Navigation Links
JCI table of contents: June 20, 2008

EDITOR'S PICK: Smoking out the mediators of airway damage caused by pollutants

New insight into how pollution and cigarette smoke damage airways has been provided by Pierangelo Geppetti and colleagues, at the University of Florence, Italy, who studied the effects of such chemicals on guinea pig airways. As discussed, in an accompanying commentary, by Sidney Simon and Wolfgang Liedtke, at Duke University Medical Center, it is hoped that this information will help in the development of therapeutics to combat the effects of pollutants and perhaps help individuals with smoke-related diseases such as chronic obstructive pulmonary disease and chronic asthma.

In the study, chemicals found in cigarette smoke were shown to activate signaling in nerves that ended in the airways of guinea pigs. These effects were abolished using a molecule that inhibited a protein known as TRPA1. Consistent with a central role for TRPA1 in sensing chemicals in cigarette smoke, no signaling in nerves that end in the airways was observed in mice lacking TRPA1 after exposure to the chemicals in cigarette smoke. Further analysis showed that alpha,beta-unsaturated aldehydes were the chemicals that activated TRPA1, suggesting that they might contribute to the airway damage that occurs in smoke-related diseases.

TITLE: Cigarette smokeinduced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents

Pierangelo Geppetti
University of Florence, Florence, Italy.
Phone: 39-055-427-1329; Fax: 39-055-427-1280; E-mail:

View the PDF of this article at:


TITLE: How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways

Sidney A. Simon
Duke University Medical Center, Durham, North Carolina, USA.
Phone: (919) 684-4178; Fax: (919) 684-4431; Email:

View the PDF of this article at:

EDITOR'S PICK: Battle of the bulge: low leptin levels undermine successful weight loss

Individuals who are obese are at increased risk of many diseases, including type 2 diabetes and heart disease. As 75%-95% of previously obese individuals regain their lost weight, many researchers are interested in developing treatments to help individuals maintain their weight loss. A new study, by Michael Rosenbaum and colleagues, at Columbia University Medical Center, New York, has provided new insight into the critical interaction between the hormone leptin and the brain's response to weight loss.

Leptin levels fall as obese individuals lose weight. So, the authors set out to see whether changes in leptin levels altered activity in the regions of the brain known to have a role in regulating food intake. They observed that activity in these regions of the brain in response to visual food-related cues changed after an obese individual successfully lost weight. However, these changes in brain activity were not observed if the obese individual who had successfully lost weight was treated with leptin. These data are consistent with the idea that the decrease in leptin levels that occurs when an individual loses weight serves to protect the body against the loss of body fat. Further, both the authors and, in an accompanying commentary, Rexford Ahima, at the University of Pennsylvania School of Medicine, Philadelphia, suggest that leptin therapy after weight loss might improve weight maintenance by overriding this fat-loss defense.

TITLE: Leptin reverses weight lossinduced changes in regional neural activity responses to visual food stimuli

Michael Rosenbaum
Columbia University Medical College, New York, New York, USA.
Phone: (212) 305-9949; Fax: (212) 851-5306; E-mail:

View the PDF of this article at:


TITLE: Revisiting leptin's role in obesity and weight loss

Rexford S. Ahima
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-1872; Fax: (215) 573-5809; E-mail:

View the PDF of this article at:

ONCOLOGY: Overcoming resistance to a cancer drug

Drugs that target members of the EGFR family of proteins have proven effective for the treatment of certain types of cancer, including breast cancer. However, in a large number of patients for whom the treatment initially works well, the tumor recurs and is resistant to the effects of the drug. New insight into the mechanisms of tumor resistance to a drug known as gefitinib, which targets EGFR, has now been provided by a team of researchers at Vanderbilt University Medical Center, Nashville, and Massachusetts General Hospital Cancer Center, Charlestown. As discussed by both the authors and, in an accompanying commentary, Mark Greene and Qiang Wang, at the University of Pennsylvania Medical Center, Philadelphia, these observations help us understand why tumors become resistant to the effects of EGFR-targeted drugs, information that is essential if more effective therapies are to be developed.

The team, led by Carlos Arteaga and Jeffrey Engelman, generated cancer cells resistant to the effects of gefitinib and found that these cells were constantly sending signals from a protein on their surface known as IGF1R. This meant that two proteins known as IRS-1 and PI3K were always associated. If this association was disrupted then the cells once again became susceptible to the effects of gefitinib. Further analysis showed that if mice with a human tumor were treated with gefitinib and a drug inhibiting IGF1R their tumors did not recur, whereas neither drug alone could prevent tumor recurrence. The authors therefore suggest that drug combinations that target both EGFR and IGF1R might be of benefit to individuals with cancers that are responsive to EGFR-targeted therapies.

