bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal variation in freshwater viral and bacterial community composition
Authors: LYMER DAVID , LOGUE JÜRG BRENDAN , BRUSSAARD CORINA P. D. , BAUDOUX ANNE‐CLAIRE , VREDE KATARINA , LINDSTRÖM EVA S.
Published: October 2007

1. The goal of this study conducted in three lakes differing in nutrient content and size was to assess the temporal variation in viral community composition and possible co‐variation with compositional changes in bacterial communities.

2. The viral community composition differed among lakes and changed over the season. Changes could also be detected on short‐time scales, i.e. over a few days. These changes were comparable in magnitude to the changes detected between months or seasons.

3. The most important environmental factors co‐varying with viral community composition, as determined by multivariate analysis, differed over the year and among lakes. Temperature and concentrations of dissolved organic carbon (DOC), total phosphorus and soluble reactive phosphorus were the most important factors.

4. Bacterial community composition also varied over the season and among lakes. The most important factors co‐varying with bacterial community composition, as determined by multivariate analysis, were also temperature and DOC concentration.

5. Correlation between viral and bacterial community composition was weak and appeared to be a result of an indirect connection rather than a direct relationship between bacteria and viruses.
Body mass index, alcohol, tobacco and symptomatic gallstone disease: a Swedish twin study
Authors: Katsika D. , Tuvblad C. , Einarsson C. , Lichtenstein P. , Marschall H.‐U.
Published: October 2007

Background/Aims.  Both genetic and environmental factors are involved in the pathogenesis of gallstone disease (GD). We aimed to examine the association between symptomatic GD and overweight (body mass index, BMI, 25–30 kg m−2), obesity (BMI > 30 kg m−2), alcohol, smoking and smoke‐free tobacco by analysing a large twin population.

Methods.  The Swedish Twin Registry (STR) was linked to the Swedish Hospital Discharge and Causes of Death Registries for GD and GD‐surgery related diagnoses. Weight, height, use of alcohol, smoking and smoke‐free tobacco were provided by STR and analysed for possible associations by conditional logistic regression.

Results.  Overweight and obesity were associated with a significantly higher risk for symptomatic GD in the whole study population (OR 1.86 and OR 3.38; CI: 1.52–2.28 and 2.28–5.02 respectively). High alcohol consumption was associated with a lower risk for GD in the whole population (OR 0.62; CI: 0.51–0.74) with no difference between discordant monozygotic and dizygotic twins (OR 1.08 and OR 0.96; CI: 0.82–1.42 and 0.79–1.16). Smoking or smoke‐free tobacco was not correlated with GD.

Conclusion.  Consistent with epidemiological studies, we found positive associations between BMI and the development of symptomatic GD. High alcohol consumption was associated with a decreased risk against GD. Tobacco use has no impact on GD.
Renal dysfunction predicts long‐term mortality in patients with lower extremity arterial disease
Authors: Pasqualini L. , Schillaci G. , Pirro M. , Vaudo G. , Siepi D. , Innocente S. , Ciuffetti G. , Mannarino E.
Published: October 2007

Abstract. Pasqualini L, Schillaci G, Pirro M, Vaudo G, Siepi D, Innocente S, Ciuffetti G, Mannarino E (University of Perugia, Perugia, Italy). Renal dysfunction predicts long‐term mortality in patients with lower extremity arterial disease.J Intern Med2007;262: 668–6.

Background. Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy.

Objectives and design. This prospective study investigated the relation between renal dysfunction and long‐term all‐cause and cardiovascular mortality in a population of nonsurgical patients with lower extremity arterial disease (LEAD).

Subjects and methods. A total of 357 patients with symptomatic LEAD underwent baseline glomerular filtration rate (GFR) estimation by the 4‐variable Modification Diet in Renal Diseases equation, and were then followed for 4.2 years (range: 1–17).

Results. During follow‐up, 131 patients died (8.6 deaths per 100 patient‐years), 79 of whom (60%) from cardiovascular causes. All‐cause death rates were 3.8, 6.6, and 15.5 per 100 patient‐years, respectively, in the groups with normal GFR, mild reduction in GFR (60–89 mL min−1per 1.73 m2) and chronic kidney disease (CKD; <60 mL min−1per 1.73 m2;P < 0.001 by log‐rank test). Compared to patients with normal renal function, the risk of all‐cause and cardiovascular death was significantly higher in patients with CKD [hazard ratio, respectively, 2.23, 95% confidence interval (CI): 1.16–4.34,P = 0.017; 2.15, 95% CI: 1.05–4.43,P = 0.03]. The association of CKD with all‐cause and cardiovascular mortality were independent of age, LEAD severity, cardiovascular risk factors and treatment with angiotensin‐converting enzyme (ACE)‐inhibitors, hypolipidaemic and antiplatelet drugs. The power of GFR in predicting all‐cause death was higher than that of ankle‐brachial pressure index (P = 0.029) and Framingham risk score (P < 0.0001).

Conclusion. Chronic kidney disease strongly predicts long‐term mortality in patients with symptomatic LEAD irrespective of disease severity, cardiovascular risk factors and concomitant treatments.
Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease
Authors: Carrero J. J. , Qureshi A. R. , Axelsson J. , Yilmaz M. I. , Rehnmark S. , Witt M. R. , Bárány P. , Heimbürger O. , Suliman M. E. , Alvestrand A. , Lindholm B. , Stenvinkel P.
Published: October 2007

Abstract.  Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, Bárány P, Heimbürger O, Suliman ME, Alvestrand A, Lindholm B, Stenvinkel P (Karolinska Institutet, Stockholm; and Karo Bio AB, Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262: 690–701.

