Distribution and Phenotype

Dunn-Meynell, A. A., Rawson, N. E., Levin, B. E. Distribution and phenotype of neurons containing the ATP-sensitive hC channel in rat brain, Brain Research 1998, 814, 41-54. 

Two main subdivisions of the temporal neocortex were investigated—the visual area IT and the auditory area STG. We did not observe important differences between IT and STG with regard to the distribution and phenotype of BrdU+ cells, and therefore these regions are presented in a common section. 

Fig. 64 Distribution and phenotype of adult-generated cells in postischemic monkey DG at short-term andlong-term survival time periods al ter surgery. Note the numerous progenitor cells forming clusters in SGZ at short-term survival some of these cells were preserved at long-term survival. Typical for the early periods after ischemia were neuronal progenitors extending processes parallel to DGL, while atlong-term survival the processes were spanning DGL. The quantity of newly generated cells with a mature neuronal phenotype increased over time...

We performed transient global cerebral ischemia on adult macaque monkeys by reversibly stopping blood flow to the brain. We labeled de novo-generated cells in postischemic animals as well as in sham-operated controls by infusing the DNA synthesis indicator BrdU, and subsequently investigated the distribution and phenotype of BrdU-labeled cells in several telencephalic regions at various time-points after ischemia. 

Distribution and Phenotype of Proliferating Cells in the Forebrain of Adult Macaque Monkeys After Transient Global Cerebral Ischemia... 

S., Single-fiber PCR in MELAS(3243) patients Correlations between intratissue distribution and phenotypic expression of the mtDNA(A3243G) genotype. Am. J. Med. Genet. 94, 201—206 (2000). 

Senni, K., BorchieUini, C., Duchesnay, A., PeUat, B., Letourneur, D., Kem, R, 1998. Antiproliferative polysaccharides modulate distribution and phenotypic expression of collagens by gingival fibroblasts. J. Biomed. Mater. Res. 40, 164—169. 

Xie, H. G., Stein, C. M. et al. (1999). Allelic, genotypic and phenotypic distributions of S-mephenytoin 4 -hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics, 9(5), 539-49. 

Boerkoel, C. F., Takashima, H., Garcia, C. A. et al. Charcot-Marie-Tooth disease and related neuropathies. Mutation distribution and genotype-phenotype correlation. Ann. Neurol. 51 190-201,2002. 

Schon-Hegrad MA, Oliver J, McMenamin PG, Holt PG Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (la)-bearing dendritic cells in the conducting airways. J Exp Med 1991 173 1345-1356. 

Figure 12. The error threshold of replication and mutation in phenotype space. The genotypic error threshold approaches zero in the case of selective neutrality. Despite changing genotypes a phenotype may be conserved in evolution whenever it has higher fitness than the other phenotypes in the population. The concept of error threshold can easily be extended to competition between phenotypes. The distribution of phenotypes is stationary provided the error rate does not exceed the maximum value pmax which is a function of the mean fraction of nearest neighbors, X, and the superiority of the master phenotype, a. The illustration shows the position of the phenotypic error threshold in the X, p plane. Selective neutrality allows more errors to be tolerated and pmax increases accordingly with increasing X. If X approaches the inverse superiority, X — a-1, the tolerated error may grow to pmax = 1, and this means the phenotype will never be lost, no matter how many errors are made in replication.

We present here the first comprehensive analysis of the distribution, quantity, and phenotype of de novo-generated cells in several regions of adult primate brain after transient global cerebral ischemia. 

A, AB, B, CB, AC and C. From numerous distribution and family studies it has been determined that the six phenotypes are directed by three common alleles pa, p, and pc (2,3, ). Using crude hemolysates ( 5) and 1,000 fold pure homogeneous type AA and BB enzymes (6) some properties of EAP, such as thermostability, pH and substrate specificity and molecular size, have been examined. From the time EAP polymorphism was first described, the use of the enzyme as a means of typing human blood has been of interest to the forensic scientist. Investigators have described successes in typing dried bloodstains stored at 20 - 25 C for 5-8 weeks and stored whole blood kept at 5 C was typed for as long as 15 months ( 7). Difficulties in typing EAP types AB (1,3), B and C (J3 ) have also been described. 

Metoprolol is a (3-blocker that has been proposed as a pharmacokinetic alternative to debrisoquine in countries where it is difficult to use debrisoquine. Metoprolol is metabolized to desmethylmetroprolol and a-hydroxymetoprolol by CYP2D6 (124). The a-hydroxymetoprolol metabolite has been shown to be bimodally distributed and to correlate with the debrisoquine oxidation phenotype (125). Again, metoprolol has been used primarily to distinguish between CYP2D6 EMs and PMs. However, in African populations, the metoprolol metabolic ratio failed to predict the PMs of debrisoquine (126). These studies would suggest that in some ethnic groups metoprolol may not be a suitable probe. 

Besides meeting its assumptions, other problems in the application of SSD in risk assessment to extrapolate from the population level to the community level also exist. First, when use is made of databases (such as ECOTOX USEPA 2001) from which it is difficult to check the validity of the data, one does not know what is modeled. In practice, a combination of differences between laboratories, between endpoints, between test durations, between test conditions, between genotypes, between phenotypes, and eventually between species is modeled. Another issue is the ambiguous integration of SSD with exposure distribution to calculate risk (Verdonck et al. 2003). They showed that, in order to be able to set threshold levels using probabilistic risk assessment and interpret the risk associated with a given exposure concentration distribution and SSD, the spatial and temporal interpretations of the exposure concentration distribution must be known. 

Gaedigk A, Bradford LD, Marcucci KA, Leeder JS (2002) Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans. Clin Pharmacol Ther 72 76-89... 

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