, unreliable and nonsignificant hormonal responses were produced by stimulation of fibers projecting through either the posterior celiac (+12% insulin and +12% glucagon) or accessory celiac (+15% insulin and +31% glucagon) branches. Since hexamethonium almost completely blocked both insulin and glucagon responses to stimulation, the effects are not likely to have resulted from inadvertent antidromic excitation of vagal afferents. Cell bodies of stimulated motoneurons, which were responsible for insulin and glucagon secretion, were found to occupy the medial two-thirds of the right (projecting through the posterior gastric branch) and left (projecting through the anterior gastric and hepatic branches) dmnX. These medial, longitudinal dmnX columns and their associated abdominal vagal branches are likely to play the predominant role in vagal control of the endocrine pancreas.
Adrenergic alpha-Antagonists↗
Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor alpha/delta locus.
The gene encoding angiogenin, a potent inducer of blood vessel formation, has been localized within the human genome. It is present as a single copy per haploid genome and is located on chromosome 14, on the basis of discordancy analysis of human-rodent hybrid cell lines. This localization was refined to 14q11 by in situ hybridization of an angiogenin probe to metaphase chromosomes prepared from both normal human lymphocytes and RPMI 8402 cells. The results from the RPMI 8402 cells also establish that the angiogenin gene resides proximal to a translocation breakpoint within the T cell receptor alpha/delta locus and therefore upstream from that locus. An AvaII RFLP, present at a frequency of 29% in an unselected collection of human placental DNAs, was identified in the coding region of the gene and results from a single silent transversion.
Angiogenesis Inducing Agents↗
Career-related psychological preferences of dietetic and restaurant/hotel and institution management students.
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Career Choice↗
Empathy in clinical dietitians and dietetic interns.
On the premise that empathy is important in patient care and nutrition counseling, the empathy levels of 217 clinical dietitians and 168 dietetic interns were measured using the Davis Interpersonal Reactivity Index. The Interpersonal Reactivity Index is designed to measure four aspects of empathy: empathic concern (EC), fantasy (FS), personal distress (PD), and perspective-taking (PT). Personal and professional characteristics were surveyed to determine possible influence on empathy. The instrument was mailed to 26 randomly selected internship programs. All of the dietetic interns and clinical dietitians who spend 80% of their time in patient care were requested to participate. The mean ages of the dietitians and interns were 35 and 25 years, respectively. Interns scored significantly higher on the EC (29.06, p less than .05) and FS (24.65, p less than .0005) scales than the dietitians (EC = 28.20, FS = 22.53). There was a highly significant negative correlation (r = -0.26, p less than .0001) between fantasy and age for dietitians and interns and between fantasy and experience for the dietitians (r = -0.23, p less than .0005). Dietitians and interns who had had graduate coursework in counselling, psychology, and/or educational psychology had significantly lower mean scores on the PD (17.14, p less than .05) and EC (27.82, p less than .05) scales and a significantly higher mean score on the PT (27.06, p less than .05) scale. Responses to an opinion question indicated that the mean for ideal percentage of time spent in direct patient contact was 70.1 for dietitians and 61.4 for interns, a highly significant difference (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
cDNA sequence of human class III alcohol dehydrogenase.
A human placental cDNA library was screened using oligonucleotide probes based on the peptide sequence of the human class III alcohol dehydrogenase. An incomplete cDNA clone covering most of the coding sequence of class III alcohol dehydrogenase was isolated from a human placental cDNA library. This was subsequently used as a probe to obtain a full-length clone from a human testicular library. The cDNA sequence codes for a protein that is identical to the enzyme purified from human liver. Southern analysis of human genomic DNA suggests that it may contain more than a single copy per haploid genome.
Alcohol Dehydrogenase↗
Role of lysines in human angiogenin: chemical modification and site-directed mutagenesis.
The role of lysines in the ribonucleolytic and angiogenic activities of human angiogenin has been examined by chemical modification and site-directed mutagenesis. It was demonstrated previously [Shapiro, R., Weremowicz, S., Riordan, J.F., & Vallee, B.L. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8783-8787] that extensive treatment with lysine reagents markedly decreases the ribonucleolytic activity of angiogenin. In the present study, limited chemical modification with 1-fluoro-2,4-dinitrobenzene followed by C18 high-performance liquid chromatography yielded several (dinitrophenyl)angiogenin derivaties. The major derivative formed had slightly increased enzymatic activity compared with the unmodified protein. Tryptic peptide mapping demonstrated the site of modification to be Lys-50. A second derivative, modified at Lys-60, was 34% active. Analysis of a third derivative indicated that modification of Lys-82 did not decrease activity. Thus, Lys-50 and Lys-82 are unessential for enzymatic activity while Lys-60 may play a minor role. No pure derivative modified at Lys-40, corresponding to the active-site residue Lys-41 of the homologous protein ribonuclease A, could be obtained by chemical procedures. Therefore, we employed oligonucleotide-directed mutagenesis to replace this lysine with glutamine or arginine. The Gln-40 derivative had less than 0.05% enzymatic activity compared with the unmodified protein and substantially reduced angiogenic activity when examined with the chick embryo chorioallantoic membrane assay. These results suggest that the angiogenic activity of the protein is dependent on an intact enzymatic active site. The Arg-40 derivative had 2.2% ribonucleolytic activity compared with unmodified angiogenin. The effects of reductive methylation of this derivative indicate that no lysines other than Lys-40 are critical.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme.
Angiotensin-converting enzyme (ACE; EC 3.4.15.1) is a zinc-containing dipeptidyl carboxypeptidase widely distributed in mammalian tissues and is thought to play a critical role in blood pressure regulation. Testis contains a unique, androgen-dependent ACE isozyme of unknown function. We have determined the cDNA sequence for human testicular ACE; it encodes a protein that is identical, from residue 37 to its C terminus, to the second half or C-terminal domain of the endothelial ACE sequence [Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G. & Corvol, P. (1988) Proc. Natl. Acad. Sci. USA 85, 9386-9390]. The full-length human testis ACE cDNA was constructed from a composite of cloned cDNAs, obtained by a combination of (i) immunoscreening and hybridization screening of a human testicular cDNA library in lambda gt11 and (ii) hybridization screening of human testis cDNAs constructed with ACE-specific primers and amplified by the polymerase chain reaction. The protein sequence inferred consists of a 732-residue preprotein including a 31-residue signal peptide. The mature polypeptide has a molecular weight of 80,073. The testis enzyme contains the second of the two putative metal-binding sites (His-Glu-Met-Gly-His) identified in endothelial ACE. This indicates that the functionally active catalytic site is within the C-terminal domain of the endothelial enzyme, accounting for the previous finding that these two structurally dissimilar isozymes are virtually identical catalytically. Of 22 testis ACE cDNAs cloned and sequenced, 3 have unique 5' regions, consisting of inserted, deleted, or substituted sequences up to 328 base pairs long, which have apparently arisen by alternative pre-mRNA splicing.
Amino Acid Sequence↗