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Biomedical subjects

J F Powell

Publications and source records attributed to J F Powell.

At least 19 recordsLinked to original sources
PubMed1995

Primary structure of solitary form of gonadotropin-releasing hormone (GnRH) in cichlid pituitary; three forms of GnRH in brain of cichlid and pumpkinseed fish.

GnRH is a decapeptide family with at least nine distinct structures. Vertebrates, except for most placental mammals, have more than one of these GnRH forms within the brain. We report chromatographical and immunological evidence that three forms of GnRH are in the brains of both cichlid (Haplochromis burtoni) and pumpkinseed (Lepomis gibbosus) fishes. We argue that the three forms correspond to those previously described as sea bream GnRH (sbGnRH), chicken GnRH-II and salmon GnRH. In contrast, only one GnRH form was present in the pituitary of the cichlid and is identified as sbGnRH by amino acid sequence. This is the first report in which the primary structure of GnRH is determined from pituitary tissue. The N-terminus was identified by monitoring the digestion of the peptide by pyroglutamate aminopeptidase with matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The amidation of the C-terminus was established using an esterification procedure for monitoring with MALDI-MS. This report supports the idea that three forms of GnRH within one species is widespread in the order Perciformes. The present study establishes sbGnRH as the third GnRH form in H. burtoni and predicts that sbGnRH is synthesized in preoptic neurons, then transported to the pituitary in the preoptic-hypophyseal axons for the release of one or both gonadotropins.

Amino Acid Sequence↗
PubMed1995

Mammalian gonadotropin-releasing hormone (GnRH) identified by primary structure in Russian sturgeon, Acipenser gueldenstaedti.

The mammalian form of gonadotropin-releasing hormone (GnRH) was purified from the brains of Russian sturgeon, Acipenser gueldenstaedti, using reversed-phase high pressure liquid chromatography (HPLC). The total concentration of mGnRH within these fish was 5.4 ng/brain. Small amounts of immunoreactive chicken GnRH-II like molecules were also detected but at insufficient quantities for purification. The primary structure of mGnRH was determined using automated Edman degradation. Because sequence data could not be obtained until after digestion by bovine pyroglutamyl amino-peptidase, it was determined that the amino-terminal residue was modified. Furthermore, mass spectrometric data and co-elution with synthetic mGnRH on HPLC confirmed that the carboxy-terminal residue was amidated. The amino acid sequence of sturgeon GnRH is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2.

Amino Acid Sequence↗
PubMed1995

Neurofilaments, free radicals, excitotoxins, and amyotrophic lateral sclerosis.

There is increasing evidence implicating abnormalities of neurofilament function in the pathogenesis of amyotrophic lateral sclerosis (ALS). The observation that the P2 blood protein phenotype is overrepresented in patients with ALS is potentially important, but needs confirmation. It should be shown that this segregation is selective for ALS. If it is, the implications outlined in Meyer's hypothesis will need to be explored, bearing in mind that much of the evidence implicating excitotoxins, free radicals, and neurofilaments in familial and sporadic ALS is still circumstantial. Thus the identification of candidate genes, the pursuit of large segregation studies, and identification of specific point mutations, remain key goals in ALS research.

Amino Acid Sequence↗
PubMed1995

Gonadotropin-releasing activities of the three native forms of gonadotropin-releasing hormone present in the brain of gilthead seabream, Sparus aurata.

