Undulating tubules in lymphocytes of an apparently healthy human donor

Summary So-called undulating tubules were found in the blood lymphocytes of an apparently healthy 33-year-old male. Undulating tubules have been noted to occur frequently in kidney cells and blood lymphocytes of patients suffering from collagen diseases and especially from SLE. They have been suggested to be a possibly pathognomonic finding in such diseases. Our result seems to contradict such an association.     

Receptors for cytomegaloviruses on the surface of human lymphocytes]

The relationships between cytomegalovirus (CMV) and lymphocytes have already been noted because of: (a) the immunological abnormalities induced by this virus, and (b) activation of latent CMV in the course of lymphocyte reactions associated with anti-histocompatibility antigen immune response. The present work shows that the lymphocyte surface may have specific receptors for CMV. Cultured fibroblasts infected with DMV were incubated with lymphocytes isolated from the blood of human immune subjects. Rosettes defined by the adherence of three or more lymphocytes around a fibroblast were formed in infected preparation while no rosettes were seen with normal control fibroblasts. Approximately 1.2 per cent of lymphocytes were involved in the formation of these rosettes. Rosette formation is inhibited when infected fibroblasts have been incubated with anti-CMV antibodies prior to the addition of lymphocytes.     

Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma.

Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.     

Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma

Summary Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vitro cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.     

Chromosome aberrations in in vitro irradiated lymphocytes from human cord blood.

An in vitro dose effect curve of dicentric chromosome aberrations in human cord blood lymphocytes has been obtained for 250-kV X-rays. This is compared with a curve prepared in an identical manner using blood from adults. The comparison shows a marginally higher dicentric yield in blood of newborns at doses above about 250 rads.     

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.Received 16 June 2004; received after revision 9 September 2004; accepted 23 September 2004     

Alkaline phosphatase in human lymphocyte subpopulations.

The levels of membrane alkaline phosphatase have been measured on different lymphocyte fractions from human peripheral blood separated on bovine serum albumin discontinuous gradients. The peak in enzyme activity was observed in a non-T-, non-B-cell fraction, rich in "null" lymphocytes; the lowest values were found in the fraction with the highest proportion of T-cells.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes.

The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enchance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.     

Chromosome aberrations in in vitro irradiated lymphocytes from human cord blood

Summary An in vitro dose effect curve of dicentric chromosome aberrations in human cord blood lymphocytes has been obtained for 250-kV X-rays. This is compared with a curve prepared in an identical manner using blood from adults. The comparison shows a marginally higher dicentric yield in blood of newborns at doses above about 250 rads.Acknowledgment. We wish to thank Miss P. Orledge of the John Radcliffe Hospital, Oxford, for samples of cord blood, Mr M.J. Corp of the MRC Radiobiology Unit, Harwell, for irradiating the samples and Mr A.A. Edwards of NRPB, for help with statistics. The work was partly supported by Euratom Contract No. 171-76-1 BIO UK.     

Early B lymphocytes in man

Summary We have confirmed in man the presence of a subpopulation of B lymphocytes which cannot reexpress their immunological receptors after challenge with antibodies. These early B lymphocytes were studied in peripheral blood, in cord blood and also, with anti-idiotypic sera, in the peripheral blood of a myeloma patient.Acknowledgments. This work was supported by CNR, Progetti finalizzati, Controllo della Crescita Neoplastica. We thank Prof. J. Urbain for helpful suggestions.     

The CD40/CD154 receptor/ligand dyadRID="†"ID="†" Review

Until recently, the expression and primary function of the cell surface receptor CD40 and its ligand CD154 were considered restricted to B and T lymphocytes, and their interactions required for the thymus-dependent humoral response. However, current work from several groups challenges this view of the CD40/CD154 dyad as a mere mediator of lymphocyte communication. A variety of non-lymphocytic cell types express both receptor and ligand, including hematopoetic and non-hematopoetic cells, such as monocytes, basophils, eosinophils, dendritic cells, fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules, cytokines, matrix-degrading enzymes, prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling has been associated with pathogenic processes of chronic inflammatory diseases, such as autoimmune diseases, neurodegenerative disorders, graft-versus-host disease, cancer, and atherosclerosis. This review focuses on the synthesis and structure of CD40 and outlines CD154/CD40 signaling pathways, and emphasizes the previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a spectrum of immunoregulatory processes and prevalent human diseases. Received 10 January 2000; revised 16 June 2000; accepted 5 July 2000 RID="†" ID="†" Review RID="*" ID="*" Corresponding author.     

RhoA/Rho-kinase and vascular diseases: what is the link?

