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Biomedical subjects

J P Harlos

Publications and source records attributed to J P Harlos.

At least 19 recordsLinked to original sources
PubMed1993

Atypical hyperplasia: frequency and mammographic and pathologic relationships in excisional biopsies guided with mammography and clinical examination.

PURPOSE: To ascertain the frequency and pathologic relationships of atypical hyperplasia in biopsy specimens obtained after clinical and mammographic examination. MATERIALS AND METHODS: Clinical, mammographic, and histologic findings were prospectively correlated in 300 consecutive excisional biopsies. RESULTS: Atypical hyperplasia was detected in 26 (17%) of 154 biopsies with benign findings and 19 (13%) of 146 biopsies with malignant findings overall (P > .05). The frequency of atypical hyperplasia was only 4% (two of 55 specimens) in clinically prompted biopsies with benign findings but 24% (24 of 99 specimens) in mammographically prompted biopsies with benign findings (P = .002), increasing to 31% (21 of 68 specimens) in benign microcalcifications and 40% (18 of 45 specimens) in benign microcalcifications associated with adenosis. Atypical hyperplasia was found most often within (16 [62%] of 26 cases) or adjacent to (nine [35%] of 26 cases) another lesion that prompted biopsy. CONCLUSION: Most atypical hyperplasia is not a random finding in benign biopsy specimens but shows a statistically significantly greater frequency in association with microcalcifications detected with mammography only, especially those in areas of adenosis.

Biopsy↗
PubMed1991

Collagen production by macrophages in tumour encapsulation and dormancy.

Dormant and regressing implants of C3H mammary carcinoma MC2 were always found to be surrounded by a cellular fibrous capsule where macrophages and T cells predominated as the cellular elements. Macrophages were always closely associated with the collagen deposition, and stained with anti-collagen type I immuno-peroxidase in tissue sections. The capacities of macrophages and T-lymphocytes to function in collagen formation was investigated with the use of Nucleopore chambers implanted i.p. in normal mice. The procollagen that entered the chambers via the pores, was assumed to have been produced by the packed layer of peritoneal macrophages that adhered firmly to the outside of washed chambers. The adherent cells all stained with Mac-1 immuno-peroxidase, and phagocytosed yeast in short-term culture. The formation of collagen fibres in the chambers was enhanced if the chambers contained T lymphocytes. It appears that macrophages have the capacity to function as collagen producing cells in tumour encapsulation.

Animals↗
PubMed1991

Measurements of compression of Ehrlich ascites tumor cells and their relevance to hematogenous metastasis.

Ehrlich ascites cancer cells were compressed between glass microscope slides by the addition of weights. The projected areas of the cells were measured, and their surface membrane integrity determined by means of trypan-blue exclusion tests under different compression loads of 0 to 800g. The results are compatible with a two-step mechanism for surface rupture; first the cell membrane is unfolded and then stretched, with modest degrees of stretching associated with membrane rupture. It is calculated that lethal surface membrane rupture of the type produced here by compression, could also be produced when cancer cells are deformed by entry and passage along relatively non-deformable capillaries. This would at least partially account for the rapid destruction of cancer cells in the microcirculation. The observation that isolated nuclei are less deformable than whole cells, may indicate that their nuclei may protect cancer cells from biomechanical trauma.

Animals↗
PubMed1990

Mechanisms for the biomechanical destruction of L1210 leukemia cells: a rate regulator for metastasis.

Mechanical trauma appears to be one significant cause of the rapid intravascular death of cancer cells and, as such, could act as an important rate regulator for the metastatic process. Intravascular mechanical trauma to cancer cells is thought to be a consequence of shape transitions, occurring when they are deformed from spherical shape by entry into, and passage along, capillaries having smaller diameters than themselves. These transitions from spherical shape require increases in surface area; first, an apparent increase in surface area is accomplished by a reversible, nonlethal surface membrane unfolding. If this is insufficient to meet geometric demands, it is followed by a true increase in surface area, resulting in increased tension in the cancer cell surface membrane, leading to its lethal rupture.

