Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung.

Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g., H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here, we show that deficiency of interleukin (IL)-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of the influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signaling could increase mortality to influenza virus infection.

Mesenchymal stem cells in cartilage repair: state of the art and methods to monitor cell growth, differentiation and cartilage regeneration.

Degenerative joint diseases caused by rheumatism, joint dysplasia or traumata are particularly widespread in countries with high life expectation. Although there is no absolutely convincing cure available so far, hyaline cartilage and bone defects resulting from joint destruction can be treated today by appropriate transplantations. Recently, procedures were developed based on autologous chondrocytes from intact joint areas. The chondrocytes are expanded in cell culture and subsequently transplanted into the defect areas of the affected joints. However, these autologous chondrocytes are characterized by low expansion capacity and the synthesis of extracellular matrix of poor functionality and quality. An alternative approach is the use of adult mesenchymal stem cells (MSCs). These cells effectively expand in 2D culture and have the potential to differentiate into various cell types, including chondrocytes. Furthermore, they have the ability to synthesize extracellular matrix with properties mimicking closely the healthy hyaline joint cartilage. Beside a more general survey of the architecture of hyaline cartilage, its composition and the pathological processes of joint diseases, we will describe here which advances were achieved recently regarding the development of closed, aseptic bioreactors for the production of autologous grafts for cartilage regeneration based on MSCs. Additionally, a novel mathematical model will be presented that supports the understanding of the growth and differentiation of MSCs. It will be particularly emphasized that such models are helpful to explain the well-known fact that MSCs exhibit improved growth properties under reduced oxygen pressure and limited supply with nutrients. Finally, it will be comprehensively shown how different analytical methods can be used to characterize MSCs on different levels. Besides discussing methods for non-invasive monitoring and tracking of the cells and the determination of their elastic properties, mass spectrometric methods to evaluate the lipid compositions of cells will be highlighted.

[National external quality assessment in auto-immunity: auto-antibodies against thyroid constituents]. / Contrôle national de qualité en auto-immunité: anticorps anti-thyroïdiens.

The French Health Products Safety Agency organized in 2005, for the scheme of the national external quality assessment, a survey on antibodies against thyroid constituents which included for the first time the quantitative assay. The purpose of this survey was to assess the quality of the different methods of these assays. The overall qualitative results are satisfactory. However, this survey pointed out a lower performance for immunodot which appeared to have been misused. Concerning the titer of antibodies, results show a broad dispersion between reagents. This confirms the lack of a real standardisation despite of the existence of the international MRC standards.

K+ channels in apoptosis.

A proper rate of programmed cell death or apoptosis is required to maintain normal tissue homeostasis. In disease states such as cancer and some forms of hypertension, apoptosis is blocked, resulting in hyperplasia. In neurodegenerative diseases, uncontrolled apoptosis leads to loss of brain tissue. The flow of ions in and out of the cell and its intracellular organelles is becoming increasingly linked to the generation of many of these diseased states. This review focuses on the transport of K(+) across the cell membrane and that of the mitochondria via integral K(+)-permeable channels. We describe the different types of K(+) channels that have been identified, and investigate the roles they play in controlling the different phases of apoptosis: early cell shrinkage, cytochrome c release, caspase activation, and DNA fragmentation. Attention is also given to K(+) channels on the inner mitochondrial membrane, whose activity may underlie anti- or pro-apoptotic mechanisms in neurons and cardiomyocytes.

Plasma alpha-MSH and acetylated beta-endorphin levels following stress vary according to CRH sensitivity of the pituitary melanotropes in common carp, Cyprinus carpio.

Pituitary melanotropes release alpha-melanocyte-stimulating hormone (alpha-MSH) and acetylated beta-endorphin (NAc beta-end) during stress responses. However, effects of stressors on plasma concentrations of these hormones are highly inconsistent among fish species. Here, we show that also within a species, the common carp (Cyprinus carpio), fish sometimes respond with elevated alpha-MSH and NAc beta-end plasma levels, and at other times not. The origin of this variable response was investigated by (1) studying the effects of corticotropin-releasing hormone (CRH) on alpha-MSH and NAc beta-end release in vitro, (2) establishing where in the second messenger pathway coupled to CRH receptors melanotrope responsiveness is determined, and (3) testing modulatory actions of other hypothalamic factors (here opioid beta-endorphin). Melanotropes were in a high or low responsive state to CRH in vitro, which was especially evident when tissue was tested from fish kept at higher ambient water temperatures, and this correlates with the variability in alpha-MSH and NAc beta-end responses in vivo. Relative rates of alpha-MSH and NAc beta-end release following stimulation with CRH in vitro match plasma level changes in vivo, and this indicates that the CRH pathway does act in vivo. cAMP did not stimulate melanotropes in the low responsive state to release hormones in vitro. Thus, the mechanism that determines the cell status, occurs downstream of cAMP accumulation. Opioid beta-endorphin differentially modulated the actions of CRH, as NAc beta-end, but not alpha-MSH, release was inhibited. This response was not observed in the stress paradigms studied. We conclude that the variation in alpha-MSH and NAc beta-end stress responses in vivo correlates with many CRH responses in vitro; whether a cell is in a high or low responsive state to CRH is determined downstream of accumulation of the second messenger. We propose that melanotropes have to be in the high responsive state to be activated by CRH during stress in carp and other teleosts.

