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B Jordan

Publications and source records attributed to B Jordan.

At least 19 recordsLinked to original sources
PubMed1999

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes.

Deletions and amplifications are frequent alterations of the short arm of chromosome 8 associated with various types of cancers, including breast cancers. This indicates the likely presence of tumor suppressor genes and oncogenes. In the present study, we have used the expressed sequence tag (EST) map of 8p11-21 to assemble a set of available cDNAs representing genes from this region. DNA arrays were prepared for expression analysis and search for genes potentially involved in breast cancer. Underexpresion in tumoral breast cells (versus normal breast) was observed for 15 transcripts. Among these, the Frizzled-related gene FRP1/FRZB, was turned off in 78% of breast carcinomas, suggesting that the lack of its product may be associated with malignant transformation. Overexpression in tumoral breast cells was observed for 13 genes. The FGFR1 gene, that encodes a tyrosine kinase receptor for members of the fibroblast growth factor family, was identified as a good candidate for one amplification unit. Taken together, our results demonstrate that such a strategy can rapidly identify genes with an altered pattern of expression and provide candidate genes for malignancies.

Breast Neoplasms↗
PubMed1999

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Adult↗
PubMed1999

Peroxynitrite-induced alterations in synaptosomal membrane proteins: insight into oxidative stress in Alzheimer's disease.

Peroxynitrite (ONOO ) is a highly reactive, oxidizing anion with a half-life of <1 s that is formed by reaction of superoxide radical anion with nitric oxide. Several reports of ONOO--induced oxidation of lipids, proteins, DNA, sulfhydryls, and inactivation of key enzymes have appeared. ONOO- has also been implicated as playing a role in the pathology of several neurodegenerative disorders, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis, among others. Continuing our laboratory's interest in free radical oxidative stress in brain cells in AD, the present study was designed to investigate the damage to brain neocortical synaptosomal membrane proteins and the oxidation-sensitive enzyme glutamine synthetase (GS) caused by exposure to ONOO-. These synaptosomal proteins and GS have previously been shown by us and others to have been oxidatively damaged in AD brain and also following treatment of synaptosomes with amyloid beta-peptide. The results of the current study showed that exposure to physiological levels of ONOO- induced significant protein conformational changes, demonstrated using electron paramagnetic resonance in conjunction with a protein-specific spin label, and caused oxidation of proteins, measured by the increase in protein carbonyls. ONOO- also caused inactivation of GS and led to neuronal cell death examined in a hippocampal cell culture system. All these detrimental effects of ONOO- were successfully attenuated by the thiol-containing antioxidant tripeptide glutathione. This research shows that ONOO- can oxidatively modify both membranous and cytosolic proteins, affecting both their physical and chemical nature. These findings are discussed with reference to the potential involvement of ONOO- in AD neurodegeneration.

Alzheimer Disease↗
PubMed1998

The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease.

Amyloid beta-peptide (Abeta) is a key factor in the neurotoxicity of Alzheimer's disease (AD). Recent research has shown that Abeta-mediated neurotoxicity involves free radicals and that Abeta peptides can initiate multiple membrane alterations, including protein oxidation and lipid peroxidation, eventually leading to neuronal cell death. Research also has emphasized the role of 4-hydroxynonenal (HNE), a downstream product of lipid peroxidation, in being able to mimic some of the effects of Abeta peptides. In the current investigation, electron paramagnetic resonance (EPR) studies of spin labeled cortical synaptosomal membrane proteins has been employed to study conformational changes in proteins, spectrophotometric methods have been used to measure protein carbonyl content, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for mitochondrial function has been used to study the effect of vitamin E on samples that were treated with Abeta or HNE. The free radical dependence of beta-amyloid-associated toxicity was confirmed by the ability of the free radical scavenger vitamin E to prevent the toxic effects of Abeta. In contrast, HNE was still toxic in the presence of vitamin E. These results support our Abeta-associated free radical model for neurotoxicity in AD brain and are discussed with reference to potential therapeutic strategies for AD.

Aldehydes↗
PubMed1998

Isolation of the gene encoding the Drosophila melanogaster homolog of the Saccharomyces cerevisiae GCN2 eIF-2alpha kinase.

