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M J Gerritsen

Publications and source records attributed to M J Gerritsen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Transition from symptomless to lesional psoriatic skin.

Numerous investigations have been carried out to describe the cellular biological changes in lesional and symptomless psoriatic skin. Although these studies have increased our knowledge of the pathogenesis of psoriasis, our insight into the relevance of the individual changes in the whole pathogenic process is still limited. Studies on the transition between symptomless and lesional skin are of importance in assessing the pathogenic relevance of the individual aspects. In this paper, the literature is reviewed with respect to the transitional changes; in particular, studies on changes at the margin of the psoriatic lesion and the response of the symptomless skin to standardized injury are reviewed. From the available studies it may be concluded that changes in the stroma (i.e. increased expression of tenascin and increased endothelial alkaline phosphatase activity) are early pathogenic features. The appearance of a predominantly lymphocytic infiltrate, in particular the extravasation of CD4+ T lymphocytes, and the suprabasal expression of keratin 16 are intermediary stages. Relatively late in the pathogenesis are increased recruitment of cycling epidermal nuclei, parakeratosis, decreased expression of filaggrin and premature expression of involucrin. In order to discover the pathogenic relevance of molecules which might have an impact on the development of psoriasis, sequential studies during transition from symptomless to lesional skin are worthwhile.

Animals↗
PubMed1994

Repeated tape stripping of normal skin: a histological assessment and comparison with events seen in psoriasis.

The aim of the present study was to investigate the response of normal human skin to repeated courses of Sellotape stripping. The skin of healthy volunteers was stripped five times at 24-h intervals. Skin biopsies were taken before stripping (day 0) and on days 2, 4, 7 and 10. The responses were studied using H & E staining and an immunohistochemical analysis of several aspects of epidermal proliferation and keratinization. Although increased proliferation (nuclear binding to Ki-67 binding), acanthosis and parakeratosis were observed, the overall histological picture did not resemble psoriatic histology completely: no micropustules of Kogoj and no thinning of the suprapapillary plate were observed. Involucrin staining followed the recruitment of cycling epidermal cells showing a statistically significant elevation of positive cell layers from day 2 onwards. Filaggrin expression showed an increase from day 2 onwards, which was statistically significant on day 7 and day 10. Using the anti-keratin antibodies KS8.12 (K13 and K16) and RKSE60 (K10) we observed a fast induction of K13/K16 expression, while the staining of keratin 10 showed the same overall intensity at different time intervals. In conclusion, the response to repeated courses of tape stripping provides an adequate model for studies on epidermal proliferation, hypergranulosis and hyperkeratosis. This approach causes a more prolonged induction of these phenomena than a single course of stripping. In contrast to the situation following a single course of stripping, repeated tape stripping induced the expression of filagrin. Therefore the repeated tape stripping model is less compatible with psoriasis than a single course of stripping.

Adolescent↗
PubMed1994

Response of the clinically uninvolved skin of psoriatic patients to repeated tape stripping during cyclosporin A treatment.

It is well established that cyclosporin A (CyA), a widely used immunosuppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effect of CyA in psoriasis is mediated through antilymphocyte activity, there is also evidence suggesting that CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of studies relating to the latter have been contradictory. Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and differentiation in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regeneration in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3-5 mg/kg/day) modulates epidermal proliferation and differentiation following standardized injury in uninvolved skin of psoriatic patients. Ten patients with severe psoriasis participated in this study. The dosages of CyA were sufficient to induce a marked and statistically significant improvement (PASI, week 0, 20.5 +/- 4.4; PASI, week 16, 4.3 +/- 0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2-cm2 area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitment of cycling cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape-stripped uninvolved skin of psoriatic patients. We conclude that epidermal hyperproliferation and abnormal keratinization are not modulated directly by CyA at therapeutic doses in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules, Neuronal↗
PubMed1994

The effect of tacalcitol (1,24(OH)2D3) on cutaneous inflammation, epidermal proliferation and keratinization in psoriasis: a placebo-controlled, double-blind study.