Modulation of intercellular communication between smooth muscle cells by growth factors and cytokines.

We recently reported that tumor necrosis factor alpha is able to cause a dose-dependent and persistent reduction in gap junctional intercellular communication between primary human smooth muscle cells. In order to study whether this observed persistent reduction in gap junctional intercellular communication is a unique feature for tumor necrosis factor alpha, the present study focuses on the effects of other growth factors and cytokines on gap junctional intercellular communication. Platelet-derived growth factor AA and BB (PDGF-AA, PDGF-BB), basic fibroblast growth factor (bFGF), interleukin-6 and interferon-gamma were able to modulate gap junctional intercellular communication between primary human smooth muscle cells in vitro. However, our results demonstrate that the magnitude and nature of the observed effects are growth factor- and cytokine-specific. PDGF-AA, PDGF-BB and interleukin-6 caused a transient reduction in gap junctional intercellular communication, while bFGF induced a transient increase in gap junctional intercellular communication. Interferon-gamma was shown to be capable of causing a persistent reduction in gap junctional intercellular communication. In addition, PDGF-AA, PDGF-BB, bFGF, interleukin-6, interferon-gamma and tumor necrosis factor alpha all stimulated smooth muscle cell proliferation. These observations suggest a more complex relationship between modulation of gap junctional intercellular communication and cell proliferation than current hypotheses imply. The implications of the observed effects of growth factors and cytokines on gap junctional intercellular communication between smooth muscle cells in relation to the process of atherosclerosis is discussed.

Intraurethral thrombosed varix: unusual cause for hematuria.

A case of an intraurethral thrombosed vein as a cause for painless hematuria is presented. In contrast to previous reports, the thrombosed varix was located in the midurethra rather than at the urethral meatus. The necessity for biopsy to differentiate from tumor is emphasized.

Minimal breast cancer: a clinical appraisal.

Eighty-five patients with a diagnosis of minimal breast cancer were evaluated. The predominant lesion was intraductal carcinoma, and axillary metastases occurred in association with minimal breast cancer in seven of 96 cases. One death occurred due to minimal breast cancer. Bilateral mammary carcinoma was evident in 24% and bilateral minimal breast cancer in 13% of the patients. The component lesions of minimal breast cancer have varied biologic activity, but prognosis is good with a variety of operations. The multifocal nature of minimal breast cancer and the potential for metastases should be recognized. Therapy should include removal of the entire mammary parenchyma and low axillary nodes. The high incidence of bilateral malignancy supports elective contralateral biopsy at the time of therapy for minimal breast cancer.

Ethylene formation in pea seedlings; its relation to the inhibition of bud growth caused by indole-3-acetic Acid.

Indole-3-acetic acid stimulates ethylene production in the nodal region of pea stems, and the gas inhibits bud growth. At all concentrations of IAA there is a close correlation between the intensity and duration of ethylene production and the bud inhibition which results. Kinetin reverses the inhibitory actions of ethylene and IAA on bud growth. It is concluded that auxins suppress bud development by stimulating ethylene formation. The possibility that auxin induced ethylene formation controls apical dominance is considered.

Inhibition of polar auxin transport by ethylene.

Applied ethylene influences the growth of etiolated pea stem sections cut from untreated plants, but has no effect on (14)C-indoleacetic acid uptake, polar transport or destruction. However, the capacity of the polar auxin transport system is markedly reduced in sections cut from plants grown in ethylene, while the velocity of auxin transport is unchanged under these conditions. Inhibition of the polar transport system by ethylene could underlie certain responses in which the gas produces symptoms of auxin deficiency.

Molecular requirements for the biological activity of ethylene.

The molecular requirements for ethylene action were investigated using the pea straight growth test. Biological activity requires an unsaturated bond adjacent to a terminal carbon atom, is inversely related to molecular size, and is decreased by substitutions which lower the electron density in the unsaturated position. Evidence is presented that ethylene binds to a metal containing receptor site. CO(2) is a competitive inhibitor of ethylene action, and prevents high concentrations of auxin (which stimulate ethylene formation) from retarding the elongation of etiolated pea stem sections. It is suggested that CO(2) delays fruit ripening by displacing the ripening hormone, ethylene, from its receptor site. Binding of ethylene to the receptor site is also impeded when the O(2) concentration is lowered, and this may explain why fruit ripening is delayed at low O(2) tensions.

Auxin-induced ethylene formation: its relation to flowering in the pineapple.

Within I day after pineapple plants are treated with naphthalene acetic acid they begin producing ethylene. It is suggested that applied auxins mimic the action of ethylene by stimulating ethylene formation, and that ethylene, not auxin, causes pineapples to flower.