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Biomedical subjects

H Pross

Publications and source records attributed to H Pross.

At least 19 recordsLinked to original sources
PubMed2001

Problems identified by tutors in a hybrid problem-based learning curriculum.

Problem-based learning (PBL) tutors (n = 27) were interviewed to identify problems they encountered in facilitating a hybrid PBL-lecture curriculum. Analysis of responses yielded six problems for students: "mini-lecturing," dysfunctional group dynamics, completing cases too quickly, superficial research, frustration with tutors who lack content expertise, and lack of support for PBL. These may arise because students lack problem-solving and interpersonal skills needed to benefit from PBL.

Curriculum↗
PubMed1994

Anti-beta 1 integrin IgG inhibits pulmonary macrometastasis and the size of micrometastases from a murine mammary carcinoma.

In the present report, we investigated the possible importance of beta 1 integrins in the growth and metastasis of a murine mammary carcinoma, SP1, and a metastatic variant, SP1-3M in vivo. CBA/J female mice bearing SP1 tumor transplants were injected with anti-beta 1 integrin IgG or control nonimmune IgG (200 micrograms per mouse; i.p.) every two days. Animals received anti-CD4 antibody (100 micrograms per mouse) at time zero to suppress immunity against rabbit IgG. Outgrowth of macroscopic metastases from SP1, but not from SP1-3M primary tumors, was markedly inhibited in animals receiving anti-beta 1 integrin IgG but not nonimmune IgG. To assess the stage(s) in the metastatic cascade affected, we examined the number and diameter of micrometastatic nodules in treated and untreated groups. The diameter of micrometastases was significantly reduced in SP1-tumor-bearing mice treated with anti-beta 1 integrin IgG compared to control IgG, although the number of nodules per cm2 of lung sections examined remained unchanged. No change in the number or size of micrometastases in SP1-3M tumor-bearing mice was observed. No difference in the binding, or complement-mediated and antibody-dependent cell-mediated cytotoxicity of anti-beta 1 integrin IgG with SP1 and SP1-3M cells was detected. The results suggest that under these conditions anti-beta 1 integrin inhibits metastatic tumor growth in lung tissue, but has minimal effect on intravasation, adhesion to target organs and extravasation.

Animals↗
PubMed1993

p21ras and protein kinase C function in distinct and interdependent signaling pathways in C3H 10T1/2 fibroblasts.

Both p21ras and protein kinase C (PKC) are believed to function downstream of plasma membrane-associated tyrosine kinases in cellular signal transduction pathways. However, it has remained controversial whether they function in the same pathway and, if so, what their relative position and functional relationship in such a pathway are. We investigated the possibilities that p21ras and PKC function either upstream or downstream of each other in a common linear pathway or that they function independently in colinear signal pathways. Either decreased expression of endogenous normal ras in fibroblasts transfected with an inducible antisense ras construct or overexpression of a mutant ras gene reduced the capacity of the phorbol ester tetradecanoyl phorbol acetate to trigger expression of the tetradecanoyl phorbol acetate-responsive and ras-dependent reporter gene osteopontin (OPN). PKC depletion decreased basal OPN mRNA levels, and the overexpression of ras restored OPN expression to the level of non-PKC-depleted cells. We propose a model in which ras and PKC function in distinct and interdependent signaling pathways.

Animals↗
PubMed1991

Capacity of CD8+ T cells to reject immunogenic variants of a spontaneous murine carcinoma: lack of non-specific (NK1.1+) effector mechanisms.

Class I MHC-expressing (Ia-) immunogenic (imm +) variants, which elicit a strong syngeneic host immune rejection response, can be isolated following 5-azacytidine treatment from the MHC-negative non-immunogenic (imm-) murine carcinoma cell line SP1 (10.1 subclone). In the present study, we have shown that CD4-depleted CD8+ T cells are both necessary and sufficient for the rejection process. Treatment of semi-syngeneic B6 X CBA F1 mice with anti-NK1.1 antibodies had no effect on the rejection of immunogenic variants, although the splenic NK (natural killer) activity of recipients was fully abrogated. Thus NK1.1+ effectors, which include most NK and LAK (lymphokine activated killer) cells, are most likely not involved in the rejection process. This finding was supported by a complete lack of NK susceptibility of SP1 cells in vitro, although variable killing by LAK and poly-I: C-induced killer cells was observed. To assess the role of NK1.1-LAK and other non-T killers (e.g. cytolytic macrophages) in vivo, we determined the specificity of the rejection process. We examined the ability of immune animals to reject a mixture of non-immunogenic parent tumour cells (or cells of an unrelated syngeneic tumour) and of the variant tumour cells used for the initial immunization. Growth of the parent tumour cells was unaffected while the same animals rejected the immunogenic tumour cells. Our findings support a primary role of tumour-specific CD8+ T cells in the rejection of imm+ variants with no detectable involvement of non-specific effector cells in the tumour destruction process.

Adenocarcinoma↗
PubMed1985

The sensitivity of placental trophoblast cells to intraplacental and allogeneic cytotoxic lymphocytes.

The NK-susceptibility of trophoblast cells to allogeneic and autologous intraplacental natural killer (NK), antibody-dependent (K), and mitogen-induced cell-mediated cytotoxicity was studied, using untreated and neuraminidase-treated trophoblast cells from normal, full-term deliveries. The work was preceded by systematic studies of placental cell separation and labelling techniques, and the effects of these techniques on the NK target, K562. The results indicated that maternal NK cells are present among intraplacental lymphocytes, but that their activity is lower than that of peripheral blood lymphocytes and they are not stimulated by interferon to the same extent as peripheral blood lymphocytes (PBL). Trophoblast cells were rarely susceptible to allogeneic NK cells, with low cytotoxicity at high effector-target cell ratios in only two of five experiments. Interferon (IF)-boosted NK cells mediated some cytolysis of trophoblasts in three of four experiments, but high effector/target cell ratios were also required for the effect to be observed. The trophoblast cells could be lysed, however, by K cells and lectin-induced cytotoxicity. Removal of surface sialic acid by neuraminidase treatment of the trophoblast cells had little effect on the susceptibility of these cells to unstimulated NK cells (one of four experiments), but resulted in susceptibility to IF-boosted NK cells in four of four experiments. Normal trophoblast cells did not compete in IF-NK(K562) assays and neuraminidase-treated cells competed weakly in only one of three such experiments, indicating that the NK "target structure" is only weakly expressed on human trophoblast cells. Intraplacental lymphocytes lysed autologous trophoblast cells to a lower extent than allogeneic PBL.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

The role of deputizing agencies in the delivery of primary health care services.

When not available to their patients, family practitioners in large cities can "sign out" to deputizing agencies, which coordinate the activities of part-time physicians on call. The physicians making use of one such agency in Toronto appeared to be representative of family practitioners in the region. One thousand of their patients seen consecutively by one physician were asked a series of questions. The majority of the 811 evaluable patients were considered to have problems justifying an after-hours call, although 16% of the problems were of a trivial nature. However, almost half of the patients with trivial problems would have gone to the local emergency room, as would 85% of all the patients. Although virtually all (94%) of the visits with the elderly were justified, 34% of the patients in this age group said they probably or definitely would not have sought emergency room care if a physician had not been available. The use of deputizing agencies should reduce the overuse of emergency room facilities and provide optimal after-hours primary medical care.

Appointments and Schedules↗
PubMed1983

The chemiluminescence response of human natural killer cells. II. Association of a decreased response with low natural killer activity.

Low natural killer (NK) responders selected from a panel of 600 normal, healthy volunteers exhibited 5- to 10-fold less cytotoxicity against the human erythroleukemic cell line K562, compared with high NK responders. Antibody-dependent cellular cytotoxicity against tumor cells, which is mediated by similar or identical effectors, was also depressed in low NK donors whereas lectin-dependent T cell killing and monocyte-mediated cytolysis of tumor cells was normal. Low NK donors exhibited normal frequencies of cells expressing the HNK-1 marker of human NK cells and highly enriched NK fractions were not impaired in their ability to recognize and bind to NK-sensitive target cells. Interferon partially activated low responder NK cells but did not restore the response to normal levels. The burst of chemiluminescence that is generated by NK cells within seconds of target cell contact was markedly impaired in low NK responder donors. We have previously shown that chemiluminescence detects reactive oxygen intermediates which are necessary but not sufficient for the activation of the NK cytolytic pathway.

Adult↗
PubMed1982

Further studies of natural killer cell function in Chediak-Higashi patients.

Spontaneous natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of blood lymphocytes against five human tumour cell lines (K562, Molt-4, HL-60, Chang, Daudi) and three mouse tumour lines (YAC, P815, RBL-5) were ten- to 100-fold lower than normal in six patients with Chediak-Higashi (CH) disease. NK and ADCC were defective at 4 hr, and less so at 18 hr. The NK activity in normals and CH patients was mediated in part by FcR+, E- effector cells. ADCC against human erythrocytes was normal in CH patients, as were lectin-dependent cytolysis and mixed lymphocyte proliferative responses. Phagocytosis of antibody-coated ox erythrocytes was normal in CH patients as well. These observations confirm that the CH syndrome is associated with a profound and selective defect in NK and ADCC activity against tumour cells, whereas other mononuclear cell-mediated functions are normal.

Adult↗
PubMed1976

Characteristics of the maternal lymphoid response of mice to paternal strain antigens induced by homologous pregnancy.

