Phenotypical mixing

The most elegant demonstration of the role of the specific receptor in limiting enterovirus infection is the report (IO) that phenotypically-mixed virions resulting from the dual infection of poliovirus type I and coxsackievirus B1, when subsequently added to cells resistant to poliovirus (by virtue of the absence of specific receptors) under conditions limiting specifically the replication of coxsackievirus RNA, yielded only poliovirus type I virions. Since only poliovirus RNA coated in coxsackievirus capsid material would be capable of initiating infection and productively multiplying, these results dramatically illustrate that the... 

The situation is somewhat more complex for virus sample amphfied or isolated directly from patient plasma, as these samples comprise a heterologous mix of related yet genetically distinct quasi-species. Often these samples contain mixtures of CCR5-tropic (R5), CXCR4-tropic (X4), and/or dual-tropic viruses these samples are classified in phenotypic ttopism assays as dual/mixed tropic (D/M) (Whitcomb etal. 2007). 

It is important to realize, that diseases such as myocardial infarction or type 2 diabetes represent a heterogeneous group of several distinct subphenotypes definable by clinical or biochemical characteristics. Thus, contradictory findings in pharmacogenomic studies may only not be the consequence of a lack of a major isolated gene effect (of the gene variant studied) and chance findings, but also be caused by the variability in the mix of distinct clinical phenotypes hidden beneath a common characterization such as type 2 diabetes and modulated by differences in the environment between studies. 

The effects of Pb on the mixed lymphocyte response (MLR) have been examined in prior studies. McCabe and colleagues [53] and Farrer and colleagues [54] demonstrated that Pb in vitro at very low concentrations (0.1 pM = 2 pg/dL) significantly enhanced the proliferation and expansion of murine alloreactive CD4+ T lymphocytes in the MLR. The expanded T cell population was found to have a high density of CD4 molecules on the cell surface making them phenotypically similar to memory/effector T lymphocytes. In a study using Lewis strain rats, Razani-Boroujerdi and coworkers [55] also found evidence for Pb-induced stimulation of the in vitro MLR. 

Calu-3 (American type culture collection ATCC HTB-55) is a human bronchial epithelial cell line derived from an adenocarcinoma of the lung [59], This cell line has been shown to exhibit serous cell properties and form confluent monolayers of mixed cell phenotypes, including ciliated and secretory cell types [60], but the cilia are formed very irregularly and seem to disappear with increasing passage number (unpublished observations, C.E. and B.F.). Calu-3 cells have shown utility as a model to examine transport [61-63] and metabolism in human bronchial epithelial cells for many therapeutic compounds [64], Furthermore, they have been used in a number of particlecell interaction studies [65-67], The interactions between respiratory epithelial cells and particulates are discussed more in detail in Chap. 19. 

Besides sperm dysfunction, comparison of PMCA4 null 129/SvJ and Black Swiss mixed background mice revealed a strain specific smooth muscle phenotype, impaired phasic contractions and an apoptotic tendency for portal vein smooth... 

In addition to cell migration, another characteristic function of the VSM synthetic phenotype is proliferation. CaMKII has been implicated in cell cycle control in a number of systems, but investigations in this area have yield mixed results. Most studies to date have relied on pharmacological inhibitors of CaMKII such as KN-62 or KN-93 (Tombes et al. 1995) and point to a positive role for CaMKII in mediating the cell cycle. Conversely, overexpression of a constitutively active mutant of CaMKIIa. suggested a negative role for kinase (Beauman et al. 2003). Interpretation of the latter studies is complicated by potential nonspecific effects... 

Etiologies for most of the LSDs have been well documented, some for almost a century. The unique variations of phenotype, age at onset, clinical progression, and severity of the individual LSDs, depend on the degree of enzymatic deprivation, determined principally by whether the mutational mix... 

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