A substantial proportion of human peripheral blood mononuclear cells (PBMC) manifested a decreased capacity to express membrane interferon-gamma receptors (IFN-gamma R) when co-cultured with Trypanosoma cruzi. Among the lymphocytes, B cells accounted for the bulk of this effect, evidenced by a marked drop in the proportion of CD19+ or CD20+ cells expressing IFN-gamma R. Decreased IFN-gamma R expression by B lymphocytes was seen as early as 3 h after co-culture with T. cruzi and persisted for at least 24 h. The parasite had no detectable effect on CD19, CD20 or DR antigen expression by B lymphocytes. Neither the proportion of B cells expressing these markers nor the membrane density of these molecules varied significantly in the presence of T. cruzi. In PBMC cultures stimulated with Staphlyococcus aureus Cowan I (SACI), T. cruzi decreased the percentages of both IFN-gamma R+ and IFN-R+bright (cells expressing above-normal levels of surface IFN-gamma R) B lymphocytes. Cell-free filtrates of T. cruzi suspensions reproduced the suppressive effects of living parasites on IFN-gamma R expression by B cells. When T. cruzi present, the intracellular levels of IFN-gamma R molecules in resting or SACI-activated B lymphocytes, represented by fluorescence intensity, were well below control values, suggesting that decreased surface expression resulted from suppressed IFN-gamma R synthesis. Among T (CD3+) cells, 10.8% to 39.6% (7 donors) expressed surface IFN-gamma R and did so at a very low level. These percentages were also reduced by T. cruzi.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitogen-activated lymphocytes co-cultured with either purified Trypanosoma cruzi trypomastigotes or the filtrate of trypomastigote suspensions in culture medium manifest a significant decrease in their capacities to express p55 interleukin-2 receptor molecules (p55IL-2R) on their membrane and proliferate. In this study we found that the cytoplasmic levels of p55IL-2R are also markedly reduced under these conditions. This inhibition appeared to result from altered gene transcription since the levels of p55IL-2R mRNA in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) dropped substantially in the presence of parasite suspension filtrate. The rates of decay for p55IL-2R mRNA determined in cultures lacking and containing the parasite filtrate after addition of actinomycin D to inhibit further RNA synthesis were comparable. These results indicated that decreased p55IL-2R mRNA was not due to decreased stability of this mRNA under our conditions and pointed to a transcriptional or pre-transcriptional modification as the likely mechanism by which T. cruzi affects activated lymphocytes. The parasite filtrate did not appear to affect transcription of c-fos or c-myc (known to occur in the very early stages of lymphocyte activation) or that of CD69 (which is concomitant with p55IL-2R transcription). Thus, decreased p55IL-2R gene transcription appears to be a somewhat selective effect of a T. cruzi-derived molecule(s) rather than the consequence of an overall shutdown of gene transcription.
Background: Leptin is a growth factor for the fetus. The sources for maternal and fetal leptin plasma levels are the adipose tissue and the placenta. Placental leptin release elevates maternal leptin levels only about 15%. We hypothesize that activated adipose tissue is an additional source for the high leptin levels in pregnancy. However it is further not clear if maternal leptin reaches the fetal circulation and supports fetal growth by that way. Aim of the study: (1) Do maternal leptin arrive the fetal circulation and (2) is maternal adipose tissue leptin production activated during pregnancy ? Methods: Placentas and adipose tissue was obtained after written informed consent of the patients. (1) Dual in vitro perfusion of isolated cotyledons (nϭ7) for 3h. Addition of 125-I-leptin and unlabeled leptin (1ϩ3, 22 ng/ml total leptin) to the maternal circulation. Control of vitality and integrity by measurement of glucose consumption, lactate production, creatinine-and antipyrin transfer. (2) Sampling of subcutaneous maternal adipose tissue during cesarean sections (nϭ10, no gestational pathology) and during other gynecological surgery (nϭ10, age matched, no malignancies). Measurement of leptin mRNA using Taqman real time PCR. Results: (1) Materno-fetal transfer rate of the labeled leptin was 4,5 Ϯ 1,4% of the initial concentration. Permeability of 125-I-leptin accounted for 0,04 Ϯ 0,02 ml min-1 g-1, and was 1,3 Ϯ 0,1 ml min-1 g-1 normalized to creatinine transfer. Existence of free 125-iodine was excluded by comparison of dialysated and undialysated fetal perfusion medium. (2) Leptin mRNA was significant higher in adipose tissue of pregnant women than in the control group (1,0 Ϯ 0,5 v. 0,5 Ϯ 0,4 rel. Units; pϽ0,05) Conclusion: (1) We could show first, that leptin from the maternal circulation passes the placenta and enters the fetal blood. There seems to be an active transplacental transport from the maternal to the fetal circulation, due to molecular weight and calculated permeability. (2) Maternal adipose tissue leptin production is activated during pregnancy. A basic leptin supply in the beginning of fetal development seems to be guaranteed by the placenta and maternal adipose tissue and was supplemented by the own leptin production of the fetus during further maturation and growth. X H Liu, H J Huang, C R Li Shenzhen Children's Hospital, Neonatology, Shenzhen, China Objective: Neonatal infants with severe respiratory failure have no response to conventional mechanical ventilation (CMV). Our goal was to evaluate the efficacy of high-frequency oscillatory ventilation (HFOV) for treatment of these infants. EFFICACY OF HIGH-FREQUENCY OSCILLATORY VENTILATION FOR TREATMENT OF SEVERE RESPIRATORY FAILURE IN NEONATESMethods: From December 1998 to December 2003, 66 infants with respiratory failure and not responsive to CMV were treated with HFOV. The primary efficacy variables were improvement in oxygenation, lung function, complications and survival. Gestational age of the studied infants was 38°À 5 wk and birth weig...
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