The aim of the present study was to discover to what extent 1,24(OH)2D3 ointment (tacalcitol; 4 micrograms/g) can modulate epidermal proliferation and keratinization, and several aspects of inflammation. Ten patients with psoriasis vulgaris were included in a placebo-controlled, double-blind study, using 1,24(OH)2D3 ointment (4 micrograms/g). Before, and after 8 weeks of treatment, punch biopsies were taken from lesions treated with the active agent and placebo-treated lesions. An immunohistochemical study was carried out using monoclonal antibodies against the hyperproliferation-associated keratin 16, against cycling nuclei, filaggrin, involucrin, T lymphocytes, Langerhans cells, CD14 and polymorphonuclear leucocytes (PMN). The Wilcoxon test for matched pairs was used for statistical analysis of results. The biopsies from the lesions treated with the active agent showed a statistically significant change towards normalization of all aspects of inflammation studied, and of epidermal proliferation and keratinization, but there did not appear to be any effect on Langerhans cells. The only parameter which showed a significant alteration in the placebo-treated lesions was the number of cycling nuclei in the epidermis (P < or = 0.02). However, the biopsies from the plaques treated with the active agent showed a greater decrease of cycling cells (decrease: Mactive = 70, Mplacebo = 53) and a lower P-value (< or = 0.01). We therefore conclude that at the cell biological level 1,24(OH)2D3 ointment (4 micrograms/g) has a substantial effect on several cell types, with regard to inflammation, epidermal proliferation and keratinization, with the exception of Langerhans cells.

Cell Division↗
PubMed1994

The effect of topical application of the platelet-activating factor-antagonist, Ro 24-0238, in psoriasis vulgaris--a clinical and immunohistochemical study.

Platelet-activating factor (PAF) is considered to be one of the most potent lipid mediators in allergic and inflammatory reactions. Suggestions that PAF is produced by cutaneous cells, and cells infiltrating the skin from the blood, have been reported. PAF has been identified in allergic cutaneous reactions and also in psoriatic lesions. The biological activity of PAF is thought to be mediated by cell membrane receptors. Studies revealed that PAF-antagonists can be active in animal models of cutaneous inflammation. In humans PAF-antagonists showed minimal therapeutic improvement in studies of antigen-induced cutaneous responses in atopic subjects. No data are available on the effects of PAF-antagonists in psoriasis. The objective of this study was to investigate the effect of a potent PAF-antagonist (Ro 24-0238, 10% solution in diethylene glycol monoethyl ether) in 10 patients with chronic plaque psoriasis, a placebo-controlled double-blind study. Clinical response was evaluated and markers of inflammation, differentiation and proliferation were studied immunohistochemically on punch biopsies taken from actively treated and placebo-treated lesions, before and after treatment. This study demonstrated that a 10% solution of the PAF-antagonist Ro 24-0238 was not effective at the clinical or cell biological level after a 4-week treatment period. The most likely explanation for these negative observations is that PAF is not a significant factor in the pathogenesis of psoriasis.

Adult↗
PubMed1994

Effective treatment with dihydrostreptomycin of naturally infected cows shedding Leptospira interrogans serovar hardjo subtype hardjobovis.

The efficacy of dihydrostreptomycin in stopping the shedding of Leptospira hardjo subtype hardjobovis was studied in naturally infected cows. Blood and urine samples were collected from dairy cows kept on a farm where the farmer had contracted L hardjobovis infection. A microscopic agglutination test and an ELISA were used to determine specific antibody responses in serum. Polymerase chain reaction was used to detect bacterial shedding in urine. On the first sample collection date, 6 cows were seropositive, and 3 of those shed leptospires in the urine. These 3 cows were treated once with 25 mg of dihydrostreptomycin/kg of body weight. Within 1 week, the 3 cows stopped shedding leptospires. Six weeks later, 8 more lactating cows were found to be shedding leptospires. These cows were also treated once with dihydrostreptomycin, and they too stopped shedding leptospires within 1 week. From then on, the whole herd was examined weekly for a period of 2 months, and all cows Leptospira-positive by polymerase chain reaction were treated once with dihydrostreptomycin. Again, all cows stopped shedding leptospires in the urine within 1 week after treatment with dihydrostreptomycin. After a single treatment of the whole herd at the same time, new infections were not seen.

Amoxicillin↗
PubMed1994

Sheep as maintenance host for Leptospira interrogans serovar hardjo subtype hardjobovis.

Transmission of Leptospira interrogans serovar hardjo subtype hardjobovis from naturally infected sheep to uninfected sheep and calves was studied. A microscopic agglutination test and ELISA were used to determine specific antibody responses in serum. Polymerase chain reaction was used to detect bacterial shedding in urine. Six sheep were derived from a dairy farm where cows were infected with L hardjobovis. Three of these sheep were seropositive for L hardjobovis, and 1 also shed leptospires in the urine. The other 2 sheep shed leptospires in the urine 7 days after the first observation date. The 6 sheep were placed on an isolated pasture together with a second group of 6 noninfected sheep. During the observation period of 140 days, 1 sheep of the second group became infected with L hardjobovis. On 5 consecutive days, a urine mixture from the 4 infected sheep was sprayed on the heads of 4 noninfected calves. Within 56 days, all calves that had been sprayed with urine shed L hardjobovis in the urine and became seropositive for L hardjobovis.

Animals↗
PubMed1993

Effect of streptomycin treatment on the shedding of and the serologic responses to Leptospira interrogans serovar hardjo subtype hardjobovis in experimentally infected cows.

Shedding patterns of and serologic responses to Leptospira interrogans serovar hardjo subtype hardjobovis (L. hardjobovis) have been studied in experimentally infected cows treated with streptomycin in comparison to experimentally infected cows receiving no such treatment. Fourteen cows were experimentally infected with L. hardjobovis, and blood and urine samples were collected weekly for 24 weeks. The microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA) were used to determine serologic responses. The polymerase chain reaction (PCR) was used to determine bacterial shedding in urine. Six weeks after infection six cows were treated with the antibiotic streptomycin (25 mg/kg body weight/day); three cows were treated only once, and the remaining three were treated for five consecutive days. After treatment all six cows had lower serologic responses compared to the untreated cows. The treated cows became also PCR-negative two days after the first treatment, whereas the eight untreated cows remained PCR-positive for at least 70 days. Cows that stopped shedding did not resume shedding within the observation period. Since streptomycin treatment reduces the period of shedding, transmission of leptospira via contaminated urine might be prevented by a single treatment of an infected herd.

Agglutination Tests↗
PubMed1993

Topical treatment of psoriatic plaques with 1,25-dihydroxyvitamin D3: a cell biological study.

Calcitriol, 1 alpha,25 dihydroxycholecalciferol (1 alpha,25 (OH)2 D3) is a natural active vitamin D3 metabolite, which has been shown to have antipsoriatic efficacy. In vitro studies have demonstrated that calcitriol influences various aspects of inflammation, epidermal proliferation and keratinization. The aim of the present study was to determine to what extent calcitriol (3 micrograms/g in white petrolatum) affects these parameters in vivo. Using an immunohistochemical assessment of recruitment of cycling epidermal cells, filaggrin and involucrin expression, T-cell accumulation, polymorphonuclear neutrophil (PMN) accumulation, amount of endothelium and ICAM-1 expression, we demonstrated that: (i) modulation of all these parameters occurred during calcitriol treatment; (ii) there was early reduction of epidermal proliferation and PMN accumulation; (iii) the order of changes was comparable with the response to treatment with calcipotriol. In conclusion, at the cell biological level, calcitriol (3 micrograms/g in white petrolatum) has a substantial effect on various elements of the psoriatic lesion.

Calcitriol↗
PubMed1992

Anti-retinal S-antigen antibodies in human sera: a comparison of reactivity in ELISA with human or bovine S-antigen.

Various studies have demonstrated anti-retinal S-antigen (S-ag) antibodies in uveitis sera in assays using bovine S-ag. Because of its molecular similarity and cross-reactivity with human S-ag, reactions with bovine S-ag have been considered a reliable indication of anti-S-ag autoimmunity. To test this assumption, the cross-reactivity of purified human and bovine S-ags was quantitated by ELISA titration of various anti-human and anti-bovine S-ag immune reagents raised in mice, rats and rabbits. Anti-human S-ag reagents appeared to be largely cross-reactive with bovine S-ag, whereas anti-bovine S-ag reagents were 6-10 times less reactive with the cross-reacting human S-ag than with bovine S-ag, thus showing a predominant role of species-specific epitopes on bovine S-ag. Furthermore, a large number of human control and uveitis sera was tested in ELISA with both human S-ag- and bovine S-ag-coated microwells. Both the numbers of positive sera and the levels of anti-S-ag antibodies in the two tests significantly correlated, but many exceptions were found, and the predictive value of reactions with bovine S-ag for the presence and levels of anti-S-ag autoantibodies was low. For individual human sera, assessment of anti-S-ag autoantibodies requires the use of human S-ag in immunoassays.

