Search PubMed⌕ Search

Biomedical subjects

A Morris

Publications and source records attributed to A Morris.

At least 127 records · Page 7Linked to original sources
PubMed1997

Measurement of menadione-mediated DNA damage in human lymphocytes using the comet assay.

The model quinone compound menadione has been used to study the effects of oxidative stress in mammalian cells, and to investigate the mechanism of action of the quinone nucleus which is present in many anti-cancer drugs. We have used the alkaline single cell gel electrophoresis assay (comet assay) to investigate the effects of low doses of this compound on isolated human lymphocytes. We found that concentrations of menadione as low as 1 microM were sufficient to induce strand breaks in these cells. Pre-incubation with the NAD(P)H quinone oxidoreductase inhibitor dicoumarol, enhanced the production of menadione-induced strand breaks. In contrast, the metal ion chelator 1,10-phenanthroline inhibited formation of strand breaks, although prolonged incubation with 1,10-phenanthroline in combination with menadione resulted in an increase in a population of very severely damaged nuclei. A marked variation in the response of lymphocytes from different donors to menadione, and in different samples from the same donor was also observed.

Antioxidants↗
PubMed1996

Membrane binding of phospholipases C-beta 1 and C-beta 2 is independent of phosphatidylinositol 4,5-bisphosphate and the alpha and beta gamma subunits of G proteins.

We have measured the membrane binding affinities of purified phosphatidylinositol-specific phospholipases C-beta 1 and C-beta 2 to membranes of varying lipid composition using fluorescence methods. Our studies show that these proteins bind with affinities of 10(-5)-10(-4) M, with a small dependence on lipid type. Binding was relatively insensitive to the presence of phosphatidylinositol-specific phospholipases C-beta s' major physiological substrate, phosphatidylinositiol 4,5-bisphosphate, as well as the presence of Ca2+, which is required for activity. The presence of purified GTP gamma S-activated alpha 11 subunits of heterotrimeric guanine nucleotide binding proteins (G proteins) did not alter the membrane binding affinity of phosphatidylinositol-specific phospholipases C-beta 1, even though alpha 11 is a potent activator of this protein. Similarly, the presence of purified beta gamma subunits of G proteins did not alter the membrane association of phosphatidylinositol-specific phospholipases C-beta 2 even though these subunits strongly activate this isoform. These results argue against a recruitment model for PLC-beta activation by G proteins, negatively charged lipids, Ca2+, or substrate, and suggest that activation occurs through association of the membrane-bound species.

Amino Acid Sequence↗
PubMed1996

Myristoylated alanine-rich C kinase substrate (MARCKS) produces reversible inhibition of phospholipase C by sequestering phosphatidylinositol 4,5-bisphosphate in lateral domains.

The myristoylated alanine-rich protein kinase C substrate (MARCKS) is a major protein kinase C (PKC) substrate in many different cell types. MARCKS is bound to the plasma membrane, and several recent studies suggest that this binding requires both hydrophobic insertion of its myristate chain into the bilayer and electrostatic interaction of its cluster of basic residues with acidic lipids. Phosphorylation of MARCKS by PKC introduces negative charges into the basic cluster, reducing its electrostatic interaction with acidic lipids and producing translocation of MARCKS from membrane to cytoplasm. The present study shows that physiological concentrations of MARCKS (<10 microM) inhibit phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in phospholipid vesicles. A peptide corresponding to the basic cluster, MARCKS(151-175), produces a similar inhibition, which was observed with both PLC-delta1 and -beta1. Direct fluorescence microscopy observations demonstrate that the MARCKS peptide forms lateral domains enriched in the acidic lipids phosphatidylserine and PIP2 but not PLC, which accounts for the observed inhibition of PIP2 hydrolysis. Phosphorylation of MARCKS(151-175) by PKC releases the inhibition and allows PLC to produce a burst of inositol 1,4, 5-trisphosphate and diacylglycerol.

Animals↗
PubMed1996

Assessment of association of D3 dopamine receptor MscI polymorphism with schizophrenia: analysis of symptom ratings, family history, age at onset, and movement disorders.

Several studies have reported an association between schizophrenia and homozygosity for the MscI restriction site in exon 1 of the D3 dopamine receptor gene, but other studies have failed to find this association. Recent reports have suggested that the association is most salient in male patients with a family history of schizophrenia. We examined this restriction site in a group of schizophrenic patients (n = 84) and in normal controls (n = 77). Patients were subdivided according to demographic and clinical features, particular attention being paid to movement disorders. No significant difference in allelic or genotypic distribution was seen between the two groups. No association was seen between homozygosity and a positive family history, age at onset of illness, clinical subtype, negative symptom score, or movement disorder scores.

Chi-Square Distribution↗
PubMed1996

Carboxyl-terminal modification influences subunit assembly of sickle hemoglobin beta chains.

The subunit assembly properties of isolated beta and Des(His-146,Tyr-145) beta chains of sickle hemoglobin were investigated by isoelectric focusing over a protein concentration range from 500-125 microM in heme. Two components (presumably tetramer and monomer) and three components (designated tetramer, dimer and monomer) were visualized for beta s and Des(His-146,Tyr-145) beta s chains, respectively. Intensitometric quantitation of Des(His-146,Tyr-145) beta s chains demonstrated a similar distribution of all three structural components before and after the addition of their heteropartner alpha chains. This is in direct contrast to the reported preferential loss of Des(His-146,Tyr-145) beta A monomer species upon assembly and points to a major role of the beta 6 residue in the overall structural homeostasis of carboxylterminal modified human beta chains.

