Cincinnati study of Chernobyl residents uncovers new cause of thyroid cancer
Cincinnati University scientists studying papillary thyroid cancer in Chernobyl residents following the 1986 nuclear plant accident have identified a novel genetic mutation event that occurs as a result of their exposure to high levels of radioiodide.
Yuri E. Nukiforov led a team of researchers from both Cincinnati University and the University of Munich in identifying a novel oncogene (a mutated and/or overproduced version of a normal gene that alone or together with other changes can convert a cell into a tumor cell) in papillary thyroid carcinomas that developed in patients exposed to radiation at Chernobyl. Their results are published in the January 3 issue of the Journal of Clinical Investigation.
Mutations of the genes BRAF, RET, or RAS are found in 70% of all cases of papillary thyroid tumors. In sporadic tumors (where patients have not been exposed to high levels of radiation), the most common genetic mutational event occurs within the BRAF gene. In contrast, mutations observed in radiation-induced tumors most commonly involve fusion of one end of the RET gene to the opposite end of various other genes to create a "chimeric oncogene." The two most common gene rearrangement types are called RET/PTC1 and RET/PTC3. Both types of mutations promote transformation of normal cells into malignant cells.
In their current study, Nukiforov and colleagues identified a novel oncogene in Chernobyl residents with papillary thyroid cancer. This oncogene resulted from fusion of part of the AKAP9 gene with one end of the BRAF gene; both genes are present within chromosome 7. The intrachromosomal AKAP9-BRAF fusion event resulted in the loss of portions of the BRAF protein that normally inhibit the kinase activity of BRAF. BRAF is then able to transmit uncontrolled signals to normal cells that promote their division and transformation into malignant tumor cells.
In an accompanying commentary, Alfredo Fusco and colleagues from Università degli Studi di Napoli "Federico II", in Naples, state that this study "provides further evidence supporting the concept that chromosomal inversions represent the most typical molecular lesion in tumors occurring in Belarus and the surrounding region after the Chernobyl accident….the peculiar susceptibility of thyroid follicular cells to chromosomal rearrangement is remarkable."
This study represents a major breakthrough in our knowledge of the genetic events involved in papillary thyroid initiation. It demonstrates that while BRAF activation is a common feature of both sporadic and post-Chernobyl thyroid cancers, it is the genetic event underlying BRAF activation that can differentiate between the two types of tumors, with a higher proportion of point mutations occurring in sporadic thyroid cancers and intrachromosomal inversion responsible for a larger percentage of radiation-induced tumors. At this stage, the signaling pathway activated as a result of these mutational events (known as the MAPK pathway) is the most attractive target for new drugs that may intervene in the development of human papillary thyroid carcinomas.
TITLE: Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer
AUTHOR CONTACT: Yuri Nikiforov
University of Cincinnati, Cincinnati, Ohio, USA.
Phone: 513-558-5798; Fax: 513-558-2289; E-mail: Yuri.Nikiforov@uc.edu
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/94.
TITLE: A new mechanism of BRAF activation in human thyroid papillary carcinomas
AUTHOR CONTACT: Alfredo Fusco
Università degli Studi di Napoli "Federico II", Naples, Italy.
Phone: 0039-0813722857; Fax: 0039-0817463749; E-mail: email@example.com
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/20.
Transplantation of monkey embryonic stem cells reverses Parkinson disease in primates
The replenishment of missing neurons in the brain as a treatment for Parkinson disease reached the stage of human trials over 15 years ago, however the field is still in its infancy. Researchers from Kyoto University have now shown that dopamine-producing neurons (DA neurons) generated from monkey embryonic stem cells and transplanted into areas of the brain where these neurons have degenerated in a monkey model of Parkinson disease, can reverse parkinsonism. Their results appear in the January 3 issue of the Journal of Clinical Investigation.
Studies of animal models of Parkinson disease as well as clinical investigations, have shown that transplantation of fetal DA neurons can relieve the symptoms this disease. However the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy.
