Interferon Gamma Alters the Phenotype of Rat Thymic Epithelial Cells in Culture and Increases Interleukin-6 Production

Rat thymic epithelial cells (TEC) in long-term culture were characterized by anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic analysis performed by a large panel of mAbs showed that the highest percentage of these cells was of the subcapsular/medullary type. Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC expression by TEC in culture as confirmed by immunohistochemistry and flow cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma- treated cultures showed higher interleukin-6 (IL-6) activity, compared to the control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6 activity was probably not a consequence of increased TEC number in IFN-gammatreated cultures because IFN did not significantly stimulate TEC proliferation in vitro. In contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is not only a regulatory molecule for T-cell proliferation, but could also be an autocrine growth factor for thymic epithelium.     

Firing rate and size distribution of the hind limb extensor and flexor motoneuronal units

Axonal spike size of extensor and flexor motoneurones were subjected to statistical analysis. Extensor motoneurones were isolated in decerebrate cats and the flexor motoneurones in spinalized cats. Smallest spikes were due to gamma motoneurones which could be further classified as small, medium and large. Extensor and flexor alpha motoneuronal units were also divided into these three subgroups. Considering the firing pattern and the cell size extensor alpha units were divided into five types: small-tonic, medium-tonic, large-tonic, large-phasic and largest-phasic. Maximum firing rate of extensor alpha units was directly related to the cell size and was distributed between 5-15, 15-20, 25-40 and 35-55 imp/sec for the small-tonic, medium-tonic, large-tonic and large-phasic motoneurones. Stabilized firing rates were distributed between 5-10, 10-15 and 15-20 imp./sec for the small-tonic, medium-tonic and large-tonic motoneurones. Flexor motoneuronal types and their maximum firing rates were as follows: small-tonic (16 imp./sec), medium-tonic (24 imp./sec), small-phasic (37.5 imp/sec), medium-phasic (30 imp./sec), large-phasic (46 imp./sec) and largest-phasic (only one or two impulses). The functional significance of the results was discussed considering the axonal spike size as an index for the cell size.     

Familie mit multipler endokriner Adenomatose (MEA TypI) und einigen zusätzlichen Besonderheiten

Zusammenfassung 3 Generationen mit 37 Mitgliedern einer Familie mit multipler endokriner Adenomatose Typ I (MEA Typ I) wurden anamnestisch und katamnestisch erfaßt. Klinische, biochemische und histologische Befunde wurden zusammengestellt: 20 Personen hatten Erkrankungen oder Befunde, die für eine MEA Typ I charakteristisch sind.Ein Patient (II 1) hatte ein chromophobes Hypophysenadenom, Epithelkörperchen- und Inselzelladenome, eine knotige Kolloidstruma und eine bilaterale knotige Nebennierenrindenhyperplasie. Dies ist das voll ausgeprägte Bild einer MEA Typ I (Wermer-Syndrom). Außerdem hatte er ein medulläres Schilddrüsencarcinom.Bei 14 Familienangehörigen ergaben sich Hinweise auf primären Hyperparathyreoidismus (pHPT), darunter waren 5 Patienten mit Nierensteinen. Die bei 3 Personen exstirpierten Epithelkörperchen erlaubten eine histologische Bestätigung der Diagnose pHPT. Die nach Möglichkeit mehrmals durchgeführte Bestimmung des Calcium- und Phosphatspiegels im Serum spielte eine Hauptrolle bei der Entdeckung von asymptomatischen Trägern des Gens.6 Patienten hatten Magen-Darmulcera: darunter waren 5 Patienten mit sicherem oder wahrscheinlichem pHPT, von denen aber nur einer (II 1) ein Gastrinom und eine Inselzelladenomatose hatte. Drei Patienten hatten eine Pankreatitis, bei zwei von ihnen nachweislich kombiniert mit pHPT. — Zweimal fand sich eine euthyreote Struma, einmal eine hyperthyreote Struma. Zwei Familienangehörige hatten erhöhte Plasmacortisolwerte; Lipome im Unterhautfettgewebe hatten ebenfalls zwei Patienten. Der Befund eines Alpha-1-Antitrypsinmangels (ZZ Phänotyp) bei zumindest 2 Patienten mit pHPT läßt an eine genetisch bedingte Verknüpfung des Defektallels Z mit der MEA Typ I denken. Weitere Familienuntersuchungen sind für eine Beweisführung notwendig.Ein Polyp im Jejunum mit heterotoper Magenschleimhaut (Fundus- und Pylorusdrüsen) ausgekleidet und blutend wurde bei diesem Syndrome noch nicht beschrieben. Der Befund wird von uns als Entwicklungsstörung des Entoderm aufgefaßt. Das bei einem Patienten (II 1) gefundene medulläre Schilddrüsencarcinom zeigt, daß die Trennlinie zwischen MEA Typ I und MEA Typ II nicht immer scharf gezogen ist.     

Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

BACKGROUND: Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. OBJECTIVES: Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. STUDY DESIGN: During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. RESULTS: Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. CONCLUSIONS: The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.     

Fever-like thermal conditions regulate the activation of maturing dendritic cells

Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity. To highlight the role of fever on adaptive immunity, we exposed murine bone marrow-derived lipopolysaccharide (LPS)- or live bacteria-maturing DCs over a 3-h period to 37 degrees C or to fever-like thermal conditions (39 degrees C or 40 degrees C). At these three temperatures, we measured the kinetics of cytokine production and the ability of DCs to induce an allogeneic mixed lymphocyte reaction. Our results show that short exposure of DCs to temperatures of 39 degrees C or 40 degrees C differentially increased the secretion of interleukin (IL)-12p70 and decreased the secretion of IL-10 and tumor necrosis factor alpha by maturing DCs. These fever-like conditions induced a regulation of cytokine production at the single-cell level. In addition, short-term exposed LPS-maturing DCs to 39 degrees C induced a stronger reaction with allogeneic CD4(+) T cells than maturing DCs incubated at 37 degrees C. These results provide evidence that temperature regulates cytokine secretion and DC functions, both of which are of particular importance in bacterial diseases.     

Low frequency of BRCA1 germline mutations in 45 German breast/ovarian cancer families.

In this study we investigated 45 German breast/ovarian cancer families for germline mutations in the BRCA1 gene. We identified four germline mutations in three breast cancer families and in one breast-ovarian cancer family. among these were one frameshift mutation, one nonsense mutation, one novel splice site mutation, and one missense mutation. The missense mutation was also found in 2.8% of the general population, suggesting that it is not disease associated. The average age of disease onset in those families harbouring causative mutations was between 32.3 and 37.4 years, whereas the family harbouring the missense mutation had an average age of onset of 51.2 years. These findings show that BRCA1 is implicated in a small fraction of breast/ovarian cancer families suggesting the involvement of another susceptibility gene(s).     

Prevalence of fragilysin gene in Bacteroides fragilis isolates from blood and other extraintestinal samples

Of 166 Bacteroides fragilis isolates, 26.2% of 103 isolates from blood and 20.6% of 63 extraintestinal isolates harbored the fragilysin gene (difference not statistically significant). Clinical characteristics and evolution were comparable in patients with B. fragilis bacteremia with or without this enterotoxin. Fragilysin seems not to be an important virulence factor in B. fragilis disease.