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Medical Education
HMS Hospitals Hone Plans for Deeper Cuts in Resident Hours

Clinical Research:
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Ambulatory Care:
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Sodium Channel Modulates Calcium-Based T Cell Activation

Drug Ads Need Plainer Language to Explain Risks

Proceedings of the HMS Faculty Council

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Sodium Channel Modulates Calcium-based T Cell Activation

"TRPM4 and other related molecules may offer attractive targets for the design of immune suppressant drugs."

The mechanisms of calcium influx and its key molecular channels have been well characterized in excitable cells such as those of the muscle and nervous system. Although calcium influx is known to occur in response to cellular signaling in nonexcitable cells like T lymphocytes, the molecules involved have remained unknown. "We have been interested in the molecular ion channels in nonexcitable cells for a long time," said Kinet.

In previous studies from his group, several genes coding for putative mammalian ion channels were cloned based on the C. elegans genome sequence. One of these, TRPM4, was shown to be a sodium ion channel that is activated in response to calcium influx. TRPM4's function, however, was unclear.

"TRPM4 seemed like a perfect match for a molecule that can affect calcium ion signals initiated by receptor stimulation," said Launay. The researchers hypothesized that the channel might modulate lymphocyte effector functions like the transcription programs leading to cytokine production.

Launay used two strategies to investigate TRPM4's role in T lymphocytes. Wild-type Jurkat T cells demonstrate an oscillatory-patterned calcium influx and release the cytokine IL-2 in response to the ligand phytohemagglutinin. When Launay expressed a dominant-negative form of TRPM4 in these cells, however, he saw a sustained calcium influx. The resulting IL-2 secretion was more than double that of wild-type. A knockdown of TRPM4 using RNA interference produced similar results, suggesting that TRPM4 plays a key role in modulating calcium oscillation in T cell activation.

As a consequence, said Kinet, "TRPM4 and other related molecules may offer attractive targets for the design of immune suppressant drugs."

--Jillian Lokere

Drug Ads Need Plainer Language to Explain Risks

Unfortunately, the average reading level of the print information may be well beyond the understanding of the average adult American, reports a study in the November 2004 Patient Education and Counseling.

An eighth-grade reading level or lower is recommended for the general public, but a college reading level is needed for the detailed risk information in the printed materials to which viewers were referred, said first author Kimberly Kaphingst, a postdoctoral fellow in the Center for Community-based Research at Dana-Farber Cancer Institute. Of the 69 different texts she evaluated, only one brochure met the eighth-grade standard.

Kaphingst, Rima Rudd, HSPH senior lecturer on society, human development, and health, and their colleagues used two literacy measures to assess the print supplements for 23 different drugs advertised in Boston on three major network stations over two months. In 2001, when the television ads were aired, direct-to-consumer prescription drug advertising expenditures had grown from about $47 million in 1990 to nearly $2.7 billion, with television's share surging from 13 percent in 1994 to about 64 percent in 2001.

For each televised ad, Kaphingst assessed key risk summaries in three types of materials suggested by the FDA--a website, a mailed brochure obtained through a toll-free number, and a concurrent print ad.

"Many of them were chock full of pharmacokinetic data and not useful from the patient perspective," said Kaphingst, who conducted the study as part of her doctoral thesis at HSPH. In two companion analyses, she found consumers also had a difficult time learning about risk information from the television ads themselves, according to an article she co-authored in the July/August 2004 Health Affairs.

"Our results clearly indicate that the FDA needs to take further steps to ensure the use of consumer-friendly plain language," Kaphingst and her co-authors write. They also recommend that physicians and pharmacists take special care to counsel patients about risk information for advertised drugs.

--Carol Cruzan Morton