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C Zurcher

Publications and source records attributed to C Zurcher.

At least 73 records · Page 4Linked to original sources

Biological and clinical consequences of longitudinal studies in rodents: their possibilities and limitations. An overview.

Rats and mice are used in gerontological research primarily because of their relatively short life spans, ease of handling, and the relatively low costs of production and maintenance under controlled environmental conditions of large number of rodents as compared to larger laboratory animal species. They are being used as models for studying intrinsic aging processes, processes that give rise to diseases associated with aging, and the influence of environmental factors on these processes. Contrary to the situation in man, longitudinal studies in rodents can be conducted under well controlled environmental conditions. It has been shown that multiple pathology, the hallmark of aging in man, also occurs in inbred strains of rodents. Some of these lesions are genetically determined and some of them are randomly distributed amongst members of the same inbred strain. Serial killing experiments are necessary to obtain information on the time of development of these lesions in order to interpret properly the outcome of investigations. Furthermore, it has been shown that a considerable variation can exist in the observed maximum ages of the longest-lived animals in cohorts of rats kept under well controlled conditions. For this reason, caution should be exercised in interpreting data from studies which claim maximum lifespan prolongation.

Aging↗

Secondary tumors after high-dose cyclophosphamide and total-body irradiation followed by bone marrow transplantation in a rat model for human acute myelocytic leukemia (BNML).

Brown Norway (BN) rats carrying a transplantable acute myelocytic leukemia (BNML) were given a supralethal combination of cyclophosphamide (80-100 mg/kg i.p.) and total-body irradiation (9.0 Gy gamma rays or 8.5 Gy X-rays) followed by isologous bone marrow transplantation. Of 110 long-term survivors (greater than 95 days), 40 (45%) died of a secondary malignancy at a median posttreatment age of 450 days. At a comparable age, non-treated control BN rats show a spontaneous tumor incidence of 5% only, which increased to 83% during the aging process. Thus the latency period for the appearance of tumors was impressively shortened. Tumors of neurogenic origin and acute leukemias were the most prominent types, in contrast with non-treated control rats.

Animals↗

Applicability of solidified water (hydrogel) in laboratory animal care.

Hydrogel was used to provide water in a solid state to rats and mice under laboratory conditions. Hydrogel was easy to handle and readily consumed by the animals. In studies extending over 10 months, no adverse effects on the condition of the animals were observed. Consumption of hydrogel as the sole source of water for nearly 2 months had no effect on the concentration of selected fecal aerobic microorganisms. Histopathological changes were not observed in the tissues of rats and mice kept for periods up to 7 months on hydrogel as the sole source of fluids. The survival time of rats and mice kept on hydrogel after exposure to supralethal doses of total body irradiation did not differ significantly from that of control animals given drinking water in bottles.

Animal Husbandry↗

Alternatives to donor matching for control of graft-versus-host disease.

Graft-versus-host disease (GvHD) after bone-marrow transplantation in dogs is controlled by many different genetic systems. In littermate combinations identical for the major histocompatibility complex (MHC) the number of systems that influence GvHD is related to the number of donor lymphocytes injected. If the number of donor lymphocytes administered is sufficiently low, minor histocompatibility systems do not influence survival after bone-marrow transplantation. With increasing numbers of donor lymphocytes the beneficial influence of MHC matching on GvH incidence and severity disappears and minor histocompatibility antigens, coded for on at least two other autosomal chromosomes as well as possibly the Y chromosome, can cause severe GvHD. In contrast, the X chromosome does not appear to carry a histocompatibility system that is of relevance to GvHD control. The severity and tissue distribution of histological signs of GvHD in recipients of bone-marrow and lymph-node cells from MHC-identical donors are similar to those in recipients of MHC-mismatched bone-marrow cells. Female donors do appear to cause severe GvHD more frequently than males. In contrast to rhesus monkey and human bone-marrow cells, dog bone-marrow cells are negative in PHA tests. This is in accordance with the generally benign course of GvHD in dogs that are treated with bone-marrow cells only from histocompatible littermate donors. The influence of the sex of the bone-marrow donor on GvHD incidence and severity is not reflected in differences between PHA tests with male and female dog lymphocytes. A better predictive test for GvH potential than the PHA test appears to be needed. Alternatives to additional donor selection for the prevention of GvHD in histocompatible recipients appear to be the use of a male donor and the removal of lymphocytes from bone-marrow-cell suspensions prior to transplantation.

Animals↗

A histopathological survey of aged Praomys (mastomys) natalensis.

This histopathological study shows that Mastomys develops a wide variety of neoplastic and nonneoplastic lesions with age. In comparing neoplastic lesions of Mastomys with those generally found in mice and rats, Mastomys is more or less unique with respect to the development of lymphoepithelial thymomas (40%), parathyroid adenomas (11%), prostatic adenocarcinomas (5%), and gastric carcinoids (4%) and the absence of brain, lung, and mammary tumors. Of the nonneoplastic lesions, prostatic (38%), thymic (12%) and parathyroid (11%) hyperplasia, and moderate to severe generalized degenerative joint disease (96%) occur rarely in mice and rats. Within the limits of this study, in which the age of the animals ranged from 18 to 39 months, a clear-cut age-related pattern was seldom found for most of the lesions occurring in Mastomys.

