Owing to their detoxifying functions, and roles in drug metabolism as well as the prevention of atherosclerosis, mammalian or serum paraoxonases (PONs) are an intriguing subject of research and a prime therapeutic and engineering target. Initially identified in mammals, PON and PON-related genes have now been found in fowls, zebra fish, and even in invertebrates such as C. elegans. The more closely-related PON genes are divided into three classes or sub-families: PON1, PON2 and PON3, that share 60-70% sequence identity (Draganov and La Du, 2003). PONs are calcium-dependent hydrolases that catalyze the hydrolysis of a broad range of esters and ... Read more

Stem cells modulate tissue formation and repair based on a complex interaction of cell autonomous and non-autonomous regulatory mechanisms. While reductionist approaches to understanding stem cell control continue to be extremely productive, understanding the physiological contexts in which stem cells function, will ultimately require definition of the microenvironments in which they live. The location of stem or precursor populations within numerous solid tissues has been described, but delineating specific associated cells and how they participate in regulating stem cell function has generally been lacking for mammalian tissues. However, the use of invertebrate-based models has created particularly productive systems in which ... Read more

Since the emergence of the role that CD1d plays in selecting the natural killer T cell population expressing the semi-invariant Vα14 T cell receptor (iNKT cells) (Bendelac et al., 1995), a great deal of research has been done to identify the natural lipid antigen involved in this process. This interest has been sparked by the critical role of iNKT cells in the regulation of immune responses and their potential involvement in autoimmunity and the control of carcinogenesis. While iNKT cells show high autoreactivity, the only cellular lipid shown to be presented by CD1d has been phosphatidyl inositol, which does not ... Read more

Introduction

The natural product pool, which includes many glycosylated secondary metabolites, is the source of over half of the world’s drug leads. For example, the antibiotics vancomycin and erythromycin, the antitumor compounds bleomycin and doxorubicin, and the antifungal agents amphotericin and nystatin all contain essential sugar attachments. Carbohydrate groups of natural product-based drugs have long been known to generally influence pharmacokinetic properties and there is an increasing recognition that these carbohydrate appendages also play a key role in drug-target interactions. These findings suggest that the alteration of glycosylation patterns on secondary metabolites is a potential strategy for the generation of novel ... Read more

One of the major therapeutic challenges that face modern clinicians is the development of bacterial resistance to antibiotics. Currently, antibiotic resistance is a major problem in the treatment of staphylococcal, enterococcal, pneumocystis, helicobacter, and mycobacterial infections, to name a few. While there are several different mechanisms by which this occurs, the common pathway in the development of bacterial resistance has been the widespread use of broad-spectrum antibiotics as single agents.

In the work summarized here, we devised a novel antibiotic, which could be used to overcome bacterial resistance to standard antibiotics. The concept is based on two principles. 1) Use of ... Read more

RNA interference (RNAi), first discovered in Caenorhabdtitis elegans and now widely found and applied in a variety of organisms such as Drosophila, zebrafish and mammalian systems, has emerged to revolutionize the field of functional genomics by inducing specific and effective post-transcriptional gene silencing for loss-of-function studies (Dykxhoorn et al., 2003). Mechanistic investigations of RNAi suggest that long double-stranded RNAs (dsRNAs) are first cleaved by the RNase III-like enzyme, Dicer, to 21-23 base pair (bp) small interfering RNAs (siRNAs). These siRNAs are resolved by ATP-dependent RNA helicase, and the resulting single-stranded RNAs are then incorporated into the RNA-induced silencing complex (RISC). ... Read more

Numerical and structural chromosome abnormalities are a common cause of inherited and acquired diseases in humans. Cytogenetic detection of genomic imbalances and rearrangements is standard diagnostic practice, and is used both prognostically and for treatment stratification, especially for neoplastic disorders. Abnormalities are recognized by chromosome banding and by fluorescence in situ hybridization (FISH). FISH permits examination of specific DNA sequences within single or multiple chromosome bands on a metaphase cell or within an interphase cell.

Locus-specific FISH probes have traditionally been composed of recombinant DNA segments that span large chromosomal targets of hundreds of thousands of base pairs, about an order ... Read more

The information generated by the genome sequencing initiatives is being gathered, cataloged and evaluated. These databases will provide fertile ground for the development of new technologies in the areas of functional genomics and molecular diagnostics. Concurrent use of these data sets, however, presents an ethical dilemma. Genomic sequence data reveals a substantial amount of sequence diversity within a population; therefore, confidentiality must be maintained so that an individual is not exposed to the risk of “genetic” discrimination. In addition, as nucleic acid tests enter this diagnostic arena, the obtaining of a high degree of accurate and reliable data from the ... Read more

Other Names: cinacalcet HCl, AMG 073.

Makers: NPS Pharmaceuticals and Amgen.

Disease Treated: (1) Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) on dialysis; (2) hypercalcemia in patients with parathyroid carcinoma.

Approval Status: Approved by the U.S. FDA on March 8, 2004 for the treatment of secondary HPT in patients with CKD on dialysis and the treatment of hypercalcemia in patients with parathyroid carcinoma.

Chemical/Biological Nature: SENSIPAR is a calcimimetic small molecule agent that has a molecular formula of C_²²H_²²F_³N.HCl and a molecular weight of 393.9 g/mol.

Administration: For secondary HPT in patients with CKD on dialysis: ... Read more

Other Names: telithromycin.

Maker: Aventis Pharmaceuticals Inc.

Disease Treated: KETEK is an antibiotic for treating respiratory infections such as acute bacterial exacerbation of bronchitis (AECB), acute bacterial sinusitis (AS) and community-acquired pneumonia (CAP), caused by susceptible strains of bacteria (e.g., Streptococcus pneumoniae).

Approval Status: Approved by the U.S. FDA on April 1, 2004 as an antibacterial agent to treat specific respiratory infections caused by susceptible bacterial infections.

Chemical/Biological Nature: KETEK’s active ingredient is an 812.03-dalton, semisynthetic antibacterial agent of the ketolide class known as telithromycin, with an empirical formula of C_⁴³H_⁶⁵N_⁵O_¹⁰. In its native form it ... Read more