Scientists Successfully Remove HIV From Human Cells

BY Dan Avery:

  "Researchers at Temple University in Philadelphia have been able to destroy HIV in human cells, rather than simply suppress it, a breakthrough in the ongoing fight against HIV/AIDS.

  “It’s an important finding because, for the first time in laboratory setting, we show that the virus can be eradicated from human culture, cell culture, said Dr. Kamel Khalili, who led the research team at Temple’s Center for Neurovirology.

  “Basically [we're] converting infected cells to un-infected cells,” he explains “And that is very important because the current therapy can not eliminate the virus from cells.”

  Dr. Khalili’s team developed molecular tools that can operate on DNA and delete HIV in cells."

  more

Prof Racaniello: the CDC has stumbled when tackling CFS, dismissing evidence that CFS is an organic disease, diverting funds designated for CFS to other programs

January 12th, 2012, by Vincent Racaniello, discovermagazine.com:

Vincent Racaniello is Higgins Professor of Microbiology & Immunology at Columbia University, where he oversees research on viruses that cause common colds and poliomyelitis. He teaches virology to graduate, medical, dental, and nursing students, and writes about viruses atvirology.ws.

The detection of a new virus called XMRV in the blood of patients with chronic fatigue syndrome(CFS) in 2009 raised hope that a long-sought cause of the disease, whose central characteristic is extreme tiredness that lasts for at least six months, had been finally found. But that hypothesis hasdramatically fallen apart in recent months. Its public demise brings to mind an instance when a virus *was* successfully determined to be behind a mysterious scourge: the case of HIV and AIDS. How are these two diseases different—how was it that stringent lab tests and epidemiology ruled one of these viruses out, and one of them in?

The first inklings of the disease now called AIDS surfaced in Los Angeles in the summer of 1981. The5 June 1981 issue of Morbidity and Mortality Weekly Report described 5 homosexual men withPneumocystis carinii pneumonia (abbreviated PCP), normally only observed in individuals with weakened immune systems. The article suggested the possibility of an immune dysfunction related to exposure to something that would make individuals vulnerable to opportunistic infections. Soon clusters of PCP and Kaposi’s sarcoma, a rare skin cancer, were observed in gay men in other urban centers. The Centers for Disease Control and Prevention established a simple case definition—Kaposi’s sarcoma or opportunistic infections—and began scouring hospital records. Over time this definition was modified, but its early use identified an ongoing epidemic, and identified groups at risk for the disease as men who have sex with men and injection drug users.

The next year the new disease was called AIDS, and soon the U.S. Public Health Service recommended that members of risk groups not donate blood or plasma. Soon came reports that the disease could be acquired by newborn babies from their mothers, and also by heterosexual contact. By the fall there were nearly 700 people who had been diagnosed with AIDS in the U.S., of whom almost 300 had died. The CDC and World Health Organization worked together to publish global data on the disease, and issue recommendations to prevent its spread.

During the early years, the epidemiology of AIDS suggested an infectious cause, and in 1983, just two years after the disease was identified, a novel retrovirus was isolated from a patient at risk for AIDS. A year later a commercial blood test was developed, which allowed comprehensive studies to be done that showed clearly that the virus, later named human immunodeficiency virus type I (HIV-1), was the cause of AIDS. This conclusion was strengthened by the transmission of AIDS to hospital workers when they inoculated themselves with HIV-containing blood by accidental needle sticks.

HIV (green) budding from an infected cell.

By 1987 the first anti-HIV drug, azidothymidine or AZT, was licensed for the treatment of AIDS. Today over 20 anti-HIV drugs have been approved. When given in combinations of three, the emergence of drug-resistant viral variants is minimized, transforming AIDS from a death sentence to a life-long chronic disease.

The story of CFS, generally defined as persistent fatigue of six months or greater not relieved by rest and accompanied by other specific symptoms, is markedly different. This syndrome was first reported in Los Angeles as well, but in 1934. There were subsequent sporadic outbreaks, some of which were reviewed by DA Henderson in 1959, who noted that females were more frequently affected, and suggested that a virus might be involved. In the 1980s Daniel Peterson identified antibodies against Epstein-Barr virus (EBV) in the blood of a group of CFS patients in Incline Village, Nevada. The CDC entered the investigation but was unable to confirm that antibodies to the virus were consistently present in patient blood. A subsequent case-control study failed to identify EBV as the causative agent of the disease, which was subsequently named chronic fatigue syndrome.