These researchers previously demonstrated that mouse embryonic stem cells can differentiate into neurons when cultured under specific conditions. These same culture conditions, technically simple and efficient, were recently applied to primate embryonic stem cells and resulted in the generation of large numbers of DA neurons. In their current JCI study, Jun Takahashi and colleagues generated neurons from monkey embryonic stem cells and exposed these cells to FGF20, a growth factor that is produced exclusively in the area of the brain affected by Parkinson disease and is reported to have a protective effect on DA neurons. The authors observed increased DA neuron development and subsequently transplanted these neurons into monkeys treated with an agent called MPTP, which is considered a primate model for Parkinson disease. These transplanted cells were able to function as DA neurons and diminished Parkinsonian symptoms.
In an accompanying commentary, J. William Langston from the Parkinson's Institute, California, describes this study as a milestone in the development of stem cell technology but cautions that while the observations are encouraging, the reported number of surviving DA neurons was very low, only 1–3% of the cells surviving, well below the estimated number of DA neurons that survive after fetal cell transplants (approximately 10%). While this may be a difference observed between transplantation in monkeys and humans, Langston stresses that it may be necessary for far more DA neurons to survive and for that survival to be long lasting in order to render this approach as a useful therapy in humans.
Langston highlights that "clearly the study reported here will advance research aimed at validating the use of stem cells to treat neurodegenerative disease" and this is most welcome particularly as investigators face yet another presidential moratorium endeavoring to limit the number of human stem cell lines that can be used for future research and treatment.
TITLE: Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model
AUTHOR CONTACT: Jun Takahashi
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Phone: 81-75-751-3450; Fax: 81-75-752-9501; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/102.
TITLE: The promise of stem cells in Parkinson disease
AUTHOR CONTACT: J. William Langston
Parkinson's Institute, Sunnyvale, California, USA.
Phone: 408-734-2800; Fax: 408-734-8522; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/23.
IL-7 wipes out HIV-1 hideouts
Recent advances in therapy for HIV disease, particularly the use of combinations of antiretroviral drugs, collectively termed highly active antiretroviral therapy (HAART), have resulted in a dramatic improvement in health status for a large number of HIV-infected individuals. Many of these people maintain clinically undetectable loads of the HIV virus, however a pool of persistently HIV-infected cells remains and prevents the complete eradication of HIV infection. New treatment strategies are now focused on increasing the turnover of latent pools of virus through activation of latent infected cells (which promotes cell death and accelerates viral clearance) and combining this approach with intense antiretroviral therapy.
In the January 3 issue of the Journal of Clinical Investigation, Roger Pomerantz, Giuseppe Nunnari, and colleagues from Thomas Jefferson University demonstrate that the growth factor IL-7 is a unique, potent, and strain-specific inducer of latent HIV-1 activation in infected individuals on virally suppressive HAART. IL-7, a molecule that promotes the growth and activation of B and T cells, was shown to also stimulate HIV-1 activation from resting T cells in order to deplete pools of HIV-1–infected cells. The authors show that a distinct viral species is activated by IL-7, and suggest that different molecules may deplete only a specific proportion of the latent HIV-1 population in individuals on HAART. IL-7 could potentially be combined with other molecules to potentially delete reservoirs of HIV-1 in new antiretroviral approaches.
TITLE: IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART
AUTHOR CONTACT: Roger Pomerantz
Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Phone: 215-503-8575; Fax: 215-503-2624; E-mail: Roger.J.Pomerantz@jefferson.edu.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/128.
Role for the A1 adenosine receptor in protecting against asthma
Levels of the signaling molecule adenosine are increased in the lungs of asthmatics, and elevations of adenosine correlate with the degree of airway inflammation, suggesting that adenosine may play a provocative role in acute asthma attacks. Therefore much research has been focused on drugs that may potentially interact with known adenosine receptors – the activation of which can have proinflammatory or anti-inflammatory effects, depending on the receptor type. Theophylline, the most widely prescribed drug for the treatment of airway disease worldwide, is able to block both pro- and anti-inflammatory actions of adenosine, potentially decreasing its efficiency. Researchers are now focused on determining the role of each adenosine receptor so that they may design drugs to interact with specific receptors and reduce airway inflammation.
As described in a report in the January 3 issue of the Journal of Clinical Investigation, Michael Blackburn led a team of researchers at the University of Texas Health Science Center and the National Institutes of Health to examine the role of the A1 adenosine receptor (A1AR) in a mouse model of lung injury and inflammation in which these mice possess elevated adenosine levels.
Blackburn et al. show that mice lacking A1AR die shortly after birth from severe inflammatory lung disease, indicating that A1AR serves an anti-inflammatory and thus protective role in the development of lung inflammation. The findings are particularly relevant in light of the fact that drugs that block A1AR are currently being investigated as a potential treatment for asthma.
In an accompanying commentary, Stephen Tilley and Richard Boucher from the University of North Carolina discuss this study and the potential clinical benefits of blocking A1 receptors in the airways of asthma patients.
TITLE: A protective role for the A1 receptor in adenosine-dependent pulmonary injury
AUTHOR CONTACT: Michael R. Blackburn
Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas, USA.
Phone: 713-500-6087; Fax: 713-500-0652; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/35.
TITLE: A1 antagonism in asthma: better than coffee?
AUTHOR CONTACT: Richard C. Boucher
University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Phone: 919-966-1077; Fax: 919-966-7524; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/13.
Breast cancer's genetic signature predicts likelihood and location of spread
Cancer metastasis – the transfer of disease from one organ to another not directly connected to it – is responsible for the majority of cancer-related deaths. It is believed that metastases arise from rare cells in the original tumor that acquire the ability to grow at a distant site. Previous studies using microarray technology – which allows researchers to determine the expression levels of genes within cells and is often described as a gene expression "signature" – have revealed that expression of a set of 70 genes in the primary tumors of breast cancer patients, called the "poor prognosis" signature, is highly predictive of the development of breast cancer spread and patient survival.
Using this technology, Joan Massagé and colleagues from Memorial Sloan-Kettering Cancer Center, New York, examined the potential of individual breast cancer cells to spread to distinct and different organs. The authors found that breast cancer cells did indeed carry the poor-prognosis signature and this signature differed little between cells. However breast cancer cells had varying abilities to spread to bone, lung, and the adrenal gland. Most interestingly, the authors found that the genes that make up the poor-prognosis signature were different to those that comprised the metastatic signature, indicating that the genes that make up the poor-prognosis signature do not control the ability of the tumor to spread to specific organs. Furthermore, they identified a bone metastasis gene expression signature that was able to distinguish between primary breast carcinomas that preferentially spread to bone from those that spread elsewhere. Use of this gene expression signature may in the future allow accurate prediction of the spread of breast cancer primary tumors to bone and subsequently help guide the treatment of breast cancers.
The study is reported in the January 3 issue of the Journal of Clinical Investigation.
TITLE: Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors.
AUTHOR CONTACT: Joan Massagué
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: 212-639-8975; Fax: 212-717-3298; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/44.
Dual and divergent roles of macrophages during liver injury and repair
Macrophages have been shown to perform both injury-inducing and reparative tasks during inflammation. In the January 3 issue of the Journal of Clinical Investigation, Jeremy Duffield and colleagues from the University of Edinburgh examined macrophage function in the injury and recovery phases of liver fibrosis in mice. They found that macrophages promote scarring during liver injury but enhance the breakdown of fibrotic tissue during recovery. The study is the first to demonstrate that functionally distinct populations of macrophages exists within the same tissue and that they play critical roles in both the injury and recovery phases of inflammatory scarring.
Scott Friedman from Mount Sinai School of Medicine discusses this important finding in an accompanying commentary.
TITLE: Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
AUTHOR CONTACT: Jeremy Duffield
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Phone: 617-525-5914; Fax: 617-525-5830; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/56.
TITLE: Mac the knife? Macrophages – the double-edged sword of hepatic fibrosis
AUTHOR CONTACT: Scott L. Friedman
Mount Sinai School of Medicine, New York, New York, USA.
Phone: 212-659-9501; Fax: 212-849-2574; E-mail: Scott.Friedman@mssm.edu.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/29
Intestinal macrophages control bacterial infection without triggering inflammation
Intestinal macrophages have long been thought to control inflammation in the intestine. However Phillip Smith and colleagues from the University of Alabama at Birmingham report in the January 3 issue of the Journal of Clinical Investigation that while resident intestinal macrophages have the ability to kill invading pathogens, they do not possess the receptors that recognize foreign pathogens, nor do they produce the molecules that trigger the inflammatory response. These characteristics distinguish intestinal macrophages from their precursors – blood monocytes – and indicate that highly proinflammatory monocytes travel to the intestine in response to injury but upon arrival they acquire profound inflammatory anergy, promoting the absence of inflammation despite the close proximity of foreign pathogens.
TITLE: Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity
AUTHOR CONTACT: Phillip D. Smith
University of Alabama at Birmingham, Birmingham, Alabama, USA.
Phone: 205-975-9254; Fax: 205-934-8493; E-mail: PDSmith@UAB.edu.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/66.
New drug found to inhibit multidrug-resistant HIV-1 strains
Inhibition of HIV-1 infection by high active antiretroviral therapy (HAART) has profoundly improved the morbidity and mortality of HIV-1–infected patients. However, the transmission of multidrug-resistant HIV strains is becoming a growing problem in newly-infected persons as the efficacy of HAART is compromised and therapeutic options are consequently limited. In the January 3 issue of the Journal of Clinical investigation, Joachim Hauber and colleagues from The Heinrich-Pette-Institute for Experimental Virology and Immunology in Hamburg report that inhibition of cellular deoxyhypusine synthase with the molecule CNI-1493 was able to suppress the replication of HIV-1 strains highly resistant to other drugs, with no measurable drug-induced effects on cell growth. Human deoxyhypusine synthase represents a novel and promising drug target for development of advanced antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.
TITLE: Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy
AUTHOR CONTACT: Joachim Hauber
Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany.
Phone: 49-40-480-51-241; Fax:49-40-480-51-184; E-mail: firstname.lastname@example.org.
SDF-1 is necessary and sufficient to promote eye disease that results in blindness
Proliferative retinopathy, characterized by the abnormal formation of blood vessels in the retina, is a major cause of blindness in working-age adults. In humans, levels of stromal cell–derived factor 1 (SDF-1) in the jelly-like substance that fills the body of the eye are increased as proliferative retinopathy progresses. In the January 3 issue of the Journal of Clinical Investigation, Edward Scott and colleagues from the University of Florida examine a mouse model of adult proliferative retinopathy and show that SDF-1 is both necessary and sufficient to promote disease and may be an ideal target for disease prevention.
TITLE: SDF-1 is both necessary and sufficient to promote proliferative retinopathy.
AUTHOR CONTACT: Edward W. Scott
University of Florida, Gainesville, Florida, USA.
Phone: 352-846-1149; Fax: 352-392-5802; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/88.
PDGF-CC promotes blood vessel growth in oxygen-starved tissues
PDGF-CC is a recently-discovered member of a large family of factors that promote the growth of new blood vessels. However little is known about how this new member functions. In the January 3 issue of the Journal of Clinical Investigation, Peter Carmeliet and colleagues from the University of Leuven show that PDGF-CC stimulates and speeds the growth, maturation, and stabilization of new blood vessels. The molecule offers novel opportunities for treating conditions in which tissues have been deprived of vital oxygen, such as angina or cardiac arrest.
TITLE: Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors.
AUTHOR CONTACT: Peter Carmeliet
Center for Transgene Technology and Gene Therapy, Leuven, Belgium.
Phone: 32-16-34-57-72; Fax: 32-16-34-59-90; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/118.
Why subtypes of acute lymphoblastic leukemia are more prone to methotrexate toxicity
Methotrexate (MTX) is a chemotherapy drug widely used to treat childhood acute lymphoblastic leukemia (ALL) by interfering with folic acid activation and preventing cell reproduction. However, the formation and accumulation of MTX polyglutamates (MTXPGs) within cells can be toxic. In the January 3 issue of the Journal of Clinical Investigation, William Evans and colleagues from St. Jude's Research Hospital, Memphis, report that different subtypes of leukemia are associated with altered folate pathway gene expression, which influences the accumulation of MTXPGs. The study points to new strategies to overcome these potential causes of treatment failure in childhood ALL.
