Cytokines and T cells in host defense

Soluble and cell-bound ligands profoundly influence the differentiative fate of lymphocytes during an immune response. Recent advances have been made in understanding the role of cytokine signals and costimulatory signals in the regulation of T cell responses associated with resistance or susceptibility to infection. There has also been recent progress in defining the requirements for the generation and maintenance of immunologic memory, a critical component of adaptive immunity.     

Determination of equine serum inhibitors for poliovirus by the gel-adsorption technique

Summary Inhibitors found in certain equine sera active against poliovirus type 1 have been determined by the gel-adsorption method using aluminiumhydroxide-gel in the absence of cells. The inhibitor belongs to the 19S-class of macroglobulins (IgM), as revealed by gel-filtration with Sephadex G 200, by DEAE-cellulose-chromatography, and by sucrose density centrifugation. It is bound to the viral surface in-vitro in the absence of tissue cells. The specific complex may be precipitated with anti-equine globulin from rabbits. The inhibitor is destroyed by papain and by 2-mercapto-ethanol. The residual infectivity (10–25%) has been found bound to the inhibitor in-vitro. Its behavior in the gel-adsorption system is not altered if the virus-inhibitor complexes have previously been diluted. — Nonsensitive mutants and double mutants have been selected. There must exist at least three different combining sites for equine inhibitors on the surface of poliovirus type 1, strain Mahoney. Equine sera may be grouped according to the specificity of their inhibitory activity. The specific binding capacity is lost if the virus is heated at 50° C for 30 min.Supported by the Deutsche Forschungsgemeinschaft, Unit Medizinische Virologie; partly presented at the 5th Viruscolloquium of the Deutsche Forschungsgemeinschaft, Marburg Sept. 1965.The authors wish to acknowledge the excellent technical assistance of MissSigrid Bonk.     

Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis

Intracellular pathogens, particularly those that target host mononuclear phagocytes, have evolved strategies to either evade or inhibit cellular mechanisms of host defense. Mycobacterium tuberculosis and Leishmania donovani exemplify a diverse group of microorganisms that have developed the ability to invade and replicate within host macrophages, leading to disease expression. Recent studies have suggested that the pathogenesis of intracellular infection may involve interference with host cell signaling. Drawing upon examples from in vitro models that focused on M. tuberculosis and L. donovani, we review evidence that activation of host cell phosphotyrosine phosphatases may contribute to pathogenesis. A leading candidate appears to be the Src homology 2 domain containing phosphotyrosine phosphatase SHP-1, the activation of which may contribute to the development of infection and disease progression.     

Emergence of translocation t(9;11)-positive leukemia during treatment of childhood acute lymphoblastic leukemia

Therapy-related acute myeloid leukemia (t-AML) characterized by the t(9;11)(p22;q23) translocation is one of the most frequent secondary malignancies. The timing of the initiation of translocation and of development of the malignant t(9;11) clone during chemotherapy is presently unknown. In the present study, we backtracked bone marrow samples from three children during treatment for acute lymphoblastic leukemia (ALL). Two patients developed a t(9;11)-positive t-AML 19 and 30 months after therapy start, whereas the third patient, diagnosed with a rare t(9;11)-positive ALL, suffered from an ALL relapse 23 months after initial diagnosis. The genomic MLL-MLLT3 (MLL-AF9) fusion site was amplified by a multiplex, nested long-range PCR and used as a clonal marker for quantification of the MLL-MLLT3-positive cells during chemotherapy. The t(9;11)-positive clone was detectable 13 and 18 months after therapy start in both t-AML cases, which was 6-12 months before clinical diagnosis of the secondary malignancy. In the t(9;11)-positive ALL patient, the identical leukemic clone reoccurred during maintenance therapy after a short molecular remission, 8 months before clinically overt ALL relapse. The time course and characteristics of the genomic breakpoints in the present t-AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage.     

Comparative study of Leishmania mexicana and Trypanosoma brucei NAD-dependent glycerol-3-phosphate dehydrogenase

The NAD-dependent glycerol-3-phosphate dehydrogenases (G3PDH, EC 1.1.1.8) of Trypanosoma brucei and Leishmania mexicana are thought to have different roles in carbohydrate metabolism. Here the physicochemical and kinetic properties of natural G3PDH from T. brucei with the recombinant homologue of L. mexicana which share 63% positional identity are compared. Despite their supposed different functions in energy metabolism of the parasites the two G3PDHs have remarkably similar properties, including pH optima and K(m) value for dihydroxyacetone phosphate (DHAP) and NADH in the formation of glycerol 3-phosphate (G3P) and for NAD+ and G3P in the reverse reaction. Both enzymes are subject inhibition by dihydroxyacetone phosphate at concentrations above 0.2 mM and are inhibited by the trypanocidal drugs suramin and melarsen oxide at sub-micromolar concentrations.     

Chairman’s Editorial: Reprioritizing Radiologist Education: Teaching Old Dogs New Tricks

Journal of Digital Imaging -     

Penetrating ocular injuries in young patients. Initial injuries and visual results

Penetrating injuries are a leading cause of unilateral visual loss in young patients. We reviewed the records of 197 patients aged 18 years or younger who underwent primary repair of a penetrating ocular injury at the Wilmer Ophthalmological Institute from January 1970 through December 1981. The injury was caused by sharp objects in 49% of cases, missiles in 35%, and blunt trauma in 14%. Of 159 patients with at least 6 months follow-up, 110 (69%) achieved final vision of 5/200 or better, and 77 patients (48%) achieved final visual acuity of 20/50 or better. The prognosis after a penetrating injury is strongly influenced by the nature of the injury and the extent of initial damage. Several factors were found to correlate with an unfavorable visual outcome, including: initial preoperative visual acuity of worse than 5/200, injuries due to blunt trauma, wounds involving the sclera, double penetrating injuries, dense vitreous hemorrhage, and wounds associated with an intraocular "BB" pellet.     

„Klar bleiben“ – ein Wettbewerb für Schulklassen zur Reduktion des Alkoholkonsums

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Alkohol ist in Deutschland im Jugendalter die populärste Droge. Alkoholpräventionsprogramme, die im Setting Schule...