Faculty Bibliography

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

The computer algorithm COMPARE provides information regarding the biological mechanism of action of a compound. In this study, excellent correlations were obtained for 2,2'-[3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)diimino]bis- benzoic acid (redoxal) and 1-(p-bromophenyl)-2-methyl-1H- naphth[2,3-d]imidazole-4,9-dione (BNID) and two well-studied dihydroorotate dehydrogenase (DHOD) inhibitors, dichloroallyl lawsone and brequinar, in terms of antiproliferative activity against tumor cell lines in vitro. When redoxal and BNID were incubated with MOLT-4 cells for 72 hr, 50% growth inhibition was achieved at 0.7 and 3.5 microM, respectively. After 24 hr of incubation, pyrimidine triphosphate pools were shown to be decreased by 50% by redoxal (1 microM) and BNID (0.25 microM). Addition of either uridine (50 microM) or cytidine (100 microM) antagonized the cellular cytotoxicity caused by either drug; uridine corrected the UTP and CTP deficit, whereas cytidine corrected only the CTP deficit. Exposure of MOLT-4 cells to a 1 microM concentration of either drug for 18 hr followed by a 1-hr exposure to [14C]bicarbonate showed a 97% decrease of incorporation of [14C] into pyrimidine triphosphates accompanied by a 91- and 82-fold increase in radioactive incorporation into L-dihydroorotate and N-carbamyl-L-aspartate, respectively. By direct exposure of DHOD prepared from MOLT-4 cell mitochondria to a range of concentrations of the two drugs, apparent Ki values of 0.33 microM (redoxal) and 0.53 microM (BNID) were determined. These data provide direct evidence for inhibition of DHOD by redoxal and BNID in MOLT-4 lymphoblasts

President Clinton had several precancerous skin lesions removed from his forehead and behind his ear during his annual medical checkup on Mar 24, 1995, the White House said on Mar 27. Press secretary Michael McCurry said he had just learned that the actinic keratoses had been removed

Margaret A. Hamburg, the New York City Health Commissioner, says that the city has stepped up efforts over the last year to counter chemical and biological terrorism. Among the efforts was a daylong drill after a simulated attack involving a bacterium, anthrax

Anyone exposed through skin or inhalation to a large enough amount of pure sarin or a similar nerve poison would probably die within minutes, officials agree, before front-line emergency crews arrived. But if emergency response was rapid enough, rescue workers could inject atropine, 2-PAM and other antidotes to those who were exposed to smaller amounts of the poison. The city's Emergency Medical Service conducts several drills each year in conjunction with city and state agencies, simulating disasters. 'But we don't specifically simulate poison attacks or other terrorist attacks because the scenario would be the same: how to get our people to safety as soon as possible,' said Charles DeGaetano, an E.M.S. spokesman. 'We're leaving ourselves very vulnerable because the infrastructure of public health has been allowed to decay,' Dr. [Joshua Lederberg] said in an interview, alluding to reports from several panels of experts

President Clinton's physician, E. Connie Mariano, said on Mar 24, 1995 that the president continued to 'demonstrate excellent health and vigor,' although he has picked up six pounds over the last 14 months