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Biomedical subjects

D M Johnson

Publications and source records attributed to D M Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1991

In vitro evaluation of GR69153, a novel catechol-substituted cephalosporin.

GR69153 is a C-7 catechol cephalosporin with a broad spectrum of activity against members of the family Enterobacteriaceae (MICs for 50% of strains tested [MIC50s], 0.008 to 0.5 micrograms/ml), Staphylococcus aureus (MIC50, 4 micrograms/ml), Pseudomonas aeruginosa (MIC50, 0.25 micrograms/ml), Haemophilus influenzae (MIC50, 0.03 micrograms/ml), Neisseria gonorrhoeae (MIC50, 0.03 micrograms/ml), and Acinetobacter spp. (MIC50, 2 micrograms/ml). Potent GR69153 activity was also demonstrated against Moraxella catarrhalis, pneumococci, beta-hemolytic streptococci, gram-positive anaerobes, and most species of coagulase-negative staphylococci. The activity of GR69153 was generally two- to fourfold greater than that of ceftazidime. Resistance level GR69153 MICs for 90% of strains tested (greater than or equal to 32 micrograms/ml) were found most often among Citrobacter freundii, Enterobacter spp. and Morganella morganii strains. GR69153 did not significantly inhibit enterococci, Xanthomonas maltophilia, the Bacteroides fragilis group, Corynebacterium jeikeium, or Listeria monocytogenes. GR69153 was bactericidal and was generally beta-lactamase stable, and MICs were only slightly increased by high inoculum concentrations. Activity was enhanced in an iron-deficient medium, and a modest MIC difference attributed to iron availability was noted between standard agar and broth test results. GR69153 was confirmed to be a potent, catechol-substituted cephalosporin with a spectrum slightly wider than that of ceftazidime, but it was less active than cefpirome or imipenem against some gram-positive pathogens and anaerobes.

Bacteria↗
PubMed1991

Emergency toxicology testing (detection, confirmation, and quantification) of basic drugs in serum by liquid chromatography with photodiode array detection.

We investigated the applicability of liquid chromatography with photodiode array detection as a serum drug screening technique in an emergency toxicology setting. Basic compounds are extracted from alkalinized serum with hexane and chromatographed on a cyanopropyl reversed-phase column. The photodiode array detector records the ultraviolet spectrum of each eluting peak for identification and quantification. More than 30 drugs/metabolites including antidepressants, antihistamines, phenothiazines, and analgesics are detected at their therapeutic concentrations or less. Quantitative run-to-run precision (CV) for antidepressant drugs at low therapeutic concentrations is less than 6%. We evaluated the potential for interference of greater than 140 compounds of clinical interest. In a split-sample study, 151 of 154 positive drug findings by the method were confirmed by alternative techniques (gas chromatography/mass spectrometry and liquid chromatography with either normal-phase or reversed-phase columns). In the three unconfirmed findings, this method detected drugs at concentrations below the limit of identification of the comparison method. Also, 275 samples judged negative by this procedure were negative by a different liquid-chromatographic method.

Analgesics↗
PubMed1990

Comparison of algorithms of testing for use in automated evaluation of sensation.

Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Békésy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Békésy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.

Algorithms↗
PubMed1987

Intravascular fasciitis: a case report of an intraoral location.

Nodular fasciitis is a benign reactive fibroblastic proliferation which usually arises from the superficial or deep fascia of the extremities and trunk. In 1981 a distinct variant, intravascular fasciitis (IVF), was reported which possessed the same clinical and histological features of more ordinary forms of nodular fasciitis but, in addition, had a striking involvement of associated arteries and/or veins. A case of intraoral IVF is presented and its clinical and histologic features are compared with those of IVF found elsewhere in the body. A brief discussion of etiology and differential diagnostic considerations is also included.

Adult↗
PubMed1987

Individual differences in auditory capabilities. I.

