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Johns Hopkins Medicine Research Highlights 2006

A sampling of our scientists' 2006 results:

Discovered that patients with papillary thyroid cancer (PTC) have poorer outcomes if they carry a mutation in the gene that triggers production of a tumor growth protein.

Proved that survival in some women with advanced ovarian cancer can be increased by delivering chemotherapy directly into the abdomen via a catheter, combined with intravenous medication.

Uncovered that ALS—Lou Gehrig’s disease—damages motor neurons, through the secretion of a warped, toxic molecule.

Alerted the U.S. Food and Drug Administration to a problem with a newly marketed catheter valve that prompted a spike in potentially deadly bloodstream infections in the pediatric intensive care unit and other ICUs.

Demonstrated that giving genetically engineered human thyroid-stimulating hormone to thyroid surgery patients before radioiodine treatment avoids the previous need to stop thyroid replacement therapy and miserable side effects.

Found that continuous low-level heat wrap therapy (CLHT) significantly reduces acute low back pain and related disability and improves occupational performance of employees in physically demanding jobs.

Co-discovered that a gene mutation in the descendants of Abraham Lincoln’s grandparents suggests that the president may have suffered from a disease that destroys the nerve cells in the cerebellum, the part of the brain that controls movement.

Determined that the subtype of HIV is a better clue to predicting rapid death from AIDS than the viral load, long the key monitor of AIDS’s progression.

Studied more than 300 couples in Uganda and found that male circumcision reduced by 30 percent the likelihood that a female who is HIV negative would become infected by an HIV-positive male.

Developed a Web-based, automated computer program that greatly simplifies the time-consuming, error-prone process of manipulating DNA sequences to determine the effect of gene mutations on individuals.

Provided the first comprehensive map of a part of the adult human brain containing astrocytes, cells known to produce growth factors critical to the regeneration of damaged neural tissue and that potentially serve as brain stem cells.

Demonstrated a 37 percent mortality rate reduction in patients being treated for stroke caused by intracerebral hemorrhage, or bleeding in the brain, by lowering by a third the dose of the clot-busting drug tPA (tissue plasminogen activator).

Performed the first large-scale analysis of interactions between proteins in human cells to yield the most detailed human “interactome” yet describing the interplay of proteins that occur in cells during periods of health or illness.

Reported that even a years-long delay in surgery for patients with small, low-grade prostate cancer does not appear to increase the risk of the disease progressing to an incurable form.

Co-discovered a mouse immune cell dubbed “IKDC” that plays dual roles as both a messenger and an attacker  that seeks out and destroys cancer.

Discovered a protein found only in cerebrospinal fluid that may be useful in identifying a subgroup of patients with multiple sclerosis (MS) or identifying those at risk for the debilitating autoimmune disorder.

Collaborated in a study that suggests hospital emergency departments are not fully prepared to deal with pediatric emergencies.

Reduced the size of seriously diseased, thickened hearts in genetically engineered obese mice by injecting the CNTF growth factor, which mimics  the activity of the appetite suppressing brain hormone leptin, and has been found to be insufficient in obese people.

Discovered a previously unrecognized role played by the gene HIF-1 in acting as a switch to transform an oxygen-poor cell’s function, thereby reducing the production of toxic molecules that could kill cells.

Identified a simple method to improve understanding of the complex molecular process that underlies cancer and thus pinpoints potential therapeutic targets and possibly enhances the screening of cancer treatments.

Created a database of disease-causing combinations of mutated human genes by discovering the genetic network in yeast cells that guards against lethal DNA damage.

Found that a single dose of the oral antibiotic azithromycin, taken after surgery for trichiasis, a leading infectious cause of blindness, can reduce the frequency with which eyelashes turn back in and abrade the eye.

Supported the findings of a study that showed aggressive use of a cholesterol-lowering drug, rosuvastatin (Crestor), significantly reverses atherosclerosis and its potentially fatal risk.

