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J M Hanley

Publications and source records attributed to J M Hanley.

9 recordsLinked to original sources
PubMed1998

The effects of IL-10 on proinflammatory cytokine expression (IL-1beta and IL-8) in hyaline membrane disease (HMD).

Deficient expression of the counterregulatory cytokine IL-10 by lung inflammatory cells may facilitate chronic inflammation and the pathogenesis of hyaline membrane disease (HMD), in premature infants. To determine if pathways which regulate proinflammatory cytokines in response to human recombinant IL-10 (rIL-10) were functional in the lungs of these neonates, bronchoalveolar lavage (BAL)-derived lung inflammatory cells (predominantly macrophages and neutrophils) from infants with HMD were cultured in the presence of lipopolysaccharide (LPS) and increasing concentrations of (rIL-10). The expression of IL-1beta and IL-8 protein was assessed 24 h later. IL-10 protein was also measured from the BAL aspirates of these newborns at 4-day intervals over the first month of life. In cell culture IL-1beta expression was inhibited by rIL-10 in a dose-dependent fashion while IL-8 expression was inhibited by higher concentrations of rIL-10. IL-10 protein was undetectable from BAL fluid of the premature infants sampled over 28 days. The results demonstrate that lung inflammatory cells, which do not express IL-10 in vivo, are capable of responding to rIL-10 in cell culture with reduction of IL-1beta and IL-8 expression. These data support the rationale for the development of rIL-10 as a potential anti-inflammatory agent in the treatment of HMD.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

A novel proteolytic activity in serum processes rat prohaptoglobin.

The heterotetrameric plasma glycoprotein rat haptoglobin previously was shown to be synthesized by hepatocytes in a precursor form, prohaptoglobin, which contains one alpha-subunit region and one beta-subunit region. Two of these molecules, each with a molecular weight of 45,000, are joined by a disulfide bond and subsequently the subunit regions of each polypeptide are separated by site-specific proteolysis, yielding the tetrameric native protein. Although some of this processing occurs intracellularly, a substantial proportion of the prohaptoglobin is secreted [J. M. Hanley, T. H. Haugen, and E. C. Heath (1983) J. Biol. Chem. 258, 7858-7869]. However, a proteolytic activity was found in rat plasma and serum which also is capable of site-specific cleavage of prohaptoglobin. Further investigation of this novel activity has demonstrated that it cleaves prohaptoglobin accurately, in the same site-specific manner as the intracellular protease, and that it most likely is not a serine protease or a metalloenzyme but can be inhibited by sulfhydryl-reactive compounds. Furthermore, it appears to be synthesized and secreted by hepatocytes, and thus may be identical to the intracellular processing protease.

Alkaloids↗
PubMed1983

Biosynthesis and processing of rat haptoglobin.

Native rat haptoglobin is an heterotetramer consisting of two alpha-subunits (Mr = approximately 9,500) and two glycosylated beta-subunits (Mr = approximately 38,000) joined by interchain disulfide bonds. We previously reported (Haugen, T. H., Hanley, J. M., and Heath, E. C. (1981) J. Biol. Chem. 256, 1055-1057) that the synthesis of rat haptoglobin is encoded by a single mRNA, and that the primary in vitro translation product is a single polypeptide, preprohaptoglobin (Mr = approximately 40,000), that contains an NH2-terminal signal sequence as well as an alpha-subunit region and a beta-subunit region. We now report that partial sequence analysis of preprohaptoglobin indicates that the protein possesses an NH2-terminal hydrophobic signal peptide of 18 amino acid residues, followed directly by the alpha-subunit region, with the beta-subunit region located in the carboxyl-terminal portion of the protein. The co-translationally processed translation product consists of a core glycosylated polypeptide, prohaptoglobin (Mr = approximately 45,000), that is devoid of the signal sequence and possesses both the alpha-subunit and beta-subunit regions of haptoglobin. Pulse-chase experiments in cultures of isolated hepatocytes, and analysis of haptoglobin biosynthetic intermediates in the various subcellular organelles of in vivo labeled rat liver indicate that: (a) in the endoplasmic reticulum, core glycosylated prohaptoglobin is dimerized and a portion of the protein is processed to form the individual alpha- and beta-subunits; (b) the carbohydrate side chains of prohaptoglobin and of core glycosylated beta-subunit (Mr = approximately 35,000) are converted to complex, sialylated side chains in the Golgi apparatus, resulting in the formation of fully glycosylated prohaptoglobin (Mr = approximately 48,000) and beta-subunit (Mr = approximately 38,000), and these forms of the protein, as well as the alpha-subunit (Mr = approximately 9,500), are secreted; (c) inhibition of glycosylation with tunicamycin does not significantly affect the rate of synthesis, processing, or secretion of the various haptoglobin polypeptides in isolated hepatocytes; (d) similar experiments conducted in the presence of colchicine also had no effect on the rate of synthesis and processing of the intermediates; and (e) the species of haptoglobin secreted in vivo and from isolated hepatocytes consist of approximately 60-70% in the form of the alpha 2 beta 2 tetramer, and the remainder as dimerized prohaptoglobin. Presumably, secreted prohaptoglobin may be processed to the native subunit structure after secretion, as we demonstrated that incubation of prohaptoglobin with either normal rat serum, rat plasma, or with the sera of other animal species results in its conversion to the corresponding alpha- and beta-subunits of the native protein.