Genomic and cDNA clones homologous to the yeast GCN2 eIF-2alpha kinase (yGCN2) were isolated from Drosophila melanogaster. The identity of the Drosophila GCN2 (dGCN2) gene is supported by the unique combination of sequence encoding a protein kinase catalytic domain and a domain homologous to histidyl-tRNA synthetase and by the ability of dGCN2 to complement a deletion mutant of the yeast GCN2 gene. Complementation of Deltagcn2 in yeast by dGCN2 depends on the presence of the critical regulatory phosphorylation site (serine 51) of eIF-2alpha. dGCN2 is composed of 10 exons encoding a protein of 1589 amino acids. dGCN2 mRNA is expressed throughout Drosophila development and is particularly abundant at the earliest stages of embryogenesis. The dGCN2 gene was cytogenetically and physically mapped to the right arm of the third chromosome at 100C3 in STS Dm2514. The discovery of GCN2 in higher eukaryotes is somewhat unexpected given the marked differences between the amino acid biosynthetic pathways of yeast vs. Drosophila and other higher eukaryotes. Despite these differences, the presence of GCN2 in Drosophila suggests at least partial conservation from yeast to multicellular organisms of the mechanisms responding to amino acid deprivation.

Amino Acid Sequence↗
PubMed1998

Topographic position of forelimb motoneuron pools is conserved in vertebrate evolution.

The neuromotor conservatism hypothesis predicts that neuromotor patterns in homologous tetrapod muscles are conserved evolutionarily despite the musculoskeletal modifications of vertebrate limbs. A complete description of the anatomical organization of the neurons innervating homologous limb muscles is a prerequisite to any test of the neuromotor conservatism hypothesis. This study uses the retrograde neuronal tracer WGA-HRP to selectively label the motor neuron pools of seven homologous forelimb muscles in mice (Mus musculus) and iguanas (Iguana iguana): Mm. pectoralis, spinodeltoideus, biceps brachii, lateral and long heads of triceps brachii, and the supraspinatus and infraspinatus (in mice) or their reptilian homolog, the supracoracoideus (in iguanas). In vertebrates, motoneurons are arranged in longitudinal columns of cells in the ventral horn of the spinal cord. Mouse motor pools average 1,952 microns in length, except the pectoralis pool which averaged 2,949 microns in length. Iguana pools average 3,196 microns in length. The number of neurons per pool ranged from 70-199 in mice and from 58-114 neurons in iguanas. In both iguanas and mice the motor pools for the spinodeltoids, biceps, and the supracoracoideus (or its mammalian homologs) lie anterior to the pectoralis and triceps motor pools. In the transverse plane, the pectoralis pool lies medial to those of the triceps. The pools of the biceps and spinodeltoids are located dorsal and lateral to those of the pectoralis and supracoracoideus (or its homologs in mammals). The resulting motor pool maps support the hypothesis that the anatomical organization of motoneurons in ancestral reptiles has been retained in these two tetrapod descendents.

Animals↗
PubMed1997

Chromosomal location of the human immunoglobulin lambda variable 8 (IGLV8) gene family outside the major lambda locus on chromosome 22q11.2.

Physical mapping of the human immunoglobulin lambda locus (IGL) on chromosome 22q11 has shown the existence of at least 52 variable region gene segments. These Vlambda genes are associated with EcoRI fragments detectable in Southern blots of genomic DNA samples. The current physical map of the IGL locus includes a unique Vlambda8 gene (IGL8a, accession no. Z73650) in a 3.7 kb EcoRI fragment. However, our Southern blot-EcoRI-restriction fragment length polymorphism studies on the Brazilian population using a specific probe for the Vlambda8 gene (pVL8 probe) have revealed the presence of two additional fragments bearing Vlambda8 sequences (8.0 kilobase (kb) at 100% frequency and 6.0 kb at 10% frequency). We have used human/rodent somatic cell hybrid DNAs to locate these new Vlambda8 genes outside the major locus on chromosome 22q11.2. Polymerase chain reactions using specific primers for the IGLV8a gene on the somatic hybrid panel showed that chromosome 8 (besides 22q11) also comprises Vlambda8 sequences. This finding represents evidence for the dispersion of the human IGLV8 gene family outside the major locus (orphan genes).

