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Vital Signs
A hijacking in Huntington's
"Footprint" is clue in schizophrenia
Words from the bench
A life-saving question
Distraction from the pain?
At hand: the latest on antibiotics
An unfounded notion
Climbing ever higher in the ranks

A hijacking in Huntington's

Scientists in 1993 discovered the gene for Huntington's disease (HD), a progressive hereditary disorder that starts as uncontrollable jerking and then moves on to dementia and death. But since that time, they've been stumped as to how a mutant version of the gene--found in one in 10,000 people--leads to the death of nerve cells in a key part of the brain. Now, researchers at Hopkins conclude that a "hijacking" is involved.

"We've known for a long time that the abnormal gene produces a flawed form of a protein called huntingtin," says lead researcher Christopher Ross, professor of psychiatry and of neuroscience, whose team reported its findings in the March 23 Science. Scientists have also known that these proteins clump together in nerve cells found in the corpus striatum, the part of the brain controlling movement and thought. But the clumping doesn't directly cause HD. "It's the way that huntingtin interacts with other proteins that's toxic," Ross says.

The normal nerve cell (left) begins to die (middle) after being injected with mutant HD genes. By adding an altered protein, the dying cell is rescued (right).
Courtesy Science

To investigate possible interactions, Ross and his team zeroed in on one particular protein called CBP, a molecule critical to gene expression and neuronal activity in the brain. The team attached fluorescent markers to huntingtin, CBP, and DNA, and found that huntingtin "hijacks" CBP away from its spot along DNA. "Without CBP," Ross says, "a pathway crucial for cell survival never gets turned on." The researchers showed this hijacking in live mice carrying the human HD gene and in postmortem brains from human HD patients.

Once they understood this interaction, the researchers worked to "rescue" CBP. They genetically engineered the CBP protein so that it now lacked the molecular areas that made it vulnerable to mutant huntingtin.

"It was no longer being hijacked," Ross reports. So far the rescue has been demonstrated only in cell cultures; Ross believes scientists now can work toward developing drugs that block the interaction between huntingtin and CBP. --Emily Carlson (MA '01)

"Footprint" is clue in schizophrenia

New evidence from a Hopkins research team strengthens the idea that a virus may contribute to some cases of schizophrenia.

Led by Children's Center pediatrician Robert Yolken, the team found the molecular "footprint" of a retrovirus in the cerebrospinal fluid in 30 percent of people with acute schizophrenia; of those with a chronic form of the illness, about 7 percent showed signs of the footprint. The footprint did not appear in the brains or cerebrospinal fluid of those without schizophrenia.

"While our report doesn't explain why the retrovirus becomes active in the first place, it presents clues as to what may happen when it does become active," Yolken says. "Our ultimate hope is that we can interfere with the retrovirus by preventing it from become active. If we can do that, it may give doctors another method of treating schizophrenia."

Schizophrenia is believed to affect as many as 1 in 100 people in the United States; it costs the U.S. $65 billion annually in healthcare and related costs. To learn more about how researchers at Hopkins's Stanley Division of Developmental Neurovirology are working to elucidate the role of infection and immunity in a control group of those with schizophrenia and bipolar disorders, visit

Words from the bench

"While working with families of chronically ill children, we realized lots of parents were saying positive things about caring for their children. We really just wanted a chance to ask the question, In what ways are things going well?"

--Hopkins assistant professor of pediatrics Robin Chernoff, on a study that found most mothers reported having "stronger" families that "had benefited" as a result of having a child with a chronic condition. The study appeared in the March Ambulatory Pediatrics.

"One of the key questions for dermatologists has been, How should we be treating acne in any given case? Here we are in the 21st century and we still don't have a clear answer to that question."

--Hopkins pediatrician and medical informatics specialist Harold Lehmann, in an evidence report for the U.S. Department of Health and Human Services, which concluded that dermatologists can't prove which acne treatments and drugs work best.

A life-saving question

Visits to the hospital ER offer an ideal opportunity for healthcare professionals to screen women for domestic abuse. But that opportunity too often goes overlooked, says School of Nursing researcher Nancy Glass.

Illustration by Tim Teebken Glass surveyed over 3,000 female patients who had been admitted to 11 emergency departments in community hospitals throughout California and Pennsylvania. Confirming the results of earlier studies, she found that only 25 percent of the women who had been abused reported being asked about recent or past abuse.

But Glass also learned that more than 80 percent of the participants--regardless of their personal histories--supported routine screening for abuse.

