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Biomedical subjects

J Hau

Publications and source records attributed to J Hau.

At least 37 records · Page 2Linked to original sources

Hepatic granulomatous response to Schistosoma mansoni eggs in BALB/c mice and olive baboons (Papio cynocephalus anubis).

Hepatic granulomatous inflammation is one of the key pathological lesions of a patent Schistosoma mansoni infection. This study was concerned with the sequential induction, formation and eventual modulation of the schistosome egg granuloma in the mouse, which develops schistosome-induced hepatic fibrosis, and the olive baboon, which usually does not. Six baboons were each infected with 1500 S. mansoni cercariae and liver biopsies were collected at weeks 6, 9, 13 and 17 post-infection (p.i.). The mice (n=25) were each infected with 100 cercariae and killed in groups of five at weeks 6, 9, 12, 18 and 21 p.i. Peak granuloma size was observed at week 6 p.i. in baboons (mean 355 +/- 65.6 microm) but at week 12 p.i. in mice (299 +/- 40.5 microm). Eosinophils were more abundant in the baboon (60.6 +/- 8.9%) than in the mouse (41.2 +/- 8.4%) at the time of maximal granuloma size (P < 0.01). Neutrophils formed 21.1 +/- 6.3% of peak mouse granulomata but were virtually absent in baboon granulomata. A feature of the modulating baboon granulomata was the emergence of multinucleated giant cells (MGCs); modulating mouse granulomata, on the other hand, were characterized by infiltration of fibroblasts and collagen deposition. Thus, by week 21 p.i. mouse granulomata were 92 +/- 16.0 microm in diameter and well delineated by concentric layers of fibrous tissue. Granulomata, however, were present in only two of the baboons at week 17 p.i. (44 +/- 61.2 microm in diameter). The other four had peri-portal cellular infiltration without granuloma formation, implying that baboon granulomata resolve spontaneously. These data suggest that high tissue eosinophilia and MGC formation are particularly efficient in bringing about the destruction of schistosome eggs and subsequent resolution of the egg granuloma without fibrosis. In conclusion, the baboon model more closely mimics the pathogenesis observed in man than does the mouse model.

Acute Disease↗

Purification, characterization, and biological compartmentalization of rat fetal antigen 1.

This study has established the rat as an animal model for the analysis of the biological role of fetal antigen 1 (FA1), a protein previously described in humans and mice. FA1 was purified from rat amniotic fluid by immunospecific affinity chromatography. Immunochemical identity between mouse and rat FA1 was established by crossed tandem immunoelectrophoresis. Molecular size was analyzed by mass spectrometry (33 kDa). The amino acid composition was determined, and the amino acid sequence was analyzed. The overall amino acid composition and sequence of the 28 first N-terminal amino acids were identical to the corresponding parts of rat preadipocyte factor 1 and rat adrenal zona glomerulosa protein. Extensive sequence similarity was found between rat and mouse FA1 (86%) and between rat and human FA1 (82%). The concentration of FA1 in fetal serum, maternal serum, urine, and amniotic fluid in rats was determined using an ELISA. The highest concentrations were found in fetal serum and amniotic fluid around Day 18 of pregnancy. This is the first report on the physicochemical characteristics and compartmentalization of rat FA1.

Amino Acid Sequence↗

Dutch university scientists increase research productivity using fewer animals per project.

The proposed general reduction in the number of animals used in research within the EU is inappropriate. If a reduction is warranted it should be related to the scientific requirements. We show that the numbers of laboratory animals used per published paper in the Netherlands has decreased by 23% between 1990 and 1997. A further reduction might be detrimental to scientific progress.

Animal Welfare↗

Undergraduate university students' views of the use of animals in biomedical research.

PURPOSE: To investigate the influences of gender, discipline, and level on undergraduate students' views of the use of animals in research. METHOD: In 1998, 888 university undergraduate students from six different programs were surveyed at Uppsala University for their views of animal use in biomedical research. Statistical analysis involved chi-square tests. RESULTS: Most students found animal use morally acceptable and believed it plays a significant role in the treatment of human diseases. Engineering, law, and medical students were the most supportive, whereas pre-school-teaching students were the least supportive. Men were more supportive than were women. Sixth-term medical and nursing students had a more positive view than did their inexperienced first-term peers. CONCLUSION: The results of this study show that university students, who will be tomorrow's decision makers, are likely to continue supporting the use of animals in biomedical research and teaching.

Adult↗

Experimental murine mycotic mastitis: a sensitive and lenient model for studies of antifungal chemotherapy.

