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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 631 records · Page 35Linked to original sources

Paradoxical effects of methylmercury on the kinetics of cytochrome c oxidase.

A stoichiometric amount of methylmercuric chloride substantially inhibits cytochrome c oxidase function under steady-state turnover conditions, where the enzyme is using its substrates, cytochrome c and oxygen, rapidly and continuously. Under these conditions, a reduction in activity of approximately 40% is observed. This is in accord with the results of Mann and Auer [Mann, A.J., & Auer, H.E. (1980) J. Biol. Chem. 255, 454-458], who used mercuric chloride and ethylmercuric chloride. Paradoxically, we found that addition of methylmercuric chloride can increase the activity of cytochrome c oxidase during its initial substrate utilization. This rate enhancement, measured under conditions where the enzyme cycles only a few times, is maximal for the resting state of the enzyme. "Pulsed" cytochrome c oxidase (i.e., enzyme that has been recently reduced and reoxidized) is considerably activated with respect to the resting enzyme, showing faster turnover rates (Antonini, 1977; Brunori et al., 1979). No significant rate enhancement upon treatment with methylmercuric chloride is seen in initial substrate utilization if the enzyme is pulsed immediately before the assay. The apparently contradictory effects of methylmercuric chloride on the resting and pulsed states of the oxidase under low turnover conditions may be reconciled by a model in which mercurial binding greatly stabilizes the enzyme in a state resembling that of the pulsed enzyme. A decrease in conformational flexibility may be the basis of the mercurial-induced diminution in activity of the enzyme during steady-state turnover conditions.

Animals↗

Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS). Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor.

Hepatic stimulator substance (HSS), a partially purified extract of weanling or regenerating adult rat liver, is an organ-specific stimulator of liver growth in vivo and in vitro. The HTC hepatoma cell line is particularly responsive to HSS. The present experiments show that HSS will stimulate HTC cells in the complete absence of serum, although graded doses of fetal cal serum (FCS), from 0.1 to 5.0%, will increase the degree of stimulation in a dose-dependent manner. In contrast, when HSS is absent, increasing doses of FCS above 0.5% inhibit DNA synthesis. Much of this inhibition is removed by prior dialysis of the FCS and maximum enhancement of the HSS-induced stimulation occurs with only 0.1-0.5% of the dialysed FCS. Sera from older animals have less or even negative effect. Evidence is presented to show that the enhanced stimulation by HSS in the presence of serum is not due to insulin, glucagon, epidermal growth factor (EGF), or platelet derived growth factor (PDGF) and that HSS does not act via a shared receptor for one of these hormones. These experiments provide further evidence that HSS is a unique stimulator of liver growth and lend support to a model of organ-specific growth control.

Animals↗

A quantitative analysis of interactions between photoreceptors in the salamander (Ambystoma) retina.

A quantitative description of the electrical properties of the photoreceptor layer in the salamander retina was obtained from earlier data on the characteristics of isolated rods and cones and on rod-rod coupling, and from new data on rod-cone and cone-cone coupling and on the rod photocurrent. Injecting -1 nA current into a rod elicits hyperpolarizations of about 20 mV in an adjacent rod and 4 mV in an adjacent cone. Responses of more distant receptors are smaller. Injecting -1 nA into a cone elicits hyperpolarizations of about 4 mV in an adjacent rod and 0.4 mV in a nearby cone. Depolarizing current evokes smaller responses. Assuming, in agreement with anatomical evidence, that each rod is electrically coupled to four rods and to four cones around it, and that there is no direct electrical coupling between cones, we found these results could be predicted from the properties of isolated rods and cones if adjacent rods are coupled by a resistance of 300 M omega and adjacent rods and cones are coupled by a resistance of 5000 M omega. The small cone-cone coupling seen is due to coupling via intervening rods. The two halves of double cones are not electrically coupled. The spectral sensitivity of both halves is a maximum around 620 nm wave-length. The rod photocurrent has been characterized by voltage-clamping rods isolated from the retina. In agreement with Bader, MacLeish & Schwartz (1979) we found the time course of the photocurrent to be approximately independent of voltage between -35 and -85 mV. The voltage responses of rods, single cones and double cones isolated from the retina obey the principle of univariance. Responses of receptors in the retina do not obey univariance. The main deviations from univariance observed can be explained if adjacent rods and cones are coupled by a resistance of 5000 M omega. Our data demonstrate that rod-cone coupling is relatively weak. We simplified our description of the photoreceptor network, by omitting cones, to investigate the spatiotemporal processing that the rod network is capable of. Computer simulations predict, as is found experimentally, that the rod voltage response to a large spot of bright light should show a much more pronounced initial transient hyperpolarization than the response to a small spot of light of the same intensity. This difference is produced by the combination of electrical coupling of the rods with the existence of a voltage-gated current, IA, in the rod membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

