Comparison of the inflammatory responses of mice infected with American and Australian Trichinella pseudospiralis or Trichinella spiralis

We have examined the response of the renal insulin-like growth factor (IGF-I) axis to acute ischemic injury in the rat Key findings included a decrease in IGF-I mRNA and peptide levels, a decrease in GH receptor gene plus protein expression and a decrease in the IGF binding proteins except for IGF binding protein I. Administration of GH to compensate for the reduced GH receptor binding corrected the IGF-I mRNA levels suggesting a relative GH deficiency. Interestingly, IGF-I receptor mRNA levels were unchanged while plasma membrane IGF-I receptor number increased two fold. This appeared to be due to a redistribution of receptors to a membrane location. IGF-I receptor autophosphorylation and tyrosine kinase activity were intact despite severe uremia for up to 6 days. We propose that this increase of functional IGF-I receptors following acute tubular necrosis will sensitize the kidney to the administration of exogenous IGF-I.     

Jungles: a new solution to the host/parasite phylogeny reconciliation problem

The problem of finding least-cost reconstructions of past host/parasite associations, given the phylogenetic histories of a set of host taxa and of their associated parasites, is known to be complex. I provide in this article a new method of implicitly listing all the potentially optimal solutions to the problem, by considering each hypothesised past association individually, in a structure I have termed a Jungle. These structures are demonstrated to enable fast acquisition of globally optimal solutions under general weighting schemes, including minimisation of total number of postulated events and maximization of postulated cospeciation events. A simple example is given, and the pocket gopher/chewing louse system investigated by Hafner and Nadler [Hafner and Nadler, Nature 332 (1988) 258] is re-examined.     

Force variability in isometric responses.

In the present study we examined the contribution of different impulse parameters to peak force variability in an isometric task. Five experiments are reported that each held constant a different impulse parameter while allowing the other impulse parameters to vary. The results indicate that change in force level is the parameter that has the greatest effect on peak force variability, although time to peak force and preload also systematically influence response variability. A formula that accommodates the relation between impulse parameters and force variability is proposed. The data suggest that even in isometric tasks, it is the force-time properties of the impulse, rather than discrete parameters such as peak force, that determine the outcome variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Workshop on a detailed characterization of Trichinella spiralis antigens: a platform for future studies on antigens and antibodies to this parasite

In order to characterize immunodominant components of T. spiralis a workshop was organized. In this the reactivity of monoclonal and polyclonal antibodies, provided by different research groups, towards total extracts from adult, new born larvae and muscle larvae as well as to excretory/secretory components of muscle larvae were tested by ELISA, Western blot and immunoprecipitation assays. As a result of this workshop T. spiralis ML antigens have been classified into eight groups (TSL-1-TSL-8) according to their recognition by monoclonal and polyclonal antibodies. Among them, TSL-1 antigens have been the most extensively characterized both biochemically and immunologically. These antigens are stage specific, originate in the muscle stichosome and are abundant in both E/S and on the larval cuticular surface. The TSL-1 antigens share an immunodominant carbohydrate epitope (tyvelose), which is unique for Trichinella and is not associated with phosphorylcholine. The data collected in this workshop has allowed both the unification of the nomenclature for T. spiralis antigens and their biochemical characterization. It also has provided a platform for further studies on the characterization of other T. spiralis antigens and indeed for other Trichinella species.     

Intra-individual variability in sentence completion responses.

Variability in responses to a sentence completion test over a 2 to 3 week interval, and the relationship between change in responses and relative response frequency in a group was studied. The major results were: (1) The content of the majority of responses was changed to some degree on retest. (2) Individual differences in number of responses changed on retest showed reasonable reliability. (3) Differences between sentence stems in the proportion of changed responses were consistent from group to group. (4) For each sentence stem, responses given by only one person change more frequently than those given by more than one person. (5) Positive correlations were obtained between the number of unique responses made by a subject and the number of responses he changed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The variability of human, BOLD hemodynamic responses

Cerebral hemodynamic responses to brief periods of neural activity are delayed and dispersed in time. The specific shape of these responses is of some importance to the design and analysis of blood oxygenation level-dependent (BOLD), functional magnetic resonance imaging (fMRI) experiments. Using fMRI scanning, we examine here the characteristics and variability of hemodynamic responses from the central sulcus in human subjects during an event-related, simple reaction time task. Specifically, we determine the contribution of subject, day, and scanning session (within a day) to variability in the shape of evoked hemodynamic response. We find that while there is significant and substantial variability in the shape of responses collected across subjects, responses collected during multiple scans within a single subject are less variable. The results are discussed in terms of the impact of response variability upon sensitivity and specificity of analyses of event-related fMRI designs.     

Pulmonary host defense responses to inhalation of sulfuric acid and ozone

The effects of simultaneous exposure to ozone (O3) and sulfuric acid [H2SO4, 0.23 microns volume median diameter (VMD)] and a single exposure to ultrafine (less than 0.1 micron VMD) H2SO4 under various conditions were studied using the infectivity/mortality and the ciliary beating frequency model systems. A 3-h exposure to a combined aerosol of 196 micrograms O3/m3 and 483 or 241 micrograms H2SO4/m3 significantly increased the susceptibility of mice to a laboratory-induced respiratory infection. However, exposure to 543 micrograms ultrafine H2SO4/m3 for 2 h or 365 micrograms/m3 2 h/d for 5 d did not significantly affect this parameter. Upper airway response, as measured by changes in hamster tracheal ciliary beating frequency, was not affected by either a 3-h combined exposure to 196 micrograms O3/m3 and 847 micrograms H2SO4/m3 or a 2-h exposure to 458 micrograms ultrafine H2SO4/m3.     

Costimulation pathways in host immune responses to allogeneic hepatocytes

BACKGROUND: This study investigated the role of the CD28/B7 (blocked by CTLA4Ig) and CD40/CD40L (blocked by MR1) costimulation pathways on in vivo host T-cell- mediated immune responses to allogeneic hepatocytes. METHODS: Survival of allogeneic hepatocytes (H-2q) in C57BL/6 (H-2b) mice untreated or treated with MR1, CTLA4Ig, L6 (control fusion protein), or a combination of MR1 and CTLA4Ig fusion protein was determined. RESULTS: Median survival time for hepatocellular allografts was 10, 84, 10, 10, and 84 days in untreated (n= 10), MR1-treated (n=7) (P<.0001), CTLA4Ig-treated (n=7) (P=0.02), L6-treated (n=3) (P, not significant), and the combination of MR1- and CTLA4Ig-treated (n=6) (P=0.0003) groups, respectively. CONCLUSIONS: Host treatment with MR1, but not CTLA4Ig, prolonged hepatocellular allograft survival. These data suggest that CD28/B7 interactions appear relatively unimportant, whereas CD40/CD40L interactions provide critical costimulator signals for T-cell-dependent immune responses to allogeneic hepatocytes.     

Human infection with Trypanosoma cruzi induces parasite antigen-specific cytotoxic T lymphocyte responses

Experimental models of Chagas' disease, an infection caused by the intracellular protozoan Trypanosoma cruzi, have demonstrated the crucial immunoprotective role played by CD8(+) T lymphocytes. These cells dominate inflammatory foci in parasitized tissues and their elimination from mice leads to uncontrolled parasite replication and subsequent death of the infected host. A trypomastigote surface antigen, TSA-1, and two amastigote surface molecules, ASP-1 and ASP-2, were recently identified as targets of CD8(+) cytotoxic T lymphocytes (CTL) in T. cruzi-infected mice. Until now, however, there was no evidence for the development of parasite-specific CTL in T. cruzi-infected humans. In this study, human CTL specific for TSA-1-, ASP-1-, and ASP-2-derived peptides were detected in the peripheral blood mononuclear cells from 21 of 24 HLA-A2(+) T. cruzi-infected patients. CTL recognition was antigen specific, A2-restricted, and CD8(+) T cell-dependent. Demonstration of human CTL against T. cruzi and against target molecules identified using the murine model provides important information for the optimal design and evaluation of vaccines to prevent or ameliorate Chagas' disease.     

Kinetics of immunological responses, resistance to reinfection, and pathological reactions to infection with Trichinella spiralis

Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.     

Pathogenicity of Theileria parva is influenced by the host cell type infected by the parasite

Theileria parva has been shown to infect and transform B cells and T cells at similar frequencies in vitro. However, the majority of parasitized cells in the tissues of infected cattle are alpha/beta T cells. The aim of this study was to determine whether the cell type infected with T. parva influenced the pathogenicity of the parasite. The initial approach, which involved inoculation of cattle with autologous cloned cell lines of different phenotypes, failed to resolve the issue, because of prolonged period of culture required to clone and characterize the cell lines resulted in attenuation of the cells. As an alternative approach, cattle were inoculated with purified populations of autologous cells that had been incubated in vitro with T. parva sporozoites for 48 h. As few as 3 x 10(4) peripheral blood mononuclear cells (PBMC) treated in this way were found to produce severe clinical reactions with high levels of parasitosis. Infections of similar severity were produced with purified populations of CD2+, CD4+, and CD8+ T cells. By contrast, infected B cells gave rise to mild self-limiting infections even when administered at a 10-fold-higher dose. In animals that received infected CD4+ or CD8+ T cells, the parasitized cells in the lymph nodes on day 11 of infection were all within the CD4+ and CD8+ populations, respectively, indicating that there had been minimal transfer of the parasite between cell types. Phenotypic analyses of cultures of PBMC infected in vitro with saturating concentrations of sporozoites revealed that parasitized B cells were abundant in the cultures after 1 week but were subsequently overgrown by T cells. The results of these experiments indicate that the cell type infected by T. parva influences the pathogenicity of the parasite.     