Three forms of gonadotropin-releasing hormone (GnRH) have been recently identified in the brain of gilthead seabream (Sparus aurata): salmon GnRH (sGnRH), chicken GnRH-II (cGnRH-II), and a novel form, Ser8-mammalian GnRH, named seabream GnRH (sbGnRH). sbGnRH is the most abundant form in the pituitaries of sexually mature seabream during the spawning season. The present study investigated the gonadotropin-releasing activities of the three native forms of GnRH found in seabream brains, as well as of two structural analogs of sbGnRH. All native forms of GnRH stimulated gonadotropin-II (GtH-II) secretion in preovulatory female seabream. cGnRH-II was found to be 7 to 8 times more potent than sbGnRH and 2 times more potent than sGnRH in inducing GtH-II release. sGnRH was found to be 3.5 to 5 times more potent than sbGnRH in inducing GtH-II secretion. These data demonstrate that cGnRH-II, which is not present in pituitaries of sexually mature seabream, is the most potent GtH-II releaser, whereas sbGnRH, 500 times more abundant than sGnRH in the pituitary of maturing fish, is the least potent. The lower potency of sbGnRH may suggest faster enzymatic breakdown, more rapid clearance from the circulation, or a lower binding affinity to the pituitary GnRH receptor. The lower bioactivity of sbGnRH may be compensated for by its high levels in the pituitary. The two analogs of sbGnRH, [D-Nal(2)6,Pro9-NEt]-sbGnRH and [D-Arg6,Pro9-NEt]-sbGnRH, were equipotent to each other and 5 times more potent than sbGnRH in inducing GtH-II release in preovulatory seabream. However, they were 5 to 6 times less active than the analog of mammalian GnRH, [D-Ala6,Pro9-NEt]-mGnRH. Strategies for designing superactive analogs of sbGnRH are discussed.

Amino Acid Sequence↗
PubMed1994

An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in schizophrenia.

The cytochrome P450 mono-oxygenases are a group of enzymes that metabolize a variety of exogenous and endogenous compounds, some of which are potentially toxic. Individual variations in the metabolism of potential toxins could influence susceptibility to disorders having genetic and environmental components, such as schizophrenia. The frequency of two common mutant alleles of the gene for the cytochrome P450 enzyme debrisoquine-4-hydroxylase (CYP2D6) was determined in 264 Caucasian schizophrenic patients and 217 controls, using the polymerase chain reaction and restriction enzyme digestions. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and the frequency of each mutant allele (CYP2D6A and CYP2D6B) did not differ between patients and controls.

Alleles↗
PubMed1993

Dental evidence for the peopling of the New World: some methodological considerations.

Turner (1985b) and Greenberg et al. (1986) proposed that New World populations originated in northern Asia and entered the Americas in three migratory waves: Macro-Indian, Aleut-Eskimo, and Na-Dene. Biological support for this model comes from Turner's unweighted pair group (UPGMA) cluster analysis of discrete dental traits in world populations. Unfortunately, UPGMA analysis often creates suspect clusters and may not be valid as a method for displaying evolutionary relationships because it assumes that rates of evolution are equal among all populations. To test whether Turner's results are an artifact of his analytical method, I analyzed his published data (Turner 1985b) using two alternative techniques that do not assume homogeneous rates of change: a Wagner distance algorithm employing the Fitch-Margoliash criterion for goodness of fit and a maximum parsimony analysis using segment-coded dental trait frequencies. Both alternative methods produce trees that are similar to the UPGMA analysis results, supporting Turner's original results and basic conclusions. Comparisons of tree topology demonstrate that there is strong congruence between trees produced by all three methods, although the placement of certain populations, such as Na-Dene, depends on the method of analysis employed.

Algorithms↗
PubMed1992

Organization of the human monoamine oxidase genes and long-range physical mapping around them.

A 265-kb yeast artificial chromosome containing sequences for human monoamine oxidase A and B (MAO-A and MAO-B) genes has been characterized. These two genes are localized within a region of about 240 kb and are arranged in a tail-to-tail configuration, with the 3' coding sequences separated by about 50 kb. A region about 2.5 Mb around the MAO loci was mapped by pulsed-field gel electrophoresis (PFGE). Comparisons between the restriction maps derived from the YAC and the long-range map derived from genomic digestions were in general agreement. The important features identified include a CpG island at the 5' end of the MAO-A and MAO-B genes, respectively. The combined information supports the order of markers within this region to be DXS77-DXS7-MAOA-MAOB.

DNA Probes↗
PubMed1992

Isolation and characterization of a candidate gene for Norrie disease.

Previous analysis has refined the location of the gene for Norrie disease, a severe, X-linked, recessive neurodevelopmental disorder, to a yeast artificial chromosome subfragment of 160 kilobases (kb). This fragment was used to screen cDNA libraries from human fetal and adult retina. As a result, we have identified an evolutionarily conserved cDNA, which is expressed in fetal and adult brain and encodes a predicted protein of 133 amino acids. The cDNA detects genomic sequences which span a maximum of 50 kb, and which are partly deleted in several typical Norrie disease patients. An EcoRI polymorphism with a calculated heterozygosity value of 43% was observed. The locus identified is a strong candidate for the Norrie disease gene.

