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Biomedical subjects

M J Van Zwieten

Publications and source records attributed to M J Van Zwieten.

14 recordsLinked to original sources

Effects of chronic oral administration of a selective 5 alpha-reductase inhibitor, finasteride, on the dog prostate.

Young mature dogs received finasteride, a selective 5 alpha-reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size and morphology was evaluated macroscopically and microscopically. Changes in glandular and fibromuscular compartments were quantitated by a point counting method on trichrome-stained sections. Finasteride administration induced a decrease of mean prostatic weights and epithelial atrophy in all treated groups. No changes in testicular weights and morphology were observed. The greatest prostatic shrinkage was obtained in the group receiving 45 mg/kg/day for 53 weeks; compared to placebo controls, the percent decreases in absolute volumes occupied by epithelium, lumens, fibrovascular stroma, and smooth muscle were 88, 97, 51 and 72, respectively. These results clearly demonstrate that prostatic shrinkage following finasteride administration results from a decrease in both glandular and fibromuscular compartments.

Administration, Oral↗

Establishment of a continuous somatostatin-producing line of medullary thyroid carcinoma cells from BALB/c mice.

A continuous line of somatostatin-producing medullary thyroid carcinoma cells was established from a transplantable tumour in BALB/c mice. Virtually all of the somatostatin immunoreactivity co-chromatographed with somatostatin 14. The tumour cells replicated in spinner cultures with a doubling time of approximately 4 days, and the concentration of somatostatin released into the culture medium increased in proportion to the number of cells. Two- to threefold increases in amounts of stored and released somatostatin were observed after treatment of the cells with bromodeoxyuridine. This cell line might be valuable for studies of somatostatin regulation in normal and neoplastic C-cells, and for other studies of C-cell biology which require a mouse model.

Animals↗

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↗

Sera from irradiated rats contain antibodies to a ubiquitous tumour-associated antigen.

Female rats of the inbred strains BN/BiRij and WAG/Rij were irradiated with 30 kV X-rays, or 15 MeV or 0.5 MeV fast neutrons. Sera were collected several months after irradiation and found to be negative for antibodies reacting with the murine mammary tumour virus as tested by a solid-phase radioimmunoassay and an immunofluorescence absorption test. We found, however, that in an immunofluorescence assay several sera from irradiated rats reacted with a cytoplasmic antigen in rat mammary, ureter and skin carcinoma cell lines as well as a mouse mammary tumour and a transformed BALB/3T3 mouse fibroblast line. No reaction was found with normal fibroblast cell lines of rat or murine origin. Endpoint titres of the sera on tumour cells ranged from 1:20 to 1:160. Of 48 sera from unirradiated rats 18 also stained tumour cells, but usually at the low dilution of 1:10. Irradiation seems to enhance antibody activity to a ubiquitous tumour-associated antigen.

Animals↗

Medullary thyroid carcinoma in female BALB/c mice. A report of 3 cases with ultrastructural, immunohistochemical, and transplantation data.

Medullary thyroid carcinoma (MTC) is a neoplasm derived from thyroidal C cells. This tumor occurs spontaneously in several animal species and is relatively common in certain strains of rats. Descriptive reports of such neoplasms in mice, however, have not been published. From several studies using female BALB/c mice, 3 animals were identified that had thyroid neoplasms histologically compatible with MTC. All three primary neoplasms and a first generation transplant from one of them contained calcitonin. Somatostatin was identified in two of three primary thyroidal neoplasms and in the first-generation transplant. Ultrastructurally, the neoplastic cells of the first-generation transplant contained membrane-bound dense-core granules that resembled those seen in normal mouse C cells. Intracisternal Type A retrovirus particles were also identified in neoplastic cells in this case. Transplantation of one of the neoplasms yielded subcutaneous masses averaging 2 cm in diameter by 3 months following transplantation in the second-generation recipients. These neoplasms resemble MTCs of man, rat, and other species and may prove of value for comparative morphologic and endocrinologic studies of C cell neoplasms and for studies of factors that regulate the synthesis and secretion not only of calcitonin but also of a variety of regulatory peptides, including somatostatin.

Animals↗

Experimental cell-mediated interstitial nephritis induced with exogenous antigens.

