Overexpression of human cyclin D1 reduces the transforming growth factor beta (TGF-beta) type II receptor and growth inhibition by TGF-beta 1 in an immortalized human esophageal epithelial cell line.

Cyclin D1 has been implicated in G1 cell cycle progression and is frequently amplified, overtranscribed, and oversynthesized in human tumors, including esophageal carcinomas. To further address the role of cyclin D1 in cell cycle control and tumorigenesis, we have stably transfected the human cyclin D1 in the nontumorigenic esophageal epithelial cell line HET-1A. These transfected cells, which express increased amounts of cyclin D1, have enhanced colony-forming efficiency and saturation density and are resistant to growth inhibition by TGF-beta 1 compared with the parental cell line or a control vector cell clone. The clones which express increased amounts of cyclin D1 exhibited a decrease in the amount of TGF-beta type II receptor, indicating a plausible mechanism for their diminished response to TGF-beta 1. Therefore, deregulated expression of the cyclin D1 gene can modulate the negative growth factor pathway of TGF-beta 1 and may disturb the control of epithelial cell proliferation in esophageal carcinogenesis.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

A systematic literature review of Native American and Pacific Islanders’ perspectives on health data privacy in the United States

BackgroundPrivacy-related concerns can prevent equitable participation in health research by US Indigenous communities. However, studies focused on these communities'' views regarding health data privacy, including systematic reviews, are lacking.MethodsWe conducted a systematic literature review analyzing empirical, US-based studies involving American Indian/Alaska Native (AI/AN) and Native Hawaiian or other Pacific Islander (NHPI) perspectives on health data privacy, which we define as the practice of maintaining the security and confidentiality of an individual’s personal health records and/or biological samples (including data derived from biological specimens, such as personal genetic information), as well as the secure and approved use of those data.ResultsTwenty-one studies involving 3234 AI/AN and NHPI participants were eligible for review. The results of this review suggest that concerns about the privacy of health data are both prevalent and complex in AI/AN and NHPI communities. Many respondents raised concerns about the potential for misuse of their health data, including discrimination or stigma, confidentiality breaches, and undesirable or unknown uses of biological specimens.ConclusionsParticipants cited a variety of individual and community-level concerns about the privacy of their health data, and indicated that these deter their willingness to participate in health research. Future investigations should explore in more depth which health data privacy concerns are most salient to specific AI/AN and NHPI communities, and identify the practices that will make the collection and use of health data more trustworthy and transparent for participants.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.     

There's more to flow-mediated dilation than nitric oxide

Flow-mediated dilation (FMD) is the standard tool used to assess endothelial function. The premise behind the standard FMD test is that it serves as an endothelial-dependant nitric oxide bioassay; however, the endothelium may release additional dilatory molecules which contribute to FMD, most notably prostacyclin and endothelial-derived hyperpolarizing factor. The relative importance of these molecules to the dilatory response may vary substantially among individuals, particularly in response to a number of diseased states. This review discusses how each of these molecules may contribute to vasodilation, and considers the circumstances in which they may vary.