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Biomedical subjects

C Zurcher

Publications and source records attributed to C Zurcher.

At least 37 records · Page 2Linked to original sources
PubMed1995

Squamous epithelial proliferative lesions associated with rhesus Epstein-Barr virus in simian immunodeficiency virus-infected rhesus monkeys.

Proliferative lesions were found on the squamous epithelium of the tongue, esophagus, or penis or haired skin of the lip, hand, or thorax of 8 simian immunodeficiency virus-infected rhesus monkeys that died of simian AIDS. The lesions were focal and consisted of hyperkeratosis, parakeratosis, and acanthosis in the skin, with additional ballooning degeneration in the tongue, esophagus, and penis. The epithelial surfaces were frequently colonized by Candida species or gram-positive cocci. Intranuclear inclusion bodies were seen in cells in the middle and superficial layers. Herpesvirus virions were found in inclusion-bearing cells by transmission electron microscopy. An Epstein-Barr-like virus was identified in inclusion-bearing cells by immunohistochemistry and in situ hybridization. No virus was detectable in basal layers of the epithelium. These lesions resemble oral hairy leukoplakia in AIDS patients and may thus provide a useful primate model to study permissive epithelial infection by Epstein-Barr-like viruses.

Animals↗
PubMed1995

Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect.

Animals↗
PubMed1994

Evidence for a diminished maturation of preosteoblasts into osteoblasts during aging in rats: an ultrastructural analysis.

Bone is subject to continuous remodeling throughout life. The age-related loss of (trabecular) bone, leading to senile osteopenia, is mainly due to impaired bone formation. Osteoblasts (OB) and osteoclasts (OC) have been identified as playing a crucial role in the process of bone turnover, but the contribution made by their precursors is not well documented. We analyzed the cells of the osteoblast and osteoclast cell lineage along the trabecular bone of tibiae and the stromal cells in the marrow of aging BN/Bi Rij rats using electron microscopy. It appeared possible to distinguish preosteoblasts (pre-OB), OB, preosteoclasts (pre-OC), OC, and inactive bone-lining cells. Periods of increase, the maximal peak, and the decrease in trabecular bone volume were defined by means of morphometric measurements of trabecular bone volume. We found a decrease of more than 10-fold in the number of OB with age, but the numbers of pre-OB, pre-OC, and OC expressed per unit bone length, although variable, were age independent. The relative bone resorption and formation surface, expressed as a percentage of the total bone surface, decreased 2- and 15-fold, respectively. In 2-year-old animals the total volume of stromal cells, part of which constitutes the stem cell compartment of the osteogenic lineage, was a quarter of that found in 1-month-old animals and a third of that found in 6-month-old animals. The loss of trabecular bone is concomitant with a sharp increase in the ratio of pre-OB/OB, the ratio of OC/OB, and in the ratio of resorption to formation surfaces. There was no relation between the ratio of pre-OC/OC with age. These data lead to the conclusion that the main factor causing bone loss with age is a diminished maturation of pre-OB into OB.

Aging↗
PubMed1994

In vivo adenovirus-mediated transfer of human CFTR cDNA to rhesus monkey airway epithelium: efficacy, toxicity and safety.

We have administered replication defective recombinant adenovirus harboring the human CFTR cDNA (Ad.CFTR) to lungs of Rhesus monkeys and assessed toxicity, efficiency of gene transfer and containment of recombinant adenovirus in the lungs. Gene transfer efficiencies, as measured by PCR analysis, were dose-dependent. Administration of low dose Ad.CFTR [1.5 x 10(7) plaque forming units (p.f.u.)] was not accompanied by any clinical chemical or histopathological changes. Mild to moderate multifocal perivascular and peribronchial lymphocytic infiltrates were found upon histopathological analysis only after administration of a high dose of recombinant adenovirus, although not accompanied by changes in clinical chemical parameters. Long-term expression (up to 128 days) was found after administration of recombinant adenovirus. Re-challenging of the monkeys treated with high-dose recombinant adenovirus resulted again in gene transfer at all levels of lungs and airways, without being accompanied by additional histopathological changes. Circulating anti-adenovirus antibodies were elicited. Animals treated with high-dose adenovirus secreted virus in pharynx and faeces for maximally 2 and 4 days after administration, respectively. These results show that recombinant adenovirus can be used for efficient delivery of genes into primate airway epithelium without signs of severe toxicity.

Adenoviridae↗
PubMed1993

Interferon-gamma prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice.

