Louis J. Sheehan, Esquire In 1985, Monday Night Football fans looked on as Washington Redskins quarterback Joe Theismann was sacked. The collision was so forceful that it snapped Theismann’s leg, breaking like, as one fan put it, a “stale chopstick.” Most audience members likely empathized with Theismann and sensed his pain, including people afflicted with a rare disorder that prevents them from feeling pain themselves, a new study suggests. http://LOUIS-J-SHEEHAN.US
Instead of using past experiences of feeling pain to commiserate, such people likely rely on the ability to imagine the pain of others, suggests the brain-imaging study, published online January 28 in Neuron.
“This fascinating and well-conducted study” gives new insights into the relationship between pain and empathy, comments Marco Loggia of the Athinoula A. Martinos Center for Biomedical Imaging in Charlestown, Mass. http://LOUIS-J-SHEEHAN.US
The study suggests that multiple brain regions, including regions involved in emotions, can be recruited to feel empathy for others’ pain. In future studies, Loggia says, it would be interesting to examine other cases when people are exposed to someone else’s feelings without ever having felt such feelings firsthand. “How can humans empathize with a dog that hurt its tail? How can a man understand menstrual pain?” Loggia asks. The answers, he proposes, may lie in the same regions of the brain that allow pain-insensitive people to empathize with others’ pain.
Study coauthor Nicolas Danziger wanted to know whether a person could empathize with an unfamiliar emotional state. Understanding other people’s emotional states, such as pain, is thought to be based on a system in the brain called the mirror system. When someone sees a quarterback break a leg, specific groups of brain cells in the spectator’s brain activate. These nerve cells are the same ones that would activate if the spectator broke his own leg.
Called mirror neurons, these cells are thought to prompt a kind of knee-jerk reaction in the brain in response to seeing others’ pain, a phenomenon researchers call automatic resonance. Put simply, these mirror brain cells don’t distinguish between monkey see and monkey do.
The activity of whole groups of interconnected neurons in one person can mirror that of whole groups of interconnected brain cells in another person, a process called “mirror matching.” Now, scientists know that entire mirror neuron systems can respond to others’ emotions, such as disgust. Seeing a disgusted person elicits mirror matching in the brain of the watcher, where the same group of nerve cells activates as if the watcher were disgusted himself.
Some researchers had proposed that mirror neurons would not exist or not respond correctly when a person witnessed an unfamiliar sensation. To test this idea, Danziger, a neurologist in the Pain Center at the Pitié-Salpêtrière Hospital in Paris, recruited a unique group of subjects.
Some people are born with rare genetic defects rendering them completely insensitive to physical pain. Danziger’s team used fMRI techniques to study the brain responses of such people as they gazed at physically painful situations.
Subjects were shown images of a finger caught in a pair of shears and of a man’s face screwed up in a painful expression. The brains of control subjects who feel pain normally showed activation patterns in two pain-sensing brain regions, the anterior mid-cingulate cortex and the anterior insula.
As it turns out, these pain-sensing regions were similarly activated in the subjects who could not feel pain. “Our first intuition is that we were expecting a huge difference between the two groups. We saw the contrary,” says Danziger.
The results suggest that these brain responses are not mirror matching systems for pain. However, the similarity of brain activation in these regions doesn’t rule out possible mirror matching in other brain regions, says Danziger.
Brain regions like the amygdala, important for emotional processing, might harbor a mirror matching system for pain, he says. The researchers couldn’t assess amygdala activation, due to fMRI interference from nearby bone.
It was in the midline brain structures that the team noticed differences between pain-insensitive subjects and control subjects. When they were able to empathize with others’ pain (as judged by a questionnaire), people insensitive to pain relied heavily on activity in these regions (parts of the prefrontal cortex and the ventral posterior cingulate cortex) involved in formulating emotional perspectives. Only pain-insensitive subjects with high empathy scores had high activity in these brain regions, whereas in control subjects, activity in these regions had little to do with the amount of empathy.
Pain-insensitive people “can only rely on the emotional regions,” says Danziger. “It’s far from automatic.” These people may be relating the physical pain they witness to emotional pain they have felt themselves.