TITLE: Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins

Carlos L. Arteaga
Vanderbilt University Medical Center, Nashville, Tennessee, USA
Phone: (615) 936-3524; Fax: (615) 936-1790; E-mail:

Jeffrey A. Engelman
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA.
Phone: (617) 724-7298; Fax: (617) 724-9648; E-mail:

View the PDF of this article at:


TITLE: Mechanisms of resistance to ErbB-targeted cancer therapeutics

Mark I. Greene
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 898-2870; Fax: (215) 898-2401; Email:

View the PDF of this article at:

IMMUNOLOGY: How an anticancer drug dampens the immune system

Drugs known as HDAC inhibitors, which have antitumor activity and can be used to treat some forms of skin cancer and some types of leukemia, are also known to have anti-inflammatory properties, but the mechanisms by which they modulate the immune system have not been determined. New data, generated by Pavan Reddy and colleagues, at the University of Michigan Cancer Center, Ann Arbor, have now indicated one mechanism by which HDAC inhibitors modulate the mouse and human immune system and the information gained has been used to develop an approach to protect mice from graft-versus-host disease after bone marrow transplantation.

In the study, two different HDAC inhibitors were shown to prevent mouse and human immune cells known as dendritic cells (DCs) from initiating proinflammatory immune responses in vitro. Further, if DCs treated ex vivo with HDAC inhibitors were injected into mice after they had received a bone marrow transplant, the incidence and severity of graft-versus-host disease was dramatically reduced. Detailed analysis revealed that the HDAC inhibitors mediated their effects by inducing DCs to express more of a molecule known as IDO, which is a suppressor of DC function. The authors therefore hope that their data provide support for studies to determine whether HDAC inhibitors might be of benefit to individuals receiving bone marrow transplants and to those with other immune-mediated diseases.

TITLE: Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenasedependent DC functions and regulates experimental graft-versus-host disease in mice

Pavan Reddy
University of Michigan Cancer Center, Ann Arbor, Michigan, USA.
Phone: (734) 647-5954; Fax: (734) 647-9271; E-mail:

View the PDF of this article at:

VASCULAR BIOLOGY: A prickly problem: hedgehog signaling in the blood vessels of the heart

New data, generated by David Ornitz and colleagues, at Washington University School of Medicine, St. Louis, have indicated a crucial role for signaling pathways that involve the protein sonic hedgehog in maintaining the blood vessels that supply the mouse heart and keep it beating. These data have implications for drug development as they suggest that antagonists of hedgehog signaling pathways, such as those being developed as anticancer therapeutics, might have unwanted side effects.

In the study, mice lacking the ability to mediate hedgehog signaling in cells that form part of the blood vessels that supply the heart were found to die of heart failure. This was because in the absence of hedgehog signaling the blood vessels of the heart were lost, meaning that the heart cells were no longer supplied with enough oxygen and died. Although these data indicate a need for caution when developing clinical antagonists of hedgehog signaling, it is possible that the degree of inhibition needed to have a clinical effect on tumor development might not have the effect on blood vessels of the heart that completely eliminating expression of the protein does.

TITLE: Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice

David M. Ornitz
Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: (314) 362-3908; Fax: (314) 362-7058; E-mail:

View the PDF of this article at:

VIROLOGY: How a measles virus infection gets going

New data, generated by Roberto Cattaneo and colleagues, have raised doubts about the current model of the initial events that lead to infection with measles virus.

Individuals inhale measles virus particles in aerosols and it is currently thought that these particles infect the cells that line the airways (respiratory epithelial cells) before being passed to immune cells that carry the virus particles to other parts of the body and then back to the airways, which again become infected and shed virus into exhaled aerosols. In the study, a measles virus unable to bind to and infect epithelial cells was found to cause symptoms of measles virus infection in monkeys even though it did not infect respiratory epithelial cells and was not being shed into exhaled aerosols. These data suggest that, in fact, inhaled measles virus particles first infect lymphocytes and are only passed to respiratory epithelial cells from the lymphocytes in the tissues. Further, they indicate that the protein that measles virus particles bind to on respiratory epithelial cells, which has yet to be identified, is likely to be found on the surface of the cells that faces the tissues rather than the surface that faces the airways, as previously assumed. As discussed in an accompanying commentary by Makoto Takeda, at Kyushu University, Japan, the results of this study should help researchers identify this protein.

