|The Management of disease - population control?
GenoMed, Inc. is a Next Generation Disease Management(TM) whose mission is to improve patient outcomes by identifying the molecular pathways that cause disease.
A St. Louis Business Journal article first reported that the company has applied for patents based on its finding that the ACE gene is associated with a large number of common diseases including virtually all autoimmune diseases.
The body's immune response to cold viruses are responsible for the symptoms a cold sufferer gets. They are the result of cytokines or interleukins acting downstream in the disease pathway from angiotensin II, which is a very early upstream signal.
Blocking angiotensin II should decrease the body's reaction to the virus, and decrease the degree and duration of cold symptoms."
GenoMed, Inc. Launches Clinical Trial Against The Common Cold
| PATENT PROTECTION, HOW ALTRUISTIC...
GenoMed has discovered and applied for patent protection on a treatment that could have wide-ranging use for over 150 common diseases that currently carry a dismal prognosis. These include diabetes and its complications (which affects 20 million in the United States alone), high blood pressure and its complications (which affects 60 million in the U.S.); emphysema and other smoking-related diseases; and many other serious diseases, including infection with HIV and progression to AIDS, common solid cancers such as lung, colon, pancreas, liver, and kidney; cancers of the blood-stream such as chronic leukemias, multiple myeloma, and lymphomas; and immune-mediated diseases such as multiple sclerosis, degenerative joint disease (osteoarthritis) and rheumatoid arthritis. cache image
EMF disease control via advertising hoardings?
"Advanced Optics primary initial product that will be marketed to users of the outdoor advertising industry is the flat-panel display, which will provide an image measuring approximately three meters by eight meters, similar in size to existing printed billboards." - Yahoo finance
"GenoMed Inc. announced today that the Company has secured an additional $900,000 in equity financing from Advanced Optics Electronics, Inc.. " -
Caution for activists:
This author recieved a weird pseudo threatening message
while researching this subject
via a lively Indymedia thread from a 'Genomed spokesperson'
Chief medical officer & CEO no less...
Cure for bird flu may already exist
08.02.2004 19:42 - Bird flu kills people because the virus is new to all of us as a species, and we overdo our immune response to the novel virus. What virologists at WHO don't yet get is that there's nothing specially destructive about the 1918 avian influenza virus, nor the influenza A virus which we don't have a proper vaccine to this year, nor the current bird flu strain. They don't possess a "killer" enzyme that turns flesh to goo.
The only thing these viruses share is novelty. They're new to our species. The people who die from them all have the same picture at autopsy. Their lungs are full of monocyte/macrophages. There's hardly any virus to be found.
Like most things in life, people are getting killed because they're over-reacting.
[my note: now that's a weird thing to say...in the context of what he is actually saying...how can anyone help if their immune system can't cope with a virus?]
GenoMed has identified a very early step in the immune response pathway which can be safely turned off without turning you into a Petri dish for infections. This is the problem with steroids. We've used our patent-pending approach against West Nile virus encephalitis this past fall. Of 8 patients so treated, 7 were cured within an average of 24 hours. Not bad, especially for the 3 patients over 70 who had at least a 50% expected risk of dying.
Please go to www.genomedics.com and click on "Flu Trial" if you'd like to learn more. Participating in the trial is easy, free (except for the cost of the meds), and possible anywhere on earth. The drugs we use--ACE inhibitors and angiotensin II receptor blockers (ARB's)--are carried in every corner drug store, and physicians around the world know how to use them safely.
Dave Moskowitz MD, MA(Oxon.), FACP
Chief medical officer & CEO
St. Louis, Missouri
(ticker symbol "GMED" on OTC Pink Sheets)
Why would this guy seek to allay such observations
as disease patenting?
the future [see hidden present] systems of control are preparing the human race for a dependance on disease...a normality virus, with which they can hold the big stick of disease on any human[s] that need 'democratizing'
in the war on terror...it is economic, phrma-based warfare...
this quote keeps ringing in my head:
"...And advanced forms of biological warfare that can "target" specific genotypes may transform biological warfare from the realm of terror to a politically useful tool."
'Rebuilding Americas Defences' - The Project for the New American Century
1. yeah! it's that thinktank made up of all those whakos- who now are in the whitehouse....
2. is this shit already in operation?
War as a evidence destroyer of secret viral experiments
Many microbiologists have started turning up dead...
are these 300 and rising the ones with the conscience?
#1 Dr. David Schwartz.. murdered at home..|
#2 Dr Benito Que... dead in the street...
#3 Dr.Set Van Nguyen..dead in airlock refrigerator.
#4 DR.Don Wiley.. vanished.. car abandoned...
#5 Dr. Vladimer Pasechnik Dead near his home. ..... Feb. 2002...
#6 Dr. Ian Langford .Russian.. beaten to death in his home...
#7 DR. V Korshunov... Russian..head bashed in...
#8 Dr A Bushlinski Russian.. murdered..
#9 Dr. I Glebov.. Russian.. Bandit attack....
and there's more...
Was Dr David C Kelly [ex-Porton Down] sacrificed to justify the dodgy case for war?
or is it all MUCH bigger than that...
"The two American scientists [Dr David C Kelly] had worked with were Benito Que, 52, and Don Wiley, 57. Both microbiologists had been engaged in DNA sequencing that could provide "a genetic marker based on genetic profiling."