Twenty-eight audiometrically normal adult listeners were given a variety of auditory tests, ranging from quiet and masked thresholds through the discrimination of simple and moderately complex temporal patterns. Test-retest reliability was good. Individual differences persisted on a variety of psychoacoustic tasks following a period of training using adaptive threshold-tracking methods, and with trial-by-trial feedback. Large individual differences in performance on temporal-sequence-discrimination tasks suggest that this form of temporal processing may be of clinical significance. In addition, high correlations were obtained within given classes of tests (as, between all tests of frequency discrimination) and between certain classes of tests (as, between tests of frequency discrimination and those of sequence discrimination). Patterns of individual differences were found which support the conclusion that individual differences in auditory performance are, in part, a function of patterns of independent abilities.

Adolescent↗
PubMed1985

The unprotected parasphenoidal carotid artery studied by high-resolution computed tomography.

A retrospective review was made of 500 consecutive thin-section axial CT scans of the adult sphenoid sinus using contrast enhancement and the bone algorithm to determine whether there was exposure of the cavernous sinus and the carotid arteries along their parasphenoidal course. At least one cavernous-carotid complex that could be considered at risk during sphenoid sinus surgery was seen in 31.4% of the patients. Of this group, 14.4% of the patients had no bony covering on one or both sides at some point along the parasphenoidal course. In 17% the bony covering was so thin it would give minimal, if any, protection from surgical trauma. A patient who had laceration of an unprotected carotid artery with development of post-traumatic aneurysm is discussed.

Aneurysm↗
PubMed1984

Amino acid sequence of human factor D of the complement system. Similarity in sequence between factor D and proteases of non-plasma origin.

The amino acid sequence of human factor D is proposed from the analysis of the peptides produced by treatment of the factor D with cyanogen bromide, iodosobenzoic acid, trypsin and V-8 protease. Comparison of the proposed sequence with the sequences of other serine esterases indicated that factor D, although it is a plasma serine esterase, is more closely related to certain proteases not found in the plasma than to other plasma serine esterases of the complement system. For example, 36% and 32% identity in amino acid sequence was found on comparison of factor D with elastase and group-specific protease, respectively. Whereas only 27% and 18% identity was observed between factor D and the other complement serine esterases, Clr and factor B, respectively.

Amino Acid Sequence↗
PubMed1984

Degradation of fenprostalene in polyethylene glycol 400 solution.

The kinetics of degradation of fenprostalene (I) in polyethylene glycol 400 solution was examined using HPLC. The degradation of I at 80 degrees C was shown to depend on the presence of oxygen and a large number of polar products were produced, as evidenced by using 3H-labeled I. Evidence that autoxidation of the polyethylene glycol 400 was concurrent with degradation of I was found from a drop in the apparent pH. Antioxidants were very effective in retarding the rate of degradation in the presence of oxygen. Degradation of I in polyethylene glycol 400 appears to arise from a reaction between the drug and reactive peroxide intermediates formed through air-oxidation of polyethylene glycol 400. This is supported by the finding that I reacts exclusively by a slow transesterification reaction in diethylene glycol, a solvent that is stable to autoxidation.

Chromatography, High Pressure Liquid↗
PubMed1984

Immunological detection of Plasmodium knowlesi antigens after electrophoretic transfer from SDS-polyacrylamide gels to diazophenylthioether paper.

Freeze-thawed extracts of mature schizonts of Plasmodium knowlesi (strain W1) were electrophoresed in sodium dodecylsulphate (SDS) polyacrylamide gels, then transferred electrophoretically to diazophenylthioether paper. The transferred antigen was probed using a purified polyvalent, polyclonal immune serum pool isolated from rhesus monkeys (Macaca mulatta). This method for identifying parasite antigens was compared with immunoabsorption, using parasites which had been metabolically labelled in vitro with 35S-methionine. The methods showed general correspondence but some antigens failed to react after transfer because of loss of antigenicity during SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Some antigens were observed preferentially after the transfer procedure, possibly because of their failure to elute from the immunoabsorbant or because they may have a low methionine content. The transfer method failed to reveal the antigen reactivity of three out of four monoclonal antibodies tested, apparently because the epitopes involved were inactivated by SDS. During P. knowlesi infection in the resistant kra monkey (Macaca fascicularis) the transfer method showed the presence by day 10 of antibodies against two components having an apparent molecular weight by SDS-PAGE similar to those of putative protective antigens described in other studies using monoclonal antibodies.