Objectives.  In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end‐stage renal disease (ESRD).

Design.  After exclusion of 23 patients with thyroid‐stimulating hormone (TSH) values outside the normal range (0.1–4.5 mIU L−1), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1–60) months. Measurements of total and free forms of thyroid hormones, s‐albumin, hs‐CRP, interleukin (IL)‐6, vascular adhesion molecule (VCAM)‐1 and insulin‐like growth factor 1 (IGF‐1) were performed at baseline.

Results.  In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut‐off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs‐CRP, IL‐6 and VCAM‐1) and lower concentration of both s‐albumin and IGF‐1. Finally, low T3 but not low free triiodothyronine was associated with worse all‐cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.

Conclusion.  This study showed that low T3 levels are independent predictors of all‐cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.
Life style habits such as alcohol consumption and physical activity in relation to serum apoB / apoA‐I ratio amongst 64‐year‐old women with varying degrees of glucose tolerance
Authors: Simonsson M. , Schmidt C. , Sigurdadottir V. , Helenius M.‐L. , Fagerberg B.
Published: October 2007

Objectives.  To investigate how life style factors such as alcohol consumption and physical activity relate to the serum apoB / apoA‐I ratio in a cohort of middle‐aged women with varying degrees of glucose tolerance.

Design.  Observational, cross‐sectional cohort study.

Setting.  Research laboratory at a University Hospital.

Subjects.  A screened cohort of 64‐year‐old postmenopausal women with varying degrees of glucose tolerance, ranging from diabetes (n = 232), impaired (n = 212) and normal (n = 191) glucose tolerance.

Main outcome measure.  ApoB / apoA‐I ratio in relation to alcohol consumption and physical activity as assessed by questionnaires.

Results.  Alcohol consumption and regular physical activity at high levels were inversely associated with the serum apoB / apoA‐I ratio independently of confounding factors such as obesity, lipid‐lowering treatment, degree of glucose tolerance and hormone replacement therapy. Alcohol seemed related to the apoB / apoA‐I ratio mainly through increasing apoA‐I, whereas physical activity seemed mainly related to lowering of apoB. Alcohol consumption above a daily intake of 8.9 g, i.e. less than a glass of wine was accompanied by a decrease in apoB / apoA‐I ratio.

Conclusions.  Amongst these 64‐year‐old women with varying degrees of glucose tolerance, a moderate alcohol intake and regular physical exercise leading to sweating were associated with lower apoB / apoA‐I ratio and these effects seem to be additive.
Specimen‐induced distortions in light microscopy
Authors: SCHWERTNER M. , BOOTH M. J. , WILSON T.
Published: October 2007

Specimen‐induced aberrations affect the imaging properties in optical 3D microscopy, especially when high numerical aperture lenses are used. Studies on aberrations are often properly concerned with the degradation of image quality such as compromised resolution or reduced signal intensity. Apart from these, aberration effects can also introduce geometric image distortions. The effects, discussed here are particularly strong when thick biological specimens are investigated. Using a high numerical aperture interferometer, we measured wavefront aberrations in transmission mode and quantified geometric distortions associated with specimen‐induced aberrations. This assessment for a range of biological specimens allows estimation of the accuracy of spatial measurements. The results show that high‐resolution spatial measurements can be significantly compromised by specimen‐induced aberrations.
A simple and efficient alternative to implementing systematic random sampling in stereological designs without a motorized microscope stage
Authors: MELVIN NEAL R. , PODA DANIEL , SUTHERLAND ROBERT J.
Published: October 2007

When properly applied, stereology is a very robust and efficient method to quantify a variety of parameters from biological material. A common sampling strategy in stereology is systematic random sampling, which involves choosing a random sampling relevant objects start point outside the structure of interest, and sampling at sites that are placed at pre‐determined, equidistant intervals. This has proven to be a very efficient sampling strategy, and is used widely in stereological designs. At the microscopic level, this is most often achieved through the use of a motorized stage that facilitates the systematic random stepping across the structure of interest. Here, we report a simple, precise and cost‐effective software‐based alternative to accomplishing systematic random sampling under the microscope. We believe that this approach will facilitate the use of stereological designs that employ systematic random sampling in laboratories that lack the resources to acquire costly, fully automated systems.
Genetic control of immune responses to Schistosoma japonicum antigen
Authors: KAJI R. , KAMIJO TAKAKO , YANO A. , KOJIMA S.
Published: October 2007

