Genetic medicine hints at bloodletting and vitamins for astronauts

 

BLOODLETTING and vitamin pills are the future for astronaut health regimes. So hints a provocative proposal on the benefits of personalised gene-based medicine for space travellers.

Humans in space are at risk of a variety of ailments, from brittle bones caused by low gravity to cancer triggered by cosmic radiation. Astronauts on the International Space Station (ISS) already take supplements to counteract ill effects, such as vitamin D for bone strength.

But when travelling further into space, such as to an asteroid or Mars, astronauts will be exposed to radiation doses close to NASA’s acceptable lifetime limits, upping their chances of developing illnesses from damaged DNA.

To reduce each individual’s risk, we should examine their genome and then design countermeasures to protect against any potential problems, say Michael Schmidt of MetaboLogics in Fort Collins, Colorado, and Thomas Goodwin of NASA’s Johnson Space Center in Houston, Texas, in a forthcoming paper in Metabolomics.

The aim is not to weed out astronauts with deficiencies, but to ensure those who fly are in the best possible condition before they go to space, says Schmidt.

For example, certain gene mutations are known to reduce the stability of DNA, and this effect is amplified by a lack of folate. A person with the mutation could take folate supplements to protect against an increased risk of genetic damage from radiation exposure.

Reduced folate levels have also been linked to vision problems experienced by roughly a quarter of astronauts returning from the ISS. It is not yet clear whether the eye problems have a genetic component, but that is the kind of thing more focused research could reveal, says Schmidt.

Even a simple treatment like preflight bloodletting could prove useful when combined with genetic analysis, the pair say. People with a genetic mutation to build up iron in their bodies are at greater risk of radiation damage in space. An older male astronaut with the mutation will have built up high concentrations of iron over his lifetime (women are less at risk because they lose iron during menstruation). Bloodletting, along with an iron-restricted diet, could be an effective way to reduce this risk.

Genetic profiles can also help inform the types of drugs astronauts take into space, says Graham Scott of Baylor College of Medicine in Houston. He is looking at personalised medicine for Inspiration Mars, a private venture which plans to send humans on a fly-by of the Red Planet in 2018.

Roughly half of astronauts have experienced back pain during missions, which is treated in space with exercise and painkillers. But people with variants of the liver gene CYP2D6 can metabolise drugs such as the painkiller codeine too quickly, potentially leading to an overdose – and there is no hospital en route to Mars. Instead, if an astronaut is known to have this mutation they can be given a lower dose or an alternative treatment.

Jasper Rine of the University of California, Berkeley, says Schmidt and Goodwin’s proposal makes sense in principle, but we don’t yet know enough about gene variations to predict which astronauts will have gene-based health problems. And in the immediate future, he thinks deep-space pioneers will have bigger things to worry about. “Those with the courage to ride into space on a rocket built by the low bidder on a government contract face a wide range of risks,” says Rine.

This article appeared in print under the headline “Gene testing to help astronauts stay fit”

http://www.newscientist.com/article/mg21829234.800-genetic-medicine-hints-at-bloodletting-for-astronauts.html#.UcuxUIbn_bg

 

Vegetable compound could become ingredient to treating leukemia

Contact: Graciela Gutierrez 713-798-4710 Baylor College of Medicine

HOUSTON – (Dec. 12, 2012) – It looks like your mother was on to something when she said, “Eat your vegetables!”

A concentrated form of a compound called sulforaphane found in broccoli and other cruciferous vegetables has been shown to reduce the number of acute lymphoblastic leukemia cells in the lab setting, said researchers at Baylor College of Medicine. The findings appear in the current edition of PLOS ONE.

“Acute lymphoblastic leukemia is a type of cancer of the white blood cells common in children,” said Dr. Daniel Lacorazza, assistant professor of pathology & immunology. “There is about an 80 percent cure rate, but some children don’t respond to treatment. For those cases, we are in need of alternative treatments.”

