Immune Cell Function Can Be Suppressed By Leading Pathogen In Newborns

Group B Streptococcus (GBS), a bacterial pathogen that causes sepsis and meningitis in newborn infants, is able to shut down immune cell function in order to promote its own survival, according to researchers at the University of California, San Diego School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. Their study, published online July 13 in the Journal of Experimental Medicine, offers insight into GBS infection - information that may lead to new medical therapies for invasive infectious diseases that affect nearly 3,500 newborns in the United States each year.



The UC San Diego researchers describe how GBS fools the immune system into reducing production of antibiotic molecules. "We have discovered that the bacteria have evolved to use a trick we call 'molecular mimicry,'" said Victor Nizet, MD, UC San Diego professor of pediatrics and pharmacy. "Like a wolf in sheep's clothing, GBS can enter our body without activating the immune cells that are normally programmed to kill foreign invaders."



The findings represent a collaborative effort between the laboratories of senior authors Nizet and Ajit Varki, MD, distinguished professor of medicine and cellular and molecular medicine. Varki is also co-director of the UCSD Glycobiology Research and Training Center, where the investigators have been exploring the interaction of bacterial pathogens with the innate immune system. Their most recent focus has been on the special role of Siglecs (short for sialic acid binding Ig-like lectins), members of the immunoglobulin family of antibodies.



Siglecs sense a chemical structure known as sialic acid - a sugar molecule that is abundant on the surface of all human cells - and send signals that control the gene expression and function of immune cells. Many specialized Siglecs receptors send negative signals, recognizing sialic acids as "self." These signals help keep the immune cells turned off under baseline conditions, avoiding unnecessary inflammation in the absence of infection or injury. Earlier this year, in a manuscript published in the journal Blood, the same UC San Diego team demonstrated that GBS decorates its own surface with sialic acid, closely resembling human molecules, and is thus able to bind Siglecs on immune cells, shutting down the cells' normal functions.



In the new study, the researchers discovered that GBS can also bind a human Siglecs receptor through a particular protein expressed on the bacterial surface. This is the first time a protein has been reported to functionally interact with Siglecs, and presents the possibility that additional pathogenic microbes may have evolved similar ways to manipulate the human immune system.



According to the study's lead author, Aaron Carlin, MD, PhD, when GBS proteins bind to Siglecs, it profoundly affects immune-cell function by decreasing its ability to engulf the bacteria, a process known as phagocytosis.
















"The immune cells reduce their production of antibiotic molecules, allowing the GBS bacteria to survive the encounter and proliferate," said Carlin, who recently completed his doctoral studies in UC San Diego's Medical Scientist Training Program.



Knowledge of the mechanisms by which crafty pathogens engage Siglec receptors to fool the immune system may reveal new targets for medical therapy. "Blocking engagement of the Siglec could help boost the immune system and aid in clearing GBS infection in the critically ill newborn," said Nizet. "Alternatively, perhaps the bacterial molecule could be exploited as a novel treatment for human diseases involving abnormal inflammation, for example, rheumatoid arthritis."



Siglecs are among the most rapidly evolving parts of the human genome. This suggests that strong natural selection pressures are present to modify their expression, according to Varki, with pathogenic microbes likely playing a critical role.



"There are important variations in Siglec expression and function between humans and other species, among human populations, and across the age spectrum. Evidence is accumulating that Siglecs may profoundly affect susceptibility or resistance to several important infectious diseases," said Varki.



According to the UC San Diego researchers, the new study likely has broad implications for understanding the propensity of certain bacterial pathogens to produce human disease. It also explains why some individuals or groups may be more predisposed to suffer more severe outcomes than others.



Approximately 20 to 25 percent of women of childbearing age are asymptomatic carriers of GBS on their vaginal mucosal surface. Newborns can become infected with GBS that invade through the placenta to initiate infection in the womb, or during delivery by exposure to contaminated vaginal fluids. Screening of pregnant women for GBS and antibiotic prophylaxis during labor is used to reduce the risk of newborn transmission, yet it estimated that approximately 3,500 newborns still develop invasive GBS infections annually in the United States. In addition to neonatal disease, GBS is increasingly associated with serious infections in adult populations such as pregnant women, diabetics, and the elderly.



This study was financed by grants from the National Institutes of Health. Co-authors contributing to the study were Yung-Chi Chang, PhD and Charles King, PhD, of the UCSD Department of Pediatrics; Nancy Hurtado-Ziola, PhD of the UCSD Department of Cellular and Molecular Medicine, and Thomas Areschoug, PhD, and Gunnar Lindahl, PhD, of Lund University in Sweden.



