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Biomedical subjects

M Huleihel

Publications and source records attributed to M Huleihel.

61 records · Page 4Linked to original sources

Effect of mouse interferon on retrovirus production by chronically infected rat cells.

Mouse interferon (IFN) inhibited retrovirus release by both mouse and rat cells with the same efficiency. However, the antiviral state developed more slowly in rat than in mouse cells, and after removal of IFN it also persisted for a longer time in rat than in mouse cells. Under conditions where IFN strongly inhibited virus production it had no effect on cell replication nor on cellular RNA or protein synthesis.

Animals↗

Rapid syncytium formation induced by Moloney murine sarcoma virus in 3T3/NIH cells and its delay by mouse interferon.

Moloney murine sarcoma virus (MSV) clone 124 was found to induce rapid syncytium formation upon infection of 3T3/NIH at a high multiplicity of infection. This effect became apparent, by light microscopy, within 1 to 2 hours, whereas by scanning electron microscopy, clusters of 4 to 25 cells were seen in their initial steps of syncytium formation within 20 to 30 minutes after virus addition. It appeared that the cell fusion was initiated by connection between the cells through virus bound to their surface. After a few more hours several neighbouring syncytia fused into giant cells containing over a hundred nuclei. Though MSV (124) stocks contained also some MLV it appeared that the syncytium inducing activity was related to the MSV particles. MLV particles were not only incapable to induce syncytium formation, they even interfered with this activity of MSV. The MSV-induced cell fusion required the adsorption of intact virions, but was independent on protein synthesis. Mouse interferon remarkably reduced the rate of syncytium development.

Animals↗

Can Fourier transform infrared spectroscopy at higher wavenumbers (mid IR) shed light on biomarkers for carcinogenesis in tissues?

Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a technique for detection of abnormal cell proliferation and premalignant conditions. In the present study, we investigate the absorbance in the sensitive wavenumber region between 2800 and 3000 cm(-1), which has been known to be due to the antisymmetric and symmetric stretching vibrations of CH2 and CH3 groups of proteins and lipids. We report common biomarkers from this region that distinguish between normal and malignant tissues and cell lines. Based on our findings, we propose that the wavenumber region around 2800 to 3000 cm(-1) in the FTIR spectra of cells and tissues could provide valuable scientific evidence at the onset of premalignancy and may be used for ex vivo and in vitro detection of carcinogenesis. To further examine the utility of these markers in cancer diagnosis and management, they are tested successfully in monitoring the changes occurring in leukemia patients during chemotherapy.

Animals↗

Differential transcriptional control of the H-2K and H-2D loci of the major histocompatibility complex in fibrosarcoma cells.

In this study we demonstrate a differential transcription of H-2K and H-2D class-I genes in two different tumor cell clones; one is highly metastatic (IE-7) and the other is not metastatic (IC-9), both derived from the same fibrosarcoma, T-10, induced in an (H-2b x H-2k)F1 mouse. The expression of the two parental H-2K alleles is transcriptionally suppressed in both of these clones. In addition the IC-9 clone does not transcribe also the H-2Dk allele. Our data rule out the possibility that this suppression results from enhanced RNA degradation, impaired polyadenylation, DNA rearrangement, or changes in DNA methylation within these genes. Interferons (IFN) are known to enhance MHC expression by acting on a consensus IFN responsive element present in the promoter region of MHC genes. However, IFN-gamma, which is the most potent IFN in this respect, failed to activate the expression of the silent MHC genes in our cells. This finding may reflect a defect within the promoter region of these genes or changes in their chromatin structure.

Alleles↗

Effect of Porphyridium sp. polysaccharide on malignant cell transformation by Moloney murine sarcoma virus.

The polysaccharide produced by the red microalga Porphyridium sp. was highly inhibitory for cell transformation of mouse fibroblast cells by an MSV-124 virus stock. This inhibition was most effective if the polysaccharide was added 2 h before or at the time of infection. The finding that the inhibition of cell transformation by MuSV-124 was reversible after removal of the polysaccharide suggested that Porphyridium sp. polysaccharide inhibited a late step after provirus integration into the host genome. Addition of the polysaccharide post-infection significantly reduced the number of transformed cells, but its effect was less marked than that obtained when the polysaccharide was added before or at the time of infection. These findings support the possibility that the polysaccharide may affect early steps in virus replication cycle, such as virus absorption into the host cells, in addition to its effect on a late step after provirus integration.

3T3 Cells↗

Aberrations in interleukin-1 expression in oncogene-transformed fibrosarcoma lines: constitutive interleukin-1 alpha transcription and manifestation of biological activity.

We have examined interleukin-1 (IL-1) expression in a series of oncogene-transformed NIH-3T3 fibroblastoid cell lines. In contrast to primary fibroblasts where IL-1 is inducible, NIH-3T3 cells (clone 490N3T) transcribe the IL-1 alpha gene constitutively. Transformation of 490N3T cells by the v-mos or v-H-ras oncogenes appears to either enhance or suppress IL-1 alpha transcription, respectively. In v-myc transfected cells, constitutive IL-1 activity could be detected intracellularly. An additional membrane-associated form of IL-1 was observed in lines transformed by protein-kinase (PK) encoding oncogenes, such as TPR-met, c-met, v-src, v-abl, v-mos and v-raf. In none of the lines tested the secreted form of IL-1 activity could be detected, and no constitutive expression of IL-1 beta was observed. Our studies manifest aberrations in IL-1 expression in oncogene-transformed fibroblastoid cell lines, detected at different regulatory levels, such as transcription, translation and compartmentalization. IL-1 is a potent pleiotropic cytokine, with regard to its target cell specificity and spectrum of activities; growth promoting effects of IL-1 on fibroblasts were reported and on the other hand this cytokine activates various anti-tumor mechanisms. Thus, endogenous IL-1 expression by tumor cells may affect the neoplastic phenotype, either by influencing the growth of the malignant cells or by modifying tumor-host interactions.

3T3 Cells↗

Depressed IL-1 production by chronic GVHD dermal fibroblasts.

Chronic Graft-versus-Host disease (GVHD) is characterized by overt immunosuppression. In addition, the skin is a major anatomical site affected in chronic GVHD for reasons not yet known. Increased collagen deposition, a mononuclear cell infiltrate in the dermis as well as loss of fat and appendages, are observed in the skin. The inflammatory cytokine IL-1 was shown to affect fibroblast proliferation and secretory activities. In the present study, IL-1 generation by dermal fibroblasts, of chronic GVHD or control mice, was assessed. It was shown that two sequential signals are needed for IL-1 generation by dermal fibroblasts; priming by lymphokines/cytokines followed by a challenge with LPS. A variety of recombinant lymphokines and cytokines (G/M-CSF, IL-2, TNF, IL-1 beta and IFNs alpha, beta and gamma) were shown to be efficient in priming dermal fibroblasts for IL-1 generation. IL-1 activity in dermal fibroblasts, most probably of the IL-1 alpha species, was located in frozen-thawed cell lysates or associated to the cell membrane, though not secreted into the culture fluids. Dermal fibroblasts from chronic GVHD mice manifested a pronounced depression in IL-1 generation upon stimulation with exogenous lymphokines/cytokines and LPS. This was observed over a wide range of concentrations of lymphokines/cytokines and LPS. The depressed ability of chronic GVHD fibroblasts to generate IL-1 was pronounced even after few passages of the cells in vitro, and upon stimulation in culture outside the suppressive milieu of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