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Biomedical subjects

J M Harris

Publications and source records attributed to J M Harris.

At least 19 recordsLinked to original sources
PubMed1992

Reduction of fibrinogen adsorption on PEG-coated polystyrene surfaces.

Reduction of protein adsorption by coating surfaces with polyethylene glycol (PEG) is well documented. The present work has four goals related to these previous studies: first, to develop chemistry providing densely packed, covalently bound PEG on polystyrene (PS); second, to determine the ability of these modified surfaces to reject fibrinogen; third, to compare the protein-rejecting ability of branched and linear PEGs; and fourth, to examine the utility of an ELISA-type procedure for measuring protein adsorption. It was found that PEG-epoxide could be readily coupled to amine groups of poly(ethylene imine) (PEI), which had been preadsorbed onto an oxidized PS surface. The PEG groups on branched PEGs appear to act as an excluded volume to repel proteins, similar to arguments previously raised for linear PEGs. The results of protein adsorption studies showed that fibrinogen adsorption is significantly reduced by coating polystyrene with either linear or branched PEGs of 1500 to 20,000 in molecular weight. The ELISA technique was found to be equivalent in sensitivity to radiolabeled fibrinogen for estimating adsorption levels. It is expected that PEG-coated PS will have much utility in a variety of biomedical applications.

Adsorption↗
PubMed1992

Chlorambucil-monoglutathionyl conjugate is sequestered by human alpha class glutathione S-transferases.

The spontaneous reaction of 110 microM chlorambucil (4-[p-[bis(2-chloroethyl)amino]phenyl]-butanoic acid; CHB) with 5 mM GSH at 37 degrees C in physiological phosphate-buffered saline for 35 min gave primarily the monoglutathionyl derivative, 4-[p-[N-2-chloroethyl,N-2-S-glutathionylethyl]amino]phenyl]-butano ic acid; CHBSG) and the diglutathionyl derivative, 4-[p-[bis(2-S-glutathionylethyl]amino]phenyl]-butanoic acid (CHBSG2) with small amounts of the hydroxy-derivatives: 4-[p-[N-2-chloroethyl,N-2-hydroxy-ethyl]amino] phenyl-butanoic acid (CHBOH) and 4-[p-[N-2-S-glutathionylethyl-2-hydroxyethyl]amino]phenyl]-butanoi c acid (CHBSGOH). The inclusion of approximately physiological amounts of human glutathione S-transferases (GSTs) A1-1, A2-2, P1-1, M1a-1a M3-3 or P1-1 (for nomenclature see Mannervik et al., 1992, Biochem. J., 282, 305) had little or no catalytic effect on these reactions as determined by loss of CHB. However, GTSs A1-1 and A2-2 were associated with a significant increase of CHBSG at the expense of CHBSG2 + CHBSGOH suggesting that these GTs sequestered CHBSG at the active site. This interpretation was supported by inhibition studies which showed that CHBSG was a pure competitive inhibitor of the activity of GSTs A1-1 and A2-2 towards 1-chloro-2,4-dinitrobenzene with Ki's of 1.3 and 1.2 microM respectively. GSH transferases P1-1 and M1a-1a were inhibited by CHBSG above 10 microM. Incubation of 2 microM CHB, a concentration which may be of more significance for chemotherapy, in the presence or absence of GST A1-2 (20-50 microM) showed catalysis of GSH monoconjugation equivalent to 18% of the spontaneous rate. However, the dominant effect again was the sequestration of CHBSG which reached 74.3 +/- 1.5 (SEM)% of the total reactants at 60 min compared to 28.9 +/- 0.3(SEM)% in controls. CHBSG, although possessing a potential electrophilic centre, showed no detectable alkylation of plasmid DNA but indirect evidence was obtained that it alkylated other cellular macromolecules. It is concluded that the contribution of GSTs to catalysis of CHB detoxication will depend on factors not previously considered, namely the relative molarities of CHB, CHBSG and GSTs, and the cellular capacity to excrete CHBSG to relieve product inhibition.

Chlorambucil↗
PubMed1992

The human glutathione S-transferase supergene family, its polymorphism, and its effects on susceptibility to lung cancer.

Cytosolic glutathione S-transferases (GSTs) are a supergene family of dimeric enzymes capable of detoxifying a number of carcinogenic electrophiles. Of the numerous components of tobacco smoke, the polycyclic aromatic hydrocarbons appear to be the principal compounds that yield substrates for these enzymes, GSTM1-1 being effective with those PAH derivatives so far studied; however, the gene locus for GSTM1 is polymorphic, containing two well-characterized expressing genes and a null allele. Use of cDNA for GSTM1-1 or appropriate fragments of genomic clones as probes in Southern blots indicated that the null allele is due to the absence of GSTM1. In preliminary experiments, described here, with lung tissue from smokers, levels of 32P-postlabeled nuclease P1-enhanced DNA adducts were inversely correlated with levels of antigen cross-reacting with antibody to GSTM1-1, suggesting that initiation depends on the expression of GSTM1-1. Since similar quantities of DNA adducts and GSTM1-1 activity have been shown to occur in bronchial and peripheral lung, however, the development of malignancy, which is usually in the bronchial region, presumably depends on additional factors that bring about promotion and progression, which are not necessarily affected by GSTM1 expression. Two epidemiological studies have been carried out in which a possible correlation between the absence of GSTM1 and lung cancer incidence is considered. In the first, involving a U.S. population sample, smokers with and without lung cancer were phenotyped, and a highly significant correlation between the absence of GSTM1-1 activity and adenocarcinoma of the lung was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Efficiency of stereopsis in random-dot stereograms.

The statistical efficiency of stereopsis was investigated by measurement of the discriminability d' of a step edge in depth in a random-dot stereogram and its comparison with d' calculated for an ideal observer model. Efficiencies of approximately 20% were found for stimuli with very few (less than 30) dots. As the number of dots was increased, efficiency fell markedly to 2% and below. Over the ranges explored in this study, there was little variation in efficiency with changes in dot density (with dot number constant) or stimulus size. Efficiency loss was also found to be almost entirely due to incomplete use of the available information rather than to intrinsic observer variance. Results were compared with two simple models that implemented possible detection strategies.

Depth Perception↗
PubMed1992

Synthesis of dye conjugates of ethylene oxide-propylene oxide copolymers and application in temperature-induced phase partitioning.

Synthesis of conjugates of the ethylene oxide/propylene oxide copolymer UCON 50-HB-5100 and the triazine dyes Cibacron Blue F3G-A and Procion Yellow HE-3G is described. The UCON-dye conjugate of Procion Yellow HE-3G is used as a ligand for affinity partitioning of glucose-6-phosphate dehydrogenase from bakers' yeast. The enzyme is first partitioned in a two-phase system composed of UCON, UCON-ligand and dextran, and the two phases isolated in separate containers. A small amount of salt is then added to the upper phase, which contains the UCON-ligand-enzyme complex, and the temperature increased above the cloud point of the UCON polymer to give a new two-phase system. The new two-phase system consists of an upper salt/water phase containing free enzyme and a lower UCON/water phase containing free UCON-ligand. Temperature-induced phase partitioning is thus seen to be of much assistance in dissociating enzyme-ligand complex, recovering enzyme and recycling UCON-ligand.

Chemical Phenomena↗
PubMed1991

Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis.

Multiwavelength detection of laser induced fluorescence for dideoxynucleotide DNA sequencing with four different fluorophores and separation by capillary gel electrophoresis is described. A cryogenically cooled, low readout noise, 2-dimensional charge-coupled device is used as a detector for the on-line, on-column recording of emission spectra. The detection system has no moving parts and provides wavelength selectivity on a single detector device. The detection limit of fluorescently labeled oligonucleotides meets the high sensitivity requirements for capillary DNA sequencing largely due to the efficient operation of the CCD detector with a 94% duty cycle. Using the condition number as a selectivity criterion, multiwavelength detection provides better analytical selectivity than detection with four bandpass filters. Monte Carlo studies and analytical estimates show that base assignment errors are reduced with peak identification based on entire emission spectra. High-speed separation of sequencing samples and the treatment of the 2-dimensional electropherogram data is presented. Comparing the DNA sequence of a sample separated by slab gel electrophoresis with sequence from capillary gel electrophoresis and multiwavelength detection we find no significant difference in the amount of error attributable to the instrumentation.

Base Sequence↗
PubMed1991

A novel glutathione transferase (13-13) isolated from the matrix of rat liver mitochondria having structural similarity to class theta enzymes.

A rat liver mitochondrial-matrix fraction was prepared and shown to have 1-chloro-2,4-dinitrobenzene(CDNB)-metabolizing glutathione transferase (GST) activity. Further fractionation by sequential gel filtration, isoelectric focusing or chromatofocusing and hydroxyapatite chromatography yielded three GSTs of pI 9.3, 8.9 and 7.5, none of which bound to a GSH-agarose affinity matrix. Most of the activity was associated with the pI-9.3 form, which was selected for further study. Its activity was tested with the following potential substrates in addition to CDNB: 1,2-dichloro-4-nitrobenzene, p-nitrobenzyl chloride, trans-4-phenylbut-3-en-2-one, 1,2-epoxy-3-(p-nitrophenoxy)propane, ethacrynic acid, menaphthyl sulphate, cumene hydroperoxide, linoleic acid hydroperoxide and 4-hydroxynon-2-enal. Appreciable activity was obtained only with CDNB and ethacrynic acid (82 and 26 mumol/min per mg of protein respectively). The apparent Km for GSH, using 1 mM-CDNB, was 1.9 mM. The enzyme is a dimer of subunit Mr 26,500. It has a free N-terminus, which has enabled the first 33 amino acids to be sequenced. This portion of primary structure has a sequence in common with members of the Theta class of GSTs (eg. 36% identity with subunit 12) and also a sequence which might function as a mitochondrial import signal. It is novel and has been named 'GST 13-13'.

Amino Acid Sequence↗
PubMed1991

Zoonotic diseases of birds.

Numerous diseases are shared by birds and humans. Many of them are true zoonosis. Chlamydiosis, salmonellosis, and tuberculosis are the primary infectious diseases. Allergic alveolitis in humans, induced by exposure to bird dander and protein, is also of great significance. The other diseases are of less common occurrence or represent oddities. [Editor's note: However, the increased incidence of AIDS and the increased use of immune system-compromising medications in humans have resulted in a drastic increase in the zoonotic diseases. Formerly rare diseases are becoming more common.]

Alveolitis, Extrinsic Allergic↗
PubMed1991

Death and bereavement.

This chapter addresses normal and abnormal grief reactions, the stages of grief and mourning, and the different types of emotional support available to clients who have lost a pet. Also included is a brief list of suggestions for helping the veterinarian counsel those persons who may have an especially difficult task in accepting a pet's death: children and solitary adults.

Animals↗
PubMed1978

Diagnostic tests and Hodgkin's disease: a standardized approach to their evaluation.

We have analyzed a series of 124 young men with Hodgkin's Disease in an attempt to clarify the role of non-invasive tests in the staging evaluation. Data are presented in a way which permits comparison between series and application of the data to decision-making models. Analysis of the data shows our patients to have had primarily limited (stage I and II) disease. In our hands certain tests were quite accurate in predicting the absence of abdominal disease (lymphangiography, hepatic scintigraphy) as determined by laparotomy, but no study appeared to eliminate the need for laparotomy in this group. Data from several other large series are also presented in the same format. The data demonstrate a large variability between institutions in the predictive value of a positive lymphangiogram. Other studies, such as splenic scintigrams, appear to have more consistent predictive values. We encourage further use of this type of data presentation.

Adolescent↗
PubMed1977

Suid evolution and correlation of African hominid localities.

Recently discovered Plio-Pleistocene vertebrate assemblages have allowed complete systematic revision of the sub-Saharan African Suidae. New phylogenies are proposed for the 7 genera and 16 species of fossil and extant representatives. Suids are common elements of African Plio-Pleistocene faunas, and their evolutionary trends, particularly in the species Mesochoerus limnetes and Metridiochoerus andrewsi, are of great correlative value. Suid data are employed in a refinement of stratigraphic correlations at Omo Shungura, Olduvai, and east of Lake Turkana (formerly East Rudolf) and in a correlation of East African and South African sites, with important implications for interpretation of hominid evolution. The suid record also bears significantly on questions of theoretical evolutionary biology.

Africa↗
PubMed1977

Apicoectomy.

Explore the source record for details and available documents.

Apicoectomy↗
PubMed1976

Teratogenesis.

In this presentation the scope of the problem of teratogenesis and the essentials of teratology are briefly reviewed. The teratogenicity of any compound is a reflection of a complex interaction of the compound with both the maternal and fetal tissues, the genetic background of the fetus, and the time sequence of gestational events. Under such circumstances the implication of a single compound as a teratogen is difficult, a fact reflected in the high percentage of congenital morphologic abnormalities for which no cause can be ascribed. Four compounds--thalidomide, anticonvulsants, alcohol, and folic acid antagonists--with a known teratogenetic effect on the musculoskeletal system are discussed, as is the role of the orthopedic surgeon in teratology.

Abnormalities, Drug-Induced↗