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Biomedical subjects

R M Allen

Publications and source records attributed to R M Allen.

At least 19 recordsLinked to original sources
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↗
PubMed1979

Enzymatic fluorometry for estimating serum total bile acid concentration.

Fasting serum total bile acid (SBA) levels were estimated by enzymatic fluorometry (EF) in 36 subjects without liver disease, 28 with hepatic lesions and impaired hepatic function, and 79 with hepatic lesions and normal function. Fasting and postprandial EF-SBA levels were compared in nine normal subjects and nine patients with cholestasis, and SBA assays by EF and gas-liquid chromatography (GLC) were compared in 28 patients with hepatic lesions and impaired function. Levels of SBA were below 9 mumole/L in all but two of the 36 subjects without liver disease, and above that level in all 28 with impaired hepatic function and 17 (24%) of the 70 with hepatic lesions and normal liver function. In most subjects, EF detected notable postprandial rises in SBA. Enzymatic fluorometric and GLC-SBA values were closely correlated (coefficient of correlation, 0.869).

3-Hydroxysteroid Dehydrogenases↗
PubMed1979

Delirium associated with combined fluphenazine-clonidine therapy.

The authors report a case of acute organic brain syndrome in a patient being treated with clonidine and fluphenazine that cleared when clonidine was discontinued. Theoretical considerations of dopamine-norephinephrine interactions are discussed in the context of the drug-drug interaction.

Adult↗
PubMed1978

The use of homologous and heterologous 125I-radioligands in the radioimmunoassay of progesterone.

Eight homologous and heterologous 125I-radioligand systems for the radioimmunoassay of progesterone were examined. Using an antiserum raised to 11alpha-hydroxyprogesterone 11-succinyl-bovine serum albumin, standard curves were set up with the homologous radioligands, 11alpha-hydroxyprogesterone 11-succinyl-[125I]-iodotyramine, -[125I]-iodohistamine and -[125I]-iodotyrosine methyl ester. Heterologous bridge systems were represented by progesterone-11alpha-oxycarbonyl-[125I]-iodotyrosine methyl ester and 11alpha-hydroxyprogesterone 11-phthalyl-[125I]-iodotyrosine methyl ester, and heterologous site systems by progesterone-3-(O-carboxymethyl)oxime-[125I]-iodotyramine, progesterone-12-(O-carboxymethyl)oxime-[125I]-iodotyramine, and progesterone-20-(O-carboxymethyl)oxime-[125I]-iodohistamine. The preparation of the steroid derivatives and iodination by a two-phase method are described. The curves obtained from the homologous radioligands were relatively insensitive compared with a tritiated system, with the tyrosine methyl ester derivative providing a more sensitive assay than the corresponding tyramine or histamine analogues. The heterologous bridge systems gave more sensitive curves than the homologous tracers whilst the 3- and 12-(O-carboxymethyl)oxime derivatives of progesterone furnished curves as sensitive as the tritiated reference. Progesterone-20-(O-carboxymethyl)oxime-[125I]-iodohistamine was not bound by the antibody.

Iodine Radioisotopes↗
PubMed1978

Phencyclidine-induced psychosis.

During a 13-month period, 9 patients with phencyclidine-induced psychosis were admitted to Darnall Army Hospital. They exhibited hostility agitation, and tangentiality and had delusions of influence and religious grandiosity. Six subjects reported auditory hallucinations, and 4 were disoriented in at least 1 sphere. Despite treatment with antipsychotic medication, the psychotic episodes often persisted for more than 30 days. Our clinical finding of prolonged psychotic reactions, together with previous reports of the effects of phencyclidine, suggests that phenycyclidine provides an intriguing drug model for schizophrenia.

Adolescent↗
PubMed1976

Serum bile acids in primary biliary cirrhosis.

Fasting serum bile acid levels were measured by gas-liquid chromatography in 56 patients with primary biliary cirrhosis. Of these, 52 (93%) had increased levels (greater than 2mug/ml), including 14 of the 18 with normal serum bilirubin concentrations. The four patients with normal bile acid levels had early lesions as judged by histological and clinical criteria. With progression of the disease, as indicated by the histological features of the lesions, total bile acid levels increased, and the ratio of serum cholic-to-chenodeoxycholic acid decreased. Ratios of serum cholic-to-chenodeoxycholic acid below 1 occurred predominantly in patients with advanced or terminal disease. These studies suggest that serial measurement of serum bile acids may aid in the evaluation of primary biliary cirrhosis.

Adult↗
PubMed1975

There is an alternative to the IQ.

Another approach was indicated for understanding the intellectual functioning of the person considered to be retarded from the viewpoint of measured intelligence. Rather than utilizing the standard, usually academically-oriented, test, the inkblot method was used to differentiate how the individual deals with familiar and unfamiliar problems. The emphasis was not on the predetermined responses and verbal meanings of the test constructor, but the language and mode of perceiving, organizing, and responding of the individual to the problems presented to him.

Adolescent↗
PubMed1975

Differential reinforcement of reaction times in developmental retardates.

The effects of differential reinforcement on reaction times to two intensities of reaction signal were investigated in 36 developmental retardates. One group was reinforced for reaction times to the higher intensity signal; a second group was reinforced for reaction times to the lower intensity signal; a third group received no reinforcement. Reaction time decreased as signal intensity increased and decreased over sessions as a function of reinforcement. Likewise, reinforcement either exaggerated or reversed differences in reaction times to each signal depending on the particular reinforcement contingency. Results were discussed in terms of attentional and motivational explanations of effects of signal intensity on reaction times of retardates.

Acoustic Stimulation↗
PubMed1975

Measuring adaptive behavior: the dynamics of a longitudinal approach.

The Adaptive Behavior Checklist was administered annually to the residents of the Miami (FL) Sunland Training Center for 4 consecutive years. As a means of assessing adaptive behavior, this checklist, was used to provide feedback as to the progress made by the residents, thus monitoring the effectiveness of the institution in achieving certain behavioral objectives. Data from a longitudinal study are presented along with the means by which the results were communicated to the staff. Correlations of the checklist with standard IQ scores were discussed as was the effectiveness of a revision of the Adaptive Behavior Checklist.

Adolescent↗
PubMed1975

Contribution of visual perceptual maturation to the ability to conserve.

The extent to which visual perceptual maturity contributes to intellectual efficiency, as measured by the ability to conserve, was investigated in educable mentally retarded and nonretarded children. Hypotheses that visual perceptual ability and conservational ability would be positively correlated and that children with more mature visual perceptual processes would be better able to conserve were supported. Relationships among visual perception, conservation, CA, MA, and IQ were discussed.

Adolescent↗