Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling

A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non-T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcgamma- and Fc epsilon -receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non-T cells.     

Hemodialysis-related headaches

BACKGROUND/AIM: Hemodialysis (HD) is a therapeutic procedure used to partially correct homeostatic disorders and prevent complications of uremia to appear in the terminal stage of renal insufficiency. The aim of this study was to evaluate and analyze the incidence and features of haedaches in patients undergoing hemodialysis. METHODS: A total of 143 patients, 50 women and 93 men, undergoing hemodialysis, were questionned about their problems with headache using a questionnary designend according to the diagnostic criteria of the Intemational Headache Classification of Headache Disorders from 2004. The patients were separated into two groups: the patients without headache and the patients with repeated headaches. Afterwards, the patients with headaches were further divided into subgroups: the patients who had the headaches before the beginning of HD and patients who experienced repeated headaches with the beginning of HD headache (HDH). In the group of patients with headaches we analyzed characteristics of headache according to which diagnoses of headaches were made, as well as the effects of HD on headaches. We also analyzed features of HDH. The patients with headache were compared to the patients without haedache regarding sex, age, duration of HD, causes of end-stage renal disease, arterial diastolic and systolic blood pressure and serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The results were statistically compared. RESULTS: In the group of 143 patients examined, 27 (18.9%) patients had headaches. There were no statistically significant differences between the group of patients with headaches and those without headache regarding to sex, age, duration of HD, causes of end-stage renal disease, serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The patients with headaches showed significantlly higher mean values of systolic blood pressure during HD in comparison to the patients without headaches (p = 0.029). There was no statistically significant difference between the two groups regarding the mean values of diastolic blood pressure. Nineteen (13.3%) patients had had headache before starting HD. HD did not have any effect on the characteristics of headaches in more than a half of these patients. In 8 (5.6%) patients we diagnozed HDH using the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. HDH showed similar caracteristics in all the patients: it appeared mostly in men, during the 4th hour of HD, lasted less than four hours, it was localized bilaterally in the frontal parts of the head, strong in intensity, throbbing and without the associated symptoms. CONCLUSION: The results of our study clearly showed that HDH was a particular entity of headache, not only because of its connenction with HD, but because it had similar characteristics in all the patients in wich it had appeared. Finding out the pathophysiological mechanisms of their occurrence would significantly improve the quality of life style of patients on hemodialysis.     

Acquired von Willebrand syndrome in multiple myeloma

Acquired von Willebrand syndrome (AvWS) is an uncommon complication of multiple myeloma (MM), and it is believed to be connected with paraprotein. The aim of this study was to determine the incidence of AvWS in patients with MM, and estimate the role of paraprotein in its occurrence. The study included 40 patients with MM. The plasma level of paraprotein, platelet adhesion on glass pearls, plasma von Willebrand factor antigen concentration, and ristocetin-induced platelet aggregation (RIPA) were measured initially. Absence of RIPA was found in six patients with MM (15%); however, all six of them had normal levels of von Willebrand factor antigen. Paraprotein was isolated from the serum of these patients. Platelet aggregation was measured in six healthy donors before and after addition of the isolated paraprotein. RIPA was significantly decreased in healthy donors in the presence of paraprotein (P<0·001). The same test was repeated with added human immunoglobulins for intravenous use without any change in RIPA. A significant negative correlation between plasma paraprotein level and RIPA was found (P<0·001). These investigations have shown that paraprotein is associated with AvWS in patients with MM.     

Assesment of Parameters of QT Interval in Children and Adolescents

Aim. To determine limits of interval QT in children and adolescents aged 0-17 years and to detect possible ethnic differences of its changes. Material and Method. Twelve lead ECGs were recorded in 1531 subjects without overt cardiovascular pathology (47.2% females, 52.8 males, 57.3% of Slavic and 42.7% of Buryat i.e. mongoloid ethnicity). Results. Corrected QT interval (QTc) exceeded 440, 460 and 480 ms in 2.3, 1.05, and 0.26% of children. Prolongation of QTc was found in 0.46% and 0.11% of Slavic and Buryat children, respectively (p=ns). Starting from the age of 8 years girls had longer QTc than boys (454.1+/-15.2 and 438.3+/-8.4 ms, respectively, p<0.05). QTc less than 350 ms was registered in 12 children (0.78%). Eight of these children with mean QTc 329.1+/-32.3 ms had family history of syncope or sudden death. Variability of absolute QT values was 8+/-14.3 ms (maximally up to 40 ms). Conclusions. QT interval is prolonged when QTc duration exceeds 440 ms in children younger than 8 years and in male adolescents or 460 ms in girls aged 8 years or older and in children during first year of life. QT interval is shortened when QTc is less than 350 ms (1st degree of shortening). In children with QTc below 330 ms (2nd degree of shortening) short QT syndrome should be excluded. Normal variability of absolute QT value during sinus arrhythm on ECG at rest does not exceed 40 ms.     

Comparative analysis of indicators of the immune status of population of the Eastern regions of the USSR]

Altogether 1,500 healthy residents of seven cities situated in the Asian part of the USSR were examined. In Novosibirsk, Tomsk, Tyumen, Norilsk, Magadan, Yakutsk and Ussuriisk, the people were examined for the blood levels of T and B lymphocytes, the ratio of regulatory subclasses of T lymphocytes, the concentration of IgG, IgM and IgA, and for the content of immune complexes. Analysis was made of the general and regional regularities in changes seen in the immune system depending on climatic and geographic factors. Parameters of the populations similarity in the regions with different environmental conditions were delineated.     

Immunoenzyme cytochemical methods, monoclonal antibodies and lectins in the diagnosis of tumors of the lymphoid tissue in children]

ICO, IPO and LT series monoclonal antibodies, lectins, PAP and APAAP methods were used to study blood, bone marrow and lymph node cells in children with acute lymphoblastic leukemia (ALL), non-Hodgkin's malignant lymphomas and Hodgkin's disease. The immunological phenotype of malignant lymphoid cells has been characterized and cytological variants of ALL and lymphomas of T and B cell origin have been distinguished.     

Intrathoracic and generalized granulomatosis in chronic diffuse liver diseases caused by the hepatitis B virus]

In 7 patients suffering from chronic diffuse liver diseases, they were combined with intrathoracic (3 patients) and generalized (4 patients) granulomatosis. Acute viral hepatitis or risk factors of infecting hepatitis viruses revealed in the case reports of 5 patients preceded the appearance of the signs of both lung and pulmonary damage. In 2 patients (without any indications in the case report to acute viral hepatitis and risk factors of infecting by hepatitis viruses) both the processes were established at a time. HBV markers were detected in all the 7 patients: in the blood serum in 3 and in the blood serum and liver tissue in 4 patients. Besides, HBsAg was identified in the smears of the lavage fluid sediment in 3 patients examined for that purpose. The role of HBV in both etiology of chronic diffuse liver diseases and granulomatosis is under discussion.