Uterine leiomyomas affect 20%-30% of women older than 35 years. Extrauterine leiomyomas are rarer, and they present a greater diagnostic challenge: These histologically benign tumors, which originate from smooth muscle cells, usually arise in the genitourinary tract (in the vulva, ovaries, urethra, and urinary bladder) but may arise in nearly any anatomic site. In addition, unusual growth patterns may be seen, including benign metastasizing leiomyoma, disseminated peritoneal leiomyomatosis, intravenous leiomyomatosis, parasitic leiomyoma, and retroperitoneal growth. In the presence of such a pattern, a synchronous uterine leiomyoma or a previous hysterectomy for removal of a primary uterine tumor may be indicative of the diagnosis. However, some extrauterine leiomyomas may mimic malignancies, and serious diagnostic errors may result. The most useful modalities for detecting extrauterine leiomyomas are ultrasonography, computed tomography, and magnetic resonance (MR) imaging. The superb contrast resolution and multiplanar capabilities of MR imaging make it particularly valuable for characterizing these tumors, which usually show low signal intensity similar to that of smooth muscle on T2-weighted images. The radiologist's recognition of this and other characteristic features may help steer the clinician toward timely, appropriate management and away from unnecessary, potentially harmful treatment.
Acute pancreatitis is one of the most common conditions for which emergent imaging is indicated. Alcohol consumption and cholelithiasis are the most common causes of acute pancreatitis in adults, whereas the majority of cases in children are idiopathic or secondary to trauma. A wide variety of structural and biochemical abnormalities may also cause pancreatitis. Although in some cases it is difficult to identify the specific cause of the disease radiologically, certain uncommon types of acute or chronic pancreatitis may have unique imaging features that can help the radiologist make an accurate diagnosis. These unusual types include autoimmune pancreatitis, groove pancreatitis, tropical pancreatitis, hereditary pancreatitis, and pancreatitis in ectopic or heterotopic pancreatic tissue. Pancreatitis may occasionally be seen in association with cystic fibrosis or pancreas divisum, or secondary to worm infestation of the pancreaticobiliary tree (eg, by Ascaris lumbricoides). In addition, primary pancreatic and duodenal masses may occasionally manifest as acute or recurrent acute pancreatitis. Knowledge of the classic imaging findings of these entities allows prompt recognition of the relevant pathologic condition, thereby preventing misdiagnosis and subsequent inappropriate or delayed management.
There are three stages of transcribing DNA into RNA. These stages are initiation, elongation and termination, and they are wellunderstood biochemically. However, despite the plethora of structural information made available on RNA polymerase in the last decade, little is available for RNA polymerase in complex with transcription elongation factors. To understand the mechanisms of transcriptional regulation, we describe the first structure, to our knowledge, for a bacterial RNA polymerase in complex with an essential transcription elongation factor. The resulting structure formed between the RNA polymerase and NusA from Bacillus subtilis provides important insights into the transition from an initiation complex to an elongation complex, and how NusA is able to modulate transcription elongation and termination.
Bacterial RNA polymerases (RNAPs) contain several small auxiliary subunits known to co-purify with the core a, b and b9 subunits. The v subunit is conserved between Gram-positive and Gramnegative bacteria, while the d subunit is conserved within, but restricted to, Gram-positive bacteria. Although various functions have been assigned to these subunits via in vitro assays, very little is known about their in vivo roles. In this work we constructed a pair of vectors to investigate the subcellular localization of the d and v subunits in Bacillus subtilis with respect to the core RNAP. We found these subunits to be closely associated with RNAP involved in transcribing both mRNA and rRNA operons. Quantification of these subunits revealed d to be present at equimolar levels with RNAP and v to be present at around half the level of core RNAP. For comparison, the localization and quantification of RNAP b9 and v subunits in Escherichia coli was also investigated. Similar to B. subtilis, b9 and v closely associated with the nucleoid and formed subnucleoid regions of high green fluorescent protein intensity, but, unlike v in B. subtilis, v levels in E. coli were close to parity with those of b9. These results indicate that d is likely to be an integral RNAP subunit in Gram-positives, whereas v levels differ substantially between Grampositives and -negatives. The v subunit may be required for RNAP assembly and subsequently be turned over at different rates or it may play roles in Gram-negative bacteria that are performed by other factors in Gram-positives.
Summary DT-diaphorase is a two-electron reducing enzyme that activates the bioreductive anti-tumour agent, mitomycin C (MMC). Cell lines having elevated levels of DT-diaphorase are generally more sensitive to MMC. We have shown that DT-diaphorase can be induced in human tumour cells by a number of compounds, including 1,2-dithiole-3-thione. In this study, we investigated whether induction of DT-diaphorase could enhance the cytotoxic activity of MMC in six human tumour cell lines representing four tumour types. DT-diaphorase was induced by many dietary inducers, including propyl gallate, dimethyl maleate, dimethyl fumarate and sulforaphane. The cytotoxicity of MMC was significantly increased in four tumour lines with the increase ranging from 1.4-to threefold. In contrast, MMC activity was not increased in SK-MEL-28 human melanoma cells and AGS human gastric cancer cells, cell lines that have high base levels of DT-diaphorase activity. Toxicity to normal human marrow cells was increased by 50% when MMC was combined with 1,2-dithiole-3-thione, but this increase was small in comparison with the threefold increase in cytotoxicity to tumour cells. This study demonstrates that induction of DT-diaphorase can increase the cytotoxic activity of MMC in human tumour cell lines, and suggests that it may be possible to use non-toxic inducers of DT-diaphorase to enhance the efficacy of bioreductive anti-tumour agents.
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