Animals↗
PubMed1984

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons.

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.

Animals↗
PubMed1984

Membrane permeability as a determinant of dexamethasone resistance in murine thymoma cells.

The variant MS23 of the murine thymoma cell line W7 , selected for growth at low concentrations of dexamethasone (7.5 nM), is cross-resistant to various unrelated drugs, including colchicine. By stepwise selection in combinations of dexamethasone and colchicine at increasing concentrations, we have isolated a series of variants with increased resistance to dexamethasone and cross-resistance to puromycin, colchicine, daunomycin, gramicidin, and vincristine. Surprisingly, resistance to triamcinolone acetonide, a glucocorticoid structurally related to dexamethasone, did not develop. Assays for specific dexamethasone and triamcinolone acetonide binding sites in variant cell extracts reveal that the glucocorticoid receptors of these variants are unchanged as compared to the W7 parental line. However, whole cell binding assays yielded reduced apparent affinity for dexamethasone in the MS23 variant and drastically reduced dexamethasone binding after selection for increased resistance. We demonstrate that this is due to reduced drug uptake. Procaine, a membrane-active anesthetic, potentiates uptake of puromycin and dexamethasone in the variants. The variants are stable, and karyotypic analysis did not reveal double minute chromosomal structures. These results demonstrate that permeability can be a rate-limiting step in steroid hormone action and is the basis for dexamethasone resistance in these variants.

Animals↗
PubMed1983

Degradation of fenprostalene in aqueous solution.

The degradation of the prostaglandin fenprostalene (III) was studied in aqueous solution. The reaction was both specific acid and base catalyzed. The only reaction found to occur was hydrolysis of the methyl ester at C-1. Activation energies for the acid- and base-catalyzed reactions were determined and are nearly identical to that for the hydrolysis of ethyl acetate, a model ester. A competing acid-catalyzed reaction of the C-1 free acid of III was found to be approximately 10 times slower than the hydrolysis of III.

Chromatography, High Pressure Liquid↗
PubMed1980

Factor D of the alternative pathway of human complement. Purification, alignment and N-terminal amino acid sequences of the major cyanogen bromide fragments, and localization of the serine residue at the active site.

The serine esterase factor D of the complement system was purified from outdated human plasma with a yield of 20% of the initial haemolytic activity found in serum. This represented an approx. 60 000-fold purification. The final product was homogeneous as judged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis (with an apparent mol.wt. of 24 000), its migration as a single component in a variety of fractionation procedures based on size and charge, and its N-terminal amino-acid-sequence analysis. The N-terminal amino acid sequence of the first 36 residues of the intact molecule was found to be homologous with the N-terminal amino acid sequences of the catalytic chains of other serine esterases. Factor D showed an especially strong homology (greater than 60% identity) with rat 'group-specific protease' [Woodbury, Katunuma, Kobayashi, Titani, & Neurath (1978) Biochemistry 17, 811-819] over the first 16 amino acid residues. This similarity is of interest since it is considered that both enzymes may be synthesized in their active, rather than zymogen, forms. The three major CNBr fragments of factor D, which had apparent mol.wts. of 15 800, 6600 and 1700, were purified and then aligned by N-terminal amino acid sequence analysis and amino acid analysis. By using factor D labelled with di-[1,3-14C]isopropylphosphofluoridate it was shown that the CNBr fragment of apparent mol.wt. 6600, which is located in the C-terminal region of factor D, contained the active serine residue. The amino acid sequence around this residue was determined.

Amino Acid Sequence↗
PubMed1979

Enantiomeric purity of naproxen by liquid chromatographic analysis of its diastereomeric octyl esters.

A sensitive and specific analytical method was developed to determine the enantiomeric purity of naproxen. A simple derivatization of naproxen with (S)-(+)-2-octanol proceeded quantitatively and gave a mixture of diastereomeric esters displaying baseline separation on liquid chromatography. The ratio of these esters was the same as the ratio of enantiomers present in naproxen samples assayed. Reproducibility of the method was excellent.

Chromatography, Liquid↗