Amino Acids↗
PubMed1983

A cinefluorographic investigation of repeated fluent productions of stutterers in an adaptation procedure.

Cinefluorography was used to study three stutterers and two nonstutterers repeating a passage made up of monosyllables. CVC target words of the form/caet/ were embedded in the passage and were analyzed to determine the effects of repeating the passage on velocities, displacements, and durations of movements of the tongue, jaw, and lower lip. Coordination among the articulators was also assessed. The investigation was undertaken to test the hypothesis that decreases in velocities and displacements, increased movement durations, and decreased latency between the onsets of jaw movements and of tongue tip movements would be associated with the repeated readings. The hypothesis was not supported by the results. A post hoc analysis showed that a decrease in the variability of instantaneous velocities (and by inference a decrease in variation in muscle stiffness) was associated with practice for the three stutterers but not for the nonstutterers. Inferences about the adaptation effect are made related (a) to the stabilization of tonic muscle activity which may be associated with a decrease in arousal, and (b) to the effects of practice.

Adaptation, Physiological↗
PubMed1981

Haptoglobin. A novel mode of biosynthesis of a liver secretory glycoprotein.

The de novo biosynthesis of the heterotetrameric (alpha 2 beta 2) serum glycoprotein, haptoglobin, was studied using a rabbit reticulocyte cell-free translation system and mRNA preparations from the livers of turpentine-treated rats. Analysis of the translation mixtures with either antisera specific for the alpha-subunit (anti-alpha-IgG) or the beta-subunit (anti-beta-IgG) or the native haptoglobin tetramer (anti-alpha 2 beta 2-IgG) resulted in each instance in the recovery of a single protein exhibiting a Mr = approximately 38,000. Cleavage of the translation product with cyanogen bromide or trypsin resulted in the generation of small peptide fragments that were specifically immunoadsorbed with either anti-alpha-IgG or anti-beta-IgG. These results indicated that the primary translation product of haptoglobin mRNA is a single polypeptide that contains the elements of both the alpha-subunit and the beta-subunit of the protein. Presumably haptoglobin is synthesized in vitro as a single precursor protein that is proteolytically processed post-translationally to form the dissimilar alpha- and beta-subunits of the native protein.

Animals↗
PubMed1981

Stuttering: in need of a unifying conceptual framework.

Perceptually fluent and disfluent speech reflect a continuum of coordination and can be best understood in terms of similar motor control processes. Speech movements may be considered to result from the interaction of inputs to motoneuron pools which alter the tuning of sensory-motor pathways and triggering inputs to specific muscles and muscle groups. A disorder incoordination may occur when any of these inputs is aberrantly affected by psychological, psychosocial or physiological variables. Specific phenomena associated with stuttering--adaptation, masking, whispering and voicing deviations--are interpreted in terms of these neuromotor processes. Therapeutic considerations are discussed.

Biomechanical Phenomena↗
PubMedDate not supplied

Swallowed partial denture: a case report.

Accidental swallowing and aspiration of dental prostheses is not uncommon and has been reported frequently in the literature. The location of a swallowed or aspirated dental prosthesis often is accomplished radiographically but this is difficult with prostheses constructed entirely of acrylic resins. A case report of an elderly patient who swallowed a removable partial denture is reviewed.

Aged↗