A strategy to reveal high-frequency RFLPs along the human X chromosome.

Fifteen human X-chromosome-specific DNA fragments, localized to particular regions of that chromosome, were used to search for restriction fragment length polymorphisms. A screening panel prepared by digesting DNA from only two females and one male with 24 restriction enzymes was sufficient to reveal two-allele polymorphisms among one-third of the probes tested. These polymorphisms, as theoretically anticipated, showed minor allele frequencies above 20%, as a rule. Such high-frequency polymorphism allowed identifying females, from pedigrees segregating three X-linked diseases, who were multiply heterozygous for polymorphic loci spread throughout the X chromosome. In addition, two of the 24 enzymes tested with these X-specific probes, Msp I and Taq I, generate fragment sizes in DNA-blotting experiments that, on average, are significantly larger than expected from nearest neighbor predicted recognition site frequencies.

Alleles↗

The question of a helminthic cause of preeclampsia.

Two recent reports have suggested that wormlike structures characteristic of helminths are associated with preeclampsia. We identified these vermiform structures in toluidine blue O-stained venous blood smears from four women with preeclampsia, cord blood taken at delivery of three of their neonates, and venous blood from five control subjects without preeclampsia and from five healthy beagle dogs. The structures, which had diameters between 30 and 670 microns, could not be concentrated by passing the blood through a 12-microns filter, yet they could be demonstrated in stained smears prepared from blood that had been filtered. We conclude that these structures are not helminths; they are most likely artifacts of staining.

Animals↗

Transient tachypnea of the newborn: the relationship to preterm delivery and significant neonatal morbidity.

Early studies suggest that transient tachypnea of the newborn is a benign disease of uncertain etiology. Consequently, prevention of this complication has not been a primary concern of obstetricians. In this study of amniotic fluid phospholipids, 55 pregnancies in which the neonate developed transient tachypnea were compared to 355 pregnancies after which respiratory distress did not occur. Thirteen neonatal complications and procedures, often associated with prematurity, were significantly increased in the infants who developed transient tachypnea. Potential risk factors for transient tachypnea were examined by stepwise discriminant analysis. Negative amniotic fluid phosphatidylglycerol, prematurity (less than 38 weeks), and 1-minute Apgar score less than 7 all made an independent contribution to the overall characterization of infants at increased risk for transient tachypnea. These findings suggest that mild fetal lung immaturity may be a factor in the pathophysiology of this syndrome, and that the relationship of perinatal factors associated with transient tachypnea of the newborn in previous studies, including maternal diabetes mellitus and cesarean birth, may be partially mediated through a neonatal surfactant deficiency.

Amniotic Fluid↗

Iatrogenic risks and financial costs of hospitalizing febrile infants.

We identified, by diagnostic categories, the iatrogenic and financial costs that arise from hospitalizing febrile infants 60 days of age or younger. Thirty-seven (19.5%) of all admissions resulted in 48 separate complications. Twenty-nine (60.4%) of these complications were preventable, and six complications (12.5%) occurred in infants who probably did not require hospitalization for therapy. Twenty-four (50%) of all complications resulted from intravenous therapy. In addition to the complications, 26 diagnostic misadventures were identified. The average length of hospitalization for all infants was 7.0 days, with a range of two to 28 days. The average cost of hospitalization in 1979-80 dollars was $2,130 per infant, with a range from $6,345 for those infants with bacterial meningitis to $1,480 for those infants with aseptic meningitis. On the average, 25.6% of the bill was for diagnostic studies and 8.3% for physician fees.

