JCI table of contents: January 4, 2006EDITOR'S PICK
Soy diet worsens heart disease
Researchers from the University of Colorado have shown that mice carrying a genetic mutation that is linked to altered heart growth and function in humans, have significantly worse heart problems if fed a soy diet, when compared to mice fed a soy-free (milk protein–based) diet. This is the first study to provide evidence that an environmental influence – in this case diet – can affect the heart. It will also force researchers to rethink the diets of their laboratory mice. The results appear in the January 4, 2006 issue of the Journal of Clinical Investigation.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease occurring in 1 in 500 individuals, and is characterized by shortness of breath, chest discomfort, and palpitations that may be a sign of life-threatening arrhythmias. While mutations in a number of genes have been linked to HCM, the variety of symptoms experienced by sufferers suggests that other genetic or environmental factors affect disease prognosis.
For years, soy-rich diets have been speculated to protect against heart disease. The biological consequences of a soy-diet have been attributed to the presence of phytoestrogens, which are plant-derived estrogen-like compounds that interact with the estrogen receptor. Leslie Leinwand and colleagues examined male and female mice that overexpressed a mutant form of the alpha myosin heavy chain gene, which is one known cause of HCM in humans. The researchers found significant growth (known as hypertrophy) of the heart of male mice fed a soy-based diet, in comparison to male and female mutant mice fed a soy-free diet.
The authors propose that the difference observed between the sexes is based on the fact that the female mice, who are constantly exposed to naturally circulating levels of estrogen compounds, are less sensitive than males to the change in estrogen level as a result of the soy diet. Interestingly, the authors observed a significant improvement in cardiac growth and function when the animals were switched to a soy-free diet. The new data provide a strong link between soy diet and the progression of cardiac disease, in mice.
In an accompanying commentary, Cathy Hatcher and Craig Basson from Weill Medical College of Cornell University discuss the influence of a soy diet on heart disease and highlight how in the future, researchers using animal models for the study of human disease will have to consider the diet fed to their animals and how it may influence the manifestation of a disease in animals of various genetic backgrounds.
TITLE: Soy diet worsens heart disease in mice
Leslie A. Leinwand
University of Colorado Health Sciences Center, Boulder, Colorado, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=24676
TITLE: Taking a bite out of hypertrophic cardiomyopathy: soy diet and disease
Craig T. Basson
Weill Medical College, Cornell University, New York, New York, USA Phone: 212-746-2201
View the PDF of this article at: https://www.the-jci.org/article.php?id=27455
Breast cancer–causing gene predicts shorter survival
In the last 5 years researchers have been examining the genes expressed during breast cancer in order to classify those genes into groups that can reliably predict the outcome of disease. In many cases, exactly how genes with prognostic significance figure into the disease process is not well understood. In a study appearing in the January 4, 2006 issue of the Journal of Clinical Investigation, Vincent Cryns and colleagues at Northwestern University report how the protein alpha-basic–crystallin, which is commonly expressed in a subtype of breast cancer tumors, is predictive of poor survival in breast cancer patients, independently of other prognostic markers, and also how this protein triggers tumor development. They reveal that alpha-basic–crystallin is overexpressed in mammary epithelial cells and causes dysregulated growth, changes in cell structure, diminished programmed cell death, and the formation of invasive carcinomas that is linked to activation of the ERK/MAPK signaling pathway. These results may facilitate the development of tailored therapies that are active against this signaling pathway. Ramon Parsons from Columbia University discusses the significance of the this study in an accompanying commentary in the same issue.
TITLE: alphaB-Crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer
Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA Phone: 312-503-0644;
View the PDF of this article at: https://www.the-jci.org/article.php?id=25888
TITLE: Is the small heat shock protein alphaB-crystallin an oncogene?
Columbia University, New York, New York, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=27462
Blocking eotaxin may help asthmatics breathe easier
Researchers at Oregon Health and Science University have shown that the nerves in the lungs, which cause the airways to narrow during asthma attacks, release eotaxin, a substance that attracts eosinophils, a type of white blood cell, to the nerves. David Jacoby and colleagues showed that the eosinophils stimulate the nerves to release acetylcholine, further narrowing the airways. When the researchers blocked the effects of eotaxin, they prevented this excessive airway narrowing. They were also able, for the first time, to isolate airway nerves from humans and maintain them in cell culture, allowing them to study how these nerves interact with eosinophils. These findings suggest that blocking eotaxin and the interactions of eosinophils with nerves will be helpful in treating asthma. The results appear in the January 4, 2006 issue of the Journal of Clinical Investigation.
TITLE: Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction
David B. Jacoby
Oregon Health and Science University, Portland, Oregon, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=25423
Turns-ons and turn-offs for smooth muscle cells
In a study appearing in the January 4, 2006 issue of the Journal of Clinical Investigation, Gary Owens and colleagues from the University of Virginia determine what causes smooth muscle cells (SMCs) to turn on or turn off the expression of certain SMC genes during healthy and disease states. Smooth muscle cells are present in many parts of the body, including blood vessel walls, stomach, intestine, lungs, and bladder, and they play a key role in stroke, high blood pressure, heart attack, gastric reflux, asthma, and incontinence. These cells can change shape and size in response to environmental triggers such as injury, and can stop or start making cell proteins that will benefit the healing process. It was previously known that serum response factor (SRF) controls SMC gene transcription by binding to structures known as CArG box DNA sequences found within the genes specifically expressed by SMCs. However, the mechanisms controlling this interaction had not been well determined. Owens and colleagues now show that it is the methylation of histones in the DNA that regulates SRF binding to CArG box chromatin of SMC genes. This suggests a novel mechanism of regulation of SMC gene expression that can influence the differentiation of SMCs during both normal development and disease states such as vascular injury.