Amino Acid Sequence↗
PubMed1992

Peopling of the Americas: paleobiological evidence.

A subjective and bivariate analysis of 8500-10,000-year-old human fossil remains from North America substantiates that the fossils' closest affinities are with Asian populations. Within North American prehistoric Indian populations, increasing brachycephalization and the possible development of a larger, broader face are two structural trends that can be identified. In those respects where Paleo-Indian specimens differ from modern northern Asians and North American Indians, they tend to resemble southern Asian and European populations. These assessments generally support the inference that populations entered the New World relatively recently but before the modern northern Asian and North American features were fully developed. Based on the data examined, no date can be specified for time of entrance of the first populations, nor can the number of founding populations be discerned.

Anthropology, Physical↗
PubMed1991

Structure of the human gene for monoamine oxidase type A.

Monoamine oxidases, type A and type B, are principal enzymes for the degradation of biogenic amines, including catecholamines and serotonin. These isozymes have been implicated in neuropsychiatric disorders. Previously, cDNA clones for both MAO-A and MAO-B have been sequenced and the genes encoding them have been localized to human chromosome Xp11.23-Xp11.4. In this work, we isolated human genomic clones spanning almost all the MAOA gene from cosmid and phage libraries using a cDNA probe for MAO-A. Restriction mapping and sequencing show that the human MAOA gene extends over 70 kb and is composed of 15 exons. The exon structure of human MAOA is similar to that described by others for human MAOB. Exon 12 (bearing the codon for cysteine, which carries the covalently bound FAD cofactor) and exon 13 are highly conserved between human MAOA and MAOB genes (92% at the amino acid level). Earlier work revealed two species of MAO-A mRNA, 2.1 kb and 4.5-5.5 kb. We now report on further cDNA isolation and sequencing, which demonstrates that the longer message has an extension of 2.2 kb in the 3' noncoding region. This extended region is contained entirely within exon 15. The two messages therefore appear to be generated by the use of two alternative polyadenylation sites. Results from the present work should facilitate the mutational analysis of functional domains of MAO-A and MAO-B. Knowledge of the gene structure will also help in evaluating the role of genetic variations in MAO-A in human disease through the use of genomic DNA, which is more accessible than the RNA, as a template for PCR-amplification and sequencing.

Amino Acid Sequence↗
PubMed1990

Atlanto-axial subluxation in Down's syndrome.

A case of atlanto-axial subluxation in a patient with Down's syndrome is described. The gradual deterioration in the patient's locomotor ability caused a delay in diagnosis. Patterns of presentation of this condition are discussed.

Adolescent↗
PubMed1989

The primary structure of bovine monoamine oxidase type A. Comparison with peptide sequences of bovine monoamine oxidase type B and other flavoenzymes.

We have isolated cDNA clones believed to encompass the full-length coding sequences for a subunit of bovine monoamine oxidase type A (MAO-A). The clones code for an apoprotein of 527 amino acid residues corresponding to a molecular mass of 59,806 Da. The inferred protein sequences show an overall similarity of 68% with partial amino acid sequences of bovine type B MAO (about 41% of the total sequence), as well as a greater similarity (greater than 90%) with some regions including that for the published sequence of the flavin-binding region. Sequence comparisons indicate that these two forms of MAO are encoded by distinct genes. Comparison of this sequence with other flavoenzymes showed similarity with regions associated with non-covalent flavin-binding sites. Analysis of mRNAs coding for MAO enzymes showed a heterogeneity of transcripts consistent with several different forms of monoamine oxidase.

Amino Acid Sequence↗
PubMed1989

Localization of human monoamine oxidase-A gene to Xp11.23-11.4 by in situ hybridization: implications for Norrie disease.

A cDNA for the neurotransmitter-degrading enzyme monoamine oxidase-A (MAO-A) has been assigned by in situ hybridization to the human X chromosome and subregionally localized to Xp11.23-11.4. As restriction fragments detected by this probe are deleted in some patients with Norrie disease, this assignment provides confirmation of the localization of the disease.

Chromosome Banding↗
PubMed1989

Monoamine oxidase deficiency in males with an X chromosome deletion.

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

Adolescent↗