Summary A high‐titre IgE‐antibody response to Schistosoma japonicum antigen (Sj) is obtained if helper T cells are appropriately induced by the infection. The antibody responses were found to be regulated by a gene(s) linked to the major histocompatibility complex. Strains of H‐2a and H‐2k haplotypes were high responders, whereas H‐2d, H‐2b and H‐2s strains were not. Results obtained by using intra‐H‐2 recombinant strains suggested that the immune‐response (Ir) gene was mapped in the I‐E subregion, although a possibility of the presence of complementary genes was not excluded. Interestingly, in low responders such as BALB/c mice, Sj‐specific carrier effect could be demonstrated when mice were infected with S. japonicum before challenge immunization with dinitrophenylated Sj (DNP‐Sj). Moreover, BALB/cas well as C3H/He was a high responder to Sj in proliferation of peritoneal exudate T‐lymphocyte enriched cells in vitro, whereas B10.S was not. Based on these observations, possible roles of Ir genes in immune responses to Sj are discussed.
Trypanosoma cruzi: Susceptibility in mice carrying mutant gene Ipr (lymphoproliferation)
Authors: BOYER M. H. , HOFF R. , KIPNIS THEREZA L. , MURPHY E. D. , ROTHS J. B.
Published: October 2007

Summary There is evidence that autoimmune aberrations may contribute to the immunopathological consequences of Chagas' disease and because of this we sought to determine whether four inbred strains of mice bearing the single autosomal recessive gene, lpr (lymphoproliferation), which controls certain autoimmune manifestations, are particularly susceptible to acute infection with the Y strain of Trypanosoma cruzi. MRL/MpJ‐lpr/lpr, C57B1/6J‐lpr/lpr, AKR/J‐lpr/lpr, C3H/HeJ‐lpr/lpr showed parasitaemias 2–10 times higher when compared to their congenic partners. Mortality was significantly higher in three of the four lpr strains. The results indicate that a single autosomal recessive gene which is associated with autoimmunity can influence susceptibility to acute T. cruzi infection in mice.
Inheritance of post‐vaccinal resistance against Plasmodium berghei infection in mice
Authors: HEUMANN A. M. , BUCCI A. , STIFFEL C. , CASAGLIA O. , ZENOBI P. , BIOZZI G.
Published: October 2007

Summary The protective effect of specific vaccination against Plasmodium berghei (P. berghei) was compared in terms of survival percentage in DBA/2, C3H, outbred albino mice and in two lines of mice produced by selective breeding for either high or low antibody responsiveness to sheep erythrocyte (H and L lines respectively). The efficacy of induced protection varies according to genetic constitution. It is very strong in H line and albino mice, intermediate in DBA/2 and very weak in L line and C3H. The inheritance of post‐vaccinal resistance to infection was studied in F| hybrids and backcrosses between C3H and the other lines. The control was polygenic in all cases. The dominance of the characteristic depends on the strain combination. On the whole the results suggest the non‐identity of the genes controlling protection in the various lines. The lack of a quantitative parameter for a more precise genetic analysis of protective immunity in inbred lines is stressed, since both anti‐P. berghei antibody production and parasitaemia proved to be unreliable.
Selective localization of intravenously injected 111indium‐labelled eosinophils in rat tissues infected with Nippostrongylus brasiliensis
Authors: MACKENZIE C. D. , SPRY C. J. F.
Published: October 2007

Summary 111Indium‐oxine‐labelled rat eosinophils were injected i.v. into rats infected with Nippostrongylus brasiliensis and controls. Radionuclide imaging was done to measure the rate and extent of radioactive uptake into different regions of the body in vivo. Radioactivity appeared first in the lungs then in the livers and spleens. The distribution of radioactivity and parasites was studied by gamma counting, histology and parasite counts. In infected rats, increased amounts of radioactivity localized in the skin, lungs and small intestines during the dermal, pulmonary and intestinal stages of the disease. It was concluded that localization of radioactivity was closely related to the tissue distribution of migratory larvae and adult worms. This technique may be of value in measuring alterations in eosinophil distribution and tissue localization in vivo, especially in helminthic infections and other disease where many eosinophils accumulate in tissues.
Antibody‐independent binding and activation of complement by Schistosoma mansoni adult worms
Authors: UNDER EWERT , HULDT GUNNEL
Published: October 2007

Summary The in vitro binding serum complement (C) components to Schistosoma mansoni worms was studied. By exposing frozen sections of adult male and female parasites to normal human serum, binding of both classical and alternative pathway C components was observed. By immunofluorescence (IFL) microscopy selective binding of C1q, C4 and C3 to the schistosomal tegument, internal structures, the intestinal tract and eggs was seen. The C4 and C3 binding was completely abolished in the presence of 10 mM EDTA. EGTA also completely inhibited binding of C4 and most of the C3 binding. These results suggest that C binding to S. mansoni adult worms occurs mostly by the classical activation pathway. However, the partial Ca2+ independence of C3 binding and the demonstrated binding of the regulatory protein β1H suggests that worms are capable also of C3 binding by the alternative pathway. No C binding occurred to intact worms. Although some in vivo bound immunoglobulin appeared to be present occasionally at the parasite surface and in the gut, this material did not account for the demonstrated extensive C deposition upon incubation of frozen sections with normal human serum in vitro. Antibody independence of the observed classical pathway C binding was further indicated by binding of isolated Clq to the same structures capable of binding C components from serum.
Action of leishmanial excreted factor (EF) on human lymphocyte blast transformation
Authors: LONDNER M.V. , FRANKENBURG S. , SLUTZKY G.M. , GREENBLATT C.L.
Published: October 2007

Summary. The effect of Leishmania tropica major excreted factor (EF) on human immune and normal mononuclear peripheral blood cells has been studied. The response of lymphocytes to stimulation either specifically with leishmanial antigens or non‐specifically with phytohemagglutinin (PHA) in the presence of EF was tested by the uptake of 3[H]thymidine. The results showed that EF inhibits the response of cells from immune donors to leishmanial antigens and from normal donors to PHA or PPD. Adherent and non‐adherent cells were separated and the effect of EF on both populations was analysed. The results showed that EF inhibited blast transformation if both EF and antigen were presented to each of the separate populations. The inhibition of the adherent cells (mainly monocytes) was more marked than the inhibition of the nonadherent population (mainly lymphocytes).
Natural agglutinins to African trypanosomes
Authors: FERRANTE A. , ALLISON A.C.
Published: October 2007

Summary Agglutinins to uncoated culture forms of the African trypanosomes, T. congolense and T.b. brucei were detected in sera from a variety of mammals not exposed to the parasites. The agglutinins in bovine serum were shown to be specific antibodies with opsonic properties selective for the species of trypano‐some. These findings suggest a possible role for the glycoprotein coat in preventing access of cross‐reacting antibodies to the plasma membrane of African trypanosomes.
Interference with anti‐trypanosome immune responses in rabbits infected with cyclically‐transmitted Trypanosoma congolense
Authors: LUCKINS A.G. , GRAY A.R.
Published: October 2007

Summary Rabbits were infected with two clones of antigenically distinct stocks of Trypanosoma congolense transmitted through Glossina morsitans. Local skin reaction development and the appearance of neutralizing antibodies were followed in animals infected with one or other of the trypanosome stocks, with both stocks simultaneously or with both stocks consecutively. There was little difference in local skin reaction development on rabbits infected with a single stock or with both stocks simultaneously but, in rabbits exposed to a heterologous stock 14 or 21 days after a primary infection reactions were reduced in size or completely absent. Neutralizing antibodies against metacyclic‐derived trypano‐somes were detected 21 days after infection in animals infected with a single trypanosome stock and, in rabbits infected with both stocks simultaneously, antibodies against each stock were also detected 21 to 28 days after infection. In rabbits challenged 14 or 21 days after primary infection the appearance of trypanocidal antibodies against the stock used for challenge was delayed from 28 to 49 days.
T‐cell mediated immunity in murine malaria. I. Induction of T‐cell dependent proliferative responses to Plasmodium chabaudi
Authors: CHEMTAI A. K. , VAECK M. , HAMERS‐CASTERMAN C. , HAMERS R. , BAETSELIER P. DE
Published: October 2007

Summary To investigate the mechanisms of cell mediated immunity to malaria, we studied different systems to measure specific activation of T lymphocytes by P. chabaudi antigens. Mice were primed by subcutaneous administration of parasite antigens followed by co‐cultivation of lymphocytes taken from the draining lymph nodes in the presence of the priming antigen. A marked proliferative response was observed which was shown to be antigen specific, T‐cell mediated and accessory cell dependent. Continuous T‐cell lines were propagated in culture by repetitive restimulation in the presence of antigen and accessory cells, followed by expansion in a conditioned medium containing T‐cell growth factors. These lines could be induced to proliferate to the priming antigen only in the presence of syngeneic accessory cells thus indicating that H‐2 restriction operates in the recognition of Plasmodium antigens by T cells. We also induced parasite specific T cells by the use of an in vitro primary ‘education’ system. Lymphocytes from unprimed mice were sensitized on parasite‐fed macrophages and were then injected subcutaneously into each hind foot pad of syngeneic animals. This led to recruitment of antigen‐reactive cells which were assayed in vitro by the ability of lymphocytes taken from the draining popliteal lymph nodes to proliferate in response to the sensitizing antigen. In vivo immunization with Plasmodium antigen fed macrophages also signalled antigen specific T cells that recruited reactive T cells in the draining lymph nodes.
Leishmania major: identification of stage‐specific antigens and antigens shared by promastigotes and amastigotes
Authors: HANDMAN E. , JARVIS H.M. , MITCHELL G.F.
Published: October 2007

Summary A battery of antisera to Leishmania major was used to identify stage‐specific antigens, or antigens expressed predominantly in amastigotes or promastigotes. At least 30 protein antigens common to amastigotes and promastigotes could be detected in 35S‐methionine labelled preparations. They ranged in molecular weight from 25000 to 165000. Two amastigote specific antigens and five antigens expressed predominantly in the amastigote were detected in biosynthetically‐labelled preparations. Five promastigote specific antigens were also identified. Antibodies from hyperimmunized mice that were resistant to reinfection with L. major recognized mainly antigens shared by the two life‐cycle stages of the parasite. Analysis of parasite antigens on ‘western blots’ provided a different picture from that obtained by immunoprecipitation and gel electrophoresis of 3SS‐methionine labelled polypeptides. Only 19 antigens were detected and they were all shared by the two parasite forms. However, the abundance and immunogenicity of some of these antigens may be different in the two life‐cycle stages of the parasite. Using the various sera, seven shared membrane antigens were identified in radio‐iodinated preparations. Antibodies from hyperimmunized resistant mice that recognized shared antigens in 35S‐meth‐ionine labelled preparations, detected four amastigote membrane antigens not detected by other sera. The function of the stage‐specific antigens remains to be established. It is expected that individual antigens produced by recombinant DNA technology will allow these studies to proceed.
The effect of protein restriction on the development of protective immunity to Leishmania mexicana
Authors: PÉREZ HILDA , ROSA MERCEDES DE LA , MALAVÉ INES
Published: October 2007

Summary Protein deprived C57BL/6 mice infected with 103 amastigotes of Leishmania mexicana showed early arrest of lesion progression during the first S weeks of infection with subsequent development of progressive non‐healing lesions. In contrast, well nourished mice similarly infected developed gradual healing lesions. The early resistance of malnourished mice to 103 amastigotes was overcome by a larger dose. After a primary inoculation with 103 amastigotes protein deprived mice failed to express protective immunity to a challenge inoculum given at 5 weeks of infection. When challenge was delayed until 10 weeks, protein deprived mice developed lesions at the site of challenge which tended to regress but were unable to manifest the high level of protective immunity seen in normally nourished reinfected controls. A challenge infection given at 5 or 10 weeks prejudiced the control of primary lesions particularly in the group of protein deprived mice challenged at 10 weeks. Equivalent levels of specific delayed hypersensitivity responses were found in protein deprived and normally nourished uninfected mice immunized with killed parasites which imply that the impaired protective immunity observed in protein deprived mice is not due to a deleterious effect of protein deprivation on the ability of the host to develop cellular responses such as delayed type hypersensitivity to Leishmania antigens.
Humoral and cellular immunity in patients with hepatic alveolar echinococcosis. A 2 year follow‐up with and without flubendazole treatment
Authors: VUITTON DOMINIQUE A. , LASSEGUE A. , MIGUET J.P. , HERVÉ P. , BARALE THÉRÈSE , SEILLÉS ESTELLE , CAPRON A.
Published: October 2007

Summary Parameters of humoral and cellular immunity were assessed in 12 patients with alveolar echinococcosis (AE) of the liver before, during and after discontinuation of treatment with flubendazole (FZ). In infected patients, before any medical treatment values of serum IgG, IgA, total haemolytic complement and C4 were significantly higher than those observed in control subjects; IgA levels were higher in jaundiced patients. Specific antibodies assayed by indirect haemagglutination and immunoelectrophoresis were present only in infected patients and were shown to decrease by the sixth month of treatment; however, similar fluctuations were observed without treatment. The percentage and absolute number of B lymphocytes, and total circulating lymphocytes, were significantly lower in patients with AE. An impairment of functional activity of T cells assayed by the leucocyte migration test, with PPD and Candidin as antigens, was demonstrated despite a normal percentage of SRBC rosettes. The ‘score’ of migration index still decreased during FZ treatment and returned to initial values after the year of follow‐up without treatment. These results suggest that human AE is associated with important immunological disturbances. Changes in humoral immunity can be unequivocally considered to be a consequence of the parasite infection. The primary or secondary nature of the impairment of cellular immune responses and its mechanisms remain to be elucidated. Flubendazole could be responsible for an increase of cellular immune alterations in these patients.
Immunological consequences of intestinal helminth infections. Humoral responses to ovalbumin
Authors: PRICE PATRICIA , TURNER K. J.
Published: October 2007

Summary Humoral responses to ovalbumin (OA) administered i.p. with Al(OH)3‐were depressed in C57BL mice immunized 5–13 days after infection with N. dubius, but not N. brasiliensis or T. muris. These two parasites induced elevated IgM responses, possibly as a result of systemic contact with parasite larvae or debris since i.v. administered N. dubius also increased IgM titres to OA. Depression of anti‐OA IgG titres by N. dubius was also observed in infected BALB/c and CBA mice given OA‐Al(OH)3 (i.p.), but not in C57BL mice given OA‐Al(OH)3 (s.c), OA‐FCA (i.p. or s.c), or OA‐B. pertussis (i.p.). These findings suggest that local effects of N. dubius within the peritoneum reduce the adjuvanticity of Al(OH)3, resulting in depressed responses to OA‐Al(OH)3.
Factors affecting the levels of antibody‐ and complement‐dependent eosinophil‐mediated damage to schistosomula of Schistosoma mansoni in vitro
Authors: BUTTERWORTH A. E. , RICHARDSON B. A.
Published: October 2007

Summary In experiments designed to test why high levels of antibody‐dependent, eosinophil‐mediated killing of schistosomula are routinely observed in this laboratory, several factors that may contribute to variations in eosinophil activity were examined. The most important factors were: (1) the source of eosinophils, with marked variation being demonstrated not only, as previously shown, between individuals, but also between different cell preparations from a single individual; (2) the serum used as a source of anti‐schistosomulum antibodies and (3) the age of the schistosomula at the time of assay. In contrast, addition of fresh normal serum as a source of complement had a relatively slight effect when the killing assay was carried out in round bottomed tubes. A more marked enhancement was observed in flat bottomed microtitre plates, and it is suggested that this enhancement may be attributable to the release of chemotactic complement components. No difference was observed between a laboratory maintained and a recently derived isolate of Schistosoma mansoni, either in initial susceptibility or in loss of susceptibility after 3·5 h of culture. In contrast to the marked effects of eosinophils under most conditions tested, there was no evidence for extensive neutrophil‐mediated damage under the same conditions.
Immunochemical comparison between worm extracts of Onchocerca volvulus from savanna and rain forest
Authors: LOBOS E. , WEISS N.
Published: October 2007

