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Biomedical subjects

L M Thompson

Publications and source records attributed to L M Thompson.

52 records · Page 3Linked to original sources
PubMed1985

An erythema infectiosum-like illness caused by human parvovirus infection.

In the spring of 1980, an epidemic of an illness that resembled erythema infectiosum occurred in Manitoba, Canada. We initiated prospective epidemiologic, clinical, and microbiologic studies of this illness among elementary-school children and their families. Initial microbiologic studies failed to identify the cause of the exanthem. After a similar illness associated with serologic evidence of human parvovirus infection occurred in London, stored specimens of 12 patients with exanthem were investigated for parvovirus infection. Eleven patients had parvovirus-specific IgM antibody, as did two family contacts and a teacher with nonexanthematous illnesses, and two asymptomatic family members. None of 28 children with measles or rubella had serologic evidence of recent parvovirus infection. Human parvovirus was detected by DNA hybridization and immune electron microscopy in the serum of one patient who later had a rash and in one unaffected family contact. Parvovirus DNA was also detected in the pharyngeal specimen of the teacher who was ill but did not have a rash. We conclude that human parvovirus infection can be asymptomatic or cause a variety of clinical manifestations, including nonexanthematous illness and an illness resembling erythema infectiosum.

Adult↗
PubMed1984

Cultural and institutional restrictions on dying styles in a technological society.

The starting medical advances of this century have created unparalleled opportunities for ill and suffering people, but these same forces have combined to make the experience of dying a terrifying, fearful, lonely vigil for many. Devoid of traditional myths, rituals, and family support, many patients now die in sterile institutional settings often appearing as mere appendages to life-supporting machines. This shift from the moral to the technical order manifests itself in doctors' fascination with gadgets, the emphasis upon parts of the body, and a concomitant blurring of distinctions concerning death, personhood, and individual rights. The patient is reduced to a secondary role in his or her own death, thus engendering a widespread desire for a sudden death. In light of these circumstances, health care personnel need to create circumstances that would give people more opportunities to die in styles commensurate with their life styles. Society must seriously study the implications of the unthinking treatment of people; and routines, policies, and procedures based on matters of mere efficiency and technological convenience must be replaced by those human and humane ceremonies, attitudes, and policies that must assure that technology's magnificent achievements do not obscure the human need for individuality and spiritual growth even during the dying process.

Attitude of Health Personnel↗
PubMed1984

Effects of adriamycin on supercoiled DNA and calf thymus nucleosomes studied with fluorescent probes.

The interaction of the antitumor drug Adriamycin with nucleotides, polynucleotides, RNA, calf thymus nucleosomes, and DNA (including pBR322 supercoiled DNA) has been studied using fluorescent probes. The lanthanide terbium is known to interact with guanine and xanthosine to produce high fluorescence enhancement. The nature of the interaction of the lanthanide with the heterocyclic ring in guanine appears to involve both the C-2 and N-7 groups. A striking decrease in fluorescence enhancement was observed with all of the polynucleotides, RNA, DNA, and nucleosomes after treatment with Adriamycin at molar ratios of 1:200 or less. It appears that Adriamycin interacts with the guanine ring, displacing or preventing terbium access to its second site of binding. However, with supercoiled DNA and nucleosomes, the displacement followed a destabilization of the helix at very low drug concentrations. The binding affinities of calf thymus DNA, pBR322 DNA, and calf thymus nucleosomes at 37 degrees for Adriamycin were of the same order of magnitude. Reaction with N-pyrene maleimide, a fluorescent probe which binds to histone H3, showed that Adriamycin interacted with the nucleosome to increase the binding of the probe (only, however, at drug ratios far greater than those required to produce effects with DNA). No compositional changes of supercoiled or nucleosomal DNA or nucleosomal histones were observed by agarose gel or sodium dodecyl sulfate:polyacrylamide gel electrophoresis, respectively. The classic intercalating agent, ethidium bromide, produced minimal displacement of the lanthanide from DNA, although an effect with RNA at high drug concentrations was observed.

Animals↗
PubMed1982

The interaction of platinum complexes with nucleosomes investigated with fluorescent probes.

The fluorescent probes, N,-(3-pyrene)maleimide, which is specific for histone H3, and terbium (Tb3+), which is specific for guanine single-stranded residues in DNA, are used to investigate the interaction of platinum complexes (cis- and trans-dichlorodiammineplatinum(II)) with rat liver and calf thymus nucleosomes. At low concentrations of the drug, lower than most of those reported previously in studies investigating the interaction of the drugs with isolated DNA, N-(3-pyrene)maleimide studies show that profound modifications occur near or in the cysteinyl binding site of histone H3. H3 dimer formation appears to be the cause of the change induced by trans-DDP; however, the effects observed with the cis-isomer do not seem to be correlated with dimer formation. At short incubation times, Tb3+ fluorescence shows small changes in DNA conformation, but they are slight when compared to the effect observed with proteins at the same length of incubation. SDS-polyacrylamide gels indicate some changes in protein composition, and agarose gels display a decrease in ethidium bromide staining of the cis-treated DNA. The results suggest that the protein portion, predominantly histone H3, as well as DNA are targets for the platinum derivatives in the nucleosome.

Animals↗
PubMed1981

Conformational changes in rat liver chromatin after liver regeneration.

N-Pyrenemaleimide, a fluorescent probe that specifically labels histone H3 of rat liver chromatin in situ, was used to monitor the accessibility of histone H3 in chromatin isolated from rat liver at different times during degeneration. At times of maximum DNA synthesis (18--24 h after hepatectomy), the accessibility of the probe was found to be markedly (40--50%) increased. This increase is abolished, however, by treatment of the chromatin fibres with high salt (2 M-NaCl) or detergent. Tryptophan fluorescence was also enhanced at points of maximum DNA synthesis, suggesting that some non-histone tryptophan-containing protein was being synthesized. The polarization of the labelled histone H3 is not markedly altered, suggesting that fibre aggregation or dissociation does not occur. Mononucleosomes extracted from sham-operated and hepatectomized animals did not exhibit any difference in binding to the probe. Also, analysis of the chromatin protein by electrophoresis on detergent- and acid/urea/ Triton-X-100-containing polyacrylamide gels showed no detectable difference in histone H3 : 1, H3 : 2 or H3 : 3 subclasses.

Animals↗
PubMed1981

Is life living? Defining death in a technological age.

Historically, humanity has assigned death to evil spirits, malevolent gods, and other supernatural agents; but by the eighteenth century, the scientific spirit began to manifest itself through more precise biologic definitions of death. Thanks to modern medical technology, these early scientific views, with their considerable margin for error, gave way in the twentieth century to criteria based on such diverse factors as total lack of response to external stimuli, absence of spontaneous muscular movements, absence of all reflexes, total collapse of the arterial blood pressure, flat electrocardiogram, and flat electroencephalograph tracings. Undoubtedly such difficult matters as organ transplants, wills, homicide, euthanasia, and abortion demand precise definitions of death; but modern medical advances have engendered visions of physical immortality with doctors as the arbiters who often define and determine death. Even so, such one-dimensional, scientific views fail to capture those nebulous social, religious, or spiritual definitions that pervade humanity's definition of death. Humanistic views of death resist the movement of death from the moral realm to a technological order that places people in a system, theory, or chart, where they are thus absolved from fear of freedom. Rather, humanistic definitions demand that humanity step beyond mechanistic definitions of death into a transcendent world of moral choices that guarantee human dignity and worth by ascribing meaning to life and death. These meanings counter the desiccating fear that something like biologic human might, through something called medical technology, defeat something called fate.

Attitude to Death↗
PubMed1980

The in situ labeling of histone H3 in chromatin by a fluorescent probe.

A sulfhydryl-specific fluorescent probe, N-3-pyrene maleimide, has been shown to label with high efficiency the sulfhydryl groups of histone H3 in nonsheared chromatin. The probe labels chromatin preparations obtained by mild homogenization or nuclease treatment of rat liver and mouse thymocyte, but not chick erythrocyte nuclei. Mononucleosomes from all nuclear preparations are labeled by the probe. The reaction is inhibited by prior reaction of the chromatin with N-ethyl maleimide. The reaction kinetics show fast and slow components representing reactions with cysteinyl sulfhydryl groups and lysyl epsilon-amino groups, respectively. Dissociation of the chromatin by urea (6 M) or sodium dodecyl sulfate (SDS) increases the fluorescence intensity (2-3 fold) and is maximal at approx. 0.01-0.02% (w/v) SDS. Histones extracted from the labelled chromatin show that approx. 80-90% of the label is associated with the histone fraction and column chromatography of this fraction shows that the label is primarily associated with histone H3. Labelling of the isolated histone fractions shows significant labelling only of histone H3. The intrinsic fluorescence of tryptophan is quenched by the labelled histone H3, but not by iodide, suggesting that non-histone (tryptophan-containing) proteins lie in close proximity to the labelled histone H3 but are not immediately accessible to external solvent. The labelled chromatin exhibits fluorescence anistropy, the anistropy parameter being 0.19 +/- 0.003 for chromatin, 0.05 +/- 0.01 for mononucleosomes and 0.0 for isolated histone H3. This demonstrates the restriction placed on the label's mobility by the chromatin fiber. The formation of a superhelix at 60-100 mM NaCl has been monitored with the probe. An increase in fluorescence intensity at 80 mM NaCl is observed with intact chromatin (but not H-1 depleted chromatin) followed by dissociation of the octamer in 1.50-2.0 M salt accompanied by a large increase in labelling.

Animals↗
PubMed1974

Factors affecting the activity and stability of alkaline phosphatase in a marine pseudomonad.

