Even as the AIDS epidemic in Los Angeles County has shifted largely to Hispanics, primary care practitioners serving this segment of the population often fail to offer either HIV testing or safer sex advice to their patients, according to a new UCLA AIDS Institute study.

The study, published in the March issue of the Journal of the National Medical Association, found that only 41 percent of these primary care providers – including doctors, nurse practitioners and physician assistants – surveyed between March and June 2004 had regularly offered advice about sexually transmitted infection or safe sex to patients during the prior six months. Only 36 percent had offered more than 20 HIV tests during the same period, despite a recommendation by the Centers for Disease Control in 2001 that physicians in high HIV-prevalence areas routinely offer HIV testing to their patients.

“What this study shows is that despite the number of new AIDS cases increasing among Hispanics in Los Angeles County, the primary care providers do not appear to be increasing their offering of HIV testing to the patients,” said Dr. Rosa Solorio, assistant professor of family medicine at the David Geffen School of Medicine at UCLA and a co-author of the study.

The providers served in primarily Hispanic communities, and 57 percent reported that they spoke Spanish with the majority of their patients.

Statistics from the Los Angeles County Department of Health show that between 1992 and 2004, the percentage of new AIDS cases among the Hispanic population rose steadily each year, making Hispanics the group with the highest proportion of new AIDS cases in the county.

The study was conducted by Dr. Mitchell Kushner as part of his master’s thesis at the UCLA School of Public Health. Solorio, who is also a member of the UCLA AIDS Institute, served as Kushner’s thesis advisor. Kushner is now the county Department of Health’s medical director for Service Planning Area 3, which includes the San Gabriel and Pomona valleys. Solorio’s research is supported by the Robert Wood Johnson Foundation, the National Institute of Mental Health, and the UCLA Pacific AIDS Education and Training Center.

Kushner and Solorio also found that the white physicians surveyed were less likely than their Hispanic, Asian or African American counterparts to take a patient’s sexual history. Overall, 59 percent of the providers surveyed were male; 25 percent were white, non-Hispanic; 27 percent were Hispanic; 9 percent were African American; 33 percent were Asian or Pacific Islander; and 6 percent listed themselves as “other.”

Though the study was small – only 85 doctors out of 191 approached responded to the survey – it still indicated that white providers were less likely to take their patients’ sexual histories, Kushner said.

“We really have to improve the sexual history-taking skills of our primary care providers, and we have to work more intensely with the larger percentage of providers, who are white,” Kushner said.

Although 87 percent of the providers surveyed had ordered at least one HIV test for one of their patients during the six-month period, the total number of HIV tests offered to patients was quite low. Six percent of providers had not ordered a single test, 27 percent had offered one to 10 tests, 24 percent had offered 11 to 20, and 36 percent had offered more than 20. Seven percent either did not know or provided no answer. Despite the low number of tests offered, 36 percent of providers reported to having at least one person test positive during the six-month period.

“These findings suggest that providers are largely testing patients who present with symptoms,” Solorio said.

According to the county Health Department, the majority of Hispanics diagnosed with AIDS tested HIV-positive less than one year prior to their AIDS diagnosis. Thus, the challenge to providers practicing in predominantly Hispanic communities appears to be early HIV detection.

Los Angeles is the second-largest epicenter for AIDS cases in the United States, behind only New York City, Solorio noted.

The racial and ethnic distribution of AIDS cases differs markedly between Los Angeles County and the rest of the country. According to data from the county Health Department, Hispanics represented the largest racial/ethnic group diagnosed with AIDS in Los Angeles County in 2004, at 48 percent, while Hispanics accounted for 19 percent of all persons diagnosed nationally.

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Established in 1992, the UCLA AIDS Institute is a multidisciplinary think-tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social science, public health, nursing, and disease prevention. Their findings have led to advances in treating HIV as well as other diseases, such as hepatitis B and C, influenza, and cancer.

Contact: Enrique Rivero

University of California – Los Angeles Continue reading →

Like a wolf in sheep’s clothing, a protein from a disease-causing bacterium slips into plant cells and imitates a key host protein in order to cripple the plant’s defenses. This discovery, reported in this week’s Science Express by researchers at the Boyce Thompson Institute (BTI) for Plant Research, advances the understanding of a disease mechanism common to plants, animals, and people.

That mechanism, called programmed cell death (PCD), causes a cell to commit suicide. PCD helps organisms contain infections, nip potential cancers in the bud, and get rid of old or unneeded cells. However, runaway PCD leads to everything from unseemly spots on tomatoes to Parkinson’s and Alzheimer’s diseases.

BTI Scientist and Cornell University Professor of Plant Pathology Gregory Martin studies the interaction of Pseudomonas syringae bacteria with plants to find what determines whether a host succumbs to disease. Martin and graduate student Robert Abramovitch previously found that AvrPtoB, a protein Pseudomonas injects into plants, disables PCD in a variety of susceptible plants and in yeast (a single-celled ancestor of both plants and animals). Abramovitch and Martin compared AvrPtoB’s amino acid sequence to known proteins in other microbes and in higher organisms, but found no matches that might hint at how the protein works at the molecular level.

“We had some biochemical clues to what AvrPtoB was doing, but getting the three-dimensional crystal structure was really key,” Martin explained. To find that structure, Martin and Abramovitch worked with collaborators at Rockefeller University. The structure of AvrPtoB revealed that the protein looks very much like a ubiquitin ligase, an enzyme plant and animal cells use to attach the small protein ubiquitin to unneeded or defective proteins. Other enzymes then chew up and “recycle” the ubiquitin-tagged proteins.

To confirm that AvrPtoB was a molecular mimic, Martin and Abramovitch altered parts of the protein that correspond to crucial sites on ubiquitin ligase. These changes rendered Pseudomonas harmless to susceptible tomato plants, and made the purified protein inactive. AvrPtoB’s function is remarkable not only because its amino acid sequence is so different from other ubiquitin ligases, but also because bacteria don’t use ubiquitin to recycle their own proteins.

“An interesting question is where this protein came from,” Martin noted. “Did the bacteria steal it from a host and modify it over time, or did it evolve independently? We don’t know.”

Regardless, the discovery “helps us understand how organisms regulate cell death on a fundamental level,” Martin said. AvrPtoB provides a sophisticated tool researchers can use to knock out PCD brought on by a variety of conditions, shedding light on immunity. The protein itself or a derivative might one day be applied to control disease in crops or in people. For now, Martin and Abramovitch are working to find which proteins AvrPtoB acts on, and what role those proteins play in host PCD.

Abramovitch and Martin collaborated with Radmila Janjusevic and C. Erec Stebbins of The Rockefeller University on this work. Funding came from a Burroughs-Welcome Investigators in Pathogenesis of Infectious Disease award, The Rockefeller University, a fellowship from the Natural Sciences and Engineering Research Council of Canada, the Triad Foundation, and the USDA National Research Initiative.

Shawna Williams
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Mary Horgan, a consultant physician in infectious diseases with Ireland’s Health Service Executive South, said recently that an increase in the number of reported HIV cases in Cork and Kerry is a cause for concern and urged residents to practice safer sex, the Irish Times reports. Horgan said that the number of HIV cases in Cork and Kerry increased by more than 25% to 80 in 2008, marking the greatest increase in recent years. The number of HIV cases in the two areas reached 49 in 2004 and 58 in 2007.

Horgan said that residents should be aware that preventing the spread of HIV is equally important in rural areas — such as Cork and Kerry — as it is in urban areas. Injection drug use accounted for a small portion of new cases, and the majority of cases were related to unprotected sex, Horgan reported. Most new HIV cases occurred among people ages 20 to 50, with a smaller number of cases recorded among foreign-born residents and an increased incidence among people born in Ireland, according to Horgan. “The safer-sex message needs to be hammered home again,” she said, adding that people should use condoms and undergo HIV tests. In addition, Horgan reported that sexually transmitted infection clinics in Cork and Kerry see about 2,500 to 3,000 new patients annually (Roche, Irish Times, 3/31).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

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Male injection drug users deported from the United States to Tijuana have four-fold higher odds of HIV infection compared to those living in Tijuana who were not deported there, according to a study to be presented at the International AIDS Conference on August 5, 2008 in Mexico City. The study, funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), will be published in the July 30 issue of the Public Library of Science (PLoS) One.

Although the study led by researchers at the University of California, San Diego School of Medicine in cooperation with Mexican health officials does not necessarily propose a causal role between the two, the findings suggest a need for further studies to examine the risk factors of displacement, as well as the need for supportive programs targeted at displaced persons on both sides of the U.S./Mexican border.

Tijuana, with an estimated population of 1.4 million, is the largest city on the U.S./Mexican border. In addition to being a major transportation route for migrants headed to the United States, Tijuana is also situated on a major drug trafficking route. It is home to Mexico’s largest number of drug users per capita and to a thriving zona roja (red light zone), work district of the city’s estimated 5,000 female sex workers.

These factors have contributed to Tijuana’s growing epidemic of HIV and other sexually transmitted infections. The study compared HIV infection among male and female injection drug users (IDUs) in Tijuana, assessing a range of potential risk factors individual, social and environmental that might contribute to higher risk of HIV and could lead to new avenues for intervention.

The researchers interviewed 1,056 IDUs, 86 percent of whom were male. Approximately two-thirds of both female and male IDUs were born outside of Baja California, and both genders had lived in Tijuana for similar durations. However, a higher percentage of females reported their move to Tijuana was planned (68 percent) compared to males (43 percent). Deportation was the most commonly cited reason for moving to Tijuana among males (57 percent, compared to 30 percent among females), with a higher proportion of men also reporting being homeless (15 percent versus 5 percent) and injecting drugs outside the home (43 percent versus 13 percent).

Controlling for sociodemographic variables such as arrests, and patterns of sexual and drug behaviors, the researchers found an unexpected relationship between the duration of time lived in Tijuana and HIV infection among male versus female IDUs. Among males, those who lived in Tijuana for shorter periods were more likely to be HIV-infected, whereas among females, those who lived in Tijuana for longer periods were more likely to be HIV-infected. Among males, this relationship was explained by the fact that a high percentage of male migrants were deported from the U.S.

“Deportation was significantly associated with HIV infection in males,” said Steffanie A. Strathdee, Ph.D., Professor and Harold Simon Chair and chief of the Division of International Health and Cross Cultural Medicine at UC San Diego’s School of Medicine. “In addition, the prevalence of HIV infection and potential risk factors differed by gender. But a finding we didn’t anticipate is that living in Tijuana for longer periods was associated with lower HIV prevalence in men which is the opposite of what we found in women. Among women, longer-term residents in Tijuana actually had a higher risk of HIV infection.”

The researchers admit that the causal implications of their findings are unclear, but the paper suggested two possible explanations: first, that deportation might be indicative of higher risk-taking in Mexican male migrants. According to Strathdee, this could suggest that mobility rather than deportation itself creates unstable social conditions that could predispose an individual to risky behaviors that lead to HIV acquisition.

“With disintegrating family support networks, sudden changes in a person’s cultural environment, homelessness and poverty, we’re more apt to see risk behaviors such as unprotected sex with sex workers, other men or sharing injection needles among male migrants,” said Remedios Lozada, M.D., the HIV/STD coordinator of Baja California, who directs the project’s field activities in Tijuana. “However, an alternate explanation could be that deportation from the United States leads to social upheaval, loss of social ties and income factors which lead to engaging in high-risk behaviors.”

The researchers conclude that further studies are needed to determine whether specific interventions by U.S. border enforcement, or Mexican repatriation policies and procedures could reduce the risk of HIV transmission. They offer as an example a Mexican government program being implemented in Tijuana by the Ministry of Health of Baja California that promotes HIV prevention and drug rehabilitation for injection drug users, providing temporary shelter, food, clothing and medical attention to Mexican nationals who have been recently deported from the United States.

Additional contributors to the study included Remedios Lozada, Patronato Pro-COMUSIDA A.C., Tijuana; Victoria D. Ojeda, Robin A. Pollini, Kimberly C. Brouwer, Alicia Vera and Lucie Nguyen, UC San Diego School of Medicine; Wayne Cornelius, UC San Diego Department of Political Science; Carlos Magis-Rodriguez, Centro Nacional para la Prevenci??n y el Control del VIH/SIDA (CENSIDA), Mexico City; and Thomas L. Patterson, UC San Diego School of Medicine and Department of Veterans Affairs Medical Center, San Diego, for Proyecto El Cuete. Funding for this study was provided by the National Institute on Drug Abuse.

