Navigation Links
JCI early table of contents for March 19, 2012


A clearer understanding of glaucoma | Back to top

Glaucoma is one of the leading causes of vision loss and blindness worldwide. In glaucoma patients, the optic nerve, which relays information from the eye to the brain, is damaged, though the molecular cause of nerve damage is unclear. Dr. Simon John, from Tufts University in Boston, and colleagues specifically wanted to understand the earliest events that lead to optic nerve damage in glaucoma. Using a mouse model of the disease, the researchers showed that inflammatory immune cells called monocytes cross blood vessels and invade the optic nerve. Remarkably, mice treated with a single X-ray treatment in eyes prior to the onset of glaucoma were protected from developing the disease later in life. Through an unknown mechanism, the X-ray treatment prevented neuroinflammation and allowed mice to avoid glaucoma development, even in the presence of other risk factors. Continuing research by the John team will examine why the X-ray treatment effectively blocked glaucoma in the mouse model system and if this strategy might someday be adapted to prevent glaucoma in humans.


Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma


Simon W.M. John

Howard Hughes Medical Institute, The Jackson Laboratory, 600 Main St., Bar Harbor, Maine 04609, USA. Phone: 207-288-6496; Fax: 207-288-6078; E-mail:

View this article at:


At the heart of it all: myosin regulatory protein key for cardiac muscle function | Back to top

A groundbreaking study by Ju Chen and colleagues at the University of California at San Diego sheds new light on the regulation of cardiac muscle contraction. The dynamic interaction of the proteins actin and myosin, which are key components of muscle fibers, is responsible for contractions. The binding of calcium to actin-bound regulatory proteins has long been regarded as the primary regulatory mechanism for muscle contraction. However, some data suggests that myosin regulatory proteins, such as ventricular myosin light chain-2 (MLC2v), might also contribute to the regulation of muscle contractions through unknown mechanisms.

The Chen team specifically examined the role of MLC2v phosphorylation on cardiac muscle. They show in cardiac tissue that MLC2v phosphorylation controls dynamic myosin and actin interactions. The team also extrapolates the molecular actions of MLC2v phosphorylation using computation models, which suggest that cross bridge attachment dynamics are controlled by MLC2v phosphorylation. Their model of MLC2v regulation of cardiac muscle contraction is supported by defects in the rate of twitch relaxation that they observed in a mouse model system in which MLC2v cannot be phosphorylated. Their study provides new appreciation for the role of myosin regulatory proteins in muscle contraction, and has important clinical implications for understanding heart disease.


Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease


Farah Sheikh

The University of California San Diego, La Jolla, CA, USA

Phone: 858-246-0754; E-mail:

View this article at:


A big role for microRNA in protecting heart tissue | Back to top

During a heart attack, a block in blood flow damages cardiac tissue. Though counterintuitive, significant tissue damage also occurs in response to the restoration of blood flow, known as ischemia/reperfusion injury, which activates stress pathways in the heart. This second wave of cardiac damage is caused by a many factors, including a disruption in the balance of calcium, which is a key regulator of heart contractions and cellular signaling. Dr. Eric Olson and his colleagues at the University of Texas Southwestern Medical Center in Dallas recently explored one of the causes of calcium overload during ischemia/reperfusion injury using a mouse model system. They suspected that regulatory RNA molecules known as microRNAs (miRNAs) may play a role in tissue damage in response to the restoration of blood flow to the heart. The team showed that miRNA-214, which is upregulated during the block in blood flow to the heart, helped protect tissue from ischemis/reperfusion injury. They found that mice that lack miRNA-214 lost heart contractility and showed an increase in fibrosis due to aberrant regulation of a key regulator of calcium influx. Their work has identified a new pathway that is important in regulating calcium homeostasis and protecting heart function.


microRNA-214 protects the heart from ischemic injury by controlling Ca2+ overload and cell death in mice


Eric Olson

UT Southwestern Medical Center, Dallas, TX, USA

Phone: 214-648-1187; Fax: 214-648-1196; E-mail:

View this article at:


Endothelial Hypoxia Inducible Factor-2alpha (HIF-2α) regulates murine pathological angiogenesis and revascularization processes | Back to top

Understanding what triggers new blood vessels to grow has clinical implications for disorders characterized by restricted blood flow, such as macular degeneration and peripheral arterial disease, and for the growth of solid tumors, which require new blood flow to maintain aggressive growth. The development of new blood vessels, termed angiogenesis, is triggered in part by low oxygen levels. A transcription factor called Hypoxia Inducible Factor can respond to low oxygen and induce the expression of multiple genes required for angiogenesis.

A research group at the University of Pennsylvania in Philadelphia delved into the detailed mechanism of how the protein hypoxia inducible factor 2α (HIF-2 α) contributes to new blood vessel formation. Led by M. Celeste Simon, the team specifically disrupted the Hif-2α gene from mouse endothelial cells, which make up the walls of blood vessels, and observed an increase in blood vessel formation. However, the blood vessels that formed in the mouse model system had reduced blood flow and poor tissue oxygenation due to ineffective vessel remodeling. Their study distinguishes the role of Hif-2α from a related gene, Hif-1α, and suggest that these genes work synergistically to promote proper blood vessel formation.


Endothelial Hypoxia Inducible Factor-2alpha (HIF-2α) regulates murine pathological angiogenesis and revascularization processes


M. Celeste Simon

University of Pennsylvania/HHMI, Philadelphia, PA, USA

Phone: 215-746-5532; Fax: 215-746-5511; E-mail:

View this article at:


Understanding how herpes simplex virus invades the central nervous system | Back to top

Herpes Simplex virus (HSV) 1 and 2 are the cause of cold sores and genital herpes, respectively, in humans. Even in the absence of outbreaks, remaining reservoirs of virus linger in the body. Both viruses can infect neurons and occasionally cause diseases such as encephalitis and meningitis, especially in people with compromised immune system. Sren Paludan and colleagues at Aarhus University in Denmark investigated what triggers increased susceptibility to HSV2 in the central nervous system using a mouse model system. The found that toll-like receptor 3 (TLR3) is critical for maintaining immunoprotective responses in the central nervous system and that mice lacking Tlr3 showed increased susceptibility to central nervous system complications following HSV-2 infection. Importantly, their work clarifies when and where TLR3 activity is necessary, and they demonstrate that TLR-3 elicits an interferon response in astrocytes following viral entry in the central nervous system. Their work clarifies the mechanisms whereby central nervous system diseases arise in HSV-infected individuals.


TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice


Sren Paludan

University of Aarhus, Aarhus C, UNK, DNK

Phone: 45-8942-1767; Fax: 45-8619-6128; E-mail:

View this article at:


Immune response gone awry: treating autoimmune disorders with rituximab | Back to top

Rituximab is an antibody therapy that targets immune cells called B cells for destruction. The FDA has approved rituximab for treatment of specific disorders characterized by too many B cells, such as B cell lymphoma, or autoimmune disorders, such as rheumatoid arthritis. However, it has been unclear why some autoimmune patients show good long-term clinical response to rituximab while others do not.

In a clinical study of patients with anti-myelin-associated glycoprotein (MAG) neuropathy, an autoimmune disorder characterized by an immune system attack towards a protein expressed in the myelin sheath of peripheral nerves, Dr. Jan Lunemann and colleagues at the University of Zurich in Switzerland sought to discover why some patients respond well to rituximab. The team looked at memory B cell expansion before and after rituximab therapy in patients, and found that a good response was associated with depletion of non-circulating B cells and reconfiguration of B cell memory. The team suggests that non-responders may benefit from additional rituximab rounds of therapy to further reduce self-reactive B cells. Their findings support continued exploration of rituximab therapy for other autoimmune disorders where B cell depletion could alleviate symptoms.


Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity


Jan Lunemann

University of Zurich, Zurich, UNK, CHE

Phone: 41-44-635-3710; Fax: ; E-mail:

View this article at:


Uncovering the links between diabetes and atherosclerosis | Back to top

Diabetic patients are at increased risk for cardiovascular disease and a hardening of blood vessel walls called atherosclerosis. One factor that drives atherosclerosis development in diabetes is abnormal blood cholesterol levels. Researchers suspect that a breakdown of LDL in early Type 2 diabetes by the low density lipoprotein receptor (LDLR) in liver leads to a compensatory increase in levels of very low density lipoprotein (VLDL).

The challenge of understanding the link between insulin and liver LDLR levels was addressed by Ding Ai and colleagues at the University of Texas Southwestern Medical Center in Dallas. Using several different mouse models, they showed that insulin receptor signaling via mTORC1 blocks LDLR breakdown by PCSK9. Thus LDLR is stabilized and more LDL is broken down, leading to disturbed cholesterol levels. Their results also help explain why rapamycin, a drug that inhibits mTORC1 and is used to suppress the immune system during transplantation, causes an increase in cholesterol levels.


Regulation of hepatic LDL receptors by mTORC1 and PCSK9


Ding Ai

Columbia University Medical Center, new york, NY, USA

Phone: 212-305-5789; Fax: ; E-mail:

View this article at:


A painful lesson: understanding what causes hypersensitivity to pain | Back to top

An increased sensitivity to pain, called hyperalgesia, can be debilitating for suffering patients. Hyperalgesia can be a complication of several disorders including stroke, fibromyalgia, diabetes, and neuropathic disorders. Inflammation, tissue damage, and nervous system disorders can all contribute to development of hyperalgesia, but the underlying molecular mechanisms are still unknown. Researchers at the Ernest Gallo Clinic in Emerville, CA set out to better understand the molecular cause of hyperalgesia. Led by Robert Messing, the team searched for the molecular target of PKCε, an enzyme that regulates hyperalgesia through a poorly understood mechanism. The research team identified a sodium channel that is targeted by PKCε in sensory neurons called nociceptors. Further, they showed depleting these specific sodium channels from nociceptors in a mouse model system blocked the development of hyperalgesia. These results provide new evidence for the molecular causes of hyperalgesia and suggest that targeting this pathway may be an effective strategy for designing new therapeutics to treat hyperalgesia.