Source:
Debra Kain


University of California - San Diego

More Support For GP Obstetricians In Rural Areas, Australia

The Australian Government will further improve incentives for GPs providing obstetric services in rural and remote areas.


At present, GPs in some larger rural communities who deliver 20 or more babies per year, or GPs in smaller communities who meet the obstetric requirements of their community, are eligible for an annual bonus procedural payment under the Government's Practice Incentive Program.


The bonus was significantly increased earlier this year. It is comprised of an incentive payment of up to $17,000 per year, with an additional loading depending on rurality. In total these doctors can receive up to $25,500 per annum.


The Government has decided to again improve eligibility by including another category of those GPs who are fully participating in the obstetric roster of the local community. This means that those GPs who may not meet the requirement of delivering 20 babies per year, but are fully involved in the local obstetric roster, may be eligible for a payment.


This change will help maintain access to obstetric services for rural and regional women.


Details about the qualification criteria and payment level will be finalised in consultation with the profession. Information will be provided to rural and remote GPs in the near future.


www.health.au

Persistent Genital Arousal In Women, Doctors Uncover New Syndrome

Doctors have identified a new sexual condition affecting women. Tentatively labelled Persistent Sexual Arousal Syndrome, its primary symptom is relatively constant, unrelieved feelings of genital arousal in the absence of genuine sexual interest or desire.


Writing in the International Journal of STD & AIDS [published by the Royal Society of Medicine], David Goldmeier and Sandra Leiblum said PSAS in women had been unrecognised until now.


"Persistent sexual arousal syndrome occurs when a woman becomes involuntarily aroused for extended periods of time in the absence of sexual desire," said Dr Goldmeier.


"This genital arousal is highly distressing as it is unprovoked and unrelieved by orgasm," he said.


The study said it was unclear what the causes of PSAS were although a link to antidepressants has not been ruled out. Clinical observations of the condition have found evidence of engorgement and oedema of the labia, vulva and clitoris.


"Due to the reluctance of women to come forward we are unsure how common the problem is," said Dr Goldmeier.



"Many women feel embarrassed to talk about the symptoms and those that have come forward have reported a high degree of distress and even sometimes, suicidal thoughts," he said.


A recent internet survey by Dr Leiblum suggests women with PSAS come from a range of backgrounds and age groups.


"Much remains to be elucidated in regard to PSAS including its prevalence, aetiology and management," they write.


"It deserves continued research not only since it is such a distressing and perplexing condition, but also because understanding its aetiology and treatment may lead to greater understanding of other aspects of female sexual response."


Although there is no specific therapy to treat PSAS, Dr Goldmeier has been working with affected women in the UK.


"It is critical that we raise awareness of persistent sexual arousal syndrome amongst clinicians and the general population," said Dr Goldmeier.


"Women should not feel marginalised by this condition and I urge them to seek assistance," he said.


Persistent genital arousal in women - a new syndrome entity [PDF 45k]


'Persistent genital arousal in women - a new syndrome entity' by D Goldmeier and S Leiblum is published in the April issue (Vol. 17) of the International Journal of STD and AIDS.


IJSA is published monthly by the Royal Society of Medicine. Its Editor is Professor Wallace Dinsmore.


ROYAL SOCIETY OF MEDICINE

New Findings May Change The Way Heart Disease Is Detected And Treated In Women, From The 'Harvard Women's Health Watch'

Results of a landmark study
suggest that many women with heart disease don't get a proper diagnosis
because they have a form of the disease that doesn't show up on the usual
diagnostic tests. The new research shows that heart disease is not one but
several disorders and may shed light on why heart disease often behaves
differently in men and women, according to the February 2007 issue of
"Harvard Women's Health Watch."


In the Women's Ischemia Syndrome Evaluation (WISE) study, women with
chronic chest pain underwent standard diagnostic procedures, including
stress tests and coronary angiograms. Earlier studies had found that among
people who show signs of trouble on stress tests, women are far more likely
than men to appear free of blockages on follow-up angiograms. This was also
true in the WISE study. But newer tests, including ultrasound of the blood
vessels, revealed heart problems the angiograms didn't pick up. Many of
these women had a condition called vascular dysfunction, in which the blood
vessels supplying the heart don't expand properly to accommodate increased
blood flow. Vascular dysfunction may affect not only the large coronary
arteries, but also the smaller vessels that serve the heart -- a problem
dubbed microvessel disease.



The WISE results may help explain why women with heart disease are
often underdiagnosed and undertreated. In men, the main problem may be a
blockage in a large coronary artery, which shows up on an angiogram, while
women are more likely to have microvessel disease that can't be seen. With
this in mind, the WISE investigators are working to develop a new system
for screening women for heart disease.



Harvard Health Publications

health.harvard.edu/women

For African-American Women On Hemodialysis, Social Support, Psychological Factors Contribute To Fatigue

African Americans account for approximately 32% of patients diagnosed with ESRD, more than any other racial group in America. While fatigue is a common side effect for ESRD patients, studies have not explored factors contributing to fatigue, especially among African American women with ESRD. In the November-December 2007 issue of Nephrology Nursing Journal, Amy G. Williams, MSN, RN, and co-authors explored physiologic (anemia, uremic malnutrition), psychological (mood disorders) and situational factors (social support) contributing to fatigue in this group in hopes of developing life-improving interventions.



The authors found a correlation between social support and uremic malnutrition; this lack of support can lead to noncompliance in dietary requirements, which in turn leads to fatigue. In addition, Williams and co-authors found correlations between anxiety, depression and fatigue.



The authors recommend further research examining the effect of social support and psychological factors on fatigue. For nephrology nurses, understanding the causes of fatigue in African American Women on hemodialysis will help focus assessments and individualized care plans for this patient population.


Fatigue in African American Women on Hemodialysis
Amy G. Williams, MSN, RN; Patricia B. Crane, PhD, RN, FAHA; Daria Kring, MSN, RN, BC
Nephrology Nursing Journal; November-December 2007
annanurse/journal



Nephrology Nursing Journal is a refereed clinical and scientific resource that provides current information on a wide variety of subjects to facilitate the practice of professional nephrology nursing. Its purpose is to disseminate information on the latest advances in research, practice, and education to nephrology nurses to positively influence the quality of care they provide. For more information, visit annanurse/journal.

Fatty Fish Consumption Associated With Lower Risk Of Kidney Cancer In Women

Preliminary research suggests that higher consumption of fatty fish in women is linked with a lower risk of renal cell carcinoma, a common form of kidney cancer, according to a study in the September 20 issue of JAMA.


Renal cell carcinoma (RCC) involving the renal parenchyma (the functional tissue of the kidney) accounts for more than 80 percent of all kidney cancers. Renal cell carcinoma incidence rates in the United States had been increasing in 1970-1990s, especially among black women and men; more recent data suggest a leveling off in this trend for most racial groups. The evidence that fish consumption, especially fatty fish, may be associated with lower risk of several cancers has not been consistent, according to background information in the article.


Previous studies have analyzed total fish consumption and have not taken into account that there are large differences between fatty fish and lean fish in the content of omega-3 fatty acids and vitamin D. Marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaneoic acid, which are present in significant amounts in fatty cold-water fish (up to 20-30 times higher content than in lean fish), have been reported to slow the development of cancer. Fatty fish has 3 to 5 times higher content of vitamin D than lean fish, and lower serum vitamin D levels have been associated with development and progression of RCC.


Alicja Wolk, D.M.Sc., of the Karolinska Institutet, Stockholm, Sweden and colleagues investigated the association between fatty fish and lean fish consumption and the risk for development of RCC in a population with a relatively high consumption of fatty fish. The participants, from the Swedish Mammography Cohort, included 61,433 women age 40 to 76 years without previous diagnosis of cancer at baseline (March 1987 to December 1990). Participants filled in a food frequency questionnaire at baseline and in September 1997. The researchers considered fatty fish to include salmon, herring, sardines, and mackerel; lean fish included cod, tuna, and sweet water fish; and other seafood included shrimp, lobster, and crayfish.


During an average of 15.3 years of follow-up between 1987 and 2004, 150 RCC cases were diagnosed. After adjustment for potential confounders, an inverse association of fatty fish consumption with the risk of RCC was found, while no association was found with the consumption of lean fish or other seafood.


"In this large population-based cohort with data on long-term diet, we found that women who consumed one or more servings of fatty fish per week had a statistically significant 44 percent decreased risk of RCC compared with women who did not consume any fish. Women who reported consistent long-term consumption of fatty fish at baseline and 10 years later had a statistically significant 74 percent lower risk," the authors write.


