Faculty Bibliography

The bleeding stomach ulcer that Secretary of State Warren Christopher suffered as a complication of a nonsteroidal anti-inflammatory drug he took for arthritis vividly illustrates the dangers of such drugs. Complications of these drugs, referred to by doctors as NSAIDs (pronounced EN-seds), are a significant public health problem. The complications have been described in a medical journal as the most prevalent serious drug toxicity in the United States. Christopher's ulcer sent him to the intensive-care unit of Ottawa Civic Hospital during President Clinton's visit to Canada the week of Feb. 20. Doctors there said the ulcer had been caused by complications of Ansaid, a nonsteroidal anti-inflammatory drug made by Upjohn Co. of Kalamazoo, Mich. It is one of 25 NSAIDs approved for marketing by the Food and Drug Administration (FDA)

The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure (vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington, MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol; (ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles (28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of an immediate diagnosis often shakes a patient's faith in the doctor. The difficulty of pinpointing the specific cause of general symptoms and the anxiety it usually causes the parents of a patient are discussed

The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, and nuclear-cytosolic trafficking of both RNA and proteins. Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors. One such putative effector, Ran-binding protein 1 (RanBP1), interacts selectively with Ran-GTP. Ran proteins contain a diagnostic short, acidic, carboxyl-terminal domain, DEDDDL, which, at least in the case of human Ran, is required for its role in cell cycle regulation. We show here that this domain is required for the interaction between Ran and RanBP1 but not for the interaction between Ran and a Ran guanine nucleotide exchange factor or between Ran and a Ran GTPase activating protein. In addition, Ran lacking this carboxyl-terminal domain functions normally in an in vitro nuclear protein import assay. We also show that RanBP1 interacts with the mammalian homolog of yeast protein RNA1, a protein involved in RNA transport and processing. These results are consistent with the hypothesis that Ran functions directly in at least two pathways, one, dependent on RanBP1, that affects cell cycle progression and RNA export, and another, independent of RanBP1, that affects nuclear protein import

Scientists in California report that a child infected with the AIDS virus at birth successfully cast off the infection by the age of 1, but some other experts doubt that the case has been fully proved

They say the boy evidently fought off the HIV infection with his natural immune defenses. The boy's blood test is now HIV-negative, no virus can be grown from his blood, and there is no laboratory or clinical evidence of HIV infection, the authors said. A few cases are on record of babies whose immune system seemed to score a rare victory over HIV. But such cases were not perfectly documented and were generally dismissed as spurious findings or laboratory errors, said the UCLA team, headed by Dr. Yvonne Bryson. With its better-documented case, Bryson's team suggests that beating HIV infection may be a real phenomenon, at least in rare cases. This category of patients would join other groups, such as the long-term survivors of HIV infection, who might have immune systems specifically capable of fighting off the virus, which could offer valuable clues to combating it

Scientists in California report that a child infected with the AIDS virus at birth successfully cast off the infection by age 1, but other experts doubt the case has been fully proved. This medical conundrum is important because if the boy did fight off the virus, HIV, his health may hold a vital clue to defeating the disease. They say the boy evidently fought off the HIV infection with his natural immune defenses. The boy's blood test is now HIV-negative, no virus can be grown from his blood, and there is no laboratory or clinical evidence of HIV infection, the authors said