Featured Research

from universities, journals, and other organizations

Researchers Suggest New Disease Model May Some Day Lead To Effective Drugs For HIV-Associated Dementia

Date:
June 10, 1998
Source:
University Of California, San Francisco
Summary:
Researchers have long believed that macrophages, the scavenger cells of the immune system, do not divide. They emerge from the bone marrow as monocytes, circulate in the bloodstream for three days, and then migrate into tissue, where they resume a variety of functional roles.

CHICAGO--Researchers have long believed that macrophages, the scavenger cells of the immune system, do not divide. They emerge from the bone marrow as monocytes, circulate in the bloodstream for three days, and then migrate into tissue, where they resume a variety of functional roles.

But in a plenary session of the Neuroscience of HIV Infection meeting here today, June 5, a UC San Francisco researcher proposes not only that these cells can divide under certain abnormal circumstances, producing identical daughter cells, but that when they do so they proliferate, affect neighboring cells and, as a result, in some cases cause disease.

While focusing on his latest findings regarding the proposed role of macrophage proliferation in AIDS dementia, Michael McGrath, MD, PhD, a UCSF associate professor of laboratory medicine, laid out a paradigm he calls "sequential pathogenesis," a process in which, he suggested, macrophages may be the key player in numerous cell-proliferation diseases, including AIDS-related lymphoma and dementia.

"Based on these studies, my colleagues and I have readjusted our thinking regarding some aspects of macrophage function," said McGrath. "We're suggesting that these replicating macrophages may be the cornerstone of some human diseases."

According to the theory of "sequential pathogenesis," HIV or, perhaps even some other genetic element, integrates itself into the genome of macrophages, next to one of several cancer-causing genes, causing these so-called oncogenes to be activated. The oncogenes then prompt macrophages to begin expressing growth factors that, in turn, trigger the proliferation of other macrophages and other cell types involved in a range of disease conditions.

McGrath and his colleagues, including Brian Herndier, UCSF associate professor of pathology, said that they have identified three different macrophage-associated oncogenes, c-fes and platelet derived growth factor A and B, as being involved in different forms of HIV-associated degenerative and proliferative diseases.

"Our theory is that, depending on where HIV integrates itself into the macrophage genome--thus determining which oncogene is turned on inappropriately--there will be an increased risk for development of cancer or dementia," said McGrath.

McGrath has previously reported elements of his paradigm in Cancer Research (1994), regarding HIV integration in HIV-associated lymphomas; in JAIDS (1995) regarding HIV-associated Kaposi's Sarcoma; and in Lancet (1997) regarding a blood test that identified elevated levels of activated macrophages in AIDS dementia.

Today, he presented data supporting a new model that he says suggests that AIDS dementia may be, in part, the result of a process involving HIV-infected macrophage division. HIV-infected macrophages have long been known to appear in large numbers in the brains of HIV-infected patients. Macrophages make many different factors harmful to the brain, and conventional strategies have sought to block the factors, unsuccessfully.

Now McGrath reports that, in AIDS dementia patients, HIV may integrate itself into the macrophage genome next to the platelet derived growth factor B oncogene. "We are showing proliferating macrophages in the brain expressing the PDGF-B product, and demonstrating that they are doing so in an area where there are increased numbers of astrocytes [cells that proliferate in response to the destruction of nearby neurons.]"

McGrath also reported that researchers have identified a class of DNA-interacting drugs related to polyamines that, he said, could be potential candidates for treatment of AIDS dementia.

"In a preliminary study, a single dose of the drug," he said, "killed dividing macrophages, and thus removed the production of substances that kill brain cells in vitro. By contrast, cytotoxan, a standard cancer chemotherapy agent, had little effect on these cells."

The technology regarding this newly described class of macrophages (therapeutic, prognostic and diagnostic) is being developed by SLIL Biomedical Corp., of San Mateo, CA.

University of California has received patents on the full technology platform, which includes potential diagnostic blood tests and drug therapies. McGrath and Herndier are chief scientific consultants to SLIL and principal founders of the company's Biomedical Analysis division.


Story Source:

The above story is based on materials provided by University Of California, San Francisco. Note: Materials may be edited for content and length.


Cite This Page:

University Of California, San Francisco. "Researchers Suggest New Disease Model May Some Day Lead To Effective Drugs For HIV-Associated Dementia." ScienceDaily. ScienceDaily, 10 June 1998. <www.sciencedaily.com/releases/1998/06/980610211444.htm>.
University Of California, San Francisco. (1998, June 10). Researchers Suggest New Disease Model May Some Day Lead To Effective Drugs For HIV-Associated Dementia. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/1998/06/980610211444.htm
University Of California, San Francisco. "Researchers Suggest New Disease Model May Some Day Lead To Effective Drugs For HIV-Associated Dementia." ScienceDaily. www.sciencedaily.com/releases/1998/06/980610211444.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins