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Johns Hopkins Medicine Research Highlights 2008

A sampling of our scientists' 2008 results:

Discovered that a “swish-and-spit” mouth-rinse saliva test captures the genetic signatures common to head and neck cancer and holds promise for screening those at high risk of these diseases.

Demonstrated that activating a protein found on some immune cells seems to halt the cells’ typical job of spewing out substances that launch allergic reactions, a finding that could lead to new treatments for reactions ranging from hay fever to asthma attacks.

Demonstrated that additional copies of the Ets2 gene can suppress colon cancer in laboratory mice, supporting other studies that suggest people with Down syndrome, who carry an extra copy of many genes, get fewer cancers of many types.

Built a three-dimensional picture of enzyme PIK3CA, which often mutates in such malignancies as colon, brain, stomach, breast and lung cancer, providing a potentially crucial visual aid to developing mutation-specific inhibitors for cancer therapy.

Conducted the first survey of African American outpatients, revealing a decades-long, lingering mistrust of physicians and medical research, stemming from the notorious Tuskegee study of syphilitic men, now precludes the much-needed participation of African Americans in clinical trials.

Uncovered a previously unsuspected cellular interaction between two proteins, IP6K2 and HDP90, that could be used to design stronger yet less-harmful anticancer drugs that would have fewer side effects.

Joined the 1000 Genomes Project to sequence the genomes of at least 1,000 people around the world to create the most detailed catalog of human genetic variation.

Identified a common genetic alteration in the CNTNAP2 gene that is associated with autism when inherited by sons from their mother—one of the strongest genetic links to autism susceptibility found to date.

Determined that a modified version of the high-protein, low-carbohydrate Atkins Diet, long advocated as a means for reducing epileptic seizures in children, can also significantly cut the number of seizures in adults with epilepsy.

Conducted the largest review of survival rates after heart transplant surgery, compiling evidence that supports raising the benchmark for designating a hospital as a high-volume hospital rise from 10 heart transplants per year to 14, thus tightening the standards used to designate which hospitals are best at performing such surgeries.

Discovered that people with cystic fibrosis who also carry a variation in the gene TGFbeta1 tend to have weaker lungs and shorter life expectancies when exposed to secondhand smoke.

Found that nevirapine, an antiretroviral drug already widely used in the developing world to prevent the transmission of HIV from infected mothers to their newborns during childbirth, also can substantially cut the risk of subsequent HIV transmission during breast-feeding.

Created Human Proteinpedia, a free-access, online repository of protein information that is contributed to and shared by researchers around the world.

Devised a “lab on a chip” used to study how changes in fluid flow direction, intensity and speed affect the growth and behavior of a single nerve cell.

Determined that the mothers of some autistic children may have made antibodies against their fetuses’ brain tissue during pregnancy, potentially causing changes that led to autism.

Used functional magnetic resonance imaging (fMRI) to discover that when jazz musicians improvise, their brains turn off areas linked to self-censoring and inhibition and turn on those that let self-expression flow.

Conducted a nationwide study that showed that patients who undergo lung cancer surgery in teaching hospitals have a 17 percent less chance of dying after surgery compared with patients undergoing lung cancer surgery at non-teaching hospitals.

Discovered that two clinically different inherited syndromes—Bardet-Biedl syndrome and Meckel-Gruber syndrome—in fact are genetic variations of the same disorder, a finding that could lead to more accurate diagnoses and changes in drug development and other therapies for seemingly disparate conditions.

Found that individual dieters are less likely to regain lost weight when they receive monthly advice directly from trained counselors rather than getting tips from weight-loss Web sites.

Determined that head and neck cancers caused by the human papillomavirus (HPV), a common sexually transmitted virus, most often were linked to certain sexual behaviors and marijuana use, whereas non-HPV related head and neck tumors were different and most often associated with tobacco smoking, alcohol use and poor oral hygiene.

Identified chemical changes associated with several genes that, with further study, might be used to predict which lung cancers are more likely to recur, and therefore prompt more aggressive treatments for higher-risk patients. 

Discovered the oldest-known record of rabbits by comparing the bones from the feet of modern-day jackrabbits with previously unidentified, 53-million-year-old fossil bones found in west-central India, extending the record of the whole category of the animal on the Indian subcontinent by 35 million years.

Participated in what is believed to be the largest study of the genetic roots of such inflammatory bowel diseases as ulcerative colitis and Crohn’s Disease.

Demonstrated in animal studies that high doses of vitamin B, or folate, found in leafy green vegetables, beans and nuts, can blunt the damaging effects of future heart attacks.

Showed that corneas from older donors share similar transplant success rates as those from younger donors, a finding likely to expand the donor pool and cornea availability. 

Discovered that blood vessels in the head can guide the development of growing facial nerve cells with blood pressure-controlling proteins, a finding that suggests that nerves appear to use blood vessels as guideposts to direct their growth in one of several possible directions.

Discovered that African-American patients with chronic kidney disease (CKD) often continue to lose their kidney function over time even when their blood pressure is kept under control, a strategy typically effective for other patients, suggesting that treating CKD in African-Americans may be much more complex than previously thought.