Summary Crude phospate‐buffered extracts of adult Onchocerca volvulus from savanna (Mali) and rain forest (Cameroon) areas were comparatively analysed using biochemical and immunological methods. SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) and isoelectric focusing revealed only minor differences between the two extracts. Out of 42 bands detectable by SDS‐PAGE at least 21 were identified as glycoproteins by their affinity to concanavalin A. High resolution analysis using two dimensional gel electrophoresis (2D‐G) showed marked differences in the polypeptide patterns of the two extracts. Some of the over 100 polypeptides demonstrable by Coomassie blue staining (especially at pIs between 4·3 and 5·6 and mol. wts over 64kD) were clearly different when the two extracts were compared. Antigenic differences between the two extracts could be detected by crossed immunoelectrophoresis using a rabbit anti‐O. volvulus hyperimmune serum. The comparison by tandem crossed immunoelectrophoresis demonstrated clearly the existence of at least three antigenic differences, four partial identities and 13 antigenic identities between the extracts. For the identification of O. volvulus antigens serologically recognized by infected patients, we combined the 2D‐G with an immunoblotting technique using a pool of highly reactive onchocerciasis sera from Mali. IgG binding antigens were then identified by incubating the blot membrane with this serum pool and with 125I‐labelled protein A followed by autoradiography. IgE binding antigens were detected using a 125I‐labelled anti‐human IgE antiserum. Whilst the overall antigenic patterns were similar, there were, however, clear differences between the antigen preparations which gives further evidence for antigenic diversity of O. volvulus from savanna and rain forest areas.
Antibody‐dependent cell cytotoxicity against Trypanosoma cruzi is only mediated by protective antibodies
Authors: LIMA‐MARTINS MARIA VIRGINIA C. , SANCHEZ GITTITH A. , KRETTLI ANTONIANA U. , BRENER Z.
Published: October 2007

Summary The antibody‐dependent cell cytotoxicity (ADCC) to Trypanosoma cruzi blood forms (Btry) using non‐adherent spleen cells is only mediated by sera from chronic chagasic patients or mice. Both display ‘lytic antibodies’ (LA), which are immunoglobulins directed against epitopes only present in living BTry, and ‘conventional serology antibodies’ (CSA). which are responsible for the positive diagnostic tests in Chagas disease. Sera from mice immunized with different T. cruzi antigens or from treated patients (displaying only CSA but not LA) are unable to mediate ADCC. These data confirm the central role played by LA in the host resistance against T. cruzi. Moreover, they probably explain why most immunizing agents used as vaccines in Chagas' disease and which ellicit CSA but not LA, do not display significant protection against T. cruzi. We also demonstrate that trypsinization of BTry increases significantly the rate of parasite destruction by ADCC, suggesting that enzyme sensitive membrane components may help BTry to evade from this immune effector mechanism.
Susceptibility to acute Trypanosoma cruzi infection in autoimmune strains of mice
Authors: NICKELL S. P. , HOFF R. , BOYER M. H.
Published: October 2007

Summary We previously observed that mice bearing the autoimmune associated Ipr gene exhibit increased susceptibility to challenge with Trypanosoma cruzi. the causative agent of Chagas' disease. We have now tested two other autoimmune prone strains of mice, BXSB and NZB, and found that these animals also show increased sensitivity to acute T. cruzi infection. When challenged with a standard dose (102) of Y strain trypomastigotes, BXSB males (BXSB‐YSB), which develop early onset autoimmune disease, suffered high mortality, while late onset autoimmune BXSB females and minimally autoimmune male BXSB mice whose Y chromosome was derived from C57BL/6J mice (BXSB‐YB 6) also recover. NZB mice were found to be highly susceptible to challenge while NZW and NZB/W were resistant. A finding common to all groups of susceptible autoimmune mice was increased plasma levels of T. cruzi specific antibody, especially IgM. The data indicate that in two of the three autoimmune prone strains examined, increased T. cruzi susceptibility appears to be linked to restricted genetic elements (i. e. Ipr gene and the YSB associated factor) which also influence the rapidity of onset of autoimmunity.
Giardia muris‐induced depression of the primary immune response in spleen and mesenteric lymph node cell cultures to sheep red blood cells
Authors: BELOSEVIC M. , FAUBERT G. M. , MacLEAN J. D.
Published: October 2007

Summary Primary in vitro plaque‐forming cell (PFC) responses to sheep red blood cells (SRBC) were examined for spleen and mesenteric lymph node (MLN) cell populations from susceptible (A/J) and resistant (B10.A) mice during the infection with Giardia muris. Spleen and MLN cells isolated from mice during the acute phase of the infection were less responsive to SRBC in vitro than those from uninfected mice. Depressed anti‐SRBC PFC response was detected earlier and was more pronounced in MLN cell cultures when compared to the response of spleen cell cultures. Spleen and MLN cells from donors infected with G. muris for 15 days had the capacity of depressing PFC response to SRBC of cells isolated from uninfected mice. This suppressor activity was localized in the plastic‐adherent fraction of spleen cell populations isolated from A/J and B10.A mice. Since G. muris is a gastro‐intestinal infection of mice, lower capacity of the MLN cells to respond to an antigenic stimulation in vitro may explain, in part, the proliferation of the trophozoites during the acute phase of the infection.
Antigen stripping from the nematode epicuticle using the cationic detergent cetyltrimethylammonium bromide (CTAB)
Authors: PRITCHARD D. I. , CRAWFORD C. R. , DUCE I. R. , BEHNKE J. M.
Published: October 2007

