Navigation Links
JCI online early table of contents: Jan. 10 2008

EDITOR'S PICK: A new way to boost red blood cell numbers

A common treatment for anemia a deficiency in red blood cells (rbcs) caused by their insufficient production, excessive destruction, or excessive loss is administration of recombinant erythropoietin (Epo), a hormone that stimulates the production of rbc precursors by the bone marrow. Unfortunately, many patients with anemia do not respond to treatment with Epo. However, a new study in mice, by Anne Angelillo-Scherrer and her colleagues at the University Hospital Center and University of Lausanne, Switzerland, has indicated that the protein Gas6 might augment or replace Epo in the treatment of patients who are hyporesponsive or resistant to Epo, respectively.

It was shown that following treatment with Epo, mouse rbc precursors released Gas6, which increased cell signaling in response to Epo treatment. In addition, mice deficient in Gas6 had decreased sensitivity to Epo and a reduced ability to recover from anemia. Administration of Gas6, either alone or in combination with Epo, was successful at treating both chronic and acute anemia in mice. The authors therefore concluded that Gas6 has a role in rbc formation and might have valuable therapeutic potential for the treatment of individuals with anemia who fail to respond to treatment with Epo.

TITLE: Role of Gas6 in erythropoiesis and anemia in mice

Anne Angelillo-Scherrer
University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Phone: 41-21-314-42-22; Fax: 41-21-314-41-80; E-mail:

View the PDF of this article at:

EDITOR'S PICK: A PIN(1) prick for lung scarring: inhibiting PIN1 reduces rodent lung scarring

Chronic asthma often results tment alone, was shown to increase expression of the AE2 alternative isoforms AE2b1 and AE2b2 and this was associated with enhanced AE2 activity in the liver. Further analysis revealed that the combination treatment led to upregulation of AE2b1 and AE2b2 expression by promoting HNF1, glucocorticoid receptor, and p300 binding to the AE2 alternate promoter, from which AE2b1 and AE2b2 are expressed.

TITLE: Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

Juan F. Medina
University of Navarra School of Medicine, Pamplona, Spain.
Phone: 34-948-194700, Ext. 4001; Fax: 34-948-194717; E-mail:

View the PDF of this article at:

HEMATOLOGY: PIP5KI-gamma ensures the cytoskeleton makes a firm attachment to the cell membrane

Many features of a cell, including its ability to move, rely on the normal functioning of the cytoskeleton that is attached to the membrane of the cell. The molecule PIP2 has an important role in regulating the function of the cytoskeleton. There are 3 forms of the protein PIP5KI, which synthesizes PIP2, and many cell types express more than one form of PIP5KI, leading to the suggestion that different forms of PIP5KI have different functions. Support for this hypothesis has now been provided by Charles Abrams and colleagues at the University of Pennsylvania, Philadelphia, who have shown that PIP5KI-gamma has a unique role in anchoring the cell membrane to the cytoskeleton of mouse megakaryocytes. Indeed, in the study, mouse megakaryocytes lacking PIP5KI-gamma were shown to exhibit defects in cytoskeleton attachment to the cell membrane and this defect could be reversed by PIP5KI-gamma but not PIP5K-beta.

TITLE: Loss of PIP5KI-gamma, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes

Charles S. Abrams
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 898-1058; Fax: (215) 573-7400; E-mail:

View the PDF of this article at:

in scarring of the lung airways (airway fibrosis) and this can cause airway obstruction. The soluble factor TGF-beta-1, produced by inflammatory cells known as eosinophils, has been shown to drive the processes that result in airway fibrosis, notably fibroblast proliferation and extracellular matrix deposition. Now, James Malter and colleagues at the University of Wisconsin School of Medicine and Public Health, Madison, have generated new data in rodents that has led them to suggest that targeting the protein PIN1 might provide a new approach to limiting airway fibrosis driven by the production of TGF-beta-1 by activated eosinophils in individuals with chronic asthma. These data include the following two observations: first, that pharmacologic blockade of PIN1 in a rat model of chronic asthma reduced TGF-beta-1 expression by activated eosinophils and airway fibrosis; and second, that mice lacking PIN1 showed reduced airway fibrosis when chronically exposed to an allergen.

TITLE: Pin1 regulates TGF-beta-1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis

James S. Malter
University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Phone: (608) 262-8888; Fax: (608) 265-0367; E-mail:

View the PDF of this article at:

DEVELOPMENT: The protein myocardin helps plug the ductus arteriosus

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects. It occurs when the ductus arteriosus (DA), the muscular artery that allows the blood coming out of the right side of the heart to by-pass the fluid filled lungs and directly enter the main blood vessel network in a fetus, fails to close after birth. Recent studies have indicated that in fullterm infants PDA frequently has a genetic basis, and Michael Parmacek and colleagues at the University of Pennsylvania School of Medicine, Philadelphia, have now identified the gene that makes myocardin and myocardin-regulated genes as candidate genes that might have a role in PDA.

In this study, mice in which the gene that makes myocardin was selectively inactivated in smooth muscle cells (SMCs) died of PDA before day 3 of life. The SMCs in the DA of these mice lacked expression of myocardin-regulated genes, which make proteins that manifest the contractile phenotype of SMCs. As elimination of myocardin in SMCs isolated from the main blood vessel of mice markedly reduced the expression of proteins responsible for the SMC contractile phenotype, the authors suggested that myocardin has a central role in maintaining the SMC contractile phenotype and that this probably explains, in part, the development of PDA in the mice lacking myocardin in SMCs.

TITLE: Myocardin regulates expression of contractile genes in smooth muscle cells and is required for closure of the ductus arteriosus in mice

Michael S. Parmacek
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 662-3140; Fax: (215) 349-8017; E-mail:

View the PDF of this article at:

HEPATOLOGY: Keeping PPAR-alpha on the go leads to hepatitis C virusinduced liver cancer

Individuals who are chronically infected with hepatitis C virus (HCV) are at increased risk of developing a type of liver cancer known as hepatocellular carcinoma (HCC). However, the mechanisms underlying this increased risk have not been determined. But now, Naoki Tanaka and colleagues at Shinshu University Graduate School of Medicine, Japan, have established that persistent activation of the protein PPAR-alpha is required for the development of HCC in mice engineered to express the HCV core protein (HCVcpTg mice).

HCVcpTg mice develop HCC that is preceded by a condition known as either fatty liver or hepatic steatosis, which is the accumulation of fat in liver cells. In the study, HCVcpTg mice expressing two functional copies of the Ppara gene developed severe hepatic steatosis followed by HCC. However, neither HCVcpTg mice expressing one functional copy of the Ppara gene nor HCVcpTg mice lacking both functional copies of the Ppara gene developed hepatic steatosis and HCC. Consistent with the idea that sustained activation of PPAR-alpha is required for hepatic steatosis and HCC, treatment of HCVcpTg mice expressing one functional copy of the Ppara gene with a PPAR-alpha agonist induced hepatic steatosis and HCC. These data have important clinical implications and led the authors to suggest that they might provide new avenues for the development of therapeutic and nutritional approaches to the treatment of individuals chronically infected with HCV.

TITLE: PPAR-alpha activation is essential for HCV core proteininduced hepatic steatosis and hepatocellular carcinoma in mice

Naoki Tanaka
Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan.
Phone: Phone: 81-263-37-2850; Fax: 81-263-37-3094; E-mail:

View the PDF of this article at:

PULMONARY: Understanding how carbon dioxide can impair lung function

Increased levels of carbon dioxide (CO2) in the blood are detected in individuals with several lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. In individuals with COPD, raised levels of CO2 in arterial blood are associated with poor outcome. New data generated in rats, by Jacob Sznajder and colleagues at Northwestern University, Feinberg School of Medicine, Chicago, have provided new insight into the mechanisms by which elevated levels of CO2 in the blood impair the function of the cells lining the lungs (alveolar epithelial cells [AECs]) increased levels of CO2 in the blood induced an increase in Ca2+ concentration and CaMKK-beta activity inside AECs, leading to rapid activation of the protein AMPK. This, in turn, caused activation of PKC-theta and thereby decreased the abundance of the protein Na,K-ATPase at the surface of AECs, impairing the ability of these cells to remove fluid from the lungs and resulting in difficulty breathing.

Jacob I. Sznajder
Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
Phone: (312) 908-7737; Fax: (312) 908-4650; E-mail:

Marla Paul
Northwestern University, Chicago, Illinois, USA.
Phone: (312) 503-8928; E-mail:

View the PDF of this article at:

IMMUNOLOGY: Pathogens have a say in the identity of the immune cells recruited to the site of infection

New data, generated by Deborah Fowell and Shoshana Katzman from the University of Rochester, has indicated that in a mouse model of infection of the connective tissues underlying the skin (the dermis) the pathogen at the infection site can modulate the type of pathogen-aggressive immune cell known as an effector T cell that accumulates.

