Overexpression of the proto-oncogene C-jun in association with low-risk type specific human papillomavirus infection in condyloma acuminata

Infection with different types of human papillomavirus (HPV) is associated with neoplasia at different anatomic sites. The “low-risk” HPVs (LR-HPV) are responsible for benign genital lesions such as condyloma acuminata. In order to clarify the tumorigenic mechanism of LR-HPV, the HPV infection status was investigated and the expression of the c-jun proto-oncogene in different HPV-related skin and genital lesions analyzed. Of the 17 condyloma specimens analyzed by Western blotting, 13 cases (76.5%) exhibited overexpression of the c-jun gene. All 13 cases harbored high copy numbers of the LR-HPV genome with an average of 926 copies per cell, whereas the other four cases had an average of 12 copies of LR-HPV per cell (P < 0.001). Further typing of HPV by Southern blotting revealed that HPV-6 and HPV-11 infections predominated in c-jun positive cases. The c-jun protein was detected much less frequently in cervical cancers (three of 29, or 10.3%) and skin warts (one of 10), and was not detected in five genital polyps or in five normal cervical tissues. These findings suggest a type 6/11-specific induction of c-jun gene expression in HPV-related neoplastic lesions. © 1996 Wiley-Liss, Inc.     

Impact of protocolized postarrest care with targeted temperature management on the outcomes of cardiac arrest survivors without temperature management

IntroductionProtocolized postarrest care that includes targeted temperature management (TTM) improves survival and neurological outcomes in cardiac arrest survivors. Whether the accumulated experience regarding the use of the protocolized approach also benefits patients who did not undergo TTM has yet to be investigated.MethodsAdults (≥18 years old) with nontraumatic cardiac arrest and who survived to intensive care unit (ICU) admission were retrospectively recruited from a single tertiary medical centre from 2006 to 2009 and 2011 to 2017. Patients were excluded if they had traumatic injuries, were pregnant, did not survive to ICU admission, regained clear consciousness within 3 h after the return of spontaneous circulation, or underwent TTM. The sum of TTM cases since 2006 and before the cardiac arrest of each enrolled patient was used as a substitute index for the amount of experience accumulated from the use of protocolized TTM care.ResultsIn total, 802 non-TTM patients were enrolled in the final analysis. The rate of survival to hospital discharge increased from 25.9% in 2006 to 33.3% in 2017. Regarding neurological recovery at hospital discharge, the incidence of favourable neurological function (cerebral performance category: 1 or 2) increased from 10.3% in 2006 to 23.5% in 2017. A multiple logistic regression indicated a significant association between the cumulative TTM case numbers and neurological outcomes in patients who did not receive TTM.ConclusionsThe improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM was associated with the cumulative number of cases receiving protocolized TTM care. In the era of TTM, the use of only historical control data might lead to bias, which is caused by overlooking the influence of a more refined protocolized postarrest care that includes TTM.

KEY MESSAGE

• The cumulative number of cases receiving protocolized TTM care, which we used as a substitute index for the amount of experience accumulated from the use of protocolized postarrest care that includes TTM, was associated with the improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM.

     

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

The development of minimally invasive and easy-to-use sensor devices is of current interest for ultrasensitive detection and signal recognition of Alzheimer''s disease (AD) biomarkers. Over the years, tremendous effort has been made on diagnostic platforms specifically targeting neurological markers for AD in order to replace the conventional, laborious, and invasive sampling-based approaches. However, the sophistication of analytical outcomes, marker inaccessibility, and material validity strongly limit the current strategies towards effectively predicting AD. Recently, with the promising progress in biosensor technology, the realization of a clinically applicable sensing platform has become a potential option to enable early diagnosis of AD and other neurodegenerative diseases. In this review, various types of biosensors, which include electrochemical, fluorescent, plasmonic, photoelectrochemical, and field-effect transistor (FET)-based sensor configurations, with better clinical applicability and analytical performance towards AD are highlighted. Moreover, the feasibility of these sensors to achieve point-of-care (POC) diagnosis is also discussed. Furthermore, by grafting nanoscale materials into biosensor architecture, the remarkable enhancement in durability, functionality, and analytical outcome of sensor devices is presented. Finally, future perspectives on further translational and commercialization pathways of clinically driven biosensor devices for AD are discussed and summarized.

Advancements of clinically driven biosensors in current Alzheimer''s diagnosis are highlighted in both in vitro and in vivo applications.     

Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation

Characteristics of the tumour that affect and predict the survival outcome of patients with cancer are prognostic markers for cancer. In non-small cell lung carcinoma (NSCLC), stage is the main determinant of prognosis and the basis for deciding options for treatment. Patients with early-stage tumour are treated by complete surgical resection, which is curative in 40-70% of patients. That there are other factors important in determining the biology of these tumours, especially genes that have a role in metastasis, is indicated. Such factors could potentially be used to further classify patients into groups according to substages that may be treated differently. During the past decade, a large number of proteins that are putatively important in carcinogenesis and cancer biology have been studied for their prognostic value in NSCLC, but none of them have been proved to be sufficiently useful in clinical diagnosis. Several markers (epidermal growth factor receptor, human epidermal growth factor receptor 2, Ki-67, p53 and Bcl-2) have been studied exhaustively. Ki-67, p53 and Bcl-2 are suggested to be important but weak prognostic markers, by meta-analyses of the results. Cyclin E, vascular endothelial growth factor A, p16(INK4A), p27(kip1) and beta-catenin are promising candidates, but require further study in large randomised clinical trial samples by using standardised assays and scoring systems. Some issues and inconsistencies in the reported studies to date are highlighted and discussed. A guideline for a multi-phase approach for conducting future studies on prognostic immunohistochemistry markers is proposed here.     

Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model

BACKGROUND: Stent-based delivery of sirolimus (SRL) has shown reduction in neointimal hyperplasia and restenosis. The purpose of this study was to evaluate the chronic vascular response and the expression of cell cycle regulators after SRL-eluting stent implantation in a porcine coronary model. METHODS: Forty-nine pigs underwent placement of 109 oversized stents (control, n=54, SRL (140 microg/cm(2)), n=55) in the coronary arteries with histologic analysis and Western blot (PCNA, p27(kip1), CD45, MCP-1, IL-2, IL-6, TNF-beta) at 3, 30, 90 or 180 days. RESULTS: At 3 days, the mean thrombus area was similar for control (0.38+/-0.19 mm(2)) and SRL (0.29+/-0.09 mm(2)) stents. After 30 days, the mean neointimal area was significantly less for the SRL (1.40+/-0.35 mm(2)) versus the control stents (2.94+/-1.28 mm(2), p<0.001). At 90 and 180 days, the mean neointimal area was similar for the SRL (3.03+/-0.92 and 3.34+/-0.99 mm(2)) as compared with control stents (3.45+/-1.09 and 3.65+/-1.23 mm(2)). Western blot analysis demonstrated an increased expression of p27(kip1) in the vessel wall at 90 days for the SRL versus control stents (p=0.05) but with increased levels of PCNA in the SRL as compared with control stents (p=0.003). CONCLUSION: SRL-eluting stents favorably modulate neointimal formation for 30 days in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained presumably due to delayed cellular proliferation despite increased levels of the cyclin-dependent kinase p27(kip1) in the vessel wall.