History of clinical transplantation

How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

Calculations on open shell small molecules using different Gaussian orbitals for electrons with different spins

An extension of Frost’s method to open shell systems using different floating spherical Gaussian orbitals for electrons with different spins is presented. The results of ab initio computations on some small molecules are given and the degree to which electron correlation is included is discussed

The electronic structure and properties of the polyenes

The self-consistent field molecular orbital theory has been used to calculate the electronic structure and properties of the first ten members of the polyene series. From these results the properties of the infinite polyene are predicted

Graphite: The ultimate large aromatic molecule

A π-band theory calculation is reported on a single layer of graphite, the nomenclature and methods of molecular orbital theory being used. Interaction between non-nearest neighbours at increasing distances is included to determine the extent of significant electron interaction. A criterion to determine this limit is defined and used. A comparative study is made of the methods available for the evaluation of double integrals over triangular fields

Theoretical studies of electrode potentials in aqueous solution. Investigation of individual contributions from electrostatic, cavity and dispersion interactions to redox potentials

Electrode potentials of some benzoquinones and naphthoquinones were calculated using ab-initio and AM1 methods. The effect of individual contributions from electrostatic, cavity and dispersion interactions were analyzed for polar and nonpolar molecules. Up to 7% of variation in the electrode potentials of quinones studied in this work is due to cavitation and 15% to the dispersion term. Both SCRF and FEP methods give reasonable agreement when 6-31G* basis set is used at the Hartree-Fock level. Comparison of the AM1 calculated electrode potentials with the AM1-COSMO results shows the superiority of the SCRF model and the importance of the inclusion of the cavity and dispersion terms

Gene-diet interactions in exposure to heterocyclic aromatic amines and bulky DNA adduct levels in blood leukocytes

Heterocyclic aromatic amines (HAAs), carcinogens produced in meat when cooked at high temperatures, are an emerging biologic explanation for the meat-colorectal cancer relationship. HAAs form DNA adducts; left unrepaired, adducts can induce mutations, which may initiate/promote carcinogenesis. The purpose of this research was to investigate the relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct levels. Least squares regression was used to examine the relationship between dietary HAA exposure and bulky DNA adduct levels in blood measured using 32 P-postlabeling among 99 healthy volunteers. Gene-diet interactions between dietary HAAs and genetic factors relevant to the biotransformation of HAAs and DNA repair were also examined. No main effects of dietary HAAs on bulky DNA adduct levels was found. However, those with the putative NAT1 rapid acetylator phenotype had lower adduct levels than those with the slow acetylator phenotype (P = 0.02). Furthermore, having five or more 'at-risk' genotypes was associated with higher bulky DNA adduct levels (P = 0.03). Gene-diet interactions were observed between NAT1 polymorphisms and dietary HAAs (P < 0.05); among the slow acetylator phenotype, higher intakes of HAAs were associated with an increase in DNA adduct levels compared to lower intakes. This study provides evidence of a biologic relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct formation. However, the lack of a strong main effect of HAAs suggests that dietary HAAs are not a large contributor to bulky DNA adducts in this population; future studies should consider relevant gene-diet interactions to clarify the role of HAAs in carcinogenesis. Environ. Mol. Mutagen., 2015. (c) 2015 Wiley Periodicals, Inc