Search PubMed⌕ Search

Biomedical subjects

N V McFerran

Publications and source records attributed to N V McFerran.

18 recordsLinked to original sources
PubMed1997

Dinucleotide and stop codon frequencies in single-stranded RNA viruses.

To identify potential selection pressures which lead to RNA sequence conservation, we examined the occurrence rates of dinucleotides in 64 single-stranded RNA virus genomes. These viruses may offer a particular insight into these pressures since their RNA-dependent RNA polymerases lack proofreading capability. This potentiates introduction of mutations into their genomes, yet unidentified selection processes conserve the genomes to a large degree. We report a strong inverse correlation between the C+G content and the occurrence of the CpG dinucleotide (r=0.71) in the RNA virus genomes, in contrast to earlier reports (Karlin et al., 1994, Journal of Virology 68, 2889-2897). We also detected significant suppression of UpA, correlating inversely with genomic U+A content. These suppressions are coupled with over-representation of the complementary pair of dinucleotides, CpA and UpG. In addition, we highlight the fact that odds ratios for dinucleotides are not independent variables, a situation apparently not widely appreciated in the literature. This led us to view the over-representation of CpA and UpG as a consequential outcome of UpA and CpG suppression in the virus genomes. Potential factors influencing these disturbances are discussed. In addition, higher than random incidence was observed for 'out-of-frame' stop codons in the viral RNA genomes, with some preferences for individual codons being exhibited by certain virus groups. The UAG codon appeared more common in the +1 frame, the UGA in the -1 frame.

Base Sequence↗
PubMed1996

Murine epidermal growth factor peptide (33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells.

A laminin-antagonist peptide, comprising amino acids 33-42 of murine epidermal growth factor (mEGF-(33-42)), interacts with a breast cancer- and endothelial cell-associated receptor, which is specific for the laminin B1 chain sequence, CDPGYIGSR-NH2 (Lam.B1-(925-933)), and is immunologically similar to a previously described 67-kDa laminin receptor. In whole cell receptor assays, mEGF-(33-42), Lam. B1-(925-933), and laminin all have IC50 values for displacement of 125I-laminin in the range 1-5 nM. Cell attachment to solid-phase laminin is also blocked by all three ligands, but in contrast to the receptor assays, mEGF-(33-42) or Lam.B1-(925-933), while equipotent with each other, were less effective than laminin. The concentrations of the peptides required to produce half-maximal inhibition of attachment were in the range 230-390 nM, but those for laminin were 1000-fold lower, in the range 0.2-0.3 nM. Like laminin, solid-phase mEGF-(33-42) supports cell attachment, and this ability is blocked by anti-67-kDa receptor antibodies. Modeling studies suggest that both peptides present a tyrosyl and an arginyl residue on the same face of a right-handed helical fold with elliptical cross-section.

Amino Acid Sequence↗
PubMed1995

Murine epidermal growth factor (EGF) fragment (33-42) inhibits both EGF- and laminin-dependent endothelial cell motility and angiogenesis.

Laminin, murine epidermal growth factor (mEGF), and the synthetic laminin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of murine laminin, CDPGY1GSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF33-42 (a linear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S-Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic chick endothelial cells, mEGF33-42 blocks both EGF- and laminin-stimulated locomotion of endothelial cells. In vivo, mEGF33-42 also blocks both laminin- and mEGF-induced angiogenesis in the chick. In the human cell line. Lam.B1(925-933) has an additive effect in coincubation with either laminin or mEGF, but it blocks their effects in the chick cells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but blocks laminin-induced angiogenesis. Thus, mEGF33-42 acts as a general laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonist in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF33-42 may be the source of the antagonistic effects seen with this peptide as compared with the laminin fragment. These findings have important implications in the design of human antiangiogenic agents, and also in the use of chick models in the study of human disease.

Amino Acid Sequence↗
PubMed1992

Pre-beta high-density lipoprotein determined by immunoblotting with chemiluminescent detection.

We describe a novel assay of pre-beta high-density lipoprotein (HDL), a unique apolipoprotein A-I (apo A-I)-containing lipoprotein particle. The pre-beta and alpha lipoproteins are separated by electrophoresis in agarose and transferred onto a membrane by capillary blotting. The membrane blot is sequentially incubated with sheep anti-human apo A-I antiserum and then with a conjugate of rabbit anti-sheep immunoglobulin and horseradish peroxidase. Chemiluminescence formed by the peroxidase-catalyzed oxidation of luminol in the presence of an enhancer is captured on photographic film, and the pre-beta HDL band is quantified by transmission densitometry. The assay is calibrated with standards prepared from a reference serum diluted in 9 mol/L urea. Within-batch precision (CV) at pre-beta HDL concentrations of 22.1 and 44.3 mg/L was 7% and 4.9% respectively. Pre-beta HDL contained 1.6% (0.65-2.6%, mean and range) of total serum apo A-I in 30 normolipidemic subjects.

Adult↗
PubMed1991

Conductance measurements in solid phase peptide synthesis. I. Monitoring coupling and deprotection in Fmoc chemistry.

Potentiated conductance shows promise for monitoring the progress of both coupling and deprotection reactions in solid phase peptide synthesis using Fmoc chemistry. Sterically hindered base may be added to the aprotic polar solvents used for synthesis, this induces ionisation of acids formed in the coupling and deprotection reactions, thus giving rise to a conductance signal in the solvent. Changes in this signal allow reactions occurring at the resin to be followed with no degradation of coupling efficiency.

Acylation↗
PubMed1985

A survey of serum antibodies to eight common viruses in psychiatric patients.

Serum antibody titres to eight neurotropic viruses were measured by enzyme immunoassay in 450 psychiatric in-patients and 143 controls. A seasonal variation in schizophrenic births was observed, with a peak incidence between March and April. Both herpes simplex virus and cytomegalovirus antibody titres correlated with age and, when this was controlled for, no significant differences emerged between any patient group and the controls. Mumps antibody titres were significantly lower in patients with mental subnormal and neurosis or personality disorder; measles and rubella antibody titres were lower in male but not female mentally handicapped patients; males had lower antibody titres to mumps, cytomegalovirus and Epstein-Barr virus than females in all groups. A decrease in mumps antibody titres was also found in schizophrenics if the medication factor was excluded. These low antibody titres may indicate an impaired immune response. Thus perinatal or childhood subclinical viral infections of the central nervous system, particularly of mumps, might lead to a range of possible psychiatric outcomes in later life.

Adolescent↗
PubMed1985

Serum and CSF antibody titres to seven common viruses in schizophrenic patients.

CSF and matched serum antibody titres to seven common viruses were measured in 20 chronic schizophrenic patients, and 17 of these were age and sex-matched with orthopaedic controls. CT scans were carried out in patients and age and sex-matched radiological controls. There was a trend for CSF viral antibody titres (except CMV, HSV and VZV) to be decreased in the patients compared to controls, statistically significant for mumps and IgG. The CSF/serum ratios showed a reduction in the patients, compared to controls, statistically significant for measles and rubella as well as mumps and IgG. Cerebral ventricular size was significantly increased in the patients compared to controls, but did not correlate with any of the antibody data. These findings suggest that there is a reduced immune response to certain common viruses in the CNS of schizophrenic patients, but possible effects of institutionalisation or current medication could only be adequately excluded by further prospective studies.

Adult↗
PubMed1981

Glyceraldehyde-3-phosphate dehydrogenase.

Conflicting experimental evidence of the pathway of catalysis for the enzyme from rabbit, pig and lobster muscle tissues is reviewed. Transient kinetic studies with the enzyme from rabbit muscle are presented. The results are shown to be consistent with the double-displacement mechanism of catalysis originally proposed by Segal & Boyer (1953). The rate constant for combination of the aldehyde form of the substrate with the NAD+ complex of the enzyme is about 3 X 10(7) M-1 S-1, and for all four subunits of the molecule the rate constant for hydride transfer in the ternary complex formed is greater than 10(3) S-1, consistent with their simultaneous participation in catalysis. Recent steady-state kinetic studies with the rabbit muscle enzyme, in contrast to earlier studies, also provide evidence to support the Segal-Boyer pathway if the kinetic effects of the negative cooperativity of NAD+ binding are taken into account. Experimental data for the binding of NAD+ to the enzyme from muscles and from Bacillus stearothermophilus, and their interpretations, are also briefly reviewed. The information currently available from X-ray crystallography regarding the structures of holoenzyme and apoenzyme from B. stearothermophilus and lobster muscle is outlined.

Animals↗