Thursday, September 25, 2008

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In a crucial step toward realizing medical treatments based on embryonic-like stem cells, researchers have found a safer way to revert adult mouse cells to an embryonic state. The new technique, reported online September 25 in Science, avoids using viruses that alter the cells’ DNA, a major goal among stem-cell researchers since these DNA mutations can lead to cancer। http://louis-j-sheehan.net

Such reprogrammed cells could sidestep the controversy surrounding therapies based on embryonic stem cells, many scientists believe, because the embryonic-like cells can be made from a person’s skin or blood cells without creating or destroying an embryo. Coaxing these reprogrammed cells into becoming, say, fresh heart or pancreas cells for transplantation back into the patient could offer new, personalized ways to treat ailments such as heart disease and diabetes.

Until now, reprogramming adult cells in lab dishes required infecting the cells with viruses that carry the four reprogramming genes. Although the scientists cripple the viruses so that they can’t replicate, the viruses can still insert these four genes directly into the cells’ DNA at random locations. These willy-nilly changes to the cells’ DNA could disrupt the cells’ own genes, occasionally in ways that cause the cells to grow out of control and form a tumor. In addition to this risk, any process that alters a cell’s DNA complicates government approval for medical use.

The new technique overcomes these problems by using a different kind of virus that does not alter the cells’ genetic code, researchers report.

“None of the cells that we produced had any evidence of any virus left” after reprogramming, says Matthias Stadtfeld, coauthor of the study and a molecular biologist at Massachusetts General Hospital in Boston.

The safer virus carries the same four genes into adult cells — Oct4, Sox2, Klf4 and c-Myc — but instead of inserting those genes into the cells’ genetic code, the virus lets the genes free-float within the cells. Proteins encoded by these genes do the actual reprogramming, and the cells’ protein-making machinery can read the four genes even if they’re adrift in the cells. Eventually, the cells degrade the genes, and the viruses get lost as the cells repeatedly divide.

“It’s very exciting because it’s the first demonstration of [reprogrammed] cells without viral integration,” comments Robb MacLellan, a stem cell expert at the David Geffen School of Medicine at the University of California, Los Angeles. “It’s a proof of concept.”

More research is needed before the technique could be used for medical therapies. Stadtfeld and his colleagues reprogrammed skin and liver cells from adult mice. Because they used mouse cells, the scientists could perform the ultimate test for whether the resulting reprogrammed cells possessed the quintessential trait of embryonic stem cells, the ability to become any type of cell in the body. That test is to insert the reprogrammed cells into mouse embryos and allow those embryos to grow into adult mice. Just as true embryonic stem cells would, these reprogrammed cells gave rise to all types of cells in every organ of the adult mice’s bodies.

The question remains whether the reprogramming feat will work for human cells, but many scientists expect that it will. “It’s likely that it will be able to be shown in human cells,” MacLellan says.

Reprogramming worked for only one of every 100,000 to 1 million cells, a conversion rate about 10 to 100 times worse than that for DNA-altering viruses। Conversion worked for the liver cells, but skin cells (which would be much easier for doctors to obtain from patients) needed a small cheat for the reprogramming to work: The researchers inserted one of the four genes into the cells’ DNA. http://louis-j-sheehan.net

Stadtfeld says the team doesn’t know yet why the skin cells needed extra help, or why the conversion rates were so low। These two problems must be solved before reprogrammed cells could be used for medical treatments. http://louis-j-sheehan.net

Even then, scientists will still need to improve other techniques for coaxing these cells into heart, pancreas or other cell types needed for therapies. These lab techniques are still under development and will probably take longer to perfect than the reprogramming methods will, Stadtfeld says. “I think it will take at least five or 10 years, because you have to be really careful before you transplant anything.”

Friday, September 19, 2008

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If I absolutely had to get into a school-yard fight back in junior high, I don’t know why it had to be with Ira Blitz। I should have known I wouldn’t stand a chance. http://Louissheehan.BraveDiary.com

First of all, unlike me, Ira had mastered a number of exotic skills that gave him a distinct advantage in almost any scrap. Punching, for instance. More important, Ira actually seemed to enjoy fighting. Whenever I faced the possibility of an after-school brawl, my first response was to submit the matter to binding arbitration and hope for a resolution satisfactory to all parties. If that didn’t work, I’d ask my family if we could move.

Most important, however, was the matter of Ira Blitz’s name. If you’re looking for a partner for an adolescent brawl, it’s always a good idea to avoid someone whose surname sounds like it applies less to a person than to a Panzer division. I’m not saying that Ira’s family handle was the only reason I lost this battle, but I would have been a lot more comfortable if he had been named, say, Ira Negotiated Settlement. As it was, however, Ira won our scuffle handily, deftly landing head-to-toe blows and finishing me off with a pop in the eye that caused me to see stars, several comets, and a large portion of the Crab nebula.

