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Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 361 records · Page 20Linked to original sources
PubMed1989

Adenosine triphosphate turnover in humans. Decreased degradation during relative hyperphosphatemia.

The regulation of ATP metabolism by inorganic phosphate (Pi) was examined in five normal volunteers through measurements of ATP degradation during relative Pi depletion and repletion states. Relative Pi depletion was achieved through dietary restriction and phosphate binders, whereas a Pi-repleted state was produced by oral Pi supplementation. ATP was radioactively labeled by the infusion of [8(14)C]adenine. Fructose infusion was used to produce rapid ATP degradation during Pi depletion and repletion states. Baseline measurements indicated a significant decrease of Pi levels during phosphate depletion and no change in serum or urinary purines. Serum values of Pi declined 20 to 26% within 15 min after fructose infusion in all states. Urine measurements of ATP degradation products showed an eightfold increase within 15 min after fructose infusion in both Pi-depleted and -supplemented states. Urinary radioactive ATP degradation products were fourfold higher and urinary purine specific activity was more than threefold higher during Pi depletion as compared with Pi repletion. Our data indicate that there is decreased ATP degradation to purine end products during a relative phosphate repletion state as compared to a relative phosphate depletion state. These data show that ATP metabolism can be altered through manipulation of the relative Pi state in humans.

Adenosine Triphosphate↗
PubMed1989

Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma. Efficacy and pulmonary deposition.

Bronchodilator responses to both nebulized albuterol (salbutamol) and ipratropium bromide and aerosol delivery to the tracheobronchial tree have been assessed in eight patients with chronic stable asthma (mean baseline FEV1, 50 percent; reversibility greater than 20 percent). Two commercially available nebulizer systems were used, namely, a Turret nebulizer operated at a compressed gas flow rate of 12 L/min (droplet MMD, 3.3 mu) and an Inspiron nebulizer driven at 6 L/min (MMD, 7.7 mu). Albuterol was given as doses of 250 micrograms, 250 micrograms, 500 micrograms, and 1,000 micrograms (cumulative dose, 2 mg) and ipratropium bromide as doses of 50 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms (cumulative dose, 400 micrograms) at intervals of 35 minutes. For albuterol, bronchodilatation was significantly (p less than 0.05) greater at all dosage levels with the Turret. For ipratropium, bronchodilatation was similar for both nebulizers. Measurements of aerosol deposition using 99mTc-labelled pentetic acid (diethylenetriamine pentaacetic acid; DTPA) showed that 9.1 +/- 1.1 percent and 2.7 +/- 0.2 percent of the dose reached the lungs during nebulization to dryness for Turret and Inspiron, respectively (p less than 0.01); distribution within the lungs was similar for the two aerosols. Selection of nebulizer apparatus can influence delivery of aerosol and subsequent bronchodilator response to albuterol in patients with chronic stable asthma but is less important for aerosol delivery of ipratropium bromide in these patients.

Adult↗
PubMed1989

Phosphorylation of 2',3'-dideoxyinosine by cytosolic 5'-nucleotidase of human lymphoid cells.

2',3'-Dideoxyinosine (ddlno) is a potent and selective inhibitor of human immunodeficiency virus in human lymphoid cells and monocytes/macrophages. Earlier studies [J. Biol. Chem. 263:15354 (1988)] showed that anabolism of ddlno in human lymphoid cells is mediated via an initial step of phosphorylation and subsequent amination to dideoxy-AMP via adenylosuccinate synthetase/lyase. Evidence was obtained that neither adenosine kinase nor deoxycytidine kinase is involved in the phosphorylation of this compound in human lymphoid cells. We now find that, in the presence of MgCl2, KCl, and inosine-5'-monophosphate as phosphate donor, purified cytosolic 5'-nucleotidase catalyzed the phosphorylation of ddlno. Although not phosphate donors, ATP, diadenosine tetraphosphate, and glycerate-2,3-bisphosphate stimulate this phosphorylation by the nucleotidase 4-5-fold. In addition to ddlno, the antiviral nucleoside analogs 2',3'-dideoxyguanosine and carbovir were substrates for this enzyme. The relative phosphorylation of these compounds varied with the concentration of the phosphate donor IMP. Approximate Km values of the nucleotidase for inosine, ddlno, dideoxyguanosine, and carbovir were, respectively, 3.4, 0.5, 0.9, and 1.7 mM. Although the substrate activity of dideoxynucleosides is inefficient, it appears likely that this nucleotidase is responsible for the metabolism of these compounds to their active nucleotides, yielding antiviral activity in human lymphoid cells.

5'-Nucleotidase↗
PubMed1989

Screening for HIV.

Explore the source record for details and available documents.

AIDS Serodiagnosis↗
PubMed1989

Pattern-evoked potentials and optic nerve fiber loss in monocular laser-induced glaucoma.

ERG and VEP responses to counterphase checkerboard stimuli were obtained from cynomolgus monkeys with monocular glaucoma induced by laser photocoagulation of the trabecular meshwork. The glaucomatous eyes showed reductions of PERG amplitude that were directly related to the histologically defined nerve damage. VEP amplitudes were also reduced in the glaucomatous eyes, but were more variable and less affected by damage than the PERG responses. An acute increase in eye pressure to 40 mm Hg in eyes without damage had no detectable effect on PERG amplitudes.

Animals↗
PubMed1989

Cell-mediated immunity in pigeon breeders' lung: the effect of removal from antigen exposure.

Eighteen precipitin-positive pigeon breeders, thirteen symptomatic (SPB), with extrinsic allergic alveolitis (EAA), and five asymptomatic (APB), without lung disease, underwent bronchoalveolar lavage (BAL). Cytospins were prepared on which differential cell counts were performed. Immunocytological methods, using monoclonal antibodies, were performed to identify lymphocyte and macrophage subsets. Marked abnormalities in cell populations were observed in both groups but with no suggestion of differences between the groups. All subjects had a lymphocytosis in BAL (SPB 45%; APB 29%). These lymphocytes were almost exclusively T-cells. The cluster designation CD4/CD8 ratio was decreased (SPB 0.86; APB 1.13) and a significantly higher proportion of these cells than normal expressed UCHL1 (an antigen associated with the common leucocyte antigen complex) indicating immune commitment. In the macrophage population increased proportions of cells expressing antigens associated with interdigitating cells (RFD1+) and mature macrophages (RFD7+) were also abnormal. When six SPB patients were relavaged after isolation from pigeons for three weeks, there was a significant reduction in the lymphocytosis and in the proportion of UCHL1+ lymphocytes. This was accompanied by reductions in the percentage of macrophages expressing RFD1 and UCHL1. We suggest that EAA in pigeon breeders is associated with a cell-mediated immune response which is down-regulated by isolating patients from exposure to pigeon derived antigens.

Adult↗
PubMed1988

Metabolic pathways for the activation of the antiretroviral agent 2',3'-dideoxyadenosine in human lymphoid cells.

The pathways of 2',3'-dideoxyadenosine (ddAdo) metabolism, a selective inhibitor of the replication of human immunodeficiency virus, were investigated with use of the human T-lymphoid cell line CCRF-CEM which is deficient in either deoxycytidine kinase or adenosine kinase activity, or both. At an extracellular concentration of 10 microM, which blocks the cytopathic effect of human immunodeficiency virus in vitro, ddAdo was found to be metabolized to its mono-, di-, and triphosphates and to dideoxyinosine monophosphate (ddIMP). The metabolism of ddAdo in the kinase-deficient mutants was found to be unchanged by comparison with that in parental cells; however, the inhibition of ddAdo deamination to 2',3'-dideoxyinosine (ddIno) by the adenosine deaminase inhibitor, 2'-deoxycoformycin, reduced ddAdo nucleotide formation in deoxycytidine kinase-deficient, adenosine kinase-deficient, and doubly kinase-deficient mutants by 42, 54, and 80%, respectively. Incubation of the CCRF-CEM cells with 20 microM L-alanosine, an amino acid antagonist that inhibits purine biosynthesis at the level of adenylosuccinate/lyase synthetase, resulted in 80% inhibition in the accumulation of ddAdo nucleotides in both wild-type and kinase-deficient mutants and also increased ddIMP accumulation 2- to 3-fold. These findings indicate that ddAdo activation in human T-lymphoblasts can occur by three metabolic pathways: directly, by phosphorylation to ddAMP by the action of either deoxycytidine kinase or adenosine kinase and, indirectly, through deamination to ddIno with consequent phosphorylation of ddIno to ddIMP, and reamination to ddAMP in a reaction catalyzed by adenylosuccinate synthetase/lyase. However, in the absence of 2'-deoxycoformycin, the activation of ddAdo to ddATP in T-lymphoid cells is primarily a function of the indirect route.

Adenosine Kinase↗
PubMed1988

Neovascularization in central retinal vein occlusion: electroretinographic findings.

Electroretinograms (ERGs) were measured in 15 patients with central retinal vein occlusion (CRVO). Seven of the patients had neovascularization of the iris (NVI) at the time of testing, and two developed NVI within one month of testing; six did not have NVI or any other form of neovascularization (NV) and were no longer considered to be at risk for NV from their present occlusion. The ERGs were recorded as a function of the stimulus intensity and to a 30-Hz flickering stimulus. A Naka-Rushton-type function was fit to b-wave amplitudes, measured as a function of stimulus intensity, to evaluate changes in ERG amplitude and sensitivity. Compared with eyes in the no-NV group, eyes developing NVI had significantly reduced ERG sensitivity and amplitudes. The distributions of sensitivity values in these two groups did not overlap. All of the eyes with NV showed large a- and b-wave and 30-Hz implicit time delays, but only one eye had a b/a-wave amplitude ratio close to or less than 1. A comparison of ERG sensitivity, amplitude data, and flicker timing data with retinal fluorescein angiography in a two-alternative forced-choice analysis showed that ERG sensitivity and amplitude loss were better than retinal fluorescein angiography at discriminating eyes with CRVO and NVI from eyes with CRVO without NVI.

Electroretinography↗
PubMed1988

Retinal sensitivity over drusen and nondrusen areas. A study using fundus perimetry.

