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Biomedical subjects

I R Hart

Publications and source records attributed to I R Hart.

At least 163 records · Page 9Linked to original sources
PubMed1981

Characterization of a murine ovarian reticulum cell sarcoma of histiocytic origin.

We have studied the M5076 tumor, a transplantable murine reticulum cell sarcoma that arose spontaneously in the ovary of a C57BL/6 mouse. This tumor displays functional and ultrastructural characteristics indicating that it is of macrophage origin. Cells from the M5076 tumor are phagocytic, form rosettes with sheep red blood cells, mediate antibody-dependent cellular cytotoxicity against 51Cr-labeled red blood cells, and display macrophage-like cytotoxicity against syngeneic tumor target cells but do not exhibit any natural killer cell activity. The tumor cells possess lysozyme, nonspecific esterase, and phosphatase activities comparable to that seen in rodent macrophages. Ultrastructural examination revealed phagocytic vacuoles and a lack of tight junctions typical of macrophage morphology. Karyotype analysis showed that M5076 tumor cells are hypodiploid with a high percentage (greater than 80%) of metacentric chromosomes that serve as an excellent marker for identification of these tumor cells.

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PubMed1981

Metastatic behavior of a murine reticulum cell sarcoma exhibiting organ-specific growth.

The metastatic properties of the M5076 tumor, a reticulum cell sarcoma of ovarian origin, were examined. This tumor metastasizes preferentially to the peritoneal viscera (liver, ovaries, spleen, and kidneys) regardless of the site or route of tumor cell injection. Subcutaneous tumor growth followed by direct invasion into the peritoneum resulted in extensive generalized peritoneal involvement. However, when tumor cells were injected in the dorsum, external ear, or footpad, fewer and primarily hepatic metastases developed. Hepatic, splenic, ovarian, and renal tumor colonies were formed after i.v. injection of tumor cells. Radiolabeled tumor cells were used to study the arrest, distribution, and survival of tumor cells injected i.v. These tumor cells were rapidly arrested in the lungs and were retained there for 3 to 4 days. They then slowly detached, recirculated, and were arrested in the liver, where they subsequently developed into tumor nodules. These results strongly support the "soil-seed" hypothesis of metastatic growth and demonstrate that long-term retention of tumor cells in an organ need not result in the formation of a clinically obvious tumor nodule.

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PubMed1981

Biological and experimental consequences of the zonal composition of solid tumors.

The K-1735 melanoma is a transplantable murine tumor which, when growing s.c., is composed of melanotic and amelanotic areas. Results from trocar transplantation studies of tumor fragments show that expression of this phenotypic diversity can be terminated within very few passages. In parallel experiments, passage of cell suspensions derived from the whole tumor maintains this heterogeneity of melanin production. The implications of these findings are discussed.

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PubMed1980

Murine melanoma: a model for intracranial metastasis.

A variant subline (B16-F10-B2) selected from the B16-F10 melanoma cell line, shows greater metastatic capacity and preferential growth in the brain after i.v. injection into C57BL/6 mice. Several biological properties of these two cell lines have been compared, in an effort to determine the mechanisms responsible for this non-random metastatic pattern. No differences in cell morphology, in vitro growth rates or exposed cell-surface proteins were detected. Quantitative analysis of tumour-cell arrest and distribution using 125IUdR-labelled cells indicated that, although initial arrest patterns of the cell lines were very similar, B16-F10-B2 cells survived in the lungs to a greater cell line had a higher mean number of chromosomes than the parent line, whereas the variance of chromosome distribution was less. We suggest that the selection of a brain-colonizing variant represents the emergence of a pre-existing subpopulation of cells, and provides a useful model for studying mechanisms of intracranial metastasis.

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PubMed1980

Cancer invasion and metastasis.

Metastasis, the spread of neoplastic cells from a primary site to distant organs, is responsible for the majority of cancer deaths. Dissemination of malignant cells throughout the body and their survival to form secondary growths is a complicated process dependent on both host and tumor properties. Although a primary tumor may release many cells, only a few survive the interactions with host defense mechanisms to yield distant cancer growths. In recent years a considerable body of evidence has accumulated which suggests that the survival of these few cells is not a random event. Rather, it represents the selection of a pre-existent metastatic subpopulation of tumor cells within the parental population. Such a process has profound implications in determining approaches to therapy and to the elucidation of those tumor-cell properties which are responsible for successful metastatic spread. These implications are discussed within the framework of what is at present known about the pathogenesis of cancer metastasis.

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PubMed1980

Effect of cytoskeleton-disrupting agents on the metastatic behavior of melanoma cells.

The effects of treatment with colchicine, cytochalasin B, and low temperature (4 degrees C) on the metastatic behavior of the B16-F10 melanoma cell line were examined. The growth of metastases and the distribution of radiolabeled tumor cells were monitored in inbred C57/BL6 mice given iv injections of B16-F10 cells. Cells treated previously with both drugs, but not with low temperature, produced fewer lung nodules than did control cells and displayed alterations in tumor dissemination patterns. In vitro studies revealed that both drugs reduced the rate of adhesion of the tumor cells to bovine endothelial cell monolayers, the rate of migration from agarose droplets, the formation of homotypic aggregates, and agglutination by wheat germ agglutinin. The drugs also induced morphologic alterations of the cells grown in monolayer culture but had little effect on cell volume.

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PubMed1980

In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties.

