Monthly Archives: December 2013

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Many expectant parents live their lives somewhere between hope and prayer. The big question, and fear, often isn’t whether the child will be a boy or girl, but whether he or she will develop in a healthy way.

The agony and ecstasy of the process was exponentially more dramatic for Gerald Thomsen and his wife Julia Todorov-Thomsen during three pregnancies that produced healthy children. Scientists who met at Stony Brook, the couple knew each phase of development for the skin, muscles, heart, brain, and everything in between.

“I tried to push out of my mind all the scenarios where things could go wrong,” Thomsen said. “There are so many complicated circuits and events.”

Indeed, Thomsen has considerably more than textbook knowledge about development, albeit with other organisms. The Stony Brook professor in the Department of Biochemistry and Cell Biology has dedicated much of the last 20 years to understanding some of the signals and processes that help animals, in his case, mostly frogs, develop.

The big picture question he explores in his lab is, “How does an embryo put itself together? How do cells with different specialties — nerve cells, skin cells — emerge from a single egg cell?”

Thomsen is interested in exploring this question at the whole animal, cellular and molecular level. In his lab, he is studying a process called induction, in which cells respond to signals from neighboring cells.

When a signal, often in the form of a protein or polypeptide, binds to a cell, it often sends a signal from the cell membrane to the nucleus, where it might start or stop a genetic process.

He’s currently working on how an understudied gene, which seems to regulate cell differentiation, might affect growth. When this gene is taken away, the frog embryo doesn’t develop tissues and organs critical for its survival.

Thomsen said many scientists in the world of developmental biology look specifically at what is new about a cell as it moves from one state to another. They want to know what genes are turning on or off. To explore that, the researchers often block them or make those genes more active, to see how that influences what a cell does.

In the late 1990s, Thomsen and a student of his, Haitao Zhu, observed a protein that interacts with a set of signals that go from the cell membrane to the nucleus, where the frog’s genetic machinery resides. When Thomsen and Zhu put the gene for that protein into the frog embryo, it generated another backbone and nervous system.

“It was really dramatic,” Thomsen recalled. The gene turned out to be a key regulator in a signaling pathway, called TGF beta.

Thomsen’s work in this arena is “a major contribution to our understanding of how embryos develop,” said Amy Sater, a professor at the University of Houston in the Biology and Biochemistry Department. “It’s had applicability across all vertebrate systems.”

Sater and Thomsen have taught the Cell and Developmental Biology of Xenopus course at Cold Spring Harbor Laboratory for the last three years. Sater has appreciated Thomsen’s sense of humor and said, “The community has a lot of confidence in [his] work.”

Thomsen has a grant right now from the Stony Brook Medical School to look at a protein to see whether it might be operating in breast or other cancers. His lab, which includes eight people, is also focused on understanding the signals that lead to regeneration. In this arena, he is studying frog and sea anemone embryos.

Adult anemones can regenerate a complex body part from a stump of tissue, he said, the same way starfish can. Frogs have a limited ability to regenerate, so he could potentially test the lab’s findings with sea anemones in frogs.

A resident of Port Jefferson, Thomsen brings special guests to his children’s classes, introducing them to adult frogs, embryos and tadpoles. His children are Liam, 7, Isabella, 5, and Luca, who is almost 3.

Initially interested in oceanography, a specialty his wife pursued, Thomsen was fascinated by biochemistry and gene regulation in the context of differentiating cells. His particular field “always has something new.”

As he felt when his children were developing, Thomsen said the process is “amazing. Even though we know a lot of detail, we also appreciate that we know these details in a spotty way.”

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The risk of AAA may be significantly reduced with lifestyle changes

Aneurysms are universally feared; they can be lethal and most times are asymptomatic (without symptoms). Yet aneurysms are one of the least well-covered medical disorders in the press. There are numerous types of aneurysms, most of which are named by their location of occurrence, including abdominal, thoracic and cerebral (brain). In this article, I will discuss abdominal aortic aneurysms, better known as a “triple-A,” or AAA. Preventing any type of aneurysm should be a priority.

What is AAA? It is an increase in the diameter of the walls of the aorta in one area, in this case — the abdomen. The aorta is the “water main” for supplying blood to the rest of the body from the heart. Abnormal enlargement weakens the walls and increases the risk that it may rupture. If the aorta ruptures, it causes massive hemorrhaging, or bleeding, and creates a substantial likelihood of death.