The search for that agent of CFS has continued to be fruitless. In addition to EBV, a host of other viruses have been found in CFS patients, including enteroviruses, measles virus, herpesviruses, and human T-lymphotropic virus type II. However, none have been consistently detected in CFS patients and therefore are not considered to cause the disease.

The possibility of a viral cause of CFS re-emerged in 2009 with the detection of a retrovirus called XMRV in the blood of a substantial fraction of CFS patients. A second laboratory subsequently identified sequences related to murine leukemia viruses, also retroviruses, in the blood of CFS patients. However, many other laboratories were unable to replicate these findings, and both papers have been retracted.

Why do the stories of AIDS and CFS have such different outcomes? One reason is that it has been difficult to reach a consensus on a clinical definition of CFS. At the onset the case definition of AIDS was simple—“Kaposi’s sarcoma or opportunistic infections”—which made it possible to rapidly and accurately identify new cases, especially among different research groups around the country. This led to the establishment of risk factors, and the epidemiological data obtained from this work made it highly likely that an infectious agent was involved, spurring the search for the causative pathogen. The case definition for CFS has undergone a number of revisions over the years. When different research groups use different definitions of the disease, it becomes difficult to compare findings. Most importantly, there is no indicator or diagnostic test that can be used to identify CFS, and since diagnosing CFS is a long and difficult process, cohorts established by different investigators vary, leading to different findings, confusion, and contention. In contrast, AIDS was readily identifiable and easily diagnosed once a blood test for HIV was developed.

Another problem is that in contrast to their excellent work on AIDS, the CDC has stumbled when tackling CFS. The CDC has dismissed evidence that CFS is an organic disease, and spent funds on investigating psychiatric and trauma-related causes, rather than infectious origins. The agency also diverted funds designated for CFS to other programs. These and other missteps alienated the CFS patient community—the opposite of what the agency accomplished with the AIDS community.

In part due to the standardized case definition of AIDS, identification of a candidate virus was relatively rapid. Determining its role in the disease was facilitated by the development of a blood test, which could be used to prove that HIV-1 caused AIDS. The relationship between HIV and AIDS was further confirmed by the development of antiviral drugs that inhibited viral replication and helped alleviate the symptoms of the disease.

Why have investigators failed to identify a virus behind CFS? (It is not due to the lack of appropriate technology; this has improved substantially since the 1980s with the development of polymerase chain reaction and rapid DNA sequencing.) One explanation for this dilemma is that an infectious agent does not cause CFS. However, there is plausible evidence for an infectious etiology, including observations that the disease is known to occur in outbreaks. Furthermore, in many cases the onset of symptoms appears to begin with a flu-like illness. Additionally, CFS is a heterogeneous disease, and may be caused by several different agents or a combination of viruses and non-infectious conditions. Another possibility is that an infection initiates an immune response that spirals out of control, leading to CFS symptoms. This scenario implies that at least some CFS patients have underlying deficits in immune regulation. If that’s true, it will be very difficult to identify the virus involved because it will likely have been eliminated from patients’ systems by the time CFS symptoms become apparent.

In retrospect, it is clear that the properties of AIDS made it an easy disease to understand. While the path to understanding CFS has been clouded by non-scientific issues, in the end the main reason why we do not understand this disease is because it is extraordinarily complex. But that never stopped a good scientist.

See also: Another cracker from the CBT school of denial: “The bastards don’t want to get better”…
See also: Harvard Medical School: EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients 
See also: The putative agent of ME/CFS can be transferred to monkeys 
See also: Almost 5% of ME/CFS patients contracted ME/CFS from a blood transfusion
See also: Cerebrospinal fluid profiles can differentiate between Lyme disease, ME/CFS and healthy controls
See also: The main characteristic of ME is an abnormally delayed muscle recovery after doing trivial things, if you don't have that, you don't have ME
See also: GET (graded exercise therapy) is torture for ME patients and directly contravenes the do NO Harm principle of the GMC
See also: Post-exercise acid exposure 50 times higher in ME/CFS patients vs healthy controls, with no reduction with repeat exercise
See also: Jan 2011, Spanish study shows that CBT and GET make things WORSE in ME/CFS !!! See also: Journal for Psychotherapy 2011: CBT and GET are ineffective and potentially harmful for many ME/CFS patients

See also: Pacific Labs in California (Snell, Stevens et al): it is dangerous to put patients with M.E. through a graded exercise program
See also: Tom Kindlon's paper: "Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"

Low-dose interleukin-2 safe and effective in treating immune-mediated diseases

By Todd Neale, Senior Staff Writer, MedPage Today:
Published: November 30, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner   
Action Points 
Low-dose interleukin-2 immunotherapy appears to be safe and effective in treating two immune-mediated diseases, hepatitis C virus (HCV)-induced vasculitis and chronic graft-versus-host disease (GVHD).


