Posts Tagged ‘control’

Rare stem cells hold potential for infertility treatments

Researchers studying infertility in mouse models found that, unlike similar types of cells that develop into sperm, the stem cells that express PAX7 can survive treatment with toxic drugs and radiation. If the findings hold true in people, they eventually could lead to new strategies to restore or protect fertility in men undergoing cancer treatment.

“Unfortunately, many cancer treatments negatively impact fertility, and men who receive such treatments are at high risk of losing their fertility. This is of great concern among cancer patients,” said Dr. Diego H. Castrillon, Associate Professor of Pathology and Director of Investigative Pathology. “The PAX7 stem cells we identified proved highly resistant to cancer treatments, suggesting that they may be the cells responsible for the recovery of fertility following such treatments.”

Infertility, which the Centers for Disease Control estimates affects as many as 4.7 million men in the United States, is a key complication of cancer treatments, such as chemotherapy and radiation therapy.

The new findings, presented in the Journal of Clinical Investigation, provide valuable insight into the process of sperm development. Known as spermatogenesis, sperm development is driven by a population of “immature” stem cells called progenitors in the testes. These cells gradually “mature” into fully differentiated sperm cells. Dr. Castrillon and his team tracked progenitor cells that express the protein PAX7 in mouse testes, and found that these cells gradually give rise to mature sperm.

“We have long known that male fertility is driven by rare stem cells within the testes, but the precise identity of these stem cells has been disputed,” said Dr. Castrillon, who holds the John H. Childers, M.D. Professorship in Pathology. “Our findings suggest that these rare PAX7 cells are the key cells within the testes that are ultimately responsible for male fertility.”

Importantly, even after exposure to toxic chemotherapy or radiation treatments, the PAX7-expressing cells continued to divide and thus could contribute to restoring sperm development.

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Is the HPV vaccine necessary?

“I often have parents ask me if their child should get the HPV vaccine and what are my thoughts about giving it. Some parents are concerned it will promote sexual activity, others think it is unnecessary and others think their child is too young. If the child falls between the recommended ages given by the American Academy of Pediatrics I strongly recommend the vaccination. It really could be the difference between life and death,” said Hannah Chow-Johnson, MD, pediatrician at Loyola University Health System and assistant professor in the Department of Pediatrics at Loyola University Chicago Stritch School of Medicine.

According to Chow there are only two shots that can prevent cancer. One is hepatitis B and the other is the Human Papilloma Virus (HPV) vaccine. HPV is the most common sexually transmitted disease and is known to cause several different types of cancer, including cervical cancer, which is the second leading cancer-cause of death in women.

“Parents need to take into consideration the anti-cancer benefits when considering if they want their child to receive the HPV vaccine,” said Chow.

According to the Centers for Disease Control and Prevention there are more than 20 million people in the U.S. infected with HPV and at least half of these are between the ages of 15-25.

HPV is transmitted through intercourse and genital contact. Both men and women can harbor the virus, which can remain in a person for years after the initial infection.

“One of the scary aspects of HPV is that a person can be infected and not even know it. He or she may have no symptoms at all and still be spreading the virus,” Chow said. “This is why I strong believe in vaccinating males and females early, well before any exposure takes place.”

Prevention is critical when it comes to HPV. According to Chow the vaccine’s protection rate is 93 percent when given before any exposure. After exposure the vaccine doesn’t treat pre-exiting viruses but will help protect against future exposure.

“HPV is a very dangerous virus that can lead to death. Since there is no cure, prevention is all the more important. This vaccine could save the life of your child,” Chow said.

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Study identifies protein that helps prevent active tuberculosis in infected patients

The discovery could help doctors identify people who are at the greatest risk for the highly contagious and potentially fatal lung disease, and it could point the way toward new treatment strategies for TB.

The study, conducted in partnership with researchers from Harvard University School of Public Health and the University of Michigan School of Medicine, was published in the Aug. 20 online edition of the journal Science Translational Medicine.

