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Biomedical subjects

F G van Zijderveld

Publications and source records attributed to F G van Zijderveld.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical features of PrP(d) accumulation in natural and experimental goat transmissible spongiform encephalopathies.

Scrapie is a transmissible spongiform encephalopathy (TSE) or prion disease, which naturally affects sheep and goats. Immunohistochemical epitope mapping of abnormal PrP accumulations (PrP(d)) in brain can help in characterizing sheep TSE sources or strains and in identifying potential bovine spongiform encephalopathy (BSE) infections of sheep. Natural and experimental TSE infections of goats were examined to determine whether the epitope mapping approach could also be applied to aid recognition of BSE infection in goats. Goats experimentally infected with the SSBP/1 or CH1641 sheep scrapie strains or with cattle BSE, together with four field cases of natural TSE in goats, were examined immunohistochemically with six different antibodies. CH1641 and SSBP/1 infections in goats, as in sheep, showed PrP(d) accumulations which were mainly intracellular. Some differences in targeting, particularly of Purkinje cells, was evident in inter-species comparisons of CH1641 and SSBP/1. PrP(d) labelling of goat BSE experimental cases showed extensive intracellular and extracellular accumulations, also similar to those in sheep BSE. Intra-neuronal PrP(d) in both goat and sheep BSE was labelled only by antibodies recognizing epitopes located C-terminally of residue His99, whereas in natural sheep TSE sources, and in sheep and goat SSBP/1, PrP(d) was also detected by antibodies to epitopes located between residues Trp93 and His99. Testing of four natural goat TSE samples showed one case in which epitope mapping characteristics and the overall patterns of PrP(d) accumulation was identical with those of experimental goat BSE. The four natural goat scrapie cases examined showed some degree of immunohistochemical phenotype variability, suggesting that multiple strains exist within the relatively small UK goat population.

Animals↗
PubMed2006

Selection and optimization of proteolytically stable llama single-domain antibody fragments for oral immunotherapy.

We previously demonstrated that oral application of the recombinant single-domain antibody fragment (VHH) clone K609, directed against Escherichia coli F4 fimbriae, reduced E. coli-induced diarrhoea in piglets, but only at high VHH doses. We have now shown that a large portion of the orally applied K609 VHH is proteolytically degraded in the stomach. Stringent selection for proteolytic stability identified seven VHHs with 7- to 138-fold increased stability after in vitro incubation in gastric fluid. By DNA shuffling we obtained four clones with a further 1.5- to 3-fold increased in vitro stability. These VHHs differed by at most ten amino acid residues from each other and K609 that were scattered over the VHH sequence and did not overlap with predicted protease cleavage sites. The most stable clone, K922, retained 41% activity after incubation in gastric fluid and 90% in jejunal fluid. Oral application of K922 to piglets confirmed its improved proteolytic stability. In addition, K922 bound to F4 fimbriae with higher affinity and inhibited fimbrial adhesion at lower VHH concentrations. K922 is thus a promising candidate for prevention of piglet diarrhoea. Furthermore, our findings could guide selection and improvement by genetic engineering of other recombinant antibody fragments for oral use.

Administration, Oral↗
PubMed2005

Escherichia coli F4 fimbriae specific llama single-domain antibody fragments effectively inhibit bacterial adhesion in vitro but poorly protect against diarrhoea.

Oral administration of polyclonal antibodies directed against enterotoxigenic Escherichia coli (ETEC) F4 fimbriae is used to protect against piglet post-weaning diarrhoea. For cost reasons, we aim to replace these polyclonal antibodies by recombinant llama single-domain antibody fragments (VHHs) that can be produced efficiently in microorganisms. Six F4 fimbriae specific VHHs were isolated. The VHH that was produced at the highest level by yeast, K609, was further analysed. 3.8 mg/L K609 inhibited 90% of bacterial attachment to intestinal brush borders in vitro. Perfusion of a jejunal segment with at least 4 mg/L K609 reduced the ETEC-induced fluid loss, but only to 30%. Preventive administration of a high K609 dose (150 mg/(piglet day)) to piglets that were challenge infected with ETEC resulted in less severe diarrhoea only at 4 and 5 days post-infection, but did not improve average daily weight gain, ETEC shedding and piglet survival. Thus, we have shown that an antibody fragment that effectively inhibited in vitro ETEC adhesion to intestinal brush borders poorly protected piglets against experimental ETEC infection.

Administration, Oral↗
PubMed2005

Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep.

Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of this study were to determine whether (1) PrPSc accumulates in biopsy samples of the tonsil or third eyelid, or both, of BSE-infected sheep before the appearance of clinical disease, and (2) such samples from BSE- and scrapie-infected sheep differ in respect of PrPSc accumulations. Homozygous ARQ sheep (n = 10) were dosed orally at 4-5 months of age with a brain homogenate from BSE-infected cattle. Third eyelid and tonsillar biopsy samples were taken at < or = 6 monthly intervals post-infection and examined immunohistochemically for PrPSc. Third eyelid protuberances were difficult to identify, resulting in many unsuitable samples; however, third eyelid samples shown to contain lymphoid follicles were invariably negative for PrPSc. In contrast, tonsillar biopsy samples became positive for PrPSc from 11 to 20 months post-infection. Consistent differences in the morphology of PrPSc granules in tingible body macrophages (TBMs) between BSE- and scrapie-infected sheep were detected with anti-peptide antibodies directed towards amino acids 93-106 of the ovine prion protein: thus, PrPSc appeared as single granules in TBMs of tonsillar sections from BSE-infected sheep, whereas clusters of PrPSc granules were observed within TBMs in the tonsils of scrapie-infected sheep. In contrast, antibodies against epitopes situated N- and C-terminally from the 93-106 region of the ovine prion protein revealed no differences between BSE- and scrapie-infected sheep in terms of PrPSc granules in TBMs.

Animals↗
PubMed2002

Early and late pathogenesis of natural scrapie infection in sheep.

The pathogenesis of scrapie infection was studied in sheep carrying the PrP(VRQ)/PrP(VRQ) genotype, which is associated with a high susceptibility for natural scrapie. The sheep were killed at sequential time points during a scrapie infection covering both the early and late stages of scrapie pathogenesis. Various lymphoid and neural tissues were collected and immunohistochemically examined for the presence of the scrapie-associated prion protein PrP(Sc), a marker for scrapie infectivity The first stage of scrapie infection consisted of invasion of the palatine tonsil and Peyer's patches of the caudal jejunum and ileum, the so-called gut-associated lymphoid tissues (GALT). At the same time, PrP(Sc) was detected in the medial retropharyngeal lymph nodes draining the palatine tonsil and the mesenteric lymph nodes draining the jejunal and ileal Peyer's patches. From these initial sites of scrapie replication, the scrapie agent disseminated to other non-GALT-related lymphoid tissues. Neuroinvasion started in the enteric nervous system followed by retrograde spread of the scrapie agent via efferent parasympathetic and sympathetic nerve fibres innervating the gut, to the dorsal motor nucleus of the vagus in the medulla oblongata and the intermediolateral column of the thoracic spinal cord segments T8-T10, respectively.

Adrenergic Fibers↗
PubMed2002

The Dutch Brucella abortus monitoring programme for cattle: the impact of false-positive serological reactions and comparison of serological tests.

The Dutch national Brucella abortus eradication programme for cattle started in 1959. Sporadic cases occurred yearly until 1995; the last infected herd was culled in 1996. In August 1999 the Netherlands was declared officially free of bovine brucellosis by the European Union. Before 1999, the programme to monitor the official Brucella-free status of bovine herds was primarily based on periodical testing of dairy herds with the milk ring test (MRT) and serological testing of all animals older than 1 year of age from non-dairy herds, using the micro-agglutination test (MAT) as screening test. In addition, serum samples of cattle that aborted were tested with the MAT. The high number of false positive reactions in both tests and the serum agglutination test (SAT) and complement fixation test (CFT) used for confirmation seemed to result in unnecessary blockade of herds, subsequent testing and slaughter of animals. For this reason, a validation study was performed in which three indirect enzyme-linked immunosorbent assays (ELISAs), the CFT and the SAT were compared using a panel of sera from brucellosis-free cattle, sera from experimentally infected cattle, and sera from cattle experimentally infected with bacteria which are known to induce cross-reactive antibodies (Pasteurella, Salmonella, Yersinia, and Escherichia). Moreover, four ELISAs and the MRT were compared using a panel of 1000 bulk milk samples from Brucella-free herds and 12 milk samples from Brucella abortus- infected cattle. It is concluded that the ELISA obtained from ID-Lelystad is the most suitable test to monitor the brucelosis free status of herds because it gives rise to fewer false-positive reactions than the SAT.

Agglutination Tests↗
PubMed2001

Active surveillance of BSE in cattle in The Netherlands.

Since January 2, 2001 a large-scale active surveillance programme for BSE started in the Netherlands in addition to the passive surveillance programme of cattle with clinical symptoms compatible with BSE. Based on decisions of the Council of European Ministers of Agriculture, the European Union launched an active surveillance system for BSE in cattle of 30 months and older. Until April 1, more than 100,000 head of cattle were tested in this scheme, including all cattle slaughtered and a large part of the cattle that died on the farm. Four animals were found positive in the active surveillance system and one cow from the passive surveillance tested positive for BSE during the first three months.

Abattoirs↗
PubMed2001

Evaluation of two enzyme-linked immunosorbent assays for detecting Salmonella enterica subsp. enterica Serovar Dublin antibodies in bulk milk.

Two enzyme-linked immunosorbent assays (ELISAs) for the detecting Salmonella enterica subsp. enterica serovar Dublin antibodies in bulk milk were developed and evaluated for potential use in control programs. The ELISAs were based on either lipopolysacharide (LPS ELISA) or flagellar antigen (GP ELISA). Sensitivity was determined with 79 case herds with a wide range of clinical signs. Specificity was determined with 125 Dutch and 200 Swedish control herds. The relation between antibodies in bulk milk, antibodies in serum, and the level of milk production of individual cows was studied with 61 case herds. The optimal optical density (OD) values of the LPS ELISA and the GP ELISA were determined to be 0.2 and 0.5, respectively. The sensitivities of the LPS ELISA and the GP ELISA were 54 and 63%, respectively, with a specificity of 98% for both ELISAs with samples from the Dutch control herds. The specificities for samples from the Swedish herds were 100% for the LPS ELISA and 95% for the GP ELISA. The sensitivity of the combination of tests was 65% when samples were run in parallel, and the specificity was 100% when samples were run in series, irrespective of whether the samples came from Dutch or Swedish control herds. The variance (R(2)) in the OD value for bulk milk samples could be explained by the percentage of seropositive lactating cows in a herd with the LPS ELISA for 51% of the samples and with the GP ELISA for 72%. The variance in the OD value was best explained by the combination of the percentage of seropositive lactating cows in the herd and the mean log(10) serum antibody titer for that herd (R(2) = 62% for the LPS ELISA and R(2) = 75% for the GP ELISA). Case herds more often tested negative by the ELISA with bulk milk when the percentage of seropositive lactating cows was less than 5%. It is concluded that both ELISAs with bulk milk can be used in control programs to distinguish between infected and noninfected herds. Specificity can be increased by using the two tests in combination. Sensitivity was relatively low for both single tests and both tests combined.

Animals↗
PubMed2000

Paratuberculosis recognized as a problem at last: a review.

This article attempts to review briefly current opinions on Johne's disease, or paratuberculosis, in ruminants caused by Mycobacterium avium subsp. paratuberculosis. Paratuberculosis has been known to be prevalent in domestic livestock, such as cattle, goats, and sheep, for more than a century. Despite this knowledge only minor efforts have been made to control the disease and, with the attention being focussed on the eradication of other diseases, the problem of paratuberculosis has been neglected in most countries in the past decades. However, recent epidemiological surveys performed in Europe showed a high prevalence of paratuberculosis in cattle and sheep, indicating that the situation has become quite alarming. In addition, the possible role of M. avium subsp. paratuberculosis in the aetiology of Crohn's disease in humans is still debated, as discussed in this article. Therefore, there is suddenly a renewed interest in paratuberculosis, and the disease is recognized as a significant problem. As a consequence, there is a need for reliable diagnostic tools for large-scale use to allow the introduction of programmes to control and eventually eradicate the disease. The current status and the possibilities for such programmes are discussed.

Animals↗
PubMed2000

Evaluation of three newly developed enzyme-linked immunosorbent assays and two agglutination tests for detecting Salmonella enterica subsp. enterica serovar dublin infections in dairy cattle.

In this study test characteristics of three newly developed enzyme-linked immunosorbent assays (ELISAs) for Salmonella enterica subsp. enterica serovar Dublin were evaluated and compared with two agglutination tests. The ELISAs involved were an indirect ELISA with serovar Dublin lipopolysaccharide (LPS ELISA), an indirect ELISA with serovar Dublin flagellar antigen (GP ELISA), and a double-antibody sandwich blocking ELISA that uses monoclonal antibodies against S. enterica subsp. enterica serovar Enteritidis flagellin (GM-DAS ELISA). The agglutination tests involved were two routine serum agglutination tests with either somatic (O) or flagellar (H) antigen. Diagnostic specificity of the three ELISAs was determined using 840 serum samples from seven dairy herds without any history of serovar Dublin infection. Cutoff values at a titer of 100, 100, and 10, respectively, for the LPS ELISA, GP ELISA, and GM-DAS blocking ELISA resulted in a specificity of 99.3, 100, and 100%, respectively. Using these cutoff values the LPS ELISA, GP ELISA, and GM-DAS ELISA were able to detect, respectively, 30, 46, and 38% of 50 fecal culture-positive animals from 13 herds with a recent serovar Dublin infection. With the same cutoff values, active carriers (n = 18) were detected for 94.4% with the LPS ELISA and for 100% with the GP and GM-DAS ELISAs. Kappa values determined on the results of all tests from 8 of the 13 serovar Dublin-infected herds and the 7 control herds demonstrated a good correlation between the results of all ELISAs and the H-agglutination test. The results of the O-agglutination test failed to correlate with those of the other tests. Using a set of sera from 170 aborting cows (with 25 abortions due to serovar Dublin), test results of the ELISAs and the H-agglutination test were comparable. The H-agglutination test may be used successfully for single sample testing, especially to diagnose abortion due to serovar Dublin. It is concluded that the ELISAs are useful diagnostic tools in serovar Dublin control programs and that they are preferred to agglutination tests for reasons of automation and costs.

Abortion, Veterinary↗
PubMed1999

Survey of infectious agents involved in acute respiratory disease in finishing pigs.

Outbreaks of respiratory disease constitute a major health problem in herds of finishing pigs and their aetiology often remains unclear. In this study, 16 outbreaks of respiratory disease with acute clinical signs in finishing pigs were investigated to determine which infectious agents were involved. From each herd four diseased and two clinically healthy pigs were examined pathologically and for the presence of viruses, bacteria and mycoplasmas. In addition, paired blood samples from 10 groupmates of the diseased pigs were tested for antibodies against commonly known causal agents of respiratory disease. A clear diagnosis was possible in 12 of the 16 outbreaks. Seven were due to an infection with influenza virus and five were due to an infection with Actinobacillus pleuropneumoniae. A combination of influenza virus and A pleuropneumoniae may have caused one other outbreak, but no clear cause could be established for the other three outbreaks.

Actinobacillus Infections↗
PubMed1999

Cell tropism of Staphylococcus aureus in bovine mammary gland cell cultures.

Staphylococcus aureus is one of the most important pathogens of the bovine mammary gland. The interaction of S. aureus with cells of the bovine mammary gland is considered to play an essential role in the pathogenesis. In this study, we identified a new target cell for S. aureus adhesion and invasion. For that purpose, cells which compose the alveoli of the mammary gland were cultured. In these cultures, two morphologically different cell types, elongated and cubic cells, were observed. Adhesion and invasion of S. aureus was studied using microscopical and microbiological methods. S. aureus adhered specifically and in large numbers (about 300 bacteria/cell) to the elongated cell type. No adhesion to the cubic cell type was observed. In addition, bacteria were also found intracellularly in the elongated cells, and enclosed in membrane vesicles. Adhesion and invasion were time dependent and reached maximum levels after 4 h. Invasion was strongly reduced by staurosporine and genistein. The newly identified target cell was further characterized.

Animals↗
PubMed1999

Sensitivity testing of veterinary pathogens with a semi-automatic image analysis system compared with tablet diffusion and agar dilution tests.

Recently a commercial computer-controlled image analysis system (IAS) was introduced to measure automatically the diameters of inhibition zones in the agar diffusion test. However, there is little information on the precision of this method. In the present study clinical isolates of Salmonella spp. (N = 104), Escherichia coli (N = 100), Pasteurella spp. (N = 99), Actinobacillus pleuropneumoniae (N = 85), porcine streptococci (N = 100), and Staphylococcus aureus (N = 95) were tested in the agar diffusion test, using nineteen different antibiotics in tablets. All inhibition zone diameters were first measured by a laboratory technician and then by the IAS. Although the zone diameters of all bacteria-antibiotic combinations measured by the IAS and those measured by the laboratory technician showed a significant positive correlation, the size of the inhibition zone diameters measured by the technician and the IAS differed significantly in 59% of the combinations. However, these differences were very small and may have no clinical relevance. The IAS was also used to calculate minimum inhibitory concentrations (MIC values) from the zone diameters. In 82% of the bacteria-antibiotic combinations MIC values calculated by the IAS showed a significant positive correlation with MIC values obtained with the reference agar dilution test. However, in 92% of the bacteria-antibiotic combinations, the calculated MIC values differed significantly from the reference values. In some cases these differences were so large that they could be of clinical relevance. The IAS was unable to measure the diameter of inhibition zones of porcine streptococci properly, due to poor contrast. We concluded that when tablets are used as antibiotic carriers the IAS accurately measures the diameter of inhibition zones for bacteria species that give good contrast between the agar and bacterial growth. MIC values determined with the IAS were only indicative of those determined with the reference agar dilution test.

Agar↗
PubMed1998

The F41 adhesin of enterotoxigenic Escherichia coli: inhibition of adhesion by monoclonal antibodies.

The anti-adhesive properties of 23 specific monoclonal antibodies (MAbs) against the F41 adhesive fimbrial antigen of enterotoxigenic Escherichia coli (ETEC) were studied in brush border adhesion inhibition tests and haemag-glutination inhibition tests with four F41-positive E. coli strains and purified F41 antigen. These MAbs recognize five epitope clusters, F41-1 to F41-5. It was proven that these epitope clusters were located on the 29 kDa F41 major fimbrial subunits. All nine MAbs against epitope cluster 1 inhibited the adhesion of F41-positive strains to brush border preparations of calf and pig intestines and the haemagglutination of sheep and guinea pig erythrocytes by the F41-positive strains and purified F41 antigen. The fourteen MAbs against the other four epitope clusters showed very little to no blocking of adhesion and haemagglutination. The results indicate that the adhesion of F41 to intestinal epithelial cells is mediated by the same domain of the 29 kDa F41 major fimbrial subunit(s) as the adhesion of F41 to erythrocytes. Irrespective of their epitope specificity F41 MAbs protected infant mice against a challenge with F41-positive ETEC. MAbs against all epitope clusters partly protected piglets against challenge with F41-positive ETEC in a similar way. Therefore, we conclude that direct blocking of the receptor binding site located on the major fimbrial subunit is not the main mechanism how antibodies protect against ETEC infection.

Adhesins, Escherichia coli↗
PubMed1998

Production of monoclonal antibodies specific for the i and 1,2 flagellar antigens of Salmonella typhimurium and characterization of their respective epitopes.

Salmonella typhimurium expresses two antigenically distinct flagellins, each containing a different H antigen (i and 1,2), the combination of which is highly specific for this serotype. In this study, overlapping recombinant flagellin fragments were constructed from the fliC (H:i) and fljB (H:1,2) flagellin genes, and the expression products were tested for binding to H antigen-specific monoclonal and polyclonal antibodies. A minimal area, 86 amino acids for H:i and 102 amino acids for H:1,2, located in the central variable domain of each flagellin was required for the binding of serotype-specific antibodies, providing further evidence for the presence of a discontinuous H epitope. Two peptides comprising these areas were shown to be highly suitable for application as antigens in an enzyme-linked immunosorbent assay detecting S. typhimurium-specific antibody.

Antibodies↗
PubMed1996

Parenteral vaccination of mice and piglets with F4+ Escherichia coli suppresses the enteric anti-F4 response upon oral infection.

We studied with a mouse model and in piglets the requirements to prime for a secondary, mucosal B-cell response against Escherichia coli F4 fimbriae, an important virulence factor of enterotoxigenic E. coli, the agent associated with postweaning diarrhoea in piglets. The major observation obtained with the mouse model was verified for piglets. Mice and piglets were primed orally or parenterally with purified F4ac antigen or whole bacterial cells carrying the F4ac antigen and were later orally infected with live F4ac+ E. coli bacteria. Cell suspensions of murine spleen or porcine serum were used to study the systemic B-cell response. Cell suspensions were also made of murine and porcine enteric lamina propria and were used to study the mucosal B-cell response. Enzyme-linked immunospot assays and enzyme-linked immunosorbent assays specific to E. coli F4ac antigen were used to quantify either the antibody-secreting cells or antibody titres in serum. Results showed that in mice only primary oral immunization with live bacteria induced an enteric immune response against the E. coli F4ac+ fimbriae. Oral immunization with killed bacteria induced hardly any mucosal immune response. Parenteral immunization induced a state of suppression that was reflected by the lack of an enteric immune response upon a subsequent oral infection with live bacteria. A comparable induction of suppression was observed in piglets using the same protocol. We conclude that parenteral vaccination of piglets with the E. coli F4ac antigen is ineffective to induce protective immunity at the mucosal level against postweaning diarrhoea and is possibly detrimental.

Animals↗