A history and overview of phenotypic variability in CYP2D6 activity

CYP2D6 is a human cytochrome P450 that is responsible for the metabolism of a large number of drugs and chemicals. Interest in CYP2D6 has largely centered on the wide interindividual variability in its catalytic activity that stems from a common genetic polymorphism in the CYP2D6 gene. Two major phenotypes exist, extensive metabolizer (EM) and poor metabolizer (PM), together with the two less studied phenotypes of ultrarapid metabolizer (UM) and intermediate metabolizer. These phenotypes are the expression of an underlying allelomorphism in CYP2D6 and are also context dependent. Several drugs that are CYP2D6 substrates display polymorphic metabolism, that is, the existence in the population of multiple phenotypes, in particular EM and PM. The most notable drugs in this regard are debrisoquine and sparteine, although there are also data for a few others, in particular, dextromethorphan and metoprolol. Many nongenetic factors can alter the expression of CYP2D6 phenotypes, the most significant of which is the presence of other drugs. In this context, the EM phenotype may not be immutable, with potential conversion into a PM phenocopy, due to significantly impaired CYP2D6 metabolism in the presence of other CYP2D6 substrates and inhibitors. This phenotype interconversion generated great concern and helped drive the movement away from phenotyping based upon drug administration to genotyping of acquired DNA samples. However, ascertaining the presence of CYP2D6 alleles in a DNA sample does not determine the metabolism and pharmacokinetics of CYP2D6 substrates in that subject: it is a forecast, much like the weather forecast and, as we all know regarding the weather, the forecast can be inaccurate at times.

Psychological adaptation to spousal bereavement in old age. The role of trait resilience, marital history, and context of death

This research examined the effect of marital status and gender on various indicators of psychological adaptation, namely depressive symptoms, loneliness, and life satisfaction. It further explores the role of trait resilience, marital history, and context of death for predicting These outcomes in bereaved individuals. Four hundred eighty widowed individuals aged between 60 and 89 were compared with 759 married peers. Main effects were found for marital status and gender for all indicators. The regression analyses illustrate the multifaceted structure of psychological adaptation. Trait resilience is a key factor in adapting to spousal bereavement, whereas marital history and the context are secondary.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

The London and Edinburgh philosophical magazine and journal of science.

3rd ser. : v.10 (1837 : Jan.-June)

Quarterly Journal of Science, Literature and the Arts.

1829 (July - Dec.)

Archives of science and transactions of the Orleans County Society of Natural Sciences.

1

The Ohio naturalist and journal of science.

Mode of access: Internet.

Proceedings of the Society for Experimental Biology and Medicine

List of members in each volume

The structure and design philosophy of OL/2, an array language,

Includes bibliographies.

A selected reading list of interest to students in the field of agricultural history and allied subjects in the Museum Library.

Compiled by Mary B. Day.

Unitarianism, its origin and history : a course of sixteen lectures /

Introduction. [Signed: H.G.S.]--Early Christian doctrine. By J.H. Allen.--Christianity from the fifth to the fifteenth century. By A.P. Peabody.--Unitarianism and the reformation. By S.C. Beach.--Unitarianism in England. By B. Herford.--The contact of American Unitarianism and German thought. By J.H. Allen.--The church and the parish in Massachusetts. Usage and law. By G.E. Ellis.--Early New England Unitarians. By A.P. Peabody.--Channing. By G.W. Briggs.--Transcendentalism: the New England renaissance. By F. Tiffany.--Theodore Parker. By S.B. Stewart.--Unitarianism and modern literature. By F. Hornbrooke.--Unitarianism and modern Biblical criticism. By J. de Normandie.--Unitarianism and modern scientific thought. By T.R. Slicer.--The law of righteousness. By G. Batchelor.--The relation of Unitarianism to philosophy. By C.C. Everett.--Ecclesiastical and denominational tendencies. By G. Reynolds.

New Zealand nature notes. Short sketches of the geology, botany, zoology, and ethnology of New Zealand (with notes on engineering-works) for the use of members of the Australasian Association for the Advancement of Science, Wellington Meeting, January, 1923.

Mode of access: Internet.