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J F Powell

Publications and source records attributed to J F Powell.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1995

No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence syndrome.

Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory sequence of the gene is polymorphic; that identified by the c2 allele has been shown by transfection studies to confer an increased rate of transcription. A recent report indicating an association between this allele and alcohol induced cirrhosis suggests that it may contribute to the genetic vulnerability to this disease. We have examined this polymorphism in patients of western European origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol dependence syndrome. We were unable to detect any association between this allele and any of these diseases.

Alcohol Amnestic Disorder↗
PubMed1995

An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia.

Since abnormalities of brain development play a role in the aetiology of schizophrenia, growth factors, known to play a role in neurodevelopment, such as neurotrophin-3 (NT-3), are therefore candidate genes for this disorder. The A3/147 bp allele of a dinucleotide repeat polymorphism in the promoter region of the NT-3 gene has been reported as occurring more frequently in a sample of Japanese schizophrenics compared to controls. We have determined the frequency of alleles of this polymorphism in 175 Caucasian schizophrenic patients and 147 control subjects. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and, in a test of allalleles, the patients and controls did not differ significantly in allele frequencies. However, the male schizophrenics were more likely than male controls to have the A3/147 bp allele (P = 0.029).

Alleles↗
PubMed1994

Three forms of gonadotropin-releasing hormone characterized from brains of one species.

Most vertebrate species have more than one form of gonadotropin-releasing hormone (GnRH) in their brains, but it is not clear whether each form has a distinct function. We report that sea bream (Sparus aurata) brains have three forms of GnRH, one of which is described herein and is called sea bream GnRH (sbGnRH). The primary structures of two forms were determined by Edman degradation and mass spectral analysis. The amino acid sequence of sbGnRH is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Ser-Pro-Gly-NH2. The second peptide is identical to a form originally isolated from chicken brains (cGnRH-II): pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2. cGnRH-II is the most ancient form of GnRH identified to date in jawed fish and the most prevalent form throughout the vertebrates. The third form of GnRH has previously been identified as salmon GnRH by cDNA studies and is confirmed here by chromatographic and immunological studies. Phylogenetic distribution of GnRH peptides suggests sbGnRH arose in the perch-like fish as a gene duplication of the existing cGnRH-II or salmon GnRH genes. All three identified GnRH peptides were synthesized and shown to release gonadotropin in vivo in the sea bream. The dominant form of GnRH stored in the pituitary was sbGnRH. Not only was the content of sbGnRH 500-fold greater than that of salmon GnRH but also cGnRH-II was not detected in the pituitary. The latter evidence suggests that sbGnRH is the endogenous releaser of gonadotropin II.

Amino Acid Sequence↗
PubMed1994

Shifting depression.

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Antidepressive Agents↗
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

Norrie disease gene: characterization of deletions and possible function.

Positional cloning experiments have resulted recently in the isolation of a candidate gene for Norrie disease (pseudoglioma; NDP), a severe X-linked neurodevelopmental disorder. Here we report the isolation and analysis of human genomic DNA clones encompassing the NDP gene. The gene spans 28 kb and consists of 3 exons, the first of which is entirely contained within the 5' untranslated region. Detailed analysis of genomic deletions in Norrie patients shows that they are heterogeneous, both in size and in position. By PCR analysis, we found that expression of the NDP gene was not confined to the eye or to the brain. An extensive DNA and protein sequence comparison between the human NDP gene and related genes from the database revealed homology with cysteine-rich protein-binding domains of immediate--early genes implicated in the regulation of cell proliferation. We propose that NDP is a molecule related in function to these genes and may be involved in a pathway that regulates neural cell differentiation and proliferation.

Amino Acid Sequence↗
PubMed1993

A continuous linkage map of 22 short tandem repeat polymorphisms on human chromosome 12.

A continuous linkage map consisting of 22 short tandem repeat polymorphisms has been constructed for human chromosome 12 using 23 non-CEPH pedigrees. The markers were distributed at an average distance of 9.35 cM (3.1-33.9 cM). Eighteen of the markers could be positioned uniquely with a likelihood of > 1000:1. The physical locations of some of the markers suggest that the map covers 85-95% of the chromosome. This framework map of 18 markers has a female length of 213 cM and a male length of 131 cM. Female recombination frequencies were greater than male recombination frequencies except in the distal portion of the short arm. The map provides confirmatory evidence for orders established previously on CEPH pedigrees and uniquely positions 4 additional markers (CD4, ATPSB, D12S56, PLA2).

Chromosome Mapping↗
PubMed1993

Androgen receptor gene polymorphisms in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is more common in men than in women (male to female ratio of approximately 2:1), suggesting a role for a sex-linked factor in the disease. The recent identification of a mutation of the androgen receptor gene in Kennedy's disease or X-linked bulbospinal neuronopathy, a rare form of progressive lower motor neurone degeneration, also associated with clinical signs of androgen insensitivity, raises the possibility that androgen function may be disturbed in other motor neurone disorders, including ALS. The Kennedy's disease mutation consists of an increased size of a highly polymorphic CAG repeat sequence in the first exon of the androgen receptor gene, coding for a polyglutamine tract. We have analysed this CAG repeat sequence in a large number of patients with typical sporadic ALS and in normal controls, in order to test the hypothesis that this polymorphism of the androgen receptor gene may influence susceptibility for ALS. We report that the distribution of alleles relating to the size of the CAG repeat sequence of the androgen receptor gene is similar in ALS and controls, indicating that polymorphisms of the CAG repeat sequence of the androgen receptor gene play a limited role, if any, in susceptibility to ALS.

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↗
PubMed1993

Selectatec gas leak.

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Anesthesia, Inhalation↗
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↗