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M Johnson

Publications and source records attributed to M Johnson.

At least 415 records · Page 23Linked to original sources
PubMed1995

Pharmacology of long-acting beta-agonists.

BACKGROUND: When first developed more than 30 years ago, beta-agonists (eg, isoproterenol) did not discriminate between beta 1- and beta 2-subtypes of the beta-adrenoceptor, resulting in effective bronchodilation but also unwanted extrapulmonary side effects. Albuterol later became the prototype selective beta 2-agonist--well tolerated and highly effective in controlling bronchospasm. The major drawback of these more selective beta 2-agonists, however, was their short duration of action (four to six hours). This problem has been largely overcome with the development of a new generation of long-acting beta 2-agonists represented by salmeterol and formoterol (not currently available in the US). This paper summarizes the mechanism of action, potency and receptor selectivity, onset and duration of action, and bronchodilator and nonbronchodilator activity of these long-acting beta 2-agonists. SUMMARY: Preclinical studies have shown both salmeterol and formoterol to be potent and selective at beta 2-adrenoceptors but to have different mechanisms and durations of action. The pharmacologic profiles of these drugs result from prolonged activation of beta 2-adrenoceptors, leading to long-lasting bronchodilation (with no evidence of tolerance or tachyphylaxis) and additional nonbronchodilator properties. The long-acting beta 2-agonists represent a therapeutic advance in the management of asthma.

Albuterol↗
PubMed1995

Nurses' perceptions of antiemetic effectiveness.

PURPOSES: To determine which antiemetics are being used with ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) for patients receiving emetogenic chemotherapy, identify the more frequently administered antiemetic regimens, and ascertain nurses' perceptions of the effectiveness of these regimens. DESIGN: Descriptive survey. SETTING: Continental United States. SAMPLE: A random sample (N = 962) of Oncology Nursing Society members who designate themselves as practicing in the area of chemotherapy. METHODS: The Antiemetic Drug(s)/Drug Combination(s) Inventory, an open-ended questionnaire soliciting information on first- and second-line antiemetic regimens for emetogenic chemotherapy protocols, was mailed to 5,950 oncology nurses. Descriptive statistics and nondistributive analysis were used to analyze the data. FINDINGS: Ondansetron was used in 7 of 10 antiemetic regimens, which accounted for 50% of the most frequently used regimens. Nurses rated first-line antiemetic combinations as highly effective. Ondansetron alone was ranked as the seventh most effective first-line antiemetic for cisplatin protocols and fifth for noncisplatin protocols. Nurses noted limitations of ondansetron use, which included delayed nausea and vomiting and the drug's high cost. CONCLUSIONS: Study participants indicated that a variety of drugs were used in antiemetic regimens. Ondansetron use has improved the control of post-chemotherapy nausea, vomiting, and retching. IMPLICATIONS FOR NURSING PRACTICE: Antiemetics are administered regularly in the hospital and home to decrease chemotherapy-related nausea, vomiting, and retching. Managing these side-effects requires superior assessment skills and extensive knowledge of pharmacologic actions. Patient and family education on antiemetics is essential in light of increased administration of outpatient chemotherapy.

Antiemetics↗
PubMed1994

Age-related changes of scleral hydration and sulfated glycosaminoglycans.

Human scleras were analyzed to determine if tissue hydration changed in an age-related fashion, and whether this change could be related to decreased levels of glycosaminoglycans. The anterior half of normal human scleras were examined with donor ages ranging from newborn to 99 years (n = 40). Tissue hydration was found to decrease by 1.06% per decade (P = 0.0012). Glycosaminoglycans were extracted from scleras with guanidine hydrochloride, purified by anion exchange chromatography and quantitated using dimethylene blue and selective enzymatic digestion. The glycosaminoglycans of the sclera were primarily dermatan sulfate and chondroitin sulfate with small quantities of hyaluronic acid. While no loss of chondroitin sulfate with age was detected, a significant age-related loss of dermatan sulfate was found (P = 0.0006, n = 14). An examination of the relationship between glycosaminoglycan concentration and scleral hydration showed that increased levels of sulfated glycosaminoglycans were associated with increased levels of scleral hydration (P < 0.02, n = 14). No improvement in the correlation could be achieved by considering either dermatan sulfate or chondroitin sulfate individually. Our results suggest that, as in other connective tissues, aging is associated with a loss of glycosaminoglycans, and their loss is coincident with decreased tissue hydration.

Adolescent↗
PubMed1994

Effect of neonatal hypoxia-ischemia on nigro-striatal dopamine receptors and on striatal neuropeptide Y, dynorphin A and substance P concentrations in rats.

