Sunday, November 1, 2009

plus 4, An exquisite container - Genetic Engineering News

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plus 4, An exquisite container - Genetic Engineering News

An exquisite container - Genetic Engineering News

Posted: 01 Nov 2009 10:56 AM PST

Nov 1 2009, 2:00 PM EST

An exquisite container

EUREKALERT

Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis

A gold nanocage covered with a polymer is a smart drug delivery system

In campy old movies, Lucretia Borgia swans around emptying powder from her ring into wine glasses carelessly left unattended. The poison ring is usually a confection of gold filigree holding a cabochon or faceted gemstone that can be broken to empty the ring's contents. It is invariably enormous so large it is rather odd nobody seems to notice it.

Lucretia would have given her eyeteeth for the "smart capsule" devised in Younan Xia's laboratory at Washington University in St. Louis. A tiny cage of gold covered with a smart polymer, it responds to light, opening to empty its contents, and resealing when the light is turned off. Infinitely more cunning and discreet than Lucretia's ring, the nanocage is too small to be seen except indirectly: billions change the color of liquid in a test tube.

No Lucretia, Xia is a healer rather than a poisoner. The smart nanocage is designed to be filled with a medicinal substance, such as a chemotherapy drug or bactericide. Releasing carefully titrated amounts of a drug only near the tissue that is the drug's intended target, this delivery system will maximize the drug's beneficial effects while minimizing its side effects.

The method for making the capsules and tests of their performance appeared online on Nov. 1, 2009, as part of the advance online publications program of the journal Nature Materials.

The first step in making a smart capsule is to mix up a batch of silver nanocubes. Tiny single-crystal cubes of silver can be made by adding silver nitrate (AgNO3) to a solution that donates electrons to the silver ions, allowing them to precipitate as solid silver. The addition of another chemical encourages the silver atoms to deposit on some parts of a seed crystal rather than others, coaxing the seeds to form sharp-edged cubes rather than misshapen lumps.

A second step clips all eight corners off the cubes.

The clipped silver cubes then serve as "sacrificial templates," on which the gold cages take shape. When the silver nanocubes are heated in cloroauric acid (HAuCl4), the gold ions in the acid steal electrons from the silver atoms in the cubes. The silver dissolves and the gold precipitates.

A gold skin forms on the silver cubes as the cubes are hollowed out from within. The silver atoms enter solution through pores that form in the clipped corners of the cubes.

"But the really cool part," says Xia, "and the cool part of nanotechnology generally, is that the tiny gold cages have very different properties than bulk gold." In particular, they respond differently to light.

The physicist Michael Faraday was the first to realize that a suspension of gold particles glowed ruby-red because the particles were extremely small. "His original sample of a gold colloid is still in the Faraday Museum in London," says Xia, Ph.D., the James M. McKelvey Professor in the Department of Biomedical Engineering. "Isn't that amazing? It's over 150 years later and it's still there."

The color is caused by a physical effect called surface plasmon resonance. Some of the electrons in the gold particles are not anchored to individual atoms but instead form a free-floating electron gas. Light falling on these electrons can drive them to oscillate as one. This collective oscillation, the surface plasmon, picks a particular wavelength, or color, out of the incident light, and this is the color we see.

The strong response at a particular wavelength, called resonance, is what makes a violin string vibrate at a particular pitch or lets a kid pump a swing high in the sky by kicking at just the right moment.

What's more, the surface plasmon resonance is tunable in much the same sense that a violin is tunable.

"Faraday used solid particles to make his colloid," comments Xia. "You can tune the resonant wavelength by changing the particles' size, but only within narrow limits. You can't get to the wavelengths we want."

The wavelengths he wants are the ones at which human tissue is relatively transparent, so that cages in the bloodstream can be opened by laser light shone on the skin.

The color of nanocages can be tuned over a wider range than solid particles by altering the thickness of the cages' walls, says Xia. As more gold is deposited and the shells thicken, a suspension of nanocages shifts from red, to purple, to bright blue, to dark blue, to the wavelengths in the near-infrared.

Xia's team wants to hit a narrow window of tissue transparency that lies between 750 and 900 nanometers, in the near-infrared. This window is bordered on one side by wavelengths strongly absorbed by blood and on the other by those strongly absorbed by water.