The research could play an important role in developing weaponized pathogens to hit selected groups of humans - identifying them by race. Two years ago, both men were found dead, in circumstances never fully explained. " - Patricia Doyle, PhD
Dr. Don Wiley [RIP]
Professor Ian Wilson and Don Wiley worked together to solve the structure of the influenza virus haemagglutinin.
Ian was a Research Fellow - the only postdoctoral fellow - in Don's laboratory during this time.
A Discussion with
Marconi Scientists Mystery
In the 1980,s over two dozen science graduates and experts working for Marconi or Plessey Defence Systems died in mysterious circumstances, most appearing to be 'suicides.' The MOD denied these scientists had been involved in classified Star Wars Projects and that the deaths were in any way connected. - click here for a list & details
Disease patenting? Cancer patenting? Disease MANAGEMENT ?
disease used as the punishment for subversive/militant thought?
will the herd evolve via this behaviorism into
not wanting to rebel
because it makes them feel ill?
Will Orwells 2- way TV be an fMRI scanner?
U.K. rail to install body scanners
LONDON, Oct. 30 (UPI) -- British railway stations will soon install airport-style security checks using body scanners and X-ray machines for increased security.
Following the July 7 London bombings that caused 52 deaths, new rail security will also allow passengers to be frisked and random bag searches made, on the orders by Alistair Darling, the Transport Secretary, the Sunday Telegraph reported.
The security changes will be tried in selected locations on the network and if successful, the government plans to implement the measures at railway stations across Britain and at the subway stations and at other transport interchanges- science daily
see here for the next level
Flashback: Remote-control for Bacteria
Radio waves switch proteins on and off.
6 December 2002 PHILIP BALL - Remote-controlled bacteria could be just around the corner. Researchers have found a way to switch cell processes on and off with radio waves. The goal is "microbial machines", Joseph Jacobson of the Massachusetts Institute of Technology in Cambridge told this week's Materials Research Society meeting in Boston.
Cells, he explained, could be equipped with a toolbox of 'software' - such as the ability to glow periodically1. Remote-controlled enzymes could cut and paste these modules as if downloading a particular program into the cells. This is a long way off, but the components are taking shape.
Jacobson's team uses an electromagnetic field to switch on and off an enzyme that snips open the genetic messenger molecule RNA. First they attach a tiny particle of gold to the enzyme. Only millionths of a millimetre across, the gold nanoparticle acts as an antenna, harvesting energy from a radio-frequency electromagnetic field. This energy breaks up the enzyme, rendering it useless. When the field is switched off, the parts of the enzyme re-assemble of their own accord.
Earlier this year the same team manipulated DNA in a similar way2 . They stuck a gold antenna to DNA strands that spontaneously curl up into hairpin structures where the two ends zip together. A radio-frequency pulse picked up by the gold antenna opened up the hairpin.
Showing that the approach works for proteins too greatly increases the range of things that might be done with it - proteins orchestrate nearly all the chemical processes in a cell. - lauralee.com
Flashback: University develops cancer 'nanobomb'
Big News Network.com Thursday 13th October, 2005 (UPI)
University of Delaware researchers say they've developed a unique nanobomb that can literally blow up cancer tumors.
Balaji Panchapakesan, an assistant professor of electrical and computer engineering and the lead investigator, said the research is in its very early stages and years from engaging in clinical trials.
Make no mistake, we are focused on eradicating cancer, Panchapakesan said, explaining the nanobombs are the result of work with carbon nanotubes -- atoms of carbon arranged in tubular form.
Originally, he said, the research team was considering using carbon nanotubes as drug delivery vehicles. But as various experiments progressed, the researchers made a startling discovery.
When you put the atoms in different shapes and forms, they take on different properties at the nanoscale, Panchapakesan said. "We were experimenting with the molecules and considering optical and thermal properties, and found we could trigger microscopic explosions of nanotubes in wide variety of conditions.
The nanobomb is very selective, very localized and minimally invasive, Panchapakesan added. It might cause what I would call nanopain, like a pin prick.
Panchapakesan recently reported on the discoveries in the journals NanoBiotechnology and Oncology Issues.
big news network.com
|PSYWAR! Weapons test gone right?
In March 2006
6 men were taken into intensive care when they suffered devastating effects after taking a drug in a medical trial at private medical research centre at Northwick Park Hospital, Harrow.
According to TeGenero, makers of the drug known as TGN1412,: The trial began at 8am on Monday in the Parexel Unit at Northwick Park. Six volunteers were injected with the drug and two with placebo. Unfortunately all six of the volunteers who had been given the drug developed serious symptoms.
The Scotsman reports:
TGN1412 had previously been tested on mice, rabbits and monkeys before human trials began. The monkeys were given doses 160 times stronger than the human volunteers without becoming sick. GERMAN prosecutors are investigating the company at the centre of the disastrous drugs trial which has left six men seriously ill in a UK hospital.
TeGenero could face charges of violating drug research laws and causing bodily harm. It also emerged that Germany's drugs testing watchdog, the Paul Erhlich Institute, only granted permission for TeGenero to test TGN1412 in the country on 17 February after "preliminary concerns" were addressed. But the institute refused to give details of these concerns. Permission to test the drug in the UK was granted on 27 January. It is unclear why human guinea pigs were picked in Britain, where they are paid around £2,000, when in Germany such healthy volunteers would have received £500. The tests were performed by
Parexel which was advertising on its website five clinical trials at its 36-bed unit at Northwick Park Hospital, including trial 68419, for a drug developed for the treatment of inflammatory diseases such as rheumatism
TGN1412, developed in a relatively small German laboratory, is part of the promising research into monoclonal antibodies that may be of great significance in neutralising or blocking a human protein (thus helping the fight against cancer) or in possibly stimulating antibodies to boost the human immune system.