Interleukin-2 increased the proportion of regulatory T cells (Tregs) in patients with hepatitis C virus (HCV)-induced vasculitis and in those with chronic graft-versus-host disease.
Low-dose interleukin-2 immunotherapy appears to be safe and effective in treating two immune-mediated diseases, two small, uncontrolled studies showed.

In the first study, David Klatzmann, MD, PhD, of Pierre and Marie Curie University in Paris, and colleagues found that interleukin-2 increased the proportion of regulatory T cells (Tregs) in all 10 patients with hepatitis C virus (HCV)-induced vasculitis and improved symptoms of vasculitis in eight, with few side effects.

In the second study, John Koreth, MBBS, DPhil, of the Dana-Farber Cancer Institute in Boston, and colleagues found that the treatment induced partial responses in about half of patients with chronic graft-versus-host disease (GVHD), with no cases of relapse or progression of the disease.

The results of both studies -- which were reported in the Dec. 1 issue of the New England Journal of Medicine -- "signal a major shift in the therapeutic use of interleukin-2," according to Jeffrey Bluestone, PhD, of the University of California San Francisco.

Overall, the treatment appeared to be safe, but the long-term effects are uncertain, he wrote in an accompanying editorial.

"Thus, these articles and others have provided a path forward for the effective use of interleukin-2 as a regulatory immunotherapy," he concluded. "Future trials involving larger numbers of patients and appropriate control groups are needed to determine the efficacy of not only interleukin-2 therapy but also other approaches to improving Treg numbers and function in autoimmune diseases and GVHD and inhibiting them in cancer."

Klatzmann and colleagues examined whether interleukin-2 could be used to treat patients with vasculitis induced by HCV that does not respond to standard antiviral therapy, rituximab (Rituxan), or both. Interleukin-2 is approved for use as an adjunctive treatment for renal cell carcinoma. It promotes survival and function of Treg cells, which inhibit immune responses.

The study included 10 patients with mixed cryoglobulinemic vasculitis who were not receiving glucocorticoid or immunosuppressant therapy (median age 58.5).

The patients received one course of interleukin-2 at 1.5 million IU per day for five days, followed by three five-day courses of 3 million IU/day at weeks three, six, and nine.

By week nine, there was a significant increase in the proportion of CD4+ T cells that were Tregs -- from 3.6% to 11.8% (P=0.004). That improvement met the primary endpoint of at least a 4% absolute increase.

Nine of the 10 patients also had a reduction in cryoglobulinemia, eight patients saw an improvement in vasculitis, and there was an overall reduction in the expression of genes related to inflammation and oxidative stress.

The treatment appeared to be safe, with no adverse events higher than grade 1 and no significant changes in circulating levels of granulocytes, red cells, or liver enzymes.

In addition, the treatment did not increase the numbers of effector T cells or induce vasculitis flare or increased HCV viremia.

"Further studies are needed to determine whether this intervention could be further modified and whether it would also be effective in the treatment of other inflammatory and autoimmune diseases, such as atherosclerosis or type 1 diabetes," Klatzmann and colleagues concluded.

Koreth and colleagues evaluated interleukin-2 as a treatment option for patients with chronic GVHD, which develops in more than half of patients who have undergone allogeneic hematopoietic stem cell transplantation.

The study included 29 patients (median age 49.5) whose disease did not respond to systemic glucocorticoid therapy.

For eight weeks, patients received daily, low-dose subcutaneous interleukin-2 -- escalating from 300,000 IU per square meter of body-surface area to 1 million IU, then to 3 million IU, if tolerated. The highest dose, however, ...

Genetic Factors Influence Serological Measures of Common Infections

Hum Hered. 2011 Oct 11;72(2):133-141. [Epub ahead of print]


Rubicz R, Leach CT, Kraig E, Dhurandhar NV, Duggirala R, Blangero J, Yolken R, Göring HH.:

Source
Department of Genetics, Texas Biomedical Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Tex., USA.

Abstract
Background/Aims: Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods: IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and -2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses.

Results: Serological phenotypes were significantly heritable for most pathogens (h(2) = 0.17-0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c(2) = 0.10-0.32). The underlying genetic etiology appears to be largely different for most pathogens.

Conclusions: Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance.

PMID: 21996708 [PubMed - as supplied by publisher]

Gamers solve the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade

ScienceDaily (Sep. 18, 2011) — Gamers have solved the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade. The gamers achieved their discovery by playing Foldit, an online game that allows players to collaborate and compete in predicting the structure of protein molecules.

