Boston University Medical Campus
School of Medicine

An international team of researchers from the Boston University Schools of Medicine and Public Health and other institutions has uncovered 13 genetic loci, linked to immune function and DNA repair, that are factors in the age of onset of menopause.

Menopause — the cessation of reproductive function of the ovaries — is a major hormonal change that affects most women when they are in their early 50s. Most prior studies of the age of onset of menopause have focused on genes from the estrogen-production pathway or vascular components.

Kathryn Lunetta

In the new study, published online Jan. 22 in Nature Genetics, a research team led by Kathryn Lunetta, professor of biostatistics at the BU School of Public Health, and Joanne Murabito, associate professor of medicine at the BU School of Medicine, identified 13 novel loci associated with menopause onset, while confirming four previously established loci. Most of the 17 loci are associated with genes related to DNA damage repair or auto-immune disease; others are linked to hormonal regulation.

“Our findings demonstrate the role of genes which regulate DNA repair and immune function, as well as genes affecting neuroendocrine pathways of ovarian function in regulating age at menopause, indicating the process of aging is involved in both somatic and germ line aging” the authors said.

Lunetta said the new findings “bring us closer to understanding the genetic basis for the timing of menopause. They may also provide clues to the genetic basis of early onset or premature menopause and reduced fertility.

“We hope that as a better understanding of the biologic effects of these menopause-related variants are uncovered, we will gain new insights into the connections between menopause and cardiovascular disease, breast cancer, osteoporosis, and other traits related to aging, and that this will provide avenues for prevention and treatment of these conditions,” she said.

According to Murabito, director of the research clinic at the Framingham Heart Study, “It will be important to determine if a genetic variant that directly influences age at menopause also increases risk for later life health conditions, such as breast cancer.”

The authors said they expected further research to identify “a substantial number of additional common variants” that impact age of menopause, and that many of them will be located in genes identified in their study. The study examined more than 50,000 women of European descent who had experienced menopause between the ages of 40 and 60.

The research team noted that a large-scale study of menopause onset in African-American women is underway, which will help to determine whether the genetic variations that affect menopause onset in African-American women are similar or substantially different for women of primarily European descent.

Besides Lunetta and Murabito, senior authors on the study include: Anna Murray, a senior lecturer in genetics at the Peninsula Medical School in Exeter (UK); and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).

The full study is available here: http://www.nature.com/ng/index.html.

Researchers Drs. Jean Bosco Tagne and Maria Ramirez along with collaborators from the Pulmonary Center, BU’s CTSI and the Whitehead Institute for Biomedical Research/MIT, provide novel insights into biological processes regulated by the transcription factor Nkx2-1 in different cell contexts, in early and late development, and in cancer. These findings recently appeared in PLoS ONE.

Maria Ramirez

Jean Bosco Tagne

Nkx2-1 regulates lung, thyroid and brain development; and is a lineage survival oncogene and prognostic factor since high levels of NKX2-1 in tumors correlate with better patient prognosis.

Using a genome-wide approach, the researchers located binding of Nkx2-1 to DNA regulatory regions using a method known as ChIP-chip. They uncovered Nkx2-1 regulatory networks in early and late lung development, and a direct function of Nkx2-1 in regulation of proliferation-related genes. They also showed that developmental targets of Nkx2-1 correlate to the endogenous levels of NKX2-1 in more than ten human non-small cell lung carcinoma data sets. Previous genomic associations between human lung cancer subtypes and developing mouse lung indicated that tumors with genomic profiles similar to early lung development correlate to poorer patient’s prognosis while tumors with gene expression profiles similar to more differentiated lung cell phenotypes correlate to better patient’s prognosis.

“The correlations identified in this work provide a rationale to sub-classify NSCLCs based on NKX2-1 and downstream targets expression patterns, and to understand the mechanisms underlying associations to survival,” explained lead author Bosco Tagne, an assistant professor of medicine at BUSM. “These findings are a substantial addition to the development and cancer fields, and an important foundation for further work in regulatory gene networks,” he added.

Click here to see the entire article.