Lethally irradiated C3H/Law mice were injected (i.v.) with C57BL/Rij allogeneic bone marrow cells to induce a delayed type graft-vs-host disease (GVHD). Signs of GVHD first became apparent in the third week after transplantation. The disease resulted in a mortality rate of 70% at 80 days. Treatment with IFN-gamma twice weekly, for a period of 6 wk, starting at the time of bone marrow transplantation (BMT), completely prevented overt GVHD, as evidenced by a lack of diarrhea and no mortality during the follow-up period of 100 days after BMT. Also, the histologic GVHD lesions in the gastrointestinal tract were almost completely abrogated by the IFN-gamma treatment. All long term survivors were proven to be chimeras. During the induction phase of GVHD, the number of Con A-induced, IFN-gamma-producing cells in the spleen was significantly reduced in the IFN-gamma-treated mice as compared with control mice. These results suggest that the normally enhanced production of endogenous IFN-gamma in the spleen at the time of hematopoietic reconstitution after BMT is down-regulated by exogenously administered IFN-gamma. This cytokine-mediated strategy to prevent GVHD might be an alternative to the current strategy of in vitro depletion of T cells for allogeneic BMT.

Animals↗
PubMed1993

Cytokeratins expressed in experimental rat bronchial carcinomas.

Cytokeratin expression in rat lung tumors was studied using polypeptide-specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous-cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross-react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub-types can therefore be used to distinguish the main sub-types of rat lung tumors and can give an indication about the degree of differentiation.

Adenocarcinoma↗
PubMed1993

A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice.

Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and tail are not involved. The lesions are characterized by epidermal hyperplasia, hyper- and parakeratosis, and single cell necrosis of keratinocytes. The dermis and epidermis are infiltrated by granulocytes and macrophages, and occasionally subcorneal and intracorneal microabscesses are formed. The number of mast cells in the dermis progressively increases with age. There is dilatation and proliferation of dermal capillaries. Similar lesions develop in the mouth, esophagus, and forestomach, which, in the mouse, are all lined by orthokeratinizing stratified squamous cell epithelium. Studies with bromodeoxyuridine confirm the increased rate of epithelial cell proliferation. Most inflammatory cells in the affected skin express Mac-1, and few express the T lymphocyte marker CD3. There is increased expression of intracellular adhesion molecule-1 on keratinocytes and endothelial cells. Infiltration of neutrophils and macrophages are also seen in the liver, lung, and several joints. The disease could not be transferred by bone marrow or spleen transplants into irradiated normal syngeneic hosts. Treatment of the mice with triamcinolone, a long-acting corticosteroid, resulted in nearly complete regression of the lesions over a period of 4 weeks, whereas systemic cyclosporin A treatment was ineffective.

Adrenal Cortex Hormones↗
PubMed1992

Acute human vs. mouse graft vs. host disease in normal and immunodeficient mice.

Recent reports of persistent engraftment of human lymphocytes and myeloid cells in hereditary immunodeficient severe combined immunodeficient mice (SCID) and beige athymic nude X-linked immunodeficiency (Bg/Nu/XID) mice have raised the question of why attempts to graft human cells into artificially immunosuppressed normal mice have failed so far. In the present study we provide evidence that this difference is due to the absence of natural antibodies in the mutant mice. We demonstrate that human PBL can be grafted in normal mice immunosuppressed by heavy doses of total body irradiation, provided the transplant is performed when the recipients lack natural antibodies in their serum, e.g. as in newborn normal mice, in mice treated with anti-mouse IgM antibody from birth, and in 3-week-old B cell-deficient CBA/N mice. In all cases, large numbers of human PBL were required. Under these conditions an acute and fatal graft vs. host disease (GVHD) developed in the recipients, regardless of whether these were artificially immunosuppressed or hereditary immunodeficient. The clinical manifestations and the histopathology of this xenogeneic acute GVHD are quite different from those of allogeneic GVHD. The former is primarily confined to the hematolymphoid tissues and locations close to accumulations of proliferating lymphoblasts, such as the peritoneal cavity in case of i.p. transplantation. The discordant xenogeneic GVHD is induced by human T lymphocytes and can be abrogated by treatment with anti-human T cell serum.

Acute Disease↗
PubMed1991

Monoclonal gammapathies in long-term surviving rhesus monkeys after lethal irradiation and bone marrow transplantation.

Late effects of total body irradiation and subsequent autologous bone marrow transplantation on the development of age-related monoclonal gammapathies (MG) were studied in 14 long-term surviving Rhesus monkeys. Together with 27 untreated control monkeys, they have been followed up for more than 20 years. In contrast with the control group, the experimental monkeys developed MG with aging in higher frequencies, earlier and mainly of the benign MG category. One experimental monkey developed a multiple myeloma, the first observed in the nonhuman primates so far. These results indicate an accelerated senescence of the immune system in the experimental monkeys as a late consequence of tissue or cell damage during irradiation.

Animals↗
PubMed1991

Flow cytometric DNA measurement and cytomorphometric analysis of formalin fixed rat mammary tumours.

