Cell losses

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

Continuous Stirred Tanks with Biomass Recycle. When the desired product is excreted, closing the system with respect to biomass offers a substantial reduction in the cost of nutrients. The idea is to force the cells into a sustained stationary or maintenance period where there is relatively little substrate used to grow biomass and where production of the desired product is maximized. One approach is to withhold some key nutrient so that cell growth is restricted, but to supply a carbon source and other components needed for the desired product. It is sometimes possible to maintain this state for weeks or months and to achieve high-volumetric productivities. There will be spontaneous cell loss (i.e., kd > 0), and true steady-state operation requires continuous purging and makeup. The purge can be achieved by incomplete separation and recycle... 

Many in vitro studies have been undertaken to explore the relative effectiveness of isothiocyanates, and associated compounds, as inhibitors of cell growth and inducers of apoptosis in cell lines, and some of these are summarised in Table 4.2. Clonal survival studies are often used to determine whether isothiocyanates inhibit initial cell anchorage and subsequent growth of sparsely seeded cells. However, differences in cell number following challenge with the isothiocyanate could be due either to decreased cell division or increased cell loss, and the authors of some in vitro studies have failed to recognise this. Other studies have, however, considered the interacting... 

Craven, P.A., Pfanstiel, J., Saito, R. and DeRubertis, F.R. (1987). Actions of sulfasalazine and 5-aminosalisylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. Gastroenterology 92, 1998-2008. 

High reticulocyte counts may indicate red blood cells loss via acute blood loss, hemolysis, or splenic sequestration. 

Sleep-wake state alterations in PD can be broadly classified into disturbances of (1) thalamocortical arousal state and (2) excessive nocturnal movement (Rye and Bliwise 2004 Rye and Iranzo 2005). The former includes the loss of sleep spindles and SWS, daytime sleepiness, and intrusion of REM sleep into daytime naps (i.e. sleep onset REM periods, or SOREMs), and the latter encompass periodic leg movements of sleep (PLMs) and REM sleep behavior disorder (RBD). The pathophysiological basis of sleepiness and SOREMs appears to be dopaminergic cell loss in PD, though excessive nocturnal movements are not as clearly related to dopaminergic deficits. 

The cause of the orexin-containing cell loss in typical narcolepsy-cataplexy remains unknown, but the HLA association is intriguing because it suggests that autoimmunity could mediate a central disease process. This is not... 

Harvey, D.C., Lacan, G., Tanious, S.R, Melega, W.R Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss. Brain Res. 871 259, 2000. 

Dihydroxybenzoic acid (DHB) is also a commonly used tool to measure the pharmacological effects of HIF-la stabilization via PHD inhibition. Recently, it was shown that mice pretreated with DHB (100 mg/kg, i.p.) showed a marked resistance to the neurotoxic effects of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) via protection of dopaminergic cell loss and striatal denervation. Importantly, this protection was seen to coincide with HIF-la stabilization, and the prevention of the MPTP-induced loss of ferroportin and striatal iron. Additionally, in these studies, DHB was also observed to block MPTP-induced reduction in mitochondrial pyruvate dehydrogenase, at both the mRNA level and through the measurement of enzyme activity in midbrain substantia nigra [26]. 

The second most documented toxicological effect occurs between OTC and the central nervous system. TMT causes cell loss in the central nervous system and TET causes brain and spinal cord edema. Brain retention of the organotin moiety increased as follows ... 

Enhancement of neuronal atrophy and cell loss during aging by severe and prolonged psychosocial stress are examples of allostatic load 856... 

Stark, A. K., Uylings, H. B., Sanz-Arigita, E. and Pakkenberg, B. Glial cell loss in the anterior cingulated cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am. J. Psychiatry 161 882-888, 2004. 

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