Amino Acid Sequence↗
PubMed1997

The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins.

Alzheimer's disease (AD) is widely held to be a disorder associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta). A beta-associated free radicals cause lipid peroxidation, a major product of which is 4-hydroxy-2-trans-nonenal (HNE). We determined whether HNE would alter the conformation of synaptosomal membrane proteins, which might be related to the known neurotoxicity of A beta and HNE. Electron paramagnetic resonance spectroscopy, using a protein-specific spin label, MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl), was used to probe conformational changes in gerbil cortical synaptosomal membrane proteins, and a lipid-specific stearic acid label, 5-nitroxide stearate, was used to probe for HNE-induced alterations in the fluidity of the bilayer domain of these membranes. Synaptosomal membranes, incubated with low concentrations of HNE, exhibited changes in protein conformation and bilayer order and motion (fluidity). The changes in protein conformation were found to be concentration- and time-dependent. Significant protein conformational changes were observed at physiologically relevant concentrations of 1-10 microM HNE, reminiscent of similar changes in synaptosomal membrane proteins from senile plaque- and A beta-rich AD hippocampal and inferior parietal brain regions. HNE-induced modifications in the physical state of gerbil synaptosomal membrane proteins were prevented completely by using excess glutathione ethyl ester, known to protect neurons from HNE-caused neurotoxicity. Membrane fluidity was found to increase at higher concentrations of HNE (50 microM). The results obtained are discussed with relevance to the hypothesis of A beta-induced free radical-mediated lipid peroxidation, leading to subsequent HNE-induced alterations in the structure and function of key membrane proteins with consequent neurotoxicity in AD brain.

Aldehydes↗
PubMed1996

[Eating behavior of 12-16-year olds of French-speaking Valais: cross-sectional survey among 962 secondary students].

Eating habits that are potentially harmful are picked up during the teens. The aim of the study is to identify the main eating habits of 12-16 year-old teenagers of central Valais in order to plan better targeted health promotion interventions. The study design is cross sectional. An anonymous questionnaire was taken by a sample of 962 teenagers. Some results: 25.2% did not have breakfast every day, 37.0% did not eat neither fruit nor vegetable the day before, 58.2% had a soda drink the day before, 5.5% of the 12 of the 16 year-old ones and 51.2% year old ones drink some alcohol over the weekends. Possible health promotion interventions are listed.

Adolescent↗
PubMed1996

Advances in burn wound care.

The development of effective topical chemotherapy, the reintroduction of burn wound excision, and the use of biologic dressings have significantly decreased the incidence of invasive burn wound infection and have contributed to the improvement in the survival that has occurred over the past four decades. The currently available skin substitutes are imperfect, and research endeavors continue in the effort to develop a nonantigenic disease-free, readily available, physiologically effective tissue that will promptly effect wound closure, reduce scar formation and thereby improve cosmetic results, and reduce the need for reconstructive surgery. As monitoring and physiologic support techniques improve and additional advances in wound care occur, the morbidity and mortality of burn patients will be further reduced.

Bandages↗
PubMed1994

Separate P2T and P2U purinergic receptors with similar second messenger signaling pathways in UMR-106 osteoblasts.

