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In vitro modulation of human leucocyte migration and migration inhibitory factor (LIF) activity by cyclic 3',5'-AMP and cyclic 3',5'-GMP.

The effects of cyclic 3', 5'-AMP (cAMP) and cyclic 3', 5'-GMP (cGMP) on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF) was studied. Leucocyte migration was not influenced by dibutyryl cAMP, while the dibutyryl derivative of cGMP significantly stimulated cell migration (1 x 10(-5)M). LIF-treated leucocytes partially escaped migration inhibition in the presence of dibutyryl cAMP (greater than or equal to 1 x 10(-6)M), while dibutyryl cGMP was inefficient. If the parent compounds cAMP and cGMP were tested, almost similar results would be obtained, although at higher concentrations of the drugs. These results represent initial experiments with a view to investigating the possible role of cyclic nucleotides in the expression of LIF activity.

Bucladesine

Epithelial migration in organ culture. A morphological and time lapse cinematographic analysis of migrating stratified squamous epithelium.

The migration of stratified squamous epithelium in organ cultures of rat palatal explants has been studied using scanning and transmission electron microscopy. The scanning microscope revealed plate-like folds at the margins, and microvilli on the bodies of cells. These structures were most highly developed on those cells nearest the leading edge of the sheet of cells and are interpreted as an index of cells that are migrating. The cells at the leading edge have broad flat pseudopodia in direct contact with the collagen bundles. A time lapse cinemicrographic study showed that the net forward movement of cells (nuclei) remote from the leading edge was at least as great as that at the leading edge immediately in front of them and the distance they travelled was greater than that of the leading edge. In transmission electron micrographs of these migrating epithelial cells from in vivo wounds, profiles that could correspond to the microvilli and plate-like folds could be found on the surface of the migrating cells. The results of this study suggest a simple model for the particular type of movement that occurs in stratified squamous epithelium in healing wounds where a mass of cells is produced that can both migrate into the wound and undergo stratification and cornification. A tracked vehicle shedding a broken track is used as an analogy of the model proposed.

Animals

Policy paper of the Committee on Ethics and Task Force on Migration and Mental Health: Migration and mental health of migrants, refugees, asylum seekers - Ethical dilemmas and concerns.

BACKGROUND: International migration is a complex phenomenon of global and historical relevance. It includes voluntary, forced, and workforce migration, shaped by diverse determinants. Push factors comprise war, persecution, and political instability, while pull factors include stability, economic opportunities, education, and favorable living conditions. Forced migration is frequently associated with displacement and a disproportionate burden of mental health disorders, which are urgent yet difficult to address due to structural, cultural, and legal barriers. METHODS: Evidence demonstrates that restricted health care access exacerbates psychiatric disorders, while treatment delays contribute to poorer outcomes. Barriers include administrative limitations, linguistic and cultural differences, stigma, and resource shortages. This policy paper was developed by the Committee on Ethics and the Task Force on Migration and Mental Health of the European Psychiatric Association (EPA). Relevant literature was reviewed and combined with the professional expertise of committee members. The draft was subsequently evaluated by the Publication Committee and the EPA Board, and revised accordingly. RESULTS: Ethical principles in refugee care are insufficiently implemented in many European countries. Core principles of medical ethics - beneficence, respect for autonomy, non-maleficence, and justice - as well as the obligation to advance psychiatric standards and apply psychiatric expertise for societal benefit, are inconsistently upheld. CONCLUSIONS: The primary duty of physicians is to promote health and well-being through competent, timely, and compassionate care. The EPA therefore advocates coordinated strategies to mitigate the mental health consequences of war, displacement, and trauma, and to secure equitable access to psychiatric services for migrants and refugees.

Humans

Effects of dialyzable leukocyte extracts (DLEs) with transfer factor activity on leukocyte migration in vitro. III. Characterization of the antigen-independent migration inhibition factor in DLEs as a neutrophil immobilizing factor.

In earlier evaluations of the agarose LMI assay as an in vitro test for studying the nature and mechanism of action of TF, we reported the existence of a component in human DLEs which caused noncytotoxic inhibition of the random migration of human PMNs. The LMI was not dependent on the stimulation of viable mononuclear leukocytes by antigen or mitogen to effect the release of mediators of cellular immunity such as LIF; rather, the LMI was promoted by the direct action of a preexisting component in DLEs on PMNs. We now present evidence that this "antigen-independent" LMI activity in DLE'S is similar to a NIF shown previously by Goetzl and co-workers to be present in acid extracts of leukocytes and to be released by phagocytosing PMNs. The comparison is drawn from several parameters: (1) cellular origin, (2) molecular weight, (3) target cell, (4) susceptibility to inactivation by heating or by incubation with pronase, trypsin, or chymotrypsin, and (5) ability to cause noncytotoxic inhibition of random migration or chemotaxis of PMNs.

Animals

Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. 1. Antigen-dependent inhibition and antigen-independent inhibition and enhancement of migration.

The effects of DLE containing TFd activity from immune human donors on PBL, obtained from individuals nonresponsive to either PPD or Cocci antigen, were evaluated in vitro by the agarose LMl technique. Several different preparations of DLE were employed to evaluate the specificity and reproducibility of the effects: (1) from donors skin test positive to PPD but negative to Cocci, (2) from donors skin test negative to PPD but positive to Cocci, (3) from donors skin test positive to both antigens, and (4) from donors skin test negative to both antigens. With PBL from other human donors used as target cells in the direct agarose LMi technique, three types of effects were demonstrated for all preparations of DLE: (1) antigen-dependent specific LMl, (2) antigen-independent or nonspecific LMl, and (3) antigen-independent enhancement of migration. The demonstration of each activity was found to depend on the concentration of DLE used and the time allowed for migration. In experiments employing purified PMN and MNL as target cells and a two-step indirect LMl assay, it was shown that the antigen-independent effects resulted from the direct of components in DLE on PMN. The antigen-independent inhibition was shown not to result from toxic effects of DLE. It was produced by DLE but not by dialyzable liver or skin extracts when tested using an amount equivalent to DLE as judged by the absorbance at 260 and 280 nm. The antigen-dependent LMl was found to require secretion of a soluble mediator of molecular weight near 69,000, believed to be LMl. Our results indicate that the agarose LMl technique is a useful in vitro assay for studies of the mechanism of action of components in DLE which can specifically convert nonimmune lymphocytes to a measurable antigen-sensitive state (i.e., transfer factor). The antigen-independent effects of DLE may be responsible in part for previously reported nonspecific beneficial effects of DLE when used in immunotherapy.

Antigens

Leucocyte migration inhibition test as an index of immunological response to measles virus I. Effect of the environment and measles virus on migration of monkey leucocytes.

The parameters of migration inhibition test of leucocytes isolated both from the peripheral blood, spleen and lymph nodes of monkeys Cercopithecus aethiops were determined. Concentration of measles virus that does not produce nonspecific migration inhibition of leucocyte obtained from sero-negative animals was also defined.

Animals

Biologic and antigenic similarity of virus-induced migration inhibition factor to conventional, lymphocyte-derived migration inhibition factor.

Macrophage migration inhibition factor (MIF) is one of a class of lymphocyte-derived mediator substances (lymphokines) which plays a role in the mechanism of cellular immunity. A variety of other soluble factors produced by non-lymphoid cells have been shown to have effects on macrophage mobility similar to that of MIF. In the present study we demonstrate that one such factor, (MIFV) derived from simian virus 40-infected kidney cells in culture, has several other properties in common with lymphocyte-derived MIF (MIFL), MIFV can be adsorbed on Sepharose bead columns conjugated with an antiserum prepared against MIFL, demonstrating at least some antigenic similarity. Moreover, MIFV can substitute for MIFL in an in vivo system involving the suppression of cutaneous manifestations of cellular immunity by intravenous injection of the lymphokine. These observations, taken in conjunction with the similarity of the in vitro effect of MIFV and MIFL, and their similar chromatographic behavior, suggest that MIFV and MIFL may be identical molecular species.

Animals

The mode of migration of neurons to the hippocampus: a Golgi and electron microscopic analysis in foetal rhesus monkey.

The mode of neuron migration from the site of their origin in the ventricular zone to area CA1 of the hippocampus was analysed with Golgi and electron microscopic methods during the first half of gestation in the foetal rhesus monkey. In the inner portion of the intermediate zone, the migrating cells have a bipolar form with one, or oaccasionally two, leading processes which do not reach the ammonic plate and with a single trailing process which usually ends within the intermediate zone. Both the nucleus and the cytoplasm of the migrating cells are relatively electron-dense and the latter contains organelles typical of young neurons as described in other brain regions. Analysis of electron micrographs from serial sections reveals that the length of the somata and of the leading and trailing processes of the migrating neurons is apposed to fascicles of radially oriented, electron-lucent, microtubule-filled fibres which are ultrastructurally similar to the radial glial fibres of the neocortex and to the Bergmann glial fibres of the cerebellum. The close (20 nm) apposition between the membranes of the migrating cell and the radial fibre is maintained even in areas where the fibres bend or curve tortuously. Migrating neurons situated at progressively more superficial levels of the intermediate zone become progressively more differentiated and complex. Thus, in the outer portion of the intermediate zone, the migrating cells acquire several additional cytoplasmic processes and occasionally a long thin axon-like process which courses into the incipient alveus. These cells have somewhat larger somata and less electron-dense nuclei and cytoplasm than the migrating neurons still situated in the inner part of the intermediate zone. Cells close to the ammonic plate usually have one to three cytoplasmic processes that enter the ammonic plate and terminate near their presumed final position. Migrating neurons situated at the lower border of the ammonic plate have a single large apical process which intermingles with neurons already in their final position and which sometimes traverses the ammonic plate. The apposition of the migrating neurons to the radial glial processes becomes less explicit as the cell soma enters the ammonic plate, reflecting the more complex three-dimensional intercellular relationships. However, the present analysis indicates that during the middle and late stages of neuronal migration to the hippocampus radial glial fibres may guide postmitotic young neurons across the intermediate zone to the ammonic plate in the same way that they guide neurons migrating to the superficial and middle layers of the neocortical plate.

Animals