Most likely, the midline brain structures, places where Danziger says “emotional work” is done, and the mirror matching systems both play a role in empathy in regular people.
“I think both mirror neuron areas and midline areas are important for intersubjectivity,” comments Marco Iacoboni, a neuroscientist studying mirror neuron systems at the University of California, Los Angeles.Louis J. Sheehan, Esquire
Saturday, April 11, 2009
test 0.00.02 Louis J. Sheehan, Esquire
A compound called sarcosine may distinguish slow-growing prostate cancers from those likely to spread and become lethal, a new study shows. And in an unexpected finding, benign prostate cells take on cancerous characteristics in lab dishes when exposed to sarcosine, suggesting that the compound is less of a bystander and more of a perpetrator in the malignancy, researchers report in the Feb. 12 Nature.
“It’s not only a biomarker for aggressive prostate cancer, but it might be involved in the biology of the cancer,” says study coauthor Arul Chinnaiyan, a Howard Hughes Medical Institute investigator and pathologist at the University of Michigan in Ann Arbor.
Tests for elevated sarcosine also outperformed the most widely used clinical test for detecting prostate cancer. http://LOUIS2J2SHEEHAN.US Conveniently, sarcosine can be identified in urine, a less invasive test than the blood analysis needed for the standard prostate-specific antigen, or PSA, test routinely given to men to check for signs of cancer.
To arrive at these findings, Chinnaiyan and his team analyzed 1,126 metabolites in samples of prostate tissue, blood and urine obtained from men with various stages of prostate cancer and from a group of men without the cancer. Sarcosine was undetectable in healthy tissue but turned up in large amounts in prostate cancer confined to the gland and in even greater levels in metastatic cancer.
A separate test showed that sarcosine levels in urine were much higher in men with prostate cancer than in men without it.
And when compared with a PSA test, sarcosine levels were “at least as good, and perhaps better, than PSA” in identifying the presence and aggressiveness of cancer, says study coauthor John Wei, a urologist at the University of Michigan.
Five other compounds also appeared in large concentrations in metastatic prostate cancer. By measuring concentrations of these compounds, doctors might someday be better able to diagnose prostate cancer and distinguish dangerous malignancies from cancer that’s unlikely to leave the prostate, the findings suggest.
Prostate cancer diagnosis is an imprecise science, says William Isaacs, a molecular biologist at the Johns Hopkins University School of Medicine in Baltimore. The typical exam combines a digital probe of the prostate to check for swelling or lumps and a blood test to reveal PSA levels. This one-two punch turns up many prostate cancers that would have gone undetected decades ago, but quite often men have PSA scores that fall into a gray area, he says. Biopsy is needed to clarify a diagnosis.
But even when a biopsy reveals cancer, it sometimes remains unclear whether the cancer is aggressive and at risk of spreading, or indolent and likely to stay put. For example, a biopsy might sample a part of the prostate with little cancer and underestimate the danger, says Cory Abate-Shen, a cancer biologist at Columbia University College of Physicians and Surgeons. So biopsy doesn’t always reveal who needs aggressive treatment, she says.
“There’s no question we need better markers,” Isaacs says. Whether sarcosine or some of the other metabolites identified in the new study will fit the bill remains to be seen. “I think people will try to repeat this work and try to get it into the clinic as fast as possible,” he says.
Meanwhile, the study authors were surprised to find that sarcosine, a metabolite of the amino acid glycine, might also play a role in abetting cancer itself. When they added sarcosine to benign prostate cells in lab-dish experiments, the cells showed cancerous behavior. Chinnaiyan expects animal experiments to clarify any direct role sarcosine might play in prostate cancer.http://LOUIS2J2SHEEHAN.US
Ideally, such research would reveal points at which scientists might intercede in the cancer process. http://LOUIS2J2SHEEHAN.US
The study is also noteworthy because it goes beyond the study of genes (genomics) and proteins (proteomics) to delve into metabolomics — the study of metabolites, Abate-Shen says. Metabolites are the end products of cell processes, and much might be learned from these compounds, she says. “But it’s not like they have a genetic code,” she says, “so it’s technically challenging.” Louis J. Sheehan, Esquire
In the 1950s and 1960s, metabolites were a hot research topic as scientists tried to figure out the roles of enzymes in cell biology, Isaacs says. Times change and metabolites were largely set aside in favor of genes, DNA, RNA and proteins — at least in the search for biomarkers, he says. With the new study, he says, “hopefully we’ll get some sort of re-emergence of people interested in metabolites. I think it’s a really important study from that point of view.” Louis J. Sheehan, Esquire
“It’s not only a biomarker for aggressive prostate cancer, but it might be involved in the biology of the cancer,” says study coauthor Arul Chinnaiyan, a Howard Hughes Medical Institute investigator and pathologist at the University of Michigan in Ann Arbor.