Animals↗
PubMed1991

Sample preparation method for polymerase chain reaction-based semiquantitative detection of Leptospira interrogans serovar hardjo subtype hardjobovis in bovine urine.

An improved method of preparing bovine urine samples was developed for the rapid, specific, and sensitive detection of Leptospira interrogans serovar hardjo (subtype hardjobovis) DNA by the polymerase chain reaction (PCR). A total of 100 leptospire-free cows, 4 experimentally infected cows, and 2 negative control cows were used. PCR results were improved by (i) using 10-ml urine samples instead of 1-ml samples, (ii) adding 10(7) to 10(8) Leptospira biflexa serovar patoc cells as a carrier to each treated sample, (iii) preventing the loss of pelleted leptospires, and (iv) minimizing the presence of PCR-inhibiting factors in the samples. The preparation method enabled us to use the PCR to reproducibly detect as few as 5 to 10 leptospires per ml of urine without the need for dot blot hybridization. In addition, we were able to estimate the number of leptospires shed by experimentally infected cows.

Animals↗
PubMed1991

Characterization of serovars of the genus Leptospira by DNA hybridization with hardjobovis and icterohaemorrhagiae recombinant probes with special attention to serogroup sejroe.

Recombinant DNA probes derived from genomic libraries of serovars hardjobovis and icterohaemorrhagiae were applied for the characterization of leptospires. Differences in hybridization signals in combination with the banding pattern appear to provide good characteristics for strain typing. The banding patterns were easy to distinguish, since the recombinant DNA probes hybridized with a limited number of fragments. They were also indicative of genomic relationships between serovars. The probes suggested the existence of four subgroups with extensive genomic homology within the serogroup Sejroe. A number of serovars outside the serogroup Sejroe showed genomic homology with these subgroups. Amplification with the polymerase chain reaction showed a correlation with the genomic homologies demonstrated by Southern analysis. Knowledge about genomic relationships between leptospiral strains, as revealed by Southern analysis, may lead to a more rational approach for primer selection for polymerase chain reaction or cloning of particular genes.

Blotting, Southern↗
PubMed1989

Detection of leptospires in urine by polymerase chain reaction.

Primers for polymerase chain reaction (PCR) were synthesized from clones derived from a Leptospira hardjo (type hardjobovis) library. One pair of synthetic oligonucleotide primers was selected for further analysis. Under experimental conditions an amplification was obtained with DNA of Leptospira interrogans of some serovars belonging to serogroup sejroe. However, very little or no amplification was observed with DNA from other serovars of this group. No amplification was observed with DNA from other serogroups, other bacteria, or eucaryotic organisms. Cattle urine, seeded with hardjobovis, was processed in several ways and subsequently subjected to PCR. Boiling of the samples or treatment with detergents appeared to be most effective. Urine samples containing fewer than 10 leptospires gave a positive result in the PCR assay. Twenty urine samples obtained from a slaughterhouse or farm cows were investigated using the PCR assay, culture isolation, dot and quick blot hybridization, and serological tests. This comparative study suggests that amplification by PCR may be a valuable method for the detection of leptospires in cattle urine.

Animals↗
PubMed1989

Immunoreactivity and cross-reactivity of human and bovine retinal S-antigen.

The reactions of human and bovine retinal S-antigen (S-ag) with polyclonal rabbit antibodies were compared in ELISA, immunoblotting and inhibition ELISA. Titrations in ELISA with plastic-adsorbed S-ags revealed that the great majority (70-100%) of human S-ag epitopes and anti-human S-ag antibodies were cross-reactive. In contrast, the cross-reactivity of bovine S-ag (25%) and anti-bovine S-ag antibodies (15-20%) indicated an important contribution of species-specific epitopes to the antigenicity of bovine S-ag. Immunoblotting of S-ag fragments after treatment with chymotrypsin confirmed these differences and also demonstrated different chymotrypsin-induced cleavage patterns of human and bovine S-ag. Thus, in assays involving partial denaturation and/or degradation of the antigens, human S-ag showed little, and bovine S-ag a marked species-specific immunoreactivity. In inhibition ELISA however, in which S-ags in solution could be studied, species-specific reactions strongly predominated for both S-ags. Anti-human S-ag and anti-bovine S-ag antibodies could be absorbed with nM concentrations of fluid phase human and bovine S-ag, respectively, whereas in both cases the cross-reacting antigen had no detectable inhibitory potential. The epitopic structures of human and bovine S-ag in solution may thus be largely different.

Animals↗