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Biomedical subjects

R M Allen

Publications and source records attributed to R M Allen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Randomised trial of an asthma self-management programme for adults.

BACKGROUND: A hospital based, community service asthma education programme for adults to improve asthma knowledge, promote compliance with medication, and reduce morbidity was evaluated. METHODS: The programme was evaluated using a randomised experimental and control group design with repeated measurements over 12 months. A volunteer community sample of 192 respondents was recruited of whom 116 satisfied the inclusion criteria. At the 12 month follow up some data were obtained for all subjects. Intervention subjects attended four 2.5 hour education sessions at weekly intervals. An asthma knowledge questionnaire was administered and compliance was assessed from diary records. Morbidity was assessed retrospectively by questionnaire, prospectively by diary, and objectively by spirometry and serial peak expiratory flow rate monitoring. The adequacy of medical treatment was also assessed. Data were collected at baseline, immediately after the intervention, and at three, six, nine, and 12 months after intervention. RESULTS: Improvements occurred in knowledge and compliance in the intervention group but the impact on morbidity was modest; this was due, at least in part, to the inadequacy of medical treatment. CONCLUSIONS: Treatment of asthma should be reviewed and optimised in conjunction with self-management programmes in order to improve health outcomes.

Adolescent↗
PubMed1994

Diagnosing ventilator-associated pneumonia: the role of bronchoscopy.

OBJECTIVE: To discuss the two diagnostic procedures used most frequently to obtain uncontaminated lower airway secretions during bronchoscopy. DESIGN: This article reviews the contributing risk factors of ventilator-associated pneumonia (VAP) and the recent studies that have assessed the usefulness of the protected specimen brush (PSB) and bronchoalveolar lavage (BAL) in the nonimmunocompromised host. RESULTS: A prompt, accurate diagnosis of VAP, including specific identification of the bacterial pathogen, remains a common challenge in the intensive-care unit. Standard clinical criteria are of suboptimal specificity for making decisions, including selecting antibiotic therapy. Bronchoscopic techniques of lung secretion sampling can be used in the intensive-care unit in an effort to overcome the effects of oropharyngeal contamination. The PSB and BAL, used appropriately, can help intensive-care clinicians formulate specific antimicrobial therapy. Evaluation of intracellular bacteria obtained by BAL has been reported to be useful in guiding empiric antibiotic therapy while the final results of cultures obtained with the PSB are pending. Prior antibiotic therapy, however, may confound the interpretation and clinical utility of results. CONCLUSION: Currently, for a patient taking antibiotic therapy, no reliable technique nor quantitative culture threshold exists to help in diagnosing suspected VAP or in guiding antibiotic therapy. If the clinical situation allows, antibiotic therapy should be discontinued for 48 hours; then, the PSB, BAL, protected BAL, or endobronchial aspiration should be used. These contemporary modalities, however, necessitate further clinical trials before widespread use is warranted.

Anti-Bacterial Agents↗
PubMed1994

Nucleotide and divalent cation specificity of in vitro iron-molybdenum cofactor synthesis.

The nucleotide and divalent cation requirements of the in vitro iron-molybdenum cofactor (FeMo-co) synthesis system have been compared with those of substrate reduction by nitrogenase. The FeMo-co synthesis system specifically requires ATP, whereas both 1,N6-etheno-ATP and 2'-deoxy-ATP function in place of ATP in substrate reduction (M. F. Weston, S. Kotake, and L. C. Davis, Arch. Biochem. Biophys. 225:809-817, 1983). Mn2+, Ca2+, and Fe2+ substitute for Mg2+ to various extents in in vitro FeMo-co synthesis, whereas Ca2+ is ineffective in substrate reduction by nitrogenase. The observed differences in the nucleotide and divalent cation specificities suggest a role(s) for the nucleotide and divalent cation in in vitro FeMo-co synthesis that is distinct from their role(s) in substrate reduction.

Adenosine Triphosphate↗
PubMed1994

Biosynthesis of the iron-molybdenum cofactor of nitrogenase.

The iron-molybdenum cofactor (FeMo-co) of nitrogenase is a unique molybdenum-containing prosthetic group that has been proposed to form an integral part of the active site of dinitrogenase. In Klebsiella pneumoniae, at least six nif (nitrogen fixation) gene products are required for the biosynthesis of FeMo-co, including NIFB, NIFNE, NIFH, NIFQ, and NIFV. An in vitro system for the synthesis of FeMo-co, which requires MgATP, molybdate, homocitrate, and at least the products of nifN, E, B, and H, has provided an enzymatic assay for the purification of many of the gene products required for FeMo-co biosynthesis. Although the structure of the cofactor has been solved recently, much about the biosynthetic pathway remains unknown. This article reviews what is known about the various components required for FeMo-co biosynthesis.

Genes, Bacterial↗
PubMed1993

Dinitrogenase reductase- and MgATP-dependent maturation of apodinitrogenase from Azotobacter vinelandii.

The requirements for iron-molybdenum cofactor (FeMo-co) activation of apodinitrogenase from Azotobacter vinelandii strain UW97, which lacks dinitrogenase reductase activity as assayed by substrate reduction, have been examined. Activation of apodinitrogenase from strain UW97 by FeMo-co requires the addition of both dinitrogenase reductase and MgATP. When the same apodinitrogenase is pretreated with dinitrogenase reductase and MgATP and then partially purified, however, it does not require these components for activation by FeMo-co. This suggests that dinitrogenase reductase and MgATP are involved in processing apodinitrogenase to a FeMo-co activatable form. This processing step coincides with a change in the subunit composition of apodinitrogenase from alpha 2 beta 2 to a form with an additional subunit (gamma) attached. The apodinitrogenase with the associated gamma subunit is apparently the form of the protein that is competent for activation by FeMo-co.

Adenosine Triphosphate↗
PubMed1992

IL-7 up-regulates the expression of IL-8 from resting and stimulated human blood monocytes.

Blood monocytes are important cellular sources of a vast array of bioactive substances, including regulatory and chemotactic cytokines. The regulation of these cytokines is of critical importance to the expression of acute and chronic inflammatory responses. IL-7, a T and B cell-activating cytokine, has recently been shown to have stimulatory effects on the expression of several monocyte-derived proinflammatory cytokines. We now describe the induction of IL-8 mRNA and extracellular protein from human blood monocytes by IL-7. The up-regulation of IL-8 mRNA by IL-7 was not altered by concomitant treatment with cycloheximide, suggesting that the direct stimulatory effects of IL-7 were not dependent upon de novo protein synthesis. In addition, IL-7 significantly potentiated the production of IL-8 from LPS-, TNF-, and IL-1-treated peripheral blood monocytes. Our findings suggest that IL-7 may play a critical role in the modulation of macrophage-derived cytokine expression and may function in vivo as an important proinflammatory cytokine.

Base Sequence↗
PubMed1992

Plausible structure of the iron-molybdenum cofactor of nitrogenase.

A plausible structure of the iron-molybdenum cofactor of nitrogenase [reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolyzing), EC 1.18.6.1] is presented based on altered substrate reduction properties of dinitrogenase containing homocitrate analogs within the cofactor. Alterations on each carbon of the four-carbon homocitrate backbone were correlated with altered substrate reduction properties of dinitrogenase containing these analogs. Altered substrate reduction properties are the basis for a model in which homocitrate is oriented about two cubane metal clusters.

Formates↗
PubMed1992

Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone.

