Causative antigen can also suppress disease - C&EN Global

Publication Date: September 11, 1972. Copyright © 1972 ... These cells eventually migrate to the brain, where they attack and destroy the myelin shea...
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uniform environment. Their swimming behavior could then be observed. Normally, Dr. McNab says, bacteria swim in a slightly erratic pattern. If they are rapidly transferred to a new en­ vironment identical to the old, they swim normally. However, if the transfer is to an environment richer in nutrient, they swim in an extremely smooth man­ ner for awhile, then revert to their nor­ mal pattern. If the new environment is poorer, on the other hand, they tumble constantly and can't maintain a con­ stant direction, again reverting to nor­ mal after a short time. This "memory" behavior, according to Dr. McNab, lasts for up to a few minutes if the environ­ mental change is positive, 10 to 15 sec­ onds if negative. Dr. McNab likens the overall swim­ ming behavior of a bacterium to a drunken walk, by which it slowly moves up favorable gradients or down unfav­ orable. Favorable gradients include various sugars and amino acids; un­ favorable, substances such as phenol and low-molecular-weight carboxylic acids. Just how bacteria sense a gradient isn't known, but Dr. McNab speculates that the mechanism might involve chemoreceptors, binding proteins on the surface of a bacterium. Such receptors have been characterized by others for two cases—galactose and ribose. Dr. McNab speculates that if a bacterium had two receptors on its surface specific to a nutrient, one which would respond quickly and one slowly, the imbalance could in some way signal the flagella by which the bacterium swims.

Causative antigen can also suppress disease < ^ \ MEDICINAL—The protein that ^ F causes a normally fatal brain dis­ ease can also be used to suppress the disease, according to Dr. Ε. Η. Eylar of Merck Institute, Rahway, N.J. At a symposium on immunity and inflamma­ tion, Dr. Eylar described the results of his experiments with monkeys as "one of the first cases of immunosuppressive treatment of an autoimmune disease with the causative antigen." Dr. Eylar and his team have been studying the Al protein, which makes up about 30% of the protein of the mye­ lin membrane (the insulating material surrounding nerve fibers). Al protein appears to be a focus for pathological events associated with myelin, the Merck scientist says. Injected into animals, it brings about an immune response leading to the production of lymphocytes that are sensitized to the Al protein. These cells eventually mi­ grate to the brain, where they attack and destroy the myelin sheath. The resulting disease, called experi­ mental allergic encephalomyelitis (EAE), causes leg weakness and paraly­ sis, loss of coordination and visual

acuity, and, finally, death. Dr. Eylar notes that EAE has been one of the most extensively studied of autoimmune diseases because of its similarity to human demyelinating diseases such as multiple sclerosis and to the paralysis that sometimes follows rabies vaccina­ tions. Analysis of human Al protein has shown it to be a single polypeptide chain of 170 amino acids. Unlike most pro­ teins, which exist in globular form, Al protein is highly unfolded, Dr. Eylar says, and its immunologic specificity appears to reside in short, unique seg­ ments of the chain. To correlate chemical structure with antigenic activity, Dr. Eylar and his team tested peptide fragments derived from the Al protein by enzymic or chemical breakdown. A major stimulus occurred, Dr. Eylar says, when they iso­ lated the segment—a nonapeptide— that induces EAE in guinea pigs and rabbits. The same peptide produced synthetically also caused the disease, he notes. Later, they isolated a different fragment containing the major EAEinducing site for the monkey—of special interest, Dr. Eylar points out, because of its possible relevance to human dis­ ease. With the cause of EAE established, emphasis shifted to treatment. Many immunosuppressive agents are partially effective against EAE if given at or near the time of sensitization, Dr. Eylar says. However, his goal was to suppress EAE under the conditions most relevant to human disease—after clinical signs have appeared, when "conventional" immunosuppressive agents are ineffec­ tive. "We chose to use the Al protein itself as the best possible suppressing agent, since it should affect only the aberrant cells responsible for the disease, not the normal cells," Dr. Eylar explains. He first determined that the protein, when appropriately administered, was com­ pletely safe. Then, in a three-year study, he found that administration of Al protein suppressed the course of EAE in 80% of the previously sensitized mon­ keys. If not treated, 100% of the mon­ keys died. Dr. Eylar notes that the monkeys that respond to the treatment appear to be permanently recovered after Al protein has been given daily for 14 days. If sup­ pressive treatment is stopped earlier, signs of the disease return. However, Dr. Eylar adds, the suppressive treat­ ment can be successfully reapplied in such cases. Correction

In the story on gel entrapment of en­ zymes (C&EN, Sept. 4, page 17), C&EN incorrectly placed Dr. K. F. O'Driscoll at the University of Toronto. He is in the department of chemical engineering at the University of Waterloo, Waterloo, Ont.

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