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J Anon

Publications and source records attributed to J Anon.

7 recordsLinked to original sources

Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells.

In t(8;21) acute myeloid leukemia (AML), the AML1/ETO fusion protein promotes leukemogenesis by recruiting histone deacetylase (HDAC) and silencing AML1target genes important for hematopoietic differentiation. We hypothesized that depsipeptide (FR901228), a novel HDAC inhibitor evaluated in ongoing clinical trials, restores gene transcription and cell differentiation in AML1/ETO-positive cells. A dose-dependent increase in H3 and H4 histone acetylation was noted in depsipeptide-treated AML1/ETO-positive Kasumi-1 cells and blasts from a patient with t(8;21) AML. Consistent with this biological effect, we also showed a dose-dependent increase in cytotoxicity, expression of IL-3, here used as read-out for silenced AML1-target genes, upregulation of CD11b with other morphologic changes suggestive of partial cell differentiation in Kasumi-1 cells. Some of these biologic effects were also attained in other myeloid leukemia cell lines, suggesting that depsipeptide has differentiation and cytotoxic activity in AML cells, regardless of the underlying genomic abnormality. Notably, the activity of depsipeptide was enhanced by 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor (DNMT). These two agents in combination resulted in enhanced histone acetylation, IL-3 expression, and cytotoxicity, suggesting HDAC and DNMT activities as a potential dual target in future therapeutic strategies for AML1/ETO and other molecular subgroups of AML.

Acetylation↗

The medical management of rhinosinusitis.

The management of rhinosinusitis depends on a number of variables related to the duration and severity of symptoms in the individual patient. Furthermore acute rhinosinusitis is managed differently than chronic rhinosinusitis. Because a variety of conservative and pharmacologic interventions are available, the physician can find it difficult to develop a cohesive and logical approach to treatment. An understanding of the pathophysiology, microbiology, and natural history of rhinosinusitis is necessary to formulate the best treatment plan for the individual patient.

Acute Disease↗

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days-an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Acute Disease↗

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Acute Disease↗

Bacteriologic findings from the nose, ethmoid, and bloodstream during endoscopic surgery for chronic rhinosinusitis: implications for antibiotic therapy.

This study addresses the bacterial flora of chronic rhinosinusitis at the time of endoscopic sinus surgery. We used the consensus definition of chronic rhinosinusitis as the presence of paranasal sinus inflammation present for greater than 12 weeks. In our patient study group, all cases of chronic rhinosinusitis had failed to respond to antibiotic therapy and had not been treated previously with surgery. By microscopic examination, chronic inflammatory changes were confirmed in the resected sinus lining of all study patients. Intraoperative cultures were obtained from the nasal vestibule, the middle meatus, ethmoid lining, and peripheral blood during and after the endoscopic procedure. We found approximately 30% of the patients with sterile sinuses, 50% with coagulase-negative staphylococci, and the remainder with a mixed group of "nonpathogenic" organisms. Anaerobes were conspicuously rare. The blood cultures were positive in 7% of cases and were consistent with an organism of the operative site. This is the first time bacteremia has been reported in association with endoscopic sinus surgery. The results suggest that chronic rhinosinusitis is not a bacterial disease, but rather the result of chronic inflammation produced by a previous acute inflammation. The incidence of positive blood cultures, while relatively low and cleared quickly, should alert the physician for the possible need for prophylactic antibiotics in patients with cardiac, prosthetic, or systemic conditions that could lead to metastatic infection.

Antibiotic Prophylaxis↗