Expression of selectin ligands on murine effector and IL-10-producing CD4+ T cells from non-infected and infected tissues

Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu.     

Immunologic immaturity, but high IL-4 productivity, of murine neonatal thymic CD4 single-positive T cells in the last stage of maturation

To determine the levels of maturation and differentiation ofmurine CD4 single-positive (SP) T cells, we compared the secondaryresponses of staphylococcal enterotoxin A (SEA)-induced neonatalthymic, adult thymic and adult splenic CD4 SP T cell blastsprepared from whole or heat-stable antigen^low CD4 SP T cells.Proliferative responses upon re-stimulation with SEA were strongin adult splenic CD4 SP T cell blasts, but quite weak in neonatalthymic and adult thymic CD4 SP T cell blasts. SEA-induced IL-2production was weaker in neonatal thymic blasts than in theadult splenic CD4 SP T cell blasts. In contrast, SEA-inducedIL-4 production was high in neonatal thymic CD4 SP T cell blasts,and low in adult splenic and thymic CD4 SP T cell blasts. Expressionof GATA-3, that directs production of IL-4 in T cells, examinedat protein and mRNA levels, was higher in neonatal thymic cellsthan in adult thymic and splenic cells. These results suggestthat neonatal and adult thymic CD4 SP T cells in the final stageof maturation are relatively immature compared with adult splenicCD4 SP T cells. The cytokine production profile of neonatalthymic CD4 SP T cells suggests that they are inclined towardsa T_h2 response.     

转FL、GM-CSF基因的人骨髓基质细胞促进脐血CD34+细胞体外扩增

研究转FL、GM-CSF基因的基质细胞对脐血CD34+细胞的扩增效应.将转FL、GM-CSF基因的入骨髓基质细胞系与脐血CD34+细胞共培养,观察细胞总数、CD34+细胞数、CFU-GM的变化情况.培养到第4周时,第(4)组(SCF+IL-3+IL-6+GM-CSF+FL)和第(8)组(HFCL/hGM-CSF+HFCL/hFL+SCF+IL-3+IL-6)的细胞总数增加到最大,分别扩增了717±24.47和709±63.63,第1周,第(5)组(HFCL+SCF+IL-3+IL-6)扩增了10.5±2.08倍,较第(8)组减少(P＜0.05).第1周时,CD34+细胞总数第(4)组和第(8)组分别扩增了8.44倍和11.5倍(P＜0.05),CD34+细胞百分率第(7)组(FCL/hFL+SCF+IL-3+II,-6)为50.2%,第(6)组(HFCL/hGM-CSF+SCF+IL-3+IL-6)为28.95%(P＜0.01).第2周,各组CFU-GM增加显著,以第(4)组和第(8)组增加最为明显,以后随扩增时间延长,造血细胞集落数、集落体积逐渐减少.表明转FL、GM-CSF基因的基质细胞,能有效的协同其他细胞因子对脐血CD34+细胞产生明显的扩增作用,能显著改变基质细胞造血功能.     

Glucocorticoids modulate TGF-beta production

TGF- is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB- isoforms affect TGF- production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-1, -2, and -3. TGF- mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-2 and -3 stimulated TGF-1 production significantly (p < 0.01 relative to control). TGF-1 stimulated TGF-2 production (p < 0.01 relative to control). TGF-3 was undetectable. Glucocorticoids significantly inhibited TGF-1 and -2 production and reduced expression of the upregulated TGF-1 and -2 mRNA induced by exogenous TGF-1, -2 or -3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF--stimulated cells, it was reduced by glucocorticoids. Thus, TGF- isoforms may stimulate production of various TGF- isoforms in the lung. Glucocorticoids then may block TGF- production by modulating mRNA levels and c-Jun.     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

Compartmentation of cardiac adenine nucleotides and formation of adenosine

Summary After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either¹⁴C-adenine or¹⁴C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 35-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substance. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart.Our findings provide evidence that at least two different adenine nucleotide compartments of the heart serve as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.A preliminary report of part of this work appeared in Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction Vol. 7 of Recent advances in studies on cardiac structure and metabolism. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976A preliminary report of part of this work appeared in Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction Vol. 7 of Recent advances in studies on cardiac structure and metabolism. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976     

Clinical applications of colour Doppler energy imaging in the female reproductive tract and pregnancy

This review describes the usefulness of colour Doppler energy (CDE) (or power Doppler) imaging to measure vascularization in the female reproductive tract. CDE imaging is characterized by an increased sensitivity to flow, and thus may be useful in low-flow states and when optimal Doppler angles cannot be obtained. In addition, longer segments of vessels and more individual vessels can be visualized with CDE imaging. The role of CDE imaging in the evaluation of stromal vasculature in normal and in polycystic ovaries is described, and the relationship between follicular vascularity and outcome following in-vitro fertilization are discussed, together with the findings obtained from the evaluation of thecal arteriole of corpus luteum in early pregnancy. The fundamental role of CDE imaging in differentiation among ovarian masses is also reviewed. We summarize the role of CDE imaging in pregnancy, and describe two new applications of three-dimensional power Doppler sonography and the use of ultrasound contrast media. In conclusion, CDE imaging can replace conventional colour Doppler when the information on the direction of flow is not useful. Moreover, the technique appears superior to others for describing microvascular architecture and determining the presence or absence of flow.     

Temperature stabilizing effect of tocopherol on rhodopsin in the pressure of fatty acids studied by differential scanning calorimetry

Institute of Cytology, Academy of Sciences of the USSR. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Institute of Physiology, Bulgarian Academy of Sciences, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. A. Vladimirov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 8, pp. 160–171, August, 1989.