Variation between observers in classifying multiple sclerosis.
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Adult↗
Biomedical subjects
H L Ford
Publications and source records attributed to H L Ford.
Expression of Mts1, a metastasis-associated gene, increases motility but not invasion of a nonmetastatic mouse mammary adenocarcinoma cell line.
The mts1 gene codes for a 101 amino acid protein belonging to the S100 subfamily of Ca(2+)-binding proteins. Mts1 is overexpressed in metastatic cancers as compared to their nonmetastatic counterparts, and although mts1 is known to be involved in the metastatic phenotype (Davies et al., 1993; Grigorian et al., 1993), the role mts1 plays in this process is not clearly understood. In order to determine what role mts1 plays in the process of metastasis, we have performed transfection studies on nonmetastatic and metastatic mouse mammary adenocarcinoma cell lines, CSML0 and CSML100, respectively (Senin et al., 1983, 1984). The metastatic variant, CSML100, expresses high levels of mts1, whereas the nonmetastatic variant, CSML0, expresses almost no mts1. CSML0 cells transfected with mts1 were assessed in in vitro motility and invasion assays, as well as in vivo metastasis assays to determine the role of mts1 in these processes. Cell lines expressing mts1 display an altered morphology as well as increased motility in modified Boyden chemotaxis chambers. However, no significant increase in in vitro invasion or in in vivo metastasis was observed. Therefore, the presence of mts1 may be important for metastasis by increasing motility, but may not be sufficient for invasion in vitro or metastasis in vivo. Very low levels of type IV collagenase activities were observed in CSML0 cells and the transfectants, as opposed to the highly metastatic CSML100 cells, where high levels of type IV collagenase activities were observed. It is possible that the presence of these proteases in addition to mts1 may be responsible for the high metastatic potential of the CSML100 in vivo.
Adenocarcinoma↗
Interaction of metastasis associated Mts1 protein with nonmuscle myosin.
The mts1 gene codes for a 101 amino acid protein which belongs to the subfamily of S100 Ca(2+)-binding proteins and is overexpressed in metastatic cancers as compared to their nonmetastatic counterparts. While the Mts1 protein is putatively involved in cytoskeletal-membrane interactions, its exact physiological role is not known. In order to gain insight into the biological function of Mts1, its expression was monitored throughout mouse embryogenesis as well as in normal adult mouse tissues. In situ hybridizations of mouse embryos showed expression of mts1 mRNA to be highest in trophoblast cells of a day 8 old embryo. In normal adult mouse tissues, immunocytochemistry revealed Mts1 expression in a T-cell specific pattern in both the thymus and spleen. These results indicate that the expression of mts1 is prevalent in motile cell types, and to further elucidate the role of Mts1, gel overlay and GST-fusion protein experiments were performed to identify proteins that interact with the Mts1 protein. Nonmuscle myosin II was found to interact with Mts1, suggesting a role for Mts1 in the process of motility and lending credence to the hypothesis that Mts1 may enhance metastatic potential by increasing the motility of cancerous cells.
Age Factors↗
Telling your patient he/she has multiple sclerosis.
It is difficult to tell a person that s/he has multiple sclerosis. The diagnosis is based on clinical findings and often cannot be made on first meeting. In many cases investigations do not help. When the diagnosis is made, the patient should be fully informed in the majority of cases. Guidelines have been developed for imparting the diagnosis. Early diagnosis will become increasingly important with the development of new treatments for multiple sclerosis.
Female↗
Bacterial meningitis in developing countries.
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Child↗
Characterization of a positive regulatory element in the mts1 gene.
The first intron of the mts1 gene, a gene that is selectively expressed in metastatic cells and in normal cells that are motile, was found to be highly homologous to the CD3 delta enhancer element. Because of the homology between the CD3 delta enhancer and the first intron of mts1, we analysed the first intron of the mts1 gene to determine whether it functions as a transcriptional regulatory element. Highly metastatic CSML-100 cells transfected with chloramphenicol acetyl transferase-containing plasmids demonstrated the ability of the mts1 first intron to function as a positive regulatory element. In vitro footprinting analysis using extracts from CSML-0 cells (which express mts1 at low levels) or CSML-100 cells (which express mts1 at high levels) identified a protected 16-nucleotide element in the first intron of mts1, regardless of the extract used. However, in vivo footprinting analysis of the same region identified the protected 16-nucleotide fragment only in the mts1 intron from CSML-100 cells, not from CSML-0 cells. Differences in the methylation pattern of the mts1 gene in CSML-100 cells and CSML-0 cells are known to exist, and may in part be responsible for the mts1 footprinting differences observed in vivo from the different cell lines.
Animals↗
Transcriptional analysis of the mts1 gene with specific reference to 5' flanking sequences.
The mts1 gene is specifically expressed in certain metastatic tumors but not in their nonmetastatic counterparts. It is also expressed in several normal cell and tissue types that exhibit the ability to be motile. The gene was cloned from both mouse and human sources and the 5' flanking regions were sequenced. The sequencing data revealed a 135-base-pair region of high homology between the mouse and human mts1 gene. This homology was observed in the vicinity of the TATA box. The 5' region of the mts1 gene was also observed to have a high degree of homology to some known promoter and enhancer sequences. To determine the role this region plays in regulating the transcription of mts1, promoter analysis was performed. Sixteen constructs were prepared in which the chloramphenicol acetyltransferase gene was fused to different regions of the mouse mts1 promoter. These constructs were analyzed in transient transfection assays in two related cell lines derived from mouse mammary adenosarcomas: CSML-0, a nonmetastatic cell line with low levels of mts1 expression, and CSML-100, a metastatic cell line with high levels of mts1 expression. Results of our transient transfection assays in conjunction with results obtained from in vitro and in vivo footprinting of the promoter region show no evidence of cis-acting control elements important for the transcriptional regulation of mts1 in these cell lines. A few nucleotides upstream of the TATA box are sufficient for maximal levels of mts1 transcription. Because no cis-acting control elements were found, restriction of mts1 transcription in CSML-0 cells must exist on some other level. mts1 was found to be hypermethylated in CSML-0 cells but not in CSML-100 cells. The possible role of methylation in progression of the nonmetastatic CSML-0 adenosarcoma cell line toward the metastatic CSML-100 adenosarcoma cell line is discussed.
Animals↗