Invasive infection withMycobacterium genavense in three children with the acquired immunodeficiency syndrome

Three children with human immunodeficiency virus infection and invasive infection withMycobacterium genavense are reported. Fever spikes, abdominal cramps and distension, diarrhea or ileus, and anemia were the predominant symptoms in the severely immunodeficient patients (CD₄ lymphocytes<0.04 × 10⁹/l). Numerous acid-fast bacilli were readily detectable by microscopy in stool samples and in lymph node biopsies, but cultures for mycobacteria remained negative.Mycobacterium genavense should be sought when invasive non-tuberculous mycobacteriosis is suspected and mycobacterial cultures from blood or other sites show limited growth. Multiple-drug regimens including amikacin, ethambutol, rifampin, and clarithromycin may be of benefit in controlling the infection, as observed in two patients.     

Phenytoin promotes Th2 type immune response in mice

The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-gamma production was reduced in phenytoin-treated mice. In addition, production of IL-1 alpha, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance.     

Acute myelomonocytic leukaemia with pseudo-Chediak-Higashi inclusions in leukaemic blasts report of an unusual case

Giant inclusions in the blast cells resembling that of Chediak-Higashi syndrome have been reported only in a handful of cases with acute leukaemia. There is a paucity of data on the ultrastructural appearance of such unique light microscopic findings. As many of such patients were reported in late seventies and early eighties [1-4] the outcome of treatment using present day multiple induction/consolidation regimens in such patients has also been rarely reported due to the rarity of such patients. We report here on a patient with acute myeloid leukaemia showing pseudo-Chediak-Higashi inclusions in leukaemic blasts with unusual ultrastructural morphology.     

Comparison of dietary intakes in four selected European populations

Summary The composition of diet and food intakes in four selected European populations were compared. Dietary data (from the World Health Organization Project on Monitoring Trends and Determinants in Cardiovascular Disease) were measured by record methods and were available for middle-aged men in Finland (n = 653), France (n =1128), Northern Ireland (n = 356), and southern Germany (Augsburg region; n = 899). Nutritional variables — which are independent of the absolute energy intake, such as the percentage supply of energy from macronutrients and the ratio of polyunsaturated to saturated fatty acids — were on the whole similar. However, striking differences were found in food intake and in the percentage supply of fat from different foods. The results indicate that detailed knowledge of consumption figures is necessary to develop prudent and acceptable nutrition intervention programs.Abbreviations CHD coronary heart disease - MONICA monitoring trends and determinants in cardiovascular disease - MUFA monounsaturated fatty acids - P/S ratio ratio of polyunsaturated fatty acids/saturated fatty acids - PUFA polyunsaturated fatty acids - SFA saturated fatty acids     

Pathology of infection caused by Dermatophilus-like organisms in porcine tonsils.

The authors investigated the occurrence of Dermatophilus-like organisms in sulphur granules of porcine tonsils. Light and electron microscopic studies, together with histochemical examination, were carried out to elucidate the mode of growth of the organism in the tonsils, the interaction between the organisms and host cells, and the nature of the radiating clubs around the organisms. Sulphur granules were found in about 15 and 70 per cent of market pigs and breeding pigs, respectively. Of the pigs having tonsillar granules, Dermatophilus-like organisms were observed in about 70 per cent of market pigs, and in nearly all breeding pigs. The organisms invaded tonsillar crypts to produce lesions resembling actinomycotic abscesses up to 5 mm in diameter. Dermatophilus-like organisms were demonstrated in various morphological forms ranging from filamentous to tuber-shaped or coccoid bodies. In the lesion, the bacterial cells adjacent to the host cell reaction showed distinct degenerative changes forming thick amorphous masses on the surface of the bacterial cells. The amorphous masses seemed to be derived from the bacterial cells but showed histochemical components different from those of the bacterial cells. These masses had numerous protrusions forming clubs. Phagocytic neutrophils close to the amorphous masses were presumed to play a role in deposition of the club material. Macrophages also appeared to participate in the inflammation leading to a granulomatous lesion. These findings suggested that the clubs might be formed by an interaction between the organisms and host cell reaction.     

System for inducible expression of cre-recombinase from the Foxa2 locus in endoderm, notochord, and floor plate.

We targeted the reverse tetracycline controlled transactivator (rtTA) to the Foxa2 locus (Foxa2(ITA)) to generate a system for regulating Cre-recombinase activity within Foxa2 expression domains, including the endoderm, notochord, and floor plate of early mouse embryos. The use of an internal ribosomal entry site to obtain rtTA expression preserves Foxa2 function of the targeted allele. Cre activity with this system reflects the level of endogenous Foxa2 activity and is also tightly controlled by doxycycline. The location of Cre activity within the broader Foxa2 expression domain can be restricted by altering the timing of doxycycline administration. Isolated floor plate expression can be obtained in this manner. This system will provide a useful tool for manipulating gene expression in endoderm, notochord, and floor plate, all of which are tissues with important structural and patterning functions during embryogenesis.     

Testosterone suppresses protective responses of the liver to blood-stage malaria

Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-mum-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an approximately 3- to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosterone-mediated suppression of resistance against blood-stage malaria.     

The nonfunctional allele TCRBV6S1B is strongly associated with Helicobacter pylori infection

To determine genetic susceptibility factors for Helicobacter pylori infection, polymorphic T-cell receptor gene elements were investigated in 203 H. pylori-infected individuals and 180 uninfected individuals (controls). H. pylori infection is highly associated with individuals homozygous for the nonfunctional TCRBV6S1B element (odds ratio = 5.9; chi(2) = 13; P = 0.00032; P value corrected for multiple comparisons [Bonferroni correction] = 0. 00063).     

G-protein-independent signaling mediated by metabotropic glutamate receptors

Synaptically released glutamate activates ionotropic and metabotropic receptors at central synapses. Metabotropic glutamate receptors (mGluRs) are thought to modulate membrane conductances through transduction cascades involving G proteins. Here we show, in CA3 pyramidal cells from rat hippocampus, that synaptic activation of type 1 mGluRs by mossy fiber stimulation evokes an excitatory postsynaptic response independent of G-protein function, while inhibiting an afterhyperpolarization current through a G-protein-coupled mechanism. Experiments using peptide activators and specific inhibitors identified a Src-family protein tyrosine kinase as a component of the G-protein-independent transduction pathway. These results represent the first functional evidence for a dual signaling mechanism associated with a heptahelical receptor such as mGluR1, in which intracellular transduction involves activation of either G proteins or tyrosine kinases.