Anti-Bacterial Agents↗

Hospitalization v outpatient treatment of young, febrile infants.

Our medical center has an unwritten policy of admitting all febrile infants younger than 2 months of age. We studied this practice during a three-year period to determine what proportion of the febrile infants who came to the outpatient department were admitted. The characteristics of the infants who were not admitted were compared with those who were. The timing of and the infant's status at a subsequent visit for those not admitted were also identified. One hundred six (35%) of 303 encounters with young, febrile infants did not result in admissions. An infant was more likely to be admitted if he was male, younger than 30 days of age, and febrile (greater than 38.5 degrees C). None of the infants who were followed up as outpatients suffered morbidity that could be directly related to their not having been hospitalized.

Age Factors↗

Lymphocyte heterogeneity in the trout, Salmo gairdneri, defined with monoclonal antibodies to IgM.

A monoclonal antibody to trout serum IgM was tested by immunofluorescence analysis with lymphocytes from thymus, spleen and head kidney. By visual examination, the antibody reacted with only a subpopulation of lymphocytes. The mean values +/- SE for positive cells were 5.2 +/- 2.3% in the thymus, 30.3 +/- 7.9% in the spleen and 12.4 +/- 3.0% in the head kidney. Flow cytofluorometric analysis revealed evidence of heterogeneity by size among the membrane IgM-positive cells of the head kidney and spleen. Depletion of head kidney cells positive for surface IgM by an immune affinity adherence technique of panning, using monoclonal anti-IgM, significantly reduced the mitogenic response to lipopolysaccharide but not to concanavalin A. It is suggested that this information supports the existence of distinct subpopulations of fish lymphocytes that may be homologous in certain respects to mammalian T and B type cells.

Animals↗

Cell biology of hematoporphyrin derivative (HPD).

Tissue culture cells were treated with hematoporphyrin derivative (HPD) and analyzed for (1) HPD uptake, (2) HPD washout, and (3) fluorescence changes. The absorption peaks were the same for HPD in solution and HPD bound to cells. HPD was taken up by all cell types rapidly within the first 10 hours of exposure, and leveled off by 20 hours of exposure. HPD came out of all cell types to control levels by 72 hours after removal of the HPD bathing solution. The HPD appeared to come out of the malignant 3-T-12 cells more slowly than from the parental (non-malignant) 3-T-3 cells. The fluorescence spectrum of HPD-treated cells changed markedly from the time that the bathing HPD solution was removed from the cells. As time progressed the weakly fluorescent 590-nm peak increased greatly and the 615-nm and 630-nm peaks decreased significantly.

Animals↗

The spatial frequency sensitivity of bipolar cells.

Retinal bipolar cells constitute the output stage of the outer layer of the retina. There are several constraints on the ability of the bipolar cell array to respond to the different spatial frequency components of the visual image, including (i) electrical coupling in the dendritic tree receiving receptor input; (iii) the "lateral inhibition" mediated by horizontal cells. Using simple mathematical models, we derive analytical expressions for the spatial frequency response of the bipolar cell array for the case in which horizontal cells are presynaptic to bipolar cells (feedforward model) and also for the case in which horizontal cells are presynaptic to receptors (feedback model). The results illustrate the importance of the three factors mentioned in determining the bipolar cells' properties. The optimal spatial frequency for stimulating the bipolar cell array, and the range of spatial frequencies transmitted onward to the inner plexiform layer, are thus related to the anatomical and electrical properties of the cells in the outer plexiform layer.

Animals↗

A new method for obtaining isolated photoreceptors from the amphibian retina.

A new method is described for obtaining isolated rods and cones by physical dissociation of the retina. The method gives a large yield of isolated photoreceptors, without any changes in membrane properties that enzymatic dissociation techniques might produce. Photovoltages and photocurrents recorded from rods isolated in this way are presented.

Ambystoma↗