Determined that schizophrenia patients hospitalized for care unrelated to their mental disorder are at least twice as likely as similar patients without schizophrenia to suffer dangerous and expensive adverse events due to the decreased quality of care given to schizophrenia patients.

Identified mutations in the gene plakophilin-2 (PKP2) that most likely cause the rare arrhythmogenic right ventricular dysplasia (ARVD), which is among the top causes of sudden cardiac death among young athletes.

Conducted comparison blood cell testing in both sexes of a once-daily low-dose aspirin, showing that it helps lower the potential for clot-forming blood cells in both men and women.

Invented a cost-effective and highly efficient way of analyzing so-called “junk” DNA using zebrafish to study RET, a gene implicated in a relatively common human birth defect involving bowel obstruction and an inherited predisposition to neuroendocrine cancers.

Used mouse mutants to define critical steps involved in learning basic motor skills.

Employed experience gained in DNA analysis of human remains following the September 11, 2001 terrorist attacks to take part in efforts to identify the bodies of more than 70 victims of Hurricane Katrina in August 2005.

Searched through all the genes in the fruit fly genome and identified those required for cell migration, which may help explain how human cancer spreads.

 Raised doubts about the cancer-prevention properties of soy products but suggested that women who consume high-dose soy supplements to guard against breast cancer could be doing themselves more harm than good.

Produced an in-depth analysis of the benefits and risks of vitamin E that was cited by the medical newsletter Science Watch as one of the top 40 “hot” scientific papers.

Found that the antibiotic ceftriaxone, commonly used to treat a variety of serious infections, may also help prevent dementia in HIV patients.

Used a commonly prescribed blood pressure medicine, losartan (Cozaar), to prevent a potentially fatal weakening of arteries in mice with Marfan syndrome, prompting efforts to begin a clinical trial of the treatment for people with Marfan.

Found  that men’s brains showed evidence of up to three times the amount of the chemical activator dopamine as women’s when exposed to amphetamines.

Discovered Lazaro, a gene in fruit flies that helps certain specialized neurons to respond more quickly to bright light, a finding that has implications for understanding sensory perception in mammals.

Found tantalizing clues to the evolutionary origins of light-sensing cells in people and other species through a study of how the so-called third eye of “side-blotched” lizards distinguishes between blue and green, possibly to tell the time of day.

Reported that a survey measuring attitudes toward the work environment in the operating room reveals that surgeons exhibit the lowest level of teamwork and nurses the highest.

Co-discovered NOS1AP, a gene that may predispose some people to abnormal heart rhythms that lead to sudden cardiac death, a condition that affects more than 300,000 Americans annually.

Discovered that the CPT1c gene protects against weight gain caused by a high-fat diet in mice, a discovery that has broad implications for understanding the genetic underpinnings of obesity and weight management.

Found that hepatitis A vaccination is safe in HIV-infected children but may be less effective in creating immunity than it is in healthy children. Consequently, health care providers caring for HIV-infected youngsters should confirm their immunity after vaccination.

Discovered that many pediatricians have knowledge gaps when it comes to diagnosing and managing food-induced anaphylactic shock, indicating a need to provide medical residents with direct experience caring for patients with food allergies.

Demonstrated that computerizing the ordering of chemotherapy and other types of intravenous drug infusions for children greatly reduces the risk of potentially dangerous medical errors.

Co-discovered that few Maryland and Delaware primary care pediatricians screen patients regularly for autism and autism-spectrum disorders as part of their overall look at possible developmental delays.

Co-discovered that the MIF protein, made by cells in response to inflammation, apparently suppresses red blood cell production in people already infected by malaria parasites, which would be an important contributor to the severe anemia that kills almost half of the two million people worldwide who die each year of malaria.

Began screening for the genes that underlie sporadic ALS (Lou Gehrig’s disease), which affects approximately 90 percent of those living with the fatal neurodegenerative illness that destroys the motor neurons that enable movement, including breathing.

Found that the protein K17, long thought to provide only mechanical support for keeping cells and tissues from literally falling apart, also influences wound healing and maintains the structural integrity of hair follicles.

Proved that a single operation that plugs up a thin layer of bone in the inner ear can successfully treat the rare but significantly debilitating syndrome known as superior canal dehiscence, which causes rapid, uncontrollable eye movements, hearing loss, and sudden dizziness.

Demonstrated in people that the slower the brain learns to control certain muscle movements, such as operating a robot-controlled joystick, the more likely it is to remember the lesson over the long haul.

Explored new ways of distinguishing between dangerous skin lesions and ones that are not as worrisome. Early diagnosis and detection of malignant melanoma are essential to containing and curing the disease.

Uncovered a surprising and novel way of lowering blood sugar levels in mice by using a protein called GCN5 to manipulate the release of sugar by liver cells, a finding that could have implications for treating conditions such as diabetes.

Identified six regions of the human genome that might play a role in genetic susceptibility to obsessive compulsive disorder, or OCD, once thought to be primarily psychological in origin.

Dramatically demonstrated stem cells’ potential for establishing new, complete and fully-working motor neuron circuits by injecting mouse embryonic stem cells into rats whose virus-damaged spinal cords resemble those of humans afflicted with nerve disease, thereby restoring enough muscle strength to move previously paralyzed hind legs.

Created computer programs, including an ordering tool for pediatric chemotherapy, an online infusion calculator, and an online total parental nutrition calculator, that help reduce and prevent medication errors when treating infants and children.

Developed guidelines to improve pediatricians’ diagnosis of skin rashes that are caused by insect bites but mimic the symptoms of such fungal infections as scabies, allergies and HIV-associated dermatoses, which often require invasive and expensive procedures.

Identified and successfully tamed an overactive VCP/pr97 protein that plays a key role in cystic fibrosis. The findings may lead to the design of therapies and drugs that restore normal cell function and prevent the disease.

Discovered protein machinery that is important for cells to keep chromosomes intact, without which yeast cells experience broken chromosomes and DNA damage that in human cells would lead to cancer.

Demonstrated that the active agent in “sacred mushrooms” can induce mystical/spiritual experiences that can prompt changes in behavior and attitude that last several months, at least.

Found that a method developed to screen body fluids for certain kinds of cells and some of the cells’ genetic blueprint is twice as accurate at spotting breast cancer cells as a pathologist’s view with a microscope.

Found that senior citizens who continue driving are less likely to enter nursing homes or assisted living centers than those who have never driven or who have given up driving.

Successfully blocked the advance of retinal degeneration in mice that had a form of retinitis pigmentosa (RP) by treating them with vitamin E, alpha-lipoic acid and other antioxidant chemicals.

Discovered, while studying yeast, another possible link between diet and aging. The research may one day lead to new strategies to slow aging and treat cancer, both of which are closely linked to changes in gene control and energy metabolism.

Developed a new tool and experimental approach for watching multiple, real-time chemical activity in cells, which could lead to accelerating the design of new drugs that would go to specific places within cells to work more efficiently.

Launched a new, federally funded collaborative research unit to develop novel treatments for HIV-related memory loss and other cognitive disorders.

Discovered that simple heat sensitivity may make testicular cancer cells susceptible to standard treatments and die off more readily, explaining why testicular cancer patients such as Tour de France winner Lance Armstrong survive far better than patients with other advanced cancers.

Initiated the largest-ever study to learn more about the early progression of chronic kidney disease in children and teenagers, an often-stealthy killer that is poorly understood.

Showed a moderate program of physical exercise in men and women aged 55 to 75 had no ill effects on the heart’s ability to pump blood and did not produce a harmful increase in heart size.

Determined that a sizeable percentage of primary care physicians probably fail to diagnose patients with chronic kidney disease (CKD) and refer them to a nephrologist for treatment.

Discovered that a pill combining the chemicals curcumin and quercetin, found in onions and in turmeric, a spice used in curries, reduces both the size and number of precancerous lesions in the human intestinal tract.

Concluded that the sting of some species of yellow jacket bees causes more severe allergic reactions than the sting of others, countering the widely held belief that most people can outgrow a dangerous allergic reaction to a sting.

Co-discovered that combining the common tuberculosis drug isoniazid with high active antiretroviral therapy (HAART) is more effective than either treatment on its own in preventing full-blown TB in people with HIV.

Demonstrated that once treatment for HIV begins, relatively inexpensive methods for monitoring disease progression are less effective than previously thought.

Found that a once-daily dose of three antiretroviral drugs combined in one pill works better as an initial treatment for HIV infection than three-drug mixtures long considered the best for early treatment of the virus.

Demonstrated that access to emergency antiretroviral drugs in rural Uganda successfully suppressed the AIDS virus in the blood of HIV-infected people to nearly undetectable levels.

Conducted a survey that found serious knowledge gaps in HIV-infected men and women in India about their antiretroviral therapy as that nation—which now has the world’s largest number of HIV-infected people— prepares to implement plans to combat the disease.

Built on previous research of a common childhood brain cancer to show that a class of drugs currently being developed to treat Alzheimer’s disease can destroy the stem cells responsible for creating and sustaining childhood brain tumors.

Found that the CDK5 enzyme, normally associated with the nervous system, appears to control the deadly spread of prostate cancer. Blocking that enzyme could make metastatic cells more susceptible to chemotherapy.

Conducted what is believed to be the first study showing that neural changes in the brains of children with serious, untreated sleep apnea indicate they suffer damage in two brain structures tied to learning ability.

Established improved guidelines for diagnosing three severe, potentially fatal genetic diseases—Loeys-Dietz, Ehlers-Danlos and Marfan syndromes—that leave patients with aortas so flimsy that they can rupture in pregnancy, labor or even lesser activities, often without warning.

Discovered that the parasite behind African sleeping sickness uses a previously unknown way of making fatty acids, a component of fat and the outer layer of all cells, providing a new drug target.

Developed an online database to aid scientists worldwide in their quests for treatments to combat such under-studied “orphaned” diseases as Bardet-Biedl, Alstrom and Meckel-Gruber syndromes, all of which appear to share flaws in the work of tiny, hair-like structures on the surface of cells called cilia.

Found a possible relationship between anemia and impaired thinking in older adults. Correction of anemia in these patients could offer a chance to prevent some forms of cognitive decline.

Uncovered evidence that reduced activity of at least four genes in the body’s nasal immune defense system decreases several key chemicals on the inner lining of the nose, and is linked to chronic sinusitis.

Co-authored new International Society for Heart and Lung Transplatation (ISHLT) criteria for heart-transplant cases, saying elderly men and women with heart failure and men being treated for prostate cancer would be good candidates for the life-saving surgery.

Painstakingly figured out how to safely perform magnetic resonance imaging (MRI) scans on men and women who have any one of 24 modern types of implanted defibrillators and pacemakers.

Warned health care workers nationwide to be on the lookout for a more aggressive form of methicillin-resistant Staphylococcus aureus (MRSA), called community-acquired MRSA. Found that the same white blood cell chemistry known to damage kidneys used for transplants may also help prevent such damage.

Discovered that the  protein TFII-I helps control a cell’s absorption of calcium, and may be behind Williams-Beuren syndrome, a rare disorder involving craniofacial defects, problems with the aorta, and mental retardation.

Determined that children with strokes, brain tumors and other cerebrovascular diseases indeed can safely undergo potentially life-saving brain-mapping cerebral angiographies, which many physicians have shunned because of side-effect concerns.

Discovered how blocking the activity of the gene NRF2, which normally protects cells from environmental pollutants, could improve the effectiveness of standard platinum-based chemotherapy drugs widely used for lung cancer.

Figured out how to accurately “test drive” chemotherapy drugs for pancreatic cancer patients by grafting bits of their tumors onto mice and determining in advance which drug treatments offer the individual patients the best therapy.

Discovered the genetic origins of at least one form of Fuchs corneal dystrophy (FCD), the leading reason for corneal transplantations in the United States.

Joined with Ugandan scientists and others to launch the first clinical safety trial in Africa of a vaccine to prevent mother-to-child transmission of HIV through breastfeeding.

Demonstrated that transplanting human stem cells into the spinal cords of rats bred to duplicate ALS (Lou Gehrig’s disease) delays the start of nerve cell damage typical of the illness and slightly prolongs life.

Determined that carefully measured, low doses of Ritalin (methylphenidate) are safe and effective for treating attention deficit and hyperactivity disorder (AD/HD) in preschoolers. However, 3- to 5-year-olds appear more sensitive to the drug’s side effects than older children and require closer monitoring.

Established the Stem Cell Resource Center, a “one-stop shop” to preserve, create, supply and test high-quality cells lines to simplify and speed up safe human stem cell research.

Found that the PSA velocity— how fast the amount of PSA increases—is an accurate gauge of tumor aggression and danger, even when PSA levels are so low as to not warrant a biopsy.

Determined that patients with non-systolic heart failure may benefit more from pacemakers to speed up the heartbeat rather than from continual, long-term use of beta blockers, drugs that slow down the heartbeat.

Linked the muscle protein myosin VI to the development of prostate cancer and its spread.

Discovered how the protein Arc contributes to long-term memory and found it could be one culprit behind such long-term, memory-based human behaviors as addiction.

Developed a fast and accurate means of tracking the blood flow for coronary disease diagnosis by using the latest in imaging software and machinery on dogs whose coronary arteries had been narrowed.

Successfully grew large numbers of stem cells taken from healthy heart tissue of adult pigs and used the cells to repair some of the tissue damage done to those organs by lab-induced heart attacks.

Invented two new gene chip technologies—the TIP-chip and the double-tiled DNA chip-- that can be used to help identify otherwise elusive disease-causing mutations in the 97 percent of the human genome that is missed by standard gene chips.

Uncovered why just a few squares of dark chocolate a day can nearly halve the risk of a fatal heart attack by decreasing the tendency of platelets to clot in narrow blood vessels.

Co-discovered that risedronate, a drug used to treat the bone loss of osteoporosis, most likely slows the breakdown of joint cartilage as it stabilizes bone loss.

Discovered that PAR-polymer may be the “smoking gun” responsible for most tissue and organ damage after a period of blood oxygen loss that is followed by a sudden restoration of blood oxygen flow.

Discovered that only one in five inner-city children with chronic asthma gets enough medicine to control dangerous flare-ups of the disease, leading to more complications and increased risk of death.

Found that sildenafil (Viagra) and other erectile dysfunction drugs could heighten the body’s natural anti-cancer activity by unmasking cancer cells so that the immune system can recognize and attack them.

Co-discovered that bone morphogenic protein 4 (BMP4) can inhibit lethal human brain cancers in mice.

Discovered that women with ovarian cancer are at increased risk of a rapid and potentially fatal recurrence if their tumor cells have high levels of the protein NAC-1 that triggers abnormal growth and slows down cell death, both hallmarks of malignancy.

Found that ranibizumab, a drug commonly used to slow the loss of central vision due to macular degeneration, shows promise in stemming a common precursor of blindness in diabetics.

Determined that kidney stones in children are becoming fairly common and may be due to too much salt and too little drinking water in the today’s diets.

Discovered that the body’s immune system cells use an “assistant ” protein, to select the best-fitting antigen—the infectious, recognizable part of a germ—to recognize the germs and attack them.

Confirmed that simple, inexpensive, low-tech measures such as hand-washing, can significantly reduce common, costly and potentially lethal ICU infections.

> Research Highlights 2005 and earlier

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