Deficits in discriminated learning remain despite clearance of long-term persistent viral infection in mice

Mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit impaired learning ability. In this report, we determined whether clearance of the virus was associated with restoration of behavioral function. Neonatal Balb/cByJ mice were persistently infected with LCMV and tested as adults in a nonconditional spatial discrimination task. The presence of viral proteins in neurons was confirmed immunohistochemically and infectious virus was quantified in the blood by plaque assay. LCMV-infected adult mice made more errors in a Y-maze avoidance task compared to sham-inoculated controls. After the initial behavioral analysis, infected and control mice received a dose of cytotoxic T-lymphocytes sufficient to clear virus from these mice. Following complete clearance of the virus, mice were re-tested in the behavioral task, 5 months after the original test. No reversal of the learning deficit was seen following viral clearance; mice that had been cleared of the virus and those that remained persistently infected behaved similarly. These data indicate that persistent LCMV infection of the CNS lasting up to 7 months results in discriminated learning impairments that are not reversed by subsequent anti-viral immunocytotherapy.     

Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography, magnetic resonance imaging and cytology

An unusual case of fetal lymphangioma diagnosed before delivery is reported in a second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on the basis of the ultrasound appearances and progression of the lesions with advancing gestation. MRI was used to evaluate the extent and the tissue characteristics of the lesions. Cytology of the fluid aspirated from the cystic lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of a lymphangioma. The parents opted for a pregnancy termination because of the rapid growth of the lesions and the poor prognosis. It is suggested that the combination of these tests could enable the early diagnosis of these tumours at a stage when the lesion is relatively limited and accessible to therapy in utero.     

Thyroid status and exercise tolerance. Cardiovascular and metabolic considerations

Both hypo- and hyperthyroidism are characterised by exercise intolerance. In hypothyroidism, inadequate cardiovascular support appears to be the principal factor involved. Insufficient skeletal muscle blood flow compromises exercise capacity via reduced oxygen delivery, and endurance through decreased delivery of blood-borne substrates. The latter effect results in increased dependence on intramuscular glycogen. Additionally, decreased mobilisation of free fatty acids from adipose tissue and, consequently, lower plasma free fatty acid levels compound the problem of reduced lipid delivery to active skeletal muscle in the hypothyroid state. In contrast, cardiovascular support is enhanced in hyperthyroidism, implicating other factors in exercise tolerance. Greater reliance on muscle glycogen appears to be the primary reason for decreased endurance. Biochemical changes with hyperthyroidism that would favour enhanced flux through glycolysis may account for this dependence on glycogen. Deviations from normal thyroid function, and the ensuing exercise tolerance, require appropriate medical therapy to attain euthyroid status.     

Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation

Actin filament assembly at the cell surface of the pathogenic bacterium Listeria monocytogenes requires the bacterial ActA surface protein and the host cell Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin polymerization in vitro, but pure ActA had no effect. However, when combined, the Arp2/3 complex and ActA synergistically stimulated the nucleation of actin filaments. This mechanism of activating the host Arp2/3 complex at the L. monocytogenes surface may be similar to the strategy used by cells to control Arp2/3 complex activity and hence the spatial and temporal distribution of actin polymerization.     

N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci

The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5 microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2 micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent drugs, and further in vitro and in vivo studies are warranted.     

Interdisciplinary approach to functional voice disorders: the psychiatrist''s role

The Trichuris muris-mouse model of intestinal helminth infection provides a convenient system to examine the immune mechanisms operating during acute and chronic infection. Particular subsets of helper T lymphocytes (CD4+Th cells) play an important role in regulating infection via the secretion of distinct groups of cytokines. Reciprocal activation of Th cell subsets is associated with either expulsion of the parasites from the intestine (Th2 cells) or chronic infection (Th1 cells). In vivo neutralization experiments using anti-cytokine monoclonal antibodies show that critical cytokines are involved, with interferon-gamma playing an important role in the establishment of chronic trichuriasis and interleukin-4 in expulsion of the parasite from the gut. This model has provided clear evidence of a crucial role for distinct cytokines in mediating host protection against intestinal helminth infection and that manipulation of the immune response through the Th cell-cytokine axis can benefit either the host or the parasite. As such, the T. muris model is poised to generate important new data relevant not only to intestinal helminthiasis but to the wider field of parasite immunity and infection in general.     

Electron spin resonance of DNA irradiated with a heavy-ion beam ([16]O[8+]): evidence for damage to the deoxyribose phosphate backbone

A major problem in the intensive care unit nowadays is the development of multiple organ dysfunction syndrome (MODS), a cumulative sequence of progressive deterioration of organ functions. While the pathogenic pathways of MODS remain to be elucidated, it is assumed that cells of the host defence system, especially the macrophages, are altered in their function. During the development of MODS it is assumed that macrophages are overactivated and that an exaggerated inflammatory response may contribute to its pathogenesis. In order to gain insight into the alterations of the functional status of the macrophage during the development of MODS, a series of macrophage functions was measured in the subsequent phases of zymosan induced generalized inflammation in mice. Male C57BL/6 mice received a single dose of zymosan intraperitoneally and groups of animals were killed after 2, 5, 8, and 12 days. Peritoneal macrophages were collected for in vitro assessment of the ADCC, the production of superoxide (O2-) and nitric oxide (NO), and complement mediated phagocytosis and intracellular killing of Staphylococcus aureus. A single intraperitoneal injection with zymosan resulted in a three-phase illness. During the third phase the animals developed MODS-like symptoms. Peritoneal cells from control animals produced very low to non-detectable amounts of O2- and NO, and the cytotoxic activity was also low. During the development of MODS, from day 7 onwards, the ability to produce O2- and NO2- became strongly elevated, as did the cytotoxic activity. These findings are in parallel with the development of MODS whereas the phagocytic and killing capacity remained essentially unaltered. The changes found could be detrimental for the organism, thus possibly contributing to the onset and development of MODS.