While my one childhood fight taught me a couple of valuable lessons (notably, to be incredibly nice to Ira Blitz until after graduation), it also raised a question: Exactly what kind of trauma had I put my body through? Why had I seen stars, for example, between the time fist hit eye and I hit asphalt? What was responsible for the singular sensation I experienced when I was hit in the stomach and had the wind knocked out of me? Why did my nose turn out to be such a sensitive—and utterly breakable—organ? What on earth is a cauliflower ear, and had I run the risk of developing such unwelcome vegetation?

Happily for us nonpugilists, we don’t have to go to Ira Blitz for the answers. Easier and less painful explanations are available from the world of science. Even if you’re a lifetime pacifist, it can be interesting to learn just what your body has been missing all these years—and why it should keep on missing it.

Among the most remarkable sources of information on the physiology of injury is Jeremy Wolfe, a professor of ophthalmology at Harvard Medical School and a senior lecturer at MIT. Nearly every year in his classes, he offers a one-hour visual-perception seminar straightforwardly entitled “Ten Things You Can Learn by Poking Yourself in the Eye.” Although such a lecture struck me as less than a natural crowd-pleaser, the students at MIT apparently think otherwise. At one of Wolfe’s presentations, he played to a crowd of 50 enthusiastic undergrads, all of whom gladly went along with his eye-poking exercises. I was not on hand to watch Wolfe’s pupils attack their pupils, but I was able to reach him on the phone, and he agreed to talk me through some of the experiments. To be perfectly candid, I was not looking forward to the experience. Spending half an hour on the phone learning how to poke yourself in the eye seemed about as appealing as hunkering down for an hour on an airline’s outsourced customer-service line, and probably more painful. Nevertheless Wolfe assured me I would be perfectly safe as long as I did the exercises very gently and attempted them only under his guidance.

Wolfe first asked me to partially close one eye and gently press a finger against the eyelid near the tear duct. What I should see, he said—apart from a good personal-injury lawyer—was a flash of light in my field of vision on the side opposite the spot where I pressed. This, Wolfe explained, illustrates the phenomenon of labeled lines.

All nerves send signals to the brain when they are stimulated, Wolfe said, but the part of the body those nerves service determines how the brain will perceive the stimulation. If you activate a tactile nerve in the skin, the brain will register the stimulation as touch. If you activate certain nerves in the ear, the brain will perceive that as sound. When you press the eyeball, you’re mechanically stimulating retinal nerves, and the brain registers that as light.

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To me it seemed that the brain whose owner has just poked a finger in his eye should register something else, like a grievance with its union. Nevertheless I tried a tentative poke and indeed got the promised flash of light. The reason the flash was on the opposite side of the eye has to do with the way the brain processes an image. In ordinary vision, the lens focuses incoming light in such a way that it flips an image upside down and backward. When the eye inverts an image, the brain knows that it must automatically compensate by flipping the picture back the right way.

Though the delicate touch I gave my eye yielded just one small flash, Wolfe said that when the eye is struck by something less forgiving—like a swinging door or Ira Blitz—many parts of the retina may be stimulated simultaneously, giving rise to a whole constellation of light. Sometimes the retina is so mechanically stimulated that a large portion of the visual cortex of the brain begins firing at once. This is what happens when you rub your eyes and your field of vision is filled with that undulating checkerboard.

Neurophysiologists have discovered that particular cells in the brain are responsible for registering particular shapes (horizontal or vertical lines, for instance), Wolfe said. If you rub your eyes too much, you send random, meaningless noise to your brain, and all the cells for all the shapes begin screaming at once. At Wolfe’s instruction, I commenced a very vigorous rub and got the promised checkerboard. To me this was enough retinal recreation for one day, so before Wolfe got me too involved in his other experiments—including the wiggle-the-eyeball and misalign-the-eyes tests—I thought it best to try my own exercise, known as hang-up-the-phone.

With my eyes thus under my belt, I went off to see what I could learn about other fistfight injuries. Perhaps the most dramatic of these is the punch in the stomach—or, specifically, the punch in the solar plexus. As most people know from experience, the solar plexus is that area just below the rib cage which, if hit just right, can cause you to feel as if you’ve had the wind—as well as the rain, the snow, and at least one kidney—knocked out of you. The term solar plexus comes from the Latin solaris, for “Try not to get punched here,” and plexus, for “We’re not kidding.”

My introduction to the perils of the solar plexus came when I was 9 or 10 years old and got into a fight with my older brother after he gave me a model of the Mayflower ship and then tried to take it back. Sibling common law usually grants an older brother unilateral rights to seize possession of any toy at any time for any reason. On this occasion, however, I had made it a point to touch a black object and recite, “Touch black, no back,” an incantation that the Supreme Court had ruled binding in 33 states, the District of Columbia, and Guam. My brother was evidently not up on recent court rulings, and a scuffle ensued, resulting in my sustaining a severe blow to the solar plexus. The loss of breath was sudden and total. I’ve never been entirely certain how long it took me to get my wind back, but family members tell me I was more or less myself again by my sophomore year in high school.

Excruciating as the experience was, however, it turns out that it was a largely harmless one. Getting the wind knocked out of you is analogous to jamming your funny bone, says physician Chris Freyberg, director of the emergency department at the Southern Arizona VA Health Care System in Tucson. It’s a temporary paralysis of the diaphragm caused by trauma to the phrenic nerve. This nerve descends from the upper part of the torso and forks off to make contact with the diaphragm on both sides. When the solar plexus is struck, the diaphragm sustains a concussion, which it transmits to the phrenic nerve. The nerve shuts down temporarily and can’t make the diaphragm contract. To the surprise and considerable disappointment of the victim, he finds he can’t draw his next breath. The worse the blow, the longer the shutdown.

Almost as sensitive to injury as the solar plexus are the exquisitely delicate nose and ears. As you know if you’ve ever flipped through a professional boxing magazine, strange, almost Picasso-esque things can happen to the face that gets in the way of too many punches. The common cauliflower ear, which gives so many professional fighters that always-fashionable fresh crudité look, is caused by a blow or other trauma to the outer ear, leading to the accumulation of blood between the cartilage and its fibrous covering. This coagulated blood then blocks the flow of new blood to the cartilage, resulting in tissue death and the buildup of scar tissue. Treatment involves draining the ear, removing the scar tissue, repositioning the fibrous covering, and giving serious thought to seeing a good career counselor.

Even if you’ve never stepped into a boxing ring, you know that almost any bump or blow can do serious damage to the proboscis, causing immediate bleeding and agonizing pain and eventually turning even a modest button nose into something closer to a buttonhook. “That’s probably why, instinctually, people have been taught to punch other people in the nose,” Freyberg says. “It’s humiliating in the sense that it’s probably the most painful spot on the face, can make you look physically deformed, and is probably the spot on the face that will become most bloodied. It’s more defaming than anything else.”

Though such fragility would make the nose seem a shabbily designed organ, it is in fact an elegant one; its very elegance is what makes it so delicate. The entire face is highly vascularized and innervated, Freyberg says. For all the different ways it has to move and all the jobs it has to do, it needs lots of blood and nerve endings. The nose, in particular, has to detect subtle smells, and for that it needs to be rich in nerves. However, that also makes it sensitive to pain. Similarly, mucous membranes are active tissues and thus have to be rich in blood, but that means an injury is going to cause them to bleed copiously.

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Making matters worse for the beak, the bone that makes up the top portion of the bridge is lighter and thinner than the surrounding skull. When you look at an X-ray, you can see this extremely fragile projection of bone sticking out. It’s very delicate and very pretty, but it also can be damaged very easily.

If there is one bad rap that’s been hung on the nose, it’s the general belief that a single fracture can instantly turn the average GQ man into the average Elephant Man, complete with the ability to drink through his nostrils. In fact, Freyberg explains, the nose bone heals as undetectably as any other bone, provided that it is set properly. It’s just that when your emergency room is a corner of the canvas at Madison Square Garden and your cosmetic surgeon is Don King, you can’t expect the best results.

Nastier than a blow to the nose, a punch in the ear, a pop in the eye, and a fist in the stomach, combined, is that body trauma most feared among men: a knee in the, uh, external endocrine system. Give the average man a choice between getting hit in the groin or having a girder fall on his head, and watch him go looking for a construction site.

The most graphic case of this kind of injury I ever saw came during a game of summer camp softball when Sidney Katz (not his real name) was playing second base (not his real position) and was hit by a line drive in the antler (not his real appendage). Apart from having to spend that night sleeping with a strategically placed ice pack—something that caused the rest of us to make fun of him from the summer of 1968 until the middle of last week—Sidney displayed a level of unbridled agony I had seen before only in the closing reel of Fiend Without a Face when the monster is trying to suck Kim Parker’s brain and spinal column out through the back of her neck. Sidney’s anguish finally subsided after several days, and he spent the rest of the summer engaging in no athletic activity more strenuous than turning on the kiln in arts and crafts.

The nose has to detect subtle smells, and?for that it needs to be rich in nerves. That ?also makes it sensitive to pain, however.