Animals↗
PubMed1989

Mechanism of mechanical trauma to Ehrlich ascites tumor cells in vitro and its relationship to rapid intravascular death during metastasis.

Many, if not most, of the cancer cells arrested in the microvasculature during metastasis appear to be rapidly killed by mechanical trauma, associated with shape-transitions, which require increases in cell surface area. The hypothesis has been advanced that such increases in surface area occur in 2 phases: First, there is an apparent increase due to surface unfolding, which is reversible and non-lethal. Second, there is a true increase, during which cell surface membranes are stretched, with an increase in membrane tension. When tension exceeds a critical level, the surface membranes rupture and this irreversible change is lethal. In the present study, cell surface area has been incrementally increased by a hypotonic environment. Down to approximately 70 mM/kg, a reversible, non-lethal increase in cell volume was observed, associated with electron microscopic evidence of unfolding. At and below 70 mM/kg, irreversible, lethal changes occurred, associated with increased susceptibility to the mechanical trauma associated with membrane-filtration. These observations are consistent with the hypothesis in question.

Animals↗
PubMed1988

Metastatic patterns of renal carcinoma: an analysis of 687 necropsies.

The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.

Adult↗
PubMed1987

Influence of the administration schedule on the therapeutic effect of interleukin-2.

The local and systemic therapeutic effects of multiple peritumoral injections of recombinant human interleukin-2 (IL-2) were tested against the syngeneic, immunogenic mammary carcinoma MC2 implanted subcutaneously into C3H/He mice. Multiple (12) low-dose injections had a greater local therapeutic effect than the same total amount of IL-2 given in 2 injections. Peri-tumoral injections were equally effective in inhibiting the growth of the injected tumors in normal and in immunized mice. The systemic therapeutic effect was manifested by the inhibition of tumors implanted contra-laterally to the injected tumors, and was only discernible in non-immunized mice.

Animals↗
PubMed1987

Spontaneous metastasis from primary C3H mouse mammary tumors.

The normal incidence of metastasis was determined in 207 C3H/He and 42 C3Hf/He mice with spontaneous mammary tumors. The effects of early versus delayed surgical removal of the tumors on the incidence of metastasis were studied in the C3H/He mice. The presence of metastases was determined by histological examination, primarily of the lungs. The incidence of metastasis was proportional to the size the primary tumors were allowed to reach before surgery, with the highest incidence in mice not surgically cured. Tumors that developed early in the life of the mice had the greater tendency to metastasize. Immunogenic and non-immunogenic tumors occurred with similar frequency among 16 metastasizing tumors tested. Primary tumors and their metastases were equally immunogenic. All of 95 metastasizing adenocarcinomas grew extensively within pulmonary vessels with no tendency for active extravasation. In contrast, each of six metastasizing mammary sarcomas extravasated actively and probably extravasated early because intravascular growth was never observed.

Adenocarcinoma↗
PubMed1986

The stability of kidney-induced selection of Lewis lung tumor cell populations, and their metastasis-related behavior.

The surface charge densities of Lewis lung carcinoma (3LL) cells were measured in tumors transplanted into subcutaneous (s.c.) sites, and into the kidneys (K), as well as in kidney tumors transplanted to, and maintained in, the s.c. site (K.s.c.). K cells showed a significant increase in net negativity in comparison with s.c. cells, which was stable over II passages. On back-transplantation of K cells to the s.c. site, the net negativity of K.s.c. cells was higher than that of the s.c. cells, but the increase was stable for only 7 passages; on subsequent passages the net negativity fell, approaching that of the s.c. cells. Detailed analyses suggest the presence in these tumors of 2 subpopulations of 3LL cells, whose proportions change in the different sites studied to produce changes in the mean electrophoretic mobilities of the whole cancer cell populations. The altered proportions of the 2 cell types in the 3 sites were not associated with major changes either in their general behavior with respect to metastasis, or in differential growth in various organs following s.c., tail vein, and left ventricular injections. Selection induced by growth in the kidney, as evidenced by physiochemical changes at the cancer cell surface, was not associated with kidney preference in metastasis or metastasis-related behavior.