Summary The cuticular antigens of adult Nematospiroides dubius were selectively removed using the cationic detergent cetyltrimethylammonium bromide (CTAB). Nonionic, zwitterionic or anionic detergents were ineffective in comparison. The biochemical profile of the antigens removed by detergent was identical to that of surface antigens removed by homogenization, with the added advantage that detergent‐stripped antigens lacked many of the background antigens (excretory/secretory‐ES and somatic) seen in homogenates. In addition, the detergent was shown to act in a non‐invasive manner as electron micrographs failed to reveal any gross damage to the nematode outer cuticle. The observed selective release of significant quantities of relatively clean nematode surface antigen by CTAB in a non‐invasive or destructive manner provides the impetus for definitive studies on the relevance of surface antigens (in the absence of ES or somatic antigens) to the overall immunogenicity of this and other parasites.
Circulating antibody—antigen complexes following Trypanosoma musculi infection in mice genetically selected to produce high or low affinity antibody
Authors: PATTISON J. R. , STEWARD M. W.
Published: October 2007

Summary Mice from lines genetically selected for the production of either high or low affinity antibody to protein antigens and which differ in their susceptibility to chronic immune complex disease were infected with Trypanosoma musculi. The parasite became patent in both lines by day 5 and no significant differences in the levels of parasites during the infection were observed between the two lines. Serum levels of both antigen non‐specific and T. musculi antigen specific immune complexes were determined during the infection by the solid phase conglutinin and C1q binding assays. In both lines, antigen non‐specific complexes were detected by day 15 after infection with maximum levels observed by day 30. At this time, low affinity line mice had significantly higher levels than did high line mice as determined by the C1q assay but not by the conglutinin assay. The deposition of immune complex like material in glomeruli, assessed by immunofluorescence, was associated with the clearance of the parasite and the presence of circulating antigen specific complexes. The pattern of localization of complexes in both lines was predominantly mesangial with some deposition in the capillaries. The intensity of fluorescence increased during the infection. Initially (day 10) only IgM was observed in the glomeruli but IgGl and IgG2b were detected from day 20 to day 40. IgG2a was only detected on day 40. However, in none of the animals was this deposition of complexes associated with proteinuria. Hence, the data presented here show that the low affinity line mice produce higher levels of smaller circulating complexes following T. musculi infection than do high affinity mice. However, this does not result in significant differences in localization and induction of renal disease as seen following chronic antigen injection.
A cell surface antigen associated with Theileria parva lawrencei‐infected bovine lymphoid cells
Authors: NEWSON JANET , NAESSENS J. , STAGG D. A. , BLACK S. J.
Published: October 2007

Summary Attempts to produce monoclonal antibodies specific for a parasite‐encoded or induced antigen on the surface of Theileria parva lawmjcei‐transformed bovine lymphocytes resulted in the identification of the monoclonal antibody J7. This antibody recognizes a membrane glycoprotein on some T. p. lawrencei‐infected bovine lymphoid cells but not on any uninfected bovine lymphoid cells. Inoculation of allogeneic recipient cattle with T. p. lawrencei‐transformed cells bearing the J7 determinant resulted in transfer of the parasite but not of the J7 epitope to the recipients' own cells. The presence of the J7 determinant could not be correlated with the parasite phenotype nor with the surface phenotype of the infected cells. It is therefore not known whether the J7 epitope is of parasite origin or whether it is a bovine differentiation antigen modified by the presence of the parasite.
Schistosoma mansoni: liver phase challenge attrition is a stage‐dependent phenomenon in guinea‐pigs vaccinated with highly irradiated cercariae
Authors: McLAREN DIANE J. , ROGERS M. V.
Published: October 2007

Summary Guinea‐pigs vaccinated with highly irradiated cercariae of Schistosoma mansoni have been examined for their ability to kill challenge parasites at the level of the liver. Skin and lung phase attrition were eliminated by surgical introduction of 4/5 day old schistosomula, or 2, 3 or 6 week schistosomes into the mestenteric vasculature of vaccinated and naive animals. These experiments showed consistently that lung schistosomula and 2 week old parasites were killed preferentially by sensitized animals, but that older worms were refractory. Liver phase immune elimination would therefore seem to be a stage‐dependent phenomenon in the vaccinated guinea pig model of schistosomiasis.
Inhibition of human peripheral blood mononuclear cell proliferative responses by released materials from Schistosoma mansoni cercariae
Authors: VIEIRA LEDA Q. , GAZZINELLI G. , KUSEL J. R. , SOUZA CECILIA P. S. DE , COLLEY D. G.
Published: October 2007

Summary During in vitro transformation of Schistosoma mansoni cercariae into schistosomula, surface and glandular materials are released into the culture medium. Extracts of these materials, termed cercarial released extracts 1 and 2 (CRE‐1 and CRE‐2), were analysed and found to consist primarily of protein and carbohydrate at ratios of 5:1 (CRE‐1) and 7:1 (CRE‐2). It was observed that inclusion of either CRE‐1 or CRE‐2 in cultures of human peripheral blood mononuclear cells (PBMN) led to decreased cell proliferation. This was true whether the cells were resting, control cultures or were stimulated with either phytohaemagglutinin or an antigenic preparation from adult S. mansoni worms. The inhibition was equally effective with PBMN of patients with active schistosomal infection or PBMN from uninfected individuals. Since these materials are released spontaneously during cercarial‐to‐schistosomular transformation they may have a putative immunosuppressive effect in decreasing anti‐schistosomular activities early after cercarial penetration.
The recognition of antigens on the surface of adult and L4 Necator americanus by human and hamster post‐infection sera
Authors: PRITCHARD D. I. , BEHNKE J. M. , CARR A. , WELLS CATHERINE
Published: October 2007