The capacity of intrarenal injections of bovine gamma-globulin (BGG) to elicit hypersensitivity reactions was studied in guinea pigs immunized with DNP BGG or BGG immune complexes in CFA or in rats immunized with BGG in CFA. In guinea pigs it was found that heat-aggregated BGG elicited inflammatory reactions in the renal cortex, whereas soluble BGG did not. In rats only aggregated BGG was used, and this was found to be effective. The reactions were characterized by a predominantly mononuclear cell infiltrate. Transfer experiments were performed in rats and it was found that reactivity was transferrable with lymph node cells but not with serum.

Animals↗

Glomerulonephritis in the owl monkey (Aotus trivirgatus): ultrastructural observations.

The kidneys of 11 clinically healthy owl monkeys (Aotus trivirgatus) acquired from four different sources were examined by light and electron microscopy. Eight of the 11 animals had morphologic evidence of glomerulonephritis. The lesions were characterized by one or more of the following changes: focal or segmental thickening of the glomerular basement membrane; proliferation of mesangial cells with increased production of mesangial matrix; and fibrosis and hyalinization of glomeruli with and without inflammatory cellular infiltration. Five of the eight animals with one or more of the above described changes had electron-dense deposits compatible with immune complex deposits in the intra-membranous and subepithelial regions of the basement membrane. The nature and source of the antigen or antigens responsible for the lesions are unknown.

Animals↗

Studies on the pathogenesis of experimental anti-tubular basement membrane nephritis in the guinea pig.

Using the model of renal disease induced in guinea pigs by immunization with bovine TBM preparations in adjuvant, the following observations were made. Animals with activity induced disease show bright staining for IgG along the TBM and only faint, inconstant staining along the GBM. Following transfer of serum animals with anti-TBM disease to normal recipients, accumulation of IgG was found predominantly in glomeruli at 4 hours, but at Days 3 and 5, IgG was seen predominantly along the TBM. There was no appreciable accumulation of neutrophils in the kidneys of recipients of anti-TBM serum, even at early intervals (4 and 24 hours) after transfer. However, within 2 days, small numbers of mononuclear cells were found. By Day 3, mononuclear cells were numerous, and multinucleate giant cells and tubular cell damage were present. After that, the lesions increased in severity and by 10 days were indistinguishable from those found in actively immunized animals at 14 to 21 days. Study of frozen section of kidneys obtained from animals with active disease at 14 days, employing sheep cells coated with rabbit antibody (IgG EA) revealed rosettes around many of the mononuclear cells in the infiltrate, indicating that they are mononuclear phagocytes (monocytes or macrophages). IgM complexed with sheep cells and complement (EAC) did not react and thus failed to provide evidence for the presence of B lymphocytes. Transfer of 7 X 10(8) lymph node cells from the TBM-immunized Strain 13 donors to normal Strain 13 recipients failed to result in renal lesions. The findings are interpreted as indicating that anti-TBM antibodies mediate the renal disease without the participation of cell-mediated immunity and further that these antibodies bring about an influx of ciculating mononuclear cells, predominantly monocytes, without attracting appreciable numbers of neutrophils.

Animals↗

Glomerulonephritis in the owl monkey (Aotus trivirgatus).

Glomerular disease was observed in 45 of 57 owl monkeys (Aotus trivirgatus). The disease was minimal in eight of the affected animals and moderate to extensive with respect to severity of the lesions and the number of glomeruli involved in the remainder. The lesions were characterized by proliferation and hypertrophy of mesangial and epithelial cells, increase in mesangial matrix, thickening of basement membranes, and sclerosis. Immunofluorescent staining suggested that the disease was an immune complex glomerulonephritis.

Animals↗

Purification of large quantities of coxiella burnetii rickettsia by density gradient zonal centrifugation.

The purification of large quantities of inactivated, phase II Coxiella burnetii by isopycnic zonal centrifugation for use as diagnostic antigen and as a vaccine is described. The fractionation of egg yolk sac-derived C. burnetii vaccine resulted in the separation of two distinct populations of organisms, each devoid of microscopically and serologically recognizable components of egg yolk sac. One population of organisms, characterized by an equilibrium density of 1.240, was rod shaped (1.0 by 0.5 mumole) with a thick, densely strained wall and prominent central body. The second population, with an equilibrium density of 1.280, had a coccobacillary shape (approximately 1 mumole in diameter), granular, sometimes fibrillar cytoplasm, thin cellular walls, and lacked a prominent nucleoid.

Animals↗