The drug agressively stimulates T-Cells helping to enhance the Immune system...what is thought to have gone wrong is that the T-Cells of the victims massively over reacted [mutated?] & started to attack their vital organs...One or more of the drug trial victims may remain in a coma for up to a year -
is this a BIO-WARFARE TEST hidden in plain sight?
PAREXEL Clinical Pharmacology Research Unit
Northwick Park Hospital
Level 7, Watford Road
Middlesex HA1 3UJ
TGN 1412 is not a chemical but a biological agent, an antibody designed to lock on to a particular target in the immune system and modify its behaviour.
commercially sensitive fallout?
TeGenero fallout will be minor
By Steve Mitchell Mar 24, 2006, WASHINGTON, DC, United States (UPI) -- TeGenero`s disastrous phase 1 trial of TGN1412 -- in which six men became seriously ill hours after receiving the drug -- has stirred up questions about the clinical trial process, but experts said the fallout for industry and the regulation of clinical trials is likely to be minimal.
'I don`t think it will have much implication for the biopharmaceutical industry,' Eric Schmidt, an analyst with S.G. Cowen, told United Press International. 'Anytime a foreign substance is tested in humans, it carries risk,' Schmidt said. 'This seemed to be an unfortunate occurrence, but also an isolated example.'
In the trial, which was being conducted at Northwick Park Hospital in London, six volunteers who received TGN1412 on March 13 developed a severe inflammatory reaction and multi-organ failure. The men were admitted to intensive care and two remain critically ill.
Jerome Yates, a medical oncologist and senior vice president for research at the American Cancer Society, told UPI he didn`t think the study indicated there was a problem with the clinical-trial process in the United States. 'Generally speaking, the way clinical trials are conducted in this country, particularly phase 1 trials, are much, much more careful,' Yates said. He added that the study design should have raised red flags before the trial was ever initiated. The warnings included that the study participants were paid approximately $3,500. 'Most institutional review boards in this country would not approve something like that because it`s a form of financial coercion,' Yates said. In addition, phase 1 trials of this type generally call for treating one patient at a time, not six simultaneously as apparently happened in this study. Healthy volunteers also are generally not included in phase 1 trials of potential cancer treatments, he said.
Still, Yates thought it was likely that regulatory authorities would review the clinical trial process. 'I think everybody will review the situation,' he said. 'You can`t take healthy people and put them in life-threatening jeopardy.'
The industry and regulatory authorities are apparently not eager to discuss the matter. The Pharmaceutical Research and Manufacturers of America, the Biotechnology Industry Organization and the Food and Drug Administration did not respond to requests from UPI for comment.
The Medicines and Healthcare products Regulatory Agency and the local ethics board approved the trial design.
TeGenero, which was developing the monoclonal antibody drug for treatment of leukemia, rheumatoid arthritis and multiple sclerosis, subsequently acknowledged that monkeys given the drug during preclinical studies developed swollen glands but insisted there was no indication the compound would cause serious problems in humans.
'We are shocked about the symptoms we have seen in the volunteers,' said Thomas Hanke, TeGenero`s chief scientific officer. 'Extensive pre-clinical tests showed no sign of any risk,' Hanke added.
Despite these assurances, The Lancet, in an editorial in the March 25 issue of the journal, called for independent scrutiny of the trial. 'Although most first-in-man trials are not associated with such dreadful events, the fact that they have occurred should lead to maximum transparency to reaffirm trust in clinical trials and their regulation,' the Lancet stated in the editorial.
The Lancet raised the issue of whether the trial protocol was followed to the letter. The protocol approved by the MHRA specified the drug should be given at two-hour intervals, but TeGenero`s Hanke said the protocol left the order and timing of administration to the discretion of the principal investigator at Parexel, a contract research organization that was conducting the trial for TeGenero.
The Lancet said both MHRA and TeGenero denied its request to see the protocol on the grounds that it was 'commercially sensitive.' The Lancet objected to this rationale, stating, 'Commercial confidentiality should not obstruct independent scrutiny of the TGN1412 protocol and trial conduct.'
The editorial added, 'Until the MHRA and police investigations are complete, it is unclear whether there was a fault with the quality of the drug, contamination, a deviation from the protocol, or whether this was an unpredicted adverse event.'
Parexel said in a statement issued this week that a preliminary audit conducted by its internal quality-assurance department supports the notion that the protocol 'was adhered to properly, and that best practices and policies and procedures were correctly followed.' The firm also noted that so far MHRA, which is investigating, 'has found no reason to recommend the discontinuation of trials at Parexel`s phase 1 unit.'
Boehringer Ingelheim, which manufactured the compound used in the clinical trial, said it conducted 'an additional review of the manufacturing documentation and the pharmaceutical release procedure' and confirmed that the material it supplied 'complied with all pharmaceutical and legal requirements.' - via monstersandcritics.com
Monoclonal Antibody Technology - The Basics
(BIO). "What is Biotechnology?" Washington, D.C.: Biotechnology Industry Organization, 1989.
Substances foreign to the body, such as disease-causing bacteria and viruses and other infectious agents, known as antigens, are recognized by the body's immune system as invaders. Our natural defenses against these infectious agents are antibodies, proteins that seek out the antigens and help destroy them.
Antibodies have two very useful characteristics. First, they are extremely specific; that is, each antibody binds to and attacks one particular antigen. Second, some antibodies, once activated by the occurrence of a disease, continue to confer resistance against that disease; classic examples are the antibodies to the childhood diseases chickenpox and measles.
The second characteristic of antibodies makes it possible to develop vaccines. A vaccine is a preparation of killed or weakened bacteria or viruses that, when introduced into the body, stimulates the production of antibodies against the antigens it contains.
It is the first trait of antibodies, their specificity, that makes monoclonal antibody technology so valuable. Not only can antibodies be used therapeutically, to protect against disease; they can also help to diagnose a wide variety of illnesses, and can detect the presence of drugs, viral and bacterial products, and other unusual or abnormal substances in the blood.
Given such a diversity of uses for these disease-fighting substances, their production in pure quantities has long been the focus of scientific investigation. The conventional method was to inject a laboratory animal with an antigen and then, after antibodies had been formed, collect those antibodies from the blood serum (antibody-containing blood serum is called antiserum). There are two problems with this method: It yields antiserum that contains undesired substances, and it provides a very small amount of usable antibody.
Monoclonal antibody technology allows us to produce large amounts of pure antibodies in the following way: We can obtain cells that produce antibodies naturally; we also have available a class of cells that can grow continually in cell culture. If we form a hybrid that combines the characteristic of "immortality" with the ability to produce the desired substance, we would have, in effect, a factory to produce antibodies that worked around the clock.
In monoclonal antibody technology, tumor cells that can replicate endlessly are fused with mammalian cells that produce an antibody. The result of this cell fusion is a "hybridoma," which will continually produce antibodies. These antibodies are called monoclonal because they come from only one type of cell, the hybridoma cell; antibodies produced by conventional methods, on the other hand, are derived from preparations containing many kinds of cells, and hence are called polyclonal. An example of how monoclonal antibodies are derived is described below.
A myeloma is a tumor of the bone marrow that can be adapted to grow permanently in cell culture. When myeloma cells were fused with antibody-producing mammalian spleen cells, it was found that the resulting hybrid cells, or hybridomas, produced large amounts of monoclonal antibody. This product of cell fusion combined the desired qualities of the two different types of cells: the ability to grow continually, and the ability to produce large amounts of pure antibody.
Because selected hybrid cells produce only one specific antibody, they are more pure than the polyclonal antibodies produced by conventional techniques. They are potentially more effective than conventional drugs in fighting disease, since drugs attack not only the foreign substance but the body's own cells as well, sometimes producing undesirable side effects such as nausea and allergic reactions. Monoclonal antibodies attack the target molecule and only the target molecule, with no or greatly diminished side effects. - accessexcellence.org
CROPS IN SECRET LOCATIONS USE GM DRUG THAT LEFT SIX CRITICALLY ILL
notopharmaceuticalexperiments on IndyMediaUk
Independent scientists have raised the alarm after media reports ommitted to mention that drugs, which left six people critically ill after a trial, are genetically modified and are being used in crops planted in secret locations across the UK.
Drug Trial Catastrophe & Safety of Secretly Tested Pharm Crops
A monoclonal antibody drug tested in a clinical trial made all six healthy volunteers violently ill, yet transgenic crop plants with similar drugs are being tested in secret locations and the unsuspecting public are being exposed without their knowledge or consent. Prof. Joe Cummins and Dr. Mae-Wan Ho
A fully referenced version of this article is posted on ISIS members' website. Details here
Drug trial reactions attest to the deadly nature of MAB drugs
The London drug trial that left six healthy volunteers dangerously ill has raised awkward questions on the science and ethics involved in all stages of drug research and development ("Drug trial catastrophe – collapse of science and ethics", this series). The drug, code named TGN1412, is a genetically engineered humanized monoclonal antibody (MAB) aimed at treating leukaemia and autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Hundreds of MAB drugs are under development, 18 of which have already been approved by the US FDA, with warnings posted on each and every one of them ("Warnings over FDA approved monoclonal antibody drugs", this series).
The violent reactions of all six human volunteers injected with TGN1412 serves as a graphic demonstration on how deadly such drugs can be.
In the aftershock of the episode, bioethicists and others have called for tighter regulation of human drug trials and a more cautious protocol. However, no one has raised the alarm over the distinct possibility that the general public might be exposed without informed consent to transgenic crops producing such drugs.
Secret pharm crops with MABs
Currently, the MAB drugs approved have mainly been prepared from cell cultures. The cost to the patients would be at least $20 000 to $50 000 per year; the colon cancer drug Erbitux costs $17 000 per month . So, only the wealthy could benefit from such drugs, if at all. Producing the drugs in transgenic farm animals or in crop plants, therefore, promises to greatly reduce the cost of MAB drugs. And plans are afoot to do just that, with reckless disregard for the safety of the general public.
Laboratory mice have already been modified to produce human antibodies and there are efforts to create farm animals producing human antibodies . Human monoclonal antibodies have been produced at relatively high levels in chicken eggs . And humanized MABs have been produced using the yeast Pichia pastoris, ‘glycoengineered' to express human patterns of glycosylation (carbohydrate chains on proteins) to avoid immunological problems arising from non-human glycosylation .
