Decreased nematode clearance and anti-phosphorylcholine-specific IgM responses in mannose-binding lectin-deficient mice.

Brugia malayi is a nematode that causes human lymphatic filariasis. Previously, we showed that mannose-binding lectin (MBL)-A is necessary for clearance of B. malayi microfilariae in mice and presence of MBL-A is linked with maximal levels of parasite-specific IgM.

Disorganization of the splenic microanatomy in ageing mice.

The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed.

Eosinophils are important for protection, immunoregulation and pathology during infection with nematode microfilariae.

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae.

Granulocytes: effector cells or immunomodulators in the immune response to helminth infection?

Granulocytes are effector cells in defence against helminth infections. We review the current evidence for the role of granulocytes in protective immunity against different helminth infections and note that for each parasite species the role of granulocytes as effector cells can vary. Emerging evidence also points to granulocytes as immunomodulatory cells able to produce many cytokines, chemokines and modulatory factors which can bias the immune response in a particular direction.

Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice.

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice.

Impact of continuous vigilance monitoring on nursing workflow.

Background: Increasing nursing time in patient care is beneficial in improving patient outcomes, but this is proving increasingly difficult with the nursing shortage, budgetary constraints, and higher patient acuity.

Objective: Nursing workflow was evaluated after the implementation of a continuous vigilance monitoring system to determine if the system enhanced patient-centric nursing care.

Methods: Work sampling observations were conducted at 3 hospitals for 6 categories of nursing activities (direct and indirect nursing, documentation, administrative, housekeeping, and miscellaneous) at baseline and at 3 and 9 months.

Alterations of splenic architecture in malaria are induced independently of Toll-like receptors 2, 4, and 9 or MyD88 and may affect antibody affinity.

Splenic microarchitecture is substantially altered during acute malaria infections, which may affect the development and regulation of immune responses. Here we investigated whether engagement of host Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adaptor protein MyD88 is required for induction of the changes and whether antibody responses are modified when immunization takes place during the period of splenic disruption. The alterations in splenic microarchitecture were maximal shortly after the peak of parasitemia and were not dependent on engagement of TLR2, TLR4, or TLR9, and they were only minimally affected by the absence of the MyD88 adaptor molecule.

Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi.

While it is known that antibodies are critical for clearance of malaria infections, it is not clear whether adequate antibody responses are maintained and what effect chronic infection has on this response. Here we show that mice with low-grade chronic primary infections of Plasmodium chabaudi or infections very recently eliminated have reduced second infections when compared with the second infection of parasite-free mice. We also show that parasite-specific antibody responses induced by infection of mice with Plasmodium chabaudi contain both short- and long-lived components as well as memory B cells responsible for a faster antibody response during re-infection.

Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells.

The capacity of splenic CD11c+ dendritic cell (DC) populations to present antigen (Ag) to T cells differs during malarial infection with Plasmodium chabaudi in mice. Both CD11c+ CD8+ and CD8- DCs presented malarial peptides on their surface during infection. However, although both DC subsets expressing malaria peptides could induce interferon-gamma production by CD4 T cells, only CD8- DCs isolated at the acute phase of infection stimulated Ag-specific T cell proliferation and interleukin (IL)-4 and -10 production from MSP1-specific T cell receptor for Ag transgenic T cells coincidental with our reported Th1 to Th2 switch at this stage in response to the pathogen.

Dendritic cells, pro-inflammatory responses, and antigen presentation in a rodent malaria infection.

An infection of mice with Plasmodium chabaudi is characterized by a rapid and marked inflammatory response with a rapid but regulated production of interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). Recent studies have shown that dendritic cells (DCs) are activated in vivo in the spleen, are able to process and present malaria antigens during infection, and may provide a source of cytokines that contribute to polarization of the CD4 T-cell response. P.

Changing emphases in public health and medical education in health care reform.

Globalisation of economies, diseases and disasters with poverty, emerging infectious diseases, ageing and chronic conditions, violence and terrorism has begun to change the face of public health and medical education. Escalating costs of care and increasing poverty have brought urgency to professional training to improve efficiency, cut costs and maintain gains in life expectancy and morbidity reduction. Technology, genetics research and designer drugs have dramatically changed medical practice.

Community refinement of glaucoma referrals.

