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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 523 records · Page 29Linked to original sources

Cloning, sequence, and expression of a human granulocyte/macrophage colony-stimulating factor.

Human granulocyte/macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is essential for the in vitro proliferation and differentiation of precursor cells into mature granulocytes and macrophages. In this report we have used a mouse GM-CSF cDNA clone to isolate human GM-CSF clones from libraries made from HUT-102 messenger RNA and mitogen-stimulated T-lymphocyte messenger RNA. The human cDNA clones contained a single open-reading frame encoding a protein of 144 amino acids with a predicted molecular mass of 16,293 daltons and showed 69% nucleotide homology and 54% amino acid homology to mouse GM-CSF. One of these cDNA clones was shown to direct the synthesis of biologically active GM-CSF using a yeast expression system. The gene for human GM-CSF appears to exist as a single-copy gene.

Amino Acid Sequence↗

Cloning determinants of pathogenesis from Pseudomonas syringae pathovar syringae.

Transposon mutagenesis and a cosmid genomic library of DNA from the bean pathogen Pseudomonas syringae pathovar syringae were used to identify and isolate sequences essential for pathogenesis. Strain PS9021, derived by Tn5 mutagenesis, was determined to be nonpathogenic on Phaseolus vulgaris cultivar Red Mexican and incapable of inducing a hypersensitive response in Nicotiana tabacum. This mutant also produced fluidal rather than firm colonies on selected agar media. A Tn5-containing EcoRI fragment from PS9021 was cloned and used to probe 1500 members of a genomic library constructed with DNA from the pathogenic parent strain and the wide host range cosmid pVK102. One member that hybridized to the probe contained a cosmid with a 30-kilobase-pair insert (pOSU3101) that complemented the mutant phenotypes when mobilized into PS9021. A restriction endonuclease cleavage site map of pOSU3101 was constructed and sequences essential for pathogenesis were determined by subcloning. Approximately 8.5 kilobase pairs of the insert were essential for restoration by complementation of pathogenesis and hypersensitive response and wild-type colony morphology in strain PS9021.

Journal Article↗

Efficacy of ciprofloxacin in experimental arthritis caused by Escherichia coli--in vitro-in vivo correlations.

Ciprofloxacin, a new carboxyquinolone, has potent in vitro bactericidal activity against the major aerobic, gram-negative bacillary pathogens that cause human pyoarthroses. We investigated the in vivo efficacy of ciprofloxacin in a rabbit model of septic arthritis due to Escherichia coli. Animals received either ciprofloxacin (80 mg/kg per day) or gentamicin (5 mg/kg per day). Ciprofloxacin was rapidly bactericidal in vivo and was significantly more effective in reducing the numbers of E. coli in synovial tissue than was gentamicin at days 10 and 17 of therapy (P less than .0005 and P less than .05, respectively). Similarly, ciprofloxacin was significantly more active than was gentamicin in reducing the numbers of E. coli in joint fluid on day 10 of therapy (P less than .0005); however, by day 17 of therapy, the numbers of E. coli in joint fluid were not significantly different in the two therapy groups. Neither regimen was effective in preventing the development of postinfectious inflammatory synovitis. There was no in vivo development of resistance to either antibiotic during therapy. Ciprofloxacin therapy was associated with significantly higher bactericidal titers in serum and joint fluid than were observed with gentamicin therapy (P less than .0005). Ciprofloxacin warrants further in vivo evaluation in invasive E. coli infections.

Animals↗

Fatal intracranial extension of spinal hemorrhage after lumbar puncture.

Lumbar puncture (LP) is sometimes performed in addition to computed tomography (CT) to exclude hemorrhage prior to anticoagulation for suspected cerebral ischemia. The LP may be complicated by spinal hemorrhage during subsequent anticoagulation. We report such a case with an eventually fatal outcome due to intracranial extension of blood. On balance, the use of LP in addition to CT in this setting appears to be unwise.

Aged↗

Monitoring demyelination in multiple sclerosis with multi-flash campimetry.