After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players. The scientists challenged the gamers to produce an accurate model of the enzyme. They did it in only three weeks.

This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Intensive research is under way to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like.

"We wanted to see if ...

The brave doctors that risk treating us are ridiculed and scoffed at by their colleagues

Posted by Marzi:
All over the world there are stories of people who suffer with this illness, but because we do not fit in the neat little boxes designed to make doctors feel smart and safe, we are treated like hypochondriacs.

Imagine having HIV before anyone knew what it was.  Imagine feeling this rotten wrong thing wrapping tendrils round your system.  Imagine going to the hospital, telling them your diagnosis and watching their body language change and their tone lower to condescension.  You know it’s biological, you know it is not psychosomatic, you know there is something rotten inside you, but they just look at you dismissively and talk quietly with the nurse about discharging you with some paracetamol.

As you become more outraged at their treatment of you, you are so ill, so tired, in so much pain, you cry and raise your voice in frustration.  They nod to you and steal glances with each other, you are only reinforcing their belief it’s all in your head.  Can you imagine living like that?  Needing help and treatment, yet unable to seek it for fear you will be intentionally misinterpreted and maligned?

That is what it is to have our diagnosis.  That is why we say we would rather have Cancer or HIV or other politically incorrect things.  Not because we don’t understand the gravity of those illnesses, having experienced what we have we would never doubt nor underestimate the suffering of others.  No it is because those illnesses have treatment, awareness, options, research, support, and statistics on survival or death.  People look at me incredulously when I say I would rather have most any other life threatening illness.  But if you were to walk in my shoes, you would understand.

There is no certainty, but I can fight against that; there is no treatment, but I can pray for one, but to have people treat you like a hypochondriac while you suffer so much quietly against all hope… that is too much.  I would rather know the likelihood of my death, than to have to fight not only this insidious illness, but with the very people who have been entrusted with the job of treating me, and yet instead they shake their heads and dismiss my suffering because I refuse to fit into their neat little boxes.  And the irony of all ironies, those few brave doctors that risk treating us, specialising in the treatment of our illness, face the same treatment metered out to us by their colleagues.  They too are ridiculed and scoffed at.  The rare doctor that can think laterally and ...  Read more>>

Nurse and Admin sacked from ATOS ...

THE NEW REPUBLIC :

Nurse Debbie Carr and admin worker Anthony Treasure are seeing life from the benefit scrounging scum perspective this evening, following their sacking from Atos Healthcare.

The pair were discovered on Facebook calling the sick and disabled “down and outs” and “parasitic wankers”.

The incidents were widely reported in the mainstream press and came shortly before the Government's de-benefitting boot-boys attempted to shut up a bunch of whining cripples by sending them threatening letters.


See also: 3 more assessed "fit for work" by ATOS die

XMRV infectivity in hematopoietic cells could be mediated by CD4 receptors

XMRV: Usage of Receptors and potential Co-receptors

Mohan Kumar Haleyur Giri Setty, Krishnakumar Devadas, Viswanath Ragupathy, Veeraswamy Ravichandran, Shixing Tang, Owen Wood, Durga Sivacharan Gaddam, Sherwin Lee and Indira K Hewlett:

For all author emails, please log on. Virology Journal 2011, 8:423 doi:10.1186/1743-422X-8-423

Published: 6 September 2011


Abstract (provisional)
Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC) patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS). Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma) cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR.


Results
Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1 - CCR8 and Bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP.


Conclusion
XMRV replication was observed in GHOST cells that express CD4, and each of the chemokine receptors ranging from CCR1- CCR8 and Bob suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.  

The complete article as a provisional PDF.

e-petition: stop unfair re-assessments for disabled people

stop unfair re-assessments for disabled people

Responsible department: Department for Work and Pensions

Stop the unfair and cruel re-assessments via ATOS for disabled people currently on Incapacity Benefit.

ESA is a flawed benefit, and puts terrible pressure and stress on vulnerable people, putting people who cannot work on lesser benefits and applying sanctions.

Source:
http://epetitions.direct.gov.uk/petitions/9834

Obituary: Ruth Brinker, Founder of Project Open Hand, the organization that serves hot meals to people with HIV and other illnesses

August 2011, Posted by Rachel Dornhelm: A memorial service is planned for September 16th to honor Ruth Brinker.  She's the 89-year-old matriarch who founded Project Open Hand. The organization serves hot meals to people with HIV and other illnesses.

Brinker passed away on Monday of natural causes. The group's Development Director Bob Brenneman told KQED News that Brinker was a fearless woman.

She started Open Hand at a very scary time here in San Francisco and at a time when a lot of people her age were figuring they can settle back and enjoy retirement.  She saw how the AIDS epidemic was affecting so many people and she knew she could do something about it and she just rolled up her sleeves and did it.

Project Open Hand now serves hot meals to some 7,200 people in San Francisco and Alameda counties every year. Brinker's work has inspired the formation of more than 100 similar groups in the U.S. and abroad.

The current executive director of Project Open Hand posted his remembrance here.

The site for the memorial has yet to be determined.

New Drug Could Cure Almost Any Viral Infection

The Huffington Post Laura Hibbard: 8/11/11: Remember when you went to the doctor for that relentless cough, and all the doctor could prescribe was plenty of fluids and rest? Thanks to a new drug developed by researchers at MIT's Lincoln Laboratory, there might be a faster cure for the common cold--as well as potentially any viral infection.

The drug, called DRACO (for double-stranded RNA activated caspase oligomerizers), has already been tested on 15 viruses, MIT news reported. All of which, including the common cold, polio, H1N1, and a stomach virus, have been successfully killed by the treatment.

The study was published in the journal PLoS One in July, and highlights the possibilities for the drug.

A serious threat is posed by viral pathogens, including clinical viruses (HIV, hepatitis viruses, etc.), natural emerging viruses (avian and swine influenza strains, SARS, etc.), and viruses relevant to potential bioterrorism (Ebola, smallpox, etc.).
Unfortunately, there are relatively few prophylactics or therapeutics for these viruses...To overcome these shortcomings of existing approaches, we have developed and demonstrated a novel antiviral approach that is effective against a very broad spectrum of viruses, nontoxic in vitro and in vivo, and potentially suitable for either prophylactic or therapeutic administration.
Our approach...is designed to selectively and rapidly kill virus-infected cells while not harming uninfected cells.
An article by TIME Magazine's Healthland's section explained that the drug works by using the "natural defense systems" of human cells against the viral infection.

In essence, the drug combines the protein in human cells, which instigate a series of reactions that prevent the virus from multiplying, with a protein that tells the infected cells to "commit suicide," or apoptosis.

Todd Rider, a senior staff scientists at the Lincoln Laboratory, told MIT News that he is optimistic about the drug's uses.

“In theory, it should work against all viruses,” he said.

According to the study, researchers are currently testing DRACO against more viruses in mice, and hope move on to testing in larger animals and humans in the future.

See also: RESEARCH shows: ME is caused by an oncogenic virus

Atos doctors could be struck off

Daniel Boffey, policy editor guardian.co.uk, Saturday 13 August 2011:

Twelve doctors employed by the firm that is paid £100m a year to assess people claiming disability benefit are under investigation by the General Medical Council over allegations of improper conduct.

The doctors, who work for Atos Healthcare, a French-owned company recently criticised by MPs for its practices, face being struck off if they are found not to have put the care of patients first.

The Observer has found that seven of the doctors have been under investigation for more than seven months. The other five were placed under investigation this year following complaints about their conduct.

It is understood that the majority of allegations concern the treatment of vulnerable people when the government's controversial "work capability assessments" were carried out, but the GMC refused to comment on individual cases. The development will add to fears over the pace and radical agenda behind the government's welfare-to-work policy, which led to protests in Westminster in May by thousands of disabled people. It will also raise concerns about ministers' commitment to Atos Healthcare, which was recently granted a three-year extension on its contract.

The government has repeatedly publicised figures showing that the "vast majority" of claimants for employment support allowance (ESA), which has replaced incapacity benefit, are fit for work. But four out of 10 of those who appealed the decision by Atos - whose parent company is run by a former French finance minister, Thierry Breton - to deny them benefits are successful on appeal, a process that costs the taxpayer £50m a year.

Last month Atos, whose staff assess around 11,000 benefit claimants a week, was savaged by the cross-party work and pensions select committee after it found that many people had "not received the level of service from Atos which they can reasonably expect".

MPs further claimed that a combination of the company's conduct and the test itself had prompted "fear and anxiety among vulnerable people".

One GP who attended an Atos recruitment fair told the Observer she feared doctors could become "agents of the state" who were deprofessionalised by involvement in a system that did not make patient care its first concern.

Campaigners for the disabled seized upon the development, claiming the government needed to go back to the drawing board. Richard Hawkes, chief executive of the charity Scope, said: "If the government wants to get disabled people off benefits and into work then it needs to get its assessment right. The test should be the first step on the road to employment. But disabled people's confidence in the work capability assessment is extremely low – and today's news will send it to rock bottom.