UMR-106 rat osteogenic sarcoma cells express two calcium signaling P2 purinergic receptors. One is a P2U receptor with EC50's for adenosine triphosphate (ATP) and uridine triphosphate (UTP) of 2.6 and 2.4 microM, respectively. The other is a novel P2T receptor for adenosine diphosphate (ADP) (EC50 0.4 microM), adenosine 5'-O-(2-thiodiphosphate). (EC50 5 microM), 2-methylthio ATP (EC50 0.2 microM), and 2-methylthio ADP (EC50 0.04 microgram M). Responses to these ligands are desensitized by ADP but not by UTP. Responses to UTP and ATP are desensitized by UTP but not by ADP or adenosine 5'-O-(2-thiodiphosphate). 2-ChloroATP interacts with both receptors at high concentrations but with only the P2T receptor at low concentrations (EC50 0.05 microM). The weak platelet P2T receptor antagonist AMP blocks this P2T and not the P2U receptor. Addition of ATP after UTP desensitization of P2U receptors inhibits subsequent responsiveness to ADP but evidence for rapid conversion of ATP to ADP complicates interpretation of this apparent antagonism of P2T receptors by ATP. A subpassage of UMR-106.P135 cells lose P2U but retain P2T ligand responsiveness. Activation of either P2 receptor increases cellular IP3 concentrations in UMR-106 cells. Neither receptor can activate divalent cation entry as evidenced by their lack of effect on Mn++ quenching of fura-2 fluorescence. Neither receptor can modify parathyroid hormone receptor-mediated elevation of cellular cyclic AMP. This receptor for ADP demonstrates many of the same characteristics of the ADP receptor which we have previously reported as a P2T receptor expressed in K562 and Dami cells.

Adenosine Diphosphate↗
PubMed1993

Communications between medical referrers and child psychiatry staff.

Communicating in organisations is often seen as the key to good practice, good relationships and good service. A survey was conducted on what communication was wanted by medical referrers to a Department of Child and Family Psychiatry, the types of feedback preferred, and its timing and content. The main finding was that paediatricians received different and better information about referred patients than general practitioners.

Child↗
PubMed1992

[Continuous oxygen therapy at home. Observations of oxygen users after an instruction program].

The benefit of continuous domiciliary oxygen therapy (OCD) directly depends on the number of hours the oxygen is used daily. The observance of a correct regime is rarely met at present. For this reason we have done a prospective study for 24 months, assessing the compliance of 64 patients from 28 to 82 years of age. All these patients received a systematic and personal programme of education for 2 days in hospital. We subsequently measured, without the knowledge, either of the patient or the person caring from them, the quarterly oxygen usage. The mean duration of oxygen therapy was 14.7 +/- 3.6 hours. It remained stable during the 2 years of observation: 51% of the patients achieved a treatment of 15 hours or more and 10%, 10 hours or less. We did not find a significant correlation between the hours of compliance and the age, sex, FEV1, FVC and PaO2 or haemoglobin saturation. A significant statistical correlation with the PaCO2 was obtained. The more educated patients had better compliance levels than those of lesser education. The results obtained were better than those found in the literature at the present time. Perhaps it is explained by the level of education given. It cannot be excluded, however, that our severe criteria for the prescription of OCD has selected a population which was more susceptible to achieving good compliance. However, these results encourage the initiation of another prospective study using a control group to make a better assessment of the impact of education on the patient and his carers by the improved compliance in OCD.

Adult↗
PubMed1991

Relatives' recall of a psychiatric interview.

One hundred seventeen patients from the Burke Rehabilitation Center (White Plains, NY) with clinically diagnosed dementia of the Alzheimer type (DAT) were identified for a case-control study (CCS) designed to assess risk factors for DAT. A psychiatric evaluation was part of the Burke dementia workup. The study sample was composed of 96 relatives who (a) were present with the patient at the psychiatric evaluation and (b) were interviewed for the CCS. The data for this study were the relatives' responses to the question "Did your relative (patient with DAT) ever see a psychiatrist?" The recall of relatives, regardless of relationship category (spouse, adult children, and others) did not exceed the 50% recall predicted by chance. When the age of the relative and length of time between the two interviews were considered, they did not modify these results.

Adult↗
PubMed1990

YAC power.

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Animals↗
PubMed1990

The 11q13 amplicon of a mammary carcinoma cell line.

Fifteen to 20% of breast carcinomas show amplification of genes located at 11q13. The HST/FGFK and INT2 fibroblast growth factor (FGF)-related genes and the BCL1 locus are usually present in the amplification units. We have investigated the structure and chromosomal location of the 11q13 amplicon of the MDA-MB-134 mammary carcinoma cell line by using in situ chromosomal and pulsed field gel hybridizations. The results indicate that a limited number of amplification units are involved in the constitution of an extended chromosomal region located on 11q. These units do not show any important rearrangement over rather large distances around the HST/INT2 and BCL1 loci.

Blotting, Northern↗