RhoA/Rho-kinase pathway plays an important role in many pathological conditions. RhoA participates in the regulation of smooth muscle tone and activates many downstream kinases. The best characterized are the serine/threonine kinase isoforms (Rho-kinase or ROCK), ROCKα/ROCK2 and ROCKβ/ROCK1. ROCK is necessary for diverse functions such as local blood flow, arterial/pulmonary blood pressure, airway resistance and intestinal peristalsis. ROCK activation permits actin/myosin interactions and smooth muscle cells contraction by maintaining the activity of myosin light-chain kinase, independently of the free cytosolic calcium level. The sensitization of smooth muscle myofilaments to calcium has been implicated in many pathological states, such as hypertension, diabetes, heart attack, stroke, pulmonary hypertension, erectile dysfunction, and cancer. The focus of this review is on the involvement of RhoA/Rho-kinase in diseases. We will briefly describe the ROCK isoforms and the role of RhoA/Rho-kinase in the vasculature, before exploring the most recent findings regarding this pathway and various diseases.     

Changes in the plasma membrane surface of lymphocytes stimulated in vivo with DNCB.

Stereological principles have been used to evaluate ultrastructural changes which accompany the transformation of lymphocytes stimulated in vivo with dinitrochlorobenzene (DNCB). Whereas unstimulated lymphocytes and blast cells have slightly more than the minimal containing plasmalemmal surface for their volume, stimulated (blast-derived) lymphocytes have an excess surface area in the order of 30%. This observation is discussed in the context of altered cell function and the biosynthesis of additional membrane components.     

Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA

Celiac disease is characterized by the presence of specific autoantibodies targeted against transglutaminase 2 (TG2) in untreated patients’ serum and at their production site in the small-bowel mucosa below the basement membrane and around the blood vessels. As these autoantibodies have biological activity in vitro, such as inhibition of angiogenesis, we studied if they might also modulate the endothelial barrier function. Our results show that celiac disease patient autoantibodies increase endothelial permeability for macromolecules, and enhance the binding of lymphocytes to the endothelium and their transendothelial migration when compared to control antibodies in an endothelial cell-based in vitro model. We also demonstrate that these effects are mediated by increased activities of TG2 and RhoA. Since the small bowel mucosal endothelium serves as a “gatekeeper” in inflammatory processes, the disease-specific autoantibodies targeted against TG2 could thus contribute to the pathogenic cascade of celiac disease by increasing blood vessel permeability.     

辛伐他汀联合用药研究进展

动脉粥样硬化是心脑血管疾病的主要病理学基础,他汀类药物是抗动脉粥样硬化的基石.辛伐他汀降低总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）作用明显,同时也降低甘油三酯（TG）和升高高密度脂蛋白（HDL）水平,是目前临床上应用最广泛的降脂药之一.诸多专家学者对辛伐他汀的联合用药也进行了广泛深入的研究,认为其不仅在抗动脉粥样硬化领域具有确切的疗效,而且在不稳定性心绞痛、冠心病的二级预防、高血压、早期糖尿病肾病以及骨质疏松等疾病中的治疗也具有重要的意义.     

Vascular stem/progenitor cells: functions and signaling pathways

Vascular stem/progenitor cells (VSCs) are an important source of all types of vascular cells needed to build, maintain, repair, and remodel blood vessels. VSCs, therefore, play critical roles in the development, normal physiology, and pathophysiology of numerous diseases. There are four major types of VSCs, including endothelial progenitor cells (EPCs), smooth muscle progenitor cells (SMPCs), pericytes, and mesenchymal stem cells (MSCs). VSCs can be found in bone marrow, circulating blood, vessel walls, and other extravascular tissues. During the past two decades, considerable progress has been achieved in the understanding of the derivation, surface markers, and differentiation of VSCs. Yet, the mechanisms regulating their functions and maintenance under normal and pathological conditions, such as in eye diseases, remain to be further elucidated. Owing to the essential roles of blood vessels in human tissues and organs, understanding the functional properties and the underlying molecular basis of VSCs is of critical importance for both basic and translational research.     

Immunoglobulin synthesis by cord blood lymphocytes.

The IgG, IgA and IgM synthesis by adult peripheral blood and cord blood lymphocytes incubated alone and with pokeweed mitogen was quantitated. The cord blood lymphocytes produced no immunoglobulin even with mitogen stimulation while the adult peripheral blood lymphocytes responded to the mitogen with a significant (p less than 0.04) increase in immunoglobulin production.     

Immunoglobulin synthesis by cord blood lymphocytes

Summary The IgG, IgA and IgM synthesis by adult peripheral blood and cord blood lymphocytes incubated alone and with pokeweed mitogen was quantitated. The cord blood lymphocytes produced no immunoglobulin even with mitogen stimulation while the adult peripheral blood lymphocytes responded to the mitogen with a significant (p<0.04) increase in immunoglobulin production.