| Staph A leading to toxic shock blocks development of other Staph disease The toxin responsible for toxic shock syndrome blocks the infecting bacterium’s production of most of its other disease-causing proteins, according to researchers at New York University (NYU). Staph is a leading cause of hospital-acquired infections, affecting approximately 500,000 patients each year. In a new study published online in the Proceedings of the National Academy of Sciences, Richard Novick, M.D. and colleagues demonstrate that the toxic shock toxin inhibits the genes that encode most of the other toxic proteins produced by Staph. “Our study essentially adds a new dimension to the way we understand bacterial pathogenesis,” says Dr. Novick. Staph ordinarily produces as many as 40 different proteins some of which are recognized by the cells and tissues of the infected individual, provoking an elaborate set of defensive reactions by the body. At the same time, there is a subset of Staph infections caused by a single toxin – such as toxic shock syndrome – that are not associated with typical local inflammation. The Staph strains producing these potentially lethal toxins generally produce few of the other proteins normally associated with disease, says Dr. Novick. “In other words, Staph has at least two different ways of interacting with its victim,” says Dr. Novick. “It can act locally by attacking tissue and causing classical abscesses, or alternatively, it may produce a potent toxin that is absorbed into the bloodstream and travels throughout the body, damaging various organs, with a possibly fatal outcome. The surprise is that the toxic shock toxin itself flips the switch between these two modes of infection, by turning down the production by the bacteria of the other proteins that contribute to the infectious process, an effect that we could never have anticipated.” “There are lots of bacterial toxins around but none has been shown to regulate or repress genes in the bacterial cell,” says Dr. Novick. “This was quite a surprising results and is brand new; yet it does make sense from the point of view of the bacterium – why waste energy and resources producing all the other toxic products when this single toxin will do the job?” |
Hepatitis C infection found not to alter HIV progression or treatment
In the midst of conflicting reports about the effect of hepatitis C virus infection on the progression of HIV disease, a Hopkins study of nearly 2,000 HIV patients shows that hepatitis C does not increase risk of death, accelerate the development of AIDS, or curb the value of antiretroviral HIV therapy.
Patients with hepatitis C are less likely to receive so-called highly active antiretroviral therapy, or HAART, than are those without hepatitis C, according to the report published in the July 10 issue of The Journal of the American Medical Association (JAMA). Patients with both hepatitis C and HIV infections experience relatively high rates of AIDS and death. In the Hopkins study, these patients did just as well on HAART as patients with HIV alone.
“Among patients prescribed HAART, we found no evidence that hepatitis C virus infection substantially alters the virologic or immunologic response to potent antiretroviral therapy. Hepatitis C virus infection should not be a barrier to aggressive antiretroviral therapy in HIV patients,” said lead author Mark Sulkowski, M.D., assistant professor of medicine in the division of infectious diseases, and medical director of the Center for Viral Hepatitis at Hopkins.
Scientists have known for some time that HIV can make hepatitis C worse and increase the progression of hepatitis C-related liver disease, but it was less clear how, and to what degree, hepatitis C affects HIV. In the United States and Europe, an estimated 16 percent to 30 percent of those with HIV also have hepatitis C due to shared methods of transmission, such as injection drug use. In Baltimore and other major cities, these numbers can be as high as 50 percent or more.
The Hopkins study included 1,995 patients enrolled between January 1995 and January 2001 at the Moore HIV Clinic of The Johns Hopkins Hospital. All were HIV positive but did not have AIDS when they entered the study, and 45 percent also had hepatitis C infection. Clinic visits and laboratory evaluations were performed at regular intervals. Patients given HAART were seen four weeks after starting treatment, and then every 12 weeks for at least two years. CD4 cell count, used to measure the strength of the immune system, was monitored at 1-year, 2-years, and 3-years following the initiation of therapy.
The researchers could not find any increased risk of the development of AIDS, death, or CD4 cell count decline among those with both HIV and hepatitis C infection, compared with those with HIV alone, according to the study.
“Our findings highlight the importance of delivering effective HIV care to patients with hepatitis C,” said Sulkowski.
Bayer Diagnostics to acquire Visible Genetics to enter into molecular testing in infectious disease market
Bayer Corporation, Diagnostics Division, of Tarrytown, N.Y. and Visible Genetics, Inc. (VGI) of Toronto, Ont., announced that they have signed a definitive agreement providing for Bayer Diagnostics to acquire VGI in a cash deal valued at $61.4 million, significantly expanding Bayer’s position in the growing nucleic acid diagnostic segment of the laboratory diagnostics market. VGI plans to hold its sharholders’ meeting to vote on the transaction during October, 2002.
“This acquisition is another milestone in our ongoing strategy to expand our infectious disease portfolio which began with our acquisition of Chiron Diagnostics in 1998,” said Rolf Classon, president of Bayer Business Group Diagnostics. “It also supports our strategy to bring to market molecular diagnostic tests that assist the physician in the diagnosis and monitoring of disease and treatment regimens.”
“VGI is pleased to be joining the Bayer organization,” said Richard T. Daly, chief executive officer of VFI. “The combination of VGI’s industry leading TrueGene products with the worldwide resources of Bayer will allow us to fully develop and grow.”
The infectious disease segment is one of the fastest growing segments within the diagnostics industry, with an annual projected growth rate of 20 percent through 2005. Bayer estimates worldwide sales for the nucleic acid infectious disease market to be approximately $1 billion per year.
Based on estimates from the United Nations AIDS program, approximately 36.1 million people worldwide were living with HIV/AIDS, with 5.3 million new cases reported in 2000. HIV/AIDS caused approximately three million deaths worldwide in 2000 and has become the fourth leading cause of mortality in the world.
| Amersham Biosciences and Sloan-Kettering will collaborate on functional proteomics Amersham Biosciences of Piscataway, N.J. will join with the Sloan-Kettering Institute of New York City in a two-year research endeavor called the Functional Proteomics Project. This project is aimed at developing the first technology to scan the entire expressed human genome in a day to test each gene for its function in a cellular process. Researchers will screen tens of thousands of genes in real time, enabling rapid identification of the genes and related proteins involved in key biological pathways or disease states. Initial areas of focus will include cancer and the immune system. Amersham Biosciences intends to use technology generated by the collaboration to create new tests for pharmaceutical and other researchers to use in automated high throughput cellular screening to discover and validate therapeutic and diagnostic targets. Memorial Sloan-Kettering hopes to gain a deeper knowledge of critical pathways, such as cell cycle, cell death, and angiogenesis. Both parties should also benefit from the generation of intellectual property rights related to the methods and technologies developed for the research, and to the new tests and targets identified. The project will use Amersham Biosciences’ IN Cell Analyzer, a high throughput cellular screening system that can scan 30,000 chemical compounds or genes in cell-based assays in less than 24 hours. Dr. Andrew Carr, President of Amersham Biosciences, said, “Our IN Cell Analyzer and experience in high throughput screening, together with Sloan-Kettering’s strengths in laboratory and clinical research, will create important targets and tests for the biotechnology and pharmaceutical industries. The identification of molecular targets known to be functionally involved in disease will help the pharmaceutical industry to develop better drugs more quickly and cost-effectively, thereby delivering significant benefits to healthcare providers and patients”. Dr. Thomas Kelly, Director of the Sloan-Kettering Institute, said, “Gene scanning technology has the potential to change the landscape of cancer research and to open the door to a new generation of diagnostics, prognostics, and therapeutics for cancer patients”. The IN Cell Analyzer was developed to enable pharmaceutical companies to test potential new drugs directly in living cells more quickly and cost-effectively. The Functional Proteomics Project will be initially staffed by a team of 20 scientists at SKI, under the leadership of James Rothman and Urs Rutishauser. The project will be funded jointly by Amershamand the Sloan-Kettering Institute. Commercial terms of the agreement were not disclosed. |
Broccoli may kill H. pylori
Researchers from Johns Hopkins and the French National Scientific Research Center reported in the May 28, 2002 Proceedings of the National Academy of Sciences that in laboratory studies sulforaphane, found in broccoli and broccoli sprouts, killed the helicobacter pylori bacterium. It is expected that this finding will quickly lead to clinical trials to test whether a diet containing sulforaphane would eliminate the infection.
In 80 to 85 percent of cases, combinations of powerful antibiotics can kill helicobacter pylori, but those antibiotics can be difficult to obtain in regions of the world where the infection is most common and persistent.
“In some parts of Central and South America, Africa and Asia, as much as 80 percent to 90 percent of the population is infected with helicobacter, likely linked to poverty and conditions of poor sanitation,” says study leader Jed Fahey, a plant physiologist in the department of pharmacology and molecular sciences at the Johns Hopkins School of Medicine. “If future clinical studies show that a food can relieve or prevent diseases associated with this bacterium in people, it could have significant public health implications in the United States and around the world.”
Laboratory experiments showed that purified sulforaphane even killed helicobacter that was resistant to commonly used antibiotics. Sulforaphane was also shown to kill the bacterium either inside or outside cells. Cells lining the stomach can act as reservoirs of helicobacter, making it more difficult to get rid of the infection, said Fahey.
It is yet to be demonstrated whether dietary sources of sulforaphane kill helicobacter, but if they do, vegetables native or adapted to various regions could be used to reduce helicobacter infection. Fahey has compiled a list of vegetables that contain sulforaphane or similar compounds.
“We’ve known for some time that sulforaphane had modest antibiotic activity,” says Fahey, who is also affiliated with the Center for Human Nutrition at the Johns Hopkins Bloomberg School of Public Health. “However, its potency against helicobacter, even those strains resistant to conventional antibiotics, was a pleasant surprise.”
Researchers at Hopkins initially isolated sulforaphane from broccoli because of its ability to boost the production of „phase 2‰ enzymes, thought to protect cells against cancer. The antibiotic abilities of sulforaphane, according to Fahey, are not well understood and likely to occur through some other mechanism.
Ulcer bacteria linked to strokes
Researchers have found that specific strains of Helicobacter pylori were highly prevalent in the blood of patients who had suffered an atherosclerotic stroke, according to a report in the July 9, 2002 issue of Circulation: Journal of the American Heart Association.
In large arteries leading to the brain, the researchers report that cytotoxin-producing strains of the bacteria appear to aggravate an already risky environment. The cytotoxin-associated gene-A (CagA) makes strains of H. pylori virulent and especially damaging to arteries. Cytotoxins attack cells, causing tissue inflammation and ultimately lesions. By attacking vulnerable areas of the artery wall, they cause inflammation and swelling, further restricting blood flow and increasing the chance of stroke.
Researchers found that only CagA-positive strains of H. pylori are associated with ischemic stroke, and that this association is confined to patients with atherosclerotic stroke.
Noting that further investigation is needed, researchers theorized that the virulent H. pylori may increase system-wide infection, which is known to increase atherosclerosis. Increased infection may also contribute to plaque instability. Unstable plaque can rupture and send a blood clot to the brain, resulting in an ischemic stroke.
| Research on ovarian cancer blood test receives legislative support The House of Representatives has passed the H. Con. Res. 385 resolution to urge an acceleration of research that could lead to earlier detection of ovarian cancer. This legislation would encourage the development and widespread use of a new blood test that uses protein patterns in the blood to detect ovarian cancer at its earliest stages (see CLP News Digest, April 2002). Correlogic Systems, Inc., of Bethesda, Md. is the developer of the proprietary algorithms and processes that identified the protein patterns. Results of research by the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) were published in The Lancet in February 2002. |