"The test is massively flawed. Now it appears that ...

White blood cells as serial killers save patients lives

By Robert Bazell, Chief science and health correspondent:
NBC News updated 8/10/2011 7:20:14 PM ET Doctors have treated only three leukemia patients, but the sensational results from a single shot could be one of the most significant advances in cancer research in decades. And it almost never happened.

In the research published Wednesday, doctors at the University of Pennsylvania say the treatment made the most common type of leukemia completely disappear in two of the patients and reduced it by 70 percent in the third. In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone. The results of the preliminary test “exceeded our wildest expectations,” says immunologist Dr. Carl June a member of the Abramson Cancer Center's research team. Dr. Edgar Engleman, a cancer immunologist at Stanford University School of Medicine who was not involved in the research calls the results “remarkable ... great stuff.”

The Penn scientists targeted chroniclymphocytic leukemia (CLL), the most common type of the blood disease. It strikes some 15,000 people in the United States, mostly adults, and kills 4,300 every year.

Chemotherapy and radiation can hold this form of leukemia at bay for years, but until now the only cure has been a bone marrow transplant. A bone marrow transplant requires a suitable match, works only about half the time, and often brings on severe, life-threatening side effects such as pain and infection. In the Penn experiment, the researchers removed certain types of white blood cells that the body uses to fight disease from the patients.

Using a modified, harmless version of HIV, the virus that causes AIDS, they inserted a series of genes into the white blood cells. These were designed to make to cells target and kill the cancer cells. After growing a large batch of the genetically engineered white blood cells, the doctors injected them back into the patients. In similar past experimental treatments for several types of cancer the re-injected white cells killed a few cancer cells and then died out. But the Penn researchers inserted a gene that made the white blood cells multiply by a thousand fold inside the body. The result, as researcher June put it, is that the white blood cells became “serial killers” relentlessly tracking down and killing the cancer cells in the blood, bone marrow and lymph tissue.

New drugs restrict pathogens entry into cells

cbc.ca

Scientists have developed a new class of molecules that target our cells' ticketing and entry system to ensure disease-causing pathogens do not gain access.

The molecules, named pitstops, could lead to new therapeutic approaches to prevent the spread of viral and bacterial infections.

The study, which is published today in the journal Cell, is the result of collaboration between researchers in Australia and Germany.

Senior author Professor Adam McCluskey and his team at The University of Newcastle designed the pitstops, which successfully block a process called clathrin-mediated endocytosis.
Endocytosis is a process that permits signalling molecules, such as neurotransmitters, hormones and nutrients, to pass through the cell membrane and into the cell.

However, the same process is hijacked by numerous bacteria and viruses that include HIV, hepatitis C and Ebola.

And, once inside the cell, viruses take control of its machinery so that they can replicate and spread infection.

Read more>>

Natural killer cells (low in ME/CFS) participate in immune response against retroviruses

Contact: Sarah Dionne

smdionne@partners.org
617-726-6126
Massachusetts General Hospital
Natural killer cells participate in immune response against HIV

Better understanding cells' activity may contribute to new treatment, prevention strategies

A new study shows for the first time that natural killer (NK) cells, which are part of the body's first-line defence against infection, can contribute to the immune response against HIV. In an article in the August 4 issue of Nature, a research team based at the Ragon Institute of MGH, MIT and Harvard reports that the HIV strains infecting individuals with particular receptor molecules on their NK cells had variant forms of key viral proteins, implying that the virus had mutated to avoid NK cell activity.

"This study suggests for the first time that NK cells can impose immune pressure on HIV, something that had previously been described only for T cells and antibodies, adding an additional cell to the repertoire of those with anti-HIV activity," says Marcus Altfeld, MD, PhD, of the Ragon Institute and Massachusetts General Hospital (MGH), senior author of the Nature report. "The challenge now will be to translate those findings into new preventive or treatment strategies."

NK cells are part of the innate immune system, which mounts a generalized response against invading organisms. In contrast to the adaptive immune system, which includes T cells and antibodies, innate immune responses are thought to be short-lived and not directed against a particular virus or bacteria. NK cells bind to virus-infected cells or tumor cells and release cell-killing proteins that destroy their targets. Because NK cells have very strong cytotoxic activity, they need to be closely controlled, so their cell membranes are studded with both activating receptors that unleash the cell-killing response and inhibitory receptors that keep it in check.

Previous research has shown that NK cells multiply during the earliest phase of HIV infection and that the cells can suppress HIV replication in cultured tissues. It also has been observed that infected individuals with particular versions of genes coding for the NK cell receptors called KIRs (killer immunoglobulin-like receptors) are better able to control HIV viral levels. But whether these genes allow NK cells to control HIV replication through direct recognition of infected cells or through another indirect mechanism is unknown. The researchers designed their study to test the hypothesis that mutations in the HIV proteins recognized by particular KIRs could allow the virus to escape NK cell activity, a finding that would support a role for NK cells in HIV control.

The Ragon investigators and colleagues at Microsoft Research began by analyzing the sequences of both HIV proteins and the genes encoding KIR molecules that regulate NK cell activity in samples from 91 infected individuals. Using tools designed to identify drug resistance mutations by detecting alterations in the viral genome found in the presence of drug, they associated particular variants in viral proteins with the presence of specific KIR genes, suggesting that the virus mutates in response to NK-cell-mediated anti-HIV activity.

The researchers also found that viral strains infecting individuals whose NK cells included an inhibitory receptor called KIR2DL2 were more likely to have variant forms of HIV that enhance viral interaction with that receptor, turning off the cell-killing activity. In cell cultures featuring NK cells with this receptor, replication of common forms of HIV was strongly suppressed, but the variant HIV continued to reproduce. Those results imply that, in the presence of NK cells expressing KIR2DL2, HIV mutates into a form that can "flip the off switch" and prevent NK cells from attacking infected cells.

"In those individuals that expressed KIR2DL2, HIV developed mutations that allowed it to evade killing by KIR2DL2-positive NK cells, but those mutations did not develop in participants who did not express that receptor," explains co-lead author Galit Alter, PhD, of Ragon and MGH. "We know that HIV mutates rapidly, and this is one of several ways that it has evolved to escape immune system pressure. But HIV does not have an unlimited ability to change its sequence, so a challenge for the future will be to combine the different anti-HIV arms of the immune system to control HIV or – if vaccines can generate the responses – to prevent infection."

Adds Altfeld, "The results of this study raise a number of interesting new questions. We need to better understand the molecular mechanisms that allow NK cells to recognize HIV-infected cells and learn how to manipulate these cells in humans for therapy or prevention. Recent animal studies have suggested that NK cells may develop immunologic memory responses, and if that ability is found in human cells, inducing such a response through vaccination is an exciting possibility we'd like to explore." Altfeld is an associate professor of Medicine and Alter an assistant professor of Medicine at Harvard Medical School.

XMRV transmission via direct cell-cell contact is more efficient than diffusion through the extracellular milieu

The Journal of Virology, August 2011,p. 7672-7682, Vol. 85, No. 15
Viral Determinants of Polarized Assembly for the Murine Leukemia Virus

Jing Jin, Fei Li,, and Walther Mothes*:

Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Ave., New Haven, Connecticut 06536

Received 28 February 2011/ Accepted 10 May 2011

Retrovirus transmission via direct cell-cell contact is more efficient than diffusion through the extracellular milieu. This is believed to be due to the ability of viruses to efficiently coordinate several steps of the retroviral life cycle at cell-cell contact sites (D. C. Johnson et al., J. Virol. 76:1–8, 2002; D. M. Phillips, AIDS 8:719–731, 1994; Q. Sattenau, Nat. Rev. Microbiol. 6:815–826, 2008). Using the murine leukemia virus (MLV) as a model retrovirus, we have previously shown that interaction between viral envelope (Env) and receptor directs viral assembly to cell-cell contact sites to promote efficient viral spreading (J. Jin et al., PLoS Biol. 7:e1000163, 2009). In addressing the underlying mechanism, we observed that Env cytoplasmic tail directs this contact-induced polarized assembly. We present here the viral determinants in the Env cytoplasmic tail and Gag that are important in this process. A tyrosine residue within the cytoplasmic tail of Env was identified, which directs polarized assembly. MLV matrix-mediated membrane targeting is required for Gag recruitment to sites of cell-cell contact. Our results suggest that MLV polarized assembly is mediated by a direct or indirect interaction between both domains, thereby coupling Gag recruitment and virus assembly to Env accumulation at the cell-cell interface. In contrast, HIV Gag that assembles outside of cell-cell interfaces can subsequently be drawn into contact zones mediated by MLV Env and receptor, a finding that is consistent with the previously observed lateral movement of HIV into the virological synapse (W. Hubner et al., Science 323:1743–1747, 2009; D. Rudnicka et al., J. Virol. 83:6234–6246, 2009). As such, we observed two distinct modes of virus cell-to-cell transmission that involve either polarized or nonpolarized assembly, but both result in virus transmission.