The murine model of mycotic mastitis was used to study the efficacy of amphotericin B (AmB). Twenty-four BALB/cJ mice at the fifth day of lactation were anesthetized and inoculated through the teat canal (two glands) with 50 microl suspension containing 5.0 x 10(7) cfu ml(-1) Candida albicans blastospores. Mice were randomly divided into two groups: untreated controls and AmB treated. Animals were euthanized 3 and 6 days after infection and treatment (4 mg kg(-1) per day intraperitoneally). The fungal burden of the mammary gland was determined by quantitative cultures. The number of C. albicans cells recovered from mammary gland homogenates were significantly lower in the AmB treated animals (both 3 and 6 days post-infection) than in the untreated controls (P<0.007 and P<0.003, respectively). The mammary glands of all untreated control animals showed marked neutrophilic infiltration, severe necrosis, and presence of blastospores, hyphae and pseudohyphae. In contrast, 10 of 12 animals treated with AmB showed only a mild neutrophilic infiltration which was restricted to alveoli and excretory ducts. All extra-mammary organs were free of infection in both groups. The results demonstrate that the murine mycotic mastitis model is suitable for investigations of new antifungal compounds. In addition, this model is more lenient than the systemic candidiasis models.

Amphotericin B↗

A simple ethological monitoring system to assess social stress in group-housed laboratory rhesus macaques.

The increasing awareness of the importance of social housing of laboratory primates results in the establishment of group housing in many facilities. Our aim was to develop a set of manageable tools to allow continuous monitoring of social relations within groups and to establish an objective, scientific ground on which changes in group composition could be based. We studied 38 adult rhesus monkeys (Macaca mulatta) grouped as five one-male/multi-female groups using focal sampling. We recorded the occurrence and direction of aggressive and non-aggressive social interactions as well as time spent inactive in proportion to social contacts, feeding and other activities. The present analysis clearly identified low-ranking animals with none or few affiliative contacts and who also spent much time inactive and separated from other low-ranking animals. This suggests that the present approach results in useful information concerning compatibility between group members and enables identification of animals experiencing high social stress.

Aggression↗

Comparison of immunospecific antibody response in young and old chickens immunized with human IgG.

Three groups of 18-month-old chickens and three groups of 5-month-old chickens were immunized with human immunoglobulin G (IgG) using one of three adjuvants in the first injection (Freund's Complete Adjuvant (FCA), Freunds Incomplete Adjuvant (FIA) and Hunter's TiterMax (HTM)) following the same immunization scheme. The specific antibody response in serum was measured by ELISA. In both older and younger chickens the serum antibody response in the FCA group reached a significantly higher level (P < 0.01) than in the FIA group and in the HTM group on week 5. The FCA group also had a significantly higher (P < 0.01) response on week 10 compared to the HTM group. Other than that, there was no significant difference between the three adjuvant groups in specific serum antibody response in older chickens. In the younger chickens the specific serum antibody response in the FCA group was significantly higher (P < 0.05) than the response in the HTM group. There was no significant difference in the chicken serum antibody response between the FCA and the FIA groups, nor was there a significant difference between the FIA and the HTM groups. Comparing the younger chickens and the older chickens immunized using the same adjuvant, the older chickens had consistently higher titres than the younger chickens, although the difference was not always significant.

Adjuvants, Immunologic↗

Mitogen-activated protein kinase-defective Candida albicans is avirulent in a novel model of localized murine candidiasis.

Candida albicans strains with a deletion of the mitogen-activated protein kinase CEK1 gene are defective in the yeast to hyphal transition on solid surfaces in vitro. The virulence of a cek1 delta/cek1 delta null mutant strain was compared with its wild-type parent strain (WT) in a novel model of localized candidiasis. The mammary glands of lactating mice (at day 5 postpartum) were infected for 2, 4 and 6 days with 50 microliter suspension containing 1 x 10(5), 1 x 10(6) and 1 x 10(7) blastopores before death. Infected and non-infected control glands were evaluated pathologically. All animals infected with cek1 delta/cek1 delta null mutant strains showed no lesions while 65% of animals infected with the WT strain had severe lesions characterized by widespread heterophilic infiltration, necrosis, and abscess formation. As an additional control, animals infected with the disrupted strain complemented with the WT CEK1, on a replicating plasmid, also showed severe pathological changes similar to the WT strain. These results clearly demonstrate that the CEK1 gene codes for a virulence determinant of C. albicans and that the mouse mastitis model is well suited for the discriminative study of the pathogenicity of different C. albicans strains.

Animals↗

Development and comparison of assays for measuring immunospecific antibody response in serum of chickens and rabbits immunized with human immunoglobulin G.

The antibody response development during polyclonal antibody production is a relevant parameter to monitor during the immunization period to be able to optimize the immunization protocol and to determine the optimal antibody harvest time. Although rabbits and other mammals are most often used for polyclonal antibody production, the chicken is a relevant alternative. There are both scientific reasons, economic reasons, and animal welfare reasons to consider when choosing the chicken instead of a mammal for this purpose, because antibodies in generous quantities can be harvested from the egg yolk. This study compared different assays for measuring antibody response in rabbit and chicken serum. An inhibition liquid phase absorption assay (ILPAA), a rocket immunoelectrophoresis (RIE) assay, and a line immunoelectrophoresis (LIE) assay were compared to ELISAs. The ELISA proved to be the most useful assay for routine use, as it was less time-consuming and because the assay could easily be adapted to both serum antibody types. However, electrophoretic assays were the most useful as combined analytical and quantitative tools and must be considered essential when analyzing specificities of polyclonal antibody preparations.

Animals↗

Reduced pathogenicity of a Candida albicans MAP kinase phosphatase (CPP1) mutant in the murine mastitis model.

Candida albicans strains with a deletion of the mitogen-activated protein kinase tyrosine phosphatase gene (CPP1) are derepressed in the yeast-to-hyphal transition on solid surfaces in vitro at ambient temperatures and this gene is therefore required for repression of the yeast-to-hyphal switch. The pathology caused by a CPP1 null mutant strain was compared with that of the null mutant into which the wild-type CPP1 gene was introduced by homologous recombination and with the wild-type parent strain in a murine mycotic mastitis model. The mammary glands of lactating mice (at day 5 postpartum) were infected for 2, 4 and 6 days with 1 x 10(5), 1 x 10(6) and 1 x 10(7) cell-forming units before euthanasia. Infected and non-infected control glands were evaluated histopathologically. The null mutant strains showed less severe pathology than the two control strains. The Cpplp tyrosine phosphatase may thus be considered a virulence determinant during localized infection in C. albicans.

Animals↗

Salivary IgA as a marker of social stress in rats.

Secretory immunoglobulin A (sIgA) has been suggested to be a potential marker of stress in the human and the dog. We describe a simple method of saliva collection from rats for quantification of salivary sIgA in the first study of sIgA as a possible stress marker in the rat. Three groups of adult male rats were housed under different conditions (singly housed, paired with a female, and group housed). The animals were conditioned for the saliva collection by presenting a chocolate reward after every session and saliva was collected by soaking filter paper discs (5 mm in diameter) with saliva directly in the rats' oral cavity. The levels of salivary sIgA were determined by a novel paper disc rocket immunoelectrophoresis using sheep anti rat IgA antiserum. The resulting rockets had similar morphology as rockets in a standard rocket immunoelectrophoresis. Males housed singly showed stable sIgA levels with little variation while those housed singly with a female showed an initial decrease in sIgA followed by a steady increase. Males housed in a group (n = 6) showed a steady decline in sIgA levels. This indicates that sIgA levels are reduced by social stress and that this molecule may be a useful marker for well-being in the rat.

Animal Welfare↗

Antibody production in rabbits and chickens immunized with human IgG. A comparison of titre and avidity development in rabbit serum, chicken serum and egg yolk using three different adjuvants.

The antibody response in rabbits and chickens (serum and egg yolk) immunized with human immunoglobulin G was studied during a 1-year immunisation period comparing the efficacy of three adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA) and Hunter's TiterMax adjuvant (HTM). Monthly boosters of the antigen in saline were administered. Adjuvants were used in the initial immunisation and in a booster at week 26. FCA was found to result in the highest titre in both species. FIA was more efficient than HTM in mediating an antibody response in rabbits. In chickens, FIA resulted in similar antibody titres in serum and egg yolk. The effect of HTM was similar to FIA in chicken serum but lower in egg yolk. The titres obtained in rabbits were approximately a factor 1.5-2.0 higher than in the corresponding chicken groups. However, the antibody productivity of the chicken, when using the egg yolk as the antibody source, was a factor 5-10 higher than that of the rabbit depending on the adjuvant used. FCA and FIA resulted in similar antibody avidity in rabbits whereas HTM had a lesser effect. In chickens FCA initially resulted in the highest antibody avidity in both serum and egg yolk, but after the booster with adjuvant the antibody avidity became similar for all three adjuvants.

Adjuvants, Immunologic↗

Detection of galactomannan and complement activation in the pregnant mouse during experimental systemic aspergillosis.

Foeto-placental infections are obtained when pregnant mice are challenged intravenously with conidial suspensions of Aspergillus fumigatus. This experimental model, which is used without any immuno-suppressive pretreatment, can be employed to screen for differences in foeto-placental infectivity of A. fumigatus strains when the number of colony-forming units (CFUs) in conidial suspensions used for infection is from 1 x 10(5) to 1 x 10(6). In the foeto-placental unit, hyphal growth was initiated at the periphery of the placental disc from which infection spread to the central parts of the placenta, the extrafoetal membranes and the foetus. Complement activation was noticed as a consequence of pregnancy and conidial inoculation, but was neither dose-dependent nor related to the extent of infection. Galactomannan was present in the plasma of infected mice and, in contrast to the situation in bovine placental aspergillosis, can be used as a good marker of foeto-placental aspergillosis.

Animals↗

Behaviour of rats in their home cages: daytime variations and effects of routine husbandry procedures analysed by time sampling techniques.

The behaviour of laboratory rats in their home cages was observed on both the mornings and the afternoons of days when cages were cleaned and compared to days when cages were not cleaned. Two different time sampling methods, 'instantaneous sampling' and 'one/zero sampling', were used and compared. In general the rats were more active in the mornings than in the afternoons. Activity, particularly locomotion and that associated with manipulation of the bedding was increased during both the mornings and the afternoons of cleaning days. Defaecation also increased on cleaning days whereas sitting decreased. The cleaning regime appeared to have a greater effect on behaviour than did time of day and the effect of cleaning lasted for several hours after the procedure had been completed. The implications for experimental design are discussed.

Activity Cycles↗