Plant-based production of recombinant antibodies has been discussed extensively. A review published in 2003  reported that six plant-derived antibodies have been developed as human therapeutics. The drug, Avicidin, developed by NeoRx and Monsanto, had some anticancer effect on colon cancer; but it caused severe diarrhoea and was withdrawn. A plant-derived antibody CaroRx produced in tobacco claims to reduce tooth decay by preventing adhesion of the bacterium Streptococcus mutans. A MAB targeting the cancer-antigen CEA was produced in tobacco, pea, rice and wheat. A humanized MAB recognizing herpes simples virus 2 was produced in soybean. Tobacco plants were transformed with a viral vector to produce antibodies targeting non-Hodgkin's lymphoma. Finally, a MAB produced in tobacco targeted human chorionic gonadotropin, and was intended for use in contraception, pregnancy detection and therapy of tumours . Plants have been transformed to produce prophylactic antibodies against rabies and other disease conditions .
We have drawn attention to the hazards of producing genetically modified vaccines and therapeutic antibodies. The main threat is the genetic pollution of major food crops resulting in food that is toxic . Humanized MABs structured to attack herpes virus or regulate the human immune system were to be produced by transgenic strains of the green alga Chlamydomonas in large plastic tubes near a beach in Hawaii Chlamydomonas is a common soil microbe so the nature and location of the production facility would risk spreading the transgenic strains and the human genes also to soil microbes .
Molecular pharming (producing pharmaceuticals in transgenic crops) is turning into a new battlefront in the struggle of the global civil society against transgenic crops. Too many governments of industrialised countries appear to be prepared to allow biotech corporations to contaminate our food supply with un- prescribed and dangerous drugs .
The precise MABs in pharm crops deemed confidential business information
There have been at least 29 field tests of transgenic crops known to be producing antibodies, but the actual genes have been deemed confidential business information (CBI). The crops modified include maize and soybean; and the companies testing the transgenic crops are Prodigene, Monsanto and Agracetus, among others. The field releases were in Hawaii, Nebraska, Wisconsin, Iowa, Indiana Minnesota, Puerto Rico, Texas and other states . Other crops and MABs may have been tested, but designated CBI, as are the actual locations of such tests, and no effort has been made to notify bystanders and neighbours that are likely to be directly exposed to the drugs. People may be exposed to MABs from transgenic crops by pollen, dust debris from leaves, stems and flowers, and from polluted surface and groundwater. Once the MAB genes escape to fertilize neighbouring crops, they will persist within the contaminated crops, by virtue of simple Hardy-Weinberg equilibrium in elementary population genetics!
There is no case for using crop plants in the open field to produce these drugs, as they could easily be produced in plant cell culture under fully contained conditions.
The secretive field trials should never have been allowed, as they are exposing people, without their knowledge or consent, to drugs that could become life- threatening, as the London drug trial so vividly demonstrated.
The location and nature of current and previous field trials should be made public now before any more damage is done, and all further field trials should be banned.
Ion channels allow the movement of ions across cell membranes, and therefore fundamental physiological processes such as muscle contraction. In 1998, we saw for the first time what an ion channel actually looks like in a paper describing the crystal structure of a potassium channel.
Ion channels are pore-forming proteins that help establish the small voltage gradient that exists across the membrane of all living cells (see cell potential), by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells.
An ion channel is an integral membrane protein or more typically an assembly of several proteins. Such "multi-subunit" assemblies usually involve a circular arrangement of identical or related proteins closely packed around a water-filled pore through the plane of the membrane or lipid bilayer. While large-pore channels permit the passage of ions more or less indiscriminately, the archetypal channel pore is just one or two atoms wide at its narrowest point. It conducts a specific species of ion, such as sodium or potassium, and conveys them through the membrane single file--nearly as quickly as the ions move through free fluid. In some ion channels, access to the pore is governed by a "gate," which may be opened or closed by chemical or electrical signals, temperature, or mechanical force, depending on the variety of channel.
Because "voltage-gated" channels underlie the nerve impulse and because "transmitter-gated" channels mediate conduction across the synapses, channels are especially prominent components of the nervous system. Indeed, most of the offensive and defensive toxins that organisms have evolved for shutting down the nervous systems of predators and prey (e.g., the venoms produced by spiders, scorpions, snakes, fish, bees, sea snails and others) work by plugging ion channel pores.
But ion channels figure in a wide variety of biological processes that involve rapid changes in cells. In the search for new drugs, ion channels are a favorite target.
Antibodies to Ion Channels
Ion channels are integral membrane proteins forming pores that allow passage of ions such as sodium, potassium, calcium, chloride, and others to traverse the hydrophopic environment of a cell's lipid bilayer membrane. Ion channels can be constitutively open, or more importantly, they can be voltage-gated or ligand gated. Voltage-gated channels open when the potential across the membrane rises above or falls below a specific threshold, while ligand-gated channels open (or close) upon binding of a ligand. Another important type of ion channels are metabotropic ion channels, which are gated by G-protein subunits or intracellular second messengers. Ion channels are among the most important proteins in biology, they are essential to neural conduction, synaptic transmission, osmosis, respiration, and many other biological processes. Impaired ion channel function can cause disease such as cystic fibrosis, in which the gene encoding a chloride channel known as CFTR carries loss of function mutations. Other ion channels have been targeted for inhibitor discovery in a variety of disease indications, and drugs targeting ion channels already generate multi-billion dollars in sales per annum.