Light in this sweet spot can penetrate as deep as several inches in the body.

"People used to do a demonstration at talks," Xia says, laughing. "They'd put a red diode laser in their mouths, and the audience could see it from outside, because the diode's wavelength is 780 nanometers, a wavelength at which flesh is pretty transparent."

Here things get even trickier and yet more amazing. The resonance actually has two parts. At the resonant frequency, light can be scattered off the cages, absorbed by them, or a combination of these two processes.

Just as they can tune the surface plasmon resonance, the scientists can adjust how much energy is absorbed rather than scattered by manipulating the size and porosity of the nanocages.

Xia illustrates the difference between scattering and absorption with a marvelous Roman artifact, the 4th-century Lycurgus Cup. The cup looks jade-green from the outside but turns pink when lit from the inside.

Modern analysis shows the ancient glass contains nanoparticles of a silver-gold alloy that scatters light strongly at a wavelength in the green part of the spectrum. When the cup is lit from inside, however, the green light is absorbed, and we see the remaining light, which is predominantly red, the complementary color to green.

It's actually the absorption component that the scientists exploit to open and close the nanocages. When the light is absorbed it is converted to heat, and the nanocages are covered with a special polymer that responds to heat in an interesting way.

The polymer, poly(N-isopropylacrylamide), and its derivatives has what's called a critical temperature. When it reaches this temperature it undergoes a transformation called a phase change.

If the temperature is lower than the critical temperature, the polymer chains are water-loving and stand out from the cage like brushes. The brushes seal the cage's pores and prevent its cargo from leaking out. If the temperature is above the critical temperature, on the other hand, the polymer chains shun water, shrink together and collapse. As they shrink, the pores of the cage open, and its contents flood out.

"It's a bit counter-intuitive," says Xia. "Typically when you go to higher temperature, a molecule will expand, but this one does the opposite."

Like everything else about this system, the polymer is tunable. The scientists can control its critical temperature by altering its composition. For medical applications, they tune the critical temperature to one right above body temperature (37 degrees Celsius) but well below 42 degrees Celsius (107 degree Fahrenheit), the temperature at which heat would begin to kill cells.

Next comes the fun part. Once they had made their smart capsules, the scientists tested them by loading them with a bright red dye called alazarin crimson, or rose madder. The dye made it easy to detect and measure any release with a spectrometer.

The cages were loaded by shaking them in a solution of the dye at a temperature above the critical temperature of the smart polymer. Next, they were dunked in an ice bath to trigger the polymer to close the pores and trap the dye inside the cages. The cages were then opened again by bathing them in the light of a near-infrared laser. Absorbed light warmed the gold cages above the critical temperature and provoked the polymer's phase change. The polymer collapsed, the cages' pores were exposed, and dye spilled out.

Next the team loaded capsules with doxorubicin, a common chemotherapy drug and, triggering the drug's release with a laser, killed breast cancer cells growing in wells on a plastic plate.

And finally, they loaded the capsules with an enzyme that snips open the cell walls of bacteria and used them to kill a bacterium that is a normal part of the flora of our mouths and throats.

Lucretia, eat your heart out.

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Finding a Better 'Position' to Deal With Disease - ABC News

Posted: 01 Nov 2009 11:03 AM PST

"Doctor's Orders" is a new feature in the collaboration between Medpage Today and ABC News. We'll be exploring medical issues of interest to physicians and their patients. In this first monthly segment, we look at the increasing body of research into the effects of yoga yoga in a variety of conditions as interest in this form of therapy grows.

At major cancer centers across the country, patients are putting themselves in a better 'position' to cope with their cancer.

Some of the biggest names in cancer care -- M.D. Anderson, Memorial Sloan-Kettering, and Dana Farber among them -- now offer their patients classes in yoga.

In the past, physicians may have written off the therapy as merely a trendy yuppie pasttime. But today, researchers -- mainly psychologists -- are asking questions about the benefits of yoga in a variety of conditions, including cancer, asthma, sleep disorders, depression, and attention disorders.

Generally, the studies have shown that yoga improves quality of life and relieves stress and anxiety associated with these conditions. Some researchers say the Ayurvedic therapy may have physiological mechanisms, like reducing cortisol levels, but those theories are still under evaluation.

