Haptoglobin, inflammation, and tumorigenesis in the MIN mouse.

We have determined that the MIN mouse, which is predisposed to adenomas of the small and large intestine, exhibits chronic inflammation characterized by the induction of haptoglobin (HP), as well as other acute phase proteins. Inflammation is initiated at about 40-70 days of age, and is maintained throughout the life of the animal. Delayed onset of inflammation brought on by dietary means is associated with a reduction in tumor number and longer life-span.

Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival.

Signal transducer and activator of transcription (STAT) proteins are involved in hematopoietic cytokine receptor signaling pathways that regulate cell proliferation, differentiation, and survival. STATs are dysregulated in acute myeloid leukemia (AML); mechanisms of dysregulation include constitutive activation and truncation of the C-terminal transactivation domain; the latter results in a beta isoform that has a trans-dominant negative effect on gene induction mediated by the full-length STAT alpha form. It was hypothesized that constitutive STAT activity might correlate with unfavorable treatment outcome in AML.

The role of regioselectively sulfated and acetylated polysaccharide coatings of biomaterials for reducing platelet and plasma protein adhesion.

A brief survey is given about the role of natural polysaccharides such as heparin (HE), heparan sulfate (HS), chondroitin sulfate (CS), and dermatan sulfate (DS) in reducing blood coagulation and their potential use as athrombogenic coatings in the development of tailor-made athrombogenic biomaterials. Furthermore, known literature and new results about platelet adhesion on regioselectively modified polysaccharides such as HE, chitosan with HE-like functional groups, and sulfated cellulose are presented in two different perfusion systems at different shear rates. Regioselectively modified polysaccharides were tested as coatings of two polymers.

Oncostatin M regulates the synthesis and turnover of gp130, leukemia inhibitory factor receptor alpha, and oncostatin M receptor beta by distinct mechanisms.

The cytokine receptor subunits gp130, leukemia inhibitory factor receptor alpha (LIFRalpha), and oncostatin M receptor beta (OSMRbeta) transduce OSM signals that regulate gene expression and cell proliferation. After ligand binding and activation of the Janus protein-tyrosine kinase/STAT and mitogen-activated protein kinase signal transduction pathways, negative feedback processes are recruited. These processes attenuate receptor action by suppression of cytokine signaling and by down-regulation of receptor protein expression.

Truncated STAT proteins are prevalent at relapse of acute myeloid leukemia.

Signal transducer and activator of transcription (STAT) proteins are implicated in the control of cell survival, proliferation and differentiation in response to hematopoietic cytokines. C-terminally truncated STAT isoforms (STATbeta), as opposed to the full length form (STATalpha), have a competitive or even transdominant negative effect on gene induction mediated by the STAT pathway. We have previously demonstrated that while constitutively active STAT proteins were detected in ten of 36 (28%) for STAT3 and eight of 36 (22%) for STAT5 in pretreatment samples from newly diagnosed acute myeloid leukemia (AML) patients, a significantly larger fraction of samples [21 of 27 (78%)] expressed STATbeta proteins.

Concepts for improved regioselective placement of O-sulfo, N-sulfo, N-acetyl, and N-carboxymethyl groups in chitosan derivatives.

In the present paper a new strategy has been studied to introduce solely or in combination N-sulfo, O-sulfo, N-acetyl, and N-carboxymethyl groups into chitosan with highest possible regioselectivity and completeness and defined distribution along the polymer chain. The aim was to generate compounds having lowest toxicity for determining the pharmacological structure function relationships among different backbone structures and differently arranged functional groups compared to those of heparin and heparan sulfate. The water-soluble starting material, chitosan, with a degree of acetylation (DA) of 0.

Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin.

Signaling by type I cytokines involves the formation of receptor homodimers, heterodimers or higher order receptor oligomers. Here we report the cloning of a type I cytokine receptor subunit that is most closely related to the common cytokine receptor gamma chain (gamma c). Binding and crosslinking experiments demonstrate that this protein is the receptor for a recently described interleukin 7 (IL-7)-like factor, thymic stromal lymphopoietin (TSLP).