Mononuclear phagocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophages produce a vast array of regulatory and chemotactic cytokines. Interleukin-8 (IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammatory events. In this investigation, we describe the effects of prostaglandin E2 (PGE2) and dexamethasone (Dex) on IL-8 mRNA and protein expression from lipopolysaccharide (LPS)-treated human peripheral blood monocytes (PBM) and alveolar macrophages (AM). We demonstrate the dose-dependent suppression of IL-8 from LPS-stimulated PBM by PGE2. Treatment of stimulated PBM with 10(-6) M PGE2 resulted in maximal inhibition, causing 60% suppression of both IL-8 mRNA and extracellular protein levels. In contrast, PGE2 (10(-6) to 10(-8) M) did not significantly alter IL-8 mRNA or protein expression from LPS-treated AM. Treatment of LPS-stimulated PBM and AM with Dex (10(-6) to 10(-8) M) resulted in 75% decline in IL-8 mRNA and extracellular protein from either cell population. Pretreatment of PBM with PGE2 or Dex 1 or 2 h before LPS stimulation caused a significant suppression of steady-state IL-8 mRNA levels; however, administration of either of these modulators 1 or 2 h after LPS stimulation failed to have an inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Cytokine-induced neutrophil-derived interleukin-8.

During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8). Neutrophils freshly isolated from whole blood were not found to constitutively express IL-8 mRNA. In contrast, when these leukocytes were cultured on plastic they were activated, leading to the significant expression of de novo steady-state levels of IL-8 mRNA. In addition, when neutrophils were treated with cycloheximide, there was evidence for "superinduction" of steady-state levels of IL-8 mRNA and inhibition of antigenic IL-8 production. Neutrophils were subsequently stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha, or interleukin-1-beta and were found to express IL-8 mRNA and antigen in both a time- and dose-dependent manner. Furthermore, neutrophils stimulated with traditional chemotactic/activating factors, such as the split product of the fifth component of complement (C5a), formylmethionyleucylphenylalanine (fMLP), and leukotriene B4 (LTB4) in a dose-dependent manner did not produce significant antigenic IL-8, as compared with unstimulated controls. In contrast, when neutrophils were exposed to either of these neutrophil agonists in the presence of LPS, the production of antigenic IL-8 was significantly elevated, as compared with either of the stimuli alone, suggesting a synergistic response. These data would suggest that the neutrophil can no longer be viewed as only a phagocyte or warehouse for proteolytic enzymes, but is a pivotal effector cell that is able to respond to mediators in its environment and generate cytokines. This latter neutrophil response may be important for either the elicitation of additional neutrophils or to orchestrate the conventional immune response at sites of inflammation.

Antigens↗
PubMed1991

Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking.

The pulmonary fibroblast's (PF) unique location allows it to communicate in a bidirectional fashion between the vascular compartment and alveolar airspace, placing it in a strategic position for the elicitation of inflammatory leukocytes into the lung. In this study, we demonstrate that PF may contribute to pulmonary inflammation through the production of a potent neutrophil chemotactic factor, interleukin (IL)-8. PF-derived IL-8 expression was dependent upon stimulation by either tumor necrosis factor (TNF) or IL-1 but not lipopolysaccharide (LPS). Both TNF and IL-1 stimulation of PF resulted in a time- and dose-dependent expression of steady-state levels of mRNA, antigen, and specific chemotactic activity consistent with IL-8. Because it was apparent that cytokine networking may exist in the lung between alveolar macrophage (AM)-derived cytokines and the production of PF-derived IL-8, we next examined an in vitro model of cellular communication within the lung. We determined that LPS-stimulated AM-conditioned media induced significant levels of PF-derived IL-8 mRNA, which was inhibited by preincubation with specific neutralizing TNF and IL-1 beta antibodies. Furthermore, when AM were directly co-cultured with PF and stimulated with LPS, the kinetic analysis of PF-derived antigenic expression of IL-8 was shifted toward the right. This suggested that PF-derived IL-8 expression in co-culture was first dependent upon activation of the AM by LPS and subsequent elaboration of macrophage inflammatory mediators. These data provide evidence that cytokine networking between AM and PF may be operative in the lung, culminating in the generation of IL-8 and elicitation of inflammatory leukocytes.

