Questionnaire survey of disease prevalence and veterinary treatments in organic pig husbandry in the Netherlands.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Kijlstra.
Explore the source record for details and available documents.
AIM: To investigate which phosphodiesterase (PDE) is involved in regulating cyclic 3'5' guanosine monophosphate breakdown in retinal pigment epithelium (RPE) cells. METHODS: cGMP content in the cultured RPE cells (D407 cell line) was evaluated by immunocytochemistry in the presence of non-selective or isoform-selective PDE inhibitors in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). mRNA expression of PDE2, PDE5 and PDE9 was studied in cultured human RPE cells and rat RPE cell layers using non-radioactive in situ hybridisation. RESULTS: In the absence of PDE inhibitors, cGMP levels in cultured RPE cells are very low. cGMP accumulation was readily detected in cultured human RPE cells after incubation with Bay60-7550 as a selective PDE2 inhibitor, sildenafil as a selective PDE5 inhibitor or Sch51866 as a selective PDE9 inhibitor. In the presence of PDE inhibition, cGMP content increased markedly after stimulation of the particulate guanylyl cyclase. mRNA of PDE2,PDE5 and PDE9 was detected in all cultured human RPE cells and also in rat RPE cell layers. CONCLUSIONS: PDE2, PDE5 and PDE9 have a role in cGMP metabolism in RPE cells.
Explore the source record for details and available documents.
In organic livestock production systems, farm-management factors are thought to play an important role in the on-farm prevalence of Toxoplasma gondii. Serological results and the results of an HACCP analysis were combined to determine important risk factors for the prevalence of this protozoan parasite. Mathematical analysis demonstrated that feeding goat whey to pigs and the presence of a high number of cats were positively correlated to T. gondii seroprevalence in pigs. Not covering roughage and the farmers' assumption that pigs can come into contact with cat feces also showed a positive relationship. In order to decrease the risk of T. gondii infecting their pigs, farmers should limit the access and number of cats on their farms and refrain from feeding goat whey to their pigs.
The presence of Salmonella and Campylobacter spp. in rodents and insectivores (n = 282) was investigated on organic farms. Infections were encountered in house mice (8 of 83 Campylobacter positive and 1 of 83 Salmonella sp. strain Livingstone positive) and brown rats (1 of 8 Campylobacter positive) but not in other species. No shared Campylobacter genotypes were found between rodent and pig manure isolates. Effective on-farm rodent management is recommended.
Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible role for autoimmunity was initially suggested, it has never reached general acceptance. Microorganisms have also been implied in the pathogenesis of AMD. Both serum antibacterial antibody levels and positive DNA tests from neovascular membranes have pointed to a possible role for Chlamydia pneumoniae in the pathogenesis of AMD. New data is providing evidence for the hypothesis that deposits between Bruch's membrane and the retinal pigment epithelium (RPE) cell layer may act as a stimulus for the local activation of the complement system. This may lead to a further growth of the deposits due to the strong chemotactic activity of certain complement activation products (such as C5a) with an influx of inflammatory cells. The buildup of cells and extracellular deposits may lead to local ischemia resulting in the activation of RPE cells. These activated RPE cells are thought to release angiogenic stimuli leading to choroidal neovascularization, which is the most serious complication of AMD. The fact that immunosuppressive drugs such as triamcinolone acetonide and anecortave acetate are capable of inhibiting choroidal neovascularization is consistent with an inflammatory component in the pathogenesis of AMD. Specific immunotherapy directed at certain cytokines or growth factors is now being investigated at both the animal and patient levels. Various clinical trials involving engineered antibodies are now being applied to block angiogenic factors such as the vascular endothelial growth factor (VEGF). An approach using gene therapy to influence angiogenesis by inducing the production of the pigment epithelium-derived factor (PEDF) was able to block neovascularization in an experimental murine model. Besides trying to block ongoing processes in AMD, retinal transplantation is now also being investigated as a treatment option. The fact that the retina is possibly an immunoprivileged tissue in combination with experimental data showing that the subretinal space is an immunoprivileged site is an indication that transplantation would not suffer from the rejection process. A larger obstacle is the question whether transplanted retinal tissue will regain its functional properties.
PURPOSE: Low gas-permeable contact lens wear of polymethyl methacrylate or hydroxyethyl methacrylate material is known to cause morphologic abnormalities in the corneal endothelial cell layer. These lenses were widely prescribed and successfully worn until their use was actively discouraged in the late 1980s and early 1990s. This study was designed to investigate whether discontinuation of low gas-permeable contact lens wear leads to an improvement of corneal endothelial cell morphology. METHODS: At the time of discontinuation and at least 5 years after discontinuation of low gas-permeable contact lens wear, noncontact specular photographs of the central corneal endothelium were made in 66 patients (14 male and 52 female, mean age 37.7 +/- 8.4, range 24.6-69.0). By computer analysis of endothelial photographs, parameters for polymegethism and pleomorphism were calculated, as well as cell density. RESULTS: Mean follow-up time between photographs was 6.8 years (SD 1.1). Sixty-one patients were refitted with rigid high gas-permeable contact lenses or high-water-content soft lenses, and 5 patients switched to spectacle wear. A small but significant recovery of the corneal endothelial cell morphology was found for the mean coefficient of variation of cell area, from 37.5 to 35.7 (P = 0.022), and for the coefficient of variation of the number of sides, from 13.1 to 12.4 (P = 0.004). The mean percentage of hexagonal cells increased from 54.2 to 56.2 (P = 0.013). Although the corneal endothelial cell morphology improved significantly on cessation of LGP contact lens wear, the values did not return to levels observed in normal, non-contact lens wearing individuals. During follow-up, the mean endothelial cell density decreased significantly (P = 0.001) from 2994 to 2890 (a 3.5% cell loss in 6.8 years), which is similar to the known normal age-related cell loss of 0.6% per year in non-contact lens wearing healthy individuals. CONCLUSION: Endothelial polymegethism and pleomorphism caused by PMMA or HEMA contact lens wear is partly reversible.
AIM: To test the hypothesis that T-bet expression is altered in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: Peripheral blood was withdrawn from 16 VKH patients before and after immunosuppressive treatment and from 16 healthy individuals. IFN-gamma, IL-2, and IL-4 in the serum and the supernatants of peripheral blood mononuclear cells (PBMC) cultured with or without phytohaemagglutinin (PHA) were measured by ELISA. T-bet mRNA and protein expression in PBMC cultured with or without PHA was detected by RT-PCR and western blot, respectively. RESULTS: The level of IFN-gamma, but not IL-2 and IL-4, was significantly higher in the supernatants of stimulated PBMC in patients than in controls. A significantly increased T-bet mRNA was found in VKH patients during an active uveitis episode, but not in quiescent patients, compared to controls. T-bet protein was detectable in VKH patients during an active uveitis episode, but not in quiescent patients nor in the healthy controls. Stimulation of PBMC with PHA resulted in a marked upregulation of T-bet mRNA and protein expression for both patients and controls with no significant difference between the two groups. CONCLUSIONS: Upregulation of T-bet may be associated with the development of a Th1 mediated immune response in VKH disease.
AIM: To investigate T-bet mRNA and protein expression on peripheral blood mononuclear cells (PBMC) in patients with Behçet's disease with active uveitis. METHODS: Blood samples were taken from 24 patients with Behçet's disease who had active uveitis and 16 healthy individuals. PBMC were subjected to analysis of T-bet mRNA and protein expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The products from PCR were sequenced. In order to determine the influence of activation on T-bet expression, the phytohaemagglutinin (PHA) stimulated PBMC from each sample were also evaluated for expression of T-bet mRNA and protein. RESULTS: A significantly increased T-bet mRNA accumulation was detected in the samples from patients with active Behçet's disease compared with that in controls. A 62 kDa band was detectable in patients with active Behçet's disease, but not in controls. No difference was found between patients with Behçet's disease who had active uveitis and normal controls concerning the expression of either T-bet mRNA or its protein after stimulation with PHA for 72 hours. CONCLUSION: Behçet's disease is associated with an upregulation of T-bet expression, which supports a role for the Th1 subset of T cells in the pathogenesis of this disease.
PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.
