Faculty Bibliography

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

The association between a new human herpesvirus-like agent and various forms of Kaposi's sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposi's sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposi's sarcoma. Polymorphism of the herpesvirus-like DNA in the Kaposi's tissue from different populations was observed by both single-strand conformational polymorphism and direct sequencing. Furthermore, the presence and expression of the virus was detected in some Kaposi's tumours by Southern and northern blotting. This herpesvirus may be involved in the pathogenesis of different kinds of Kaposi's sarcoma seen among distinct and unrelated populations

Two patients receiving experimental treatment for advanced breast cancer at one of the country's most prestigious cancer hospitals were given massive overdoses of two chemotherapy drugs. One patient died, and the other suffered permanent heart damage. The incidents occurred at Dana-Farber Cancer Institute in Boston, a Harvard teaching hospital, late last fall. Officials at the hospital said they were at a loss to explain how such a serious medical error, which apparently resulted from a doctor's mistaken order last November, escaped attention until a clerk picked it up in a routine review of data last month. The patient who died was Betsy Lehman, an award-winning health columnist for the Boston Globe. The news, detailed Thursday in an article published in the Globe, was all the more unsettling because Lehman, as a health reporter, was presumably knowledgeable about her treatment and would have chosen her hospital with care. Lehman, who was 39, died Dec. 3 at the hospital

Two patients receiving experimental treatment for advanced breast cancer at Dana-Farber Cancer Institute in Boston, a Harvard teaching hospital, were given massive overdoses of two chemotherapy drugs. Betsy A. Lehman, a health columnist for the Boston Globe, died; a second patient suffered permanent heart damage. Doctors apparently refused to heed her warnings that something was drastically wrong and ignored the results of tests indicating heart damage

[Sarin] was identified in two earlier poisonings elsewhere in Japan. Dr. [Matthew Meselson] said reporters from Japanese television showed him the results of tests performed with an instrument known as a mass spectrometer. Surprisingly, the trace was so clear cut that it had to have come from pure sarin, whereas material made by an amateur group would be expected to have many impurities. Dr. Meselson said he wondered if trace shown to him had come from the laboratory reference sample used for comparison, not the material used in the attacks. Although Dr. Meselson said he did not get any follow-up, it was clear that Japanese scientists know how to do the proper chemical analyses and laboratories 'ought to have been revved up' to handle investigation of the latest subway attack. The nerve gas that Japanese officials say killed eight people and injured thousands of others is one of the most potent toxins known. HISTORY Developed in the 30's by the German chemical industry. Used by the Nazis as a chemical warfare agent. CHARACTERISTICS In liquid form, sarin can be absorbed through the skin. Sarin changes to a gas through ordinary vaporization and becomes much more harmful when it is inhaled. SYMPTOMS Tightness of the chest, slowing heart rate and dropping blood pressure. Nausea and vomiting, abdominal cramps, diarrhea. Headache, drowsiness, convulsions and coma. TREATMENT First aid measures include mouth-to-mouth resuscitation and decontamination of sarin on clothes with common liquid bleaches and soapy water. If the victim is not overwhelmed by large amounts of gas and if the standard antidote, atropine, isgiven in time the symptoms may be temporary

Sarin, the nerve gas that Japanese officials say was used in a terrorist attack on the Tokyo subway system yesterday, is one of the most potent poisons known. Amounts smaller than a milligram can disrupt communications between nerves, leading to suffocation from paralysis of the diaphragm and other muscles used in breathing, according to toxicologists and textbooks. If enough sarin is inhaled or absorbed, a victim quickly develops tightness of the chest and begins gasping for breath. The heart rate slows and the blood pressure can drop to dangerous levels. Sarin also can cause nausea and vomiting, abdominal cramps, diarrhea, headache, drowsiness, convulsions and coma