By David N. Leff

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Calling someone a "knee-jerk so-and-so" accuses the target person of acting automatically, thoughtlessly, recklessly. The term comes from a familiar neurological test, in which the patient sits up high with his leg hanging loose. A smart tap just below the kneecap causes a normal person's leg to kick upward instantly.

In another diagnosis of limb function, a slight pin scratch across the ball of the foot normally scrunches all the toes together. But in a patient afflicted with spastic paraplegia (SP), the big toe juts outward sideways. "This completely abnormal big-toe response," observed molecular geneticist Jamili Hazan, "is a sign of pyrimidal or corticospinal disease. (See BioWorld Today, Nov.10, 1999, p. 1.)

Even before doing these telltale tests, the first thing a neurologist looks for in a person suspected of SP is his or her peculiar way of walking. "All of the SP patients," Hazan told BioWorld Today, "have a very special gait, known as 'scissors gait.' One leg swings across the other instead of going straight forward, producing a crisscross motion of the limbs in walking."

Although marked by unusual features, SP isn't an unusually rare disorder. "It affects about one live birth in 30,000," Hazan noted, with no geographical, ethnic or gender preference. And it comes in one of two markedly difference types - "pure" and "complicated." SP's "pure" version is limited to paralysis of the lower limbs, she said, "not life-threatening, but varying from only a mild stiffness to wheelchair-bound to bedridden."

"Complicated" SP can add to this basic symptom, Hazab went on, "additional features, such as mental retardation, dementia, epilepsy, ataxia, ichthyosis ('alligator skin' or 'fish skin') deafness and optic atrophy, to name a few. Also, SP can indiscriminately strike a newborn or someone over 70."

Five years ago, the French National Institute of Health and Medical Research (INSERM) assembled a task force to clear up the bafflement as to SP's pathophysiology and weird variability. At Genoscope, the National Sequencing Center, post-graduate Jamili Hazan headed a team that set out to clone SP's gene, and identify its protein product.

Their quest culminated in Nature Genetics for November 1999, with a paper - of which she is lead author - titled "Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia."

Hazan has now moved on to a postdoctoral appointment at Guy's Hospital in London, but the SP research in France continues. "The lab will go on to find out," she observed, "if this spastin protein is really nuclear, as we presumed. Then another lab will produce some antibodies against the protein, to see where it is expressed. Apparently spastin is ubiquitously expressed, but you've got to look more precisely in the different regions of the brain. And another lab will try to create a mouse mutant of this gene."

Meanwhile, she pointed out, having determined that all the many affected families they studied have mutations in the spastin gene they discovered, "we can diagnose the gene in people, and do genetic counseling, even though that's pretty delicate. Because the severity of SP's symptoms is highly variable," Hazan concluded, "you can't tell an expectant mother that she's going to have a very severely affected child - or not."

Findings Elucidate Mechanism Of Paraquat Herbicide's Toxicity, How Inhaled Antidote Works

Paraquat is a widely used herbicide. Besides killing weeds, it helps cotton farmers harvest their crop, by defoliating the mature plants, leaving the bolls easy picking. The U.S. Drug Enforcement Agency has sprayed paraquat from helicopters to bomb fields of poppy and marijuana in Mexico.

However, paraquat (PQ) is a highly poisonous chemical compound. When ingested, inhaled or absorbed through the skin, it can cause severe liver and kidney damage, plus lethal pneumonia. But its mode of action has remained a controversial medical mystery.

Now a research article in the Oct. 26, 1999 Proceedings of the National Academy of Sciences (PNAS) reports: "A mechanism of paraquat toxicity involving nitric oxide synthase [NOS]."

Its co-authors find that "NOS plays important roles in neurotransmission, smooth muscle relaxation, inflammation, host defense and regulation of cell death, depending in part on the localization of the specific isoform in tissue."

Their studies "suggest that PQ acts as an acceptor of NOS electrons - with likely impact on the pulmonary pathophysiology of PQ poisoning." They point out, "Severe PQ poisoning produces adult respiratory distress syndrome, pulmonary hypertension, edema, and progressive lung fibrosis, which may explain why patients suffering from PQ poisoning improve when treated with inhaled nitric oxide."

Far Fewer Male Monkeys Than Male Humans Are Color-Blind, Gene Analysis Determines

Men are much more likely than women to be color-blind. In fact, 8 percent of Caucasian males have some form of impaired color vision, linked to three types of color-sensitive pigment in their eyes. Each of these responds to a different wavelength of light.

Like humans, Old World monkeys also have trichromatic color vision, but it seems that color blindness is far rarer in these primates than in man. A brief paper in Nature, dated Nov. 11, 1999, reports, "Dichromatism in macaque monkeys."

Its 13 Japanese co-authors analyzed wavelength-specific gene sequences from 3,153 macaque monkeys - 1,199 male and 1,954, female. Of 755 males and 653 females within this cohort, they found "only three DNA samples from males that lacked the exon-5 fragments of the L gene" - which is sensitive to long wavelengths of light. This 0.4 percent frequency, the co-authors noted, contrasted with 2 percent dichromatism in a survey of 30,000 Caucasian male humans.