TITLE: Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

Roberto Cattaneo
Mayo Clinic, Rochester, Minnesota, USA.
Phone: (507) 538-1188; Fax: (507) 266-2122; E-mail:

Robert J Nellis
Mayo Clinic, Rochester, Minnesota, USA.
Phone: (507) 284-5005; E-mail:

View the PDF of this article at:


TITLE: Measles virus breaks through epithelial cell barriers to achieve transmission

Makoto Takeda
Kyushu University, Fukuoka, Japan.
Phone: 81-92-642-6138; Fax: 81-92-642-6140; Email:

View the PDF of this article at:

INFLAMMATION: Immune cells cause inflammation by destroying an anti-inflammatory protein

Among the first cells of the immune system to respond to microorganisms that invade our body are neutrophils. Although neutrophils are considered the "good guys" in such circumstances, they also contribute to the noninfectious chronic inflammation that underlies various diseases, including autoimmune diseases such as rheumatoid arthritis. One mechanism by which neutrophils protect us is to internalize microorganisms and destroy them using proteins known as neutrophil serine proteases (NSPs), but whether NSPs have a role in noninfectious chronic inflammation has not been clearly determined. However, using mice lacking two very similar NSPs, PR3 and NE, a team of researchers at the Max-Planck-Institute of Neurobiology, Germany, have now shown that these two NSPs have a crucial role in one form of noninfectious chronic inflammation. Detailed analysis revealed that PR3 and NE destroy an anti-inflammatory molecule known as PGRN and in this way help to promote inflammation in the absence of invading microorganisms. The authors therefore suggest that these data provide rationale for considering inhibitors of NSPs as anti-inflammatory drugs.

TITLE: Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin

Kai Kessenbrock
Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Phone: 49-89-8578-3588; Fax: 49-89-8578-3790; E-mail:

Dieter E. Jenne
Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Phone: 49-89-8578-3589; Fax: 49-89-8578-3790; E-mail:

View the PDF of this article at:


Contact: Karen Honey
Journal of Clinical Investigation

Related medicine news :

1. Ranbaxy Receives Tentative Approval to Manufacture and Market Galantamine Tablets on an Exclusive Basis
2. Schering-Plough/Merck Pharmaceuticals Announce FDA Filing Acceptance of New Drug Application for Loratadine/Montelukast Tablet
3. JCI table of contents: Sept. 4, 2007
4. FDA Seeks to Regulate Complementary and Alternative Medicine; Products Such as Vegetable Juice Could Be Restricted for Medical Use
5. Actavis Launches Carvedilol Tablets in the U.S.
6. Mylan Announces Final FDA Approval for Carvedilol Tablets
7. Ranbaxy Gains Approval to Manufacture and Market Carvedilol Tablets in the U.S. Market
8. Actavis Launches Amlodipine Tablets in the U.S.
9. Implantable device designed to detect, stop seizures under study at MCG
10. Stevens Health, Technology and Society roundtable: Sept. 19
11. Fruity vegetables and fish reduce asthma and allergies
Post Your Comments:
(Date:11/24/2015)... ... ... Willey , has answered a new calling – to relieve snoring and sleep apnea for ... and sleep apnea through oral appliance therapy. He is one of a number ... of four in the Illinois area. , Dr. Willey’s location is at 11825 ...
(Date:11/24/2015)... ... November 24, 2015 , ... Dr. Kevin Day, local ... help the community stress less this holiday season. During the Indiana winter months, ... people's lives and the team at AlignLife want to help provide the tools needed ...
(Date:11/24/2015)... OR (PRWEB) , ... November 24, 2015 , ... Dehydration, ... too much body water to perspiration in the hot sun, and heat stroke and ... Fresh water advocate and radio host Sharon Kleyne. Every cell, system and structure requires ...
(Date:11/24/2015)... ... , ... There’s nothing better than giving the gift of green this holiday ... , This year, gardens are popping up in the most unexpected places. A variety ... Gardens’ African Keyhole Garden Bed ($499) , Water conscious gardeners – and that should ...
(Date:11/24/2015)... ... November 24, 2015 , ... Tudore Tranquility is a new restaurant in Tokyo, ... plant-based fine dining menu that is full of flavorful and creative dishes that exceed ... wedding dinner or a small intimate event. The décor looks stunning with gold and ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... Abaxis, Inc. (NasdaqGS: ABAX ), a ... the medical, research, and veterinary markets worldwide, announced today ... present at the 27 th Annual Piper Jaffray ... a.m. ET. The conference will be held at The ... City . Abaxis, Inc. is a ...
(Date:11/24/2015)... Edelris announce today that they have ... Poxel, CNRS, UCBL and ENS-Lyon on a new treatment to ... Hepatitis B virus (HBV) infection is a major public ... worldwide, 20 to 40% of them being at risk of ... existence of an effective preventive vaccine, the HBV infection is ...
(Date:11/24/2015)... MONROVIA, Calif. , Nov. 24, 2015 ... company developing engineered monoclonal antibodies for the treatment of ... announced that Bassil Dahiyat , Ph.D., president and ... in December: , 2015 Piper Jaffray Healthcare ... ET Location: New York, NY ...
Breaking Medicine Technology: