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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

Development of laminin receptor agonists: identification of important functional residues by alanine scanning.

An antagonist of cellular adhesion and motility, acetyl-C-[S-Acm]-VIGYSGDRC-[S-Acm]-NH(2) (mEGF(33-42)), shares homology with the agonist sequence CDPGYIGSR-NH(2). It has been proposed that the latter peptide binds to the high affinity 67 kDa laminin receptor. Both peptides have equal affinities for the receptor and similar conformations have been derived for both. We have examined the importance of individual non-homologous residues with respect to receptor binding and antagonistic properties of mEGF(33-42). Alanine scanning of non-conserved residues in the N-terminal half of mEGF(33-42) caused loss of biological activity with respect to cell attachment, receptor binding and migratory response. Substitution of alanine for serine (position 6) caused loss of laminin-specific cell attachment and receptor binding activities. However, the peptide did stimulate migration suggesting that this peptide may be a non-specific stimulator of migration. In contrast, alanine substitution for the C-terminal Cys-S-Acm had no apparent effect on the attachment or receptor binding activities of the peptide but generated an agonist from the antagonist parent. Comparison of the modelled folds of the alanine containing peptides revealed the presence of significant helical content in those peptides capable of stimulating migration and suggests that a reduction in bulk in the N-terminal residues is not conducive to adopting a productive binding conformation.

Alanine↗
PubMed2000

Yellow nail syndrome presenting as non-immune hydrops: second case report.

The yellow nail syndrome is characterized by slowly growing yellow discolored nails and lymphoedema, with onset generally after puberty. We report on a newborn infant who, at 23 weeks, was found to have hydrops on antenatal ultrasonography and bilateral chylothorax at delivery. His mother has the yellow nail syndrome, with typical nail changes, and bronchiectasis. There seemed to be no other etiology for the non-immune hydrops, and this is the second documented case of the prenatal manifestation of this condition.

Adult↗
PubMed2000

Myelination in the splenium of the corpus callosum in adult male and female rats.

Previous work reported increases in the number of myelinated axons in the splenium of the rat corpus callosum between 25 and 60 days of age. In the present study, we quantified the area occupied by myelinated axons using a light microscopic point counting technique at 60, 120 and 180 days. Myelinated axons increased across these ages (p=0.001). Thus, myelination of the rat corpus callosum persists well into adulthood.

Age Factors↗
PubMed2000

Binding properties of octaaminocryptands.

Complexation and protonation equilibria were studied in aqueous solution for a new range of aminocryptand ligands, N(CH2CH2NHCH2RCH2NHCH2CH2)3N, (R = m-xylyl, p-xylyl, 2,5-furan, 2,6-pyridine) and demonstrate that stability constants for first transition series ions Co2+ to Zn2+ are relatively high. X-ray crystallography shows that the cryptands are reasonably well preorganized for complexation. The furan-spaced cryptand L6.H2O crystallizes in the rhomobohedral space group R3 (no. 148) with a = 14.645(1), b = 14.645(1), and c = 25.530(4) A, whereas the m-xylyl-spaced cryptand L4 crystallizes in the triclinic space group P1 (no. 2) with a = 9.517(1), b = 15.584(2), and c = 23.617(4) A. The highest formation constant (log beta21 = 33.07) is observed for the dicopper cryptate of a pyridine-spaced cryptand, suggesting involvement in complexation of donors from the spacer link. This pyridine-spaced host also shows good selectivity for copper(II) over zinc(II), making it a possible candidate for treatment of copper-excess pathology.

Journal Article↗
PubMed2000

The expression of membrane-associated 67-kDa laminin receptor (67LR) is modulated in vitro by cell-contact inhibition.

The interaction of cells with their substratum is an important determinant of cell behaviour, influencing attachment, proliferation, and motility. Such interactions are mediated by cell surface receptors which bind to attachment factors, like the glycoprotein laminin in basement membranes. We have previously shown that expression of the 67-kDa laminin receptor (67LR) is elevated in proliferating retinal microvasculature compared with mature, quiescent vessels. Here, we examined 67LR mRNA and protein expression in primary cultures of retinal microvascular endothelial cells (RMEC) and in the breast cancer cell-line T47D during stages of contact inhibition. In both cell types, the expression levels of 67LR mRNA and membrane-associated 67LR protein were significantly increased during the proliferative phases of monolayer formation. As the cells achieved contact inhibition, 67LR expression was reduced to comparatively low levels. Thus, the differential expression of 67LR between dividing and contact-inhibited cells may indicate a role for this receptor during proliferative processes.

