Co-expression of bovine growth hormone (GH) and human GH antagonist genes in transgenic mice

Bovine growth hormone (bGH) transgenic (Tg) mice have been shown to possess enhanced growth phenotypes and exhibit severe glomerulosclerosis. One amino acid substitution in GH, i.e. G119R in bGH or G120R in human (h) GH, results in GH antagonists (GHAs). GHA-Tg mice exhibit dwarf phenotypes and normal kidneys. In order to investigate the possibility of GHAs as pharmaceutical agents for the treatment of human diseases with excessive GH levels, we cross bred mice that express bGH with those that express hGHA. Double positive Tg mice were identified that express both genes although at different levels. Kidney histological studies revealed that the double positive Tg mice with high GHA/GH expression ratios possessed normal or near normal kidneys, whereas those with low GHA/GH ratios exhibited glomerulosclerosis similar to GH-Tg mice. Thus, co-expression of GH and GHA genes in vivo results in animal phenotypes and kidney histopathologies which are a reflection of the relative expression levels of each gene.     

Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 2. Exploring interactions at the proximal (S2) binding site

In an effort to increase the thrombin inhibitory activity of a novel series of inhibitors (i.e., 1a), substituents were incorporated at the C-3" position of the C-3 aryl ring (2). Consistent with the X-ray crystallography studies, small hydrophobic groups at the C-3" site (Br and Me) enhanced thrombin inhibitory activity by 8-fold. However, a few more hydrophilic substituents (NO2 and OMe) also enhanced the potency of the series. The biological results are discussed in terms of molecular modeling studies.     

3D integration review

3-D integration delivers value by increasing the volumetric transistor density with the potential benefit of shorter electrical path lengths through use of the shorter third dimension. Several researchers have studied various aspect of 3Di such as bonding level, through silicon via processes and integration, thermomechanical reliability of the vias, and the impact of the vias on devices. In this paper, we review some of the literature with a view to understanding the key options and challenges in 3Di. We al...     

Contribution to the treatment of acute bovine mastitis with cefquinome

The recombinant human colony-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are hematopoietic cytokines that increase neutrophil number and enhance their function. In patients with HIV infection, G-CSF and GM-CSF have reversed or prevented neutropenia even during periods of full-dose myelotoxic therapy. Both colony-stimulating factors (CSFs) also have improved defects in neutrophil function in the setting of HIV infection. In non-neutropenic animal models of opportunistic bacterial or fungal infections, use of CSFs has increased survival. Future clinical applications of CSFs may include the adjunctive treatment of specific HIV-related opportunistic infections in addition to an expanding role in the treatment of HIV-associated neutropenia and defects in neutrophil function.