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More than 80 black Christian leaders and AIDS advocates in California on Friday at a conference in Los Angeles agreed to use houses of worship to provide HIV tests, distribute educational materials and “talk openly” about HIV/AIDS, the… San Francisco Chronicle reports. Participants at the conference signed a “covenant” outlining their commitment to HIV/AIDS outreach and education programs, according to the Chronicle. Participants also gave their support to a bill (AB 1142) in the California Legislature, sponsored by Assembly member Mervyn Dymally (D), that create a Statewide African-American HIV/AIDS Initiative, which, among other things, would declare a state of emergency in the black community. The bill is expected to be considered by the Assembly Appropriations Committee this week, according to the Chronicle. In California, African Americans — who account for about 7% of the state population — account for about 18% of the state’s reported AIDS cases, according to state Department of Health Services figures. “Without a doubt, this is the worst public health crisis that has ever affected African Americans in this country,” MacArthur Flournoy, an African-American HIV/AIDS expert at the California health department’s Office of AIDS, said. Flournoy and other conference participants said many churches still consider HIV/AIDS as “sinful” and do not consider fighting the spread of the disease as part of their “overall mission,” according to the Chronicle. “You need to get over your issues and address (sex) from the pulpit,” Rev. Russell Thornhill of the Unity Fellowship of Christ Church in Los Angeles said at the conference, adding, “You cannot be afraid to give out a condom” (Johnson, San Francisco Chronicle, 5/14).

“Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily HIV/AIDS Report, search the archives, or sign up for email delivery at www.kaisernetwork/dailyreports/hiv.. The Kaiser Daily HIV/AIDS Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →

Every year, about 500 million people worldwide are infected with the parasite that causes dysentery, a global medical burden that among infectious diseases is second only to malaria. In a new study appearing in the June 15 issue of Genes and Development, Johns Hopkins researchers may have found a way to ease this burden by discovering a new enzyme that may help the dysentery-causing amoeba evade the immune system.

“This is the first enzyme to be identified that looks like it could mediate immune system evasion,” says Sin Urban, Ph.D., an assistant professor of molecular biology and genetics at Hopkins.

The EhROM1 enzyme, it turns out, is part of an ancient group of enzymes – they are found in every branch of life from bacteria to man – known as rhomboid enzymes. In most animals, rhomboid enzymes seem to play a role in cell-to-cell communication, but a couple of years ago Urban found that malaria parasites use rhomboid enzymes for a more sinister purpose: to enter host cells uninvited.

That led his team to scour the DNA of other parasites to see if any of them also had genes that encode rhomboid enzymes. They found that the dysentery-causing amoeba Entamoeba histolytica contains one rhomboid enzyme and named it EhROM1.

“Plasmodia, the parasites that cause malaria, grab onto a host cell and push their way in,” explains Urban. “Once inside they use rhomboid enzymes to cut themselves loose.” But amoebas don’t enter cells to cause dysentery, so Urban’s team set out to figure out how these parasites use EhROM1.

They first identified protein targets cut by EhROM1 by looking for amoeba proteins that had structural signatures similar to those cut by malaria rhomboids. They found these signatures in a family of proteins – lectins – that are found on cell surfaces. The researchers put both proteins into cells and verified that EhROM1 does cut one particular lectin, and the more EhROM1 they added, the more lectin pieces resulted.

Every cell has on its surface proteins recognizable by sentries of the immune system that constantly survey the body for intruders, and amoebas are no different. To evade the immune system, amoebas shift all their surface proteins to the rear end of the cell then, like a dump truck, shed these proteins into the fluid around them.

Lectin, it turns out, is one of the proteins that during immune evasion moves to the rear and is shed by the amoeba. So collaborating researchers at Stanford University then looked to see if EhROM1 follows lectin and sure enough found that EhROM1 clusters at the cap – the cluster of surface proteins waiting to be shed.

“We’re excited to see if EhROM1 plays a specific role in the cap shedding during immune evasion,” says Urban.