Ion channels are usually not available as purified antigens for immunization. Rather, antibodies against ion channels are being developed by immunization with whole cells or cell membranes that express or over-express the ion channel of interest. Alternatively, immunization can be carried out with peptides, fragments, or recombinant structural domains derived from ther channel of interest. Antibodies against ion channels can be evaluated further by a technology known as patch-clamp, that can measure currents through single ion channel molecules. In patch-clamp experiments, neutralizing antibodies manifest themselves by blocking the ion flux through the channel of interest following activation with applicable ligand.
- METHODS FOR STUDY OF ION CHANNELS
Ion channels in the immune system as targets for immunosuppression.
Cahalan MD, Chandy KG.
Department of Physiology and Biophysics, University of California, Irvine 92697-4560, USA. firstname.lastname@example.org
The discovery of a diverse and unique subset of ion channels in T lymphocytes has led to a rapidly growing body of knowledge about their functional roles in the immune system. Potent and specific blockers have provided molecular tools to probe channel structure-function relations and to elucidate the involvement of K+, Ca2+, and Cl- channels in T-cell activation and cell volume regulation. Recent advances in analyzing Kv1.3 channel structure-function relationships have defined binding sites for channel blockers, which have now been shown to be effective in suppressing T-cell function in vivo. Ion channels may provide excellent pharmaceutical targets for modulating immune system function. - ncbi.nlm.nih.gov
Flashback: T-cell signaling control is achieved
BERKELEY, Calif., Nov. 17 (UPI) -- U.S. Department of Energy scientists have created synthetic membranes that, for the first time, enable them to directly control T-cell signaling activity.
By going inside a living immune system cell and physically moving its T-cell signaling molecules, the Lawrence Berkeley National Laboratory researchers demonstrated the "bull's eye" of an immunological synapse, long thought to amplify T-cell signaling, actually works to extinguish the signal
Scientists say they combined nanotechnology with biochemistry to create the unique synthetic membranes.
"This marriage of inorganic nanotechnology with organic molecules and cells enables us to go inside a living cell and physically move around its signaling molecules with molecular precision," said Jay Groves, a Berkeley Lab/UC-Berkeley chemist. "Our experimental beaker has now become the inside of living cells and we can watch chemical reactions take place there."
Groves is the principal co-author, along with Michael Dustin, a cellular immunologist at New York University, of a paper detailing the research that appears in the Nov. 18 issue of the journal Science.
Berkeley Lab is a U.S. Department of Energy national laboratory that conducts unclassified scientific research, managed by the University of California.
Pentagon Program Promotes Psychopharmacological Warfare
The Advantages and Limitations of Calmatives for Use as a Non-Lethal Technique, a 49 page report obtained last week by the Sunshine Project under US information freedom law, has revealed a shocking Pentagon program that is researching psychopharmacological weapons. Based on "extensive review conducted on the medical literature and new developments in the pharmaceutical industry", the report concludes that "the development and use of [psychopharmacological weapons] is achievable and desirable." These mind-altering weapons violate international agreements on chemical and biological warfare as well as human rights. Some of the techniques discussed in the report have already been used by the US in the "War on Terrorism".
Modes of Delivery:
A number of weaponization modes are discussed in the report.
These include aerosol sprays, microencapsulation, and insidious methods such as introduction into potable water supplies and psychoactive chewing gum.
JNLWD is investing in the development of microencapsulation technology, which involves creating granules of a minute quantity of agent coated with a hardened shell. Distributed on the ground, the shell breaks under foot and the agent is released. A new mortar round being developed could deliver thousands of the minute granules per round.
The team concludes that new delivery methods under development by the pharmaceutical industry will be of great weapons value. These include new transdermal, transmucosal, and aerosol delivery methods.
The report cites the relevance of a lollipop containing fentanyl used to treat children in severe pain, and notes that "the development of new pain-relieving opiate drugs capable of being administered via several routes is at the forefront of drug discovery", concluding that new weapons could be developed from this pharmaceutical research."
sunshine project 2002
Genetic alteration through Viral infection:
Gene-doping - placed on the list of banned substances by the World Anti-Doping Association last year -
involves the transfer of extra genes into the body to build up key areas such as muscle, tissue or
red blood cells. This is usually done by injecting, or sometimes inhaling, the necessary DNA, usually
"encapsulated" in a virus. -
The goal of the Smart Dust project is to build a self-contained, millimeter-scale sensing and communication platform for a massively distributed sensor network. This device will be around the size of a grain of sand and will contain sensors, computational ability, bi-directional wireless communications, and a power supply, while being inexpensive enough to deploy by the hundreds. source
'Smart Dust' for Monitoring Ready for Sale
Bio machinery - sensors
Engineered Bio-Molecular Nano-Devices/Systems
Program Managers: Dr. Donald Leo
The Engineered Bio-Molecular Nano-Devices/Systems (MOLDICE) Program will develop and demonstrate novel hybrid (biotic-abiotic) nanoscale interface technologies that enable direct, real-time conversion of bio-molecular signals into electrical signals. Biological systems exhibit remarkable sensitivity, selectivity, and efficiency that could be exploited in engineering systems should appropriate interfaces become available.
Biological systems have well-defined sensing units, signal processing units, and actuation sub-systems that determine responses to specific stimuli. While significant effort has gone into understanding the sensing systems of biology (e.g., receptor and transmembrane proteins), the intra-cellular signal processing system is still the subject of many ongoing research efforts. The objective of this program is to develop hybrid bio-molecular devices/systems that use biological units (e.g., Protein Ion Channels/Nanopores, G-Protein Coupled Receptors, etc.) for performing the sensing function but use silicon circuitry to accomplish the signal processing.