"Our results support the hypothesis that frequent consumption of fatty fish may lower the risk of RCC possibly due to increased intake of fish oil rich in eicosapentaenoic acid and docosahexaneoic acid as well as vitamin D," they write. "Our results, however, require confirmation because this is the first epidemiological study addressing this issue."


Editor's Note: This study was supported by grants from the Swedish Cancer Foundation, the Swedish Research Council/Longitudinal Studies, and V?stmanland County Research Fund Against Cancer. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.


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Trust For America's Health Releases Report On Connection Between Women's Health And Stalled Infant Mortality Rates

Trust for America's Health (TFAH) released a report, Healthy Women, Healthy Babies, in conjunction with the release of the Annie E. Casey Foundation's KIDS COUNT DATABOOK 2008. The report explains why after 40 years of progress, infant mortality rates in the U.S. have stalled since 2000. TFAH finds that the deteriorating health of American women, due in part to wide-spread chronic disease epidemics like obesity and diabetes, is taking a toll on American infants, resulting in stagnated improvement when it comes to infant health. TFAH's report offers recommendations for Congress and the American health system to aggressively improve the health of new-born infants.


"In the wake of all the great medical breakthroughs over the last 40 years, one would assume that infant mortality rates would plummet. Instead, medical progress has been cancelled out in the delivery room by the deteriorating health of childbearing-aged women and their lack of health care access; and infant mortality rates have stalled as a result," said Jeff Levi, Executive Director of Trust for America's Health. "American women, children and families simply deserve better."


Levi added, "We know now that an infant's chances of sickness, disability and survival often hinge on the health of the mother, before she even becomes pregnant. Therefore, the way to reduce risks to new born babies is to invest in a woman's health throughout her childbearing years. If we concentrate our efforts most on those hit hardest by the biggest health problems - low-income and minority women - we will once again see healthier babies and dropping infant mortality rates."


"Two of the most disturbing trends in our 2008 KIDS COUNT Data Book that we are releasing today are the increase in the rate of low-birthweight babies and the lack of progress in infant mortality," said Laura Beavers, coordinator of the national KIDS COUNT project at the Annie E. Casey Foundation. "The Trust for America's Heath's report, Healthy Women, Healthy Babies provides us with the information we need to turn this around and to begin to once again see steady progress on both of these critical indicators."


Healthy Women, Healthy Babies reports that approximately 30 percent of women who give birth have some form of pregnancy complication, which cost the U.S. at least $26.2 billion in 2005. Prematurity and low birth weights are often associated with health issues in the mother, such as diabetes, high blood pressure, or obesity. Many experts now believe that because the early weeks after conception are critical to a baby's development, traditional prenatal care, which usually begins in the first three months of a pregnancy, comes too late to prevent many serious maternal and child health problems. The way to ensure infant mortality rates resume their fall is to assure that all women are insured and have access to primary care. If we improve the health of all women aged 15-44 and execute earlier interventions for those with chronic health conditions and risks, we will also see better birth outcomes.















KEY RECOMMENDATIONS OF Healthy Women, Healthy Babies, which were drawn from interviews and comments from 10 leading experts in maternal and child health, include:



-- Fully Implement and Enhance Medicaid Policies.

- Assuring better health coverage for poor women through state expansion of Medicaid coverage. States should have the authority to cover women without a federal waiver and allow Medicaid benefits to follow women after the birth for 24 months. Both changes would significantly reduce infant mortality.


-- Expand Other Programs that Provide Primary Care and Other Services to Women of Childbearing Age.


- Federal programs like the Healthy Start Infant Mortality Reduction Program, Community Health Centers, Title X Family Planning and Title V Maternal and Child Health Block Grant need better funding to reach all those at risk.


-- Make Research on Preconception Health and Health Care a Priority.


- Research needs to be jump-started through increased funding at organizations like the Centers for Disease Control's National Center on Birth Defects and Developmental Disabilities, the National Center for Chronic Disease Prevention and Health Promotion, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.


Healthy Women, Healthy Babies was supported by a grant from the Annie E. Casey Foundation.



Trust for America's Health is a non-profit, non-partisan organization dedicated to saving lives by protecting the health of every community and working to make disease prevention a national priority. healthyamericans.


The Annie E. Casey Foundation is a private charitable organization, whose primary mission is to foster public policies, human-resource reforms, and community supports that more effectively meet the needs of today's vulnerable children and families. For more information, visit aecf.

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