Tests for elevated sarcosine also outperformed the most widely used clinical test for detecting prostate cancer. http://LOUIS2J2SHEEHAN.US Conveniently, sarcosine can be identified in urine, a less invasive test than the blood analysis needed for the standard prostate-specific antigen, or PSA, test routinely given to men to check for signs of cancer.
To arrive at these findings, Chinnaiyan and his team analyzed 1,126 metabolites in samples of prostate tissue, blood and urine obtained from men with various stages of prostate cancer and from a group of men without the cancer. Sarcosine was undetectable in healthy tissue but turned up in large amounts in prostate cancer confined to the gland and in even greater levels in metastatic cancer.
A separate test showed that sarcosine levels in urine were much higher in men with prostate cancer than in men without it.
And when compared with a PSA test, sarcosine levels were “at least as good, and perhaps better, than PSA” in identifying the presence and aggressiveness of cancer, says study coauthor John Wei, a urologist at the University of Michigan.
Five other compounds also appeared in large concentrations in metastatic prostate cancer. By measuring concentrations of these compounds, doctors might someday be better able to diagnose prostate cancer and distinguish dangerous malignancies from cancer that’s unlikely to leave the prostate, the findings suggest.
Prostate cancer diagnosis is an imprecise science, says William Isaacs, a molecular biologist at the Johns Hopkins University School of Medicine in Baltimore. The typical exam combines a digital probe of the prostate to check for swelling or lumps and a blood test to reveal PSA levels. This one-two punch turns up many prostate cancers that would have gone undetected decades ago, but quite often men have PSA scores that fall into a gray area, he says. Biopsy is needed to clarify a diagnosis.
But even when a biopsy reveals cancer, it sometimes remains unclear whether the cancer is aggressive and at risk of spreading, or indolent and likely to stay put. For example, a biopsy might sample a part of the prostate with little cancer and underestimate the danger, says Cory Abate-Shen, a cancer biologist at Columbia University College of Physicians and Surgeons. So biopsy doesn’t always reveal who needs aggressive treatment, she says.
“There’s no question we need better markers,” Isaacs says. Whether sarcosine or some of the other metabolites identified in the new study will fit the bill remains to be seen. “I think people will try to repeat this work and try to get it into the clinic as fast as possible,” he says.
Meanwhile, the study authors were surprised to find that sarcosine, a metabolite of the amino acid glycine, might also play a role in abetting cancer itself. When they added sarcosine to benign prostate cells in lab-dish experiments, the cells showed cancerous behavior. Chinnaiyan expects animal experiments to clarify any direct role sarcosine might play in prostate cancer.http://LOUIS2J2SHEEHAN.US
Ideally, such research would reveal points at which scientists might intercede in the cancer process. http://LOUIS2J2SHEEHAN.US
The study is also noteworthy because it goes beyond the study of genes (genomics) and proteins (proteomics) to delve into metabolomics — the study of metabolites, Abate-Shen says. Metabolites are the end products of cell processes, and much might be learned from these compounds, she says. “But it’s not like they have a genetic code,” she says, “so it’s technically challenging.” Louis J. Sheehan, Esquire
In the 1950s and 1960s, metabolites were a hot research topic as scientists tried to figure out the roles of enzymes in cell biology, Isaacs says. Times change and metabolites were largely set aside in favor of genes, DNA, RNA and proteins — at least in the search for biomarkers, he says. With the new study, he says, “hopefully we’ll get some sort of re-emergence of people interested in metabolites. I think it’s a really important study from that point of view.” Louis J. Sheehan, Esquire
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