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Biomedical subjects

C T Hansen

Publications and source records attributed to C T Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1984

Immune characteristics of the beige-nude mouse. A model for studying immune surveillance.

Double immunodeficient mice, homozygous for both the beige and the nude genes, were developed on C57BL/6N-beige and N:NIH(S)-nude background through five steps of mating. The animals were healthy and had a life span comparable to that of regular nude mice. Beige and regular nude mice showed a significant difference in natural killer (NK) activity, with mean +/- SE values of 6 +/- 1.0% and 25 +/- 2.8%, respectively. The response to the T-cell mitogens phytohaemagglutinin and concanavalin A was similar in beige and NIH mice of the same genotypes for the nude genes. Both groups of nu/nu mice also showed some response in these assays, as well as in the plaque-forming cell assay, indicating that nude mice are not completely devoid of functional T or T-like cells. The nude genes were found to increase the response to the B-cell mitogen lipopolysaccharide in both the beige and NIH animals, whereas the response was reduced in mice of the beige genotypes. The viable, low NK beige-nude mice here reported on may be a valuable tool for studying factors involved in host defence against tumours. Interestingly, no spontaneous tumours have so far been observed in such mice.

Animals↗
PubMed1984

Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects.

To elucidate the in vivo role of natural killer (NK) cells, the growth of several murine and human tumors was studied in four variants of athymic, nude mice with different levels of NK activity. Beige-nude mice, homozygous for both the beige and the nude genes, had very low levels of NK activity, and their response to the B-cell mitogen, bacterial lipopolysaccharide, was lower than that of high-NK, adult NIH nude mice. Young and adult NIH nudes had different NK levels and showed different response in assays for K-cell, T-cell, and B-cell activity. The B-cell-defective NIH-II mice had slightly lower NK levels than adult NIH animals, but much lower response in the antibody-dependent cell-mediated cytotoxicity assay. No correlation was found between host NK activity and the s.c. growth of various human (LOX, CEM, K562) and murine (YAC-1) tumor cells. Low NK activity was not associated with increased lung colony formation in a metastasis model using i.v.-injected human (LOX) and murine (B16F10) melanoma cells. No relationship was found between host NK activity and the rate of elimination of i.v.-injected 5-iodo-2'-deoxyuridine-labeled LOX, B16F10, and YAC-1 cells from lungs, liver, or spleen. The results fail to support the view that NK cells exert significant direct effects on tumor cells in vivo.

Animals↗
PubMed1982

Strain and sex variation in the susceptibility to streptococcal cell wall-induced polyarthritis in the rat.

Sixteen inbred rat strains were examined for susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis. The findings indicated that 2 or more genetic loci, as well as sex-related factors, played a major role in determining susceptibility to arthritis in this model. Breeding studies demonstrated that susceptibility was a dominant or codominant trait. A positive association between the severity of arthritis and the development of chronic inflammation in multiple tissues was also observed. In strains that were relatively resistant to arthritis, chronic inflammation was generally limited to the spleen. Since translocation of the poorly degradable and phlogogenic streptococcal cell walls to the synovium and other tissues appears to initiate inflammation, these studies suggested that susceptibility might be the result of a defect in host mechanisms limiting cell wall dissemination.

Animals↗
PubMed1982

Natural killer cell activity in the rat. Analysis of effector cell morphology and effects of interferon on natural killer cell function in the athymic (nude) rat.

Athymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3- to 5-fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2- to 7-fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinuous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL-enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single-cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate-forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the target cell tested.

Animals↗
PubMed1982

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

Alloxan↗
PubMed1981

Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenotype.

The genetic basis for autoimmunity in NZB mice has been investigated through analysis of recombinant inbred lines produced by mating NZB mice with two different non-autoimmune strains. Several genes (at least six) were found to be necessary for the production of eight traits characteristic of the NZB mice that were studied. No fundamental genetic defect (an "autoimmunity gene") was identified that could give rise to the various autoimmune traits studied. This study strongly suggests that NZB disease results from the actions of several separate genes that together result in the characteristic manifestations of autoimmunity.

Animals↗
PubMed1981

T cell abnormalities in NZB mice occur independently of autoantibody production.

By means of a series of crosses and backcrosses, ZB.CBA/N mice were prepared bearing largely NZB autosomal genes, but having X chromosomes derived only from CBA/N mice. The CBA/N X chromosome carries a gene, xid, that is associated with the lack of a B cell subset necessary for most of the spontaneous autoantibody production by NZB mice. These ZB.CBA/N mice failed to develop autoantibodies to T cells, erythrocytes, or DNA. The availability of mice that were mostly NZB, but which failed to make autoantibodies, especially anti-T cell antibodies, allowed us to study possible T cell regulatory defects in NZB mice in the absence of either antibodies reactive with such T cells or other autoantibodies. We found that such mice had derangements of T cell regulation as did the NZB mice. These observations strongly suggest that the t cell abnormalities of NZB mice are not caused by the B cell hyperactivity of these mice, but rather represent independent defects. Thus, NZB mice appear to have primary defects in both the B cell population and the T cell population. Whether or not these are separate, or derive from a common precursor cell abnormality, remains to be determined.