Animals↗
PubMed1986

The validity of negative necropsy reports for metastases in solid organs.

This communication concerns the statistical significance of negative reports, when solid organs are examined for metastases deep to their surfaces, by standard slicing techniques at necropsy. By taking into account factors influencing tumour detection including slice thickness, metastatic tumour size and number, the probabilities of incidence of false negative reports may be calculated and values for the undetected tumour bulk may be obtained. A graph is reproduced which facilitates the assessment.

Autopsy↗
PubMed1984

Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells.

The arrest of B16 melanoma cells and the subsequent development of tumors have been studied following left intraventricular injections (LVI) into mice of radiolabelled and unlabelled cells respectively; the proportions of cardiac output going to different target organs were also determined by LVI of radiolabelled microspheres. B16 cell arrest in the various target organs was as predicted by relative arterial blood supply, except in the lungs and liver where more radioactive counts were detected than could be accounted for in terms of initial arterial dissemination alone; and the numbers of counts remaining in all organs after 24 h were related to the numbers of counts initially obtained. When the incidence of tumor-bearing organs was related to the cell arrest patterns, the organs could be divided into two major distinct groups. Within both of these groups, the patterns of tumor incidence were correlated with cancer cell delivery. These results on a model system suggest that the two major hypotheses used to account for metastatic patterns are not mutually exclusive: the "soil" effect divides the target organs into the two major groups; however, within these groups the incidence of tumors is explicable in terms of the "mechanical" hypothesis.

Animals↗
PubMed1983

Differences in the peripheries of Lewis lung tumor cells growing in different sites in the mouse.

The peripheries of Lewis lung (3LL) tumor cells growing in different organs of the mouse were studied by cell electrophoresis and electron microscopic quantitation of colloid iron hydroxide (CIH) adsorption before and after incubation with neuraminidase. The results show that cells growing in the kidney after direct injection have significantly higher anodic mobilities than cells growing in the subcutaneous sites from which they were derived, or in intramuscular sites, liver or spleen. The proportional contributions of cell surface sialic acids were similar in all sites. Electron microscopy of cells reacted with CIH indicates that the increased surface charge density of the tumor cells growing in the kidney is due to the presence of increased densities of non-CIH-binding ionogenic groups. Before neuraminidase treatment, the surface distribution patterns of CIH were indistinguishably random for 3LL cells growing in all sites. After neuraminidase treatment, significantly more clustering of CIH particles was observed on 3LL cells with a history of growth in the kidney than in subcutaneous sites. The changes observed in the 3LL cells growing in the kidney were irreversible, and persisted on multiple back-transplantation to subcutaneous sites. Detailed analysis of the results shows the changes to be due to the preferential selection of a subpopulation consisting of approximately 10% of the original (subcutaneous) tumor-cell population. This evidence for an irreversible site-induced selection of a pre-existing sub-population of 3LL cells contrasts with the reversible (modulation) site-induced adaptation previously observed by us in Walker-256 cancer cells, and therefore indicates that both selective and adaptive processes can occur. Even in the case of the 3LL cells, site-specific selection is not general, since the changes were observed in tumors growing in the kidney but not in the other anatomic sites. At present we cannot comment on the relevance of these reported changes to naturally occurring metastasis.

Animals↗
PubMed1981

The effect of neuraminidase- and ribonuclease-susceptible surface anionic groups on the aggregation of embryonic chick neural retina cells.