In the study, it was observed that at the site of dermal infection with the parasite Leishmania major, soluble molecules (known as chemokines) that attracted Th2 effector cells were detectable, whereas chemokines that attracted Th1 effector cells were not detectable. Consistent with this, only cytokines produced by Th2 cells were found that the site of L. major infection. Further analysis indicated that L. major induced the production of the chemokine CCL7, which attracts Th2 effector cells. The authors therefore concluded that pathogens can modify the chemokine profile at the site of dermal infection and thereby modulate the type of immune effector T cell that is recruited.

TITLE: Pathogen-imposed skewing of mouse chemokine and cytokine expression at the infected tissue site

Deborah J. Fowell
University of Rochester, Rochester, New York, USA.
Phone: (585) 273-3680; Fax: (585) 273-2452; E-mail:

View the PDF of this article at:

GASTROENTEROLOGY: TLRs given the NOD: the protein NOD2 negatively regulates TLR signaling

A substantial subset of individuals with the inflammatory bowel disease Crohn disease (CD) have mutations in their CARD15 gene, which is the gene that allows individuals to make the protein NOD2. The mechanisms underlying the link between CARD15 mutations and CD have not been clearly determined. One possibility, however, is that the genetic mutations lead to the generation of mutant forms of NOD2 that are unable to negatively regulate signaling by a receptor for bacterial products known as TLR2; the dysregulated TLR2 signaling is then proposed to activate an excessive inflammatory response in the gut. New data generated in mice has led Warren Strober and colleagues at the National Institutes of Health, Bethesda, to extend this hypothesis such that they have proposed that NOD2 negatively regulates signaling by multiple receptors for bacterial products

In the study, activation of NOD2 by its ligand MDP was shown to protect mice from experimental colitis, a model of CD, by downregulating signaling through many different TLRs, not just TLR2. Further analysis showed that the effects of NOD2 required the downstream signaling molecule IRF4. The authors therefore suggested that MDP activation of NOD2 controls the innate immune response to commensal bacteria in the gut by negatively regulating signaling through multiple TLRs and that the absence of such regulation in individuals with CARD15 mutations leads to increased susceptibility to CD.

TITLE: Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis

Warren Strober
National Institutes of Health, Bethesda, Maryland, USA.
Phone: (301) 496-6810; Fax: (301) 402-2240; E-mail:

View the PDF of this article at:

METABOLIC DISEASE: How antioxidant therapy may play a role in the treatment of type 2 diabetes

The incidence of type 2 diabetes in Western society is on the rise, due largely to an increasing prevalence of obesity. Dysfunction of skeletal muscle mitochondria, the powerhouses of a cell, is associated with type 2 diabetes; however, whether this association is causal or consequential has not been understood. A new study by Jennifer Rieusset and her colleagues at INSERM U870, France, has shed light on this question and has provided evidence that alterations in mitochondrial function are the result, and not the cause, of insulin resistance (which usually precedes full-blown clinical type 2 diabetes) in mice.

Mice fed a high-fat, high-sucrose diet (HFHSD) developed insulin resistance and type 2 diabetes. The authors found that mitochondrial defects were present in diabetic, but not pre-diabetic glucose intolerant, mice. The mitochondrial disruptions were subsequently shown to be the result of the generation of reactive oxygen species (ROS), highly reactive molecules implicated in a number of cellular disruptions. Indeed, ROS production coincided with mitochondrial dysfunction, and antioxidant treatment blocked the mitochondrial alterations in muscle cells. The authors therefore concluded that treatment of diabetics with medications that either block ROS production or counteract their deleterious effects might improve the success of conventional therapies.

TITLE: Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice

Jennifer Rieusset
INSERM U870, Facult de Mdecine Lyon Sud, Oullins, France.
Phone: 33-4-26-23-59-20; Fax: 33-4-26-23-59-16; E-mail:

View the PDF of this article at:

NEPHROLOGY: Claudin 16 and claudin 19 synergize to select what escapes through the kidney

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a genetic disorder that can lead to kidney failure. It is characterized by calcium and magnesium loss by the kidneys, due to mutations in the genes CLN16 and CLN19, which encode the claudin family proteins claudin 16 and claudin 19, respectively. Claudins are important components of cellular tight junctions, areas where two cells meet and form a barrier that is almost impermeable to fluid. Loss of function in tight junctions is believed to be responsible for FHHNC, although the mechanisms underlying the specific roles of claudins 16 and 19 in the process have not been understood. A new study by Daniel Goodenough and colleagues at Harvard Medical School, Boston, has revealed that these claudins interact synergistically, and that this interaction regulated the permeability of tight junctions to chloride molecules. FHHNC-causing mutant forms of either CLDN16 or CLDN19 disrupted this interaction and abolished the synergistic effect, providing important insights into the mechanisms underlying FHHNC.