"We're recommending that 100 percent of hospitals screen 100 percent of women," says Glass. "If we don't ask all women, we won't be able to intervene."

Glass, however, cautions ER personnel to keep a woman's future safety in mind when reporting abuse to officials: "We need to make sure the right resources, such as social workers and shelters, are available before contacting the police." -- EC

Distraction from the pain?

No patient enjoys having a bronchoscope inserted through her mouth or up her nose. "It's very uncomfortable without enough anesthesia," says Hopkins pulmonologist Gregory Diette. Unfortunately, doctors sometimes can't provide enough pain control without causing harmful side effects, like respiratory or heart problems.

So instead Diette and Hopkins colleague Noah Lechtzin try to transport patients a soothing spring meadow, where stately mountains rise in the background, and a calming stream babbles nearby. Okay, so the scene is actually staged with a mural and a cassette tape player. But the effect appears to be helpfully distracting.

With funding from Hopkins, the two pulmonologists mounted a flag-sized nature scene in the rooms where patients prepared for, underwent, and recovered from bronchoscopies. Patients also listened to taped nature sounds.

The findings: Those in the intervention group, who received the same amount of anesthesia as those in the control group, were 43 percent more likely to report pain control as "very good" or "excellent," and 63 percent more likely to report the ability to breathe as "very good" or "excellent."

"We should consider using this type of intervention in bronchoscopy and any potentially painful procedure when people are awake," recommends Diette. He and Lechtzin, who presented their findings in April at the American Thoracic Society annual conference, plan to study the feasibility of implementing this distraction therapy with oncology patients as well. -- EC

At hand: the latest on antibiotics

Partly in response to growing public concern over antibiotic resistance and the inappropriate prescribing of drugs, Hopkins experts have developed a solution--an easily navigated, regularly updated digital handbook for physicians in private practice and hospitals. The Antibiotic Guide, or ABX Guide, offers free and up-to-the-minute information on more than 160 drugs and 140 diseases.

"One of the biggest challenges doctors face is trying to keep up with the latest research on antibiotics," says Walter Atha, director of the ABX Guide project and a Hopkins emergency medicine physician. New information can change by the week or even the day, with researchers finding that certain combinations of drugs shouldn't be used, or that one particular drug is no longer effective against certain bacteria. With the ABX Guide, even doctors in remote rural clinics can tap into the latest information on drug choices, interactions, resistance, and even FDA recalls--all via handheld PC or the Internet.

Unlike existing digital guides, says Atha, all the information in the ABX Guide is "based on the best scientific evidence"-- annotated and reviewed by specialists at Hopkins, as well as by experts at other institutions, who write specific sections.

The ABX Guide grew out of the Hopkins Initiative Point of Care-Information Technology (POC-IT), and was conceived and spearheaded by Sharon McAvinue, POC-IT's director. Johns Hopkins holds the copyright to all POC-IT content. Future guides will cover specialties including HIV/AIDS, arthritis, and asthma.

An unfounded notion

Good news for breast cancer patients--a new Hopkins study challenges the notion that breast cancer increases a woman's risk of colorectal cancer.

"Overall, we found that women with breast cancer were 5 percent less likely to have colon cancer and 13 percent less likely to develop rectal cancer compared to women in the general public," says lead author Craig J. Newschaffer, assistant professor of epidemiology at Hopkins's Bloomberg School of Public Health. The study appeared in the March 16 issue of The Lancet.

Newschaffer and his colleagues aren't sure why they saw reduced risk for colorectal cancers but offer a few possibilities: Perhaps women with breast cancer receive more thorough medical care, or make beneficial changes to their lifestyles once they receive the breast cancer diagnosis. "Another possibility is that these women were exposed to factors that increased their risk of breast cancer but protected against colorectal cancer," says Newschaffer.

He stresses, however, that breast cancer patients and their physicians should not feel safe to let down their guards against colorectal cancer, an oft-deadly disease. "Breast cancer," he says, "does not provide immunity from colorectal cancer."

Climbing ever higher in the ranks

Johns Hopkins Medical School is No. 2 in the nation and gaining on top-ranked Harvard, according to U.S. News & World Report's annual ranking. While Harvard earned an overall score of 100, Hopkins was a close second with 94, up from 73 points last year. Hopkins earned high marks in a variety of specialty programs, including Pediatrics and Internal Medicine, which both ranked No.1; Geriatrics, Drug/Alcohol Abuse, and AIDS, which all ranked No. 2; and Women's Health, which ranked No. 3, up from fifth place last year.

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