Innovative ideas will be explored for the development of interfaces (to ion channels and receptors) that enable the real-time (temporal) transduction of molecular (stochastic) events into electrical signals. A critical focus of this program is the exploitation of temporal (kinetic) information for the real-time analysis and detection of molecular targets.
- source: DARPA
Brain Cells Fused with Computer Chip
By Ker Than - LiveScience Staff Writer
posted: 27 March 2006
The line between living organisms and machines has just become a whole lot blurrier. European researchers have developed "neuro-chips" in which living brain cells and silicon circuits are coupled together.
The achievement could one day enable the creation of sophisticated neural prostheses to treat neurological disorders or the development of organic computers that crunch numbers using living neurons.
To create the neuro-chip, researchers squeezed more than 16,000 electronic transistors and hundreds of capacitors onto a silicon chip just 1 millimeter square in size. They used special proteins found in the brain to glue brain cells, called neurons, onto the chip. However, the proteins acted as more than just a simple adhesive.
"They also provided the link between ionic channels of the neurons and semiconductor material in a way that neural electrical signals could be passed to the silicon chip," said study team member Stefano Vassanelli from the University of Padua in Italy.
The proteins allowed the neuro-chip's electronic components and its living cells to communicate with each other. Electrical signals from neurons were recorded using the chip's transistors, while the chip's capacitors were used to stimulate the neurons.
It could still be decades before the technology is advanced enough to treat neurological disorders or create living computers, the researchers say, but in the nearer term, the chips could provide an advanced method of screening drugs for the pharmaceutical industry.
"Pharmaceutical companies could use the chip to test the effect of drugs on neurons, to quickly discover promising avenues of research," Vassanelli said.
The researchers are now working on ways to avoid damaging the neurons during stimulation. The team is also exploring the possibility of using a neuron's genetic instructions to control the neuro-chip. - www.livescience.com
Effects of Laser Light on Tissue
There are five actions of laser light on tissue that will be helpful to better understand this type of therapy.
1. Accelerated Tissue Repair
The most common example of the conversion of light energy into chemical energy is photosynthesis, where plants manufacture food from carbon dioxide and water. Light energy from the sun is the essential item in that process. No reasonable person disputes photosynthesis, it is a well known process that converts photons of light energy into chemical energy. The action of laser light is quite similar to photosynthesis in plants. Photons of light from a laser penetrate deeply into tissue and power the synthesis of adenosine triphosphate (ATP). ATP is a molecule that is a major carrier of energy from one reaction site to another in all living cells. Increases in ATP as a result of laser light increases the energy available to the cell so that the cell can take in nutrients faster and get rid of waste products. In straight forward terms, the cells of tendons, ligaments and muscles are repaired faster as a result of exposure to laser light. How much faster? A good rule of thumb is that the time for healing is reduced by 2/3rd of the time that would normally take with all other factors remaining the same. i.e. rest, feed, training, etc.
2. Rapid Formation of Collagen
Collagen is the most common protein found in the body. It is estimated that 80% of a horses body is made up of this important fibrous protein. Various types of tissue make up the body. Connective tissue is the most widely distributed. In connective tissue, fibroblast cells produce the ground substance and tissue fibre. The "extra" energy from laser light is used by fibroblasts to increase collagen production. Collagen is the essential protein required to replace old tissue or to repair tissue injuries. Perhaps the most common example of collagen is the clear sticky substance found around open wounds. Wounds are healed or closed over very rapidly by the application of laser light. There is also less scar tissue formed when laser light is applied to the area.
3. Beneficial Effect on Nerve Cells and the Production of B-Endorphins
Laser light has a highly beneficial effect on nerve cells which block pain transmitted by these cells to the brain. Studies have shown that laser light increases the activity of the ATP dependent NA-K pump. In this case, laser light increases the potential difference across the cell membrane moving the resting potential further from the firing threshold, thus, decreasing nerve ending sensitivity. A less understood pain blocking mechanism involves the production of high levels of painkilling chemicals such as endorphins and enkephelins from the brain, adrenal gland and other areas as a result of exposure to laser light.
4. Accelerated Lymphatic System Activity and Reduction in Edema
Everyone wants to reduce the swelling in a horses leg. The problem is that the veins in the leg are only capable of removing one component of the swelling. Blood vessels can remove the water but not the dirty protein solution that is present. So, if a treatment modality accelerates blood flow, this part of the problem is not solved. The lymphatic system is required to take away dirty proteins from edema. Conclusions drawn from research, indicate that laser light is capable of doubling the size of the lymphatic ducts in the area of exposure and rapidly removing the protein waste. Another important aspect of the study showed that laser light was capable of "perfect" regeneration of the lymphatic system in the immediate area with no leakage and no confused network of ducts. In the normal regeneration of lymphatic systems, the ducts are leaky and the duct network is complex and confusing, leading to a tendency to have the same problem occur in the same area.
5. Formation of New Capillaries and Increased Blood Flow
Many types of treatments will increase blood flow. It has been shown that laser light does this extremely well, there is no question about that point. But, what is not commonly recognized is that laser light will significantly increase the formation of new capillaries in damaged tissue. It is the formation of new capillaries that speeds up the healing process, closes wounds quickly and reduces scar tissue.
Using laser light, team guides flies by remote control
Researchers at the School of Medicine have created a high-tech puppet show, only their marionettes are alive and have no strings attached. With the help of some genetic tweaking, the team got fruit flies to walk, jump and fly on command - simply by flashing a light at them.
Over centuries, to better understand the brain's normal functions and the roots of disease, scientists have devised many methods of manipulating animal behavior, but they have had to rely on invasive techniques like stimulating nerves and muscles with implanted electrodes. The new Yale study marks the first time an animal's behavior has been shaped by remote control without such invasive tactics. "We do not have to poke them with electrodes," says Gero A. Miesenbock, M.D., an associate professor of cell biology at the medical school, who led the study.
The research, which appeared in the April 8 issue of the journal Cell, prompted a flurry of international headlines that made comparisons to video games and mind control. It even became fodder for Jay Leno's monologues on The Tonight Show - twice.
But jokes aside, Miesenbock says that the research is a new way to learn how nerve cells govern behavior, and that it will open new avenues to understanding neurological illnesses. "Initially, scientists are often passive observers," Miesenbock says. "But at some point, active control becomes essential in order to establish causes and mechanisms."
Using meticulous genetic techniques, Miesenbock and graduate student Susana Q. Lima, now a postdoctoral fellow at Cold Spring Harbor Laboratory on Long Island, inserted rat ion channels, microscopic pores that admit calcium into cells, in nerve cells that control fruit flies' escape movements. In rats, these channels activate cells by opening in the presence of adenosine triphosphate (ATP), but Miesenbock and Lima injected the flies with a "caged" form of ATP that only functions when exposed to light.
The tiny flies were placed into an arena the size of a dime, where they dawdled until Lima and Miesenbock flashed laser pulses at them, which "liberated" the caged ATP and caused the flies to perform characteristic escape responses. The flies behaved on cue up to 82 percent of the time. "There was all this hope that it would work," Miesenbock says, "but I think the extent to which it did was a very pleasant surprise."
Because escape behavior also occurs when a fruit fly detects a shift from light to darkness that might signal danger - from a descending fly swatter, say - the researchers did the same experiment on a strain of flies in which the visual system was engineered to be insensitive to light, and they got the same response. In another experiment that hints at the technique's potential for restoring neural function, Miesenbock and Lima even got headless flies to perform the trick. Because of the architecture of their nervous system, fruit flies can live for a day or more without their heads, but they remain motionless. However, when equipped with Miesenbock and Lima's "phototriggers," the headless flies took flight whenever the laser was turned on.
In addition to studying the escape circuit, Miesenbock and Lima placed their phototriggers in fruit fly neurons that produce dopamine, a neurotransmitter involved in movement that has been implicated in Parkinson's disease and addiction. When they activated the cells with light, the flies displayed "quite surprising" behaviors reminiscent of dopamine pathologies in humans, Miesenbock says, adding that before these experiments, "very little was known about what these neurons do."
"It's a really cool technique," says Ronald L. Davis, Ph.D., a professor of molecular and cellular biology at Baylor College of Medicine, citing the study's unique strengths as "the untethering of the animal, and using light as the stimulus."
The method is also extraordinarily precise: in one experiment, Miesenbock and Lima were able to place rat ion channels in just two of the 100,000 cells that make up the fly nervous system. And the procedure allows scientists to selectively turn on parts of an intact nervous system. These parts need not be next to each other, and their locations need not be known in advance. This creates enormous potential for discovering which groups of neurons control which aspects of behavior.
Both Miesenbock and Davis say that applying the technique to human illness is still far off, and for now, Miesenbock is sticking to fruit flies. Next he plans to probe the neural activity around their courtship behavior - essentially, he'll be playing Cupid. "It's not just the sex act that interests us," he says, but "it'll get us on The Tonight Show again, I'm sure."
Fly brains manipulated by remote control - Laser-activated chemicals target specific neurons
"This is a new approach to neuroscience," said Gero Miesenbock from the Yale University School of Medicine. "We can not only passively observe but actively control behavior."
Besides being unwieldy to work with, electrodes can inadvertently stimulate nearby neurons. The new phototrigger technique can target just one type of neuron to activate, using a genetic preselection trick.
The remote control setup - developed by Miesenbock and Susana Lima, both from Yale University School of Medicine - can be broken down into three components: a lock, a key and a trigger. The lock is an ion channel - a kind of protein that allows charged particles to pass through a cell membrane.
The researchers genetically altered particular neurons to have an ion channel not normally found in fruit flies. The key is a molecule called adenosine triphosphate, or ATP. By binding to the ion channel, ATP makes the neuron fire. Typically, ATP is a form of fuel, or "energy currency," inside cells, "but there is very little of it flowing in between cells," Miesenbock said. So the scientists had to inject ATP into the fly brains. To regulate the firing of the altered neurons, the researchers isolated the injected ATP in a molecular cage that breaks open when struck with an ultraviolet laser beam.Lima and Miesenbock placed their ion channel lock in the giant fiber system, a small set of nerve cells that controls the fruit fly's escape movements - like jumping and wing flapping.
When flashed with a 200-millisecond laser trigger, flies outfitted with locks and keys responded between 60 and 80 percent of the time with the expected escape behavior. And this was not because the laser scared the flies. In fact, blind flies reacted in the same way. The laser light penetrates the flies' cuticle, or "skin," to free the caged ATP.
A genetic switch
Being able to select classes of neurons to stimulate with high precision provides a separate genetic tool for understanding how the brain controls behavior.