Perinatal hypoxic-ischemic brain injury was induced in 7- to 8-day-old rats by ligating the left carotid artery with subsequent exposure to 9% oxygen atmosphere for 2.5 h. The animals were killed 7 days later and grouped according to the degree of brain injury sustained after hypoxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, was reduced to 64% of contralateral tissue. The protein content was not altered in other groups including control animals exposed to air and in sham-operated animals exposed to hypoxic conditions. The concentration of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-like immunoreactivity (DLI) from brains with extensive damage were increased to 481% and 285% of the contralateral side, respectively. Hypoxia-ischemia increased striatal neuropeptide Y-like immunoreactivity (NPYLI) concentration from brains with extensive damage to 157% of contralateral side, but when the results were expressed as total NPYLI content per striatum, NPYLI content in striatum with extensive damage remained unaltered. Substance P-like immunoreactivity (SPLI) concentration and total content per striatum from brains with extensive damage were reduced to 66% and 43% of the contralateral side, respectively. D1 and D2 receptor density in animals killed 10 days after injury was reduced by 24% and 22% of control, respectively, in striatum from brains with extensive damage. These results indicate complex changes in brain neuropeptides following neonatal hypoxia-ischemia. Damage in the substance P system could have functional effects on dopaminergic transmission while the increase in NPYLI and in DLI concentrations may respectively reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The decrease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in separate neurons.

Aging↗
PubMed1994

Inhibitory actions of salmeterol on human airway macrophages and blood monocytes.

The effect of beta 2-adrenoceptor agonists, salmeterol and salbutamol on thromboxane B2 release from human airway macrophages and peripheral blood monocytes has been examined. Salbutamol (0.1-100 microM) had no inhibitory effect on the release of thromboxane B2 from human airway macrophages. Salmeterol (0.1-100 microM) caused dose-dependent inhibition of thromboxane B2 release from human airway macrophages stimulated by either zymosan or calcium ionophore A23187. This inhibition was not blocked by propranolol (1 microM). The activity of adenylyl cyclase in homogenates of human airway macrophages was increased by NaF (10 mM) by 8.5-fold and salmeterol (100 microM) and isoprenaline (10 microM) by 1.6- and 1.4-fold, respectively. Isoprenaline alone was inhibited by propranolol (1 microM). Salmeterol caused a biphasic inhibition of peripheral blood monocyte thromboxane B2 release. The inhibition at low (10 nM) concentrations of salmeterol was blocked by propranolol and that at higher concentrations (100 microM) was unaffected. The long lipophilic tail of salmeterol had similar inhibitory effects on the airway macrophages to salmeterol itself, and on the peripheral blood monocytes its action resembled that of the highest concentrations of salmeterol used. It is concluded that salmeterol inhibits mediator release from human airway macrophages by a beta-adrenoceptor independent mechanism and from blood monocytes by both beta-adrenoceptor and non-beta-adrenoceptor mechanisms. The latter mechanism may be associated with the lipophilic properties of the salmeterol molecule.

Adenylyl Cyclases↗
PubMed1994

Plasma pyridoxal phosphate in anxiety disorders.

One hundred and eighty-nine subjects with either generalized anxiety disorder, panic disorder, or obsessive-compulsive disorder were evaluated for plasma pyridoxal phosphate (PLP) levels and compared with normal controls. There was no difference in plasma PLP levels between the anxiety disorder groups and normal controls. Low levels of plasma PLP were found in 42% of the controls. Our results suggest that previous reports of low PLP levels in psychiatric patients are unlikely to be significant in the etiology of the psychiatric disorders.

Adult↗
PubMed1994

Hemoglobin stimulates mononuclear leukocytes to release interleukin-8 and tumor necrosis factor alpha.

Incubation of human mononuclear leukocytes (MNL) with human stroma-free hemolysate (SFH), purified adult hemoglobin Ao (HbAo), and oxidized HbAo (METHb) caused MNL to release compounds into the supernate that mediated neutrophil (polymorphonuclear leukocytes, PMN) chemotaxis and PMN adherence to human umbilical vein endothelial cells (HUVEC). Chemotaxis and PMN adherence to HUVEC were reduced significantly when supernates were preincubated with neutralizing antibodies to interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), respectively, suggesting that IL-8 and TNF-alpha played significant roles in mediating these activities. Greatest chemotactic activity was observed in supernates of MNL treated with HbAo; while greatest PMN/endothelial cell (EC) adherence activity was observed in supernates of MNL treated with METHb. Furthermore, PMN/EC adherence activity was a function of METHb content in each hemoglobin solution. PMN chemotaxis, PMN adherence to HUVEC, and cytokine release increased as a function of increasing incubation time. Chemotactic activity was detected in HbAo-treated and METHb-treated MNL supernates after incubation for 6 hours and was maximal by 10 hours. IL-8 was detected in both HbAo and METHb-MNL supernates by 4 hours. PMN/EC adherence activity was detected in HbAo-MNL supernates at 10 hours and in METHb-MNL supernates at 4 hours. TNF-alpha was detected in METHb and HbAo-MNL supernates at 4 and 12 hours, respectively. These results suggest that hemoglobin solutions stimulate MNL to release IL-8 and TNF-alpha in quantities sufficient to induce PMN chemotaxis and PMN adherence to HUVEC. This is a US government work. There are no restrictions on its use.

Cell Adhesion↗
PubMed1994

The distribution of excitatory amino acid receptors in the normal human midbrain and basal ganglia with implications for Parkinson's disease: a quantitative autoradiographic study using [3H]MK-801, [3H]glycine, [3H]CNQX and [3H]kainate.

Quantitative receptor autoradiography using [3H]MK-801, [3H]glycine, [3H]CNQX and [3H]kainate was employed to determine the distribution and density of excitatory amino acid (EAA) binding sites in the midbrain and basal ganglia of the normal human nervous system. Detailed knowledge of the anatomy and subtype specificity of glutamate receptors is important both in understanding the normal physiology of basal ganglia neurotransmission and the pathophysiological changes occurring in diseases affecting the basal ganglia such as Parkinson's disease (PD). In PD, glutamate receptor activation may contribute to cell death of dopaminergic neurones in the substantia nigra. In addition, perturbation of glutamate neurotransmission resulting from dopamine depletion in the basal ganglia is likely to contribute to the clinical manifestations of motor dysfunction. The distribution and density of ligand binding representing N-methyl-D-aspartate (NMDA), AMPA (2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptors has a heterogeneous distribution in the human midbrain and basal ganglia. In the substantia nigra relatively high densities of [3H]MK-801 and strychnine-insensitive [3H]glycine binding sites representing NMDA receptors were present, whereas only moderate densities of [3H]CNQX and [3H]kainate binding sites were present, compared to other regions. In both the medial globus pallidus and subthalamic nucleus, binding sites representing NMDA, AMPA and kainate receptors were all present at low density. These findings suggest that the clinical usefulness of modifying glutamatergic neurotransmission in these basal ganglia nuclei may be limited by the relatively low density of EAA binding sites present.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Age-accumulation of fluoride in an experimental population of short-tailed field voles (Microtus agrestis L.).

This paper reports on the effects of a diet of vegetation contaminated by atmospheric fluorides upon the growth and age-accumulation of fluoride by a laboratory-maintained population of the short-tailed field vole, M. agrestis, a wild herbivore. Offspring of the voles fed the contaminated diet generally had lower growth rates and body weights during infancy and early adulthood than those fed a reference diet. The concentration and total fluoride burden of the femur were significantly higher in voles fed the contaminated diet. Following birth, the incisors of all offspring appeared normal, regardless of diet. Later, from approaching weaning onwards, the incisors of offspring weaned on to the contaminated diet showed marked morphological changes and severe dental lesions. Fluoride concentrations in the femur increased rapidly in late-suckling infants whose mothers were fed the contaminated diet, but appeared to reach an equilibrium concentration in adults which coincided with a slowing of the growth rate. Age is clearly an important influence upon the toxicology of fluoride because it affects the rate of accumulation by skeletal tissue.

Age Factors↗
PubMed1994

Arrays of complementary oligonucleotides for analysing the hybridisation behaviour of nucleic acids.

Arrays of oligonucleotides corresponding to a full set of complements of a known sequence can be made in a single series of base couplings in which each base in the complement is added in turn. Coupling is carried out on the surface of a solid support such as a glass plate, using a device which applies reagents in a defined area. The device is displaced by a fixed movement after each coupling reaction so that consecutive couplings overlap only a portion of previous ones. The shape and size of the device and the amount by which it is displaced at each step determines the length of the oligonucleotides. Certain shapes create arrays of oligonucleotides from mononucleotides up to a given length in a single series of couplings. The array is used in a hybridisation reaction to a labelled target sequence, and shows the hybridisation behaviour of every oligonucleotide in the target sequence with its complement in the array. Applications include sequence comparison to test for mutation, analysis of secondary structure, and optimisation of PCR primer and antisense oligonucleotide design.

Base Sequence↗
PubMed1994

N-methyl-D-aspartate (NMDA) receptors in the spinal cord and motor cortex in motor neuron disease: a quantitative autoradiographic study using [3H]MK-801.