Summary The surface antigens of adult Necator americanus were recognized by post‐infection hamster sera and resolved at molecular weight 93000, 67000, 46000, 43000, 32000 and 25000. L4 larvae in contrast had one major surface antigen, resolving at 93000. These antigens were also recognized by a range of human sera, although on a differential basis. This suggests that the human sera tion. However, the results do indicate that the hamster model might be of immunological relevance to the human disease state, in that infected hamster recognized the full cuticular antigen spectrum of adult Necator. This, at least, gives the experimenter a convenient reference point from which to conduct further experiments incorporating parameters such as re‐infection, anthelmintic treatment and genetic variability to study the effect of these modifications on the serological response.
Vaccination of mice against malaria with soluble antigens. I. The effect of detergent, route of injection, and adjuvant
Authors: PLAYFAIR J. H. L. , SOUZA J. B. DE
Published: October 2007

Summary Mice were vaccinated against lethal blood stage P. yoelii malaria with lysates of parasitised blood prepared in various detergents. Two injections, containing 25 ng of protein, of a Triton X‐100 lysate gave optimal protection when injected intraperitoneally with saponin as adjuvant. Such lysates provide a starting point for the isolation of potential antigens for vaccination, selected for their protective activity in vivo.
Multiple cross‐reactivities amongst antigens of Plasmodium falciparum impair the development of protective immunity against malaria
Authors: ANDERS R. F.
Published: October 2007

Summary The majority of protein antigens of the malaria parasite Plasmodium falciparum contain short sequences that are extensively repeated in tandem arrays. Some antigens contain a single block of repeats whereas in other antigens there may be two or more blocks of related repeats. The repetitive sequences in an individual antigen may be highly conserved but more usually there is some degeneracy which occasionally is extensive. The repetitive sequences encode immunodominant epitopes to which much of the antibody response in malaria is directed. Recently, we have found that there are extensive cross‐reactions amongst the epitopes encoded by related repetitive sequences. These cross‐reactions may involve different blocks of repeats in the one antigen or repetitive sequences in different antigens. It is proposed that these cross‐reactions interfere with the normal maturation of a high affinity antibody response in malaria by causing an abnormally high proportion of somatically‐mutated B cells to be preserved during clonal expansion.
Lysis and immobilization of Giardia murk trophozoites in vitro by immune serum from susceptible and resistant mice
Authors: BELOSEVIC M. , FAUBERT G.M.
Published: October 2007

Summary To define the potential role of antibody in host defence against Giardia muris, comparative assessment of in‐vitro anti‐trophozoite effects of immune serum obtained from susceptible (A/J) and resistant (BI0.A) mice was done. Two anti‐parasite effects of serum were identified and quantified: lysis and immobilization of trophozoites. These giardicidal activities were present in the serum from both A/J and BlO.A mice. Maximal lysis of trophozoites by serum from A/J or B1O.A mice was 40 to 50. The lysis of trophozoites was abolished after incubation of serum at 56 C for 30 min. The addition of exogenous complement restored lytic activity of heat‐inactivated serum. The immobilization of trophozoites was dependent on both the duration of incubation and concentration of serum. After 30 min of incubation, over 98 of trophozoites were immobilized by immune serum from A/J or B1O.A mice. There was no apparent relationship between the capacity of immune sera from A/J and BI0.A mice to kill trophozoites in uitro and the ability of these strains of mice to control the infection with G. muris.
Murine spleen and lymph node cellular composition and function during cyclophosphamide and splenectomy induced resistance to Toxoplasma gondii
Authors: JONES THOMAS C. , ALKAN SEFIK , ERB PETER
Published: October 2007

Summary Murine toxoplasmosis caused by a low virulence, cyst‐forming strain of Toxcoplasma gondii (Pe strain) is characterized by splenomegaly, lymphadenopathy, decreased delayed‐type hypersensitivity (DTH), and the presence of toxoplasma cysts in brain tissue. Cyclophosphamide (CY) in a single dose of 100 mg/kg injected 3 days before infection, or splenectomy 3 weeks before infection, augmented DTH and decreased the number of toxoplasma brain cysts. CY‐induced augmentation of resistance during the first 3 weeks of murine toxoplasmosis was associated with: (1) an increase in mononuclear phagocytes and a decrease in T lymphocytes (including Lyt2+ cells) in spleens and lymph nodes; (2) suppressed toxoplasma antigen induced proliferation of cultured spleen cells: (3) augmentation of antigen induced proliferation of cultured lymph node cells; and (4) low levels of interferon‐γ production in both spleen and lymph node cultures. The best correlate of the enhanced in‐vivo effects of CY was proliferation of nylon wool‐purified lymph node cells to toxoplasma antigen. The presence of Lyt2+ cells in lymph nodes of toxoplasma infected mice inhibited maximal proliferation.