Elderly patients with drusen and good visual acuity have a decrease in dark-adapted retinal sensitivity in the central retina. We used the fundus camera stimulator to determine whether this sensitivity loss is caused directly by the presence of drusen. We measured retinal sensitivity over drusen and in drusen-free areas in eight patients with drusen and age-related macular degeneration (AMD). There was no significant difference in sensitivity between drusen and nondrusen areas in each patient. The sensitivity loss seen in patients with drusen thus seems to reflect a more diffuse disease of the retina and retinal pigment epithelium and is not a direct effect of drusen. More marked sensitivity losses are found in even small areas of more advanced AMD changes, suggesting that a large focal loss in retinal sensitivity may be an indicator of developing AMD changes.

Aged↗
PubMed1988

Immunocytochemical studies of cytochrome oxidase subunits in skeletal muscle of patients with partial cytochrome oxidase deficiencies.

Muscle biopsies from 17 patients with partial cytochrome oxidase deficiencies were investigated using immunocytochemical techniques for the localisation of cytochrome oxidase subunits. Antisera to subunits II/III (mitochondrially coded) and subunits IV, Vab, VIbc, VIIa, VIIbc and VIII (nuclear coded) showed clear particulate immunoreactivity in the muscle fibres of normal control biopsies. In the patients studied, muscle fibres with absent or decreased cytochrome oxidase activity also showed decreased immunoreactivity affecting all enzyme subunits. Particularly close correlation was seen between percentages of fibres showing absent enzyme activity and those showing decreased immunoreactivity for subunits II/III which are catalytic in function. The regulatory subunits IV-VIII were affected to varying degrees with different patterns of subunit loss occurring in individual muscle fibres.

Adolescent↗
PubMed1988

Cytochrome oxidase deficiency: immunological studies of skeletal muscle mitochondrial fractions.

We report a 2-year-old girl who presented with delayed development, weakness and persistent vomiting. She had a demyelinating peripheral neuropathy. The activity of cytochrome oxidase in skeletal muscle from the patient was 10% of controls. Immunochemical studies using antibodies to holo-cytochrome oxidase and the individual subunits showed a low concentration of all detectable subunits.

Child, Preschool↗
PubMed1988

A rapid and sensitive solution hybridisation assay for the quantitative determination of specific viral RNA sequences.

A solution hybridisation assay has been developed which allows the quantitation of specific viral (RNA) sequences in infected cells. The assay makes use of single-stranded (ss) RNA probes of known polarity synthesised at high specific activity in vitro from cDNA clones of the relevant viral gene by the SP6 or T7 RNA polymerase. These probes are used together with samples containing the RNA to be detected at a known concentration to construct a calibration curve to relate RNase resistant radioactivity following solution hybridisation to amount of RNA. The amount of RNA in experimental samples is then determined using the calibration curve that is produced each time the assay is performed. The UKtc strain of Rotavirus growing in BSC-1 cells was used to develop this method but with the substitution of suitable cDNA clones it could be applied to any viral system.

DNA↗
PubMed1988

Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats.

The effects of elevated dietary ascorbic acid and iron on copper utilization were examined. Male Sprague-Dawley rats were fed one of two levels of Cu (deficient, 0.42 microgram Cu/g, or adequate, 5.74 micrograms Cu/g), Fe (moderate, 38 micrograms Fe/g or high, 191 micrograms Fe/g), and ascorbic acid (low, 0% or high, 1% of the diet) for 20 d. High Fe decreased (p less than 0.05) Cu absorption only in Cu-deficient rats. High ascorbic acid significantly decreased tissue Cu levels in Cu-adequate rats. High Fe with ascorbic acid caused severe anemia in Cu-deficient rats and decreased plasma ceruloplasmin by 44% in Cu-adequate rats. Cu,Zn-superoxide dismutase activity in erythrocytes was decreased (p less than 0.05) by 14% during Cu deficiency but was not affected by Fe or ascorbic acid. These results may be important to individuals with high intakes of Fe and ascorbic acid.

Absorption↗
PubMed1988

Lipid storage myopathy associated with low acyl-CoA dehydrogenase activities.

A man with a painful proximal myopathy had excess lipid deposition in skeletal muscle, excretion of dicarboxylic acids in urine and low acyl-CoA dehydrogenase activities in skeletal muscle mitochondria. In addition he had little immunoreactive short-chain and medium-chain acyl-CoA dehydrogenase enzyme protein compared with normal controls. Following treatment with riboflavin there was considerable improvement in his clinical condition which was confirmed by further biochemical and morphological investigations.

Acyl-CoA Dehydrogenases↗
PubMed1988

Lipid storage myopathy due to glutaric aciduria type II: treatment of a potentially fatal myopathy.

Several patients with lipid storage myopathies have been described, although in most cases the biochemical defect is unclear. A child is reported who presented with severe muscle weakness at age six months. She had lipid storage myopathy due to glutaric aciduria type II. It is probable that her brother died from the same disorder at the age of three months. She has responded well to treatment with a low-fat diet, riboflavin, carnitine and glycine.

Carnitine↗