Complement Killing of Yersinia enterocolitica and Retention of the Bacteria by Leucocyte Removal Filters

We report studies on the complement sensitivity of four strains of Yersinia enterocolitica , serotypes O:3, O:9, O:5,27, and O:20, isolated from blood units involved in transfusion fatalities. Complement in fresh CPD plasma killed Y. enterocolitica within 4 h at 22°C in 100% of the experiments. The bactericidal action was serotype and complement activation pathway dependent. Both classic and alternate pathways seemed to be active, but the latter to a lesser degree. When the classic pathway was blocked by chelation of Ca²⁺ no complete killing was obtained. Complement did not enhance or condition Yersinia for leucocyte filter retention. Direct removal of Yersinia by filtration was also related to serotype; all strains were reduced by filtration in heat-inactivated plasma, and all except serotype O:5,27 were reduced in Ca²⁺ -chelated plasma. Our findings may explain why plasma products and platelet concentrates are rarely involved in Yersinia sepsis related to transfusion.     

Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.     

Ligamentum flavum hematoma. Report of two cases.

Two patients presenting with signs and symptoms suggestive of nerve root compression secondary to extradural masses were found to have ligamentum flavum hematomas. Both patients had neurological deficits preoperatively and regained normal function postoperatively. There was no significant antecedent injury in either case. The symptom course was longer than that for spontaneous epidural hematoma. In one case, there was remodeling of bone, initially suggesting either infection or tumor.     

Molecular mechanisms of apoptosis in the cells of the immune system in human aging

Summary: Aging is associated with progressive decline in immune functions and increased frequency of infections, autoimmunity, and cancer. Among immune functions, a decline in T‐cell functions during aging predominates. In this review, I discuss the molecular signaling of three distinct pathways of apoptosis, namely the death receptor pathway, the mitochondrial pathway, and the most recently described endoplasmic reticulum stress pathway, and the relative sensitivity of naïve, central memory, and effector memory CD8⁺ T‐cell subsets to apoptosis. In addition, I review apoptosis, especially via death receptor pathway, in naïve and various memory subsets of CD4⁺ and CD8⁺ T cells (with primary emphasis on CD8⁺ naïve and memory subsets) in human aging and discuss the role of apoptosis in immune senescence.     

HIV seroincidence among patients at clinics for sexually transmitted diseases in nine cities in the United States

Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s, it is not clear whether they reflect a decreasing number of new HIV infections. Direct measurement of HIV incidence through follow-up cohort studies is difficult and costly. We estimated HIV incidence and trends in incidence among men who have sex with men (MSM) and heterosexual men and women at clinics for sexually transmitted diseases (STDs) by using a recently developed serologic testing algorithm that requires only a single blood specimen. Cross-sectional anonymous serosurveys were conducted at 13 STD clinics in nine cities in the United States from 1991 through 1997. Before anonymous HIV testing, demographic and clinical information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from persons estimated to be recently infected. Incidence among MSM was 7.1% (95% confidence interval (CI): 4.8-10.3), 14 times higher than that among heterosexuals, which was 0.5% (CI: 0.4- 0.7). Incidence among MSM and heterosexuals remained unchanged during the time studied. Decreasing rates of new AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections among MSM and heterosexual patients attending these clinics.     

P-glycoprotein (MDR 1 gene product) in cells of the immune system: Its possible physiologic role and alteration in aging and human immunodeficiency virus-1 (HIV-1) infection

P-glycoprotein, a 170-kd glycoprotein encoded by theMDR 1 gene, is a member of a highly conserved superfamily of ATP-binding cassette (ABC) transport proteins. It shares extensive homology with numerous bacterial and eukaryotic ABC transport proteins. P-glycoprotein acts as an energy-dependent efflux pump that appears to transport structurally diverse agents ranging from ions to peptides. P-glycoprotein (P-gP) has been implicated as playing a role in multidrug (MDR) resistance in cancer, chloroquine-resistantPlasmodium falciparum infection, and possibly human immunodeficiency virus-1 (HIV-1) resistance to nucleoside compounds. A number of normal tissues in humans and rodents have been shown to express high levels of P-gp. The expression and function of P-gp in cells of the immune system have been explored in the past 2 years. This review presents a state of the art regarding the expression, regulation, and function of Pgp in cells of the immune system. In addition, its alteration in aging and HIV-1 infection is reviewed. A possible physiologic role of P-gp in cytokine secretion, antigen processing/presentation, and effector functions is also discussed.     

Human immunodeficiency virus-associated changes in signal transduction

It is well established that the activation of T lymphocytes by mitogen/antigen is accompanied by a rise in intracellular free calcium ([Ca²⁺]_i), changes in membrane potential, metabolism of inositol phospholipid, and activation of protein kinase C. Theseearly events of signal transduction culminate inlate events of lymphocyte activation, namely, DNA synthesis, lymphokine production, and cellular proliferation. In this study we examined the effect of human immunodeficiency virus (HIV) on changes in membrane potential and [Ca²⁺]_i levels. The membrane potentials were markedly decreased (depolarized) in T cell lines infected with HIV (H9/HTLV IIIb) and did not respond normally to phytohemagglutinin (PHA) or anti-T3 (anti-CD3) monoclonal antibody compared to uninfected H9 cell line. The basal [Ca²⁺]_i levels in H9/HTLV IIIb cells were increased in comparison to those in H9 cells; however, there was very little further increase in [Ca²⁺]_i in H9/HTLV IIIb cells following activation with PHA or anti-T3 monoclonal antibody. This is in contrast to a significant rise in [Ca²⁺]_i in H9 cells following similar stimulation. These data demonstrate abnormalities in the plasma membrane potential and [Ca²⁺]_i levels in chronically infected T cells with HIV. These abnormalities in signal transduction of the T-cell activation pathway could be responsible for T-cell dysfunction in patients with HIV infection.