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Biomedical subjects

M C Cohen

Publications and source records attributed to M C Cohen.

At least 73 records · Page 4Linked to original sources

Production of lymphokines affecting tumor cells by T-T hybridomas.

T-Cell hybridomas were constructed by fusing BW5147, an AKR lymphoma, with concanavalin A-stimulated murine splenic lymphocytes. The hybrids which were formed were studied for their ability to produce a lymphokine which inhibits tumor cell migration (TMIF) as well as macrophage migration (MIF) using in vitro assays. Clones were identified which affected tumor cell motility without exerting similar effects on murine macrophages, although the opposite effect was not observed. Although noncoordinate production of these factors cannot be unequivocally established, these results demonstrate that clones can be constructed that preferentially secrete TMIF. In these experiments, we also tested the supernatants for another lymphokine effect on tumor cells; namely, the ability to inhibit tumor cell binding to endothelial monolayers. A number of clones were identified that lacked TMIF activity, but could inhibit the tumor cell-endothelial interaction, suggesting the possibility that these effects may be due to separate mediators.

Animals↗

In vitro migration of tumor cells from human neoplasms: inhibition by lymphokines.

We have previously described a noncytotoxic lymphokine, TMIF, with the capacity of inhibiting the in vitro migration of a variety of serially passaged experimental animal tumors, but not non-neoplastic cells. In the present study, we describe conditions for the assay of human tumor cell movement utilizing agarose microdroplets. Using this procedure, we were able to demonstrate that TMIF is as effective in inhibiting the in vitro migration of suspensions of tumor cells obtained from spontaneous human neoplasms, as it is in inhibiting model tumor systems. This finding demonstrates that responsiveness to TMIF is not merely a property conferred on tumor cells by prior serial passage. Also, by demonstrating that tumors of human origin are responsive, the present study raises the possibility that studies of TMIF in neoplastic disease may provide information of prognostic value. Also, they provide the hope that if TMIF proves therapeutically effective in animal models, those results may be translated to human disease.

Cell Migration Inhibition↗

The tumor disappearance reaction: an in vivo effect of a noncytotoxic lymphokine active against tumor cells.

A lymphokine, tumor migration inhibition factor (TMIF), that can inhibit the migration of tumor cells in vitro without cytotoxic effect has been described. TMIF can be produced in vitro or in vivo. In the present study, it is demonstrated that administration of TMIF can lead to a transient decrease in recoverable tumor cells from the peritoneal cavities of otherwise untreated mice. This result, which appears to be due to a direct effect of the mediator, rather than a consequence of inflammatory cell accumulation, is analogous to the effect of macrophage migration inhibition factor (MIF) on macrophages in the well known macrophage disappearance reaction. These findings demonstrate that TMIF can exert an effect in vivo predicted from its in vitro properties, and raise the possibility that this effect can be exploited in an appropriate therapeutic model.

Animals↗

Application of the strange situation attachment paradigm to a neurologically impaired population.

Mother-infant attachment was studied in 24 mother/impaired infant dyads. The infants, from 12 to 26 months chronological age, manifested primary neurological impairment or undiagnosed delay in gross and fine motor development. Measures of general development and degree of child impairment significantly differentiated "classifiability" of attachment in the Ainsworth scheme; thus, the most severely impaired infants were rated "not classifiable." For those infants who were fully classifiable (80% of the sample), only 1 measure of general development or degree of impairment differentiated quality of attachment classification. Infants rated higher on a measure of social responsiveness were more likely to possess secure attachments than those receiving lower ratings on the measure.

Brain Diseases↗

Lymphokine-induced migration inhibition of murine tumor cells derived from solid neoplasms.

We have previously described a noncytotoxic lymphokine, tumor migration inhibition factor, with the capacity of inhibiting the in vitro migration of a variety of tumor cells maintained by animal passage in ascitic form. In the present study, we demonstrate that it is possible to prepare viable, motile tumor cell suspensions from solid tumors and that those cells migrate better than cells that had been propagated in ascitic form. Such preparations derived from solid tumors are inhibited by tumor migration inhibition factor to a degree comparable to that achieved with cells from ascitic tumors. Comparative studies utilizing a methylcholanthrene-induced fibrosarcoma as well as solid and ascitic forms of P815 mastocytoma and Ehrlich tumor demonstrate that responsiveness to tumor migration inhibition factor is not merely a property conferred upon tumor cells by prior animal passage in suspension. These results provide a further suggestion that the capacity for lymphokine-induced migration inhibition is a general property of tumor cells. This in turn raises the possibility that this capacity might vary in a predictable manner with malignant potential.

Animals↗

Migration inhibition of endothelial cells by lymphokine-containing supernatants.

Many of the reactions of cellular immunity are mediated by soluble lymphocyte-derived factors (lymphokines). One important category of lymphokine action involves effects on cell motility. These effects have been described mainly with respect to inflammatory cells. In this report, we describe the ability of a lymphocyte product to inhibit the migration of endothelial cells in a system in vitro. The responsible factor is distinct from a previously described mediator that inhibits the migration of tumor cells. The ability of lymphocytes to influence the migration properties of endothelial cells is consistent with data of others showing a relation between the immune system and processes involving neovascularization.

Cell Line↗

Characterization of the lymphokine responsible for migration-inhibitory activity against tumor cells.

Lymphokine-containing supernatants have the ability to inhibit the migration of a variety of tumor cells in vitro in the absence of cytotoxic effects. In the present study, this tumor migration inhibition activity has been characterized in order to determine whether the responsible factor is the same or different from other known migration-inhibitory lymphokines. Since no preparations purified to homogeneity are generally available for these various factors, a variety of indirect procedures is necessary to make this determination. The profile of effects of monosaccharides, protease inhibitors, and neuraminidase on tumor migration inhibition factor, taken in conjunction with previously reported studies of other physicochemical and biological properties, provides evidence that tumor migration inhibition factor is distinct from both migration inhibition and leukocyte-inhibitory factor. A lymphokine with migration-inhibitory activity against tumor cells is a good candidate for a variety of protective functions in vivo.

Animals↗

Correlation between agarose microdroplet and capillary tube procedures as assays for migration inhibition of target cells.

We have compared the capillary tube assay for migration inhibition studies with our modification of the agarose microdroplet technique, using several sources of factors with inhibitory activity (lymphokines, bacterial factors) and a variety of cell types (inflammatory exudate cells, tumor cells). In all circumstances both procedures gave quantitatively similar results, and high statistical correlation was found. These results suggest that the two procedures are measuring similar properties, and in any case may be used interchangeably as assays.

Animals↗

Human macrophage migration inhibition factor: evidence for subunit structure.

Macrophage migration inhibition factor (MIF) derived from human lymphoid cell lines was found to lose biologic activity on dialysis. Although activity was not recovered in the dialyzate, mixing experiments demonstrated that the components in the retentate and dialyzate could reassociate to restore activity. The fragment of larger molecular weight (less than 10,000) could inhibit the activity of intact MIF, whereas the smaller molecular weight fragment (5,000 to 10,000) could not. These findings suggest that human MIF is composed of at least two noncovalently linked subunits. In analogy to the situation for certain bacterial toxins, one of these may represent an attachment piece for a target cell membrane receptor.

Cell Line↗

In vitro and in vivo production of chemotactic inhibitors by tumor cells.

The ascites fluid or peritoneal washings of DBA/2 mice bearing the P815 mastocytoma have been found to contain a chemotactic factor inactivator (CFI) which inactivates the bacterial chemotactic factor as well as the chemotactic activity associated with the C3 and C5 fragments when assayed on rabbit neutrophils. The amount of CFI is proportional to the number of tumor cells in the peritoneal exudate. The inactivator is also found in tumor cell hemogenates as well as in culture fluid from tumor cells growing in vitro. The activity is heat-labile but is not affected by protease inhibitors. Its molecular weight is greater than 50,000 daltons, based on Sephadex chromatography and sucrose density gradient ultracentrifugation studies. In C57BL/6 mice, which reject the mastocytoma, CFI levels decrease in proportion to the decreasing numbers of tumor cells.

Animals↗

Nonpharmacologic control of essential hypertension in man: a critical review of the experimental literature.

