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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 559 records · Page 31Linked to original sources
PubMed1991

Salmeterol: a novel drug for the treatment of asthma.

The beta-stimulant bronchodilators have proved clinically very effective in the treatment of reversible airways obstructive disease. However, the currently available drugs are relatively short-acting. Salmeterol, a new long-acting, beta 2-adrenoceptor agonist has been developed and shown to induce persistent relaxation of airways smooth muscle in vitro and sustained bronchodilatation in vivo, and to have significant anti-inflammatory activity in the lung, suppressing inflammatory mediator release and inflammatory cell infiltration and inhibiting vascular permeability and oedema formation. Clinical studies in asthmatic patients have demonstrated that salmeterol causes bronchodilatation for 12-14 hours. In addition, treatment with salmeterol produces a marked increase in morning peak flow, a reduction in diurnal variation, and the elimination of nocturnal asthma symptoms. The combination of long-acting bronchodilator and anti-inflammatory effects suggests that salmeterol may represent an important new advance in the treatment of bronchial asthma.

Adrenergic beta-Agonists↗
PubMed1991

Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation.

The enzyme ornithine decarboxylase (ODC) has been implicated in the control of cell growth, differentiation and tumor promotion. To further elucidate its precise role a murine ODC cDNA was inserted into the retrovirus-derived vector pMV7 and retrovirus-like particles were used to infect NIH3T3 and rat 6(R6) fibroblasts. Derivatives were obtained that stably express a 5-40 fold increase in ODC enzyme activity. Despite these high levels of enzyme activity the cells retained a normal morphology and displayed no major changes in growth properties in monolayer culture or in agar suspension. On the other hand, R6 cells that expressed high levels of ODC displayed a marked increase in susceptibility to morphologic transformation by an activated c-H-ras oncogene. These results provide the first evidence that ODC can cooperate with an activated oncogene in the process of cell transformation. Although the mechanism is not known, these findings may be relevant to the multistage carcinogenic process.

Animals↗
PubMed1991

Parthenogenetic activation and development of fresh and aged human oocytes.

OBJECTIVE: To develop a systematic study of the parthenogenetic activation and early development of human oocytes. DESIGN: Human oocytes (both freshly retrieved and remaining unfertilized after exposure to spermatozoa) were exposed to alcohol or calcium ionophore and examined for evidence of activation. SETTING: Academic research department of a teaching hospital. PATIENTS, PARTICIPANTS: Couples donating oocytes were undergoing therapy for infertility with in vitro fertilization or gamete intrafallopian transfer. INTERVENTIONS: Gonadotropin-releasing hormone agonist and human menopausal gonadotropin were administered at therapeutic doses. MAIN OUTCOME MEASURES: After application of activation stimuli at varying doses and durations, oocytes were examined for evidence of meiotic reactivation, pronuclear formation, deoxyribonucleic acid content, and cleavage. RESULTS: Fresh and aged human oocytes can be activated parthenogenetically using a calcium ionophore but at lower rates than seen for mouse oocytes (typically 50% to 60% versus 90% to 100%, respectively). Ethanol was a poor activating agent (maximum activation rate 16%). Human parthenotes can complete division to the eight cell stage. CONCLUSIONS: These results indicate that parthenote embryos may provide a source of material to study changes that occur during early human development. The data also raise the possibility that some early human pregnancy losses may involve oocytes that have been parthenogenetically activated spontaneously.

Calcimycin↗
PubMed1991

Assignment of Emery-Dreifuss muscular dystrophy to the distal region of Xq28: the results of a collaborative study.

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy associated with cardiomyopathy that is distinct from the Duchenne and Becker forms of X-linked muscular dystrophy. Linkage analysis has assigned EDMD to the terminal region of the human X chromosome long arm. We report here further linkage analysis in two multigenerational EDMD families using seven Xq28 marker loci. Cumulative lod scores suggest that EDMD is approximately 2 cM from DXS52 (lod = 15.67) and very close to the factor VIII (F8C) and the red/green color pigment (R/GCP) loci, with respective lod scores of 9.62 and 10.77, without a single recombinant. Several recombinations between EDMD and three proximal Xq28 markers suggest that the EDMD gene is located in distal Xq28. Multipoint linkage analysis indicates that the odds are 2,000:1 that EDMD lies distal to DXS305. These data substantially refine the ability to perform accurate carrier detection, prenatal diagnosis, and the presymptomatic diagnosis of at-risk males for EDMD by linkage analysis. The positioning of the EDMD locus close to the loci for F8C and R/GCP will assist in future efforts to identify and isolate the disease gene.

Chromosome Mapping↗
PubMed1991

Nursing administration model for administrative practice.

The winds of change have swept in a new era for nursing. Complex decisions can be aided by a conceptual model for nursing administration practice. The authors discuss how the Iowa Model of Nursing Administration can be used by nurse administrators to solve administrative problems. Two practical examples are described.

Decision Making, Organizational↗
PubMed1990

Neurochemical effects of an acute treatment with 4-methylaminorex: a new stimulant of abuse.

4-Methylaminorex (4-MAX) is an amphetamine analog which has recently gained attention due to its potential as a stimulant of abuse. The present study characterized the acute neurochemical changes elicited after a single dose of 4-MAX. Thus, dose-response and time-response studies were conducted in order to assess the effects of this drug on monoaminergic and neuropeptide systems in extrapyramidal and limbic structures. The most dramatic responses in the dose-effect experiments (animals killed 3 h after treatment) were a 2-fold increase in neostriatal homovanillic acid levels and a decrease in neostriatal tryptophan hydroxylase activity to 33% of control in the 20 mg/kg group. Because all animals in the 20 mg/kg group experienced convulsions, 10 mg/kg was used for the time-response studies. The most striking effects in these studies included a reduction in dopamine concentrations to 71% of control, and an increase to 270% of control in the concentrations of dihydroxyphenylacetic acid 30 min after 4-MAX administration. In addition, neostriatal neurotensin and dynorphin A levels increased to approximately 200 and 400% of control, respectively, 18 h after a 10 mg/kg dose. These data suggest that 4-MAX is a potent dopamine releaser, which decreases tryptophan hydroxylase activity in a manner similar to other amphetamine-related drugs. However, in contrast to other amphetamine analogs, 4-MAX has potent convulsant actions.

Animals↗
PubMed1990

Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis.

Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.

Adult↗
PubMed1990

The pharmacology of salmeterol.

The pharmacology of salmeterol hydroxynaphthoate (SALM) has been investigated in respiratory tissues in vitro and in animal models in vivo. In guinea pig trachea and human bronchial smooth muscle, SALM was more potent than isoprenaline (ISO), salbutamol (SALB), and clenbuterol (CLEN). The duration of action was greater than 7 h, whereas that for ISO, SALB, and CLEN was 2, 11, and 45 min, respectively. The sustained activity of SALM was reversed by sotalol, but was reestablished when the beta-blocker was removed. SALM was greater than 3000-fold weaker than ISO in cardiac tissues, indicating high beta 2-adrenoceptor selectivity. In the conscious guinea pig, aerosolized SALM, SALB, and CLEN caused dose-related bronchodilatation. The activity of SALM persisted for at least 6 h, compared with less than 2 h for SALB and CLEN. SALM is also a potent inhibitor of mediator release from human lung, this effect being sustained for up to 20 hours. In guinea pig airways in vivo, SALM inhibited histamine-induced plasma protein extravasation for approximately 8 h. Salmeterol is a potent and selective beta 2-adrenoceptor agonist with a unique profile of action. It induces persistent bronchodilatation, sustained suppression of mediator release, and long-lasting inhibition of edema formation. This combination of properties may represent an important new advance in the treatment of bronchial asthma.

Adrenergic beta-Agonists↗
PubMed1990

The filtration characteristics of the aqueous outflow system.

To determine the filtration characteristics of the aqueous outflow system, microspheres (0.18 micron -1.1 micron) were perfused through enucleated human and bovine eyes. The microspheres were smaller than morphologically determined flow dimensions, and yet a significant fraction of all sizes of microspheres were captured. The bovine (calf) aqueous outflow system was found to be a far more efficient filter than was the human outflow system. Combining the experimental results with morphological observations and theoretical calculations leads to the conclusion that 'sticky wall' interactions are responsible for much of the microsphere capture, and that the site of filtration may be distinct from the site of flow resistance. Consequently, the dimension of the sites generating flow resistance cannot be determined from filtration studies.

Animals↗
PubMed1990

A boxing technique for making moulages of facial defects.

A technique using irreversible hydrocolloid in conjunction with conventional boxing method is described for making impressions of facial defects. The technique improves control of impression material without causing distortion of soft tissue adjacent to facial defects.

Colloids↗
PubMed1990

Prostaglandin D2 modulates human neutrophil intracellular calcium flux and inhibits superoxide release via its ring carbonyl.

We compared the effects of prostaglandin D2 (PGD2), prostaglandin F2 alpha (PGF2) and various ketones on superoxide (OX) release by human neutrophils, which had been stimulated by N-formyl methionyl leucyl phenylalanine (FMLP). Our data suggested that the ring carbonyl of PGD2 is essential to its inhibitory effect on OX release, but the carbonyl group as a ketone, alone is not sufficient. Using the fluorescent Ca2+ probe, Fura-2AM, we found that PGD2 increased the rate of decline of FMLP stimulated intracellular free Ca2+ (Ca)i, but that PGF2 had no effect. cAMP altered FMLP stimulated (Ca)i, in a pattern similar to PGD2. Furthermore, the ring carbonyl of PGD2 is crucial to its effect on OX as well as on (Ca)i.

Calcium↗