The findings underscore the importance of maintaining sufficient levels of vitamin D to effectively combat the pathogen that causes TB. The researchers found that the protective protein, interleukin-32, can induce the killing of the TB bacterium only in the presence of sufficient levels of vitamin D.

An estimated one-third of the world’s population is infected with tuberculosis, but the disease is latent in 90 to 95 percent of infected people, meaning that they experience no symptoms and are not contagious. Interleukin-32 contributes to maintaining that latent state and preventing active infection. In 2012, nearly 9 million people worldwide became sick with TB and there were 1.3 million TB-related deaths, according to the U.S. Centers for Disease Control and Prevention.

A new urgency for developing new approaches to identify individuals at risk, maintain immunity and treat active disease has arisen in recent years as TB has re-emerged as a global health threat — thanks in part to the rise of extremely drug-resistant bacteria. “Until now, there had been no way to predict, based on biological factors, why latently infected individuals do not develop active tuberculosis,” said Dennis Montoya, a postdoctoral scholar in the division of dermatology at the David Geffen School of Medicine at UCLA and the study’s lead author. “We were surprised to find many differences between people with latent TB and healthy people, suggesting that people with latent TB may have activated immune systems that are protecting them from developing active infection.” In people with active TB, the disease-causing bacteria have overcome the defenses of the immune system, causing symptoms to develop in the lungs. Previous studies have focused on finding biological markers of disease progression in those patients. The new study, however, was the first to look for markers of protection in the blood of people with latent TB — those who are infected but have not developed symptoms.

The researchers analyzed gene expression profiles of hundreds of TB patients in four countries, as well as evaluating genes from activated immune cells shown in the laboratory to have the ability to kill the TB bacteria. They discovered that in people who were infected with TB but had higher levels of interleukin-32 (IL-32), the disease was more likely to be latent, and that — in laboratory experiments — IL-32 was able to stimulate the immune system to kill TB-causing bacteria, but only in the presence of sufficient vitamin D levels.

Vitamin D is produced in the skin upon exposure to sunlight, but approximately one-third of American adults — particularly members of ethnic minorities with darker-pigmented skin and lighter-skinned people who receive minimal sun exposure — lack sufficient levels of vitamin D, and vitamin D deficiency has been found to be associated with a higher risk for active TB.

“When vitamin D levels were low, IL-32 was not able to kill the bacteria,” said Dr. Robert Modlin, the Klein Professor of Dermatology at UCLA and the study’s senior author. “However, if we simulated the effect of supplementing individuals by adding vitamin D to the culture of the activated immune cells that had low vitamin D levels, IL-32 regained its ability to kill. Our findings suggest that raising standards for daily intake of vitamin D could help to protect against a TB pandemic.”

Further studies are needed to determine if vitamin D supplementation helps prevent TB. But Modlin, a dermatologist, favors oral supplementation rather than increased sun exposure, which can increase the risk of skin cancer.

Although TB remains a leading killer in many parts of the world, the incidence of the disease has been declining in the U.S. since a resurgence that peaked in 1992, according to the CDC. A total of 9,945 cases were reported in 2012, and 569 people died from the disease in 2010, the most recent years for which U.S. data are available. In the U.S., unlike in many poorer countries, patients known to have latent TB infections are typically treated with antibiotics to prevent progression to the active disease. But strains of the tuberculosis bacteria are becoming resistant to the antibiotic drugs, increasing the threat of a multidrug-resistant TB pandemic that could affect the U.S.

“Our current strategy of antibiotic therapy, as well as methods of identifying which patients will develop severe disease, have remained essentially unchanged for decades,” said Harvard’s Barry Bloom, the study’s co-author. “Our findings of specific markers in the blood that can tell us which people are at risk can help countries focus limited resources on patients who have lower levels of this protein. In addition, this may point the way to new treatments for a disease that greatly needs them.”

The research builds on the team’s previous work that found that vitamin D is important for killing TB bacteria.

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