The distribution and density of NMDA receptors in spinal cord and motor cortex was compared in motor neuron disease (MND; 10 cases) and controls (8 cases) using [3H]MK-801 autoradiography. In the spinal ventral horn of MND cases, [3H]MK-801 binding was reduced and there were fewer focal hot spots of binding. These changes are likely to reflect loss of motor neurons (MN) bearing NMDA receptors. [3H]MK-801 binding was increased in intermediate spinal grey matter and deeper layers of the motor cortex in MND cases compared to controls. This may represent either an adaptive response to MN loss or a pathophysiological phenomenon contributing to MN degeneration.

Aged↗
PubMed1994

Formoterol on airway smooth muscle and human lung mast cells: a comparison with salbutamol and salmeterol.

Formoterol, like salbutamol and salmeterol, relaxed isolated preparations of guinea-pig trachea and human bronchus, and inhibited antigen-induced mediator release from human lung fragments in a concentration-related fashion. In each case, these actions were mediated through beta 2-adrenoceptors, with formoterol being 50-120-fold more potent than salbutamol, and 2-27-fold more potent than salmeterol. The duration of action of formoterol was longer than that of salbutamol in all preparations, but was markedly shorter than that of salmeterol, whose actions persisted for many hours despite continuous or extensive washing of the tissues. In conscious guinea-pigs, inhaled formoterol, salbutamol and salmeterol all caused dose-related inhibition of histamine-induced bronchoconstriction. Formoterol was again more potent (10-20-fold) than either salbutamol or salmeterol. However, while the actions of a threshold-effective dose of formoterol persisted for less than 3 h, somewhat longer than those of salbutamol (< 1.5 h), an equivalent dose of salmeterol was active for at least 6 h. Therefore, while formoterol is a potent beta 2-adrenoceptor agonist in vitro and in vivo, and is consistently longer-acting than salbutamol, its duration of action is markedly shorter than that of salmeterol.

Albuterol↗
PubMed1994

A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin.

BACKGROUND: The management of heparin therapy in patients who have a subtherapeutic activated partial thromboplastin time (APTT) despite high doses of heparin is problematic because the risk of heparin-associated bleeding increases with dose. Results of experimental studies in animals indicate that when the APTT response to heparin is blunted by infusion of procoagulants, dose escalation can be avoided without compromising efficacy, by monitoring treatment with a heparin assay. METHODS: A randomized, controlled trial was conducted in which patients with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis who required 35,000 U or more of intravenous heparin by continuous infusion during the previous 24 hours were allocated to have their heparin therapy monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a heparin level of 0.2 to 0.4 U/mL by protamine titration. RESULTS: Three (4.6%) of 65 patients in the anti-factor Xa group experienced recurrent venous thromboembolism compared with four (6.1%) of 66 patients in the APTT group (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti-factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4). During the period of heparin therapy before warfarin treatment was begun, the patients in the APTT group required a statistically significantly greater amount of heparin compared with the patients in the anti-factor Xa group. The daily mean APTT was subtherapeutic in patients in the anti-factor Xa group, and it was within the therapeutic range in the APTT group. The daily mean anti-factor Xa levels for both groups were within the therapeutic range. CONCLUSION: The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.

Acute Disease↗
PubMed1994

Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.

A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Evidence for a p53-independent pathway for upregulation of SDI1/CIP1/WAF1/p21 RNA in human cells.

SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent contact-inhibited or serum-deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth-arrest-inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of gamma-radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild-type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis.

Antimetabolites↗
PubMed1994

Lenticular alterations in hypertensive rats.

Cataract development has been reported in Dahl salt-sensitive (DS) hypertensive rats with high-salt intake. An alteration in ionic transport and electrolyte balance has been reported to be associated with hypertension in these animals. A morphological evaluation of the lenses of salt-sensitive 'cataract-prone' (DS) and salt-resistant (DR) control animals is lacking. We undertook this investigation to evaluate changes in lenticular morphology and in systolic blood pressure (SBP) following administration of high-salt. Both DS and DR rats were given high-salt for up to 33 weeks. Lenses were extracted at desired intervals following the initiation of the high-salt diet and processed for light and transmission electron microscopy. Except for some variations between animals, our study showed that DR rats, in general, exhibited normal SBP and relatively normal morphology. In comparison, the lenses of DS hypertensive rats demonstrated the following major changes: (1) some epithelial cells showed multilayering, nodule formation, pyknotic nuclei, swelling of cell organelles, presence of a large number of lysosomes, and distension of intercellular spaces, (2) disorganization of the bow and (3) swelling of fiber cells in the equatorial region. These changes were similar to those observed in precataractous stages during the development of several types of experimentally induced cataracts and indicate an alteration in normal electrolyte balance as well as hyperosmolarity. Changes in ion transport and electrolyte imbalance have been reported in the lenses of DS rats on high-salt diet. These alterations and a defect in the sodium-potassium pump may be responsible for cataract development in these hypertensive rats.

Animals↗