A novel serine-dependent proteolytic activity is responsible for truncated signal transducer and activator of transcription proteins in acute myeloid leukemia blasts.

Hematopoietic cytokine receptor signaling involves activation of signal transducer and activator of transcription (STAT) proteins that are thought to control cellular differentiation. Truncated STAT isoforms (beta forms, rather than the normal alpha forms) have been described and found to block the normal signaling function of the alpha isoforms. We recently demonstrated STATbeta isoforms in bone marrow samples from 21 of 27 (78%) acute myeloid leukemia (AML) patients.

Nuclear magnetic resonance studies of solvent flow through chromatographic columns: effect of packing density on flow patterns.

NMR (nuclear magnetic resonance) techniques have been used to measure and characterise solvent flow through chromatographic columns. NMR imaging was used to track an injection of D2O. PGSE (pulsed gradient spin echo) NMR was used to measure the flow-rate dependence of axial and transverse apparent diffusion.

Regulatory effects of fever-range whole-body hyperthermia on the LPS-induced acute inflammatory response.

The thermal component of fever is one of the most poorly understood aspects of inflammation. To evaluate the role of fever-range hyperthermia on acute inflammation, BALB/c and C57BL/6 mice were exposed to mild, long-duration whole-body hyperthermia (WBH), and serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, and the acute phase proteins (APPs) alpha1-acid glycoprotein and haptoglobin were analyzed. WBH alone did not affect serum concentrations of these cytokines or APPs when compared with controls.

Dual electroencephalogram markers of human sleep homeostasis: correlation between theta activity in waking and slow-wave activity in sleep.

To investigate the relationship between markers of sleep homeostasis during waking and sleep, the electroencephalogram of eight young males was recorded intermittently during a 40-h waking episode, as well as during baseline and recovery sleep. In the course of extended waking, spectral power of the electroencephalogram in the 5-8Hz band (theta activity) increased. In non-rapid eye movement sleep, power in the 0.

Biocompatibility testing of new polymers in a moving implant bed.

Total reconstruction of the auricle requires a skillful surgical technique and an appropriate material for the shape-supporting frame. Up to now, there is no such material apart from autologous rib cartilage. The combination of chronic microtraumatization of adjacent tissue caused by the mobility of an implant bed such as the auricle and the foreign-body reaction to currently available artificial polymers frequently results in extrusion.

Oncostatin M and interleukin 6 inhibit cell cycle progression by prevention of p27kip1 degradation in HepG2 cells.

We analysed the regulation of G1-phase progression in relation to cytokine receptor signalling in HepG2 hepatoma cells, stably transduced with the IL-10 receptor after stimulation with Oncostatin M (OSM), IL-6, Leukaemia Inhibitory Factor (LIF) and IL-10. All cytokines induced STAT3 phosphorylation to approximately the same level, but only OSM, and to a lesser extent IL-6, induced STAT5 phosphorylation. The cytokines also stimulated phosphorylation of ERK in the order of decreasing effectiveness: OSM > IL-6 > LIF > IL-10.

Coadministration of interleukin-18 and interleukin-12 induces a fatal inflammatory response in mice: critical role of natural killer cell interferon-gamma production and STAT-mediated signal transduction.

The administration of therapeutic doses of recombinant cytokines to patients with malignant disease can be complicated by systemic toxicities, which in their most severe form may present as a systemic inflammatory response. The combination of interleukin (IL)-18 and IL-12 has synergistic antitumor activity in vivo yet has been associated with significant toxicity. The effects of IL-18 plus IL-12 were examined in a murine model, and it was found that the daily, simultaneous administration of IL-18 and IL-12 resulted in systemic inflammation and 100% mortality within 4 to 8 days depending on the strain employed.

[Psychosocial, economic and physical status of former leprosy patients in Uganda].

