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Biomedical subjects

C Zurcher

Publications and source records attributed to C Zurcher.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects of 3,4,3',4'-tetrachlorobiphenyl on thyroid function and histology in marmoset monkeys.

Marmoset monkeys were treated with oral doses of 0.1, 1 or 3 mg 3,4,3',4'-tetrachlorobiphenyl (TCB) per kg body weight 2 times a week for 18-23 weeks. Histological examination of the thyroid gland revealed a dose-dependent follicular cell hyperplasia. The morphological changes were associated with various disturbances of thyroid function. The average serum thyroxine (T4) levels during the treatment period were reduced by more than 99% in monkeys receiving 3 mg TCB/kg, by 81% in marmosets on a dose of 1 mg TCB/kg, and by 35% with 0.1 mg TCB/kg. The reduction in serum T4 levels was established from the earliest time point (2 weeks) throughout the whole dosing period (18-23 weeks). The reduction in serum T4 levels was reflected in decreased free thyroxine (FT4) index in the 1 and 3 mg TCB/kg dose groups. Serum triiodothyronine (T3) levels were lowered in the 3 mg/kg dose group already after 2 weeks. Evidence for decreased binding to carrier proteins is suggested by increased T3 resin uptake in the highest dose group. Levels of thyrotropin (TSH) were increased in the highest dose group as a feedback response to the dramatically reduced serum T4 levels.

Animals↗
PubMed1988

Development and application of a rat tumor model for human bronchial carcinoma.

Five squamous cell carcinomas were induced in the lungs of WAG/Rij rats by radiation emitted from isotopes iridium-192 or iodine-125. Tumor fragments were transplanted subcutaneously in syngeneic hosts for propagation of the tumors. A lung cancer model based on implantation of tumor fragments in the lung has been developed. Tumor implants in the lung grew into large invasive squamous cell carcinomas. Metastases in the renal cortex were frequently observed. Tumor growth was determined from repeated chest radiographs. Volume changes after cytostatic treatment could be monitored accurately up to several months. Squamous cell carcinomas transplanted subcutaneously responded as heterogeneously to a variety of cytostatic drugs as did their human counterparts. Responses of the tumor line L17 to doxorubicin were similar when tumors were growing intrapulmonarily or subcutaneously. However, the response of L33 tumors to cisplatin was different, depending on the location. The tumors growing in the lungs provide a model for realistic testing of regimens involving radiation doses, cytostatic drugs, and combinations thereof.

Animals↗
PubMed1987

Differential behavior of human bronchial carcinoma cells in culture.

A feeder layer culture system suited to grow carcinoma cells derived from solid human lung tumors was developed. This report deals with culturing of the four main histological types of lung carcinomas observed in 37 patients: 19 squamous cell, 6 adenocarcinomas, 7 small cell, and 5 large cell carcinomas. The cultures were initiated from 24 fresh human surgical specimens and from 14 human lung tumors grown as xenografts in nude mice. Three different patterns of behavior in culture were found to be characteristic for squamous cell, adenocarcinomas, and small cell carcinomas, respectively. The culture pattern presented by the primary cultures did not appreciably change after passaging in vitro for periods of up to 2 years, even after infinite cell lines were established. Cultures of large cell carcinoma showed one or more of these patterns. From these patterns cells could be cloned and subsequently cultured as separate stable lines. The system described facilitates the identification of specific types of human lung carcinomas almost immediately (within 1 h) after plating (Phase I) as well as during culture.

Adenocarcinoma↗
PubMed1987

Effects of acute graft-vs-host disease on the liver of the brown Norway rat.

In this study we examined the effects of acute graft-vs-host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non-GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase-positive rough ER and the morphological appearance of macrophages as compared to 60% in the non-GVHD liver. The low percentage of fluorescent-positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.

Acute Disease↗
PubMed1987

Lung damage following bone marrow transplantation: II. The contribution of cyclophosphamide.

The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.

Animals↗
PubMed1987

Late effects of cyclophosphamide and total body irradiation as a conditioning regimen for bone marrow transplantation in rats (a preliminary report).

The longterm survival and occurrence of neoplastic and nonneoplastic lesions following total body irradiation (TBI), 8.5 Gy, with or without additional cyclophosphamide (Cy; 100 mg kg-1 i.p.) treatment as a conditioning regimen for bone marrow transplantation (BMT) were studied in male BN/BiRij rats. The two groups of rats that were treated with Cy (Cy and Cy + TBI) that survived beyond 100 days after treatment, had a severely decreased median (post treatment) survival time (Cy + TBI: 14.5 months and Cy: 14.1 months). Survival time in the TBI group was moderately decreased (18.5 months) as compared with the untreated controls (27.2 months). All treatment modalities were carcinogenic according to the raw data. After Cy-treatment a high incidence of, frequently multiple, malignant nerve-sheath tumours (Cy: 66 per cent, Cy + TBI: 31 per cent, controls: 2 per cent) was observed. TBI induced an increased occurrence of a great variety of tumours, especially mesenchymal tumours. This effect was more pronounced in animals receiving TBI alone as compared to animals receiving the combined treatment of Cy + TBI; an effect that most likely resulted from the longer median survival after TBI. The multi-target effect of TBI was also reflected in the occurrence of nonneoplastic effects in a variety of tissues, including high incidences of biliary cysts in the liver and severe testicular atrophy. The most important Cy-induced nonneoplastic lesion was incisor dysplasia, which resulted in feeding problems that could only be partly overcome by administering powdered food. Early mortality in the Cy-treated groups was associated with emaciation and generalized organ atrophy. A more definitive estimate of the late effects of supralethal chemoradiotherapy as part of a treatment of malignant disease has to await the results of various conditioning regimens for BMT in rats employing the acute BN myelocytic leukaemia (BNML) as a rat model for human acute myelocytic leukaemia (AML).

Animals↗
PubMed1987

Changes in vasopressin and testosterone in the senescent brown-Norway (BN/BiRij) rat.

Although earlier reports in the literature suggested degenerative changes in the senescent hypothalamo-neurohypophyseal system (HNS), recent investigation showed hyperactivity of this system in the old Wistar (WAG/Rij) rat. In the brain, changes were found in those sites of extrahypothalamic vasopressin (VP) fiber termination that are testosterone-dependent. In the present study, further evaluation of these changes was performed in male Brown-Norway (BN/BiRij) rats. Immunocytochemical staining of VP binding sites in renal tubuli of the senescent, 33-month-old rats was occasional, and could only slightly be enhanced up to weak staining by in vitro preincubation with the peptide, in contrast to the intense staining observed in young, 3-month-old rats. Although VP plasma levels of young and old rats did not differ significantly and no change in either urine or plasma osmolality was observed, urinary VP concentration and 24-hour urinary VP excretion were significantly increased in senescent rats. The activation of the hypothalamo-neurohypophyseal system (HNS) in the senescent rat seems thus to compensate for a decreased responsiveness to VP in the aged kidney. Testicular weight in the senescent animals declined by 40% and a highly significant decrease of 80-90% was observed in total and free testosterone plasma levels. Consequently, changes in peripheral organs in senescent rats may well underly the changes observed in the brain of these animals.

Aging↗
PubMed1987

Engraftment of stem-cell-enriched bone marrow fractions in MHC-identical dogs after fractionated total-body irradiation.

Discontinuous albumin density gradients were used to obtain enrichment of hemopoietic stem cells and depletion of T lymphocytes in aspirated dog bone marrow. Colony forming units in agar (CFU-C) were determined to evaluate the degree of enrichment achieved. An average CFU-C concentration factor of 12.4 was obtained. All transplantations in the study were carried out between DLA-identical sibling combinations. The number of CFU-C administered varied from 0.2 to 5.5 X 10(5)/kg and the number of nucleated cells transfused varied from 0.1 to 1.0 X 10(8)/kg. Stem cell concentrates were found more difficult to engraft than unmodified bone marrow following standard conditioning with a single total-body irradiation (TBI) dose of 7.5 Gy. The efficacy of different TBI-fractionation schedules for obtaining sustained engraftment of CFU-C-enriched grafts in identical bone marrow transplantation (BMT) was determined. A total dose of 12 Gy TBI delivered in two equal fractions of 6.0 Gy (72-hr interval) resulted in sustained engraftment of stem cell grafts in 7 of 7 evaluable dogs. A TBI dose of 9 Gy in two fractions of 4.5 Gy (72-hr interval) resulted in sustained engraftment in 5 of 7 evaluable dogs. The two dogs with engraftment failure received low total cell numbers (10(7) cells/kg) and low CFU-C numbers. 9 Gy of TBI in two fractions of 4.5 Gy (24-hr interval) resulted in sustained engraftment in 11 of 12 evaluable dogs. A significant improvement of engraftment was obtained by increasing the total dose of TBI, which necessitates fractionation into two fractions of TBI. The lower-total-dose TBI (9 Gy) produced less early and late toxicity than the total high-dose (12 Gy) TBI. The incidence of engraftment was similar for the two dosages, however the recovery of peripheral leukocyte counts was slower after 9 Gy TBI. In the dog, optimal conditioning for lymphocyte-depleted hemopoietic stem cell grafts can be obtained by increasing the dose of TBI and concomitant fractionation.

Animals↗
PubMed1987

The influence of H-2 genetic factors on the development of benign monoclonal gammopathy in ageing H-2 congenic C57BL and BALB mice.

The role of H-2 genetic factors in the development of benign monoclonal gammopathy (BMG) was investigated in six H-2 congenic C57BL and BALB strains (C57BL/10.ScSn and BALB.B: H-2b; B10.D2 and BALB/c: H-2d; B10.BR and BALB.K: H-2k) during ageing. The frequencies of homogeneous immunoglobulins (H-Ig), both single and multiple, in the three C57BL strains were higher than those in the corresponding three BALB strains. No relationship was found with a particular H-2 haplotype. The most frequent H-Ig isotype within the C57BL strains was IgG2a, within BALB.B and BALB.K mice IgG3 and in BALB/c mice IgG1. Categorization of the monoclonal gammopathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 2-5% and 3-9% of the C57BL and BALB mice positive for H-Ig, respectively. Multiple myeloma or B-cell lymphoma were found to be responsible for about 1% of the paraproteinaemias in all strains. Persistent, non-progressive MG, most likely BMG, was detected in 70-81% and 39-46% of the C57BL and BALB mice positive for H-Ig, respectively. The remaining 14-24% and 50-58% of the, respectively, C57BL and BALB mice positive for H-Ig could not be evaluated in time. The H-2 haplotypes under investigation were not associated with the onset, occurrence, multiplicity, persistence or isotype of the MG developing in these H-2 congenic C57BL and BALB strains during ageing.

Aging↗
PubMed1986

A rat lung cancer model based on intrapulmonary implantation of tumour material.

A lung cancer model based on implantation of tumour fragments in the posterior lobe of the right lung of WAG/Rij rats by a surgical procedure has been developed. Two transplantable squamous cell carcinomas which were induced by implanted iridium-192 wires in the lung, were used in this study. The characteristics of these tumours following intrapulmonary implantation are reported with respect to growth rate, invasiveness and metastasizing capacity. The tumour volumes are determined by X-ray chest radiographs. Mean tumour volume doubling times are about 9 days. This system provides a means to evaluate treatment regimens involving irradiation and chemotherapeutic drugs.

Animals↗
PubMed1986

Induction of lung tumors by radioactive isotopes implanted in the rat lung.

Squamous cell carcinomas were induced in the lungs of male WAG/Rij inbred rats by radiation emitted from the isotopes iridium-192 or iodine-125. These isotopes were implanted by a surgical procedure in the lungs of young rats. Forty rats received implants of 192Ir wires and 20 animals, of 125I seeds. In a 14-month observation period, 30 of the 40 animals with implants of 192Ir wires developed tumors. Malignant hemangioendotheliomas occurred with the highest frequency (50%). From the lungs of 12 rats, squamous cell carcinomas were found. In the observation period of 17 months, 3 rats with implants of 125I seeds developed tumors, among which 1 squamous cell carcinoma could be identified. Tumor fragments were transplanted in syngeneic hosts for propagation of the tumors. Histologic appearances of tumors remained constant in subsequent passages. Responses of transplanted tumors growing in the flanks of syngeneic hosts to doses of radiation, methotrexate, or vinblastine were determined. Although the histologic appearances of the 5 squamous cell carcinomas were similar, tumor-doubling times and responses to irradiation and chemotherapeutic drugs were different. Small cell or large cell carcinomas were not observed.

Animals↗
PubMed1985

Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma.

The effects of the treatment of multiple myeloma (MM) with APD-bisphosphonate on bone destruction, the dissemination pattern of the MM, and toxicity for normal and malignant cells were investigated in an animal model, the 5T2 MM. This mouse MM very closely resembles the human disease, including the typical bone lesions. It was demonstrated by radiography, microradiography, and histologic investigation that the treatment of the 5T2 MM with APD-bisphosphonate protected the mice against a loss of bone to a significant extent. It seemed that the treatment with APD not only diminished the bone destruction by the MM but also led to the formation of new bone in already-affected bone tissue. The growth pattern of the MM was not substantially influenced by the treatment, even though there was an indication that APD exerts some cytotoxic effect on the MM cells.

Animals↗
PubMed1985

Lung damage following bone marrow transplantation: I. The contribution of irradiation.

High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. About one-fourth of all BMT patients die from IP. In about half of these cases, an infectious agent, particularly cytomegalovirus, is involved. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at a low dose rate (LDR; 0.05 Gy/min). The dose-response curves found were very steep. In the LDR group, lung function studies were performed. There was a strong correlation between the increase in ventilation rate and the death pattern. The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD50/180 at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors such as remission-induction chemotherapy, cyclophosphamide, methotrexate, cyclosporin A, graft-versus-host disease, etc., might be involved in the high incidence of IIP in man after BMT.

Animals↗
PubMed1985

OKT4 and OKT4A antibody treatment as immunosuppression for kidney transplantation in rhesus monkeys.

A mixture of OKT4+4A monoclonal antibodies (reactive with T4 cells) was tested for its immunosuppressive potential in rhesus monkeys receiving a kidney allograft. The kidney transplant model used in this study was designed to mimic the clinical situation. Therefore, all animals received a low dose of azathioprine and prednisolone, and the effectiveness of monoclonal antibody treatment was assessed in nontransfused and transfused recipients. The treatment very effectively suppressed acute graft rejection in untransfused recipients. In transfused recipients, which show an improved graft survival, no additional favorable effect of OKT4 + 4A treatment was seen when this treatment was given at the time of transplantation. It is possible that transfused recipients that reject their kidney in an acute fashion do not benefit from the OKT4 + 4A treatment because they have generated primed effector cells that belong to a T4-negative subpopulation or a T4-positive subpopulation with high affinity for donor cells. When the OKT4 + 4A treatment was given at the time of graft rejection in transfused recipients, thus treating chronic rather than acute rejection, a modest improvement in graft survival was observed. It seems, therefore, that anti-T4 antibodies will be of limited value for clinical transplantation and should be used in combination with other immunosuppressive drugs.

Animals↗
PubMed1985

Idiopathic paraproteinaemia V. Expression of Igh1 and Igh5 allotypes within the homogeneous immunoglobulins of ageing (C57BL/LiARij X CBA/BrARij)F1 mouse.

The role of genetic factors linked to the immunoglobulin loci and the development of idiopathic paraproteinaemia (IP)--a benign B-cell proliferative disorder--was investigated in F1 hybrid mice of low (CBA/BrARij) and high (C57BL/LiARij) IP frequency strains. Igh1 and Igh5 allotypes were used as markers for the (parental type) origin of homogeneous immunoglobulins (H-Ig) which appeared in the sera of the F1 mice with ageing. The frequencies of H-Ig in the F1 mice were intermediate with those of the parental strains. The isotype distribution of the H-Ig was 27%, 24%, 12%, 12%, 11%, 10%, 3% and 1% for IgG2a, IgM, IgG1, IgG3, IgG2b, IgD, IgA and IgE, respectively. H-Ig of the IgG2 subclass carried the Igh1b (C57BL) allotype in 98% and the Igh1a (CBA) allotype in 2% cases. Of the IgD H-Ig, 70% carried the Igh5b and 30% the Igh5a determinant. The Igh1 allotype distribution in the bone marrow and spleen plasma cells showed a large variation in the Igh1a/Igh1b ratio among old individual mice and often also between bone marrow and spleen within a single animal with or without a H-Ig component. The categorization of the paraproteinaemias on the basis of their origin showed that 10% of the H-Ig were the result of a transient monoclonal B-cell proliferation; multiple myeloma or lymphoma was found to be responsible for about 1% of the paraproteinaemias; H-Ig fulfilling the criteria for IP were detected in about 42% of cases. The origin of the remaining old age paraproteinaemias could not be determined. These data indicate that the F1 mice develop monoclonal proliferative disorders in a manner more similar to the C57BL than to the CBA parental strain. The allotype associated genetic material from the parental C57BL strain was shown to be mainly responsible for the development of IP in ageing F1 mice.

Aging↗