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Mitotic spindle fiber orientation in relation to cell migration in the neo-cortex of normal and reeler mouse.

The angular distribution of mitotic spindle fibers has been studied in the telencephalic ventricular zone (VZ) of mouse embryos and has been found to be monophasic and invariant during the early cortical histogenesis both in the normal and in a reeler embryo. This observation suggests that the orientation of mitotic spindle fibers is independent of nerve cell migration in the embryonic cortex.

Animals

In vitro assessment of delayed hypersensitivity in the human. Inhibition of cell migration from agarose microdroplets.

The in vitro migration inhibition responses of peripheral blood leukocytes from tuberculin skin test positive and negative donors were tested to validate and determine optimal conditions for the agarose droplet method in the human. In vitro migration inhibition was observed in skin test positive donors in the presence of 25 microgram PPD/ml of medium using both unfractionated leukocytes and a mixture of immune lymphocytes with allogeneic polymorphonuclear leukocyte indicators. The supernatants of tuberculin positive lymphocytes cultured with PPD also inhibited the migration of human polymorphonuclear leukocytes and guinea pig peritoneal exudate cells but did not alter that of murine peritoneal exudate cells. These studies establish that the agarose droplet method is an efficient approach to the in vitro assessment of cell-mediated immunity in the human and define suitable indicator cell populations for assay of human lymphokines.

Animals

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male

The influence of the gut microflora and of dietary fibre on epithelial cell migration in the chick intestine.

1. The renewal of the intestinal mucosal epithelium has been investigated in germ-free and conventional chicks given a practical chick diet and a low- and high-fibre diet, using tritiated thymidine to label the nuclei of mucosal cells undergoing division. 2. Villus height, crypt depth and number of mitoses in the crypt were generally, although not always significantly, greater for conventional chicks than for germ-free chicks at all sites investigated in the intestine, and all became progressively lower from the upper intestine to the lower intestine. 3. There was a linear relationship between the height of the radioactively labelled mucosal cells on the villus and the period after injection, and the rates of epithelial cell migration were higher for conventional than for germ-free chicks, the relative differences being greater in the lower intestine than the upper intestine. 4. The inclusion of wheat bran as a source of dietary fibre had no effect on the rate of epithelial renewal, either in germ-free or conventional birds.

Animals

Correlation between inhibition of indicator cell migration and tuberculin hypersensitivity in patients with suspected tuberculous inflammation of the uveal tissue.

Peripheral blood lymphocytes from patients with suspected tuberculous inflammation of the uveal tissue were examined for their capacity to produce in vitro a migration inhibition factor in the presence of specific antigen. Three modifications of the capillary tube migration technique were used to demonstrate MIF. The indicator cells were guinea pig peritoneal macrophages and human peripheral blood leucoytes. A correlation was found between the migration of indicator cells influenced by lymphocytes from Mantoux-positive donors in the presence of specific antigen and the tuberculin sensitivity. The possible uses of the in vitro tests as a correlate to cellular hypersensitivity in vivo in the human system are discussed.

Animals

Lamina propria macrophages of intestine of the guinea pig. Possible role in phagocytosis of migrating cells.

The macrophages of lamina propria were commonly found both in the small and the large intestine of guinea pigs, mice, rats, and in human duodenum. The frequency of macrophage occurrence was highest in the lamina propria of villous apices of the small intestine and beneath the lining epithelium of the large intestine. In the cytoplasm of lamina propria macrophages localized in those regions, Feulgen-positive (DNA-containing) granules could be observed particularly in the guinea pig intestine. Autoradiography of the latter, 3 to 5 days after [3H]thymidine injection, showed the coincidence of occurrence of labeled Feulgen-positive granules in the macrophage cytoplasm with the appearance of labeled epithelial cells and sheath-fibroblasts in the region of lamina propria containing the highest accumulation of macrophages, i.e., at the apices of villi of the small intestine and beneath the lining epithelium of the large intestine. Labeled nuclei of macrophages were observed scarcely and much less frequently than were labeled cytoplasmic granules. No labeled Feulgen-positive granules could be seen in macrophages 1/2 hr, 1, 2, and 7 days after [3H]thymidine injection. It is suggested that the lamina propria macrophages may play a role in the phagocytosis of some migrating cells of the intestinal mucosa, most probably of the sheath-fibroblasts and/or intraepithelial lymphocytes.

Animals

Cell migration from clotted plasma droplets in vitro: development of a new method for MIF assay.

A new in vitro method for MIF assay has been developed using cells contained in clotted plasma droplets. It gives results concordant with the capillary tube method for H37 Ra Mycobacteria sensitized mice and PPD sensitized healthy persons. The technique is applicable to any migratory cell population and requires only a small number of cells for performance. It is technically simple, not time consuming and practicable both in patients and experimental animals.

Animals

[Hematopoietic stem cell migration study in dogs].

The migration rate of stem hemopoietic cells (SHC) of the bone marrow was studied by two methods in experiments on 54 dogs. In the first case the dogs were irradiated with an absolute lethal dose (550 R) subtotally, shielding two knee-joints. Seven days after the first irradiation under inactivation of shielded parts with 2000 R dose the survival rate was 12.5% and after 14-day inactivation all the dogs survived. In the second case firstly both knee-joints were irradiated with 2000 R dose. All the animals died following subsequent subtotal irradiation of the areas previously irradiated with 550 R dose if the second irradiation was performed 7 days after the first one. Prolongation of the time intervals between irradiations up to 31 days lead to 20% survival of the animals. It was concluded that SHC migration in dogs is much lower than in mice.

Animals

Mastocytoma cell migration in vitro: inhibition by MIF-containing supernatants.

Supernatants with macrophage migration inhibition factor (MIF) activity were obtained from cultures of antigen-stimulated guinea pig and human lymphocytes, and from SV40-infected monkey kidney cells. The monkey and human but not guinea pig preparations were effective in inhibiting migration of mastocytoma cells as well as macrophages. This inhibition of migration was not associated with cytotoxicity and was reversible.

Animals

Mononuclear cell migration inhibition in children with nephrotic syndrome.

The relative number of T/B lymphocytes and the response of peripheral blood mononuclear cells to PHA in the migration inhibition test was studied in a group of patients with idiopathic nephrotic syndrome. It has been found that the level of T lymphocytes and the response to PHA was decreased in patients in particular those with frequent relapses. The possible implications of these finding for pathogenesis of idiopathic nephrotic syndrome is briefly discussed.

B-Lymphocytes

In vitro evaluation of cell-mediated immunity to Epstein-Barr herpesvirus by cell migration inhibition tests.

Migration of peripheral leukocytes in samples from sensitized [Epstein-Barr virus (EBV) antibody-positive] humans was greatly inhibited when challenged by antigen prepared from EBV-producing P3HR-1 cells but not by antigen prepared from EBV-nonproducing RAJI cells, EBV-negative human fibroblasts, or epithelial cells. Such inhibition was not observed when peripheral leuocytes from subjects or neonates not sensitized to EBV were challenged. Similar results were obtained in a two-stage test when the same leukocyte samples were challenged in vitro by antigen prepared from P3HR-1 cells and the cell-free supernatant was assayed for migration inhibition factor (MIF) in the guinea pig macrophage migration inhibition test; migration of guinea pig peritoneal exudate cells was greatly inhibited by the supernatant filtrates of leukocyte cultures only from subjects positive for EBV-antibody. Furthermore, this inhibitory effect was not observed if supernatant filtrates from leukocyte cultures challenged by antigens prepared from RAJI cells, fibroblasts, or epithelial cells were used. The EBV antigen transformed peripheral leukocytes and induced early antigen production in RAJI cells; however, a "killed" preparation (by UV irradiation) was sufficient for eliciting MIF production.

Antibodies, Viral

In vitro correlate of tranplantation immunity: spleen cell migration inhibition in the lizard, Calotes Versicolor.

Sensitization to skin allografts in the lizard, Calotes versicolor, was assessed using the in vitro capillary migration inhibition (MI) assay. In the presence of the respective donor antigen, an appreciable degree of MI of sensitized spleen cells was observed as early as 4 days after grafting. A maximum level was attained on day 7 and this response was maintained as long as one month after grafting with only slight fluctuations in the level of MI. When the clinical manifestations of graft rejection culminated on day 35, the degree of MI was still at the maximum level. MI of allograft-sensitized spleen cells is an antigen specific event, and the same level of inhibition is observed whether the specific antigen is provided in the form of intact spleen cells or spleen extract.

Animals