Vision is dependent on proper function of several intraocular structures. Immune responses to eliminate invading pathogens from the eye may threat vision by causing damage to these structures. Therefore, immunological defence of the eye should be carefully balanced between efficacy and maintenance of functional integrity. The eye is equipped with several regulatory mechanisms to prevent certain immune and inflammatory responses and is, therefore, regarded as an immune privileged site. The retinal pigment epithelium (RPE) contributes to the immune privileged status of the eye as part of the blood-eye barrier and by the secretion of immunosuppressive factors inside the eye. RPE cells, however, may also play an important role in the development of immune and inflammatory responses in the posterior part of the eye. During the last decade it has become clear that RPE cells are highly sensitive to a variety of inflammatory cytokines. Under inflammatory conditions, RPE cells produce a myriad of cytokines that may activate the resident ocular cells or attract and activate leukocytes. Cytokine stimulation of RPE cells causes profound effects, including nitric oxide secretion, cell surface expression of MHC class II and adhesion molecules and abrogation of barrier function. This article provides a comprehensive review of the literature concerning RPE cells and cytokines.
Cytokines play an important role in the pathogenesis of various corneal diseases and during corneal graft rejection. Furthermore, cytokines may also play a role in the maintenance of the integrity of the normal cornea. This review focuses on the effects of several cytokines in corneal immunopathology, including the type of the corneal immune response, angiogenesis, chemotaxis, apoptosis, wound healing, corneal disease, and transplantation. It may provide clues for the future treatment of corneal disease and corneal transplantation rejection.
AIMS: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, Vogt-Koyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. METHODS: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). RESULTS: A higher proportion of CD4(+) T cells expressing Fas was noted in patients with Behcet's disease (25.70 +/- 7.32%), VKH syndrome (19.60 +/- 11.02%), and idiopathic anterior uveitis (20.81+/- 7.40%) compared with controls (14.02 +/- 6.30%). The expression of Fas on CD8(+) cells from patients with Behcet's disease (9.47 +/- 6.97%) and VKH syndrome (6.84+/- 5.5%) was also higher than that seen in controls (3.47+/- 2.75%). There was no difference in FasL expression on T cells between patients and controls except that a lower expression of FasL on CD8(+) T cells was noted in patients with idiopathic anterior uveitis. CONCLUSION: A disturbed expression of Fas and FasL on T cells is present in patients with Behcet's disease, VKH syndrome, and idiopathic anterior uveitis, which may be involved in the perpetuation and recurrence of uveitis.
PURPOSE: The mechanisms involved in reactivations of latent ocular Toxoplasma gondii (Tg) infections in immunocompetent patients are poorly understood. In view of the possible role of T cells in the immunopathogenesis of the disease, ocular infiltrating T cells obtained from patients with recurrent ocular toxoplasmosis were characterized phenotypically and functionally. METHODS: Ocular infiltrating T cells were recovered from vitreous fluid (VF) samples of 10 patients with active recurrent ocular toxoplasmosis. Two patients with uveitis of other origins were included as control subjects. T-cell lines (TCLs) were generated by mitogenic stimulation and tested for reactivity to Tg and human retinal protein extracts. The TCLs of three patients were cloned by limiting dilution. Tg-reactive T-cell clones (TCCs) were characterized with respect to their phenotype, T-cell receptor variable (TCR V)-beta gene usage, HLA restriction, and cytokine secretion profile. RESULTS: Reactivity to Tg could be detected only in the TCLs of patients with ocular toxoplasmosis. None of the TCLs showed reactivity to human retinal antigens. All tested intraocular Tg-specific TCCs (n = 23) were CD3+CD4+ and displayed differential TCR Vbeta usage. Twenty-one TCCs were HLA-DR restricted and two TCCs were restricted by HLA-DP. The majority of the intraocular Tg-specific TCCs showed a bias toward a T-helper (Th)0-Th2 cytokine profile. CONCLUSIONS: The data indicate that T cells specific for the triggering microorganism infiltrate the eye of patients with recurrent ocular toxoplasmosis. The functional characteristics of the VF-derived Tg-specific T cells and their presence at the site of inflammation suggest their involvement in the local inflammatory response of ocular toxoplasmosis.
OBJECTIVE: To determine the cause and describe the clinical features of unilateral anterior uveitis with sectoral atrophy of the iris in the absence of associated keratitis. DESIGN: Retrospective, observational case series. PARTICIPANTS: Thirty-one patients with unilateral anterior uveitis with sectoral iris atrophy and without (previous) keratitis. METHODS: The patients were selected from our database of 592 patients with anterior uveitis. MAIN OUTCOME MEASURES: We reviewed the clinical data on the 31 patients and the results of diagnostic anterior chamber fluid analysis for 24 of the 31 patients. Specifically, production of local antibodies against herpes simplex virus (HSV) and varicella zoster virus (VZV) was determined and the polymerase chain reaction was performed to demonstrate the DNA of HSV, VZV, and cytomegalovirus (CMV) in the aqueous samples. RESULTS: Main clinical characteristics of anterior uveitis with iris atrophy included unilateral involvement with a prolonged course and recurrent exacerbations in all cases. Elevated intraocular pressure during intraocular inflammation occurred in 90% of patients (28 of 31). Visual outcome was favorable because 29 of 31 patients (94%) retained a visual acuity of 20/32 or more. The causal agent was identified as HSV in 83% (20 of 24) and VZV in 13% (3 of 24) and was inconclusive in one case. The patients with HSV uveitis were younger than those with VZV uveitis (mean age at onset 34 and 65 years, respectively; P = 0.0056). CONCLUSIONS: Unilateral anterior uveitis with sectoral atrophy of the iris without associated (previous) keratitis is a distinct entity among herpetic eye diseases. Recurrent unilateral anterior uveitis with iris atrophy and/or elevated intraocular pressure has most likely been caused by HSV.
BACKGROUND: Several ocular side effects including uveitis, have been reported following topical beta blocker treatment for glaucoma and ocular hypertension. The incidence of these side effects was investigated in the Netherlands. METHODS: A prospective observational design was used whereby monthly questionnaires were sent to all practising ophthalmologists in the Netherlands during 3 consecutive months. Questionnaires were returned at the end of each month. Any patient whose topical beta blocker therapy was altered because of an ocular reaction was noted on this questionnaire. Ophthalmologists who did not return their questionnaires were interviewed by telephone at the end of the study period. The number of patients using topical beta blockers was derived from drug sales figures. RESULTS: 70% (328/467) of the ophthalmologists in the Netherlands participated in the study. During the 3 month study period 34 cases were reported: 15 patients had periorbital dermatitis, in eight patients eyelids and conjunctiva were affected, in seven patients the conjunctiva was affected, and four patients had punctate keratitis. The calculated incidence of ocular side effects during topical beta blocker therapy was 1.51 cases/1000 patient years. CONCLUSION: Topical beta blocker therapy is associated with few clinically important ocular side effects. No cases of uveitis were reported.
AIM: To evaluate the effects of beta blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. METHODS: A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparations were then incubated with betaxolol, metipranolol, timolol, or carteolol. After incubation for 1 hour the histamine content of the supernatant was analysed by automated fluorometric analysis. Cell viability was tested by measuring lactate dehydrogenase (LDH) concentrations. RESULTS: Betaxolol and metipranolol in concentrations between 10(-2) M and 10(-3) M liberated histamine from human blood cells in a dose dependent manner. Carteolol and timolol had no effect on histamine at these concentrations. At the same concentrations LDH was also detected in the supernatants of cell suspensions incubated with metipranolol or betaxolol. CONCLUSIONS: Betaxolol and metipranolol induce substantial histamine release from human leucocytes, probably as a result of their cytotoxic effect.
PURPOSE: To investigate whether mucosal immune responses directed against the ubiquitous parasite Toxoplasma gondii can be detected in tears of healthy humans. METHODS: Nonstimulated tears and blood were obtained from 62 healthy humans (mean age, 35 +/- 10 [SD] years). Serum anti-T. gondii immunoglobulin titers were determined by Sabin-Feldman (SF) dye test. Western blot analysis was used to compare the anti-T. gondii repertoire in tears and serum, and antibody avidity was determined by urea elution. Diluted tear and serum samples were incubated with the intact parasite to determine whether the antibodies found in tears and serum are capable of binding to surface exposed antigens of T. gondii. RESULTS: Eighty-one percent of the individuals tested had an anti-T. gondii IgA response in their tears, whereas only 23% had evidence of systemic immunity against the parasite. There was no apparent relation between chronic infection and presence of anti-T. gondii IgA in tears. Characteristically, the antigens recognized by the IgA antibodies in tears were often limited to at least one of four antigens with molecular weights of 74, 70, 49, and 34 kDa. The avidity of the anti-T. gondii IgA antibodies in tears was similar to the avidity of serum IgG antibodies. IgA antibodies directed against the 49- and 74-kDa antigens recognized epitopes exposed on the surface of the parasite. CONCLUSIONS: A major finding of this study is that tears of many individuals, chronically infected or not, contain IgA antibodies against T. gondii. It is not known whether these frequently observed antibody responses are the result of common mucosal immune responses against T. gondii or represent the natural antibody repertoire.