Biomedical subjects

B G Blair

Publications and source records attributed to B G Blair.

5 recordsLinked to original sources

PubMed2006

Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells.

Transforming growth factor-beta type 1 (TGF-beta) has been implicated as both a tumor suppressor and a tumor promoter in many solid epithelial cancers. We have previously demonstrated that the cyclin dependent kinase (CDK) inhibitor p21 acts as a molecular switch in determining a growth inhibitory versus growth proliferative response to TGF-beta in the spontaneously immortalized human mammary epithelial cell line MCF-10A. We now demonstrate that this proliferative effect of TGF-beta is mediated through the proinflammatory cytokine, interleukin-1alpha (IL-1alpha). Using gene expression array analysis, we identified IL-1alpha as a cytokine specifically upregulated only in cells lacking p21 and only upon TGF-beta stimulation. Cell proliferation assays verified that recombinant IL-1alpha was capable of inducing a growth proliferative response in p21 null MCF-10A cells, while neutralizing antibodies against IL-1alpha prevented the growth proliferative effects of TGF-beta. Mechanistically, both the CDK and proliferating cell nuclear antigen (PCNA) inhibitory functions of p21 were responsible for preventing TGF-beta induced cell proliferation, but only PCNA inhibition by p21 regulated IL-1alpha gene expression. These studies demonstrate a novel role for IL-1alpha in mediating a proliferative response to TGF-beta signaling, and suggest that therapies directed against IL-1alpha could abate the growth proliferative effects of TGF-beta without compromising its tumor suppressive function.

Cell Line, Tumor↗

PubMed1999

Regulation of cellulose-inducible structures of Clostridium cellulovorans.

Scanning electron microscopy was used to detect ultrastructural protuberances on the cellulolytic anaerobe Clostridium cellulovorans. Numerous ultrastructural protuberances were observed on cellulose-grown cells, but few were detected on glucose-, fructose-, cellobiose-, or carboxymethylcellulose (CMC)-grown cells. Formation of these protuberances was detected within 2 h of incubation in cellulose medium, but 4 h incubation was required before numerous structures were observed on the cells. When a soluble carbohydrate or CMC was mixed with cellulose-grown cells, the ultrastructural protuberances could no longer be detected. In fact, no protuberances were observed within 5 min following the addition of glucose, cellobiose, or methylglucose to cellulose-grown cells. The presence of these protuberances corresponded with the binding of the Bandeiraea simplicifolia BSI-B4 isolectin to the cell. Cellulose-grown cells had a greater level of observable lectin binding than cellobiose-grown cells, and lectin binding was not detected on glucose- or fructose-grown cells. In addition, lectin binding ability was lost by cellulose-grown cells following the addition of glucose, fructose, or methylglucose to the cellulose medium. A cellulose-affinity protein fraction expressing cellulase activity was also detected in cell extracts of cellobiose- or cellulose-grown cultures. However, this protein fraction was not detected in extracts of glucose-grown cultures, and was rapidly lost (within 5 min) following the addition of glucose to cellulose-grown cultures. The ability of C. cellulovorans to adhere to cellulose was also affected by the energy substrate, but not in the same manner as the protuberance formation or the cellulase-containing protein fraction. Rather, cellobiose-, cellulose-, and CMC-grown cultures adhered to cellulose, but this adherence was not affected by addition of glucose to the medium. This is the first report that soluble carbohydrates caused the rapid loss of some cellulose-inducible systems of C. cellulovorans.

Bacterial Adhesion↗

PubMed1998

Accidental nuclear war--a post-cold war assessment.

BACKGROUND: In the 1980s, many medical organizations identified the prevention of nuclear war as one of the medical profession's most important goals. An assessment of the current danger is warranted given the radically changed context of the post-Cold War era. METHODS: We reviewed the recent literature on the status of nuclear arsenals and the risk of nuclear war. We then estimated the likely medical effects of a scenario identified by leading experts as posing a serious danger: an accidental launch of nuclear weapons. We assessed possible measures to reduce the risk of such an event. RESULTS: U.S. and Russian nuclear-weapons systems remain on a high-level alert status. This fact, combined with the aging of Russian technical systems, has recently increased the risk of an accidental nuclear attack. As a conservative estimate, an accidental intermediate-sized launch of weapons from a single Russian submarine would result in the deaths of 6,838,000 persons from firestorms in eight U.S. cities. Millions of other people would probably be exposed to potentially lethal radiation from fallout. An agreement to remove all nuclear missiles from high-level alert status and eliminate the capability of a rapid launch would put an end to this threat. CONCLUSIONS: The risk of an accidental nuclear attack has increased in recent years, threatening a public health disaster of unprecedented scale. Physicians and medical organizations should work actively to help build support for the policy changes that would prevent such a disaster.

Disasters↗

PubMed1998

Comparison of staining techniques for scanning electron microscopic detection of ultrastructural protuberances on cellulolytic bacteria.

Cell surface protuberances found on cellulolytic bacteria, but not on noncellulolytic bacteria, can be detected by scanning electron microscopy. Cationized ferritin typically has been used as a stain to increase the microscopic resolution of these protuberances; however, as a cation it binds only to negatively charged molecules. Thus, binding of cationized ferritin to cell surface molecules can be affected by the cell's physiological state. We incubated the noncellulolytic bacterium, Clostridium beijerinckii, in different media at various temperatures to obtain cells with different growth rates and physiological states. Staining of these cells with cationized ferritin showed that slower growing cells exhibited more protuberant structures than faster growing cells. This provided a clear correlation of ultrastructural protuberances with physiological changes associated with growth rate. On the other hand, cells stained with osmium tetroxide exhibited no protuberant structures regardless of growth rate. Because various cations are known to induce aggregation of surface proteins on some cellulolytic Clostridia, we incubated the cellulolytic bacterium, Clostridium cellulovorans, in media containing glucose, cellobiose, or cellulose. Ultrastructural protuberances were evident on all cells stained with cationized ferritin, but extensive protuberances were detected only on cells grown in cellulose and stained with osmium tetroxide. For cells stained with cationized ferritin, the presence of ultrastructural protuberances was correlated with growth rate rather than induction of cellulolytic systems. By contrast, cells stained with osmium tetroxide showed a clear correlation between protuberant structures and cellulolytic activity.

Clostridium↗

PubMed1996

Regulation of the cellulolytic activity of Eubacterium cellulosolvens 5494: a review.

Eubacterium cellulosolvens 5494 is a cellulolytic gram positive bacterium isolated from the rumen. Substrate specific regulation has not been previously demonstrated in any members of this genera. However, we have recently found that E. cellulosolvens regulates some of its membrane proteins. Growth on different substrates, including cellulose and cellobiose, gave different SDS-PAGE profiles of proteins from the membrane fraction. Using scanning electron microscopy, we also found that growth of E. cellulosolvens on cellulose induces an ultrastructural complex that is not present when grown on any other substrate. Further study revealed that this ultrastructure was subsequently lost when an alternative substrate was made available to cellulose growing cells. We also found that cellulose, cellobiose, and maltose utilization are inhibited in the presence of a glucose analog, indicating glucose is the preferred substrate.

Cellobiose↗