How such a minor injury could cause such exquisite pain was long a mystery to me, and no doubt to Sidney. Some answers, however, were available from Irwin Leventhal, a urologist at Mount Sinai Hospital in New York City. What makes a hit in the groin so painful, Leventhal says, is the same thing that makes other sensations in that area so pleasurable: an enormously high number of sensory nerve endings. When an area of the body is innervated so generously, any sensation—whether good or bad—is going to be felt very acutely. What’s more, glands don’t have a whole lot of give, so if one is hit, it’s going to absorb the whole force of the blow. Finally, while all other glands are located deep within the body, male reproductive glands are outside, since sperm cannot be produced normally at temperatures above 96 degrees. Whatever additional protection they’d get by being tucked away is thus lost.

Making matters still worse is that pain in this particular area tends not to stay there but to radiate throughout the groin and up into the abdomen (and occasionally out to any other man standing within a 100-yard radius). This, Leventhal explains, is due to the phenomenon known as referred pain, which causes a sensation originating at one spot to travel along the nerve root to other parts of the body.

In this case, the nerves that cause the most discomfort are the perineal, which innervates the groin, and the pudendal, which runs from the spinal column to the groin and scrotal area. For anyone unlucky enough to have his pudendal and perineal nerves traumatically stimulated, Leventhal recommends ice for the first 24 hours to minimize swelling, heat for the next 24 to stimulate blood flow and hasten healing, and perhaps giving up softball for a pastime like quoits, or perhaps some online Quidditch.

For pain-phobes like myself, avoiding this kind of injury has always seemed like the better part of physical valor. After Sidney Katz, I made it a point never to play baseball again without the protection of a good athletic cup—as well as a saucer, salad plate, and place setting for six. After Ira Blitz, I made it a point never to engage in another school-yard quarrel without first getting in touch with Bono. And after the Mayflower, I made it a point to turn all models directly over to my brother—including any I might one day be lucky enough to date. I admit this strategy won’t ever earn me a heavyweight belt, but it won’t earn me any other kind of belt either, and that has always seemed like a pretty good trade-off.

Tuesday, September 2, 2008

Louis J. Sheehan, Esquire

Researchers have often given Egyptians living around 4,000 years ago credit for having first domesticated wildcats and then bred the tame felines. However, discoveries on the Mediterranean island of Cyprus indicate that people domesticated felines there by about 9,500 years ago, long before the cat-worshipping Egyptians' time.

Working among the remains of Shillourokambos, a village on Cyprus that was inhabited between 10,300 and 9,000 years ago, a team led by archaeologist Jean-Denis Vigne of the CNRS-National Museum of Natural History in Paris unearthed a cat's skeleton from a small grave. The animal's remains lay near a larger grave that contained a human skeleton along with offerings such as polished stones and flint tools. An adjoining pit contained 24 seashells.

Lack of any remaining collagen in the roughly 8-month-old cat's bones obstructed efforts to estimate its age based on radiocarbon measurements. The creature's location in previously dated sediment at the site indicates that it lived between 9,500 and 9,200 years ago, Vigne says. Its size resembles that of a modern African wildcat.

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HERE, KITTY. The discovery of a 9,500-year-old feline skeleton (above) suggests that some of the earliest domesticated cats resembled today's African wildcats, such as the one pictured below.K. Debue

In early agricultural villages such as Shillourokambos, wildcats were probably domesticated to kill mice attracted by grain stocks, Vigne theorizes.

Scientists have suspected for some time that people brought either wild or domesticated cats to Cyprus more than 9,000 years ago. A feline jawbone was discovered nearly 20 years ago at a site on the island dating to the ancient time.

It now appears that the first colonizers of Cyprus tamed cats, the French investigators conclude in the April 9 Science. "The association of [a human grave] with both seashells and a cat grave strengthens the idea of a special burial, indicating that a strong relationship existed between cats and people," Vigne says.

No sign of butchering appears on the cat's bones, he adds, further suggesting that the animal wasn't eaten or mutilated but was a pet or had some other special relationship with people. It's not clear how the cat died, Vigne notes.

The new feline find underscores the emerging view that colonizers of Cyprus propagated a sophisticated culture, remarks archaeologist Alan H. Simmons of the University of Nevada, Las Vegas.

A recently completed excavation of a 12,000-year-old site on Cyprus, directed by Simmons, shows that residents there hunted pygmy hippos and several other native animal species nearly to extinction within about 2 millennia. Island settlers then brought over a variety of animals from the mainland, Simmons says.

At Shillourokambos and a nearby site from the same period, animal remains include sheep, goats, pigs, wild deer, and even a few cattle.http://louisjjjsheehan.blogspot.com