What’s more, the EhROM1 enzyme is remarkably similar to those found in malaria parasites, suggesting that any potential drugs targeting EhROM1 might be able to treat two of the world’s most prevalent diseases.

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The research was funded by the National Institutes of Health and the Burroughs-Wellcome Fund.

Authors on the paper are Leigh Baxt and Upinder Singh of Stanford University, and Rosanna Baker and Urban of Hopkins.

On the Web:
biolchem.bs.jhmi.edu/bcmb/faculty/Faculty_detail.asp?PersonID=1232

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Source: Audrey Huang

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Outbreaks of HIV linked to blood transfusions have occurred throughout Central Asia since an outbreak of the virus was discovered at a children’s hospital in Shymkent, Kazakhstan, the Chicago Tribune reports (Rodriguez, Chicago Tribune, 9/16).

Twenty-one health workers and health officials in Shymkent were put on trial for medical malpractice following the HIV outbreak. A medical investigation conducted by CDC identified transfusions of tainted blood as the source of the Shymkent HIV outbreak. Since summer 2006, 118 children who received blood transfusions at the hospital have tested positive for HIV. Ten of the children have died from AIDS-related illnesses. Seventeen health workers in Shymkent in June were sentenced to prison after being convicted of criminal negligence following the outbreak (Kaiser Daily HIV/AIDS Report, 6/28).

Attorneys for the convicted doctors claimed that the children contracted HIV through mother-to-child transmission. However, the women were tested and found to be HIV-negative, Katira Bekbolova, a lawyer for the parents of the HIV-positive children, said. According to court records, officials tried to cover up the outbreak. A court-ordered evaluation of supplies and procedures at the hospitals found that syringes and catheters routinely were reused and that the hospitals did not have an adequate supply of catheters (Chicago Tribune, 9/16).

The parents of the HIV-positive children say that doctors charged them $20 for 14 ounces of blood and shared the profits with the local blood bank. Some of the doctors in Shymkent say their low wages force them to find ways of earning additional income, and a profit of up to $10 on each blood transfusion is a significant amount because doctors’ salaries begin at $175 monthly. Judge Ziyadinkhan Pirniyaz, who presided over the case, gave suspended sentences to senior health official Nursulu Tasmagambetova and three others. The remaining defendants received jail sentences ranging from a few months to eight years. Pirniyaz listed evidence of negligence, abuse of patients and theft of health funds. The attorneys for the children’s parents said they will appeal the decision.

“Salaries are very low, and even increases don’t make a difference because of inflation,” Amangeldy Shopaer — deputy chief physician at the Shymkent Infectious Diseases Hospital, where all the HIV-positive children have received treatment — said. The children’s families say government neglect has compounded their situation. In addition, many of the children’s families have been forced to move after experiencing HIV/AIDS-related discrimination (Kaiser Daily HIV/AIDS Report, 6/28). Kazakh authorities have reacted to the outbreak by building a new children’s hospital in Shymkent. In addition, old hospitals will receive new equipment, doctors will be retrained and hospital administrations will undergo weekly inspections, the Tribune reports.

According to the Tribune, nine people in Andijan, Uzbekistan, in March contracted HIV after receiving blood transfusions from an HIV-positive donor who recently had been released from prison. In addition, officials in Osh, Kyrgyzstan, in July fired several doctors for infecting 22 people, including 17 children, with HIV.

Although HIV prevalence is low in Central Asia compared with other former Soviet republics, experts say the region could experience an increase in cases if prevention is not made a priority, the Tribune reports. “Shymkent rang a bell for Central Asia,” Nicolas Cantau — regional director of the AIDS Foundation East-West office in Almaty, Kazakhstan — said, adding that the region is “in the same place Ukraine was seven years ago, when authorities missed an opportunity to contain the problem and now have seen (nearly) 1% of their population become HIV-positive.” There are an estimated 12,000 HIV cases in Kazakhstan, the Tribune reports (Chicago Tribune, 9/16).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →

The US Food and Drug Administration (FDA) is informing consumers that ConAgra is extending its recall of ALL Peter Pan and Great Value peanut butters dating back to October 2004 – this also includes peanut butter toppings. The FDA is urging consumers to get rid of any Peter Pan or Great Value peanut butters purchased since October 2004, or any beginning with the 2111 product code.