Biopolymers↗
PubMed1996

Primary structure of a cytosolic malate dehydrogenase of the amitochondriate eukaryote, Trichomonas vaginalis.

The nucleotide sequence of a gene coding for a 37 kDa subunit of a cytosolic malate dehydrogenase of Trichomonas vaginalis was established. The sequence of a gDNA clone and a cDNA clone, which lacked seven amino-terminal codons, were identical, indicating an absence of introns from the gene. Cell fractionation combined with sequencing of peptide fragments of the purified enzyme showed that the gene codes for an expressed cytosolic enzyme. The derived amino acid sequence was closely related to cytosolic malate dehydrogenases from animals and plants and from the eubacteria Thermus aquaticus and Mycobacterium leprae and was more distant from the enzyme of mitochondria and from Escherichia coli and certain other eubacteria. In phylogenetic reconstructions this enzyme shared a most recent common ancestor with other cytosolic enzymes.

Amino Acid Sequence↗
PubMed1996

A practical strategy for detection of major chromosome aneuploidies using ratio-mixing fluorescence in situ hybridization.

We describe the use of ratio-mixing FISH to visualize simultaneously probe sets specific for chromosomes 13, 18 and 21 as well as both sex chromosomes in uncultured lymphocytes and amniocytes. This method has the advantage of a smaller sample requirement than uni-colour FISH and potential for analysis of a larger number of chromosome aneuploidies using a minimum number of different probe haptenization and detection systems. An unselected series of uncultured lymphocytes and amniocytes was used to investigate the reliability of ratio-mixing FISH for diagnostic applications. The results indicate that the five-colour ratio-mixing FISH is a reliable technique and can be used for simultaneous detection of major aneuploidies. However, as a diagnostic approach, the strategy of using a three-colour ratio-mixing FISH and a dual colour to detect the five clinically important aneuploidies on two slides from the same sample, appears to be simpler and more practical.

Aneuploidy↗
PubMed1996

Empyema thoracis and lung abscess due to Gemella morbillorum.

A case of empyema and lung abscess in an elderly patient who presented with clinical features of congestive cardiac failure is described. Gemella morbillorum was cultured from pleural exudate found postmortem to be associated with a lung abscess. To our knowledge this is the first reported case of infection with this organism in this setting. We discuss the clinical spectrum and management of infection with this infrequently encountered organism.

Aged↗
PubMed1996

Gender and ethnic differences in social constraints among a sample of New York City police officers.

Gender and ethnic differences in social constraints on and off the job among a sample of 372 police officers was examined. Positive and negative social interactions with supervisors and coworkers, and perceptions of the work environment as well as support and resentment of the job from family and significant others, was included. As hypothesized, women and minority men reported more negative social interactions on the job, such as criticism, bias, and sexual harassment. Few differences were observed for positive social interactions on or off the job, and where differences emerged, women and minority men reported more favorable social interactions. These findings are discussed in terms of implications for intervention, policy, and future research.

Adult↗
PubMed1996

Longitudinal genotype analysis and quantification of hepatitis C virus in haemophilic patients receiving interferon-alpha therapy.

Haemophilic patients have a high prevalence of hepatitis C virus (HCV) infection because of the use of unsterilized clotting factor concentrates. Six major genotypes of HCV have been distinguished so far, with epidemiological evidence suggesting that genotypes 1-3 are common in the indigenous UK and US populations. The aim of this study was to analyse the changes in viral load and composition of the HCV quasispecies in haemophilic patients receiving therapy with interferon-alpha (IFN-alpha) using the four major methods currently available for HCV genotyping. The most consistent genotype results were obtained using restriction fragment-length polymorphism (RFLP) analysis when compared with the DNA sequence analysis, and showed that the dominant genotype can change in patients with mixed genotype infections treated with IFN-alpha. This study indicates the difficulties in studying this group of patients with mixed HCV genotype infections, and that frequent sampling is necessary, together with viral load measurement to monitor response to IFN-alpha therapy.

Adult↗
PubMed1995

An n-allele model for progressive amplification in the FMR1 locus.

An n-allele model is developed for the FMR1 locus, which causes the fragile X syndrome, where n is the number of triplet repeats in the first exon. Frequencies in the general population and in index families are used to generate an n to n + delta transition matrix that predicts specific risks in satisfactory agreement with observation. However, until sequencing distinguishes between stable and unstable alleles with the same value of n, it is premature to infer whether allelic frequencies at the FMR1 locus are at equilibrium or, as some have suggested, are evolving toward higher frequencies of the pathogenic allele.

Alleles↗
PubMed1995

Head injuries in lateral impact collisions.

Individual non-minor injuries (Abbreviated Injury Scale (AIS) > or = 2) to the head that occurred to belted and unbelted drivers and front seat passengers on the stuck side of impacted vehicles were examined. Injury type, injury combination, collision severity in relation to type of injury as well as contact sources were assessed. Forty-eight percent of injuries were moderate in severity (AIS 2). The most common type of injury was the diffuse brain injury, typically marked by a short period of unconsciousness, which occurred in collisions of lower severity than focal brain and skull fracture injuries. One-hundred and five out of 216 (48.6%) of contact sources for all injury types originated from outside the vehicle and such exterior sources were more likely to result in high severity injuries. Thirty percent of injuries resulted from head contacts with other vehicles. The most frequent vehicle interior contact source was the side window glass. Diffuse injuries tended to occur independently of other injury types and were more likely to originate from an interior rather than exterior contact. Preventative measures for head injury reduction in lateral collisions are discussed. Overall, the data show that proposed and present European and U.S. lateral impact test methods do not address many head injury problems such as those included in this study.

Abbreviated Injury Scale↗