TITLE: Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex

Daniel A Goodenough
Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 432-1652; Fax: (617) 432-2955; E-mail:

View the PDF of this article at:

HEPATOLOGY: Understanding how two drugs can be better than one for the treatment of a liver disease

Primary biliary cirrhosis (PBC) is a liver disease characterized by diminished expression of the liver protein AE2 and destruction of the bile ducts. The latter leads to a buildup of the waste product bile in the liver (a process known as cholestasis), which causes liver scarring and organ failure. The traditional treatment for PBC, administration of the bile acid ursodeoxycholic acid (UDCA), is ineffective for a subset of patients. However, these individuals often benefit from a combination treatment of glucocorticoid and UDCA, although the mechanisms underlying how either treatment alleviates PBC are poorly understood. In a new study, Juan Medina and his colleagues at the University of Navarra School of Medicine, Spain, have provided evidence for how UDCA and glucocorticoids work together to enhance AE2 activity in the liver.

Treatment of cultured human liver cells with a combination of UDCA and the glucocorticoid dexamethasone, but not with either trea

Contact: Karen Honey
Journal of Clinical Investigation

Related medicine news :

1. HIV denialists spread misinformation online -- consequences could be deadly; and more
2. Consequences of online HIV denial; and more
3. Online Epidemic Gives Clues to Bird Flu Spread
4. MedHelp to Add Top Stanford Surgeons and Specialized Forums to Online Health Community
5. Online Celebrity Shoe Charity Auction for Womens Heart Health Opens Bidding
6. Syndicom to Launch Online Community for DePuy Spine
7. Elder Caregiving Site Wins WebAward for Outstanding Online Community
8. Peer-Reviewed, Online Database Showcases Local, County and State Pandemic Planning
9. CIGNA Behavioral Health Offers Members Online Provider Profiles
10. Dynamic Energy Systems Goes Online and On-Demand
11. North Shore-LIJ Health System Begins Online Posting of Hospital Infection Rates, Other Performance Information
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... The Visiting Nurse Association (VNA) of Somerset ... of specialty vendors and unique items from across the nation, this holiday-themed event will ... services offered by the VNA. The boutique will be open Saturday, November 4 ...
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, a leader ... been awarded a contract by the Center for Medicare and Medicaid Services (CMS). ... the enterprise use of Agile methodologies in a consistent and high value manner ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and fastest ... to open a flagship location in Covington, LA at 401 N. U.S. Highway 190, ... next to Office Depot in the Holiday Square shopping center. Its location allows it ...
(Date:10/12/2017)... Rockville, Maryland (PRWEB) , ... October 12, 2017 ... ... a magnetic drug delivery system that we intend to develop to enable prevention ... regimens can lead to severe hearing loss, especially in pediatric patients. For cisplatin, ...
(Date:10/12/2017)... ... 12, 2017 , ... Women-owned and Grand Rapids-based workplace wellness ... in Wellness® by Best and Brightest. OnSite Wellness will be honored at the ... 7:30 a.m. to 2 p.m. at the Henry Autograph Collection Hotel, located at ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... Texas , Oct. 11, 2017  True ... services, has amplified its effort during National Breast ... about hereditary cancer risks. ... of Clinical Oncology calculated that more than 10 ... have inherited mutations in BRCA1 or BRCA2 and have ...
(Date:10/10/2017)... 10, 2017  NDS received FDA 510(k) clearance in May 2017 ... display stand specifically designed for endoscopy environments. An innovative secondary monitor ... clinical solution to support the improvement of patient outcomes, procedural efficiency, ... ... ...
(Date:10/7/2017)... IRVING, Texas , Oct. 6, 2017   ... industry with more than $100 billion in purchasing power, ... industry news and information. The Newsroom is ... chain and industry trends, infographics, expert bios, news releases, ... Besides having access to a wealth of resources at ...
Breaking Medicine Technology: