Faculty Bibliography

Histone amino termini are post-translationally modified by both transcriptional coactivators and corepressors, but the extent to which the relevant histone modifications contribute to gene expression, and the mechanisms by which they do so, are incompletely understood. To address this issue, we have examined the contributions of the histone H3 and H4 amino termini, and of the coactivator and histone acetyltransferase Gcn5p, to activation of a small group of Gcn4p-activated genes. The histone H3 tail exerts a modest (about 2-fold) but significant effect on activation that correlates with a requirement for Gcn5p and is distributed over multiple lysine residues. The H4 tail also plays a positive role in activation of some of those genes tested, but this does not correlate as closely with Gcn5p coactivation. Microarray experiments did not reveal a close correspondence between those genes activated by Gcn4p and genes requiring the H3 or H4 tail, and analysis of published microarray data indicates that Gcn4p-regulated genes are not in general strongly dependent on Gcn5p. However, a large fraction of genes activated by Gcn4p were found to be repressed by the H3 and H4 amino termini under non-inducing conditions, indicating that one role for Gcn4p is to overcome repression mediated by the histone tails

PROBLEM/CONDITION: Survivors of collapsed or damaged buildings from the attack on the World Trade Center (WTC) were among those most exposed to injury hazards, air pollution, and traumatic events. REPORTING PERIOD: This report summarizes data from health outcomes collected during interviews conducted from September 5, 2003, to the close of the World Trade Center Health Registry (WTCHR) enrollment on November 20, 2004. DESCRIPTION OF SYSTEM: WTCHR will be used to monitor periodically the mental and physical health of 71,437 enrollees for 20 years. The analysis is limited to 8,418 adult survivors of collapsed buildings (n = 5,095) and buildings with major or moderate damage (n = 3,323), excluding those who were involved in rescue and recovery. RESULTS: A total of 62.4% of survivors of collapsed or damaged buildings were caught in the dust and debris cloud that resulted from the collapse of the WTC towers, and 63.8% experienced three or more potentially psychologically traumatizing events. Injuries were common (43.6%), but few survivors reported injuries that would have required extensive treatment. More than half (56.6%) of survivors reported experiencing new or worsening respiratory symptoms after the attacks, 23.9% had heartburn/reflux, and 21.0% had severe headaches. At the time of the interview, 10.7% of building survivors screened positive for serious psychological distress (SPD) using the K6 instrument. After multiple adjustments, data indicated that survivors caught in the dust and debris cloud were more likely to report any injuries (adjusted odds ratio [AOR] = 3.9; p< or =0.05); any respiratory symptom (AOR = 2.7; p< or =0.05); severe headaches (AOR = 2.0; p< or =0.05); skin rash/irritation (AOR = 1.7; p< or =0.05); hearing problems or loss (AOR = 1.7; p< or =0.05); heartburn (AOR = 1.7; p< or =0.05); diagnosed stroke (AOR = 5.6; p< or =0.05); self-reported depression, anxiety, or other emotional problem (AOR = 1.4; p< or =0.05); and current SPD (AOR = 2.2; p< or =0.05). Adjustment for SPD did not diminish the observed associations between dust cloud exposure and physical health outcomes. Building type and time of evacuation were associated with injuries on September 11, 2001 and reported symptoms; building type (collapsed versus damaged) also was associated with mental distress. INTERPRETATION: Two to three years after September 11, survivors of buildings that collapsed or that were damaged as a result of the WTC attack reported substantial physical and mental health problems. The long-term ramifications of these effects are unknown. Many survivors were caught directly in the dust and debris of collapsing towers, a dense cloud of particulate matter that might have produced or exacerbated these health effects. PUBLIC HEALTH ACTION RECOMMENDED: Long-term follow-up of building survivors and all other persons enrolled in WTCHR should be maintained, with particular attention to those persons exposed to the dust cloud. Some of these findings might lead to building designs that can minimize injury hazards.

Cats, tigers and leopards are known to have been infected with the virus in Asia and Europe. An author of the article, Dr. Albert Osterhaus, a virologist and veterinarian at Erasmus Medical Center, has performed experiments showing that cats can give the virus to other cats. But whether they do so in real life, and if so how often, is unknown. The team has found that cats can be infected through the respiratory tract. Cats can also be infected when they ingest the virus, which is a novel route for influenza transmission in mammals. But cats excrete only one-thousandth the amount of virus that chickens do, or less, he said. Among the many unknowns is how long cats can excrete the virus, the minimal amount of virus it takes to cause infection and whether cats can excrete the virus without developing signs of illness

The science on the H5N1bird flu virus may not support these conclusions. In fact, two important studies published just last month in top science journals show that this bird flu virus is still multiple mutations away from being able to pass easily among humans. This bird flu appears to be better absorbed by the deep pockets of bird lungs, whereas human flu is absorbed by the cells of our upper airways. Dr. David Swayne, director of the Southeast Poultry Laboratory at the U.S. Department of Agriculture, has worked on avian influenza for many years. He takes all highly pathogenic bird flus seriously, including H5N1, but he feels they can most often be controlled. Swayne told me that H5N1 might still be eradicated in birds with the help of 'better diagnostic tools and improved strategies to protect birds from infection.'