Archival paraffin embedded material was used to examine whether additional quantitative criteria would be helpful to discriminate between histologically benign and malignant rat mammary tumours. To this end nuclear DNA content expressed as DNA ploidy index (DI) was measured using flow cytometry (FCM). A total of 63 benign and malignant mammary tumours were investigated. Thirteen out of 38 (34%) mammary carcinomas were DNA aneuploid against 0 out of 25 benign mammary tumours. Aneuploidy was not significantly increased in tumours showing histological signs of greater malignancy such as cribriform-comedo type or invasive growth. In addition to DI other quantitative criteria indicative for malignancy, such as mitotic count and nuclear morphometric characteristics, were estimated in 24 benign and malignant tubulopapillary tumours, a category where the histological classification may be difficult. It appeared that five out of nine noninvasive tubulopapillary carcinomas and six out of seven invasive carcinomas had abnormal values for either DI, mitotic count or nuclear area or for a combination of these parameters. Each single parameter however was abnormal only in a minority of the malignant tumours. In this respect our data are in accordance with the fact that rat mammary carcinomas are clinically and histologically less malignant than their human counterparts.

Adenocarcinoma↗
PubMed1991

Relative biological effectiveness for neutron carcinogenesis in monkeys and rats.

The risks of total-body irradiation with large doses of X rays (average dose 6.7 Gy) and fission neutrons (average dose 3.4 Gy) were investigated by keeping a group of long-term surviving monkeys from an experiment on acute effects under continuous observation. On the basis of the number of animals developing tumors in each group as a function of the total observation period and the average absorbed dose, relative biological effectiveness (RBE) values between 4 and 5 have been derived at these high dose levels. In experiments on mammary carcinogenesis in rats the highest RBE values are observed for neutrons with energies of 0.43 to 1 MeV as produced by the p + T reaction or by the fission process. Based upon linear dose-response curves for neutrons and X rays, a maximum RBE value of 15 was observed for induction of adenocarcinomas in WAG/Rij rats. Appreciably higher RBE values would be obtained if the results of the gamma-ray exposure, indicating a nearly quadratic dose-response relationship, were used as a baseline. For radiation protection applications it should be realized, however, that such an increase will be caused by the lower efficiency of low-linear-energy-transfer radiation rather than by an increase in efficiency of the neutron irradiation at low doses.

Adenocarcinoma↗
PubMed1990

Experimental immune mediated arthritis in rhesus monkeys. A model for human rheumatoid arthritis?

The induction of experimental arthritis in rhesus monkeys was studied by intradermal immunization of bovine type II collagen and antigens derived from Mycobacterium tuberculosis, Streptococcus pyogenes, and Eubacterium aerofaciens. The tested bacterial antigens proved to be not arthrogenic. Bovine type II collagen induced clinical arthritis in 50% of the rhesus monkeys. Type II collagen induced arthritis in rhesus monkeys proved to be a potential model to study clinical, serological, histological, genetic, and immunologic features associated with human RA.

Animals↗
PubMed1989

Radiation carcinogenesis in experimental animals.

Exposure of man to relatively high doses of ionizing radiation is generally restricted to accidental situations, with very limited knowledge about the actual doses received. Animal experiments can be performed under standardized and controlled conditions and can provide information on the dose-response relationships for radiation carcinogenesis. The risk of inducing neoplastic late effects after total-body irradiation with relatively high doses has been demonstrated for larger animals, such as monkeys and dogs. The bone marrow, the mammary glands and the lungs are among the tissues with the highest susceptibility for radiation carcinogenesis. Experimental results on tumour induction in rodents are summarized with emphasis on the effectiveness in dependence on radiation quality and fractionation or dose rate.

Animals↗
PubMed1988

Chronic toxicity of 3,4,3',4'-tetrachlorobiphenyl in the marmoset monkey (Callithrix jacchus).

Cotton top marmoset monkeys (Callithrix jacchus) were orally dosed with 3, 1, 0.1 or 0 mg 3,4,3',4'-tetrachlorobiphenyl (TCB)/kg body weight twice per week for 18-23 weeks. Severe toxicity occurred in the highest dose group. Clinical signs of toxicity were a rapid decrease in body weight, alopecia, abnormal nail growth, nodular enlargement of the nipple area and scaly skin. Haematological analysis of peripheral blood revealed mild leukocytosis and anemia. Biochemical alterations observed were elevated triglyceride levels and cholesterol levels. Histopathology revealed dose dependent changes in a variety of tissues. Squamous metaplasia was found in skin and adnexa as well as in salivary glands. In the stomach, parietal cells were decreased and mucus producing cells were increased. The duodenal mucosa was hyperplastic. Ovaries showed an absence of corpora lutea. In the thyroid follicular cell hyperplasia and hypertrophy were noted. Toxicity was less severe in marmoset monkeys dosed with 1 mg TCB/kg, while minor toxic effects were observed in the animals dosed with 0.1 mg TCB/kg. The marmoset monkey appears to be less sensitive to the toxic action of TCB than the rhesus monkey. The pattern of histological and biochemical changes induced by TCB in marmoset monkeys is comparable to that described in humans and in other primate species exposed to PCBs. The marmoset monkey model may be valuable for investigations on human-related toxicity of PCBs.

Animals↗