Blotting, Southern↗
PubMed2000

Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer.

BACKGROUND: Currently outer quadrant breast tumors are not felt to have significant drainage to the internal mammary nodal chain. We evaluated the incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy for all breast quadrants. METHODS: Eighty women were prospectively studied by technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative gamma probe identification of sentinel nodes. IMSN detected were surgically removed. RESULTS: Ten of 80 ( 12%) patients had IMSN identified in addition to axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients with positive IMSN also had positive AXSN. CONCLUSIONS: Patients undergoing lymphatic mapping for the management of breast cancer should have radiolabelled tracer and gamma probe sentinel node identification regardless of tumor location in the breast.

Biopsy↗
PubMed2000

Postoperative management of pediatric tracheostomy: results of a nationwide survey.

OBJECTIVE: A survey was undertaken to document the postoperative care of pediatric tracheostomies by otolaryngologists. STUDY DESIGN: This study represents the results of a national survey of 564 otolaryngologists covering a broad scope of postoperative pediatric tracheostomy issues considered for patients younger than 2 years and patients older than 5 years. RESULTS: Of the surveys sent, 134 responses were received, portraying a certain standard management scheme that seems to be used by most respondents. CONCLUSIONS: Very little difference was seen in respondents' management of patients younger than 2 years of age as compared with those who are older than 5 years. Furthermore, agreement between actual practice and published recommendations seems to vary with some management issues. The results of this study provide a means by which otolaryngologists may familiarize themselves with national trends in the postoperative management of pediatric tracheostomies.

Child↗
PubMed2000

Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.

PURPOSE: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharmacokinetics and toxicological properties of NX1838 were determined following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four biweekly bilateral injections of 0.10 mg per eye followed by two biweekly bilateral injections of 1.0 mg per eye. RESULTS: Plasma and vitreous humor NX1838 concentrations were linearly related to the dose administered. NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life. Vascular endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vitreous humor after 28 days was fully active. No toxicological effects or antibody responses were evident. CONCLUSIONS: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.

Animals↗
PubMed2000

Structural investigations of the CuA centre of nitrous oxide reductase from Pseudomonas stutzeri by site-directed mutagenesis and X-ray absorption spectroscopy.

Nitrous oxide reductase is the terminal component of a respiratory chain that utilizes N2O in lieu of oxygen. It is a homodimer carrying in each subunit the electron transfer site, CuA, and the substrate-reducing catalytic centre, CuZ. Spectroscopic data have provided robust evidence for CuA as a binuclear, mixed-valence metal site. To provide further structural information on the CuA centre of N2O reductase, site directed mutagenesis and Cu K-edge X-ray absorption spectroscopic investigation have been undertaken. Candidate amino acids as ligands for the CuA centre of the enzyme from Pseudomonas stutzeri ATCC14405 were substituted by evolutionary conserved residues or amino acids similar to the wild-type residues. The mutations identified the amino acids His583, Cys618, Cys622 and Met629 as ligands of Cu1, and Cys618, Cys622 and His626 as the minimal set of ligands for Cu2 of the CuA centre. Other amino acid substitutions indicated His494 as a likely ligand of CuZ, and an indirect role for Asp580, compatible with a docking function for the electron donor. Cu binding and spectroscopic properties of recombinant N2O reductase proteins point at intersubunit or interdomain interaction of CuA and CuZ. Cu K-edge X-ray absorption spectra have been recorded to investigate the local environment of the Cu centres in N2O reductase. Cu K-edge Extended X-ray Absorption Fine Structure (EXAFS) for binuclear Cu chemical systems show clear evidence for Cu backscattering at approximately 2.5 A. The Cu K-edge EXAFS of the CuA centre of N2O reductase is very similar to that of the CuA centre of cytochrome c oxidase and the optimum simulation of the experimental data involves backscattering from a histidine group with Cu-N of 1.92 A, two sulfur atoms at 2.24 A and a Cu atom at 2. 43 A, and allows for the presence of a further light atom (oxygen or nitrogen) at 2.05 A. The interpretation of the CuA EXAFS is in line with ligands assigned by site-directed mutagenesis. By a difference spectrum approach, using the Cu K-edge EXAFS of the holoenzyme and that of the CuA-only form, histidine was identified as a major contributor to the backscattering. A structural model for the CuA centre of N2O reductase has been generated on the basis of the atomic coordinates for the homologous domain of cytochrome c oxidase and incorporating our current results and previous spectroscopic data.

Amino Acid Sequence↗
PubMed2000

Effects of the anti-migraine drug sumatriptan on muscle energy metabolism: relationship to side-effects.

Sumatriptan succinate (Imitrex) is a 5-HT (5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5-20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.

Adenosine Triphosphate↗
PubMed2000

Antibody response to Burkholderia cepacia in patients with cystic fibrosis colonized with Burkholderia cepacia and Pseudomonas aeruginosa.

INTRODUCTION: This study was designed to determine the relationship between formation of serum antibodies to lipopolysaccharide (LPS) core antigen of Burkholderia cepacia and pulmonary colonization with B. cepacia and Pseudomonas aeruginosa in patients with cystic fibrosis (CF), and to define if an enhanced host humoral immune response to B. cepacia was related to a poor clinical outcome. METHODS: Serum IgG to B. cepacia LPS core antigen was measured in adult cystic fibrosis patients colonized with B. cepacia and P. aeruginosa, and serial titres were measured in 13 B. cepacia and 41 P. aeruginosa colonized patients followed prospectively over 18 months. RESULTS: The median B. cepacia antibody titre was significantly greater in the patients colonized with B. cepacia compared to those colonized with P. aeruginosa, a group which grew B. cepacia intermittently from their sputum. and nine healthy controls. The median antibody titre at recruitment into the study was significantly greater in patients who later went into exacerbations compared with those who remained clinically stable. but there was no difference between B. cepacia antibody titres in patients who died and those who survived the study duration. DISCUSSION: The degree of overlap of serum IgG levels to B. cepacia LPS core antigen in cystic fibrosis patients colonized with B. cepacia and P. aeruginosa does not allow this antibody to be used in a clinical context to define infection status. The magnitude of the humoral response to B. cepacia may influence occurrence of pulmonary exacerbations, but a more exuberant humoral immune response to B. cepacia core LPS is not the mechanism by which pulmonary deterioration occurs.

Adolescent↗
PubMed2000

Brain aging and midlife tofu consumption.

OBJECTIVE: To examine associations of midlife tofu consumption with brain function and structural changes in late life. METHODS: The design utilized surviving participants of a longitudinal study established in 1965 for research on heart disease, stroke, and cancer. Information on consumption of selected foods was available from standardized interviews conducted 1965-1967 and 1971-1974. A 4-level composite intake index defined "low-low" consumption as fewer than two servings of tofu per week in 1965 and no tofu in the prior week in 1971. Men who reported two or more servings per week at both interviews were defined as "high-high" consumers. Intermediate or less consistent "low" and "high" consumption levels were also defined. Cognitive functioning was tested at the 1991-1993 examination, when participants were aged 71 to 93 years (n = 3734). Brain atrophy was assessed using neuroimage (n = 574) and autopsy (n = 290) information. Cognitive function data were also analyzed for wives of a sample of study participants (n = 502) who had been living with the participants at the time of their dietary interviews. RESULTS: Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption. A similar association of midlife tofu intake with poor late life cognitive test scores was also observed among wives of cohort members, using the husband's answers to food frequency questions as proxy for the wife's consumption. Statistically significant associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios comparing endpoints among "high-high" with "low-low" consumers were mostly in the range of 1.6 to 2.0. CONCLUSIONS: In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life.

Aged↗
PubMed2000

Ras-GAP binding and phosphorylation by herpes simplex virus type 2 RR1 PK (ICP10) and activation of the Ras/MEK/MAPK mitogenic pathway are required for timely onset of virus growth.

We used a herpes simplex virus type 2 (HSV-2) mutant with a deletion in the RR1 (ICP10) PK domain (ICP10DeltaPK) and an MEK inhibitor (PD98059) to examine the role of ICP10 PK in virus growth. In HSV-2-infected cells, ICP10 PK binds and phosphorylates the GTPase activating protein Ras-GAP. In vitro binding and peptide competition assays indicated that Ras-GAP N-SH2 and PH domains, respectively, bind ICP10 at phosphothreonines 117 and 141 and a WD40-like motif at positions 160 to 173. Binding and phosphorylation did not occur in cells infected with ICP10DeltaPK. GTPase activity was significantly lower in HSV-2- than in ICP10DeltaPK-infected cells. Conversely, the levels of activated Ras and mitogen-activated protein kinase (MAPK), and the expression and stabilization of the transcription factor c-Fos were significantly increased in cells infected with HSV-2 or a revertant virus [HSV-2(R)] but not with ICP10DeltaPK. PD98059 inhibited MAPK activation and induction-stabilization of c-Fos. Expression from the ICP10 promoter was increased in cells infected with HSV-2 but not with ICP10DeltaPK, and increased expression was ablated by PD98059. ICP10 DNA formed a complex with nuclear extracts from HSV-2-infected cells which was supershifted by c-Fos antibody and was not seen with extracts from ICP10DeltaPK-infected cells. Complex formation was abrogated by PD98059. Onset of HSV-2 replication was significantly delayed by PD98059 (14 h versus 2 h in untreated cells), a delay similar to that seen for ICP10DeltaPK. The data indicate that Ras-GAP phosphorylation by ICP10 PK is involved in the activation of the Ras/MEK/MAPK mitogenic pathway and c-Fos induction and stabilization. This results in increased ICP10 expression and the timely onset of HSV-2 growth.

Amino Acid Motifs↗
PubMed2000

Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time.

OBJECTIVES: To compare the laboratory and clinical outcome of patients who received solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). METHODS: A randomized, double-blinded study to assess the ability of SDP and FFP to reduce a prolonged prothrombin time (PT) to </=15 s in patients with acquired coagulation deficits. RESULTS: 45 patients (22 SDP vs. 23 FFP) were treated with 71 infusions. There were no significant differences in mean dose of plasma infused (7.8 ml/kg for SDP vs. 8.0 ml/kg for FFP, p = 0.46), percentage of patients who corrected their PT to </=15 s (32% for SDP vs. 26% for FFP, p = 0.67), or percentage of patients whose bleeding ceased (27% for SDP vs. 22% for FFP). CONCLUSION: No clinical or statistically significant differences were observed after infusion with SDP or FFP in patients with acquired coagulation deficits.

Adult↗
PubMed2000

Uncontrolled oxygen administration and respiratory failure in acute asthma.

STUDY OBJECTIVES: To determine if 100% oxygen administration adversely influences gas exchange in acutely ill asthmatic subjects. DESIGN: Prospective preinterventional and postinterventional comparison. SETTING: University hospital emergency department. PATIENTS: Thirty-seven asthmatic subjects seeking care for symptomatic exacerbations. INTERVENTIONS: Twenty minutes of 100% oxygen administration by face mask. MEASUREMENTS AND RESULTS: Arterial blood gases and FEV(1) were measured before and during the last minute of oxygen administration. On presentation, the subjects had moderately severe airway obstruction (FEV(1), 49.1 +/- 3.6% of predicted); hypocarbia (PaCO(2), 36.8 +/- 1.1 mm Hg); hypoxemia (PaO(2), 70.2 +/- 2.5 mm Hg); and respiratory alkalosis (pH, 7.43 +/- 0.01). During oxygen breathing, 25 patients (67.6%) experienced elevations in PaCO(2) ranging from 1 to 10 mm Hg (mean, 4.1 +/- 0.6 mm Hg; p = 0.0003). The increase was considered to be a physiologic manifestation of the Haldane effect (ie, < or = 2 mm Hg) in 10 subjects, but in the remaining 15 subjects (40.5% of the total studied), the elevation represented worsening gas exchange. In seven of these patients (46.7%), hypercapnic respiratory failure developed (PaCO(2) before oxygen, 39.6 +/- 0.6; during oxygen, 44.7 +/- 0.7 mm Hg; p = 0.005), and in six patients (40%), it worsened (PaCO(2) before oxygen, 46.8 +/- 1.9; during oxygen, 52.0 +/- 3.1 mm Hg; p = 0.03). In general, the tendency toward hypercarbia was the greatest in the participants with the most severe airway obstructions. CONCLUSIONS: Our data demonstrate that the administration of 100% oxygen to acutely ill asthmatics may adversely influence carbon dioxide elimination.

Acute Disease↗