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* Corresponding author. Mailing address: Microbial Pathogenesis, Yale School of Medicine, 295 Congress Ave., BCMM 335, New Haven, CT 06536. Phone: (203) 737-2203. Fax: (203) 737-2630. E-mail: walther.mothes@yale.edu.

Role of mu-opioids as cofactors in HIV infection

J Neurovirol. 2011 Jul 7. [Epub ahead of print]
Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis.

Banerjee A, Strazza M, Wigdahl B, Pirrone V, Meucci O, Nonnemacher MR.:

Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA, 19102, USA.

Abstract
About one third of acquired immunodeficiency syndrome cases in the USA have been attributed to the use of injected addictive drugs, frequently involving opioids like heroin and morphine, establishing them as significant predisposing risk factors for contracting human immunodeficiency virus type 1 (HIV-1). Accumulating evidence from in vitro and in vivo experimental systems indicates that opioids act in concert with HIV-1 proteins to exacerbate dysregulation of neural and immune cell function and survival through diverse molecular mechanisms. In contrast, the impact of opioid exposure and withdrawal on the viral life cycle and HIV-1 disease progression itself is unclear, with conflicting reports emerging from the simian immunodeficiency virus and simian-human immunodeficiency virus infection models. However, these studies suggest a potential role of opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T lymphocytes, and monocyte-derived macrophages express opioid receptors, it is likely that intracellular signaling events triggered by morphine facilitate enhancement of HIV-1 infection in these target cell populations. This review highlights the biochemical changes that accompany prolonged exposure to and withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal cellular physiological functions especially within the central nervous system. More importantly, it collates evidence from epidemiological studies, animal models, and heterologous cell systems to propose a mechanistic link between such physiological adaptations and direct modulation of HIV-1 production. Understanding the opioid-HIV-1 interface at the molecular level is vitally important in designing better treatment strategies for HIV-1-infected patients who abuse opioids.

Nevada leukaemia cluster: Evidence of an infectious etiology, Could it be... (XMRV) a retrovirus?

Xmrv Positive:

Nevada leukaemia cluster: Evidence of an infectious etiology. 14 children got ill with Acute lymphocytic Leukemia in the space of 4 years, including 9 cases within a few months. The CDC investigated, and reported. Could it be... Gulp... A retrovirus? fallon county is near Reno Nevada.

Full ARTICLE

A subset of Chronic Fatigue Syndrome is caused by HIV

International M.E. Association:

Several possible mechanisms for exercise and activity dysfunction in people with HIV have been reported. Structural and inflammatory muscle abnormalities in people with HIV, which may impair the muscle's ability to extract or utilize oxygen during exercise, have been widely reported. HIV infection-mediated myopathy, as identified by the presence of necrosis (cell death), nemaline rod bodies (rod-shaped inclusion bodies consisting of alpha-actinin and desmin), inflammation, and vasculitis (inflammation of microvasculature) were found in 26% of individuals infected with HIV who either had never taken antiretroviral therapy or had a low lifetime dose, indicating a deleterious effect of HIV infection on skeletal muscle. Read more>>

See also: The main characteristic of ME is an abnormally delayed muscle recovery after doing trivial things, if you don't have that, you don't have ME

Some doctors pooh-pooh diseases that are proven to have a pathogenic cause telling them that the pain they're experiencing is just a figment of their imagination

By Patricia Nell Warren | July 03, 2011:

This isn't the first time that the medical establishment has pooh-poohed a growing cohort of patients, telling them that the pain and agony they're experiencing is just a figment of their imagination.

Witness the stand-offish posture that the CDC and most doctors still maintain towards chronic fatigue syndrome. For decades now, because of the deep depression that often impacts people with CFS, some authorities view CFS as a mental illness. Today the CDC still classifies CFS as a "disorder," not an infectious disease, saying, "The cause or causes of CFS remain unknown." As recently as 1993, a Lancet article characterized CFS as a psychiatric condition. Yet some observers still have the opinion that CFS will be found to have a viral cause - possibly a retrovirus.

Some doctors even pooh-pooh diseases that are proven to have a pathogenic cause, like Lyme disease - whose cause (insect bites that transmit infection by a nasty bacteria) has been scientifically proven beyond a shadow of a doubt. Yet amazingly enough, there are still doctors around the United States who won't treat Lyme disease as such because they insist that the depression that often accompanies Lyme makes it a "mental illness." Read more>>