Although most faculty, staff and students were enjoying the intercession break, work continued on the student residence. Notable progress in major systems includes completed connections to Boston Water and Sewer and National Grid (natural gas). Plumbing, electrical, cable television and security systems have been roughed-in throughout the building. HVAC (heating ventilation air conditioning) is also roughed-in from the second to top floor.

Dry wall work continues

Interior update
All residential floors are in the process of having the interior walls completed. This means that taping, sanding and drywall work is proceeding throughout the structure. Tile work is scheduled to begin at the end of January. The large interior elevator is up and running!

More visible work on the exterior

Exterior view.

Exterior metal work continues on the South East elevation and the South West curtain wall. Work on the ninth level should be completed within the next week with work on the first and second levels continuing. Removal of the temporary exterior elevator begins next week.

The nine-story, $40 million structure is designed by Beacon Architectural Associates with a brick and precast façade. Its 104 two-bedroom suites that include bath, kitchenette and living spaces will accommodate 208 students, each with individual bedrooms, the standard for graduate student housing. Walsh Brothers is the contractor for the building, which is expected to be complete June 2012.

Click here to see recent residence construction news. For a complete listing of student residence news, click here.

A review article by researchers at Boston University School of Medicine (BUSM) debunks the widely-believed concept that hypertension, or high blood pressure, is the result of excess salt causing an increased blood volume, exerting extra pressure on the arteries. Published online in the Journal of Hypertension, the study demonstrates that excess salt stimulates the sympathetic nervous system to produce adrenalin, causing artery constriction and hypertension.

The research was led by Irene Gavras, MD, and Haralambos Gavras, MD, both professors of medicine at BUSM.

Irene Gavras

Haralambos Gavras

“The purpose of this paper is to correct an erroneous concept that has prevailed for many years, even though scientific evidence has mounted against it,” said Irene Gavras, who is also a physician in Boston Medical Center’s Hypertension practice.

The term “volume-expanded hypertension” implies that excess salt leads to the retention of extra fluid within the arterial circulatory system, causing an increase in blood volume and added pressure on the arterial walls. However, research has shown that conditions characterized by the expansion of blood volume from other causes, such as the secretion of antidiuretic hormone or the excessive elevation of blood sugar, do not cause a rise in blood pressure because the extra fluid is accommodated by the distention of capillaries and veins.

“The body’s circulatory system is a highly flexible vascular system with the capacity to open up new capillaries and distend veins in order to accommodate increased fluid volume,” said Irene Gavras.

Through a review of numerous studies, the researchers demonstrated that the mechanism of hypertension resulting from the excessive consumption and retention of salt stimulates the sympathetic nervous system in the brain to increase adrenaline production. The increased adrenalin being circulated throughout the body causes the arteries to constrict, which results in resistance to blood flow and a decrease in circulatory volume.

The over-activation of the sympathetic nervous system – part of the autonomic nervous system that helps maintain the body’s homeostasis – has been recognized clinically as a characteristic of hypertension that accompanies renal failure, which is the most typical example of elevated blood pressure from excessive salt retention. Diuretics, which remove excess salt, are widely used to treat this type of hypertension. However, this study provides convincing evidence that the sympathetic nervous system should be the focus of further investigations into treatments for hypertension.

“The implication of our findings shows that the optimal treatment for hypertension, for cases associated with renal failure, should not only include diuretics but also the use of drugs that block the central sympathetic nervous system,” said Irene Gavras.

This research was supported by a series National Institutes of Health (NIH) grants.

Jeffrey H. Samet, MD, MA, MPH, a professor of medicine and community health sciences at BUSM and BUSPH, has been installed as the president of the American Board of Addiction Medicine (ABAM) and The ABAM Foundation. Samet will serve in this volunteer position for two years. In this role he will lead ABAM in the formal certification of physicians as experts in addiction medicine, establish and accredit physician post-graduate addiction medicine training programs, and thus advance the quality of medical care for substance use disorders related to alcohol, tobacco and other addicting drugs, including some prescription medications.

Jeffrey Samet

ABAM is an independent medical specialty board established in 2007 to certify addiction medicine physicians from several specialties, including emergency medicine, family medicine, internal medicine, obstetrics and gynecology, pediatrics, preventive medicine, psychiatry and others. Prior to ABAM’s formation, only one medical specialty (psychiatry) offered sub-specialized training and certification in addiction.

“Addiction medicine is a unique field, encompassing elements of a range of medical specialties that come into contact with patients with addictive disorders,” explained Samet. “We want addiction prevention, screening, intervention and treatment to become routine aspects of medical care wherever health care is provided. ABAM-certified physicians will also be able to address common medical or psychiatric conditions related to the use of addictive substances.”

The Faculty Staff Assistance Office (FSAO) is now open on the Boston University Medical Campus. FSAO provides University employees with free and confidential counseling and referrals for personal or work-related issues. Bonnie Jean Teitleman directs the office and Karen Brouhard, a FSAO counselor with clinical interests that include interpersonal violence and autism spectrum disorders, works with her on the Medical Campus.

Karen

Bonnie

“There are many stresses that occur in people’s lives that can interfere with job performance,” says social worker Brouhard. FSAO is available to speak with employees on a variety of issues spanning from depression to substance abuse, to domestic violence, to relationship and family issues as well as work issues including conflict, performance, change, morale and leadership.

Click here to visit the FSAO website and to learn more about the services they provide. The Medical Campus office is located in the Solomon Carter Fuller Mental Health Center, 85 E. Newton Street, M-809. For more information or to make an appointment call (617) 353-5381, email or complete an online form.

In the United States, the cost paid for statins (drugs to lower cholesterol) in people under the age of 65 who have private insurance is approximately 400 percent higher than comparable costs paid by the government in the United Kingdom (U.K.). These findings, from the Boston University School of Medicine (BUSM) Boston Collaborative Drug Surveillance Program, are the first results of a comprehensive comparison of prescription drug costs between the U.S. and U.K. The study appears on-line in the journal Pharmacotherapy.

Expenditures for prescription drugs remain a large part of the ongoing debate on the costs of medical care in the U.S. and U.K. Because of the many complex and interactive variables that contribute to these costs, well-defined estimates of the actual and relative usage and costs for the two countries have not been reliably documented.

Data for this study came from two large electronic medical databases, one in each country. Costs were derived from private health insurance claims in the U.S., while the costs were originated from a general practice research database constructed in 1990 in the U.K.

The study is based upon a 2005 sample of 280,000 people age 55-64 in each country. Statins were prescribed to an estimated 32.7 percent of people in the U.S. and 24.4 percent in the U.K. In the U.S. the estimated annual cost of statins ranged from a high of $1,428 for simvastatin (generic unavailable), to a low of $314 for lovastatin (available in generic formulation). In the U.K. the annual cost varied from a high of $500 for atorvastatin (generic not available), to a low of $164 for simvastatin (available in generic). The estimated cost per pill was at least twice as high for each statin prescribed in both countries.

When the annual cost for each annual statin user together with the number of users were combined, the total estimated cost for statin users was $69.5 million in people covered by private insurance companies in the U.S. The total estimated annual cost for statin users covered by the government in the U.K. was $15.7 million.

Hershel Jick

“In addition to differences in overall statin use and per unit costs, another significant factor contributing to the disparity of costs appears to be the availability and utilization of generics,” said lead author Hershel Jick, MD, Director Emeritus of BUSM’s Collaborative Drug Surveillance Program and associate professor of medicine at BUSM.

According to the researchers, simvastin was approved in the U.S. for sale in generic formulation in late June 2006. Accordingly, within the next six months more than 60 percent of users switched from the brand preparation to the generic. The resultant estimated cost was reduced more than 60 percent. According to the researchers, however, it still was four times higher than that in the U.K.

BUSM’s Boston Collaborative Drug Surveillance Program was established in 1966. It was the first group to conduct formal epidemiologic research to quantify the potential adverse effects of prescription drugs utilizing in-hospital monitoring and had a pioneering role in the development and application of methods in drug epidemiology.

A team of scientists from Boston University School of Medicine (BUSM) have identified a novel compound that inhibits viruses from replicating. The findings, which are published online in the Journal of Virology, could lead to the development of highly targeted compounds to block the replication of poxviruses, such as the emerging infectious disease Monkeypox.

John O'Connor

The basic research was led by Ken Dower, PhD, a postdoctoral fellow in the laboratory of John Connor, PhD, assistant professor of microbiology at BUSM who is corresponding author on the paper. They worked with Scott Schaus, PhD, associate professor of chemistry from the Boston University College of Arts & Sciences and co-principal investigator in the Center for Chemical Methodology and Library Development (CMLD). The researchers collaborated with the United States Army Medical Research Institute for Infectious Diseases (USAMRIID), who conducted the experiments involving Monkeypox at their laboratory in Maryland.

Poxviruses, such as smallpox, vaccinia virus and the Monkeypox virus, invade host cells and replicate, causing disease. Smallpox, a deadly poxvirus that killed hundreds of millions of people worldwide, was declared eradicated by the World Health Organization in 1979 after successful vaccination efforts. Recent data shows that the number of people being infected by Monkeypox is increasing globally.

Utilizing state of the art screening techniques, vaccinia and a library of chemicals from CMLD, Dower and his colleagues looked for compounds that could stop vaccinia from replicating inside human cells. They identified several. In studying how one of these compounds work, they discovered that the virus can enter the cell in its presence, but once the virus was inside, the compound inactivates an essential piece of virus machinery.

USAMRIID researchers then tested the efficacy of the chemical compound on the Monkeypox virus. Their experiments demonstrated similar results, showing that this chemical compound has the ability to inhibit different varieties of poxviruses.

“The compound we identified forces the catastrophic failure of the normal virus amplification cycle and illustrates a new drug-accessible restriction point for poxviruses in general,” said Connor. “This can help us in developing new compounds that fight poxviruses infection.”

This research was funded by the National Institutes of Health (NIH) and the U.S. Department of Defense’s Defense Threat Reduction Agency (DTRA).

The inclement weather of winter will be upon us soon and construction on the student residence is keeping pace by meeting major milestones.

Dry wall in progress. View from living area into two-bedroom apartment.

By Dec. 24 all window installation in the residential portion of the building will be completed. Temporary electrical power will be initiated by Dec. 30 allowing general building services such as heat and elevator to be operational. The interior elevator installation is nearly done and should be available to tradespeople by the end of December. This means that the exterior lift will be removed mid-January.

Progress on the exterior of the student residence.

Drywall work is scheduled for all floors of the residence with the second, third and sixth floors well underway. The fourth and fifth floors are nearly done with final taping and sanding in process.

Metal work on the exterior façade continues on the south east elevation and the south west curtain wall.

The nine-story, $40 million structure is designed by Beacon Architectural Associates with a brick and precast façade. Its 104 two-bedroom suites that include bath, kitchenette and living spaces will accommodate 208 students, each with individual bedrooms, the standard for graduate student housing. Walsh Brothers is the contractor for the building, which is expected to be complete June 2012.

Click here for other recent news on the student residence construction.

The BUSM Outreach Van Project is sponsoring a Warm Winter Accessory and Toiletry Drive! Do you have extra hats, gloves, and scarves at home? Leftover toiletries from holiday hotel stays? OVP will be distributing warm winter accessories and toiletries to homeless and needy clients and families in East Boston this winter.

Help support their Warm Winter Accessories and Toiletry Drive by donating

• NEEDED: Winter hats, gloves, scarves, earmuffs AND unused toiletries (shampoo, soap, deodorant).
• WHEN? Jan. 3-6.
• WHERE? BUSM 1st floor hallway, left at the lobby on the way to Bakst Auditorium.
• WHY? To help the homeless of East Boston stay warm this winter!

Questions? Contact Nicole Economou, chair of OVP PR Committee, ne2125@bu.edu or 631-748-0561