Mice mated with H-2 incompatible males were shown to have an increased frequency of specific allocluster-forming spleen cells to paternal strain erythrocytes. The time course of the response was similar to that expected following a skin allograft. The graft-versus-host responsiveness of the maternal lymphocytes was generally elevated in the post-partum period in matings with males incompatible at either the H2 locus or non-H2 loci. The implications of these responses with respect to their different lymphocyte mediators and possible interactions are discussed with the view that a B-cell mediated immune response to paternal antigens may be contributory to foetal survival.

Animals↗
PubMed1975

Comparative in vitro sensitivity of twom methylcholanthrene-induced murine sarcoma lines to humoral and cellular immune cytotoxicity.

MC57M and G are the tissue-culture derivatives of two methylcholanthrene-induced murine C57Bl sarcomas. Their sensitivity to immune cytoxic3, cytostatic or cytolytic spleen cells and sera was compared in parallel in vitro assays. The level of cross-reactivity displayed by the two lines was found to depend on the nature of the immune effector rather than on the assay which was used. It was high with immune spleen lymphocytes, alone or in the presence of decomplemented antisera, and low with antisera in the presence of rabbit complement. MC57G cells were more sensitive than MC57M cells to both effectors. Both cell lines were insensitive to antibody-dependent cell-mediated cytotoxicity. Preliminary evidence is presented, suggesting a probable involvement of embryonic and Moloney leukemia virus-induced cell surface antigens in the vitro sensitization of the two tumor lines to immune sera.

Animals↗
PubMed1975

Surface markers on human b and t lymphocytes. VI. Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations.

The spontaneous lymphocyte mediated cytotoxicity (SLMC) of cells from normal donors against 19 different established cell lines was analysed. All normal lymphocytes were cytotoxic in all combinations tested in a17h 51-Cr release assay. ALMC was found to be mediated by a minor subpopulation of lymphocytes with Fc/C3 receptors. Non-cytotoxic SRBC binding T-lymphocytes could be induced to become cytotoxic by the addition of Con A to the incubation medium. SLMC and lectin-induced cytotoxicity were briefly characterized. It is argued that SLMC is a non-specific non-immunological reaction which must be taken into consideration when lymphocytes from cancer patients are tested against tumour-cell lines in vitro. Futhermore, SLMC and letin-induced cytotoxicity are proposed as functional markers for Fc/C3-binding lymphocytes and SRBC binding lymphocytes respectively.

Azides↗
PubMed1975

"Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell.

Normal mice contain cytolytic cells with specificity for in vitro grown mouse Moloney leukemia cells. Such killer cells are most frequent in the spleens; lymph node and bone marrow contain less and thymus virtually no killer activity. Peak activity is found around one to three months of age. Spleen cells from genetically athymic mice are as active killer cells as those from normal mice of the same strain. Treatment with anti-theta serum plus complement followed by removal of adherent and surface Ig positive cells by filtration through anti-Ig columns will leave between 1-5% of the original spleen cell population from a normal mouse. These cells have the morphology of small lymphocytes and perhaps contain all of the total original killer activity of the spleen against the Moloney leukemia cells. Such killer enriched cells are devoid of T and B lymphocytes and largely fail to function in antibody induced, cell-mediated lysis against antibody-coated chicken erythrocytes. It is concluded that the spontaneous selective cytotoxic activity of normal mouse spleen cells against Moloney leukemia cells is exerted by small lymphocytes of yet undefined nature.

Age Factors↗
PubMed1974

Cytotoxic immune cells with specificity for defined soluble antigens. IV. Antibody as mediator of specific cytotoxicity.

Spleen cells from mice immunized against ovalbumin (OA) or dinitrophenylated mouse serum albumin (DM) were found to be specifically cytotoxic in vitro towards target cells (chicken red blood cells) coated with these antigens. Inhibition of specific cytotoxicity was observed when free soluble antigen was added to the incubation mixtures. DM-immune cell cytotoxicity could be specifically and completely inhibited by DNP-lysine and was thus shown to be hapten specific. Complete and specific inhibition was also observed for OA-immune cell cytotoxicity using OA as inhibitor, but compared with the inhibition curves obtained with DNP-lysine, the OA cytotoxicity inhibition curves were shifted by a factor of about one hundred towards lower molar inhibitor concentrations. Very similar results were observed when the serum antibodies of DM- and OA-immune animals were analyzed by passive hemagglutination inhibition. With increasing time after immunization, both cytotoxicity inhibition curves and agglutination inhibition curves, shifted to lower antigen or hapten concentrations. Specific cytotoxicity against antigen-coated target cells was induced in nonimmune spleen cells (a) by serum from immune animals, and (b) by supernatants from in vitro immune cell cultures. In both instances, the factor which induced antigen-specific cytotoxic activity could be absorbed on anti-mouse Ig columns, thus demonstrating its immunoglobulin nature. The ability of target cell bound antibodies to induce cytotoxicity in nonimmune spleen cells was restricted to the 7S antibody class.

Animals↗