A word of caution, though: The studies that have been done so far have yielded soft findings, with little hard data to back up the conclusions. That said, there is no denying that yoga is becoming a presence even in the ivory towers of academic medicine.

Yoga for Cancer Patients

Alyson Moadel, PhD, of Albert Einstein College of Medicine in Bronx, N.Y., has been tracking the effects of yoga on breast cancer patients at Montefiore Medical Center for the past eight years.

In 2007, Moadel reported early findings from the study in the Journal of Clinical Oncology: Patients who did yoga saw improvements in social and emotional well-being, compared with those who didn't.

When data on patients undergoing chemotherapy were excluded, yoga also significantly improved overall quality of life.

"I think it's going to be an important complementary modality," Moadel said. "I don't think it's the only one, but I think it is an important one for dealing with stress and anxiety."

Yoga classes are offered three times a week at Montefiore. Patients gather in a conference room for the seated yoga sessions, which include stretching in a mix of seated and standing poses for the first hour of the class. Then the instructor dims the lights for meditation, breathing and relaxation.

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Carousel Club stripper, Jack Ruby reunited in Deep Ellum mural - Dallas Morning News

Posted: 01 Nov 2009 10:34 AM PST

After Jack Ruby made a huge splash by killing Lee Harvey Oswald on live television, Joyce Gordon became a ripple.

Gordon, who was 20, worked as a stripper at Ruby's Carousel Club on Commerce Street in downtown Dallas. Now, at 66, she is thought to be the last living woman who danced at Ruby's club during that period in November 1963.

"I did what I did," she said last week. "No sense regretting what you've done. I had no education and I had to have a way to support my child, and that was the way I did it."

This month marks the 46th anniversary of one of the most dramatic episodes in American history. President John F. Kennedy was assassinated on Nov. 22, 1963, Oswald was arrested for his murder, and Ruby shot and killed him on Nov. 24.

Entrepreneurs and artists are still paying homage to the characters who played major and minor roles in the massive investigations of Oswald and Ruby. Gordon, a green-eyed redhead who went by the stage name Joy Dale, became one of those characters.

Gordon has appeared in a few assassination documentaries over the years but, for the most part, has kept a low profile. Like most people, she has lived in modest obscurity.

Randy Redmond, a colorful Dallas businessman, is putting a little gloss on her golden years. He is immortalizing Gordon, Ruby and two other Carousel Club strippers on a mural in back of his building at 2616 Commerce in Deep Ellum. Redmond rents the building for parties, and the mural adorns the entrance to a faux speakeasy in the alley.

Gordon, her youth restored with waterproof paint, is portrayed sitting on the hood of a police car with the Dallas skyline in the background.

"My daughters think it's kinda cool," she said.

Last of burlesque

Gordon was born in Sulphur Springs in 1943 and was raised in Oak Cliff. She dropped out of high school and got married at 15. By age 17, divorced with a baby girl, she migrated to Houston and began waitressing at a neighborhood bar. Dancers from a strip club across the street came in for drinks and encouraged her to participate in an amateur night.

"It scared the livin' hell outta me, but I did it. I had to have a shot of VO [whiskey] before I went out on stage," she recalled.

And so was born the 12-year career of stripper Joy Dale.

In the early '60s, strip joints were a far cry from the so-called gentleman's clubs of today, where the dancers usually appear topless and perform "lap dances" for tips. When you think of Joy Dale, think of a bouffant hairdo, ankle-length black gown and long black gloves a la Gypsy Rose Lee.

The music was provided by a live band. And the show often included comedians or ventriloquists or singers. All of them, including the dancers, belonged to a union of entertainment workers. The Carousel represented the threadbare last gasp of vaudeville burlesque.

Gordon made $150 a week, which was pretty good money back then. She and her fellow performers of that era – Little Lynn, Jada, Chris Colt, Bubbles Cash, Tammi True, Kathy Kay – ended their acts with bare breasts, but the law required strategic places to be covered with adhesive "pasties," often adorned with glittering sequins and tassels. Bikini-style pants usually covered their bottoms. Only a few girls were daring enough to wear G-strings, Gordon said.

"These girls today go down to nothin'," she said.

Customers did not stick dollar bills in G-strings, and the girls did not hang upside down from a pole, she said.

"There was none of that. The stage was up high or there was a ring around it where they could not reach you, and you were not allowed to accept tips from them," Gordon said.

"If someone asked you to have a drink with him, you could either do it or not."

Ruby 'was crying'

Gordon and her 3-year-old daughter, Cynthia, were riding a city bus to a doctor's appointment at Parkland Memorial Hospital on Nov. 22, 1963. Several weeks earlier, Cynthia had almost lost an eye in a freak accident. She needed a checkup.

"We got to the corner of Houston and Commerce [near Dealey Plaza] and a motorcycle policeman stopped the bus and got on and looked around," Gordon recalled. "Word of what happened had gotten out and people were screaming and crying."

By the time the bus arrived at Parkland, Gordon said, doctors had pronounced President Kennedy dead. After the eye appointment, she and Cynthia took the bus to the Carousel Club, a second-floor walkup across from the Adolphus Hotel.

It would be the last time she ever spoke to Jack Ruby.

"We got there and he was hysterical," she said. "He was crying and hollering and saying he would shoot the son of a bitch who did it. I told the FBI that, too."

When she and Cynthia got on the bus to go home, Ruby was getting his shoes shined, tears rolling down his cheeks as he stroked his pet dachshund, Sheba. The president had been dead about three hours.

Two days later, on Sunday morning, Ruby made history when police tried to move Oswald from the police station's lockup to the county jail. He parked near the police station, locked Sheba in the car and joined the chaotic crowd of reporters chronicling the transfer. Then, he stepped forward with a Colt .38 snub-nose and killed Oswald on live television.

Gordon and her boyfriend were at home in Oak Cliff when they heard the news on the radio. She went crazy, she said.

"Tommy had to slap me to keep me from going more hysterical," she said.

Gordon, who was pregnant with her second daughter, danced for another month at the Carousel Club. Ruby was in jail for killing Oswald. His trusty bartender was left to run the club. Ruby was convicted of murder and faced life in prison. He died of cancer in 1967.

Ruby was a nice guy, Gordon recalled. Sure, once in a while he might beat up a customer who needed it, but he was considerate, too. Every night after the Carousel closed, he would send a pot of coffee out to the parking lot attendant who worked the graveyard shift, Gordon said.

Ruby was going to let her work as a hostess at the club during her pregnancy and said he would buy her some flashy maternity clothes.

"I guess I saw too much of the good side of Jack," she said.

To this day, some conspiracy theorists believe the Mafia and the CIA conspired to kill Kennedy and that they used Oswald as a patsy. Some believe Ruby was in the Mafia and that his bosses ordered him to shoot Oswald to cover up their involvement in the assassination.

Gordon doesn't buy those theories. Ruby was just an eccentric who lost his head, a busybody who wanted to be at the center of things in Dallas, she said.

"He reminded me of a little old lady in a small town who wanted to know everything going on," she said. "If there was a Mafia in Dallas, I didn't know about it."

Redmond, the building owner who commissioned the mural, met Gordon years ago and became fascinated with her story and her knowledge of Ruby.

"Nobody ever recognized him, and he's a part of Dallas history," Redmond said.

Life after dancing

Gordon danced professionally for another seven or eight years after the assassination. She traveled the strip club circuit and saw the country.

"I wouldn't have gotten to do that if I hadn't been a dancer," she said.

After her career as an entertainer ended, she turned to bartending. She worked some joints on Harry Hines in Dallas and then went upscale, tending bar at the Top O' the Cliff Club on the penthouse level of the Bank Tower at Oak Cliff.

"I never talked about being a dancer and Jack and all of that when I worked there," she said.

Gordon won't reveal how many times she's been married. Right now, she lives in a mobile home outside Kaufman with "cats, two dogs and a husband." She's been married to Ted Gordon for 22 years. He's a retired Navy veteran and she works one day a week as bookkeeper at a Deep Ellum locksmith shop.

Gordon spends her time taking care of Ted, a cancer survivor. He walks with the help of a walker. She's had both knees replaced and uses a cane. But their infirmities don't stop them from playing shuffleboard and drinking Miller Lite every Friday night down at the VFW hall.

Gordon also is a seamstress. She makes cloth dolls and enters them in the arts and crafts competition at the State Fair of Texas.

"I enter every year and I win something every year," she said.

If you stop by the locksmith shop in Deep Ellum, you can buy one of her dolls.