Conditions optimum for the assay of alkaline phosphatase of marine pseudomonad B-16 (ATCC 19855) and for maintaining the activity of the enzyme have been determined. The pH for optimal activity of the cell-bound enzyme was 9.0, whereas that for the enzyme after its release from the cells exceeded 9.4. Release was effected by first washing the cells in 0.5 M NaCl and then suspending them in 0.5 M sucrose. In the absence of salts, the activity of the cell-bound enzyme decreased rapidly at 25 C and less rapidly at 4 C. This loss of activity could be arrested but not restored by adding Mg(2+). In the presence of Na(+), activity of the cell-bound enzyme dropped to about 50% of that prevailing initially, but in this case adding Mg(2+) restored enzyme activity completely. The activity of the enzyme after its release from the cells into 0.5 M sucrose was approximately 50% of that of the equivalent amount of enzyme in the original cells. This activity was relatively stable at both 25 and 4 C. Adding Mg(2+) to the released enzyme restored its activity to that of the cell-bound form. The synthesis of alkaline phosphatase by the cells was not affected by adding 50 mM inorganic phosphate to the growth medium. The K(m) of the released enzyme for p-nitrophenyl phosphate was found to be 6.1 x 10(-5) M.

Alkaline Phosphatase↗
PubMed1974

Biochemical localization of alkaline phosphatase in the cell wall of a marine pseudomonad.

The various layers of the cell envelope of marine pseudomonad B-16 (ATCC 19855) have been separated from the cells and assayed directly for alkaline phosphatase activity under conditions established previously to be optimum for maintenance of the activity of the enzyme. Under conditions known to lead to the release of the contents of the periplasmic space from the cells, over 90% of the alkaline phosphatase was released into the medium. Neither the loosely bound outer layer nor the outer double-track layer (cell wall membrane) showed significant activity. A small amount of the alkaline phosphatase activity of the cells remained associated with the mureinoplasts when the outer layers of the cell wall were removed. Upon treatment of the mureinoplasts with lysozyme, some alkaline phosphatase was released into the medium and some remained with the protoplasts formed. Cells washed and suspended in 0.5 M NaCl were lysed by treatment with 2% toluene, and 95% of the alkaline phosphatase in the cells was released into the medium. Cells washed and suspended in complete salts solution (0.3 M NaCl, 0.05 M MgSO(4), and 0.01 M KCl) or 0.05 M MgSO(4) appeared intact after treatment with toluene but lost 50 and 10%, respectively, of their alkaline phosphatase. The results suggest that the presence of Mg(2+) in the cell wall is necessary to prevent disruption of the cells by toluene and may also be required to prevent the release of alkaline phosphatase by toluene when disruption of the cells by toluene does not take place.

Alkaline Phosphatase↗
PubMedDate not supplied

Microencapsulated vaccines to provide prolonged immunity with a single administration.

Vaccines that provide lasting immunity with a single administration of the antigen can reduce the cost of routine immunization programs while increasing their efficacy by lessening the need for patient compliance. The authors have been developing methods for using biodegradable polymer microspheres to encapsulate vaccines. These microcapsules are designed to provide timed release of the antigen on a schedule that mimics conventional booster shots. The microspheres are made from poly-DL-lactide-co-glycolide. The rate of biodegradation of this polymer is controllable by varying the molar ratio of the monomers. High performance liquid chromatography was used to measure release kinetics in vitro, and a process was developed for the encapsulation of water soluble protein antigens. This process then was used to prepare a microencapsulated vaccine for type A botulism made using a recombinant C fragment antigen. A series of 27 adult C57BL/6J mice were used to study the efficacy of this vaccine. Six mice injected with saline filled microspheres served as a control group. Plasma samples were taken weekly to measure antibody levels using enzyme linked immunosorbent assay. At 14 weeks, 21 immunized mice and six control subjects were used for an aerosol challenge test with botulinum toxin. All control subjects died within 72 hrs. Fifteen (71%) of the immunized mice survived.

Animals↗
PubMedDate not supplied

An infection inhibiting urinary catheter material.

Catheter associated bacteriuria is a common infection in hospitals and nursing homes. An infection inhibiting catheter material for fabricating urinary catheters is being developed. The material consists of silicone rubber elastomer compounded with chlorhexidene gluconate (CHG) matrix. The antibiotic is released in sustained fashion over at least 4 weeks. A method was established for adding CHG to silicone rubber. To protect the CHG, it is suspended in a water soluble wax that also modulates CHG release from the elastomer. It was found that CHG is randomly dispersed in the elastomer and that the primary release mechanism is by diffusion. The antibacterial activity of the material with a range of 0.1 to 5% CHG by weight was examined using in vitro zone inhibition testing. The new material demonstrated significant inhibitory activity against three pathogens tested (Escherichia coli, Proteus mirabilis and Staphylococcus epidermidis.). The release rate of CHG was measured in vitro using high performance liquid chromatography (HPLC). With 5% CHG loading, the antibiotic was released at a steady rate of approximately 8.4 mg/cm2/day for periods extending beyond 4 weeks. This new material for urinary catheters has the potential to provide protection against infection and surface colonization.

Animals↗