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December 16, 1998 RESEARCH BRIEFS Role of Muscle in Type II Diabetes QuestionedMost hypotheses concerning type II diabetes—the late onset form of the disease afflicting about 6 percent of Americans—have assumed that in response to insulin secretion, muscle tissue takes up the majority of glucose in the blood. However, using genetically manipulated mice, a new study published in the November Molecular Cell challenges this assumption. Wanting to examine the role of muscle in type II diabetes, C. Ronald Kahn, the Mary K. Iacocca professor of medicine at HMS andJoslin Diabetes Center, and his colleagues at Joslin, HMS, and the National Institutes of Health, used Cre-loxP mediated recombination to knock out the insulin receptor (IR) in skeletal muscle and heart, leaving the IR intact in the rest of the body. Not unexpectedly, the researchers found that muscles of these mutant mice no longer responded to insulin and did not take up glucose. Although researchers expected this lack of muscle uptake to increase blood glucose levels, surprisingly, the animals' blood glucose levels remained normal. Kahn says the normal levels may indicate that other tissues play a larger role in glucose metabolism than previously thought. Alternatively, signals from other tissues may be needed to tell the muscle to take up glucose. In addition to normal blood glucose levels, other results regarding lipid metabolism surprised the researchers. The mice showed high serum triglyceride and free fatty acid levels, a problem that many researchers had thought was due to insulin resistance in liver and fat cells, rather than defects in muscle. "This shows that the concept of what goes on in diabetes needs to be rethought," Kahn says. HIV Patients Continue
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| Doctors at HMS found that 76.1 percent of HIV patients from a study in Boston use alternative therapy in addition to conventional HIV medications. |
Patients sought the additional therapies to help boost their immunity,
gain weight, fight infections,
and relieve diarrhea, nausea, and fatigue. Each spent an average
of $1,159 annually on alternative care. They often used the alternative
therapies even if they had received other medications to treat the
same symptoms, and 81 percent of patients surveyed said these therapies
helped. Several patients eventually discontinued treatment because
of cost, suggesting that some used the therapies despite financial
hardship. Fairfield and her colleagues say more studies are needed
to confirm or dispel the effectiveness of the treatments.
In Aortic Surgery, Less Is Sometimes More
Surgeons once adhered to the dogma that bigger is better, or "the larger the incision, the better the operation." But in the November Archives of Surgery, Richard Cambria, associate professor of surgery at HMS and MGH, and Lars Svensson, of the Lahey Hitchcock Clinic in Burlington, Mass., write that surgeons now have options to perform less invasive techniques in open cardio-aortic and aortic operations.
For instance, Cambria says a team of surgeons at MGH has done over 150 minimally invasive operations in the past four years to repair abdominal aortic aneurysms, or aortas that have a swelling and therefore the potential to burst. So far, the less invasive technique has decreased surgical mortality and shortened hospital stays.
In the past, the condition required making an incision in the abdomen and replacing the aneurysm with an artificial blood vessel made of Dacron. "Even in the best of hands, that is major surgery" resulting in a 2 to 5 percent operative mortality, Cambria says. In contrast, surgeons at MGH can accomplish the same goal by passing tubing, or a graft, up through femoral arteries in the groin to the site of the aneurysm. A stent, or cylindrical metal wire similar to the mesh supporting tomato plants, connects the intact aorta above and below the aneurysm. Closing off the swelling from circulating blood, the stented graft eliminates the risk of rupture.
The surgery has a record of less than 1 percent mortality at MGH. Cambria warns, however, that because the procedure is so new, long-term follow-up has not been assessed. Still, he says, "There's no question that the procedure will become more widespread.
--Briefs above by Judy Silber
Genes for Development Show Consistency Across Time and Species
Now that the entire genome of the worm C. elegans has been sequenced, researchers are comparing those genes with genes of other organisms. In the Dec. 11 Science, they report some surprising findings. "The biggest surprise is that about half of the genes involved in development match genes in other organisms," says Gary Ruvkun, professor of genetics at HMS and Massachusetts General Hospital.
He and Oliver Hobert, research fellow in genetics, surveyed worm development genes, which constitute about one eighth of the entire worm genome. Most of the genes code for proteins that fit into growth factor signaling pathways or transcriptional regulatory cascades. In addition to the overall genetic similarities among organisms, they found that worm genes for some regulatory cascades perfectly matched those found in distantly related species.
Only 10 percent of development genes showed no detectable sequence similarity to other genes in the databases analyzed, compared to 50 percent novelty for the entire genome, Ruvkun and Hobert report. The lack of novelty in the set of worm developmental control genes and their high degree of similarity among species suggests that there has been evolutionary pressure to conserve the set of genes that regulates development in metazoa, multicellular animals.
Yet the findings also reveal that evolutionary divergence has occurred in developmental genes so C. elegans lacks some genes that are found in vertebrates and even other invertebrates.
"Thus the genome sequence reveals universals in develop-mental
control that are the legacy of the metazoan complexity before the
Cambrian explosion, as well as genes that have been more recently
invented or lost in particular
phylogenetic lineages," write the authors.
In Aortic Surgery, Less Is Sometimes More
Surgeons once adhered to the dogma that bigger is better, or "the larger the incision, the better the operation." But in the November Archives of Surgery, Richard Cambria, associate professor of surgery at HMS and MGH, and Lars Svensson, of the Lahey Hitchcock Clinic in Burlington, Mass., write that surgeons [DEMO]ve options to perform less invasive techniques in open cardio-aortic and aortic operations.
For instance, Cambria says a team of surgeons at MGH has done over 150 minimally invasive operations in the past four years to repair abdominal aortic aneurysms, or aortas that have a swelling and therefore the potential to burst. So far, the less invasive technique has decreased surgical mortality and shortened hospital stays.
In the past, the condition required making an incision in the abdomen and replacing the aneurysm with an artificial blood vessel made of Dacron. "Even in the best of hands, that is major surgery" resulting in a 2 to 5 percent operative mortality, Cambria says. In contrast, surgeons at MGH can accomplish the same goal by passing tubing, or a graft, up through femoral arteries in the groin to the site of the aneurysm. A stent, or cylindrical metal wire similar to the mesh supporting tomato plants, connects the intact aorta above and below the aneurysm. Closing off the swelling from circulating blood, the stented graft eliminates the risk of rupture.
The surgery has a record of less than 1 percent mortality at MGH. Cambria warns, however, that because the procedure is so new, long-term follow-up has not been assessed. Still, he says, "There's no question that the procedure will become more widespread.
—Briefs above by Judy Silber
Genes for Development Show Consistency Across Time and Species
Now that the entire genome of the worm C. elegans has been sequenced, researchers are comparing those genes with genes of other organisms. In the Dec. 11 Science, they report some surprising findings. "The biggest surprise is that about half of the genes involved in development match genes in other organisms," says Gary Ruvkun, professor of genetics at HMS and Massachusetts General Hospital.
He and Oliver Hobert, research fellow in genetics, surveyed worm development genes, which constitute about one eighth of the entire worm genome. Most of the genes code for proteins that fit into growth factor signaling pathways or transcriptional regulatory cascades. In addition to the overall genetic similarities among organisms, they found that worm genes for some regulatory cascades perfectly matched those found in distantly related species.
Only 10 percent of development genes showed no detectable sequence similarity to other genes in the databases analyzed, compared to 50 percent novelty for the entire genome, Ruvkun and Hobert report. The lack of novelty in the set of worm developmental control genes and their high degree of similarity among species suggests that there has been evolutionary pressure to conserve the set of genes that regulates development in metazoa, multicellular animals.
Yet the findings also reveal that evolutionary divergence has occurred in developmental genes so C. elegans lacks some genes that are found in vertebrates and even other invertebrates.
"Thus the genome sequence reveals universals in develop-mental
control that are the legacy of the metazoan complexity before the
Cambrian explosion, as well as genes that have been more recently
invented or lost in particular
phylogenetic lineages," write the authors.