The role of cell surface charge in cellular interactions has been the subject of conflicting reports. The major contribution to the net cell surface negativity of all mammalian cells studied is made by the sialic acid moieties of the surface glycoproteins, while ribonuclease-susceptible sites have been shown to contribute to the lesser extent on some cell types. Experiments were done to determine whether these anionic groups at the cell periphery affect the aggregation and sorting behaviour of embryonic chick neural retina cells when cultured alone or in combination with embryonic heart cells. The net negative surface charge density, as determined by cell electrophoretic mobility, of neuraminidase- or ribonuclease-treated cells was significantly decreased immediately after incubation with the enzymes, and the treatment with neuraminidase resulted in a reduction in the binding of colloidal iron hydroxide particles at the cell surface. Both enzymes caused reduced aggregate size in gyratory shaker cultures of neural retina and mixed cell suspensions, and fewer neural retina cells adherent to microtest plate surfaces, but no differences were seen in their histological appearance or sorting pattern in mixed shaker culture. The results indicate that the neuraminidase- and ribonuclease-susceptible groups at the periphery of embryonic neural retina cells play a role in some aspects of cell contact behaviour in ways other than reduction in net negative surface charge.

Animals↗
PubMed1979

On the mechanism of binding of human lymphocyte products to guinea pig macrophages.

When lymphocytes from a majority of patients with cancer are incubated with encephalitogenic factor, a lymphocyte product is released that reduces the anodic electrophoretic mobilities of guinea pig macrophages and fixed, tanned sheep erythrocytes. Although these reactions are not specific for cancer, it is distinctly possible that in patients with cancer, products from stimulated lymphocytes are capable of altering the surfaces of the patients' own macrophages, thereby modifying the course of their disease. In this paper, we attempt to elucidate some mechanisms for the binding of lymphocyte products to macrophages, such as occurs in the macrophage electrophoretic mobility (MEM) test, since this may be of general interest. Binding of lymphocyte product to macrophages has been monitored by measurements of their electrophoretic mobilities and by electron microscopic determination of the density of binding of electron-dense, cationic colloidal iron hydroxide particles to their surfaces. The results show that the lymphocyte products reduce the net surface negativity of the macrophages by (coulombic) binding of this net positively charged material to sialic acids at the macrophage surface. Product-binding can be prevented by prior treatment of the macrophages with neuraminidase. It appears that only a minority of sialic acids are involved in the binding process, which occurs without demonstrable blocking of adjacent sialic acids or redistribution of such sites over the macrophage surface. Parallel experiments with fixed tanned erythrocytes also suggest that binding of lymphocyte product is not solely determined by surface sialic acids, although it cannot occur without them.

Animals↗
PubMed1978

Comparison between the macrophage electrophoretic mobility (MEM) and the fixed tanned erythrocyte electrophoretic mobility (FTEEM) tests in the detection of cancer.

When peripheral lymphocytes from patients with a history of cancer are incubated with encephalitogenic factor (EF), in 90% of cases the resulting products reduce the net surface negativity of guinea-pig macrophages, used as detector cells, as revealed in the macrophage electrophoretic mobility (MEM) test. The MEM test is positive in 36% of people with no history of cancer. Formaldehyde-fixed tanned sheep erythrocytes have been used as detector cells in place of guinea-pig macrophages, in a fixed tanned erythrocyte electrophoretic mobility (FTEEM) test, with lymphocyte products identical to those used in MEM tests. In patients with a history of cancer, positive results were obtained in 28/42 cases with the FTEEM test compared with 32/42 in the MEM test. In people with no history of cancer, negative results were obtained in 16/18 cases with the FTEEM test, compared with 12/18 in the MEM test in the present series, and 51/69 in a more extensive series. These differences are not significant. Cases in which discrepancies are revealed between the two tests are discussed in terms of individual case histories.

Animals↗
PubMed1978

Translational movements of macrophages through media of different viscosities.

The extent of the migration of guinea-pig peritoneal macrophages from capillary tubes over the surfaces of plastic Petri dishes, was quantitated by planimetry. It was observed that the amount of migration decreased as the viscosity of the medium was increased by the addition of agarose. An essential component of translational movement is the formation of adhesions between cells and their substrata. It is suggested on the basis of the present migration and adhesion experiments, that the increased viscosity reduces migration by retarding the formation of adhesions between the cells and their substrata. The experiments do not support the suggestion that agarose adsorbed to the dish surface affects the adhesion-dependent arm of migration or that viscous 'drag' on whole cells (over the viscosity range of 0.71 to 3.9 x 10(-3) N s m-2) reduces their movements.

Animals↗