2,3-Dihydro-dithiin and -dithiepine-1,1,4,4-tetroxides: small molecule non-peptide antagonists of the human galanin hGAL-1 receptor.

The neuropeptide galanin modulates several physiological functions such as cognition, learning, feeding behavior, and depression, probably via the galanin 1 receptor (GAL-R1). Using an HTS assay based on 125I-human galanin binding to the human galanin-1 receptor (hGAL-R1), we discovered a series of 1,4-dithiin and dithiipine-1,1,4,4-tetroxides that exhibited binding affinity IC50's to hGAL-R1 ranging from 190 to 2700 nM. Two of the dithiepin analogues, 7 and 23, behaved pharmacologically as hGAL-R1 antagonists in secondary assays involving adenylate cyclase activity and GTP binding to G-proteins.

The role of H2-O and HLA-DO in major histocompatibility complex class II-restricted antigen processing and presentation.

The function of major histocompatibility complex (MHC) class II molecules is to sample exogenous antigens for presentation to CD4+ T helper cells. After synthesis in the endoplasmic reticulum, class II molecules are directed into the endosomal system by association with the invariant chain (Ii), which is sequentially cleaved, generating class II dimers loaded with Ii-derived peptides (CLIP). These class II-peptide complexes are physiological substrates for H2-M/HLA-DM, a resident of the endosomal/lysosomal system which facilitates the removal of CLIP from newly synthesised class II alpha beta dimers.

Molecules of the cycling hair follicle--a tabulated review.

In this review we tabulated molecules which have been experimentally identified to be associated with, or play a role in, hair follicle growth. While compiling these data we were impressed by the fact that this field is only now beginning to be developed in terms of molecular analysis. Ironically, hair was used in some of the earliest molecular approaches to biologic structure (e.

Evaluation of new anti-infective drugs for the treatment of chronic carriage of Salmonella. Infectious Diseases Society of America and the Food and Drug Administration.

The chronic carriage of salmonellae is defined as the shedding of a Salmonella species for > or = 1 year, as documented by an initial positive culture of a stool sample obtained at least 1 month after resolution of the acute illness and repeated positive cultures for at least 1 year. Clinical trials of investigational anti-infective drugs for the treatment of the salmonella carrier state may be conducted with a placebo control or an active concurrent control. A crossover design also may be employed for establishing efficacy.

Evaluation of new anti-infective drugs for the treatment of cholera. Infectious Diseases Society of America and the Food and Drug Administration.

Cholera is an acute gastrointestinal infection caused by Vibrio cholerae. It is characterized by watery diarrhea that may lead to massive fluid loss, which in turn may result in hypotension, shock, and death within hours. Key to the treatment of cholera is fluid replacement.

Evaluation of new anti-infective drugs for the treatment of typhoid fever. Infectious Diseases Society of America and the Food and Drug Administration.

Typhoid fever is an acute febrile illness caused by Salmonella typhi. The evidence of blood-borne infection required for study entry includes clinical signs and symptoms plus confirmation of the presence of S. typhi in blood or other tissues or body fluids.