New assay methods have been devised to quantitate tumor cell invasion of tissues of differing histological complexity maintained as organ cultures in vitro (chorioallantoic membrane of chicken, mouse urinary bladder, and canine blood vessel. In addition to quantitating tumor cell invasion, these methods also allow recovery of invasive cells for comparison with noninvasive cells. These methods have been used to select variant sublines from murine B16-F1 and B16-F10 melanoma lines that display significantly greater tissue-invasive abilities than the parent lines. B16 variant sublines selected in vitro for increased invasiveness through the bladder wall or vein also show a significant increase in their ability to form spontaneous and experimental metastases in vivo. In contrast, cells from the same parent cell line selected for increased invasiveness through the chorioallantoic membrane do not show significant alterations in metastatic behavior. We conclude that invasive variants can be isolated from the parent B16 tumor by several in vitro methods and that the level of expression of the invasive phenotype in vivo may be determined by the severity of the selection procedure in vitro.

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PubMed1980

Role of organ selectivity in the determination of metastatic patterns of B16 melanoma.

The preferential growth of B16 melanoma metastases in specific organs was studied. Following the i.v. injection of B16 melanoma cells into syngeneic C57BL/6 mice, tumor growths developed in the in situ lungs and in grafts of pulmonary or ovarian tissue implanted either s.c. or i.m. In contrast, neoplastic lesions failed to develop in control grafts of similarly implanted renal tissue or at the site of a surgical trauma. Parabiosis experiments suggested that the growth of the B16 melanoma in ectopic lung or ovary tissue was due to the immediate arrest of circulating neoplastic cells and not to shedding of malignant cells from foci growing in the in situ lungs. Quantitative analysis of tumor cell arrest and distribution using cells labeled with [125I]-5-iodo-2'-deoxyuridine indicated that the growth of tumors in the implanted organs was not due to an enhanced initial arrest of B16 cells. No significant differences in immediate tumor cell arrest were detected between implanted fragments of lungs (tumor positive) and kidney (tumor negative) or between organ-bearing and contralateral control limbs. We conclude that the outcome of metastasis is dependent on both tumor cell properties and host factors. This conclusion supports the "seed and soil" hypothesis to explain the nonrandom pattern of cancer metastasis.

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PubMed1979

Binding of canine IgM and IgG to protein A of Staphylococcus aureus: a simple method for the isolation of canine immunoglobulins from serum and the lymphocyte surface.

The binding of normal canine serum IgG and IgM to staphylococcal protein A is described. Virtually all (greater than 99%) of IgG and up to 90% of IgM could be removed from canine serum, utilizing this phenomenon. The nature of the bound material was confirmed by immunodiffusion in agar, radioimmunoassay, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Attempts to elute differentially IgG and IgM from protein A-Sepharose columns, using gradients of pH or the chaotropic agent sodium thiocyanate, were unsuccessful. This phenomenon provides a basis for the isolation of canine IgM from serum. Lymphocyte surface IgM, studied by lactoperoxidase-catalyzed membrane radioiodination and solubilization in nonionic detergent, also showed the property of binding to staphylococcal protein A.

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PubMed1979

The distribution of immunoglobulin-containing cells in canine small intestine.

Peroxidase conjugated antisera to canine immunoglobulins G and A and to human immunoglobulin M, have been used to study the distribution of immunoglobulin-containing cells in the small intestine of the young and adult dog. At all levels of the small bowel of the adult dog, IgA:IgM:IgG cells have a 2:1:1 ratio while the greatest number of immunocytes is found in the duodenum and decreases towards the distal portion of the small intestine. The young puppy shows a predominance of IgM-containing cells in the small intestinal lamina propria during early life but the adult pattern of immunocyte distribution has been achieved by weaning.

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PubMed1979

The selection and characterization of an invasive variant of the B16 melanoma.

Several in vitro properties of two variant cell lines of the B16 melanoma (B16-F10 and B16-BL6) with markedly different spontaneous metastatic behavior were examined. The two cell lines were compared with regard to their in vitro growth rate, ability to migrate, ability to adhere to a variety of substrata, detachment rates, production of plasminogen activator, and cell surface proteins as determined by lactoperoxidase-catalyzed iodination. Growth rates in vitro, attachment rates, and qualitative patterns of cell surface proteins were almost identical. B16-F10 cells (the less spontaneously metastatic line) produced greater amounts of plasminogen activator, were more motile in vitro, and detached more readily from plastic than the more invasive B16-BL6 cells. The study of tumor cell variants, selected for different biologic behavior, is a valuable approach to the elucidation of those mechanisms responsible for their malignant activity.

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PubMed1978

The quantitative assessment of normal canine small intestinal mucosa.

Quanitative methods of assessing the architecture of small intestinal mucosa have been applied to biopsy material from normal dogs. Mucosal samples taken from four predetermined sites show that there are significant quantitative differences between the various levels of the small bowel. Animals of one year of age and older show no correlation between age or weight and mucosal dimensions. The significance of these findings, in relation to examination of biopsy material from cases of clinical small intestinal disease, is discussed.

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PubMed1978

The quantitative assessment of mucosa in canine small intestinal malabsorption.

Histological sections from the small intestines of dogs showing clinical signs of small intestinal malabsorption have been examined using morphometric techniques. Weibel graticule measurements appear to be a useful adjunct to the subjective assessment of villus atrophy. Severe clinical signs of small intestinal malabsorption may be associated with a patchy distribution of lesions throughout the small bowel.

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