Animals↗
PubMed1981

Studies on congenital osteopetrosis in tl and ia rats using organ culture.

We studied bone resorption in rats bearing the ia and tl osteopetrotic mutant genes by measuring the release of previously incorporated 45Ca from the long bone shafts of 19-day fetuses. Fetuses from matings of ia/ia to ia/+ rats showed good bone resorptive responses. There was a significant increase in 45Ca release in control cultures compared to killed bones, with further stimulation by parathyroid hormone (PTH) and no bimodal distribution. Fetuses from matings of ia/ia rats to ia/ia rats showed similar resorptive responses. The responses were greater in media supplemented with serum than in media containing bovine serum albumin. Serum from ia/ia rats did not inhibit resorption of ia/ia or normal bones. In contrast, matings of tl/+ to tl/+ heterozygotes produced 18 of 71 fetuses which showed markedly decreased bone resorptive responses and were therefore considered to be tl/tl. These "non-responders" showed no significant cell-mediated control resorption compared with killed bones and no response to PTH, 1,25-dihydroxyvitamin D or prostaglandin E2. The remaining animals, which were presumptive heterozygotes or homozygous normals, showed significant control resorption and responded with further increases to all three stimulators. Morphologically the tibiae from the fetuses of non-responders were not grossly abnormal, but lacked typical multinucleated osteoclasts. Osteoclasts were found in most samples from responsive fetuses.

Animals↗
PubMed1981

A study of mouse strains susceptibility to Bacillus piliformis (Tyzzer's disease): the association of B-cell function and resistance.

Tests were conducted on 11 inbred strains of mice and an NIH outbred stock. It was found that only the CBA/N and C3. CBA/N mice (strains deficient in IgM production) were highly susceptible to Bacillus piliformis infection. Susceptibility to infection was determined by induction of typical surface liver lesions and the ability to maintain serial passage without concurrent administration of cortisone. Mice deficient in T-cell function (Nu/Nu/++) were as resistant to Bacillus piliformis infection as intact immunologically competent mice. The data suggested that resistance to Tyzzer's disease was, at least in part, a B-cell function.

Animals↗
PubMed1980

N:NIH(S)-nu/nu mice with combined immunodeficiency: a new model for human tumor heterotransplantation.

A new "nude" mouse model was developed by successive crossings and backcrossings between athymic nu/nu mice, on an N:NIH(S) background, and female CBA/N mice that have an X-linked immune defect in B-lymphocyte function. The resulting doubly congenic N:NIH(S(II-nu/nu mice maintained the marked thymic hypoplasia and poor development of hair of the nu/nu mice. In contrast to nu/nu and CBA/N mice, in this new mouse model both T-cell zones of lymph nodes and the spleen were depleted of lymphocytes. Lymphocytic follicles were rare and diminutive; not germinal centers were noted. The nodal cortical and paracortical areas were represented principally by connective tissue, endothelial cells, and macrophages, including giant multinucleated cells. No medullary cords were recognized. The mice with combined immunodeficiency supported the growth of human tumor xenografts and were susceptible to murine viral hepatitis.

Animals↗
PubMed1979

Litter sizes in inbred strains of rats (Rattus norvegicus).

The average litter sizes and reproductive performance of twenty-five inbred strains of rats, maintained in a conventional colony in Pittsburgh, and twenty-six inbred strains, maintained in a barrier facility at the National Institutes of Health, were calculated from data collected for periods of 3 and 10 years, respectively. There were considerable variations in both parameters in each of the two colonies studied. In addition, there were quite wide variations in male to female ratios among inbred strains (0.80 to 1.42).

Animals↗
PubMed1979

Characterization of a congenitally LPS-resistant, athymic mouse strain.

C57BL/10ScN (nu/nu) mice have B cells and macrophages unresponsive to a phenol-water extracted preparation of Escherichia coli K 235 LPS. This unresponsiveness was demonstrated in vitro by the inability of spleen cells to incorporate 3H-thymidine after a 48 hr incubation with LPS (Ph) and by the inability of LPS (Ph) to inhibit macrophage phagocytosis of 51 Cr-labeled, opsonized sheep erythrocytes. Furthermore, macrophage cultures stimulated with LPS (Ph) produced low levels of LAF and PGE2 when compared with macrophages from the LPS-sensitive C3H/HeN and C3H/HeN (nu/nu) strains. Therefore, the C57BL/10ScN (nu/nu) strain is similar in its LPS unresponsiveness to the well-characterized C3H/HeJ and C57BL/10ScCR strains. The combination of endotoxin unresponsiveness and the athymic nature of this mouse strain may provide a powerful new tool for studying the cellular events mediating endotoxicity.

Animals↗