Antibodies↗
PubMed1990

Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor.

Accumulating evidence supports the hypothesis that neuroendocrine hormones may participate in immunologic processes. In our study we have determined that UK-14304 (UK) and norepinephrine (NE), both alpha 2-adrenergic agonists, can augment LPS-stimulated TNF from elicited macrophages (MO). The increase in TNF production was concentration dependent with an EC50 for UK and NE of 8.1 +/- 2.6 and 0.52 +/- 0.17 nM, respectively. The concentration-effect curve for UK and NE was shifted to the right by the alpha 2-antagonist yohimbine (10(-6) M), with new EC50 of 49.7 +/- 12.2 (p less than 0.001) nM and 10.3 +/- 22 nM. The augmenting effect of UK on MO TNF production was assessed over a 7 log LPS response curve. Within a single population of MO 10 nM UK shifted the LPS-induced TNF curve eightfold to the left with the greatest increase in TNF production at lower LPS concentrations. At the transcriptional level, Northern blot analysis demonstrated that UK increased LPS-induced TNF mRNA accumulation. This augmentation in TNF mRNA accumulation was blocked by yohimbine. The presence of a MO alpha-adrenergic receptor was established by demonstrating binding of the alpha 2-adrenergic antagonist 3H-yohimbine to membranes prepared from MO. This binding was rapid, saturable, reversible, and blocked by UK, clonidine, and phentolamine. These investigations support the role of alpha 2 adrenergic agonists as immunostaining compounds that may regulate cytokine production during an inflammatory response.

Animals↗
PubMed1986

Intrahepatic sources of biliary-like micelles.

To study the hepatocellular origins of biliary lipids, bile acid-lipid micelles were isolated from rat liver subfractions in vitro by Sephadex G-100 column chromatography, using 10 mM sodium taurocholate in the column eluant. Micelles of similar size to biliary micelles were obtained from microsome suspensions and from Golgi content that had been isolated in 5 mM sodium taurocholate-containing subcellular fractionation media. The phospholipid composition of these "biliary-like' micelles was similar but not identical to that of biliary micelles; cholesterol was detected in the micelles from Golgi content but not microsomes. 'Biliary-like' micelles could not be isolated from plasma membranes (including highly purified canalicular membranes), Golgi membranes or liver cytosol. These data suggest that biliary lipid micelles (or micelle precursors) may originate from the endoplasmic reticulum and Golgi apparatus.

Animals↗
PubMed1986

Tranquilizers and sedative/hypnotics: appropriate use in the elderly.

In treating the elderly patient, it is generally true that the fewer pharmacologic agents needed, the less the potential for drug interactions and puzzling toxic reactions. Nevertheless, sedative/hypnotics and anxiolytic drugs (mostly the benzodiazepines) are safe and effective therapy for the older patient, when the appropriate indications and dosages are observed. On the other hand, the toxic potential of nonbenzodiazepines (eg, barbiturates and pseudobarbiturates) and of even the relatively safe alternatives (eg, chloral hydrate, diphenhydramine, and hydroxyzine) render them less useful for the treatment of sleep disturbances. A final nonpharmacologic note: the physician should bear in mind that a balanced medical and psychological approach to sleep disturbance and anxiety in the elderly often yields success. This includes establishing a bedtime routine and using behavioral techniques, such as relaxation training, biofeedback, and even self-hypnosis. Patients can often be referred to a center where these approaches are employed.

Aged↗
PubMed1985

DRGs: implications for biomedical communications.

Diagnostic Related Groups (DRGs) form the basis for a new means of reimbursing hospitals for services provided to Medicare patients. A brief outline of the DRG system and a partial description of constraints of the system are introduced. Ramifications of this new prospective payment system and implications for biomedical communicators are presented and discussed.

Cost Control↗