Search PubMed⌕ Search

Biomedical subjects

J M Jones

Publications and source records attributed to J M Jones.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification of peroxisomal acyl-CoA thioesterases in yeast and humans.

A computer-based screen of the Saccharomyces cerevisiae genome identified YJR019C as a candidate oleate-induced gene. YJR019C mRNA levels were increased significantly during growth on fatty acids, suggesting that it may play a role in fatty acid metabolism. The YJR019C product is highly similar to tesB, a bacterial acyl-CoA thioesterase, and carries a tripeptide sequence, alanine-lysine-phenylalanineCOOH, that closely resembles the consensus sequence for type-1 peroxisomal targeting signals. YJR019C directed green fluorescence protein to peroxisomes, and biochemical studies revealed that YJR019C is an abundant component of purified yeast peroxisomes. Disruption of the YJR019C gene caused a significant decrease in total cellular thioesterase activity, and recombinant YJR019C was found to exhibit intrinsic acyl-CoA thioesterase activity of 6 units/mg. YJR019C also shared significant sequence similarity with hTE, a human thioesterase that was previously identified because of its interaction with human immunodeficiency virus-Nef in the yeast two-hybrid assay. We report here that hTE is also a peroxisomal protein, demonstrating that thioesterase activity is a conserved feature of peroxisomes. We propose that YJR019C and hTE be renamed as yeast and human PTE1 to reflect the fact that they encode peroxisomal thioesterases. The physical segregation of yeast and human PTE1 from the cytosolic fatty acid synthase suggests that these enzymes are unlikely to play a role in formation of fatty acids. Instead, the observation that PTE1 contributes to growth on fatty acids implicates this thioesterase in fatty acid oxidation.

Amino Acid Sequence↗
PubMed1999

Simultaneous transhiatal esophagectomy and coronary artery bypass grafting without cardiopulmonary bypass.

A 69-year-old patient underwent simultaneous transhiatal esophagectomy for carcinoma of the esophagogastric junction and benign spindle cell gastric tumor and coronary artery bypass grafting without cardiopulmonary bypass. A standard technique of transhiatal esophagectomy was used. The long saphenous vein was grafted to the left anterior descending artery and to the distal circumflex artery. The total theatre time was 6.5 h and the total ischemic time was 19 min. The patient made a good recovery and was discharged on day 18. He is enjoying an active lifestyle 6 months post-operatively.

Aged↗
PubMed1999

Great pains: famous people with headaches.

Have headaches influenced the course of history? It is very difficult to prove, but there is no doubt that head pains have affected some of the most influential people in history. This review explores how headaches have affected some of the world's most famous people.

Epilepsy↗
PubMed1999

Heterozygosity of p21WAF1/CIP1 enhances tumor cell proliferation and cyclin D1-associated kinase activity in a murine mammary cancer model.

The p21(WAF1/cIP1) cyclin-dependent kinase (cdk) inhibitor is a regulator of the G(1)-S cell cycle checkpoint. Despite the importance of p21 in cell cycle inhibition, its role as a tumor suppressor is uncertain. p21 mutations are infrequent in human tumors, and p21 null mice exhibit no increased tumor incidence. To ascertain whether p21 could influence tumor formation or progression in the context of other oncogenic stimuli, we crossed p21-deficient mice with mammary tumor susceptible Wnt-1 transgenic mice. The p21+/+, p21+/-, and p21-/- Wnt-1 transgenic female offspring were monitored for mammary tumor incidence and growth rates. p21 status had no effect on the age at which mammary tumors formed. However, p21+/- mammary tumors grew significantly faster than p21+/+ and p21-/- mammary tumors. The increased growth rates were confirmed by mitotic index counts and by BrdUrd labelling assays, indicating that a significantly higher percentage of p21+/- tumor cells were in S phase and mitosis than their p21+/+ and p21-/- counterparts. Moreover, cyclin D1-associated phosphorylation of retinoblastoma protein was significantly increased in p21+/- tumor lysates compared with p21+/+ and p21-/- lysates. These results are consistent with data indicating that reduced levels of p21 can facilitate cyclin/cdk complex formation while enhancing cdk activity. Thus, a reduction of p21 dosage may promote tumor progression in the presence of other oncogenic initiators. The dependence of p21 on prior oncogenic stimuli for its tumor-promoting activities suggests that it may behave as a tumor modifier gene rather than as a tumor suppressor gene.

Age Factors↗
PubMed1998

Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.

The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis. We report the complete coding sequence and exon organization of the human SCN8A gene. The predicted 1980 amino acid residues are distributed among 28 exons, including two pairs of alternatively spliced exons. The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse. Consensus sites for phosphorylation of serine/threonine and tyrosine residues are present in cyoplasmic loop domains. The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A. Single nucleotide polymorphisms in intron 19 and exon 22 were also identified. We localized SCN8A to chromosome band 12q13.1 by physical mapping on a YAC contig. The cDNA clone CSC-1 was reported by others to be a cardiac-specific sodium channel, but sequence comparison demonstrates that it is derived from exon 24 of human SCN8A. The genetic information described here will be useful in evaluating SCN8A as a candidate gene for human neurological disease.

Alternative Splicing↗
PubMed1998

Embryonic stem cell lines derived from human blastocysts.

Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.

Animals↗
PubMed1998

Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic.

The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4 subunit of the voltage-gated calcium channel. To evaluate the role of this channel subunit in human neurological disease, we determined the chromosomal location and intron/exon structure of the human CACNB4 gene. The 1560-bp open reading frame of the CACNB4 cDNA predicts a 58-kDa protein with an amino acid sequence that is 99% identical to the rat protein. The 13 coding exons of CACNB4 span >55 kb of genomic DNA. Human cerebellar RNA contains one major CACNB4 transcript that is 9 kb in length. Expression of CACNB4 was detected in cerebellum, kidney, testis, retina, lymphoblasts, and circulating lymphocytes. Retinal transcripts were localized by in situ hybridization to ganglion cells and the inner nuclear layer. Analysis of the GeneBridge 4 radiation hybrid mapping panel localized CACNB4 to position 791 cR on human chromosome 2, in a conserved linkage group on human 2q22-q31 and mouse chromosome 2. We localized CACNB4 to the 1.3-Mb YAC clone 952F10 in Whitehead contig WC861, along with the polymorphic markers D2S2236 and D2S2299. The chromosomal linkage of three of the four beta subunit genes to homeobox gene clusters associates the evolutionary origin of the beta gene family with the events that generated the four HOX clusters early in vertebrate evolution.

Alternative Splicing↗
PubMed1998

Pax2 expression and retinal morphogenesis in the normal and Krd mouse.

The Kidney and retinal defects (Krd) mouse carries a 7-cM transgene-induced deletion on chromosome 19 that includes the Pax2 locus. Adult mice heterozygous for the Krd deletion (Krd/+) are haploid for Pax2 and have a variable, semidominant phenotype characterized by structural defects of the kidney, retina, and optic disc. Renal and ocular anomalies present in heterozygous Pax2 mutants in both mice and humans support the hypothesis that haploinsufficiency of Pax2 underlies the Krd phenotype. To understand the embryonic basis of ocular defects observed in adult Krd/+ mice, we used immunohistochemistry, digital three-dimensional reconstructions, and quantitative morphometry to examine Pax2 protein distribution and ocular development in normal and Krd/+ mice from E10.5 to P2. In +/+ embryos, Pax2 immunopositive (Pax2+) cells demarcate the embryonic fissure as it forms in the ventral optic cup and optic stalk. After closure of the embryonic fissure, Pax2 immunostaining disappears from the ventral retina, but persists in a cuff of cells encircling the developing optic disc, the site where ganglion cell axons exit the retina. In Krd/+ embryos, Pax2+ cells in the posterior optic cup and the optic stalk undergo abnormal morphogenetic movements and the embryonic fissure fails to form normally. This results in an abnormal organization of the Pax2+ cells and ganglion cell axons at the nascent optic disc. The abnormal morphogenetic movements of the Pax2+ cells in the embryonic retina and optic stalk and the initial misrouting of the ganglion cell axons give rise to retinal and optic disc defects observed in the adult Krd/+ mice.

Animals↗
PubMed1998

Versatile action of Escherichia coli ClpXP as protease or molecular chaperone for bacteriophage Mu transposition.

The molecular chaperone ClpX of Escherichia coli plays two distinct functions for bacteriophage Mu DNA replication by transposition. As specificity component of a chaperone-linked protease, it recognizes the Mu immunity repressor for degradation by the peptidase component ClpP, thus derepressing Mu transposition functions. After strand exchange has been promoted by MuA transposase, ClpX alone can alter the conformation of the transpososome (the complex of MuA with Mu ends), and the remodeled MuA promotes transition to replisome assembly. Although ClpXP can degrade MuA, the presence of both ClpP and ClpX in the reconstituted transposition system did not destroy MuA essential for initiation of DNA replication by specific host replication enzymes. Levels of ClpXP needed to overcome inhibition by the repressor did not prevent MuA from promoting strand transfer, and ClpP stimulated alteration of the transpososome by ClpX. Apparently intact MuA was still present in the resulting transpososome, promoting initiation of Mu DNA replication by specific replication enzymes. The results indicate that ClpXP can discriminate repressor and MuA in the transpososome as substrates of the protease or the molecular chaperone alone, degrading repressor while remodeling MuA for its next critical function.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

6-hydroxydopamine lesion of rat nigrostriatal dopaminergic neurons differentially affects nicotinic acetylcholine receptor subunit mRNA expression.

Nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in the rat substantia nigra (SN) was assayed by semiquantitative RT-PCR following 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal dopaminergic neurons. Six months after unilateral injection of 6-OHDA or saline into the SN, total RNA was isolated from ipsilateral and contralateral tissue samples. RT-PCR amplifications were performed with template titration using primers specific for sequences encoding 1. nAChR alpha 2-alpha 7 and beta 2-beta 4 subunits 2. Glutamic acid decarboxylase 3. Glyceraldehyde 3-phosphate dehydrogenase for normalization of template mass. PCR products specific for alpha 3, alpha 4, alpha 5, alpha 6, alpha 7, beta 2, beta 3, and glutamic acid decarboxylase were detected in the reactions containing SN RNA. This is the first evidence that alpha 7 may be expressed in the SN. alpha 2 and beta 4 PCR products were not detected in SN reactions, although they were observed in hippocampus and thalamus control reactions. A comparison of ipsilateral and contralateral SN RT-PCR reaction products showed substantial decreases in alpha 5, alpha 6, and beta 3 product yields following 6-OHDA, but not sham treatment. Neither the SN of sham-lesioned rats nor the thalamus of 6-OHDA-lesioned rats yielded similar results, indicating that the effects observed in 6-OHDA-treated SN were not caused by local mechanical damage or a nonspecific response, respectively. Effects of 6-OHDA treatment on alpha 3, alpha 4, alpha 7, beta 2, or glutamic acid decarboxylase product yields from SN samples were small or undetectable. The results suggest that alpha 5, alpha 6, and beta 3 subunit-encoding mRNAs are expressed at substantially higher levels in dopaminergic than in nondopaminergic cell bodies in the SN.

Animals↗
PubMed1998

A re-audit of pulmonary function laboratories in the West Midlands.

In 1991 the West Midlands Pulmonary Function Audit Group examined the consistency between pulmonary function laboratories in the West Midlands. Three healthy subjects visited 22 centres and performed a standard set of pulmonary function tests. Demographic data on nine hypothetical subjects was also supplied for the laboratories to produce predicted values. Equipment was checked for accuracy using standard methods. The 1991 audit revealed significant inter-laboratory variability. Sources of error were identified and after consultation, recommendations were made to improve consistency. In addition, national and regional training workshops were organized for laboratory staff. In 1995 the audit was repeated using the same three subjects. Significant differences continued for all predicted results except for residual volume (RV) and forced vital capacity (FVC) and for all measured results except for functional residual capacity (FRC). However, improvements in the coefficient of variation were seen compared with 1991 for predicted forced expiratory volume (FEV1), total lung capacity (TLC), gas transfer (TLCO), FVC, FRC and RV. Similar improvements were seen in measured results for FEV1 and FVC. Increased variation was seen for predicted corrected transfer factor (KCO) and actual RV. The majority of variables in the 1995 audit had a coefficient of variation of less than 5% between laboratories. Analysis of the predicted results from the hypothetical subjects continued to show unacceptable variation reflecting continuing computer algorithm inconsistency. The improvements seen are encouraging and suggest that a regular audit programme is worthwhile.

Adult↗
PubMed1998

Ethnic minority psychology in the 20th century: reflections and meditations on what has been and what is next.

The launching of a new journal on ethnic minority psychology is placed in the context of events of the 20th century that precede it and make it possible. Citing the Dulles conference in 1978 on the role of ethnic minority issues in psychology, the author describes how the creation of the American Psychological Association (APA's) Office of Ethnic Minority Affairs and related governance structures made the creation of APA Division 45 (Society for the Psychological Study of Ethnic Minority Issues) possible, and hence their journal, Cultural Diversity and Ethnic Minority Psychology. Issues of conflict and cooperation among ethnic minority groups are discussed as the challenge to create unity from diversity is faced. Consideration of the steady increase in doctorally trained ethnic minority psychologists, relevant research, and organizational structures provides a basis for a publication outlet for these ideas. The challenges for ethnic minority psychology in the 21st century include research on the cultural diversity underlying ethnic minority groups and the similarities revealed by these differences, as well as the differences themselves. The new journal must fulfill the broad promise of the psychological study of ethnic minority issues on which Division 45 was founded.

Ethnopsychology↗
PubMed1997

The phiX174-type primosome promotes replisome assembly at the site of recombination in bacteriophage Mu transposition.

Initiation of Escherichia coli DNA synthesis primed by homologous recombination is believed to require the phiX174-type primosome, a mobile priming apparatus assembled without the initiator protein DnaA. We show that this primosome plays an essential role in bacteriophage Mu DNA replication by transposition. Upon promoting transfer of Mu ends to target DNA, the Mu transpososome undergoes transition to a pre-replisome that permits initiation of DNA synthesis only in the presence of primosome assembly proteins PriA, DnaT, DnaB and DnaC. These assembly proteins promote the engagement of primase and DNA polymerase III holoenzyme, initiating semi-discontinuous replication preferentially at the Mu left end. The results indicate that these proteins play a crucial role in promoting replisome assembly on a recombination intermediate.

Bacterial Proteins↗