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.     

Advanced use of an esthetic indirect posterior resin system

With the advent of newer indirect posterior restorative materials, one current resin restorative system still stands out as a proven leader in the dental marketplace. This article focuses on the multiple use of an all-microfill, laboratory-processed, indirect resin restorative system. Three cases are presented and criteria for long-term success are reviewed and discussed.     

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.     

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.     

Thymic carcinoma. Ten years' experience in twenty patients

Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the outcome of treatment in thymic carcinoma, we reviewed a 10-year (1982 to 1992) experience with 20 consecutive patients in Taichung Veterans General Hospital. There were 9 men and 11 women: ages ranged from 34 to 70 years old (mean 51.4 years). None of these patients had concomitant myasthenia gravis. All of the patients received surgical intervention, and the diagnosis was made by pathologic study. Postoperative staging was made according to the modified Masaoka staging system. None of our patients were in stage I. One patient (5%) had stage II disease, 12 (60%) stage III, and 7 (35%) stage IV. The pathologic subtypes of thymic carcinoma included eight squamous cell carcinomas, seven undifferentiated carcinomas, one lymphoepithelioma-like carcinoma, one clear-cell carcinoma, 1 mucoepidermoid carcinoma, and two carcinoid tumors. Curative resection could be done in seven patients (35%). The overall cumulative survival was 45.9% at 3 years and 34.4% at 5 years. The median survival times for patients with complete and incomplete resection were 39.0 months and 14.3 months, respectively (p = 0.1752). The median survival times of patients with postoperative radiotherapy and without postoperative radiotherapy were 39.3 months and 15.0 months, respectively (p = 0.0738). The median survival times of patients with squamous cell carcinoma and undifferentiated carcinoma were 25.4 months and 11.3 months, respectively (p = 0.1464). Our data show that complete resection, postoperative radiotherapy, and squamous cell carcinoma do not indicate a significantly favorable result, even though they result in longer median survival times. Yet a positive trend of favorable outcome in patients who received postoperative radiotherapy is ambiguously shown.