TITLE: Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics
AUTHOR CONTACT: William Evans
St. Jude's Children's Research Hospital, Memphis, Tennessee, USA.
Phone: 901-495-3663; Fax: 901-525-6869; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/110.
New players in insulin secretion
Insulin secretion is critically dependent on the proper function of a complex network of interactions. In the January 3 issue of the Journal of Clinical Investigation, two articles by Yoshiaki Kido and colleagues from Kobe University and Erik Renström and colleagues from Lund University examine the roles of PKC-lambda and the CaV2.3 calcium channel, respectively, in mediating biphasic insulin secretion following glucose stimulation.
In an accompanying commentary, Shao-Nian Yang and Per-Olof Berggren from the Karolinska Institutet, Sweden, further discuss the roles of this enzyme and calcium channel in both normal beta cell physiology and pathophysiology as it pertains to diabetes.
TITLE: PKC-lambda regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic beta cells.
AUTHOR CONTACT: Yoshiaki Kido
Kobe University Graduate School of Medicine, Kobe, Japan.
Phone: 81-78-382-5861; Fax: 81-78-382-2080; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/138.
TITLE: CaV2.3 calcium channels control second-phase insulin release
AUTHOR CONTACT: Erik Renström
Diabetes Programme at Lund University, Lund, Sweden.
Phone: 46-46-222-06-39; Fax: 46-46-222-77-63; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/146.
TITLE: CaV2.3 channel and PKC-lambda: new players in insulin secretion
AUTHOR CONTACT: Per-Olof Berggren
Karolinska Institutet, Stockholm, Sweden.
Phone: 46-8-51775731; Fax: 46-8-51779450; E-mail: per-olof.Berggren@molmed.ki.se.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/16.
Immune complexes as therapy for autoimmunity
For several decades, intravenous Ig (IVIg) has been used as a treatment for a variety of immune-related diseases, including the rare autoimmune disorder thrombocytopenia purpura, which occurs as a result of autoantibody binding to platelet surface antigens and is manifest as an acute platelet shortage. Despite years of use, the mechanism of its immunomodulation is still unclear. In the January 3 issue of the Journal of Clinical Investigation, Alan Lazarus and colleagues from St. Michael's Hospital in Toronto Canada use a mouse model of immune thrombocytopenia purpura to provide insight into the mechanism of IVIg's action and report that the Fc-gamma receptor is key to its therapeutic effect.
In an accompanying commentary, Raphael Clynes from Columbia University discusses these results and the rationale for the development of Fc-gamma receptor–targeted therapeutics for the treatment of autoimmunity.
TITLE: Can antibodies with specificity for soluble antigens mimic the therapeutic affects of intravenous IgG in the treatment of autoimmune disease?
AUTHOR CONTACT: Alan H. Lazarus
St. Michael's Hospital, Toronto, Ontario, Canada.
Phone: 416-864-5599; Fax: 416-864-3021; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/155.
TITLE: Immune complexes as therapy for autoimmunity
AUTHOR CONTACT: Raphael Clynes
Columbia University, New York, New York, USA.
Phone: 212-305-5289; Fax: 212-305-1392; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/25.
Endothelial lipase represents the road sometimes taken for fatty acid uptake
Lipoprotein lipase (LPL), an enzyme primarily found in adipose (fat) tissue, is thought to be the only enzyme that generates fatty acids from triglyceride-rich lipoproteins in the circulation. While individuals lacking the LPL gene suffer from massive accumulation of triglycerides, the surprising observation that their adipose tissue mass and lipid content in their fat cells remains normal has intrigued researchers. In the January 3 issue of the Journal of Clinical Investigation, Rudolph Zechner and colleagues from the University of Graz, Austria, report that a recently discovered enzyme, endothelial lipase, provides an alternate pathway for the uptake of fatty acids in lipoprotein lipase–deficient adipose tissue in mice. This finding greatly contributes to our understanding of the metabolism of plasma lipoproteins.
TITLE: Endothelial lipase provides as alternative pathway for FFA uptake in lipoprotein lipase–deficient mouse adipose tissue
AUTHOR CONTACT: Rudolph Zechner
University of Graz, Graz, Austria.