Lacorazza and his colleagues focused on purified sulforaphane, a natural compound found in broccoli believed to have both preventive and therapeutic properties in solid tumors. Studies have shown that people who eat a diet rich in cruciferous vegetables have a lower risk of some cancers.

“There have not been definitive studies showing how this compound interacts with blood cancers,” Lacorazza said.

To study how this compound would act on acute lymphoblastic leukemia, researchers, led by Dr. Koramit Suppipat, lead author of the study who performed this work while a clinical fellow in the Texas Children’s Cancer and Hematology Centers, incubated human-derived leukemic cell lines and primary lymphoblasts from pediatric patients with the compound. The cancer cells died while the healthy cells obtained from healthy donors were unaffected. Studies tested in pre-clinical mouse models showed similar results.

Lacorazza said the compound works by entering the cells and reacting with certain proteins. More studies will be needed, but researchers believe this compound could one day be used as a treatment option in combination with current therapies. They also are working to determine which proteins are affected by sulforaphane and how. This could identify a new treatment target that might be affected by other types of cancer cells as well.

“Sulforaphane is a natural product. However, what we used in this study is a concentrated purified form,” said Lacorazza. “So while eating cruciferous vegetables is good for you, it will not have the same effect as what we saw in the lab.”

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Others who contributed to the study include Chun Shik Park and Ye Shen, both with the department of pathology & immunology at BCM; and Xiao Zhu, with the Summer Medical and Research Training Program (SMART) at BCM. Lacorazza is also with the department of pediatrics, BCM. Suppipat is currently a clinical instructor in the department of medicine at King Chulalongkorn Memorial Hospital in Bangkok, Thailand.

Funding for this study came from The Gabrielle Angel Foundation for Cancer Research and the Alkek Award for Pilot Projects on Experimental Therapeutic at BCM

Study: Exposure to herbicide may increase risk of rare disorder: atrazine / choanal atresia

Contact: Dana Benson
benson@bcm.edu
713-798-4710
Baylor College of Medicine

HOUSTON – (Sept. 28, 2012) – A common herbicide used in the United States may be linked to an increased risk of a congenital abnormality of the nasal cavity known as choanal atresia, say researchers at Baylor College of Medicine and other Texas institutions.

The study by Dr. Philip Lupo, assistant professor of pediatrics – hematology/oncology at BCM and Texas Children’s Cancer Center, is scheduled for publication in The Journal of Pediatrics.

Choanal atresia is a disorder where the back of the nasal passage is blocked by tissue formed during fetal development. It is a rare condition but can be serious because it affects a baby’s ability to breath. It is typically treated through surgery.

Very few risk factors for choanal atresia have been identified, however chemicals that disrupt the maternal endocrine system may be associated with risk, according to Lupo. The study focused on atrazine, which is the most commonly used herbicide in the U.S. – especially in corn crops – and is believed to be an endocrine disrupter.

“Endocrine disrupters aren’t fully understood, but it is believed they interfere with or mimic certain hormones, thereby blocking their proper function and potentially leading to adverse outcomes,” Lupo said.

The study found that mothers who lived in Texas counties with the highest levels of estimated atrazine application were 80 percent more likely to have children with choanal atresia or stenosis compared to women who lived in the counties with the lowest levels. Choanal stenosis is a less severe form of the condition.

Data for the study was collected from the Texas Birth Defects Registry.

“Our results warrant more detailed exploration before any public health or policy-related recommendations are made,” Lupo said, “but this study is a good first step in trying to understand the origin of this birth defect, including a possible role of atrazine.”

 

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The study was funded in part by the Centers for Disease Control and Prevention-funded Texas Center for Birth Defects Research and Prevention through a cooperative agreement with Texas Department of State Health Services as well as the Title V Office of Texas DSHS. Others involved in the research included A. J. Agopian, Yi Cai, Peter H. Langlois, and Mark A. Canfield.

