Detection of Anticancer Drug-Induced Cardiotoxicity Using VCAM1-Targeted Nanoprobes.

Chemotherapy-induced cardiac toxicity is an undesirable yet very common effect that increases the risk of death and reduce the quality of life of individuals undergoing chemotherapy. However, no feasible methods and techniques are available to monitor and detect the degree of cardiotoxicity at an early stage. Therefore, in this project, we aim to develop a fluorescent nanoprobe to image the toxicity within the cardiac tissue induced by an anticancer drug.

Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter.

We have identified three new human tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms with single nucleotide (nt) substitutions at -862, -856, and -574 nt relative to the TNF-alpha transcription start site. The -862 and -856 nt TNF-alpha promoter polymorphisms occur with high frequency in Caucasian and Cambodian individuals and are each non-randomly associated with three extended HLA haplotypes. This study, in which 61 independent TNF-alpha promoters were analyzed spanning from -977 to +93 nt relative to the TNF-alpha mRNA cap site, establishes a new canonical TNF-alpha promoter sequence.

HLA-Cw alleles associated with HLA extended haplotypes and C2 deficiency.

There are four MHC-linked complement genes, BF, C2, C4A and C4B, that are inherited as single DNA units, known as complotypes. Extended haplotypes were initially defined by studying the distribution of complotypes in relation to HLA-B and HLA-DR loci in Caucasian families. In order to analyze the distribution of HLA-Cw alleles in relation to extended haplotypes, we studied a large panel of MHC homozygous and heterozygous cell lines representing previously described Caucasian-derived extended haplotypes and 14 patients with complete C2 deficiency.

Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes.

tinman, a mesodermal NK2-type homeobox gene, is absolutely required for the subdivision of the early Drosophila mesoderm and for the formation of the heart as well as the visceral muscle primordia. Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development. Here, we show that most of these vertebrate tinman-related genes can readily substitute for Drosophila tinman function in promoting visceral mesoderm-specific marker gene expression, but much less in promoting cardiac-specific gene expression indicative of heart development.

Association of an HLA-DQ allele with clinical tuberculosis.

Context: Although tuberculosis (TB) is the leading worldwide cause of death due to an infectious disease, the extent to which progressive clinical disease is associated with genetic host factors remains undefined.

Objective: To determine the distribution of HLA antigens and the frequency of 2 alleles of the tumor necrosis factor alpha (TNF-alpha) gene in unrelated individuals with clinical TB (cases) compared with individuals with no history of clinical TB (controls) in a population with a high prevalence of TB exposure.

Design: A 2-stage, case-control molecular typing study conducted in 1995-1996.