Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
Military forces - ground, air and water - send scouts and frontline units ahead in advance of the main military punch lines. They may have learned a thing or two - specifically, two - from the body's immune defenses. Ahead of their multilayered adaptive immunity they deploy the innate immune system. Innate means "built-in."
Many infections are dealt with in their earliest stages by the innate immune system. At first this was thought to be a fairly simple response, but it now seems that there are different arms of the innate reaction that distinguish different types of infective pathogen. One key molecular player in innate immunity, Nod1 by name, can sense specific fragments - muropeptides - of the proteinaceous cell wall component of Gram-negative bacteria.
Results from French, German and U.S. co-authors suggest that Nod1 acts as a sentinel molecule in the epithelial cells (the frontline skin surface) against invasive pathogens. Nod1 discriminates intracellular Gram-positive and Gram-negative microorganisms, and helps shape subsequent adaptive immune responses, once innate has done its job.
This subtle division of labor is laid out in a recent issue of Science, dated June 6, 2003, and titled "Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan." Its senior author is microbiologist/immunologist Dana Philpott, an associate professor of cell biology and infection at the Pasteur Institute in Paris.
"Our finding," she told BioWorld Today, "reports detection of the first intracellular bacterial infection - its direct action in the body by the innate immunity system vs. the adaptive T and B cells of the adaptive immunity. The latter produce cytokines and directly kill invading bacteria.
"Nod1," she explained, "is a member of a family of proteins probably involved in inflammation and/or bacterial detection. It's specific for peptidoglycan, which mainly occurs in Gram-negative bacteria. Peptidoglycan," Philpott continued, "is a component of the bacterial cell wall. Once the bacterium has breached the cytoplasmic barrier, the Toll-like receptors [TLR] present their binding domain to the cellular space. For instance, if you have bacteria in the blood, these TLRs would be more involved in detecting that infection. Toll-like,'" she recounted, "is a German word meaning Wow! How cool that is! Or Holy Cow!'
"In the body," Philpott pointed out, "the epithelial cells are really the first barrier that a bacterium would come up against. Skin, lung, intestine or genitourinary tract, it's always epithelial cells that are first encountered by any bacterial pathogen. Most times," she recounted, "when they're found in the colon, where we have tons of bacteria and their products, we don't want an extra cellular sensing system. But if a bacterium can breach the barrier and get into the cell, that's when we need the backup system, which would be the NOD proteins. So the epithelium is at the forefront of the battle between the bacteria and the host. It's really the front line of the innate system."
Aranesp Anti-Anemia Drug Paid Off In Cancer Patients On Or Off Weekly Chemotherapy Doses
Anemia is a common problem in cancer patients treated with chemotherapy. Yet, as many as 400,000 cancer patients suffer from anemia due to the disease itself, unrelated to chemotherapy. Despite its prevalence, and symptoms of severe physical and mental exhaustion, anemia in cancer patients is under-recognized and undertreated.
A clinical trial reported in the British Journal of Cancer on June 16, 2003, found that a therapeutic compound trademarked Aranesp from Amgen Inc., dosed once a month, corrects anemia and maintains hemoglobin levels in cancer patients not undergoing chemotherapy.
The journal article is titled "A dose- and schedule-finding study of darbepoetin alpha [Aranesp's chemical name] for the treatment of chronic anemia of cancer." The Phase II study is the first to evaluate the dose and schedule of an erythropoietic agent in patients with chronic anemia of cancer not receiving chemotherapy.
The trial's findings are regarded as significant because cancer patients not receiving chemotherapy usually visit their physicians once a month. Dosing Aranesp every few weeks reduces the burden of frequent clinic visits on the patient, caregiver and oncology practice.
Co-authors representing 24 medical groups in 10 states took part in the survey, which gave enrolled patients subcutaneous injections of the drug once a week for 12 weeks. "Darbepoetin alpha effectively increased hemoglobin concentration when given weekly, thrice or four times. Less-frequent administration," the report concluded, "may benefit patients with chronic anemia of cancer and their caretakers alike."
New Primary Open Angle Glaucoma (POAG) Data Confirm Juvenile As Well As Adult Onset
Glaucoma, a complex, multifactorial eye disease, is among the leading causes of visual loss in the industrial world. POAG, or primary open angle glaucoma, is the major form of this disorder, which has adult onset. It's a highly prevalent optic neuropathy and a salient cause of irreversible blindness.
InSite Vision Inc., of Alameda, Calif. - an ophthalmic therapeutics, diagnostics and drug-delivery company - announced the linkage of a gene variant promoting a more rapid progression of glaucoma. The report appears in the June 2003 issue of the journal Clinical Genetics under the title "Association of the myocilin mt.1 [POAG gene] promoter variant with the worsening of glaucomatous disease over time."
"The results of this study," the article said, "indicate substantial evidence that the TIGR/MYOC [TIGR = trabecular meshwork induced glucorticoid response gene] mt.1(+) gene variant provided a strong marker for accelerated worsening of both optic disc and visual field measures of glaucoma progression above and beyond other risk factors." The study is based on information gathered at Philadelphia-based Wills Eye Hospital from 147 adult patients with POAG, who were followed up for some 15 years.
Point mutations in the gene's coding region have been confirmed to be involved in a substantial number of familial juvenile glaucoma cases. This finding, the article pointed out, "could have useful, practical implications for glaucoma management."