Endotoxin-induced uveitis is primarily dependent on radiation-resistant cells and on MyD88 but not TRIF.

TLR4 activation by LPS (endotoxin) is mediated by the MyD88 and TRIF intracellular signaling pathways. We determined the relative activation of these pathways in murine ocular tissue after LPS exposure. Additionally, we explored whether BM-derived or non-BM-derived cells were the major contributors to EIU. Mice deficient in TRIF or MyD88 and their congenic (WT) controls received 250 ng ultrapure LPS ivt at 0 h. Ocular inflammation was assessed by histological analysis at 4, 6, and 24 h, and additionally, in MyD88(-/-) mice, intravital microscopy was performed at 4 h and 6 h to assess adherent, rolling, and infiltrating cells in the iris vasculature and tissue. Cytokines associated with the MyD88 and TRIF intracellular signaling pathways were analyzed in ocular tissue at 4 h. BM chimeric mice (WT→WT, TLR4(-/-)→WT, WT→TLR4(-/-)) received 250 ng LPS by ivt injection, and ocular tissues were examined by histology at 6 h. Lack of MyD88 resulted in a markedly diminished cellular response and reduced production of MyD88-related cytokines 4 h post-LPS treatment. In contrast, lack of TRIF led to reduced production of TRIF-related cytokines and no change in the cellular response to LPS. Therefore, the MyD88 pathway appears to be the dominant TLR4 pathway in EIU. Only WT → TLR4(-/-) chimeric mice were resistant to EIU, and this suggests, surprisingly, that non-BM-derived (radiation-resistant) cells in the eye play a greater role than BM-derived cells.

Cyclic variations of erythropoietin excretion in a patient with congenital hypoplastic anaemia: Diamond-Blackfan syndrome.

Urinary erythropoietin excretion was followed daily during a period of one month in a child who had a congenital hypoplastic anaemia with periodic episodes of anaemia and a spontaneous increase in erythropoiesis. Erythropoietin excretion varied so that the highest value was ten times greater than the lowest one. It could be suggested that oscillations in erythropoietin prpoduction are secondary to the intermittent changes in the bone marrow. This finding could be included among a variety of oscillation phenomena that hematopoiesis exhibits.

A specific, fluorescent activity staining procedure applied to plasma and red blood cells in congenital factor XIII deficiency.

The activity staining procedure introduced by Stenberg & Stenflo (1979) has been applied to studies on human blood transamidases (transglutaminases; endo-gamma-glutamine:epsilon-lysine transferases; e.g. factor XIII). The technique combines agarose gel electrophoresis with activity staining based on the transamidase catalysed incorporation of monodansylthiacadaverine (N-(5-amino-3-thiapentyl)-5-dimethylamino-1-naphtalenesulfonamide) into casein. The method permits detection of plasma factor XIII activity down to 1% of the normal adult standard. The technique was used on plasma from two patients with tentative congenital plasma factor XIII deficiency (based on clot solubility). No activity was found in platelet poor as well as in platelet rich plasma which confirmed the diagnosis. In the erythrocytes studied in genetic determinations of the plasma and red blood cell transamidases. Using immunoelectrophoresis, the plasma factor XIII b subunit was found to be 43% and 44% of the concentration in normal standard plasma.

[Immunoelectrophoretic method for the determination of factor VIII-related antigens]. / Imunoelektroforetska metoda u odredivanju F. VIII srodnog antigena.

Immunological examination of F VIII related antigen gave some new information on the nature of congenital defects of F VIII, in haemophilia A and von Willenrand's disease. Besides classic method in diagnostics of von Willebrand's disease, the determination of F VIII related antigen can be used as a diagnostic criterium in distinguishing von Willebrand's disease from some mild forms of haemophilis, as well as in detection of haemophilia carrier. In addition, the study on the relationship of immunological value of F VIII related antigen and biological activity of F VIII offers more data on the possibility of detection of so-called "hypercoagulability" and states proceeding thrombosis. The method for determination of F VIII related antigen (Rocket electrophoresis--Laurel) as well as the values of F VIII in health persons of our population is described in this paper.

[Diagnosis of von Willebrand's disease]. / Danasnje mogucnosti dijagnostike von Willebrand-ovog oboljenja.

Diagnosis and differential diagnosis of von Willebrand's disease was a special problem. Criteria up to date: prolonged bleeding time, reduced platelet adhesiveness, decreased F. VIII coagulant activity, as well as a particularly behaviour after the infusion of F. VIII, were not sufficient to differentiatie this disease from other congenital disorder of F. VIII. Recent investigations, introducing the immunological methods for determination of F. VIII--related antigen, as well as the investigation of ristocetin induced platelet aggregation, give the new approach in the diagnosis of von Willebrand's disease. Authors presented preliminary results of investigations of F. VIII--related antigen in the patients with von Willebrand's disease, as well as the results of investigation of the patients with hemophilia A and normal subjects, as a control group.

[Treatment of acute lymphocytic leukemia in children with combination chemotherapy and irradiation of the central nervous system]. / Akutna limfocitna leukemija u dece lecene hemioterapijom i zracenjem centralnog nervnog sistema

From July 1972 until April 1975 51 children with acute lymphocytic leukemia had been treated with combination chemotherapy and central nervous system irradiation. First remission was induced in 46 patients. 13 patients died during the first and second year of treatment. Central nervous system leukemia developed only in 3 patients. In 9 patients chemotherapy had been stopped after 30 months of treatment. These results are very encouraging and we hope that majority of our patients will survive 5 years without relapse.