Aging↗

Factors controlling the engraftment of transplanted dog bone marrow cells.

The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrome was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility complex (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rate of hemopoietic recovery correlated with the number of BM cells given. Approximately 2 x 10(7) autologous and 1 x 10(8) MHC identical BM cells.kg-1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogenic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TI were early greying in all animals, and secondary uterine inertia in female dogs after 7.5 Gy TBI. Fertility in males or females was not changed by radiation. An increased incidence of pancreas fibrosis was noted in dogs receiving two fractions of 6.0 Gy TBI.

Animals↗

The effect of aging on the hepatic metabolism of sulfo-bromophthalein in BN/Bi female and WAG/Rij male and female rats.

The effect of aging on sulfobromophthalein (BSP) metabolism was studied in three groups of rats-BN/Bi female and WAG/Rij male and female rats-of different ages ranging from 3 to 30 months. Under Nembutal anesthesia, BSP biliary transport maximum (Tm) and relative storage capacity (S) were determined by a single infusion rate method by directly determining Tm from bile samples collected through a common bile duct cannula. Tm values expressed as micrograms of BSP per min per g of liver were highest in the youngest rate (3-month-old) as compared with the older rats (12-, 24-, 30-month-old) for all three rat groups. Tm gradually decreased as age increased and at the age of 24 or 30 months reached a value of 66 - 70% of the highest values for 3-month-old rats. The percentage of conjugated BSP in the bile measured during the Tm period remained essentially unchanged with age in all three rat groups. S values, expressed as mg of BSP stored per mg or BSP per ml of plasma per g of liver, remained unchanged (BN/Bi female) or even increased (WAG/Rij male and female) with age. As a consequence, S values expressed per rat were higher in older age groups than in the youngest one for all three rat groups. In contrast with previous reports by other authors on man and rats, the BSP Tm appears to decrease with age regardless of rat and sex, while S does not show such a decrease.

Aging↗

Lasting engraftment of histoincompatible bone marrow cells in dogs.

Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

Animals↗

Gastrointestinal decontamination of dogs treated with total body irradiation and bone marrow transplantation.

Procedures for total and selective gastrointestinal decontamination of dogs are described. The selective procedure removed only Gram negative aerobic bacteria, yeast and fungi. Dogs receiving total decontamination were less susceptible to the GI syndrome following total body irradiation (TBI) than dogs receiving conventional care. After TBI and allogeneic bone marrow transplantation, serum albumin levels decreased in conventional animals, but remained normal in totally or selectively decontaminated animals. Exogenous infections occurred frequently in both irradiated, and totally decontaminated animals, but were absent in selectively decontaminated animals. Endogenous infections after total body irradiation were prevented only by total decontamination. Endogenous infections occurred in selectively decontaminated animals, but with milder clinical symptoms than in conventional animals. Appearance of donor type leukocytes and serum gamma globulin was slower in decontaminated animals than in conventionally treated controls. Acute graft versus host disease caused by a limited number of lymphocytes of a DLA identical littermate donor were prevented by selective gastrointestinal decontamination. Complications due to late immune reconstitution obscured the effect of decontamination on delayed graft versus host disease.

Animals↗

Respiratory disease in rats associated with a filamentous bacterium: a preliminary report.

A naturally occurring, chronic disease of the respiratory tract was investigated from the time of its onset to completion of life-time studies in a colony of rats. The disease was characterized by peribronchial lymphoid cuffing, suppurative bronchitis, bronchiectasis and bronchial abscesses. Its onset in the colony occurred a few months after an epizootic of Sendai virus infection. Limited retrospective serological testing indicated that Mycoplasma pulmonis may have been present in the colony at that time and continued to persist throughout life in some rats in the colony. Although of uncertain significance, light and electron microscopy consistently demonstrated many filamentous bacteria between the cilia on respiratory epithelium and free in bronchial exudate in these cases. Attempts to culture this organism on artificial media were unsuccessful.

Animals↗

Aortic body tumours and hyperplasia in the rat.

The histologic features of aortic body neoplasia, hyperplasia, and normal aortico-pulmonary paraganglia were described for a series of 56 rats of several strains. Argyrophilic cytoplasmic granules were demonstrated in chief cells of the aortic body lesions, and electron microscopic examination disclosed the presence of electron-dense, membrane-bound granules in these cells. In a series of ageing rats, hyperplasia and neoplasia of the aortico-pulmonary paraganglia occurred more frequently in female WAG/Rij rats than in males of that strain, and more frequently than in males and females of the BN/Bi strain or of the (WAG X BN)F1 hybrid. No apparent causal relationship to chronic hypoxia could be shown, in that no correlation between the development of aortic body neoplasia or hyperplasia and cardiopulmonary disease was found. Aortic body lesions did not appear to occur as part of a multiple endocrinopathy syndrome, although hyperplasia and neoplasia of various endocrine organs occurred relatively frequently in the WAG/Rij strain.

Aging↗