Tropomyosin implicated in host protective responses to microfilariae in onchocerciasis

A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a tropomyosin isoform (termed MOv-14) has been shown previously to confer protective immunity in rodent models of onchocerciasis. The full-length sequence (designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33 kDa and shares 91% identity with tropomyosins from other nematodes, falling to 57% identity with human alpha-tropomyosin. Ov-TMY-1 migrates with an apparent molecular mass of 42 kDa on SDS/PAGE and is present in all life-cycle stages, as determined by immunoblotting. Immunogold electron microscopy identified antigenic sites within muscle blocks and the cuticle of microfilariae and infective larvae. Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable protection against microfilariae conferred by vaccination with a PBS-soluble parasite extract. In contrast, little or no MOv14-specific antibody was present in mice inoculated with live microfilariae, in which resistance is mediated by antibody-independent mechanisms. In human infections, there was an inverse correlation between anti-tropomyosin IgG levels and densities of microfilariae in the skin. Seropositivity varied with the relative endemicity of infection. An immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N terminus of the MOv14 protein by using sera from protectively vaccinated mice. Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp tropomyosin, believed to be responsible for hypersensitivity in individuals exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O. volvulus epitope were detected in human infections. It is concluded that antibody responses to tropomyosin may be important in limiting microfilarial densities in a proportion of individuals with onchocerciasis and have the potential to mediate hypersensitivity reactions to dead microfilariae, raising the possibility of a link with the immunopathology of infection.     

Heart rate variability and newborn heart rate responses to illumination changes.

Investigated heart rate (HR) response patterns to the onset and offset of a 30-sec increase in illumination in 16 human newborns. Ss were divided into 2 groups based on a measure of pretrial HR variability. Only Ss with the high pretrial HR variability responded significantly to the change in stimulation. The response to onset was characterized by a significant quartic trend containing both decelerative and accelerative components. The response to offset only approached significance and had a pattern similar to the onset response. Although the occurrence of systematic response patterns was related to the level of pretrial HR variability, this measure of autonomic lability may have been related to influences associated with delivery and not to stable individual differences. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protective immune responses against protease-like antigens of the murine malaria parasite Plasmodium vinckei

The Plasmodium falciparum proteins serine repeat antigen (SERA) and serine repeat protein homologue (SERPH) have similarity in sequence with cysteine proteases in a well-conserved protease domain. We identified three SERA homologues from the murine malaria parasite Plasmodium vinckei and evaluated immune responses to the protease domains of these proteins. Mice that developed protective immunity to P. vinckei after serial infection and cure demonstrated humoral and cell-mediated responses against the SERA homologue protease domains. Mice immunized with Salmonella typhimurium expressing the protease domain of one of these antigens demonstrated cellular responses against the antigen and increased survival against lethal challenge with P. vinckei. Our results suggest that the protease domains of SERA and SERPH are worthy of additional study as potential components of a malaria vaccine.     

Possible reasons for the variability of human responses to IAC-CPR

OBJECTIVE: To propose reasons for the variability of the hemodynamic responses and survival data observed when interposed abdominal compression cardiopulmonary resuscitation (IAC-CPR) is performed on humans in cardiac arrest. METHODS: Critical content review of all studies performed in the United States examining IAC-CPR in humans and of selected animal studies addressing hemodynamic mechanisms of CPR. Articles in the English language dealing with human IAC-CPR studies from 1970-1993 were retrieved using the MEDLINE database of the National Library of Medicine. RESULTS: IAC-CPR does not consistently improve coronary perfusion pressure (CPP) over standard CPR in humans and is capable of decreasing as well as increasing CPP. This variability does not seem dependent on the manner in which abdominal compressions are performed. Because of the limited response to standard CPR, significant increases in return of spontaneous circulation would be expected with IAC-CPR if a large percentage of patients were to have favorable increases in CPP. However, other patients may be adversely affected by decreases in CPP during IAC-CPR, with unsuccessful resuscitation of those individuals. Return of spontaneous circulation also may be enhanced using IAC-CPR due to other factors reflected in the initial arrest rhythm and in arrest-population demographics. CONCLUSION: IAC-CPR should not be recommended for routine use until the mechanism of its beneficial effects is known and until those patients who are likely to benefit from the technique can be better identified.     

Potential impact of Pneumocystis genetic diversity on the molecular detection of the parasite in human host

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.     

New host and ocean records for the copepod Ommatokoita elongata (Siphonostomatoida: Lernaeopodidae), a parasite of the eyes of sleeper sharks

Seven of 8 Pacific sleeper sharks (Somniosus pacificus Bigelow and Schroeder, 1944) captured in Prince William Sound, Alaska, were actively infected, and all 8 had been at one time infected with the parasitic copepod Ommatokoita elongata (Grant, 1827) (Siphonostomatoida: Lernaeopodidae). Active infections consisted of adult females and chalimus larvae that had attached to the corneas of the sharks' eyes. This report documents a new host record and possibly the only reliable record of this parasite from a host other than the Greenland shark, Somniosus microcephalus (Bloch and Schneider, 1801). It also documents the first time O. elongata has been identified outside of the Atlantic Ocean or its locally adjacent straits and seas.