August 21, 2009

Aliquots — research highlights from VUMC laboratories

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:


Building the brain’s protective barrier

Choroid plexuses (ChPs) are secretory organs in the brain. Four ChPs (one in each of the brain’s hollow ventricles) produce cerebrospinal fluid (CSF) and other neuroprotective molecules, and function as the blood-CSF barrier. Despite the crucial roles of the ChPs, the signaling mechanisms that regulate their production during development are poorly understood.
Xi Huang, a graduate student in the laboratory of Chin Chiang, Ph.D., and colleagues explored the development of the hindbrain ChP. They showed that Sonic hedgehog (Shh), a secreted signaling molecule with crucial roles during development, is expressed in hindbrain ChP epithelial cells.

They identified a distinct domain of the hindbrain ChP that does not express Shh, but that does respond to Shh, and they demonstrated that this Shh target zone functions as a progenitor domain to produce cells of the hindbrain ChP. Their findings, reported in the Aug. 1 issue of Development, reveal a novel role for Shh production and signaling in driving the growth of the hindbrain ChP throughout development.
Leigh MacMillan


Pancreatic cancer linked to blood type

Pancreatic cancer is one of the deadliest cancers, with a 5-year survival rate of less than 5 percent. But besides a family history of the disease, there are few established risk factors. To identify possible genetic risk factors, an international consortium of investigators conducted a genome-wide association study in 4,550 individuals with pancreatic cancer and 4,396 controls.

The patients were drawn from 21 studies, including two studies conducted among Chinese in Shanghai and directed, respectively, by Wei Zheng, M.D. Ph.D., and Xiao-Ou Shu, M.D., Ph.D.

hey identified a single nucleotide polymorphism (SNP) – a single “letter” variation in the genome – on chromosome 9q34 associated with increased pancreatic cancer risk. The SNP lies in a gene that encodes ABO blood type, a finding consistent with epidemiologic evidence that people with A, B and AB blood types have increased risk of pancreatic cancer compared to those with blood type O.

The study reported in Nature Genetics could improve risk assessment for the highly lethal cancer and exemplifies the large-scale, international collaborative research to identify genetic susceptibility factors for cancer.
Melissa Marino


Antibiotic use sparks TB resistance

Fluoroquinolones (e.g. levofloxacin, ciprofloxacin) are the most commonly prescribed antibiotics in the United States. They could become first-line drugs for tuberculosis treatment, but the effect of widespread use of these drugs on fluoroquinolone resistance in Mycobacterium tuberculosis has not been fully characterized.

Rose Devasia, M.D., M.P.H., Timothy Sterling, M.D., and colleagues studied records and assessed fluoroquinolone resistance in clinical samples from 640 TennCare (Medicaid) patients with culture-confirmed tuberculosis. They determined that the overall proportion of M.

tuberculosis isolates with fluoroquinolone resistance was relatively low (3.9 percent). However, prior exposure to fluoroquinolones for more than 10 days, particularly more than 60 days before the tuberculosis diagnosis, was associated with a high risk of fluoroquinolone-resistant tuberculosis (20.8 percent).

The study in the Aug. 15 American Journal of Respiratory and Critical Care Medicine highlights the importance of considering the diagnosis of tuberculosis in patients with suggestive symptoms and limiting the use of prolonged or repeated courses of fluoroquinolones.
Leigh MacMillan


Sugar not so sweet for kidney cells

In diabetes, elevated glucose levels can trigger the formation of sugar-modified proteins (advanced glycation end products, or AGEs) that can damage cells. AGEs may play a role in the development of diabetic nephropathy (DN), a progressive kidney disease caused by long-standing diabetes.

However, how these products damage the kidney is not clear.
To examine how sugar-modified proteins might induce pathologic changes in the diabetic kidney, Paul Voziyan, Ph.D., Ambra Pozzi, Ph.D., and colleagues incubated collagen IV – a major component of the kidney extracellular matrix – with glucose or methylglyoxal, another compound that contributes to AGE formation.

In the Journal of the American Society of Nephrology, they report that kidney cells plated on either glucose- or methylglyoxal-modified collagen exhibit several alterations in their behavior and function, including proliferation, migration, and adhesion. Based on these findings, the authors propose mechanisms by which these modifications can affect kidney cell function and contribute to diabetic nephropathy. Understanding these mechanisms could suggest novel strategies for the treatment of diabetic nephropathy by inhibiting AGE modifications.
Melissa Marino

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012