It takes about two months to grow the new bladder on a scaffold outside the body. After implantation, the engineered bladder enlarges over time in the recipient. The researchers say they expect that the new bladder will last a patient's lifetime, but the longevity will be known only as the children grow older. A major advantage of his technique is that rejection cannot occur because the cells used to create a new bladder are from the patient, not from another individual. So an ultimate aim -- still years off -- is to develop the technique to grow a wide variety of other tissues, possibly even organs, to help relieve the shortage of donor organs available for transplanting, said the research team's leader, Dr. Anthony Atala. He directs the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center in Winston-Salem, N.C. After the new bladder formed, in about seven to eight weeks, Dr. Atala removed a large portion of the patient's bladder. Then he sewed the newly created tissue to what is known as the neck of the bladder and to the rest of the remaining portion of the patient's natural bladder

Most published recommendations for treatment of pediatric nerve agent poisoning are based on standard resuscitation doses for these agents. However, certain medical and operational concerns suggest that an alternative approach may be warranted for treatment of children by emergency medical personnel after mass chemical events. (1) There is evidence both that suprapharmacological doses may be warranted and that side effects from antidote overdosage can be tolerated. (2) There is concern that many emergency medical personnel will have difficulty determining both the age of the child and the severity of the symptoms. Therefore, the Regional Emergency Medical Advisory Committee of New York City and the Fire Department, City of New York, Bureau of Emergency Medical Services, in collaboration with the Center for Pediatric Emergency Medicine of the New York University School of Medicine and the Bellevue Hospital Center, have developed a pediatric nerve agent antidote dosing schedule that addresses these considerations. These doses are comparable to those being administered to adults with severe symptoms and within limits deemed tolerable after inadvertent nerve agent overdose in children. We conclude that the above approach is likely a safe and effective alternative to weight-based dosing of children, which will be nearly impossible to attain under field conditions

Dr David Katz, director of the Yale prevention research center, recently published a book, The Flavor Point Diet, in which he explores the idea that being stimulated by too many flavors stimulates more hunger. But many patients lack the discipline and do not manage to achieve a healthier lifestyle, no matter what the road map. So it is necessary to consider dietary aides. Without a perfect diet drug, many are looking with interest at Acomplia (rimonabant), a promising drug in late-stage clinical trials that works directly by blocking appetite (endocannabinoid) receptors in the brain

GOALS/BACKGROUND: Reports of segmental colitis with diverticula regard this entity as a local disease. Our goal was to reexamine the association of diverticula to colitis and question the relationship of colonic diverticulosis with generalized inflammatory bowel disease (IBD). STUDY: A retrospective database review of more than 1,600 patients matched 100 cases with IBD and colonic diverticulosis with a control group of 100 patients with IBD without diverticulosis. Patients were matched by gender, IBD diagnosis, and date of birth. Variables examined included disease distribution, strictures, fistulae, extraintestinal manifestations (EIMs), family history, and age at IBD diagnosis. RESULTS: For all IBD diagnoses, more sigmoid inflammation occurred in cases with diverticular disease: 82% versus 65% for controls (P = 0.005), and in the rectum: 85% versus 69% for controls (P = 0.005). In the Crohn's disease with diverticulosis subset, sigmoid inflammation was more common: 70% versus 42% for controls (P = 0.007), and in the rectum: 70% versus 46% for controls (P = 0.02). Disease distribution was otherwise similar throughout the colon, ileum, and jejunum. The incidence of strictures (P = 0.99) and fistulae (P = 0.69) was similar. EIMs were more frequent in cases with diverticulosis: 28% versus 16% (P = 0.05). Family history of IBD was similar: 26% for cases and 16% for controls (P = 0.12). Age at IBD diagnosis was significantly greater in diverticulosis cases compared with controls: 51.5 years (+/-17.6) versus 42.8 years (+/- 17.5) (P < 0.001), respectively. CONCLUSIONS: We observed an increased frequency of sigmoid and rectal inflammation, EIMs, and an older age of IBD onset in cases with diverticulosis. This suggests a role for diverticula in IBD beyond that of a mere coincidental finding