Aim: To describe a Manchester-based glaucoma referral refinement scheme designed to reduce the number of false-positive referrals to the hospital eye service. To report on the first years results of this scheme and its financial costs to the NHS.

Methods: Patients with suspected glaucoma, instead of being referred to their GP and then on to the hospital eye service, were referred to a group of specially trained community optometrists working to an agreed set of referral criteria.

Utilization and effectiveness of a weight-based heparin nomogram at a large academic medical center.

Objective: To determine the utilization rate of a weight-based heparin nomogram and to assess the performance of the nomogram outside of experimental conditions.

Study Design: Prospective cohort analysis.

Patients And Methods: A total of 747 consecutive patients treated with intravenous heparin therapy for any indication on an internal medicine service were evaluated for the utilization rate of the weight-based nomogram, the time needed to exceed heparin's therapeutic threshold (activated partial thromboplastin time [aPTT] of > 1.

A surplus of physicians? The view of internists at a single institution.

Background: The sizable increase in the United States physician workforce over the last 25 years has led to a concern by health policy analysts that we are training too few generalist physicians, too many specialists and too many doctors altogether. Nearly all analysts' studies report that the United States currently has an adequate or more than adequate supply of physicians; however, few reports discuss practicing physicians' view of the issues.

Objective: To determine internists' opinion regarding the current and future physician supply and specialty mix.

A web-based risk management and medical-legal curriculum for graduate medical education.

An educational Web site on the topic of risk management and medical-legal issues was designed. The site incorporates a 25-question multiple-choice quiz where resident responses were stored in a database for quantitative analysis. Residents who browsed the educational module scored significantly higher on the quiz (81%) than those who did not (62%).

Factors influencing the career choices of physicians trained at Yale-New Haven Hospital from 1929 through 1994.

Purpose: To examine factors that influenced, positively or negatively, the specialty career choices of physicians trained at Yale-New Haven Hospital (YNHH) from 1929 to 1994.

Method: The authors sent questionnaires to 4,888 physicians who had trained or were training in YNHH-sponsored residency programs. The physicians rated 36 factors posited to be influenced in career choice on a seven-point Likert scale from very negative to very positive.

Beta-amyloid peptides initiate the complement cascade without producing a comparable effect on the terminal pathway in vitro.

Activation of the classical complement cascade by beta-amyloid peptides has been hypothesized to underlie the neurodegeneration observed in Alzheimer's diseased brains. In this study, various lots of synthetic beta-amyloid peptides, A beta(1-40), A beta(1-42), and A beta(25-35), were tested for their ability to activate both early complement cascade events and formation of the membrane attack complex through terminal pathway activation. Unlike recent reports which did not assess activation of complement terminal pathway, we found that concentrations of beta-amyloid which activated early cascade events, to an extent comparable to aggregated IgG, failed to elicit formation of comparable levels of membrane attack complex.

The presence of the complement cascade does not lead to neuronal cell death in primary hippocampal cultures.

To investigate the consequences of complement activation on neuronal viability, the effects of serum treatment on neuron-rich and mixed neuronal/glial cultures were evaluated. The neurotoxicity observed following treatment with either human or rat serum was variable and did not appear to be mediated through a complement-mediated mechanism. Serum lots lacking CH50 activity induced neurotoxicity, and heat treatment of toxic lots of either human or rat sera did not abolish toxicity.

cAMP is not involved in interleukin-1-induced interleukin-6 release from human astrocytoma cells.

We have previously shown that activation of the phosphatidyl-inositol/phospholipase C pathway could induce interleukin 6 (IL-6) release from U373MG human astrocytomes cells. We also found that, although interleukin 1 beta (IL-1 beta) did not activate phosphatidy-linositol turnover, it induced, a robust release of IL-6. In the present study, we examined the role of adenylate cyclase/cyclic 3',5'-adenosine monophosphate (cAMP) pathway in IL-6 release.

Regulation of the release of interleukin-6 from human astrocytoma cells.

Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD.

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization.

A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been identified in mammalian brain using recombinant DNA technology. Alterations in the activity of these acetylcholinegated ion channels have been implicated in a number of central nervous system disorders including Alzheimer's disease (AD). The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by side effects that are the result of activation of both cholinergic and noncholinergic pathways in the central and peripheral nervous systems.