Reported from the first wide-scale evidence from the Multiethnic Study of Atherosclerosis (MESA) that severe overweight is linked prolonged inflammation of heart tissue and the subsequent damage leading to heart failure.

Discovered a possible link between an enzyme involved in Alzheimer’s disease and the development of schizophrenia and related psychiatric disorders, a finding that could provide a new target for developing therapies.

Identified a membrane protein called Pirt, which appears to regulate the ability of another protein, TRPV1, to channel a nerve’s full pain response to both heat and spice, a discovery that could lead to development of drugs that target these pain-conveyors without unfavorable side effects.

Demonstrated that the chemical BH4 (tetrahydrobiopterin), commonly used to treat phenylketonuria (PKU), a rare genetic disorder that can cause irreversible brain damage, also may hold wider promise as a treatment for millions of Americans with potentially lethal enlarged hearts caused by high blood pressure.

Led a multicenter study that fine-tuned the dosage and timing for administering clot-busting tissue plasminogen activator (tPA) to patients with strokes caused by bleeding within the brain, a new treatment that dramatically decreases death and disability in patients who suffer this often-lethal subset of stroke.

Held one of the largest single-day events to screen young athletes in the U.S. for early signs of life-threatening defects in their hearts, testing more than 300 teenage participants in the track and field championship games of the Maryland Public Secondary Schools Athletic Association.

Discovered that the cognitive decline often seen in coronary artery disease patients most likely stems from the disease itself, and not from bypass surgery or other treatments for the disease as earlier research had suggested.

Established a human cell-based system for studying sickle cell anemia by developing a stem cell line containing the mutation that causes the disease and demonstrating a faster and more efficient method of reprogramming cells that might also speed the development of stem cell therapies for other conditions.

Employed a short-term, very high dose regimen of the immune-suppressing drug cyclophosphamide, dubbing it the HiCy treatment, which seemed to slow the progression of multiple sclerosis (MS), might even restore neurological function lost to the disease, and provide an approach that could be the linchpin of a significant advance for MS treatment.

Discovered the enzyme that allows amoeba to evade the body’s immune system and cause dysentery, which affects 500 million people worldwide annually.

Discovered in fruitflies that the gene called apontic that helps regulate cell movement, a finding that sheds light on how cancer cells might spread.

Discovered that prostate cancer patients whose tumors recurred are three times more likely to survive the disease long-term if they undergo salvage radiation therapy within two years of the recurrence, especially if their initial tumor was fast-growing.

Developed a new numbered index that grades how well each of 25 anti-HIV drugs in five commonly used drug groups suppresses the virus and keeps the disease in check, offering the first explanation for why only certain drug combinations are effective because they include at least one high-scoring medication.

Found that patients with depression have an increased risk of developing type-2 diabetes—and that patients with type-2 diabetes have an increased risk of developing depression.

Discovered that the chemical marks on DNA are similar among family members and can change as we age, which may contribute to increased, age-related and familial risk of susceptibility to diseases such as diabetes and cancer.

Reported that the blood pressure drug losartan does appear effective at slowing the enlargement of the aorta in children with very severe Marfan syndrome.

Found that the beneficial psychological impact of psilocybin, the alkaloid contained in “sacred mushrooms,” appears to last more than a year to increase a sense of well-being or life satisfaction.

Developed the first experimental “stuffy nosed” mice with inflamed nasal tissues not unlike those suffered by the 31 million Americans who live with chronic sinusitis, allowing researchers to better study the condition and to develop new therapies. 

Discovered that the Notch protein found on surface of human embryonic stem cells (hESCs) helps them “decide” which kind of cell they will become, a finding that may be useful for developing stem cell therapies.

Demonstrated that kidneys recovered from African American donors who died from cardiac arrest offer the best survival rate for African American recipients of a deceased-donor kidney, contrary to the long-held belief that kidneys from white brain-death donors offer the best deceased-donor transplant survival rate for either black or white recipients.

Reported that a review of 616 patients whose pancreatic cancers were surgically removed between 1993 and 2005 revealed that those who were treated with a combination of chemotherapy and radiation after surgery survived longer than those receiving surgery alone.

Discovered that the same multistep, molecular protein reaction process that allows animals to adapt to different light intensities also is involved in the adaptation to changes in environmental temperature, raising the possibility that similar multistep processes may allow mammals to sense small changes in internal body temperature.

Concluded along with other researchers that the hemoglobin A1c (HbA1c) blood test, currently used for monitoring people already being treated for diabetes, may have a far wider use in identifying the estimated six million people in the U.S. who have diabetes but don’t know it.

Reported on an analysis of a diverse sample of 13,000 initially healthy men and women that revealed that inadequate levels of vitamin D—obtained from milk, fortified cereals and exposure to sunlight—lead to a substantially increased risk of death.

Showed compelling evidence that an exceptionally strong immune system, not a defective strain of the HIV virus, enables some people who have had HIV for years to show extremely low levels of it in their blood, never progress to full-blown AIDS, and remain symptom-free even without treatment. The findings on these “elite suppressors” offer hope to vaccine researchers attempting to harness the body’s immune system to halt the progression of HIV disease.

[Up to August 20]

> Research Highlights 2006 and earlier

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