The Agency says it will continue informing consumers of any other products made with the potentially Salmonella-tainted peanut butters that were distributed to consumers.

Symptoms of foodborne illness caused by Salmonella:

– Fever
– Diarrhea
– abdominal cramps

People with poor underlying health or weak immune systems run the risk of Salmonella invading the bloodstream and causing serious, infection – even fatal ones.

If you have recently consumed one of these products and are experiencing either fever, diarrhea or abdominal cramps you should contact your doctor or health care provider immediately. If you are a provider of food and hear of any consumer becoming ill after consuming these products you should report it to your local health department, says the FDA.

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Finding how the fowl-borne bacteria Campylobacter jejuni makes at least a million Americans miserable for a week each
year is on the plates of two Medical College of Georgia microbiologists.

Raw and undercooked poultry and meat, raw milk and untreated water are sources for Campylobacter, the most common bacterial
cause of diarrhea in the United States, according the U.S. Public Health Service.

But finding how these bacteria that happily co-exist with chickens and turkeys burrow their way into intestinal cells to eat
and make people sick in the process should provide direction on how to stop them, say Drs. Stuart A. Thompson and Christopher
M. Burns.

“The basic problem with Campylobacter is that we don’t know how it causes disease,” says Dr. Thompson, who recently received
his third National Institutes of Health grant to answer this question and develop a vaccine. “To understand how to treat a
bacterium, you have to understand how it causes disease.”

He and Dr. Burns, co-principal investigator on the latest grant, are learning that the mindless microorganism is an
incredibly skilled survivor.

“What we are working on is one of the basic mechanisms of any bacterial disease: that bacteria regulate their own genes in
order to cause whatever disease process they cause,” says Dr. Thompson. “Bacteria exploit their hosts to live.” And the human
body is ripe for picking. “Think about it, inside human cells are tons of goodies, all kinds of sugars and other elements. If
bacteria can get there, cause the cells and tissue to become inflamed, cells starts releasing all these nutrients and the
bacteria have things to eat. In fact, bacteria don’t want to kill a host because then they run out of nutrients.”

All this exploitation requires being responsive to the environment. “Organisms can sense where they are in people and respond
by changing their gene expression so they are making the right proteins for the environment they happen to be in,” says Dr.
Burns.

The researchers are exploring this exploitation to learn how gene regulation changes. Dr. Burns is using microarray
technology to look at gene expression in Campylobacter, which has one of the smallest genomes of any free-living bacteria, a
fact that should simplify the search somewhat. Dr. Thompson is using proteomics to look at protein expression patterns of
genes. “Mostly it’s trying to work out regulatory pathways,” he says.

As an example, temperature, which can regulate some protein expression, may play a role in why Campylobacter live harmlessly
in normally warm chickens and makes cooler humans sick. In looking at proteins turned off and on in chickens and people, Dr.
Thompson zeroed in on one called CJ1461 that is turned on in people. The “wild hope” he had that this unusual protein was
involved in gene regulation appears to a reality.

When the researchers disabled the protein, gene regulation went haywire, Dr. Thompson says. “So we have hit on something that
affects a large number of different processes in the cells. The genome of Campylobacter had been sequenced so CJ1461 was
known, but there was only an educated guess as to what it did. What it appears to be is a DNA methylase, which means it adds
methyl groups to DNA to somehow change gene regulation,” says Dr. Thompson.

“One of the things that we are finding is that CJ1461 controls how the cell can swim,” says Dr. Thompson. “Campylobacter have
little tails called flagella so they can swim, and their ability to swim is critical for getting where they need to go.”

One place Campylobacter want to go is to the intestinal wall where they can get inside cells, eat and hide from the immune
system. But they have to work hard to get there, including swimming through the thick mucus constantly being shed by the gut.
CJ1461 is involved in the gene regulation necessary to produce much-needed tails for the task. The protein also appears to
affect the bacteria’s ability to take up iron, which is scarce and necessary for life.

CJ1461 also seems to work as a lifesaver for Campylobacter by helping the bacteria survive oxygen radicals released by the
immune system when it sees the invaders. These oxygen radicals also prompt the intestinal inflammatory response that makes
people sick.

