切割前房结通路对家兔房室结电生理特性的影响

为进一步了解房室结整体电生理特性以及消融治疗房室结折返性心动过速的机制，选择性切割无房室结双径现象离体家兔心的前房结通路（Ｋｃｈ三角前区）观察其对房室结电生理参数的影响。与切割前相比，切割后ＡＨ间期、房室结功能不应期、房室结前传文氏周长、室房逆传文氏周长及ＶＡ间期延长（分别为４５．６４±８．６８ｍｓｖｓ３８．２３±６．１３ｍｓ，１６６．３４±１５．３３ｍｓｖｓ１４４．４８±１０．８６ｍｓ，１６３．３７±１７．２２ｍｓｖｓ１３８．３６±１２．４３ｍｓ，２０２．６０±４１．５０ｍｓｖｓ１６８．５０±２０．３０ｍｓ，６８．６０±１．６０ｍｓｖｓ５４．５０±７．１０ｍｓ，Ｐ均＜０．０５）。提示毁损房室交界区特定部位可以影响房室结整体电生理特性。     

Antibody response to intravenous immunization following splenic tissue autotransplantation in Sprague-Dawley rats

The response to intravenous challenge with sheep erythrocytes was determined in Sprague-Dawley rats following autotransplantation of splenic tissue into the subcutaneous tissue, peritoneal cavity, or a surgically created omental pouch. There was a marked rise in heterophil antibody titer following intravenous challenge in ten control animals, and no rise in titer in nine of ten asplenic animals. Heterophil antibody titers increased in all of the animals with transplants, but the response in some was less than that in control animals. Thus autotransplanted splenic tissue demonstrated immunologic responses similar to those of normal, intact spleen.     

Long-term therapy for pulmonary hypertension in children

This review recounts recent advances in the understanding and treatment of the processes that cause pulmonary hypertension in infancy and childhood. New discoveries have begun to unveil connections between the basic physiological mechanisms responsible for the regulation of pulmonary vascular tone and the abnormal responses of the pulmonary vasculature in a variety of disease conditions. These discoveries raise hope for new therapeutic interventions that may improve the high mortality and morbidity of both children and adults with pulmonary vascular disease. In the meantime, treatment efforts continue to be focused on the relief of pulmonary vasoconstriction with inhaled nitric oxide and intravenous prostacyclin in the short term and oral calcium channel blockers as the mainstay of long-term therapy. Lung transplantation often remains as the only viable option for continued survival when the pulmonary vascular disease is progressive.     

Establishment and characterization of cloned human thymic epithelial cell lines. Analysis of adhesion molecule expression and cytokine production

The thymic stromal microenvironment is required for the generation of immunocompetent T lymphocytes. However, the different thymic stromal cell types have not been fully characterized and their roles regarding T-cell development are not completely understood. To address the phenotypic characteristics of the epithelial component of the human thymic microenvironment as well as its functional involvement in T-cell development, we have established cloned thymic epithelial cell (TEC) lines from fetal and postnatal human thymuses by an explant technique, repeated subculture, and limiting dilution cloning. These cloned TEC lines were shown to be derived from cortical epithelium and to express a number of cell-surface molecules including CD40, major histocompatibility complex (MHC) HLA-ABC and HLA-DR antigens, homing- associated cell-adhesion molecule (H-CAM), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 3 (LFA-3), and beta 1 subfamily integrins. Finally, both postnatal and fetal TEC clones were shown to produce interleukin-1 alpha (IL-1 alpha), IL-6, and IL-7. These well-defined cloned TEC lines may provide useful tools for the study of TEC biology and for the understanding of the precise role played by TEC in human T-cell development.     

Platelet adhesion to fibronectin in flow: the importance of von Willebrand factor and glycoprotein Ib

We describe glycoprotein (GP) Ib as a mediator of adhesion to fibronectin, specifically in flow. A monoclonal antibody (MoAb) directed to the von Willebrand factor (vWF)-binding site on this receptor or the absence of this receptor on the platelet membrane, in the case of a patient with the Bernard-Soulier syndrome, reduced platelet coverage to fibronectin to approximately 30% of the control value. A MoAb directed to the GP Ib-binding site on vWF showed a similar effect. With washed platelets in the absence of plasma vWF, the inhibitory effect of the anti-GP Ib antibody was the same as with whole blood. No inhibition with the anti-GP Ib antibody was observed when we used blood from patients with severe von Willebrand disease (vWD) or from a patient with vWD type I (platelet low). Addition of vWF to vWD blood resulted in restoration of adhesion. Immunoelectron microscopy on platelets adhering to fibronectin showed that GP Ib was homogeneously distributed over the entire surface of the platelet. vWF was present at the central zone and the edges of the platelet and at the basal interface between the platelet and the fibronectin surface. No direct binding of vWF to fibronectin could be demonstrated. These data indicate that GP Ib-mediated adhesion to fibronectin fully depends on vWF and that normal levels of plasma or platelet vWF are sufficient for optimal adhesion to fibronectin. The data suggest that the presence of platelets during perfusion is a prerequisite for vWF to support platelet adhesion to fibronectin.     

Mercury as an environmental stimulus in the development of autoimmunity – A systematic review

Autoimmune diseases result from an interplay of genetic predisposition and factors which stimulate the onset of disease. Mercury (Hg), a well-established toxicant, is an environmental factor reported to be linked with autoimmunity. Hg exists in several chemical forms and is encountered by humans in dental amalgams, certain vaccines, occupational exposure, atmospheric pollution and seafood. Several studies have investigated the effect of the various forms of Hg, including elemental (Hg⁰), inorganic (iHg) and organic mercury (oHg) and their association with autoimmunity. In vitro studies using peripheral blood mononuclear cells (PBMC) from healthy participants have shown that methylmercury (MeHg) causes cell death at lower concentrations than iHg albeit exposure to iHg results in a more enhanced pro-inflammatory profile in comparison to MeHg. In vivo research utilising murine models susceptible to the development of metal-induced autoimmunity report that exposure to iHg results in a lupus-like syndrome, whilst mice exposed to MeHg develop autoimmunity without the formation of immune complexes. Furthermore, lower concentrations of IgE are detected in MeHg-treated animals in comparison with those treated with iHg. It appears that, oHg has a negative impact on animal models with existing autoimmunity. The research conducted on humans in this area is diverse in study design and the results are conflicting. There is currently no evidence to implicate a role for Hg⁰ exposure from dental amalgams in the development or perpetuation of autoimmune disease, apart from some suggestion of individual sensitivity. Several studies have consistently shown a positive correlation between iHg exposure and serum autoantibody concentrations in gold miners, although the clinical impact of iHg remains unknown. Furthermore, a limited number of studies have reported individuals with autoimmune disease have higher concentrations of blood Hg compared to healthy controls. In summary, it appears that iHg perpetuates markers of autoimmunity to a greater extent than oHg, albeit the impact on clinical outcomes in humans is yet to be elucidated.     

Mitochondrial dysfunctions in circulating T lymphocytes from human immunodeficiency virus-1 carriers [see comments]

In several models of lymphocyte apoptosis, two alterations of mitochondrial function precede advanced DNA fragmentation: (1) a reduction of mitochondrial transmembrane potential (delta psi m) and (2) an increase in mitochondrial generation of superoxide anion. Here we show that two fluorochromes allow for the identification of analogous mitochondrial perturbations in circulating T lymphocytes from human immunodeficiency virus (HIV)-1+ donors. The first among these fluorochromes, the cationic lipophilic dye DiOC6(3), measures delta psi m; the second marker, hydroethidine (HE), is nonfluorescent, unless it is oxidized by superoxide anions to the product ethidium (Eth). CD4+ or CD8+ cells from clinically asymptomatic HIV-1 carriers contain a significantly elevated percentage of cells endowed with enhanced HE --> Eth conversion and/or reduced DiOC6(3) uptake as compared with normal controls. Phenotypic characterization of (HE --> Eth)high cells from HIV+ donors shows that these cells possess a low delta psi m, thus demonstrating a functional alteration of mitochondria. In addition, (HE --> Eth)high cells display a reduced incorporation of the cardiolipin- specific dye nonyl-acridine orange (NAO), showing a structural defect of the cardiolipin-containing inner mitochondrial membrane. Control experiments involving rotenone, an inhibitor of the respiratory chain complex I, indicate that the reactive oxygen species responsible for HE --> Eth conversion is generated during mitochondrial electron transport. In synthesis, it appears that mitochondrial alterations occur in a significant percentage of circulating T lymphocytes from HIV- 1 carriers. The extent of delta psi m reduction, as determined ex vivo, correlates with the frequency of cells undergoing DNA fragmentation after overnight in vitro culture. These observations may be important for the understanding and for the direct ex vivo quantitation of HIV- triggered lymphocyte destruction.