TITLE: Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo
Gary K. Owens
University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=26505
Cancer detection: spinning biological trash into diagnostic gold
Scientists have started to examine small proteins and peptides present in human blood serum in the hope that these molecules might reflect biological events associated with disease and consequently be useful as diagnostic disease markers. In a study appearing in the January 4, 2006 issue of the Journal of Clinical Investigation, Paul Tempst and colleagues from Memorial Sloan-Kettering Cancer Center examined the peptides present in serum samples from patients with advanced prostate, bladder, or breast cancer, as well as from healthy individuals and identified certain peptides that were cancer-type–specific markers. These peptides proved to be enzymatic breakdown products generated after the blood was collected from the patients. Previously thought to be "biological trash", this study instead highlights that small peptides identified in human serum may in fact be "diagnostic gold" and serve as easily identifiable disease biomarkers.
In an accompanying commentary, Lance Liotta and Emanuel Petricoin from George Mason University stress that, "the impact of these results on cancer biomarker discovery efforts is significant." They explain that currently, following blood collection, it is standard practice for enzyme inhibitors to be added to the blood to suppress enzymatic breakdown. The report from Tempst et al. now suggests that this suppression may in fact be preventing the generation of biomarkers that hold great promise in the detection of disease - in this case prostate, bladder or breast cancer.
TITLE: Differential exoprotease activities confer tumor-specific serum peptidome patterns
Memorial Sloan-Kettering Cancer Center, New York, New York, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=26022
TITLE: Serum peptidome for cancer detection: spinning biologic trash into diagnostic gold
Lance A. Liotta
George Mason University, Manassas, Virginia, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=27467
How chromosomal leap frog causes cancer in B cells
MALT lymphoma is a cancer of B cell lymphocytes that usually develops in lymphatic tissues in the stomach, thyroid, lungs or eyes. At least 3 different chromosomal translocations – where parts of chromosomes are interchanged – have been implicated in the development and progression of MALT lymphoma. In a study appearing in the January 4, 2006 issue of the Journal of Clinical Investigation, Xiaolu Yang and colleagues from University of Pennsylvania School of Medicine, show how a chromosomal translocation that results in fusion of the cIAP2 region on chromosome 11 with the MALT1 gene on chromosome 21, contributes to MALT lymphoma. In an accompanying commentary, Francesco Bertoni and Emanuele Zucca from the Oncology Institute of Southern Switzerland, delve deeper into the molecular consequences of this most common chromosomal translocation in MALT lymphoma, explaining how the resulting fusion product can act as an oncogene.
TITLE: cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=25641
TITLE: Delving deeper into MALT lymphoma biology
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
View the PDF of this article at: https://www.the-jci.org/article.php?id=27476 DERMATOLOGY
Getting to the root of human hair follicle stem cells
In a study appearing in the January 4, 2006 issue of the Journal of Clinical Investigation, Jonathan Vogel and colleagues from the National Cancer Institute successfully isolated and characterized genes expressed by human hair follicle stem cells. The isolation, cultivation, and propagation of these stem cells are important for tissue-engineering approaches to treating disorders of the hair and skin.
Stem cells in the skin and hair follicles are the ultimate source of cells that regenerate the skin and the growth of new hairs. Vogel and colleagues used sophisticated techniques to engraft human scalp tissue onto mice and then isolated and examined living human hair follicle stem cells. The authors identified a panel of marker proteins expressed on the surface of these elusive cells that can be used in future research to aid in their identification. They go on to note important differences between mouse and human stem cell markers.
In an accompanying commentary, George Cotsarelis from University of Pennsylvania School of Medicine, discusses the importance of these results: "investigators can now readily extract and study very specific follicular cell types for the ability to regenerate hair and skin, with the hope of developing novel methods for treating skin and hair disease."
TITLE: Characterization and isolation of stem cell–enriched human hair follicle bulge cells
Jonathan C. Vogel
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=26043
TITLE: Gene expression profiling gets to the root of human hair follicle stem cells
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA Phone: 610-902-2400;
E-mail: firstname.lastname@example.org. View the PDF of this article at: https://www.the-jci.org/article.php?id=27490
Transplantation patients: enigmas or chimeras?
University Hospital Zurich researchers have determined a way in which to prevent the harmful immune response to newly transplanted organs, which can lead to organ rejection. The study appears in the January 4, 2006 issue of the Journal of Clinical Investigation.
Transplantation medicine is potentially useful in treating a variety of diseases, but the need for life-long suppression of the immune response limits the usefulness of this therapeutic approach. Strategies have been previously designed to try and eliminate the recipient's immune response to the transplanted material, however this apparent tolerance seldom persists for long periods of time. Rare cases of acceptance of transplanted material after patients have discontinued use of immunosuppressive drugs have been observed and this is often the result of what is known as macro- or microchimerism – where greater than or less than 1% of donor cells are found in the recipients blood, respectively. For stable graft acceptance to occur, the recipient's T cells must remain unresponsive to the transplanted material over the long term.
In this new study, Weldy Bonilla and colleagues investigated whether persistence of donor cells is the cause or consequence of long-lasting T cell unresponsiveness. They show that when less than 1% of donor cells were found in the blood of graft recipients, graft-specific T cells were not present and donor cell–specific T cell unresponsiveness was long-lasting. The results suggest that inducing donor cell microchimerism at the time of solid organ transplantation may be beneficial for transplant recipients.
TITLE: Microchimerism maintains deletion of the donor cell–specific CD8+ T cell repertoire
Weldy V. Bonilla
Prionics AG, Zurich, Switzerland.
Phone: +41-44-200-21-28; Fax: +41-44-200-20-10;
View the PDF of this article at: https://www.the-jci.org/article.php?id=26565
Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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