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J R Subjeck

Publications and source records attributed to J R Subjeck.

53 records · Page 3Linked to original sources

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.

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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.

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Colloidal iron hydroxide-binding to the surfaces of chick embryo fibroblasts transformed by wild-type and a temperature-sensitive mutant of Rous sarcoma virus.

The densities of colloidal iron hydroxide (CIH) particles binding to the surfaces of chick embryo fibroblasts were determined before and after transformation with wild type Rous sarcoma virus and a temperature sensitive (ts) mutant of this virus. On the basis of in vitro behavior, cells transformed by the ts virus manifest a malignant phenotype at 36 degrees C (permissive temperature) and appear normal at 41 degrees C (non-permissive temperature). At the permissive temperatures there is a significant increase in CIH particle-binding to spaces of cell surface between microvilli on the wild type and ts transformed cells. At the non-permissive temperature this significant increase in binding is only observed on the wild type transformant, while the density found on the ts transformant is not significantly different from the untransformed state. Therefore, in vitro characteristics of normalcy and malignancy are reflected in changes in the CIH binding properties of the cell surface spaces between microvilli. The CIH densities observed on the microvilli are significantly different from the density on the spaces between them for each of the classes of cells studied at either temperature. The microvilli are found to bind a lower density of particles in five of the six cases. No correlations between microvilli particle density and transformation to in vitro malignant characteristics were observed.

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Some electrical properties of the peripheries of murine 3T3 cells with respect to viral transformation and reversion.

Mouse 3T3, Simian virus 40 transformed 3T3 cells (SV3T3) and two SV3T3 lines showing reversion of their transformed phenotype (Rev 3 and Rev 5) have been studied with respect to electrophoretic mobilities and colloidal iron hydroxide (CIH) binding density visible by electron microscopy, before and after incubation with neuraminidase or ribonuclease. The results show that, in general, the marked changes in both sets of surface parameters associated with transformation are largely reversed in the Rev 5 revertant, and only partially reversed in the Rev 3 line. It was also observed that, in common with Ehrlich ascites tumor (EAT) cells examined previously, the densities of CIH-particles bound over the microvilli of all the cell types was 1.5 to 2.7 times higher than those bound to the spaces between them. In contrast to the EAT cells, the higher density of CIH particles bound over the microvilli was not due to neuraminidase-sensitive binding sites.

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The binding of cationized ferritin at the surfaces of ehrlich ascites tumor cells: the effect of pH and glutaraldehyde fixation.

The densities of cationized ferritin (CF) particles binding to the surfaces of cultured Ehrlich ascites tumor cells were determined at pH 7.4, where the ferritin stain was applied either prior to or following glutaraldehyde fixation. The densities were also determined with CF adjusted to pH 1.9 and applied after fixation. For all fixed samples there was a higher density of particles bound to microvilli than to the spaces between them. Treatment with neuraminidase removed more particles from microvilli than from the inter-microvillus spaces, but did not reduce the levels of binding to the same value. When cationized ferritin is applied prior to fixation, an aggregation of the CF particles at the cell surface was observed, with the internalization of some clusters. This effect was independent of neuraminidase treatment.

Aldehydes↗

Nitroimidazole inhibition of lactate production in CHO cells.

Misonidazole (MISO) and desmethylmisonidazole (DMM) inhibit lactate production in CHO cells under aerobic conditions. This inhibition is time and dose dependent. At the 20 mM level DMM is stronger in producing this inhibition of lactate than is MISO. This inhibiton of lactate production suggests that these compounds are capable of inhibiting the glycolytic pathway. The resultant energy deficiency may be an explantation for the toxicity of these compounds under hypoxic as well as aerobic conditions. The increased dependency on glycolysis of hypoxic cells may correspond to the analogous increase in toxicity of hypoxic cells to nitroimidazoles.

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Cancer immunotherapy: stress proteins and hyperthermia.

Heat shock proteins (hsps) can induce anti-cancer immune responses by targeting associated tumour antigens to the immune system. Hsps are not merely carriers of antigen but can also induce maturation of dendritic cells (DCs), resulting in a more efficient antigen presentation. However, improvement of hsp-based vaccines is still desirable if one is to realize their full therapeutic potential. Since the immune system consists of different elements functioning together in a highly integrated way, a combination therapy utilizing important immunomodulators together with hsp-based vaccination may improve therapeutic response. Hyperthermia has been shown to have important stimulatory effects on several cellular and organismal endpoints related to the immune system. This review highlights advantages and disadvantages of various ways of using stress proteins in cancer immunotherapy. It also overviews the interaction of hyperthermia with heat shock protein therapy and the related effects on the host's immune response.

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