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Here, we review the armamentarium on in vitro/ex vivo models of HIV sexual transmission and discuss how these models can be applied to study candidate microbicides. 相似文献
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A. Ari Hakimi Ying-Bei Chen James Wren Mithat Gonen Omar Abdel-Wahab Adriana Heguy Han Liu Shugaku Takeda Satish K. Tickoo Victor E. Reuter Martin H. Voss Robert J. Motzer Jonathan A. Coleman Emily H. Cheng Paul Russo James J. Hsieh 《European urology》2013
Background
Historically, VHL was the only frequently mutated gene in clear cell renal cell carcinoma (ccRCC), with conflicting clinical relevance. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC including PBRM1, SETD2, BAP1, and KDM5C. PBRM1, SETD2, and BAP1 are located in close proximity to VHL within a commonly lost (approximately 90%) 3p locus. To date, the clinical and pathologic significance of mutations in these novel candidate tumor suppressors is unknown.Objective
To determine the frequency of and render the first clinical and pathologic outcome associated with mutations of these novel candidate tumor suppressors in ccRCC.Design, setting, and participants
Targeted sequencing was performed in 185 ccRCCs and matched normal tissues from a single institution. Pathologic features, baseline patient characteristics, and follow-up data were recorded.Outcome measurements and statistical analysis
The linkage between mutations and clinical and pathologic outcomes was interrogated with the Fisher exact test (for stage and Fuhrman nuclear grade) and the permutation log-rank test (for cancer-specific survival [CSS]).Results and limitations
PBRM1, BAP1, SETD2, and KDM5C are mutated at 29%, 6%, 8%, and 8%, respectively. Tumors with mutations in PBRM1 or any of BAP1, SETD2, or KDM5C (19%) are more likely to present with stage III disease or higher (p = 0.01 and p = 0.001, respectively). Small tumors (<4 cm) with PBRM1 mutations are more likely to exhibit stage III pathologic features (odds ratio: 6.4; p = 0.001). BAP1 mutations tend to occur in Fuhrman grade III–IV tumors (p = 0.052) and are associated with worse CSS (p = 0.01). Clinical outcome data are limited by the number of events.Conclusions
Most mutations of chromatin modulators discovered in ccRCC are loss of function, associated with advanced stage, grade, and possibly worse CSS. Further studies validating the clinical impact of these novel mutations and future development of therapeutics remedying these tumor suppressors are warranted. 相似文献107.
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Heli Koukkunen Karri Penttilä Ari Kemppainen Ilkka Penttilä Matti Halinen Tapio Rantanen Kalevi Pyörälä 《Scandinavian cardiovascular journal : SCJ》2013,47(5):302-306
Objective - To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. Design - The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. Results - MI diagnosis was confirmed with elevated TnT (> 0.10 µg/l) in 108 patients, in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (> 5.0 µg/l), in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD ( p < 0.001). Conclusion - Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis. 相似文献
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Ari George Chacko Santhosh George Thomas K. Srinivasa Babu Roy Thomas Daniel Geeta Chacko Krishna Prabhu Varghese Cherian Grace Korula 《Clinical neurology and neurosurgery》2013
Objective
An awake craniotomy facilitates radical excision of eloquent area gliomas and ensures neural integrity during the excision. The study describes our experience with 67 consecutive awake craniotomies for the excision of such tumours.Methods
Sixty-seven patients with gliomas in or adjacent to eloquent areas were included in this study. The patient was awake during the procedure and intraoperative cortical and white matter stimulation was performed to safely maximize the extent of surgical resection.Results
Of the 883 patients who underwent craniotomies for supratentorial intraaxial tumours during the study period, 84 were chosen for an awake craniotomy. Sixty-seven with a histological diagnosis of glioma were included in this study. There were 55 men and 12 women with a median age of 34.6 years. Forty-two (62.6%) patients had positive localization on cortical stimulation. In 6 (8.9%) patients white matter stimulation was positive, five of whom had responses at the end of a radical excision. In 3 patients who developed a neurological deficit during tumour removal, white matter stimulation was negative and cessation of the surgery did not result in neurological improvement. Sixteen patients (24.6%) had intraoperative neurological deficits at the time of wound closure, 9 (13.4%) of whom had persistent mild neurological deficits at discharge, while the remaining 7 improved to normal. At a mean follow-up of 40.8 months, only 4 (5.9%) of these 9 patients had persistent neurological deficits.Conclusion
Awake craniotomy for excision of eloquent area gliomas enable accurate mapping of motor and language areas as well as continuous neurological monitoring during tumour removal. Furthermore, positive responses on white matter stimulation indicate close proximity of eloquent cortex and projection fibres. This should alert the surgeon to the possibility of postoperative deficits to change the surgical strategy. Thus the surgeon can resect tumour safely, with the knowledge that he has not damaged neurological function up to that point in time thus maximizing the tumour resection and minimizing neurological deficits. 相似文献110.