Multi-flash campimetry is a computer-implemented psychophysical technique that allows a rapid and extensive assessment of visual flicker sensitivity. Multi-flash field maps generated from the data typically reveal the presence of 'islands' of degraded temporal resolution in multiple sclerosis (MS) patients, but not in normal control observers. These distinct 'islands' presumably reflect the influence of demyelination as well as a variety of other possible transient factors, such as edema and inflammation of the optic nerve. The question addressed in the present study concerned a means of distinguishing among such influences. The strategy employed was to test MS patients more than once over a period of several months. Under the assumption that there is little or no significant remyelination in the central nervous system, it was argued that 'islands' that remain present over time should be those that principally reflect demyelination. Transient changes that appear in the fields of MS patients probably reflect the influence of other mediating factors. Examples of multi-flash field maps are presented to illustrate this point and to serve as an initial assessment of the reliability of the technique. It is concluded that multi-flash campimetry may prove to be an effective aid in documenting the degree of progressive visual involvement in MS, and provide a means of monitoring the clinical course of demyelination in the visual system.

Adult↗

Genetic damage in CHO cells exposed to enzymically generated active oxygen species.

The genetic toxicity of active oxygen species produced during the enzymic oxidation of xanthine has been investigated using Chinese hamster ovary (CHO) cells. Incubation of cells with xanthine plus xanthine oxidase resulted in extensive chromosome breakage and sister-chromatid exchange and gave a small increase in frequency of thioguanine-resistant cells (HGPRT test). Inclusion of superoxide dismutase or catalase in the xanthine/xanthine oxidase system inhibited chromosome breakage, whereas only catalase prevented SCE and mutant induction. It is concluded that hydrogen peroxide is responsible for most of the genetic effects observed in CHO cells exposed to xanthine/xanthine oxidase but that superoxide plays a key role in chromosome breakage.

Animals↗

An international collaborative study of 'genetic drift' in Salmonella typhimurium strains used in the Ames test.

An international collaborative study of the response of 5 Salmonella typhimurium strains (TA1535, TA1537, TA1538, TA98 and TA100) to 4-nitroquinoline-N-oxide was performed. A laboratory's 'in-house' stock of these strains was compared with a set of reference strains, using a standardized protocol. The prime objective of this study was to investigate whether the ability of these strains to produce spontaneous or induced mutants had changed during their prolonged cultivation in different laboratories, i.e. to investigate their 'genetic drift'. Any observed change in mutability might contribute to the variations between laboratories in the results of the Ames test. A second objective was to obtain information on the extent of intra- and inter-laboratory variation when a standardized protocol was used. 38 laboratories participated in this study. The data were analysed statistically by 3 groups using different models and the same conclusion was reached: genetic drift is found in some strains in some laboratories, but does not contribute significantly to inter-laboratory variation in the Ames test. When the inter-laboratory variation was analysed there was considerable correlation between results for the 'in-house' and the reference strain, and between results for different strains in the same laboratory (Margolin et al., accompanying paper).

4-Nitroquinoline-1-oxide↗

Relation of the relative dose response to liver concentrations of vitamin A in generally well-nourished surgical patients.

In 12 adult, generally well-nourished, surgical patients, liver vitamin A concentrations obtained by the analysis of liver biopsies were compared with the relative dose response ( RDR ). RDR is defined as the percentage increase in plasma retinol level relative to the plasma retinol level 5 h after the oral administration of a standard oral dose (450 micrograms) of retinyl acetate. Liver vitamin A values, expressed as retinol, and corresponding RDR values were 14 micrograms/g (28%), 30 micrograms/g (15%), and 58 to 434 micrograms/g (0 to 12%). Other indicators of vitamin A nutriture, which did not correlate with liver vitamin A concentrations in this group, were serum retinol level, serum retinol-binding protein concentration, and the percentage saturation of serum retinol-binding protein. The relative distribution of fatty acyl esters in liver retinyl ester did not change with total liver reserves. The relative percentage of retinol to total liver vitamin A, however, was higher (greater than 5%) when reserves were less than or equal to 30 micrograms/g. Although the RDR cutoff point of greater than 14% suggested earlier by others is in reasonable accord with our results, a somewhat higher RDR cutoff value (possibly 20%) may agree better with the suggested criterion of a liver vitamin A concentration of 20 micrograms/g, expressed as retinol, as a minimally adequate reserve.

Adult↗