By David N. Leff
Editor's note: Science Scan is a roundup of recently published, biotechnology-relevant research.
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - both autoimmune afflictions - often occur in the same patient. Now they apparently share the same common denominator. It's a molecule of the immune system called B Lymphocyte Stimulator - BLyS.
BLyS is a naturally occurring immune-system growth-factor protein. It works by binding to B cells, which promote secretion of antibodies - the body's frontline defense against infection and cancer - not to mention friendly fire against autoimmune antigenic targets, attacking constituents of the SLE and RA in patients' bodies.
RA patients in the U.S. number more than 2.5 million. The disorder can lead to severe disability, and, in extreme cases, death. There are 500,000 SLE sufferers, whose symptoms include kidney dysfunction, joint inflammation, skin rashes - and also possible death.
Scientists at the University of Alabama in Birmingham checked on the level of BLyS in the blood of 150 SLE patients. It was a good deal higher in those who also had more of an antibody that attacks the patient's own DNA. Their presentation was titled, "A role for B Lymphocyte Stimulator (BLyS) in Systemic Lupus Erythematosus."
At the University of Southern California in Los Angeles, rheumatologists examined the blood of 185 patients with SLE, RA and other systemic autoimmune diseases. They found that BLyS was greater by far than in the blood of normal individuals, as they reported in a paper titled: "Elevated B Lymphocyte Stimulator (BLyS) levels in patients with systemic immune-based rheumatological diseases."
Both groups reported their findings on Oct. 30 to the annual scientific meeting of the American College of Rheumatology, in Philadelphia. Taken together with previous animal studies, the two academic teams concluded that excess BLyS causes overproliferation of antibody-producing B cells in SLE and RA subjects.
Craig Rosen, executive vice president for research and development at Human Genome Sciences Inc. (HGS), in Rockville, Md., assessed these new studies as providing "a clear rationale that we should test the hypothesis that an anti-BLyS antibody may be an effective therapy for SLE and RA." HGS announced discovery of BLyS in July 1999. (See BioWorld Today, July 13, 1999, p. 1.)
Neurobiological Voyeurism Of Female Rats In Heat Reveals Hormonal Basis Of Reproductive Behavior
The term "lordosis" does not mean a surfeit of nobility. It does mean a characteristic piece of body language in certain female mammals, indicating to their wannabe lord and master (of the moment), "Come and mount me; I'm in the mood for copulation." It consists of the female arching her back to expose her rump. (See BioWorld Today, Feb.11, 2000, p. 1.)
This behavior pattern is a boon to neurobiologists who study the metabolic basis of reproduction in human and subhuman animals. Thus a research article in the Proceedings of the National Academy of Sciences (PNAS) dated Nov. 7, 2000, opens with this explanation:
"Lordosis is a reproductive behavior, characterized by the rigid dorsiflexion of the spinal column and elevation of the hind quarters observed in mating female rodents. The lordosis posture allows intromission by the male and is due to elevated circulating levels of estradiol (E) and progesterone (P) from the ovaries, which occurs during proestrus, accompanied by gentle pressure on the vagina from the male." The PNAS paper itself bears the title: "A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors."
In charge of lordosis are receptors for these two ovarian steroid hormones, E and P. To discover behaviorally relevant genes targeted by them in the brain's hypothalamus, the co-authors ovariectomized rats to ablate their own hormones, then treated them with E alone or E plus P. "We show here," they report, "that one interesting messenger RNA within the hypothalamus that is repressed by P after E priming encodes the protein 25-Dx, the rat homolog of the human membrane-associated P-binding protein Hpr6.6."
It isn't entirely a females-only show. "P," the paper notes, "initiates the acrosomal reaction of sperm during conception [as well as] rapid effects on female rodent reproductive behavior."
Ten Cloned Calves From Aged Cow Refute Fears That Clones From Old Donors Have Lower Life Expectancy
Animal scientists at the University of Connecticut, Storrs, have reported answering a burning question. It concerns a study a year later on Dolly, the cloned sheep, which showed that her cells seemed prematurely old. That finding raised serious doubts about whether cells from adult animals could become young again through cloning - and threatened the hope that future medical treatments could be developed based on cloned cells.
To study the way clones age, the Storrs team produced 10 identical cloned calves from a 13-year-old cow. They report, in the November 2000 issue of Nature Genetics, "Normal telomere lengths found in cloned cattle." The Brief Communication found that cloned cattle have normal telomere lengths, that shortened telomeres of donor cells are restored by the cloning procedure.
Reactive Oxidation, Nitration Species, Arraigned In Pathology Of Neurodegenerative Diseases
Oxygen isn't the only element that shoots destructive ions into cells under stress. Nitrogen is another. Cells are equipped to disarm these highly reactive molecules, but neurodegenerative diseases, notably Alzheimer's and Parkinson's, may result when these defense systems are overwhelmed by oxidation or nitration.
Authors of a paper in Science dated Nov. 3, 2000, make this point. They are neuropathologists at the University of Pennsylvania, Philadelphia. Their article is titled "Oxidative damage linked to neurodegeneration by selective a-synuclein nitration in synucleinopathy lesions."
"Our findings," their article concludes, "suggest that . . . elucidation of the role of oxidative and nitrative injury in mechanisms underlying these and other neurodegenerative disorders may lead to the identification of therapeutic targets to prevent or reverse these diseases."