Many nonpharmacologic (behavioral) techniques are being proposed for the therapy of essential hypertension. The research in this area is reviewed and divided roughly into two categories: the biofeedback and relaxation methodologies. While feedback can be used to lower pressures during laboratory training sessions, studies designed to alter basal blood pressure levels with biofeedback have not yet been reported. The absence of evidence for such changes through biofeedback limits the usefulness of this technique in hypertension control. The various relaxation methods, such as yoga, transcendental meditation, progressive muscle relaxation, and others have shown more promise. With varying degrees of experimental vigor, many of these techniques have been associated with long-lasting changes in blood pressure. The strengths and weaknesses of the various authors' research designs, data and conclusions are discussed, and suggestions for further experimentation are offered.

Autogenic Training↗

Mechanisms of tumor immunity. An overview.

The involvement of the immune system in the host response to tumors is complex and involves both lymphocytes and lymphocyte-derived mediators, as well as inflammatory cells and various other agents such as complement. These activies are not confined to cytodestructive processes; recent studies demonstrate that the migration characteristics of tumor cells may be modified by immunologically derived substances. The multiplicity of possible immune system-neoplastic cell interaction is unfortunately balanced by the multiplicity of mechanisms that serve to interfere with an effective immune response to tumors. These mechanisms may reflect pathologic derangements of normal immunoregulatory processes or may involve the production of suppressive substances by the tumors themselves. In either case, a number of genetic and other predisposing factors must contribute to the ultimate resolution of the battle between host and tumor. Successful strategies for immunologic intervention must take these parameters into account.

Cell Movement↗

Inhibition of migration of tumor cells in vitro by lymphokine-containing supernatants.

Lymphokine-containing supernatants derived from seven different human lymphoid cell lines and lymphokine-containing supernatants from concanavalin A-stimulated murine lymphocytes were found to be capable of reversibly inhibiting the migration of tumor cells in vitro. The tumor cell lines used in these studies were the P815 mastocytoma, Ehrlich ascites, Walker carcinosarcoma, Hepatoma 129, and Sarcoma 37. Preliminary physiochemical evidence suggests that the mediator, here termed TMIF, is distinct from MIF. In any case, these results suggest the possibility that lymphokines other than lymphotoxin or macrophage-activating factors may play a role in tumor immunity.

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↗

Solitary unilocular cyst of the lung with features of persistent interstitial pulmonary emphysema: report of four cases.

Neonatal interstitial pulmonary emphysema (IPE) is a well-characterized lesion usually presenting in preterm newborns as a complication of respiratory distress syndrome and/or assisted ventilation. Occasionally, IPE may occur spontaneously in infants with no underlying pulmonary disease. Persistence of IPE (PIPE) may be diffuse or localized. Localized PIPE usually presents as multiple cysts 0.3 to 3 cm in one or more lobes of the lung. In this report, we describe four cases of unilocular large cysts (up to 5 cm in diameter) partially lined by uni- and multinucleated histiocytes in a foreign body type reaction and showing gas dissection of the surrounding parenchyma (present in case 1). These histological features favored the diagnosis of PIPE and the cases were interpreted as such, since no other clear-cut diagnosis could be defined. However, because the lesion was limited to one lobe, and the children were full term, asymptomatic at birth and without history of respiratory distress or assisted ventilation, differential diagnosis with other pulmonary cystic lesions of infancy is mandated.

Child, Preschool↗

Persistent interstitial pulmonary emphysema-like cyst associated with metastatic synovial sarcoma.

Interstitial pulmonary emphysema is characterized by the presence of gas dissecting the interstitial tissues of the lung. Clinically, it may be acute or persistent, and the latter can be further categorized as localized or diffuse. Usually, it appears in preterm neonates with a history of assisted ventilation or respiratory distress. Although far from frequent, the localized variety of persistent interstitial pulmonary emphysema (PIPE) can develop spontaneously in full-term babies or infants without any obvious underlying pulmonary disease. Histologically, PIPE is characterized by the presence of uni- and multinucleated histiocytes lining the inner surface of the cysts. In this report, we describe a 15-year-old male with synovial sarcoma (SS) of the right ankle diagnosed 4 years previously who developed pulmonary metastasis, one of which presented cystic changes with features of PIPE.

Adolescent↗