=============================================================== == == == ----------- ALS INTEREST GROUP ----------- == == ALS Digest (#27, 05 MAR 1993) == == == == To subscribe, to unsubscribe, to request back issues, == == to contribute notes, etc. to ALS Digest, please send == == e-mail to: == == bro@huey.met.fsu.edu (Bob Broedel) == == == == All interested people may "broadcast" messages to == == to ALS Digest subscribers by sending to: == == als@huey.met.fsu.edu == == == =============================================================== (1) ===== AUTOIMMUNE ========== Date : Fri, 5 Mar 1993 14:50:25 +0100 Sender : "Neuroscience Information Forum" NEURO1-L@UICVM.BITNET From : Paul.Herrling@PKFLTG.PHARMA.SANDOZ.CH Subject: ALS To : bob broedel A new paper investigating autoimmune aspects of ALS: ------------------------------------------------------------------- Magnelli et al. "The action of amyotrophic lateral sclerosis immunoglobulins on mammalian single skeletal muscle Ca++ channels" J. Physiol. 461:103-118 (1993) ------------------------------------------------------------------- Cheers, Paul Herrling (2) ===== SCIENTISTS IDENTIFY GENE DEFECT ========== Washington Post (04 MAR 93)P Scientists Identify Gene Defect Linked to Lou Gehrig's Disease By David Brown, Washington Post Staff Writer Researchers have identified a gene defect that occurs in some cases of amyotrophic lateral sclerosis, a cruel, and ultimately fatal, nerve disorder commonly known as Lou Gehrig's disease. The genetic mutation, described in today's issue of the journal Nature, surprised its discoverers because it occurs in a protein found in all cells. ALS, on the other hand, is characterized not by damage to numerous organs but by the degeneration of a highly specific region of the spinal cord. The disease strikes about one in every 100,000 persons, generally arising after age 50. Although scientists have known for nearly a century that nerve cell death is the essential step in ALS, they have known virtually nothing about what leads up to that event. The new finding will help unravel the complicated - and apparently very drawn out - chain of events culminating in the disease. The defect described this week was found in a group of families with hereditary ALS, a rare form that accounts for about 10 percent of cases. "What does this mean for all of ALS? Why is it that only those tissues affected in ALS are vulnerable to this mutation? There are many doors that this opens, but it doesn't answer what's inside them," said Carl Leventhal, head of degenerative nerve diseases at the National Institute of Neurological Disorders and Stroke. Specifically, the investigators found that ALS sufferers in 13 of 18 families carried a mutation in the gene for superoxide dismutase (SOD), a cellular peacekeeper whose job is to disarm highly reactive chemicals called "free radicals." Free radicals destroy cellular membranes, strands of DNA and essential enzymes. So-called anti-oxidant compounds, such as SOD, prevent or limit the damage. Because the mutation was not found in five families with hereditary ALS, the defect cannot be the only cause of the disease. However, other genes modulate the action of SOD, so it is possible that all forms of the disease operate through the same general mechanism of oxidative injury. Free-radical damage is most often seen in acute illnesses, such as strokes or heart attacks, in which blood flow to living tissue is cut off or greatly reduced. Though researchers have speculated free radicals might play a role in some brain disorders, ALS was not high on the list of possible candidates. "One of the reasons we find ourselves wide-eyed and really excited is that we had not really taken the idea seriously," said Robert H. Brown Jr., one of the 32 authors of the paper in Nature. ALS destroys motor neurons in the brain and spinal cord, the cells responsible for stimulating muscles. For unknown reasons, the eyes and bladder are often spared. Sensation and thinking are also unaffected. ALS patients are often paralyzed but fully conscious for years, dying of respiratory failure or, if they are placed on artificial breathing devices, of other complications of the illness. Life expectancy is about five years after diagnosis. There is no treatment, and the new findings are not likely to lead to one in the immediate future. At this point, the researchers do not know if the gene defect results in insufficient amounts of SOD, or in an overactive form of the protein. Both are plausible hypotheses on biochemical grounds, though the former is more likely, experts say. "The therapies would be quite the opposite of each other, depending on which mechanism it is," said Teepu Siddique, a neurologist at Northwestern University and another of the authors. "That is why it is important to know more before one talks of therapy." Some scientists have recently speculated that motor neurons of ALS patients die from a curious phenomenon called "excitotoxicity," in which nerve cells are essentially tickled to death by a stimulating neurotransmitter called glutamate. In a complicated, and still speculative, biochemical scenario, SOD may function to reduce the concentration of glutamate around nerve cells to reasonable levels. In New Guinea, the Mariana Islands and a few other scattered areas of the Western Pacific, ALS occurs at rates 100 times greater than elsewhere in