This is the same woman who proudly, without hesitation, shows a visitor an old publicity photo of herself wearing an alluring smile and little else.

But she doesn't have as many mementos as one might expect. One of those "jealous husbands" tore up a bunch of that stuff years ago, she said.

"He's the one I don't count because I got it annulled. He was still married to somebody else when he married me," Gordon said.

"Once I was through with 'em, I was through."

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Seniors face conflicting advice on cancer tests - Deseret News

Posted: 01 Nov 2009 11:10 AM PST

CHICAGO — Arthur Cohen was a healthy, active 85-year-old when his Toronto doctor recommended a colonoscopy to check for early signs of colorectal cancer.

The colonoscopy — Cohen's first — revealed two polyps. During surgery to remove them, the elderly man's colon was perforated and a cascade of complications followed. Cohen developed sepsis, peritonitis and kidney failure and stayed in intensive care for a full month.

Of course, most colonoscopies go smoothly, for older as well as younger adults. Still, Cohen's son Carl, of Skokie, Ill., wonders about his dad's decision to have the procedure. "It never occurred to him that he could suffer a major quality-of-life setback," Cohen said.

As the baby boomers prepare to join the 65-plus set over the next decade, medical experts are weighing the benefits and costs of cancer screenings for seniors. Mammograms for women in their 80s, colonoscopies for men and women 75 and older, and PSA (prostate specific antigen) blood tests for older men are especially controversial.

The purpose of screenings is to detect cancer early, when treatments are most likely to be effective, and to save lives. That the tests do so for colon, breast and cervical cancer has been well-established for middle-age adults but is not indisputable for those who are older, as most studies have been done in people younger than 65. Research on routine PSA screening has yet to prove a definitive benefit at any age.

On the other side are the potential costs, which can include unnecessary treatments for cancers that never would have become life-threatening, the anxiety and distress associated with cancer diagnosis, the complications associated with screening procedures or therapies, and medical expenses.

Take colon cancer. Although detecting a polyp is advantageous at age 50, the benefits are less clear at 80. Typically, polyps take 10 to 15 years to become cancerous and potentially life-threatening, and often seniors will die of other ailments before it happens, said Dr. Neal Persky, a geriatrics specialist at the University of Michigan.

But the idea it may not be advisable for older adults to undergo cancer screenings is much debated.

Some experts argue there shouldn't be firm age cutoffs because seniors aren't all alike. Some 80-year-olds are robust and can easily live another dozen years, while others have very limited life expectancies, experts said.

"As long as a person is in good health and would be a good candidate for treatment, then they are a reasonable candidate for screening," said Robert Smith, director of cancer screening at the American Cancer Society.

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Your views: Letters to the editor - Florida Today

Posted: 01 Nov 2009 11:24 AM PST

(3 of 3)

In the NFL, you will not see the losing team receive a bonus. Yet corporate executives, who lose billions of dollars, receive millions of dollars in bonuses.

In the NFL, losing teams do not have salary caps tightened. All teams have salary caps, which are the same, and losing teams receive draft picks to strengthen their teams and make the more competitive.

It is time to restore competition to Wall Street and financial institutions.

A touchdown is a touchdown.
Chuck Loiko

Merritt Island

Early detection key in rare breast cancer

As many of us know, October was Breast Cancer Awareness Month. The advantages of early detection and treatment are essential in battling this disease.

We wanted to expand the awareness about a very aggressive type of breast cancer that cannot be detected by examining for a lump.

This type of breast cancer is known as inflammatory breast cancer, or IBC. Its signs are a breast rash, swelling and possibly an inverted nipple. This cancer's defeat comes more readily with early detection and treatment.

A relative discovered IBC early, and 21 months later, she is a survivor.

Our families pray that all women become aware of this rare and very aggressive breast cancer.
Pat and Judy Hughes

Satellite Beach

Deceased husband gets lots of junk mail

I'd like to know where junk mail senders get their addresses?

My husband has been dead 15 years. However, in the past two years, he has:

-- Qualified for a gold Visa card.

-- Been asked to come in to a local doctor's office for a hearing test.

-- Qualifed for a free cremation.

And it goes on and on. He never lived at my address, yet he gets more mail than I do. Go figure!
Josephine R. Busshaus

Melbourne

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