This study investigates the general living condition, the psychosocial, economical and physical situation of 161 leprosy patients previously treated at the St. Francis Leprosy Hospital at Buluba/Uganda, basing on interviews and clinical examinations. The results point to a negative correlation between general education and specific knowledge of leprosy and highlight a serious psychosocial situation of previously treated leprosy patients.

Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase.

Leukemia inhibitory factor (LIF) signals via the heterodimeric receptor complex comprising the LIF receptor alpha subunit (LIFRalpha) and the common signal transducing subunit for interleukin-6 cytokine receptors, gp130. This study demonstrates that in different cell types, the level of LIFRalpha decreases during treatment with LIF or the closely related cytokine oncostatin M (OSM). Moreover, insulin and epidermal growth factor induce a similar LIFRalpha down-regulation.

Receptor subunit-specific action of oncostatin M in hepatic cells and its modulation by leukemia inhibitory factor.

The related cytokines, interleukin-6 (IL-6), oncostatin M (OSM), and leukemia inhibitory factor (LIF) direct the formation of specific heteromeric receptor complexes to achieve signaling. Each complex includes the common signal-transducing subunit gp130. OSM and LIF also recruit the signaling competent, but structurally distinct OSMRbeta and LIFRalpha subunits, respectively.

Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate: flow characteristics and platelet adhesion.

The present study addresses the problem of simultaneous surface modification of various polymers, i.e. polysulfone (PSU), polycarbonate (PC), and polyurethane (PU), which constitute the Ultraflux AV 600 S hollow fibre hemodialyser.

Involvement of the acute phase protein alpha 1-acid glycoprotein in nonspecific resistance to a lethal gram-negative infection.

Resistance to gram-negative infection can be induced by pretreating animals with several agents such as turpentine and interleukin (IL)-1. Because these agents are powerful inducers of acute phase proteins, we wondered whether these proteins, more particularly alpha(1)-acid glycoprotein (alpha(1)-AGP), are involved in nonspecific resistance to infection. Turpentine and IL-1 protect completely against a lethal challenge of Klebsiella pneumoniae when given 48 and 12-48 h before the challenge, respectively.

Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression.

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin.

NMR microscopy of the uptake, distribution and mobility of dissolution media in small, sub-millimetre drug delivery systems.

NMR techniques were used to study the drug release process from small (sub-mm) lipophilic matrix theophylline beads. NMR microscopy was used to follow the ingress of the dissolution medium into the beads. Pulsed gradient spin echo (PGSE) NMR and 3D NMR imaging were used to measure the mobility and distribution of liquid within fully liquid penetrated beads.

Regulation by Gi2 proteins of v-fms-induced proliferation and transformation via Src-kinase and STAT3.

We previously showed that Gi2 proteins interfere with the transduction of CSF-1 receptor (CSF-1R) proliferation signals (Corre and Hermouet, 1995). To identify CSF-1R pathways controlled by Gi2, we transfected v-fms, the oncogenic equivalent of CSF-1R, in NIH3T3 cells in which Gi2 proteins were inactivated by stably expressing a dominant negative mutant form of the alpha subunit of Gi2 (alpha i2-G204A). Expression of alpha i2-G204A resulted in decreased Src-kinase activity, delayed activation of p42 ERK-MAPK, decreased cyclin D1 expression and reduced proliferation in response to serum.

Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction.

Thymic stromal lymphopoietin (TSLP) is a newly identified cytokine that uniquely promotes B lymphopoiesis to the B220+/IgM+ immature B cell stage. In addition, TSLP shares many biological properties with the related cytokine IL-7. This can be explained by the finding that the receptor complexes for TSLP and IL-7 both contain the IL-7R alpha-chain; IL-7Ralpha is paired with the common gamma-chain (gammac) in the IL-7 receptor complex and the unique TSLP-R chain in the TSLP receptor complex.

Measurement of acute phase proteins in the rat brain: contribution of vascular contents.

A localized acute phase response occurs in the brain in Alzheimer's disease. Acute phase proteins have previously been measured in brain homogenates to quantify this response. The extent to which measurements of these proteins reflect brain parenchymal contents, as opposed to vascular contents, is unknown.