Phone: 43-316-3801900; Fax: 43-316-3809016; E-mail: Rudolf.firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/161.
PKC-zeta helps direct development and movement of stem cells
A small proportion of human stem cells continuously enter the blood and then rapidly return to the marrow but the molecular events that regulate the movement of these primitive cells are largely unknown. In the January 3 issue of the Journal of Clinical Investigation, Tsvee Lapidot and colleagues from The Weizmann Institute of Science in Israel describe how stromal cell–derived factor 1 (SDF-1) binds to its cell surface receptor, CXCR4, and elicits specific biological responses in primitive blood precursor cells, that include PKC-zeta activation.
In an accompanying commentary, Connie Eaves from the British Columbia Cancer Agency, discusses the clinical implications of these results particularly with regard to developing new agents to enhance the development and movement of stem cells throughout the body.
TITLE: Atypical PKC-zeta regulates SDF-1–mediated migration and development of human CD34+ progenitor cells.
AUTHOR CONTACT: Tsvee Lapidot
The Weizmann Institute of Science, Rehovot, Israel.
Phone: 972-8-9342481; Fax: 972-8-9344141; E-mail: Tsvee.Lapidot@weizmann.ac.il.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/168.
TITLE: SDF-1 tells stem cells to mind their P's and Z's
AUTHOR CONTACT: Connie J. Eaves
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Phone: 604-877-6070; Fax: 604-877-0712; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/27.
Multiple drugs negatively affect Vitamin D status and may damage bones
Vitamin D is essential for maintaining the calcium balance vital for healthy bones. Prolonged therapy with antiepileptic drugs, among others, has been shown to cause Vitamin D deficiency or osteomalacia (softening of the bones), however the events underlying this process have remained unknown until now. In the January 3 issue of the Journal of Clinical investigation, J.M. Pascussi and colleagues show that the level of CYP24 – the enzyme that inactivates Vitamin D metabolites – is increased via activation of the pregnane X receptor (PXR) following the administration of some antiepileptic drugs to mice.
In an accompanying commentary, Michael Holick from Boston University stresses that it is likely that the drugs described in this study are not the only ones that affect PXR and that further scrutiny will no doubt reveal that several other families of drugs and xenobiotics can have a similar affect. Holick cautions that the Vitamin D status of patients on almost any type of medication should be closely monitored.
TITLE: Possible involvement of pregnane X receptor–enhanced CYP24 expression in drug-induced osteomalacia.
AUTHOR CONTACT: J.M. Pascussi
INSERM 632, Montpellier, France.
Phone: 33-4-67613369; Fax: 33-4-67523681; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/177.
TITLE: Stay tuned to PXR: an orphan actor that may not be D-structive only to bone.
AUTHOR CONTACT: Michael F. Holick
Boston University School of Medicine, Boston, Massachusetts, USA.
Phone: 617-638-4545; Fax: 617-638-8882; E-mail: email@example.com.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/32.
Production of IgM antibodies predicts aggressive development of multiple sclerosis
It has been postulated that the demyelinating disease multiple sclerosis (MS) is an autoimmune condition and considerable research has been focused on identifying the particular antigen(s) associated with this disease. Increasing evidence indicates that IgM antibodies produced by B cells are involved in MS as intrathecal synthesis of IgM, but not other antibodies such as IgG or IgA, correlates with levels of myelin basic protein in the cerebrospinal fluid, an index of myelin destruction. In the January 3 issue of the Journal of Clinical Investigation, Luisa Maria Villar and colleagues from Hospital Ramón y Cajal, Madrid, examined the B cell subpopulation responsible for IgM secretion in a group of MS patients and found that the presence of intrathecal IgM antibodies that recognize myelin lipid was a very accurate predictor of aggressive disease progression in MS.
TITLE: Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS.
AUTHOR CONTACT: Luisa Maria Villar
Hospital Ramón y Cajal, Madrid, Spain.
Phone: 34-913368795; Fax: 34-913368809; E-mail: firstname.lastname@example.org.
A PDF of this article this article is available at: http://www.jci.org/cgi/content/full/115/1/187.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.
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