The exact incidence of aneurysms is difficult to quantify, since some people may die due to its rupture without an autopsy being done; however, estimates suggest that they occur in 4-9% of the population [1].

The cause of AAA is not known, but it is thought that inflammation and oxidative stress play an important role in weakening smooth muscle in the aorta [2]. The consequence of this is an abnormally enlarged aorta, or AAA.

People who are at highest risk for aneurysms are those over 60 years old [3]. Other risk factors include atherosclerosis, or hardened arteries, high blood pressure, race (Caucasian), gender (male), family history, smoking and having a history of aneurysms in other arteries [4]. Some of these risk factors are modifiable, such as atherosclerosis, high blood pressure and smoking. Men are more than four times more likely to have a AAA [5]. Though males are at a higher risk, females are at a higher risk of having a AAA rupture [6]. So, gender is important for differentiating the incidence, but also the risk of severity.

Is it important to get screened for AAA? The short answer is yes it is important, especially if you have risk factors. You should talk to your physician. Although some people do experience nondescript symptoms, such as pain in the abdomen, back or flank pain [7], the majority of cases are asymptomatic. A smaller AAA is less likely to rupture and can be monitored closely with noninvasive diagnostic tools, such as ultrasound and CT scan.

Sometimes cost is a question when comes to screening, but a recent study showed unequivocally that screening ultimately reduces cost, because of the number of aneurysms that are identified and potentially prevented from rupturing [8].

What are the treatments?

There are no specific medications that prevent or treat abdominal aortic aneurysms. Medications for treating risk factors, such as high blood pressure, have no direct impact on an aneurysm’s size or progression. But the mainstay of treatment is surgery to prevent rupture. Two surgical techniques may be utilized. One approach is the endovascular repair, which is minimally invasive, and the other is the more traditional open surgery [9]. A recent comparison of these approaches in a small randomized controlled trial had similar outcomes: a mortality rate of 25%. This was considered a surprisingly good statistic.

The good news is that surgery has resulted in a 29% reduction in rupture of the AAA [10].

When using the minimally invasive EVAR technique mentioned above, the specialist who performs the surgery may make a difference. A recent study’s results showed that surgeons had better outcomes, in terms of mortality rates and length of hospital stay, compared to interventional radiologists and cardiologists [11]. This was a retrospective (looking in the past) study, which is not the strongest type of trial.

When to watch and wait and when to treat is a difficult question; surgery is not without its complications, and risk of death is higher than many other surgeries. AAA size is the most important factor. In women, AAAs over 5.0 cm may need immediate treatment, while in men, those over 5.5 cm may need immediate treatment [12]. Smaller AAAs, however, are trickier.

The growth rate is important, so patients with this type of aneurysm should have an ultrasound or CT scan every six to 12 months. If you have an aneurysm, have a discussion with your physician about this.

Lifestyle changes

One of the most powerful tools against AAA is prevention; it avoids the difficult decision of how to best avoid rupture and the complications of surgery itself. Lifestyle changes are a must. They don’t typically have dangerous side effects, but rather potential side benefits. These lifestyle changes include smoking cessation, exercise and dietary changes.

Smoking cessation

Smoking has the greatest impact, because it directly impacts the occurrence and size of AAA. It increases risk of medium-to-large size aneurysms by at least fivefold. One study found that smoking was responsible for 78% of aortic aneurysms larger than 4 cm [13]. Remember, size does matter in terms of risk of rupture. So for those who smoke, this is a wake-up call.

Impact of Fruit

A simple lifestyle modification with significant impact is increasing your fruit intake. The results of two prospective (forward-looking) study populations, Cohort of Swedish Men and the Swedish Mammography Cohort Study, showed that consumption of greater than two servings of fruit a day decreased the risk of AAA by 25% [14]. If you do have AAA, this same amount of fruit also decreased the risk of AAA rupture by 43%. This study involved over 80,000 men and women, ages 46 to 84, with a follow-up of 13 years.

The authors believe that fruit’s impact may have to do with its antioxidant properties; it may reduce the oxidative stress that can cause these types of aneurysms. Remember, the quandary has been when the benefit of surgery outweighs the risks, in terms of preventing rupture. This modest amount of fruit on a daily basis may help alleviate this quandary.

So what have we learned? Screening for AAA may be very important, especially as we age and if we have a family history. Surgery results to prevent rupture are similar, regardless of the type. However, keep in mind that surgery for AAA has a significant mortality risk. At the end of the day, lifestyle changes, including smoking cessation and increased fruit intake, are no-brainers.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.