the world. The reason is unknown, although one theory is that it is linked to consumption of wild seeds high in a glutamate-like substance. The seeds were especially important in the native diet during World War II when the Japanese confiscated cultivated crops. In recent years, rates of ALS have fallen to about one-tenth of its previous level, according to Leonard T. Kurland, a neurologist and epidemiologist at the Mayo Clinic, who has been studying the disease in the Western Pacific since 1953. Some people who lived in villages where ALS was endemic but left while teenagers nevertheless developed the disease 20 to 30 years later. This suggests a short-lived exposure, or possibly even a single event, may set a process of nerve cell degeneration in motion that a person will not recognize for decades. (3) ===== GROOTE EYLANDT ========== To : bro@huey.met.fsu.edu From : ZINJMAN@uog.pacific.edu Subject: Re: Groote Eylandt Date : Mon, 1 Mar 93 14:18:11 PST I have seen passing mention made of (1) high als/pdc rates on Groote Eylandt, Northern Australia, and (2) that Groote Eylandt has the same soil and drinking water composition as Guam and the other hyperendemic foci areas for als/pdc in the Western Pacific. My initial searches of the MEDLINE database has not yielded anything on the above. If any subscribers have information/references to pass on, I'd be most appreciative. Gary Heathcote, Anthropology Program, College of Arts and Sciences, University of Guam, UOG Station, Mangilao, Guam 96923 FAX: 671-734-7930 (4) ===== ORIENTATION ========== >Date : Tue, 02 Mar 93 08:28:59 EST >From : Mary ann Johnson >Subject: ALS communications >To : Bob Broedel > >I am interested in being a part of the e-mail group about ALS. >Do you envision it as being research oriented? or applied? >Mary Ann H. Johnson >Virginia Tech Extension Communications. Please let me know. >JNAYRAM@vtvm1.cc.vt.edu > Speaking for myself, I am searching for applied information about how to be a care giver to an ALS patient. The orientation of the group should go as subscribers wish. If needed, we can break down into a multi-group format. My outreach efforts are being directed to *all* who are interested in the topic of ALS. Time will tell. What are your expectations? Hopefully you will stick with us. rgds,bro P.S. It is no longer necessary to stick with the "digest" format. All are welcome and invited to broadcast messages to the group via the address: als@huey.met.fsu.edu (5) ===== INFO RE The Online Journal of Current Clinical Trials ========== Date : Mon, 1 Mar 1993 14:44:57 CST Sender : NEW-LIST - New List Announcements From : Electronic Publishing Section Subject: NEW: OCLC-JOURNALS OCLC-JOURNALS on LISTSERV@OCLC.ORG - OCLC electronic journal publishing The OCLC-JOURNALS list is provided as a means of distributing information about OCLC electronic journal publishing, including information about The Online Journal of Current Clinical Trials, published as a joint venture between the American Association for the Advancement of Science (AAAS) and OCLC Online Computer Library Center. New articles published in OJCCT are announced on this list. The OCLC-JOURNALS list will eventually become a moderated discussion list covering topics associated with OCLC electronic publishing; subscriber postings to the list will be ignored until that time. Also associated with this list are informational files, including descriptive, pricing, and subscription information about journals published electronically through OCLC's electronic publishing services. To subscribe to the OCLC-JOURNALS list, send: SUBSCRIBE OCLC-JOURNALS Your Name as the body of a mail message to the list SERVER address (LISTSERV@OCLC.ORG). For example, SUBSCRIBE OCLC-JOURNALS Jane Doe. List Owner: Deb Bendig (e-pub@oclc.org) (6) ===== Regeneron (re CNTF) ========== RTf 03/02 1646 Nasdaq stocks close with sharp gains NEW YORK, March 2, Reuter - Nasdaq stocks gathered steam in late afternoon trading to close up 1.23 pct, boosted by gains in technology and biotechnology stocks. Investors showed little interest at the early stages of the session, but bargain-hunters stepped in to snap up slumping shares as the afternoon progressed, traders said. The Nasdaq composite ended up 8.21 points to 677.72. Gainers beat losers three to two on moderate volume of 207 million. The index on Monday ended a three-session winning streak with a 0.19 pct drop. Biotechnology shares regained luster after being hammered in recent weeks by disappointing product news and investor jitters over Clinton administration policies. A positive Wall Street Journal article on Amgen aided the group, traders said. Genzyme rose 1-1/2 to 33-1/2, Biogen gained one to 31 and Regeneron Pharmaceuticals gained three to 15-1/4. Amgen closed down 1/8 to 37-1/2 after rising 1-3/8 on Monday. Among technology issues Microsoft rose 3-1/8 to 84-3/8. Dick Gunter, senior vice president at Wedbush Morgan, described the day as a short-term bounce from recent losses. "I can't look at this and say the market has turned and will be up for any sustained period of time," he said. -- R. Jacobsen 212/912-7195 REUTER (7) ===== CARE GIVER ========== Date: 2 Mar 1993 12:09:26 U From: "Chris Oseto" Subject: ALS To: "BOB BROEDEL" My wife passed away on 26 December 1992 from ALS. I would be pleased to provide any information from the perspective of a care giver. == end of als 27 ==