Faculty Bibliography

Two sets of studies by Dr. Comstock in the 1940s and '50s had a critical impact on the federal government's response to tuberculosis. One set led public health officials to reject the tuberculosis vaccine known as BCG, which had been under consideration for routine use among American children. Dr. Comstock attributed the discrepancies among the trials to variations in different strains of the BCG vaccine and a lack of standard manufacturing techniques. Later, genetics studies documented that there was no uniformity among BCG vaccines, said Dr. Richard E. Chaisson, a tuberculosis researcher at Johns Hopkins. In the trial, Dr. Comstock and his family took INH themselves to convince the participants of his belief in the therapy's safety, Dr. Chaisson said. After the trial, Dr. Comstock returned and gave INH to those who had received the placebo

The premise: Ann Lord (Vanessa Redgrave) is lying on her deathbed at home, attended by her daughters. Wracked with pain, she appears to be dying of some kind of cancer and is receiving intravenous narcotics. Ann begins to talk about events of 50 years earlier, reliving the untimely death of her former beau Buddy at the wedding of his sister, as she, Ann, jilts Buddy and spends the night with his best friend, Dr. Harris Arden. For the rest of her life, she has blamed herself for Buddy's death and, in a feverish state on her deathbed, relives that fateful night. The nurse in attendance tells her daughters that the characters Ann is talking to and about 'might be real people and they might not' -- she seems to doubt that the memories are real. Indeed, Ann is frequently confused and delirious as death approaches and, among other things, hallucinates that she is visited by Dr. Arden wearing a stethoscope and that her night nurse is in a formal gown

Mutations within PCSK9 (proprotein convertase subtilisin/kexin type 9) are associated with dominant forms of familial hyper- and hypocholesterolemia. Although PCSK9 controls low density lipoprotein (LDL) receptor (LDLR) levels post-transcriptionally, several questions concerning its mode of action remain unanswered. We show that purified PCSK9 protein added to the medium of human endothelial kidney 293, HepG2, and Chinese hamster ovary cell lines decreases cellular LDL uptake in a dose-dependent manner. Using this cell-based assay of PCSK9 activity, we found that the relative potencies of several PCSK9 missense mutants (S127R and D374Y, associated with hypercholesterolemia, and R46L, associated with hypocholesterolemia) correlate with LDL cholesterol levels in humans carrying such mutations. Notably, we found that in vitro wild-type PCSK9 binds LDLR with an approximately 150-fold higher affinity at an acidic endosomal pH (K(D) = 4.19 nm) compared with a neutral pH (K(D) = 628 nm). We also demonstrate that wild-type PCSK9 and mutants S127R and R46L are internalized by cells to similar levels, whereas D374Y is more efficiently internalized, consistent with their affinities for LDLR at neutral pH. Finally, we show that LDL diminishes PCSK9 binding to LDLR in vitro and partially inhibits the effects of secreted PCSK9 on LDLR degradation in cell culture. Together, the results of our biochemical and cell-based experiments suggest a model in which secreted PCSK9 binds to LDLR and directs the trafficking of LDLR to the lysosomes for degradation.

''I've found it constructive to cloak one's power,'' Dr. Hogness wrote in a family biography, adding that ''nevertheless, when people push me, they find they don't get very far.'' ''The first big study we did was a determination of the actual cost of medical education,'' Dr. Hogness said. ''Nobody had ever done that.'' Grabbing a bullhorn, Dr. Hogness smiled and said, ''Thank you all for coming,'' easing the confrontation

By most useful definitions, I am an insomniac. Like Alan Berliner, director and star of HBO's provocative new documentary Wide Awak e, I, too, do most of my best work in the middle of the night, and I, too, risk my wife's wrath when I am subsequently not available in the early morning to respond to our infant's pleading cries

'If I sat next to a passenger with drug resistant tuberculosis, I would not be happy if I caught it, because I'd be getting a serious disease and need to take toxic drugs for two years and still face death,' [Mario Raviglione] said. 'They did the right thing.' While Speaker's case was unusual in many aspects, it followed the standard ways doctors detect and treat tuberculosis. Doctors detect TB largely through skin tests, X-rays and laboratory tests. After taking sputum and lung secretions from a suspect, doctors smear a portion of the specimen on a glass slide. They add chemical stains to help detect TB bacteria (often nicknamed red snappers) when they look through a microscope. [Frank Plummer], who also directs the National Microbiology Laboratory in Winnipeg, said the discordance between the two laboratories in this case 'doesn't make sense' and that he hoped a review would 'solve the mystery.'

On Tuesday, the disease center and the National Jewish Medical and Research Center in Denver, where Speaker has been a patient in isolation since June 1, said he did not have XDR-TB. A series of new tests at both institutions shows that Speaker has multiple-drug-resistant TB, or MDR-TB. The condition is still dangerous, but more drug treatments are available. The test findings also raised questions about the accuracy of TB tests at the disease center, a national and reference laboratory for the disease. The center reported in May that its tests showed that Speaker had XDR-TB based on cultures from a bronchoscopy, a lung procedure, at a hospital in Atlanta. On Tuesday, the disease center and the Denver hospital said that as a matter of routine procedure they had performed new tests using three laboratory methods on TB bacteria isolated from Speaker on three occasions. Those new tests consistently showed MDR-TB

''If I sat next to a passenger with drug resistant tuberculosis, I would not be happy if I caught it, because I'd be getting a serious disease and need to take toxic drugs for two years and still face death,'' Dr. [Mario C. Raviglione] said. In an e-mail message to other county officials in May, Dr. Steven Katkowsky, director of Fulton County Health Department in Atlanta, which oversaw Mr. Speaker's case, defended making the issue public. At the time, Dr. Katkowsky wrote that ''if we don't say anything as a pre-emptive strike, the questions of what did you know, when, and what did you do are bound to come up.'' Dr. [Frank Plummer], who also directs the National Microbiology Laboratory in Winnipeg, said that the discordance between the two laboratories in this case ''doesn't make sense'' and that he hoped ''a review will solve the mystery.''

''Any time there is a concern or a conflict with a test result, we will automatically review those results and see if there is a clear explanation for the difference,'' Dr. [Mitchell L. Cohen] said. Dr. Charles Daley, head of the infectious disease division at National Jewish, said: ''This discrepancy among results happens all the time in labs that do drug-resistance testing, including reference labs. It's a frustration we have to deal with.'' Now, he said, ''We are sure of our results.'' In discussing the discordant findings, Dr. Cohen said that scientists urgently needed improved laboratory techniques and that there were ''a variety of potential explanations.'' Among them are obtaining specimens in different ways or on different days and variations in the bacteria