PKC epsilon phosphorylation of NaV1.8 increases sodium channel function and produces mechanical hyperalgesia in mice


Robert Messing

Univ. of Calif. San Francisco, Emeryville, CA, USA

Phone: 510-985-3950; Fax: 510-985-3101; E-mail:

View this article at:


Learning from mistakes: why a promising therapy for follicular lymphoma failed | Back to top

Follicular lymphoma is a cancer characterized by abnormal proliferation of immune cells called B cells. One therapeutic strategy, Interleukin (IL) -12 therapy, was predicted to increase the clearing of malignant B cells by activating natural killer (NK) cells and T cells, components of the immune system. Unfortunately, this strategy had very limited efficacy in a previously conducted clinical trial of follicular lymphoma patients. Dr. Stephen Ansell and colleagues at the Mayo Clinic in Rochester, MN wanted to understand why IL-12 therapy had failed. They found that activation of the IL-12 pathway exhausted T cell populations through a previously unknown mechanism, rather than stimulating clearance of tumor cells. When the therapy was designed, it was hoped that IL-12 would promote T cell responsiveness through the production of interferon gamma (IFN-γ), which stimulates immune system activity. The research team found that instead T cell exhaustion is induced in patients by IL-12-induced expression of TIM-3, a family member of T-cell immunoglobulin and mucin domain proteins, that negatively regulates immune response. Thus, their study explains why IL-12 therapy was ineffective in treating follicular lymphoma patients and highlights the importance of TIM-3 downstream of the IL-12 pathway.


IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma


Stephen Ansell

Mayo Clinic, Rochester, , USA

Phone: 507-284-3805; Fax: ; E-mail:

View this article at:

Contact: Sarah Jackson
Journal of Clinical Investigation

Related medicine news :

1. Dr. Betty Vohr honored for Early Hearing Detection and Intervention Excellence
2. Nearly 800,000 deaths prevented due to declines in smoking
3. Study: US tobacco-control efforts prevented nearly 800,000 cancer deaths between 1975 and 2000
4. Mild Winter Heralds Early Sneezin Season
5. New blood test for early cancer detection developed by Ben-Gurion University researchers
6. Fever control using external cooling reduces early mortality in septic shock patients
7. Researchers see differences in Autism brain development as early as 6 months
8. To avoid early labor and delivery, weight and diet changes not the answer
9. Positive parenting during early childhood may prevent obesity
10. Anesthesia in Early Childhood May Be Linked to ADHD
11. Same Genes Key to Early & Late-Onset Alzheimers: Study
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading Health ... technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly growing ... form that can be easily incorporated into liquid products, while reducing costs to end ...
(Date:10/13/2017)... ... 2017 , ... Lori R. Somekh, founder of the Law Office of ... elder law and special needs planning attorneys. “Membership in ElderCounsel helps our office remain ... to network with elder law attorneys nationwide,” said Somekh. , ElderCounsel ...
(Date:10/13/2017)... LUIS OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... Alzheimer’s or dementia. However, many long-term care insurance companies have a waiver for care ... is the 90-day elimination period, when the family pays for care, is often waived, ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Ellevate Network, ... in business to advocate for action towards gender equality at their inaugural Summit in ... around the globe, and reached a social audience of over 3 million. To watch ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at ... of the most popular and least understood books in the Holy Scriptures, Revelation. The ... that have baffled scholars for centuries. Many have tossed it off as mere rubbish, ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... 11, 2017  Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), ... in Las Piedras, Puerto Rico , ... Following a ... sustained minor structural damage, temporary loss of power and ... been completed, manufacturing operations have resumed, and the company ...
(Date:10/4/2017)... , Oct. 4, 2017  South Korean-based healthcare ... CPR training aide "cprCUBE" on Kickstarter. The device will ... during cardiac arrests with better efficiency compared to the ... offers real-time feedback on efficacy of the compression for ... campaign has a goal to raise $5,000. ...
(Date:10/2/2017)... , Oct. 2, 2017  AllianceRx Walgreens Prime, ... formed by Walgreens and pharmacy benefit manager Prime Therapeutics ... new brand, which included the unveiling of new signage ... , as well as at a few other company-owned ... new brand to patients, some of whom will begin ...
Breaking Medicine Technology: