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Biomedical subjects

J Fransen

Publications and source records attributed to J Fransen.

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

Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia.

Skin-derived antileukoproteinase (SKALP), also known as elafin, is a serine proteinase inhibitor first discovered in keratinocytes from hyperproliferative human epidermis. In addition to the proteinase inhibiting domain which is directed against polymorphonuclear leukocyte (PMN) derived enzymes such as elastase and proteinase 3, SKALP contains multiple transglutaminase (TGase) substrate domains which enable crosslinking to extracellular and cell envelope proteins. Here we show that SKALP is constitutively expressed in several epithelia that are continuously subjected to inflammatory stimuli, such as the oral cavity and the vagina where it co-localizes with type 1 TGase. All epithelia from sterile body cavities are negative for SKALP. In general, stratified squamous epithelia are positive, whereas pseudostratified epithelia, simple/glandular epithelia and normal epidermis are negative. SKALP was found in fetal tissues of the oral cavity from 17 wk gestation onwards where it continued to be expressed up to adult life. Remarkably, in fetal epidermis SKALP was found from week 28 onwards, but was downregulated to undetectable levels in neonatal skin within three months, suggesting a role during pregnancy in feto-maternal interactions or in the early maturation phase of the epidermis. Immunoelectron microscopy revealed the presence of SKALP in secretory vesicles including the lamellar granules. In culture models for epidermal keratinocytes we found that expression of the endogenous SKALP gene provided protection against cell detachment caused by purified elastase or activated PMNs. Addition of exogenous recombinant SKALP fully protected the keratinocytes against PMN-dependent detachment whereas superoxide dismutase and catalase were only marginally effective. These findings strongly suggest that the constitutive expression of SKALP in squamous epithelia, and the inducible expression in epidermis participate in the control of epithelial integrity, by inhibiting PMN derived proteinases.

Adult↗
PubMed1995

Interactions between Ostertagia ostertagi and Cooperia oncophora in calves.

Development of immunity to Ostertagia ostertagi and Cooperia oncophora and interactions between both species in primed calves were investigated after homologous, heterologous and concurrent challenge infections. Worm counts, faecal egg output, IgG1 and IgG2 antibodies and the presence of globule leucocytes were used to evaluate the possible interactions. Results show that immunity build-up against O. ostertagi is slow in comparison with C. oncophora. The presence of early fourth-stage larvae and globule leukocytes in the O. ostertagi primed groups was significantly different to that of a previously uninfected control group. Ostertagia ostertagi and C. oncophora IgG1 antibodies were high in the previously exposed groups compared with uninfected controls and C. oncophora antibodies cross-reacted strongly with O. ostertagi antigens. There was no conclusive evidence for an interaction between C. oncophora and O. ostertagi. Globule leukocytes, IgG1 antibodies and early fourth-stage larvae seem to be related to development of immunity to O. ostertagi.

Animals↗
PubMed1993

The presence of an early L4 larvae population in relation to the immune response of calves against Ostertagia ostertagi.

The influence of different levels of infection with Ostertagia ostertagi on the development of a protective immune response in calves was investigated. Four groups of calves were infected with either 5000 (Group A), 10,000 (Group B), 20,000 (Group C) or 40,000 (Group D) infective larvae (O. ostertagi L3) weekly until treatment began. Group E functioned as controls. All animals were treated with oxfendazole (9 mg ml-1) at Week 17 (Groups A, B and E) or Week 18 (Groups C and D). Sixteen days post-treatment all calves received a challenge infection of 150,000 O. ostertagi L3 spread over 10 consecutive days. Faeces and blood were collected weekly for egg counts and to assess levels of pepsinogen, gastrin and IgG1 and IgG2 Ostertagia antibodies. All calves were necropsied 31 days post-challenge for worm counts. Egg counts and pepsinogen levels were proportional to the infection level during the first few weeks of the experiment. Only in the high-dosed Group D was a gastrin response evoked. Ostertagia IgG1 antibodies increased between Day 25 and Day 95, and in the non-infected control group an antibody rise was observed from Day 67 onwards. All measured parameters except Ostertagia antibodies showed a gradual decrease from Day 70 until the day of treatment. At necropsy there was no significant difference between the groups in the total worm populations. Only the composition of the worm populations differed, with 35% early L4 (EL4) larvae in the previously infected Groups A, B, C and D and only 5% in the control Group E. The results indicate a slow immune response against O. ostertagi in cattle and question the possible role of the EL4 stage in developing immunity.

Animals↗
PubMed1993

The constitutive exocytotic pathway in microvillous atrophy.

Microvillous atrophy is a disorder within the intractable diarrhea of infancy syndrome. The disease is believed to stem from a transport defect that prevents exocytosis of brush border-related material. We investigated this hypothesis by examining the direct constitutive exocytotic pathway using sucrase-isomaltase as a representative protein. We also studied various other brush border and lysosomal marker enzymes. The biosynthesis and localization of selected intestinal epithelial enzymes were studied in small-intestinal mucosal biopsy specimens from a total of nine children with microvillous atrophy by: (a) metabolic labeling in organ culture, (b) radioiodination and immunoprecipitation, (c) indirect immunoperoxidase immunocytochemistry, and (d) immunogold electron microscopy. The results demonstrated that brush border enzymes were synthesized normally and could be located in the apical brush border membrane and on microvillous membrane within microvillous inclusions. Brush border enzymes were not detected in the "secretory granules" that accumulated within the apical cytoplasm of epithelial cells. Lysosomal enzymes were only detected within lysosomal bodies. Thus, the direct constitutive pathway is not involved in microvillous atrophy, and a disturbance of endocytosis or the indirect constitutive pathway is unlikely. Any transport defect in the disease probably involves a different, unidentified exocytotic pathway.

Atrophy↗
PubMed1992

In vivo studies on the mechanism of action of the broad spectrum anticonvulsant loreclezole.

In animal models of epilepsy the anticonvulsant profile of loreclezole resembles that of barbiturates and benzodiazepines. We examined whether the increase in seizure threshold to pentylenetetrazole infusion produced by 10 mg/kg of loreclezole, pentobarbital or diazepam could be reversed by a spectrum of benzodiazepine partial inverse to full inverse agonists (FG-7142 beta-carboline carboxylate, CGS-8216, Ro-15-4513 and DMCM) or by a benzodiazepine neutral antagonist (Ro-15-1788). The doses of the benzodiazepine inverse agonists were chosen to produce a 20-40% decrease in seizure threshold. The seizure threshold increase produced by loreclezole and pentobarbital was reduced by all the benzodiazepine inverse agonists and potentiated by Ro-15-1788. Diazepam was antagonized by the benzodiazepine inverse agonists and by the neutral antagonist. The generality of this finding was examined in amygdala-kindled rats. The decrease in the duration of forepaw clonus and the reduction in behavioural stage34 produced by loreclezole, pentobarbital and diazepam was reversed by CGS-8216. Ro-15-1788, which itself showed anticonvulsant effects in this model, antagonized the effects of diazepam, but not loreclezole or pentobarbital. Thus loreclezole behaves more like a barbiturate than a benzodiazepine in these two in vivo models. This suggests a possible mechanism of action of loreclezole at a neuromodulatory site within the GABAA receptor complex, which is unlikely to be a benzodiazepine receptor.

Animals↗
PubMed1991

Gastrin and pepsinogen changes during an Ostertagia ostertagi challenge infection in calves.

Daily changes in serum gastrin and pepsinogen concentration have been studied during two types of infection with Ostertagia ostertagi in calves. In a first experiment two calves were trickle infected (10 times 10,000 L3 Ostertagia) and two animals received a single infection of 100,000 L3 Ostertagia. Gastrin and pepsinogen changes are discussed in relation to adult wormburdens. The second experiment involved 8 calves and was designed to investigate pepsinogen and gastrin changes following a challenge infection in previously sensitized calves. The high dosed group was infected with 5,000 L3 O. ostertagi during 30 days, the low dosed group received 500 L3 O. ostertagi and group 3 served as uninfected control. At day 41 post infection all animals were treated with oxfendazole and on day 61 challenged with 100,000 L3 O. ostertagi. Only in the high dosed group a distinct pepsinogen and gastrin reaction was noticed. Both parameters dropped to almost preinfection levels after treatment. Two days post challenge a moderate rise (+/- 1,000 mU tyr) of the pepsinogen concentration was observed in the previously infected animals and gastrin showed a temporary slight increase in several animals 8 to 10 days post challenge. The effect of treatment and challenge infection is discussed in relation to gastrin and pepsinogen changes and immunity.

Animals↗
PubMed1990

The in vitro antifungal activity of ketoconazole, zinc pyrithione, and selenium sulfide against Pityrosporum and their efficacy as a shampoo in the treatment of experimental pityrosporosis in guinea pigs.

The fungistatic and fungicidal activity of ketoconazole, zinc pyrithione, and selenium sulfide against Pityrosporum, a yeast thought to play a pathogenic role in seborrheic dermatitis and dandruff, was assessed in Dixon broth for Pityrosporum ovale and Sabouraud broth for Pityrosporum pachydermatis. Ketoconazole inhibited growth at concentrations ranging from 0.001 to 1 micrograms/ml. For zinc pyrithione and selenium sulfide higher concentrations were needed. In a guinea pig model the efficacy of treatment with four shampoos (Nizoral [Jansen], EDS Zinc [Schering], Zinkan [Lederle], and Selsun [Abbott]) was compared. The animals were inoculated for 7 consecutive days on intact skin. The lesions were scored for erythema, folliculitis, and hyperkeratosis 24 hours after the last inoculation and after treatment. Final evaluations were made 13 days after infection (10 days after last shampoo application). Treatment with undiluted and diluted (1:10) shampoos showed consistently superior clinical and mycologic results for Nizoral shampoo. None of the shampoos produced side effects.

Animals↗
PubMed1990

Pathology of natural infections of Schistosoma spindale Montgomery, 1906, in cattle.

The pathology of natural Schistosoma spindale infections in cattle in Sri Lanka was studied. Hepatic lesions were moderate with periportal cell infiltration and periportal epithelioid cell granulomas within perilobular zones. Submucosal and mucosal granulomas accompanied by cellular changes were present in the small and large intestine. Two unusual observations included the migration of an adult worm from the mesenteric veins to the mucosa of the small intestine in one bull and the presence of epithelioid cell granulomas containing slender living eggs in the urinary bladder of one animal. Intensities of infections, histopathological changes and immunological responses are discussed and comparison is made with other schistosome species.

Animals↗
PubMed1989

Mammomonogamus laryngeus (Railliet, 1899) infections in cattle from Sri Lanka.

During one year 1249 male cattle were examined for Mammomonogamus laryngeus infections in the slaughterhouse at Kandy, Sri Lanka. The overall prevalence was 40% with only light monthly variations (34 to 52%). The infection rate was highest (47%) in 2 to 2.5 year old animals. In infected animals an average of 6.4 parasite pairs was found with higher numbers in older animals. The majority of worms were located on the posterior side of the epiglottis. Lesions observed were mucosal plugs at the site where the parasites were attached to the mucosa and moderate to severe erosions and ulcers in other zones.

Age Factors↗
PubMed1989

The prevalence and pathology of Schistosoma nasale Rao, 1933 in cattle in Sri Lanka.

During 1987 a total of 1393 cattle was examined for Schistosoma nasale infection at the Kandy slaughterhouse, Sri Lanka. The overall prevalence was 12.6% (monthly range 3-17%). Based on the appearance of macroscopic lesions, 6 types (0-5) were recognized; type 5 being the most severe, with cauliflower-like growths obstructing the nasal cavity. Older bovines with 8 permanent incisors were more heavily infected (29.1%) than younger ones with no permanent incisors (6.0%). The severity of the lesions increased also with the age of the animals. Observations on the localization of the lesions showed that the first sessile nodular areas appear on the medial septum, on the dorsal edge of the ventral nasal concha and on the lateral wall of the middle meatus of the nasal cavity. Later, they gradually spread over the whole mucosal surface of the anterior part of the cavity but were rarely found further than 10 cm posterior to the nasal opening. The histopathology showed that granuloma formation due to the presence of eggs was the most common feature of the respiratory mucosa.

Abattoirs↗
PubMed1989

The prevalence and identity of Sarcocystis cysts in cattle in Belgium.

Muscle tissue from the oesophagus, diaphragm and heart of 100 cattle slaughtered in Belgium was examined for Sarcocystis infection by microscopic examination of tissue and artificial digestion. Intact sarcocysts or cystozoietes were recovered from 97% of the cattle examined. There was a difference in sensitivity between the method (digestion or histology) used and the muscle processed. The digestion of the oesophagus muscle resulted in the highest number of positive animals whereas the heart muscles contained most cysts during histological examination. Thin-walled cysts were recovered from all positive animals especially in the heart and they were indistinguishable from those of S. cruzi. Thick-walled cysts were recovered from 56% of animals but these could not be identified as S. hirsuta and/or S. hominis on morphological grounds. A correlation between pathological changes and the infection grade could not be proved.

Animals↗
PubMed1989

Treatment of experimental zygomycosis in guinea pigs with azoles and with amphotericin B.

Nonpredisposed Albino guinea pigs were infected intravenously with Rhizopus microsporus var. rhizopodiformis or with Rhizopus oryzae. Both strains were highly pathogenic. They killed all control animals between days 4 and 7 and between days 5 and 9 after infection, respectively. All animals presented invasion of almost all internal organs and skin eruptions developing into ulcers. Oral treatment with ketoconazole, itraconazole, fluconazole or saperconazole was inefficacious. Parenteral treatment with amphotericin B prolonged survival and was life-saving in 9 out of 12 guinea pigs infected with Rh. microsporus var. rhizopodiformis and in 5 out of 12 infected with Rh. oryzae. More active therapy is needed.

Amphotericin B↗
PubMed1989

Secretion of a precursor form of lysosomal alpha-glucosidase from the brush border of human kidney proximal tubule cells.

We have shown previously (R.P.J. Oude Elferink, E.M. Brouwer-Kelder, I. Surya, A. Strijland, M. Kroos, A.J.J. Reuser, J.M. Tager, Eur. J. Biochem. 139, 489-495 (1984)) that human urine contains considerable amounts of a precursor form of lysosomal alpha-glucosidase (about 50% of the total alpha-glucosidase activity present). We have now purified alpha-glucosidase from human kidney. Only about 5 to 10% of the total lysosomal alpha-glucosidase present in kidney comprises the precursor form of the enzyme. By means of immunocytochemistry using monoclonal antibodies, the precursor of alpha-glucosidase was detected in the brush border of the proximal tubule cells. Taking into account the amount of precursor alpha-glucosidase excreted daily into the urine and the amount present in the kidneys, we conclude that extensive secretion of precursor alpha-glucosidase occurs from the brush border of the proximal tubules.

Blotting, Western↗
PubMed1988

Clinical pathology of experimental Schistosoma curassoni infections in sheep and goats.

The clinical pathology of Schistosoma curassoni infection in sheep and goats was studied for 22 weeks following experimental infection with 7000 and 4000 cercariae, respectively. Excretion of eggs began at week 7 after infection: in goats the numbers increased to 30 to 50 eggs per gram faeces (epg) at weeks 8 to 18, followed by a reduction. In a pregnant goat, epg values increased markedly before and after parturition. The mean faecal egg counts in sheep were lower than in goats, increasing to a maximum level of 30 epg at weeks 16 and 17 after infection. Infected sheep maintained growth rates roughly comparable with controls, whereas infected goats failed to gain as much weight as the controls. Infected goats and sheep produced eosinophil counts of about 3 x 10(3) mm-3, five and eight weeks after infection, respectively. Sheep developed a progressive anaemia from week 11 after infection, in goats blood values remained within normal limits. Differences in serum protein concentration were observed between infected and uninfected goats about nine weeks after infection, but not in sheep. Increased total protein values, hyperglobulinaemia and lowered albumin to globulin ratios were features of infected goats. Serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase, total lactate dehydrogenase and bilirubin were not significantly changed. The mean recovery in sheep was 608 worms, in goats 428 worms, but the total tissue egg counts were higher in the latter. Of the total eggs deposited in the goats 92 per cent were found in the liver with 51.5 per cent in the ovine liver. The histopathological changes were studied.

Animals↗