The epigenetics of increasing weight through the generations ” resulting in amplification of obesity across generations “

Re-Post from 2008

Contact: Dipali Pathak
pathak@bcm.edu
713-798-4710
Baylor College of Medicine

Overweight mothers give birth to offspring who become even heavier, resulting in amplification of obesity across generations, said Baylor College of Medicine researchers in Houston who found that chemical changes in the ways genes are expressed – a phenomenon called epigenetics — could affect successive generations of mice.

“There is an obesity epidemic in the United States and it’s increasingly recognized as a worldwide phenomenon,” said Dr. Robert A. Waterland, assistant professor of pediatrics – nutrition at BCM and lead author of the study that appears in the International Journal of Obesity. “Why is everyone getting heavier and heavier? One hypothesis is that maternal obesity before and during pregnancy affects the establishment of body weight regulatory mechanisms in her baby. Maternal obesity could promote obesity in the next generation.”

Waterland and his colleagues studied the effect of maternal obesity in three generations of genetically identical mice, all with the same genetic tendency to overeat. One group of mice received a standard diet; the other a diet supplemented with the nutrients folic acid, vitamin B12, betaine and choline. The special ‘methyl supplemented’ diet enhances DNA methylation, a chemical reaction that silences genes.

“We wanted to know if, even among genetically identical mice, maternal obesity would promote obesity in her offspring, and if the methyl supplemented diet would affect this process,” said Waterland. “Indeed, those on the regular diet got fatter and fatter with each generation. Those in the supplemented group, however, did not.”

“We think DNA methylation may play an important role in the development of the hypothalamus (the region of the brain that regulates appetite),” said Waterland.

“Twenty years ago, it was proposed that just as genetic mutations can cause cancer, so too might aberrant epigenetic marks – so called ‘epimutations.’ That idea is now largely accepted and the field of cancer epigenetics is very active. I would make the same statement for obesity. We are on the cusp of understanding that,” he said.

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Waterland is also a researcher at the USDA/ARS Children’s Nutrition Research Center at BCM and Texas Children’s Hospital. Others who contributed to this research include Kajal Tahiliani, Marie-Therese Rached and Sherin Mirza of Baylor College of Medicine and the USDA/ARS Children’s Nutrition Research Center in Houston and Michael Travisano of the University of Minnesota in St. Paul.

Funding for this work came from the National Institutes of Health, the March of Dimes Birth Defects Foundation and the U.S. Department of Agriculture.

When the embargo lifts, this report is available at the website of the http://www.nature.com/ijo/index.html.

For more information on basic science research at Baylor College of Medicine, please go to http://www.bcm.edu/fromthelab/.

Mutation causes defective Natural Killer cells

 

Natural Killer (NK) cells defend the body against infectious diseases and cancer by recognizing and killing stressed or infected cells and patients with NK deficiencies are susceptible to severe viral infections. In this issue of the Journal of Clinical Investigation, researchers at Baylor College of Medicine report on a patient with an NK cell deficiency caused by a mutation in CD16, which codes for a protein on the surface of NK cells that recognizes antibodies. To determine the exact role of CD16 in NK cell cytotoxicity, Jordan Orange and colleagues studied the effect of mutant CD16 in a human NK cell line. The mutant CD16 was unable to interact with another NK cell protein, CD2, which is required for cytotoxic activity in NK cells. Patients carrying this mutation were highly susceptible to viral infection. This study identifies a potential cellular mechanism that underlies human congenital immunodeficiency.

TITLE:

Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity

AUTHOR CONTACT:

Jordan Orange

Baylor College of Medicine, Houston, TX, USA

Phone: 832-824-1319; E-mail: orange@bcm.edu

View this article at: http://www.jci.org/articles/view/64837?key=c3d74ae1bcfb3e9124da

Study shows link between morbid obesity, low IQ in toddlers

Contact: April Frawley Birdwell afrawley@vpha.health.ufl.edu 352-273-5817 University of Florida

GAINESVILLE, Fla. – University of Florida researchers have discovered a link between morbid obesity in toddlers and lower IQ scores, cognitive delays and brain lesions similar to those seen in Alzheimer’s disease patients, a new study shows.

Although the cause of these cognitive impairments is still unknown, UF researchers suspect the metabolic disturbances obesity causes could be taking a toll on young brains, which are still developing and not fully protected, they write in an article published in the Journal of Pediatrics this month.

“It’s well-known that obesity is associated with a number of other medical problems, such as diabetes, hypertension and elevated cholesterol,” said Daniel J. Driscoll, M.D., Ph.D., a UF professor of pediatrics and molecular genetics and microbiology in the College of Medicine and the lead author of the study. “Now, we’re postulating that early-onset morbid obesity and these metabolic, biochemical problems can also lead to cognitive impairment.”

Researchers compared 18 children and adults with early-onset morbid obesity, which means they weighed at least 150 percent of their ideal body weight before they were 4, with 19 children and adults with Prader-Willi syndrome, and with 24 of their normal-weight siblings. Researchers chose lean siblings as a control group “because they share a socioeconomic group and genetic background,” Driscoll said.

The links between cognitive impairments and Prader-Willi syndrome, a genetic disorder that causes people to eat nonstop and become morbidly obese at a very young age if not supervised, are well-established. But researchers were surprised to find that children and adults who had become obese as toddlers for no known genetic reason fared almost as poorly on IQ and achievement tests as Prader-Willi patients. Prader-Willi patients had an average IQ of 63 and patients with early-onset morbid obesity had an average of 78. The control group of siblings had an average IQ of 106, which falls within the range of what is considered normal intelligence.

“It was surprising to find that they had an average IQ score of 78, whereas their control siblings were 106,” Driscoll said. “We feel this may be another complication of obesity that may not be reversible, so it’s very important to watch what children eat even from a very young age. It’s not just setting them up for problems later on, it could affect their learning potential now.”

While performing head MRI scans of subjects, researchers also discovered white-matter lesions on the brains of many of the Prader-Willi and early-onset morbidly obese patients. White-matter lesions are typically found on the brains of adults who have developed Alzheimer’s disease or in children with untreated phenylketonuria, the researchers wrote.

These lesions could be affecting food-seeking centers of the brain, causing the children to feel hungrier. But they are most likely a result of metabolic changes that damage the young, developing brain, Driscoll said.

More studies are needed to understand what is causing these cognitive impairments, said Merlin Butler, M.D., Ph.D., a professor of pediatrics at the University of Missouri and chief of genetics and molecular medicine at Children’s Mercy Hospital and Clinics.

“This could be a really significant observation,” Butler said. “It’s an interesting concept. It’s a whole new area of investigation.”

The findings are preliminary and additional studies are planned, Driscoll said. Jennifer Miller, M.D., a UF assistant professor of pediatric endocrinology and the first author of the study, and other researchers from UF, All Children’s Hospital in St. Petersburg, Fla., and Baylor College of Medicine also took part in the research.

Although there was no known genetic cause for early-onset morbid obesity in the subjects studied, Driscoll said there are likely genetic and hormonal factors at play that researchers have yet to discover, particularly since these children are becoming obese at a time when their parents still control what they eat. The researchers studied several sets of fraternal twins where one twin was lean and the other morbidly obese, yet their parents reported that each ate the same amount of food. In one case, the obese child actually ate less, Driscoll said.

Driscoll is also careful to point out that adults or children who become obese later in childhood are not at-risk for these cognitive impairments because their brains are sufficiently developed to fend off damage from obesity.

“We’re all mindful that this is an obese society,” he said. “We all need to be more careful with respect to what we eat, but in particular, that’s very important for children under 4.”

* Reposted for Filing