regional medical center: News From The Journal Of Clinical Investigation: July 2, 2012

News From The Journal Of Clinical Investigation: July 2, 2012

Main Category: Heart Disease
Also Included In: Lymphoma / Leukemia / Myeloma;Â Â Neurology / Neuroscience
Article Date: 03 Jul 2012 - 2:00 PDT

email to a friend Â

printer friendly Â

opinions Â <!--

rate article

Patient / Public: not yet rated

Healthcare Prof: not yet rated

CARDIOVASCULAR DISEASE
Gene variant reduces cholesterol by two mechanisms

High levels of low-density lipoprotein (LDL) cholesterol increases the risk for coronary heart disease. A variant in the human gene encoding the protein sortilin is associated with reduced plasma LDL levels and a decreased risk of heart attack. This variant results in markedly higher sortilin protein expression in liver. Dr. Daniel Rader and colleagues at the University of Pennsylvania in Philadelphia have uncovered a two-pronged mechanism for the change in LDL observed. Using a mouse model system, the Rader team found that increased liver sortilin is responsible for reducing secretion of APOB, a protein that transports LDL to tissue, and also triggers LDL breakdown. Both of these effects were dependent on a cellular process known as lysosomal targeting. Their data provide functional evidence that genetically-increased hepatic sortilin in humans reduces LDL by increasing LDL degradation, thus removing LDL from circulation, as well as decreasing APOB.

TITLE: Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism

NEUROBIOLOGY
Why pain and depression frequently occur together

Pain and depression frequently occur simultaneously in patients, but the reason for this association is unclear. Dr. Jianren Mao and colleagues at Harvard Medical School in Boston, MA report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, underlies the link between pain and depression. They found that chronic pain in rats induced depressive behavior that was associated with increased IDO1 expression in the brain's hippocampus region. In addion, they noted higher IDO activity in blood plasma from patients with both pain and depressions. In rats, loss of the Ido1 gene or inhibition of IDO1 activity in the brain by pharmaceuticals increased both pain-related and depressive behavior. The Mao team's results reveal that IDO1 is central to the concurrence of pain and depression, suggesting a new strategy to treat both conditions is to modulate brain IDO1 activity.

TITLE: Brain Indoleamine 2, 3-Dioxygenase Contributes to Comorbidity of Pain and Depression

NEUROBIOLOGY
Cyclocreatine treatment for X-linked mental retardation syndrome

Creatine deficiency causes an X-linked mental retardation syndrome characterized by speech and language disorders with severe cognitive impairment. This syndrome, which is caused by defects in the creatine transporter (CRT) encoded by SLC6A8, is currently untreatable because the transporter is a barrier to creatine entry into brain cells. Dr. Joseph Clark and colleagues at the University of Cincinnati in Cincinnati, OH developed a mouse model with a brain specific deletion of Slc6a8. They showed that the mice recapitulate the human syndrome, and moreover the Clark team was able to successfully treat mice with cyclocreatine, a creatine analogue. Their work establishes cyclocreatine as a promising treatment for CRT deficiency, one of the most common causes of X-linked mental retardation.

TITLE: Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency

ONCOLOGY
Location, location, location: gene target of translocation linked to multiple myeloma

Multiple myeloma is a plasma cell cancer that causes clusters of abnormal plasma cells to build up in the bone marrow, preventing the production of normal blood cells and causing anemia, renal failure, and bone destruction. Twenty percent of multiple myeloma patients have a chromosomal translocation, an abnormal rearrangement of genes that some times results in the joining together of two or more genes that are normally separated. In these multiple myeloma patients, the Wolf-Hirschorn syndrome candidate 1 gene (WHSC1) is translocated, but the cancer-causing mechanism is still unclear. After examining this translocation for clues, Dr. Michael Tomasson and colleagues at Washington University School of Medicine discovered that another gene, one encoding the small nucleolar RNA (snoRNA) ACA11, is located within the WHSC1 gene and is also involved in multiple myeloma. Through genetic and cellular assays, they found that the translocation caused ACA11 to be abnormally overproduced in the cells of multiple myeloma patients, causing increased cancer cell growth, chemotherapy resistance, and suppressed oxidative stress. In the accompanying commentary, Drs. Riccardo Taulli and Pier Paolo Pandolfi note that ACA11 is overproduced in other cancers and modulation of RNA networks with snoRNAs such as ACA11 could be an exciting new strategy for cancer therapies.

TITLE: Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress

ACCOMPANYING COMMENTARY TITLE: "Snorkeling" for missing players in cancer

Additional

References

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

APA

Please note: If no author information is provided, the source is cited instead.

Add Your Opinion On This Article

'News From The Journal Of Clinical Investigation: July 2, 2012'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

regional medical center

Selasa, 03 Juli 2012

News From The Journal Of Clinical Investigation: July 2, 2012

Add Your Opinion On This Article

Tidak ada komentar:

Posting Komentar