Symptoms include diarrhea, cramping, abdominal pain and fever; in the worst-case scenarios, which are fortunately rare,
people develop Guillain-Barre’ syndrome, a paralysis-inducing autoimmune response to a bacterial or viral infection.

Drs. Burns and Thompson hope their studies will help identify targets for better treatments for the disease and ultimately a
vaccine to prevent it.

In the meantime, they encourage consumers to cook poultry products thoroughly and carefully wash their hands, pots, utensils,
counters and anything else that comes in contact with raw poultry.

For more information about Campylobacter and other food-borne illnesses, visit fightbac.

Contact: Toni Baker
tbakermcg.edu
Medical College of Georgia Continue reading →

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have discovered new information about how human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency (AIDS), possibly evades eradication from the body. In a study published in the August 16, 2004 Journal of Virology*, NCI HIV and AIDS Malignancy Branch scientists identified several possible gene targets and two drugs to flush out long-lasting HIV reservoirs that current treatments do not affect.

They also established a connection between HIV and several other genes not previously associated with the virus and found new possible targets for blocking HIV replication.

Current AIDS drugs, called antiretrovirals, target HIV replication. However, these drugs cannot completely eradicate the virus from the body because HIV rests in some cells in a non-replicating stage called latent infection. The gene targets uncovered by the NCI researchers may be used to activate HIV
within these cells, inducing its replication and thereby making the virus more vulnerable to treatment.

“The persistence of latent HIV reservoirs is one of the main barriers to the eradication of HIV infection,” said principal investigator Steven Zeichner, M.D., PhD. “Our studies show that agents targeting specific genes can be used to force HIV out of latency. In a clinical setting, forcing HIV out of latency while maintaining good control of HIV replication using antiretroviral drugs may reduce or eliminate these reservoirs.”

The researchers explored gene expression in latently-infected cells, and found that while these cells appear very similar to uninfected cells, they have a different pattern of gene expression. For example, genes whose products appear to create a favorable environment for viral replication – such as those inhibiting cell growth – were expressed at a lower level in latently-infected cells.

Such differences in gene expression point to potential targets for therapy. Causing these genes to be expressed at a higher level could induce HIV replication, creating an opening for conventional therapies to operate.

Zeichner and his research fellow, Vyjayanthi Krishnan, Ph.D., had success doing just that with a compound called resveratrol. Resveratrol activates Egr1, a gene whose product causes cell growth to slow, creating favorable conditions for HIV replication. Zeichner believes resveratrol may mimic the effects of active HIV replication on the cell cycle. His lab is currently in the process of testing other agents to target genes involved in cells’ transition out of latent infection.

Their success in stimulating replication in latently-infected cells “suggests that there may be additional new ways to manipulate HIV latency, and perhaps deplete latently infected reservoirs or even perhaps eliminate HIV infection,” Zeichner said.

Zeichner’s team also examined differences in gene expression between latently-infected cells and actively-infected cells, generating further possible therapeutic targets. They induced HIV replication in latently-infected cells and monitored their gene expression patterns over time. A total of 1740 genes out of 9127 studied showed statistically significant differences in expression throughout this period. Genes involved in the MAPK signaling pathway, which promotes viral replication, were expressed at a higher level; genes preventing transcription of DNA were expressed at a lower level.

Some of the genes that were expressed differently in infected cells are genes that have been linked to some cancers, suggesting that HIV requires some of the same functions that are implicated in the development of cancer. Many of these genes are already the subject of drug development efforts directed at cancer and other disorders.

While Krishnan, the first author on the study, cautions that their data are far from clinical application, she believes “the results may provide an early hint at strategies that drugs target cellular activity, rather than the virus itself.” Unlike current AIDS drugs, such therapies “may be less likely to engender drug resistance by HIV.”

For more information about cancer, visit the NCI Web site at cancer or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

* Krishnan, V and Zeichner, SL. “Host Cell Gene Expression During HIV-1 Latency and Reactivation, and Effects Targeting Genes Differentially Expressed in Viral Latency.” Journal of Virology, Volume Issue. 16 August 2004.

CONTACT:
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