One page summary on the article below

Major94

scientificamerican1180-90.pdf

Home >Biology homework help >One page summary on the article below

Carbohydrates Sugars and chains of sugar units are the most abundant consdtuent

of living matter. New carbohydrates are still being discovered, as

are new roles for them in normal biological processes and disease

T he four major classes of com pounds essential to life are nucle ic acids, proteins, lipids and car

bohydrates. Over the past 30 years the first three classes have received much attention from chemists and biologists, whereas during most of that time the carbohydrates were largely neglected, partly in the belief that their chemistry and biology had been fully worked out. In the past decade, however, research on carbohydrates has been revived and is now expanding rapidly. As a result of many new developments carbohydrate research is today broad and diverse.

The study of carbohydrates and their derivatives has greatly enriched chemis try, particularly with respect to the role of molecular shape and conformation in chemical reactions. Recent carbohy drate investigations have played a deci sive role in the characterization of vari ous antibiotics and antitumor agents. Such studies have led to the discovery of new biosynthetic reactions and enzymic control mechanisms and are contribut ing significantly to the understanding of many fundamental biological processes, for example the interaction of cells with their environment and with other cells. As a result revolutionary new methods for combating bacterial and viral infec tions and for targeting drugs on diseased cells and organs are being envisioned. Carbohydrate research has also pro vided a basis for recognizing the en zyme deficiency underlying several ge netic disorders and has led to the hope that they can be treated effectively. A common theme behind many of the recent findings, which is also a powerful driving force in carbohydrate research, is the realization that monosaccharides (the basic units of carbohydrates) can serve, as nucleotides and amino acids do, as code words in the molecular lan guage of life, so that the specificity of many natural compounds is written in monosaccharides.

Carbohydrates are sugars or (like starch and cellulose) chains of sugars. To most people sugar is the common household foodstuff, which to the chem ist is sucrose. Chemically the molecule

by Nathan Sharon

of sucrose consists of two monosac charides, or simple sugars, glucose and fructose, that are hooked together; it is thus a disaccharide. More than 200 different monosaccharides have been found in nature, all of which are chemi cally related to gl ucose or fructose. As a rule they are white crystalline solids that dissolve readily in water. Some of them have not been obtained in amounts suffi cient for testing their sweetness, but they are still called sugars, as are the mon osaccharides that are found to be not sweet.

Glucose is the best-known'monosac chari de; indeed, it has probably been in vestigated more thoroughly than any other organic compound. It was un doubtedly known to the ancients be cause of its occurrence in granulated honey and wine must. References to grape sugar, which is glucose, are to be found in Moorish writings of the 12th century. In 1747 the German pharma cist Andreas Marggraf, whose isolation of pure sucrose from sugar beets is an example of the chemical art of the time at its best, wrote of isolating from raisins "eine Art Zucker" (a type of sugar) dif ferent from cane sugar; it was what is now called glucose. The action of acids on starch was shown to prod uce a sweet syrup from which a crystalline sugar was isolated by Constantine Kirchoff in 1811. Later workers established that the sugar in grapes is identical with the sug ar found in honey, in the urine of diabet ics and in acid hydrolysates of starch and cellulose. The French chemist Jean Baptiste Andre Dumas gave it the name glucose in 1838. The structure of gl u cose and of several other monosac charides, including fructose, galactose and mannose, was established by about 1900, mainly by the brilliant work of the German chemist Emil Fischer, who thereby laid the foundations of carbohy drate chemistry.

Monosaccharides rarely exist as such in nature. They are found in the form of various derivatives, from which they can be liberated by hydrolysis with aqueous mineral acids or with enzymes. The most abundant of the derivatives

are polysaccharides, which are made up of sugar units formed into giant mole cules that can consist of as many as 26,000 monosaccharides (as in cell u lose from the alga Valonia). Sugars also occur frequently as oligosaccharides, which are compounds made .up of from two to 10 monosaccharides. Sugars are frequently found in combination with other natural substances.

The "Water of Carbon"

The name carbohydrate was original ly assigned to compounds thought to be hydrates of carbon, that is, to consist of carbon, hydrogen and oxygen in the gen eral formula C"(H20),,. Indeed, glucose and other simple sugars such as galac tose, mannose and fructose do have the general formula CSHI20S. They are typ ical hexose monosaccharides, meaning that they have six carbon atoms. With the accumulation of more data the defi nition has been modified and broadened to encompass numerous compounds with little or no resemblance to the orig inal "water of carbon . " Carbohydrates now include polyhydroxy aldehydes, ke tones, alcohols, acids and amines, their simple derivatives and the products formed by the condensation of these different compounds through glycosid ic linkages (essentially oxygen bridges) into oligomers (oligosaccharides) and polymers (polysaccharides).

Much of the current interest in carbo hydrates is focused on such substances as glycoproteins and glycolipids, com plex carbohydrates in which sugars are linked respectively to proteins and lip ids. They are termed glycoconjugates. It should also be noted that in the excite ment about nucleic acids a simple fact is being forgotten: they too are complex carbohydrates, since monosaccharides are among their major constituents (ri bose in RNA and deoxyribose in DNA).

Carbohydrates are the most abundant group of biological compounds on the earth, and the most abundant carbohy drate is cellulose, a polymer of glucose; it is the major structural material of plants. Another abundant carbohydrate

CELL-SURF ACE ROLE of a carbohydrate, mannose, is indicated in this scanning electron micrograph made by Fredric Silverblatt and Craig Kuehn of the Veterans Administration Hospital in Sepulveda, Calif. Cells from tissue on the inside of the human cheek occupy the

background of the micrograph; the white cylindrical objects are Esch erichia coli bacteria. The mannose, which is on the cell membrane, is not visible, but it is causing the E. coli to adhere to the tissue surface. Such adherence to surfaces is the first step in a bacterial infection.

is chitin, a polymer of acetylglucos amine; it is the major organic compo nent of the exoskeleton of arthropods such as insects, crabs and lobsters, which make up the largest class of or ganisms, comprising some 900,000 spe cies (more than are found in all other families and classes together). It has been estimated that millions of tons of chitin are formed yearly by a single spe cies of crab!

Carbohydrates are also the fuel of life, being the main source of energy for living organisms and the central path way of energy storage and supply for most cells. They are the major prod ucts through which the energy of the sun is harnessed and converted into a form that can be utilized by living organisms. According to rough estimates, more than 100 billion tons of carbohydrates are formed each year on the earth from carbon dioxide and water by the process of photosynthesis. Polymers of glucose, such as the starches and the glycogens, are the mediums for the storage of ener gy in plants and animals respectively. Coal, peat and petroleum were probably formed from carbohydrates by microbi ological and chemical processes.

Carbohydrates comprise only about I percent of the human body; proteins comprise 15 percent, fatty substances 15 percent and inorganic substances 5 per cent (the rest being water). Nevertheless, carbohydrates are important constitu ents of the human diet, accounting for a high percentage of the calories con sumed. Thus some 40 percent of the cal orie intake of Americans (and some 50 percent of that of Britons and Israelis) is in the form of carbohydrates: glucose, fructose, lactose (milk sugar, a disaccha ride of glucose and galactose), sucrose and starch.

Sucrose is a major food sugar. Its world production rose from eight mil lion tons in 1900 to nearly 88 million in 1977. No other human food has shown an increase in production on this order in the same period. The amount of su crose produced by a country is an in dex of its average income. In the richer

e CARBON OXYGEN

countries, such as the U.S., Britain, Aus tralia and Sweden, the annual consump tion is between 40 and 50 kilograms of sucrose per person, whereas in the poor er ones, such as India, Pakistan and Chi na, it is five kilograms or less. It has of ten been suggested that the high sucrose diet may have detrimental effects on the health of people in developed countries, being responsible to some extent for the increase in such diseases as diabetes, obesity and dental cavities.

Carbohydrates are the raw materials for industries of great economic im portance, such as wood pulp and paper, textile fibers and pharmaceuticals. The principal industrial carbohydrate is un doubtedly cellulose: its worldwide use is estimated at 800 million tons per year. Polysaccharides with gelling properties, such as agar, pectic acid and carrageen ans, are important in the food and cos metic industries.

Research Difficulties

The major polysaccharides I have mentioned-cellulose, starch, glycogen and chitin-are relatively simple poly mers: they are homopolymers, made up of one type of monomer (glucose or ace tylglucosamine). This seeming simplici ty, perhaps even dullness, of structure is probably one of the reasons .carbohy drates seemed to lack interest.

Another important reason chemists tended to shy away from the study of carbohydrates stemmed from the many chemical problems encountered in deal ing with these materials. Sugars are mul tifunctional compounds with several hydroxyl (-OH) groups, usually four or five in the hexose sugars, most of which are of approximately equal chemical re activity. The manipUlation of a single selected hydroxyl group is often a seri ous problem to this day. Blocking one hydroxyl group or leaving one free can be achieved only with great difficulty and requires the careful design and exe cution of a complex series of reactions. The synthesis of a disaccharide is there fore a considerable achievement; trisac-

charides have rarely been synthesized, and there are only a few reports on the synthesis of higher saccharides.

By way of contrast, in protein chemis try peptide.s made up of dozens of amino acids can readily be synthesized, not only manually but also by automatic methods. At least three proteins, insulin (made up of 51 amino acids), ribonu clease (124) and lysozyme (129), have been synthesized. One reason for the rel ative ease of such syntheses is that the number of steps involved in the prepa ration of a peptide is considerably less than the number required for the syn thesis of an oligosaccharide of similar size. It is even more important that a far larger number of isomeric oligosaccha rides (the same in composition but dif ferent in structure) than of oligopeptides can be obtained from a given number of corresponding monomers.

An added complication for the chem ist is that whereas proteins and nucleic acids are linear polymers, polysaccha rides are commonly branched. This characteristic greatly increases the num ber of possible structures and therefore the difficulties of studying polysaccha rides. Luckily for carbohydrate chem ists many of the possible structures are apparently not formed in nature.

The recent revival of interest in carbo hydrates can be ascribed primarily to the introduction of much improved methods. Carbohydrate chemists in the first half of this century had to rely al most exclusively on carefully controlled chemical transformations and on opti cal measurements (chiefly polarimetry) in the investigation of the structures of monosaccharides and their derivatives. Work at that time was further limited by the lack of good separation techniques and by the need of a substantial quantity (a gram or more) of material for many of the experiments. The advent of chro matography in its various forms and of powerful instrumental analytical meth ods, such as nuclear-magnetic-reso nance spectroscopy (requiring only mil ligrams of material), mass spectrometry (requiring only micrograms) and X-ray-

THREE MONOSACCHARIDES are (left to right) glucose, fructose and galactose. Carbobydrates being sugars or cbains of sugars, mono saccbarides are tbe basic units of tbe cbains. Glucose, fructose, galac tose and many otber simple sugars fit tbe original definition of carbo-

hydrates as h)draks of carbon, consisting of carbon, bydrogen and oxygen in tbe general formula C"(H20),,. Witb glucose, fructose and galactose tbe formula is C6H 1206; they are hexoses: they have six carbon atoms. More than 200 monosaccharides have been found.

GLENLIVET AGED 12 YEARS

diffraction analysis, and the availability of highly specific enzymes acting on car bohydrates have given rise to a com plete transformation in the approach to the problem of carbohydrate structure. Moreover, combinations of these tech niques can provide information faster, more conveniently, in greater detail and with smaller quantities of material than was formerly possible. Maurice Stacey of the University of Birmingham has observed that ascertaining the constitu tion of a new carbohydrate would have taken three years in the 1930's but can now be done in less than three weeks.

New and Unusual Saccharides

One result of the introduction of the powerful new techniques was the dis covery of many new saccharides, both simple and complex. In recent years the number of rare sugars isolated from nat ural sources has increased rapidly. They have provided the carbohydrate chemist with new and challenging problems of structural determination and synthesis. I shall illustrate this state of affairs with examples from an area in which I have been active, the amino sugars: sugars in which one or more hydroxyls are re placed by an amino group.

In 1875 a young physician named George Ledderhose was working during the summer semester in the laboratory of Friedrich Wohler in Gottingen when Ledderhose's uncle, Felix Hoppe-Sey ler, a noted physiological chemist, invit ed him to dinner. At his uncle's sugges tion he took the remains of the lobster they had eaten back to the laboratory, where he found that the claws and the shell dissolved in hot concentrated hy-

_ CARBON C) OXYGEN o HYDROGEN

SUCROSE

drochloric acid and that on evaporation the solution yielded characteristic crys tals. He soon identified the crystalline compound as a new nitrogen-containing sugar, which he named giycosamin.

During the next 20 years much evi dence was gathered to indicate that the new sugar has a structure derived by the replacement of the hydroxyl group at tached to carbon No.2 in the glucose molecule by an amino group. With the synthesis, which was still not definitive, of the amino sugar by Emil Fischer and H. Leuchs in 1903 the problem of its structure appeared to have been solved. The structure of glucosamine was unequivocally established, howev er, only in 1939, when Norman Haworth achieved an unambiguous synthesis that proved Fischer was correcLin assigning the "gluco" structure to the amino sug ar. A second amino sugar, galactos amine, was isolated in 1914 by P. A. Levene and Frederick B. La Forge at the Rockefeller Institute for Medical Re search from acid hydrolysates of carti lage, tendon and aorta, but its structure was firmly established only in 1945, again attesting to the enormous difficul ties such substances present. At the time that was thought to be the end of the amino-sugar story. By 1960, however, some 20 new amino sugars had been dis covered. The number is now over 60.

The first of the "new" amino sugars, found in 1946, was N-methyl-L-glucos amine, a constituent of the antibiotic streptomycin. Soon many other new amino sugars were identified in antibiot ic substances. Indeed, some antibiotics have an oligosaccharide-like structure. They include the streptomycins, the neomycins and other aminoglycoside

STRUCTURE OF SUCROSE is depicted. Sucrose is common household sugar. It is a disac charide: it consists of two monosaccharide molecules (glucose and fructose) joined together.

antibiotics such as the kanamycins and the paromomycins, all of which are employed clinically against bacterial in fections. Another aminoglycoside anti biotic is puromycin, a well-known in hibitor of protein synthesis. The potent and clinically useful antitumor agents daunomycin and adriamycin, which have proved to be effective in the treat ment of acute leukemia, are also amino glycosides; they contain the rare 3-ami no sugar daunosamine.

To learn more about the mode of ac tion of these antibiotics and to improve on them it is imperative to synthesize analogues with different amino-sugar constituents, because it is known that structural features of the sugar compo nents often exert a decisive influence on the pharmacological properties of the antibiotics. This objective has given strong impetus to the development of new methods of synthetic-amino-sugar chemistry and has opened the way to the preparation of new and improved anti biotics that are remarkably effective against microorganisms resistant to the natural amino glycoside antibiotics. In no case, however, are the monosaccha ride constituents alone effective in vitro in killing bacteria or in inhibiting the growth of tumors.

Interestingly enough, several disac charides such as trehalosamine are ac tive against bacteria. Herbert A. Blough and Robert L. Giuntoli of the University of Pennsylvania School of Medicine re ported last year that the monosaccha ride 2-deoxyglucose applied to the site of an infection is highly effective in the treatment of genital herpes infection, a widespread form of venereal disease caused by the herpes simplex virus, for which no cure had been available. The sugar is believed to interfere with the synthesis of glycoprotein in the virus by virtue of its similarity to mannose, an important constituent of the viral glyco proteins.

New amino sugars and other types of sugar have been isolated in recent years not only from antibiotics but also from other sources, in particular from the polysaccharides of bacteria. One of the most important is the 3-lactic-acid ether of glucosamine, known as muramic acid. This amino sugar, which is limited to bacteria, was isolated for the first time by R. E. Strange and F. A. Dark in Brit ain in 1956. (For a while it was nick named the strange and dark compound.) Its acetylated derivative, acetylmuramic acid, and acetylglucosamine form the polysaccharide backbone of the pepti doglycan in the wall of the bacterial cell.

Another new sugar is ribitol, a reduc tion product of ribose. It is a constituent of the teichoic acids, which were discov ered by James Baddiley in Britain in the 1950's. Teichoic acids are polymers of ribitol phosphate or glycerol phosphate found in Gram-positive bacteria. In the cell wall of these organisms they act as

and The most comprehensive

authoritative scientific reference in the world.

Van Nostrand's Scientific

Encyclopedia a $69.50 value

Yours $295 for only

when you join The Library of Science for a trial period and agree to take 3 more books-at handsome discounts-over the next 12 months.

Find the answers to virtually all your scien tific questions, in the thoroughly updated and expanded fifth edition of Van Nostrand's SCIEN TIFIC ENCYCLOPEDIA. It has been hailed by The New York Times as "an amazing job of editing for both the general and scientific reader."

Thousands of photos, diagrams, graphs and charts completely illuminate the ENCYCLOPEDIA's clear and thorough coverage of every scientific field-including archaeology, as tronomy, general science, biology, medicine, physics, ethology and meteorology. Whether you're looking for a basic explanation of earth quakes or a comprehensive analysis of nuclear reactors-you'll find it all in Van Nostrand's SCIENTIFIC ENCYCLOPEDIA. What is The Library of Science? The Library

• Enlarged and exhaustively updated edition of an acclaimed classic, first published in 1938.

• A mammoth 9" x 12" volume covering everything scientific from abacus to zygote, in 2,370 pages, 7,200 editorial entries, 8,000 cross-references and 2.2 million words ..• plus 2,450 photos, diagrams, and charts as well as 550 tables.

• Authoritatively compiled by over 180 internationally respected scientific experts.

of Science is a very special book club. A club dedicated to keeping members of the scien tific community (and knowl edgeable amateurs) aware of the important advances and the speculative thinking in their own and related fields.

Begin enjoying the Club's benefits by accepting Van Nostrand's SCIENTIFIC ENCYCLOPEDIA. It's the perfect guide to the marvels of science ... and it's a great bargain, too!

If reply card has been removed, please write: The Library of Science-Dept. 2-AC7, Riverside, N.J. 08075 to obtain membership information and application.

THE NEW NIKON F3 A masterpiece of pace-setting technology and surpassing precision, the new Nikon F3 has no equal among 35mm sIrs. Strikingly handsome, it more than hints at the incredible automatic efficiency beneath its flawless finish. And its capacity for superlative photography is both awesome and inspiring.

Imagine exposures control/ed to millisecond accuracy by electronic microprocessors and quartz crystal technology!

Imagine enjoying this kind of accuracy with any of the nearly 70 lenses, 4 interchange able viewfinders and hundreds of other accessories in the Nikon F3 system!

Imagine all this and much more in a camera built to Nikon professional standards. So rugged and reliable that it has been selected by NASA for use aboard the Space Shuttle. 'ret light. compact. and ingeniously designed to give you magnificent pictures - automatically.

LIK E NO OTHER CAMERA ON EARTH

immunological determinants and as re ceptors of bacteriophages, that is, virus es that infect bacteria.

An important sugar of unusual struc ture is neuraminic acid, the parent com pound of the sialic acids, which are ubiquitous in nature except for plants. Neuraminic acid is a nine-carbon sugar acid with an amino group in its mole cule. Today 20 sialic acids are known, most of which were discovered during the past decade by Roland Schauer of the University of KieI. They are among the major constituents of mucins, such as those secreted by the respiratory and urogenital tracts, and are also found in the eye socket. By virtue of their nega tive charge they impart to the mucin molecules an extended rodlike struc ture. They are therefore responsible for the high viscosity of the mucins. Only because of the mucins' sialic acid can they act as lubricants for the rotation of the eyeball, preventing the cornea from drying out and protecting it from dam age by grains of dust.

In the oral cavity and the gastrointes tinal tract the viscous glycoproteins in corporating sialic acid envelop foods, making them slippery and protecting the tender mucous surfaces from mechani cal damage. In the cervical canal of the uterus a highly viscous plug of mucin keeps bacteria out of the uterine cavity and hence out of the abdominal cavity. This viscous barrier is lowered at the time of ovulation to admit spermatozoa. Glycoproteins rich in sialic acid that are secreted by mucous glands of the vagi na also lubricate both coitus and child birth.

A rare diamino sugar, the first of its kind, that I have been studying for the past 20 years is bacillosamine. I discov ered it in a polysaccharide of Bacillus Iichenz/ormis in 1958 while I was work ing in the laboratory of Roger W. Jean loz at the Massachusetts General Hospi tal. Only recently, through the joint ef forts of a number of co-workers, were we able to establish its structure. We then went on to synthesize the corre sponding galactose derivative in the be lief that it too must occur in nature. To our great satisfaction 2,4-diamino 2,4,- 6-trideoxygalactose was identified last year in natural products by workers in Stockholm and Tokyo.

A major breakthrough, which opened new horizons in biochemistry and had an immediate impact on medicine, was the discovery of sugar nucleotides and their manifold roles as intermediates in the biosynthesis of monosaccharides, oligosaccharides and polysaccharides and of complex carbohydrates. The first sugar nucleotide, uridine diphosphate glucose (UD P-glucose), was discovered by Luis F. Leloir and his co-workers in Argentina in 1949; for this discovery Leloir received a Nobel prize in 1970. At about the same time that Leloir de scribed UD P-glucose James T. Park and

e CARBON e OXY G E N

f3 LACTOSE

LACTOSE is a disaccharide consisting of glucose linked with galactose. It is the sugar of milk and therefore (with such other sugars as glucose, fructose and sucrose) is one of the carhohy drates making up a large part (40 percent in the U.S.) of the calorie intake in the human diet.

Marvin J. Johnson of the University of Wisconsin observed the accumulation of similar compounds in Staphylococcus aureus bacteria that had been exposed to penicillin.

More than 100 different sugar nucleo tides have now been identified. Most of them have the general structure of nu cleoside diphospho sugar with any of the five nucleosides: adenosine, guano sine, cytidine, uridine and deoxythymi dine. The sugar exhibits a large variety of structures, some of which are extreme ly rare.

Biosynthetic Intermediates

The nucleoside can be considered as a handle that holds the sugar in a form ready for transformation into other sug ars or for transfer to suitable acceptors. UDP-glucose is the sugar nucleotide most commonly found in biological ma terials and is the starting compound for the formation of numerous other sug ars. In many organisms it is converted into UD P-galactose, which is the source of galactose for the formation of lac tose. UD P-glucose is also the donor of glucose for the synthesis of gluco sides (for example phenyl-/3-glucoside), oligosaccharides (such as sucrose and trehalose), polysaccharides (including starch and glycogen) and other glucose containing compounds.

The discovery of sugar nucleotides led not only to the understanding of the biosynthesis of unusual monosaccha rides and of complex saccharides but also to the discovery in 1965 by Phillips W. Robbins of the Massachusetts In stitute of Technology and by Jack L. Strominger of the University of Wiscon sin School of Medicine of a new type of activated sugars: the lipid-linked sugars. They are sugar derivatives linked by a monophosphate or diphosphate bridge to polyprenols, long-chain unsaturated

lipids. One example of such a lipid is bactoprenol, which in the form of its sugar diphospho derivative is an inter mediate in the biosynthesis of bacterial lipopolysaccharides and peptidoglycan.

In 1970 Leloir demonstrated for the first time that similar compounds, the dolichol phosphates, participate in the biosynthesis of glycoproteins by animal cells. In bacteria the lipid-linked inter mediates, which are hydrophobic (wa ter-repelling), serve for the transport of activated sugars or oligosaccharides from the cytoplasm of the cell through the lipid-rich cell membrane to the cell surface, where polysaccharides such as the cell-wall peptidoglycan are laid down. In animals the role of these inter mediates remains to be established.

As a result of investigations of the participation of the lipid-linked sugars in the biosynthesis of complex carbohy drates, new mechanisms for the assem bly of biological polymers have been discovered. For example, with proteins and simple polysaccharides (such as gly cogen) the biosynthesis proceeds by the addition of a single monomeric unit, in its activated form, to the growing poly mer chain, whereas in complex carbohy drates the mechanism is often different. In the synthesis of the cell-wall pep tidoglycan a peptide derivative of the disaccharide acetylgl ucosamine-acetyl muramic acid is first synthesized on the lipid carrier. This repeating unit is sub sequently polymerized and is only then attached to a polymeric acceptor. A similar mechanism operates in the bio synthesis of bacterial lipopolysaccha rides, except that the repeating unit con sists of a trisaccharide of mannose, rhamnose and galactose.

In the biosynthesis of the carbohy drate units of glycoproteins linked to the amino acid asparagine an oligosaccha ride consisting of two residues of acetyl glucosamine, nine of mannose and three

e CARBON o OXY G E N o HYDROGEN

CELLULOSE

e CARBON o OXY G E N o HYDRO G E N

AMYLOSE (STARCH)

e CARBON o OXY G E N o HYDROGEN

GLYCOGEN (WITH BRANCHING)

THREE POLYSACCHARIDES are (from Ihe lop) cellulose, starch and glycogen. They are homopolymers, meaning that they are made up of one type of monomer. In each of the polysaccharides depicted the monomer is glucose. The individuality of these polysaccharides and others arises from the length of the polymer chain (which in cel-

lulose may run to several thousand units), the type of linkage between the sugar units and the occurrence of branches. Three basic units of each polysaccharide are shown here. Cellulose is a major structural component in plants. Starch and glycogen serve respectively in plants and animals for the storage of the energy that is derived from food.

of glucose is first assembled on a lipid carrier by a complex sequence of reac tions in which both sugar nucleotides and lipid-linked sugars participate. The preassembled oligosaccharide is trans ferred en bloc to specific asparagine res idues on the growing polypeptide chain and is then "processed" to its mature, final form. This processing includes the removal by special glycosidases of the glucose and most of the mannose and their replacement by tails consisting of sialic acid, galactose and acetylglucos amine (as has been found in many serum glycoproteins and in certain viral glyco proteins). The replacement proceeds by the stepwise addition of the individu al sugars from the corresponding sugar nucleotides; for example, acetylglucos amine is added by transfer from UDP acetylglucosamine and galactose from UDP-galactose.

Research on sugar nucleotides in rela tion to the biosynthesis of bacterial-cell wall peptidoglycan has led to the clarifi cation of the mechanism of action of penicillin, which is still the most useful antibiotic. The unique effectiveness of penicillin results from the fact that pep tidoglycan is not found in any organisms other than bacteria. It is therefore an excellent target for selective chemo therapeutic agents that kill the bacte ria without affecting their host.

Genetic Diseases

A completely different reason for the new wave of interest in carbohydrates stems from the fact that many of the hereditary or genetic diseases of man for which the molecular basis has been established are defects of carbohydrate metabolism, mostly of complex saccha rides. One of the diseases is galactos emia, a rare familial defect in galactose metabolism caused by the lack of a single enzyme: galactose phosphate uri dyl transferase. Because of the absence of this enzyme afflicted infants cannot utilize galactose or galactose-contain ing compounds, in particular lactose. Breast-feeding literally poisons such in fants. The galactose, which is ordinarily converted into glucose and eventually into energy, accumulates in the infant's blood in the poisonous form of galac tose phosphate, causing severe neural retardation and often early death.

Mainly as a result of the efforts of Herman M. KaJckar and his collabora tors at the National Institute of Arthri tis and Metabolic Disorders in the late 1950's the diagnosis of galactosemia can be made before the disease is far advanced. The procedure tests for the presence of the enzymes that metabolize galactose. If one of the enzymes is miss ing and the infant is given a diet free of galactose, all symptoms of galactosemia disappear and development becomes normal.

Most other genetic defects of carbo-

If you'd like to know more about the way we make Jack Daniel's, drop us a line.

AGING JACK DANIELS WHISKEY calls for hot summers, cold winters and a few men like Lawrence Burns .

Summer's heat causes our whiskey to seep inside the barrel's char. (Here's where it gains body and color.) Our cold winter air brings it back out . And barrelmen like Burns keep track of this gentle activity year after year after year. For a whiskey, there's no better resting place than a Jack Daniel's warehouse . And from the looks of Mr. Burns , there's nothing wrong with it for a man .

CHARCOAL MELLOWED

6 DROP

6 BY DROP

Tennessee Whiskey· 90 Proof· Distilled and Bottled by Jack Daniel Distillery Lem Mollow, Prop., Inc., Route I, Lynchburg (Pop. 361), Tennessee 37352

Placed in the National Register of Historic Places by the United States Government.

"The Physicist's Fire'

U.S. Pat. No. 4,069,808

Hot, even, slow-burning, easy to start, is how TIME described the s imple, elegant fire designed by research physicist Lawrence Cranberg. (Science Section, Dec. 22, 1975).

Place logs on the patented Texas Fire frame® grate to form a sl ot-shaped cavity that faces you. Ignite paper in the cavity.

Eureka! The fire takes hold quickly, burns evenly, s teadily in the cavity. That means the cavity throws a beam of radiant energy at you, so the fire is hot but fuel-efficient. Feel the warmth 10 to 15 feet from the fire.

Texas Fireframe's height-adjustable arms give you easy s et-up and a new option for control of the fire. The arms lock by friction.

From The New York Times (Dec. 29, 1977, p. C4)

"This new Texas Fireframe grate uses a new principle . . . It is insured that more BTU's will be used to heat people in front of the fire, rather than heating mas onry."

From Scientific American (August, 1978, pp. 142-146)

"Little of the radiated heat was lost up ward to the overhang or the chimney, nearly all of it must have been coming out into the room . . . The burning was s lower with this arrangement, and flames were uniform across the length of the slot (cavity) and required no rotation or stirring of t4e l ogs."

From Texas Fireframe Mail "I am especially amazed at how rapidly

the fire catches and disperses without kin dling." J. D. Barrier, Univers al City, Tx.

"It is easy to rebuild the fireslot while the fire is going." R. D. Keith, Olympia, Wa.

"The greatest thing s ince the invention of fire." D. D. Walsh, Madison, Ct.

Back to wood? No! Forward with wood and new technology: The Physicist's Fire and The Texas Fireframe® Grate.

Fully assembled, n o fasteners, t "-deep steel bars, all welded construction. Model U-25: 25" front width, 21" back width, IS" high, IS" deep. Model 5-25: 25"x21xI5xI3. Model U-17: 17"xI3xI3xI3. Model U-33: 33"x29xI5xI5.

Simple, copyrighted instructions.

Please send ___ U-25Units @ $42.95 (28 Ibs.)

___ 5-25 units @ $42.95 (26 Ibs.)

- __ U-17 units@$34.95 (20 Ibs.) ___ U-33 units @ $54.95 (34 Ibs.)

Add 10% for shipping in U.S. Check for $ ___ enclosed.

Nallle _ _____ ____ ___ _ _

Address _ ___ ____ ____ __ _ City State _ Zip ___ _

TEXAS FIREFRAME CO. P.O. Box 3435 Austin, Texas 78764

100

hydrate metabolism cause mental retar dation and often early death. The best characterized among them are the mu copolysaccharidoses: disorders of mu copolysaccharide metabolism, such as Hurler's syndrome and Hunter's syn drome, and disorders of glycolipid me tabolism, such as Tay-Sachs disease, which occurs at a relatively high inci dence (one birth in 3,000 births) among Ashkenazi (eastern European) Jews. In most of these diseases the mlssmg en zyme normally functions to degrade complex saccharides.

In the mucopolysaccharidoses large quantities of complex carbohydrates (the mucopolysaccharides) accumulate in the lysosorn,es, the subcellular organ elles where large molecules are normal ly broken down. Increased quantities of mucopolysaccharides are also secreted in the patient's urine. Cells taken from the skin of a patient and grown in tissue culture also accumulate mucopolysac charides. In the early 1970's Elizabeth F. Neufeld of the National Institute of Arthritis, Metabolism, and Digestive Diseases found that this accumula tion can be prevented by providing the cells with the missing polysaccharide degrading enzymes. Unfortunately at tempts to treat patients by administering the appropriate enzymes have not yet been successful.

A disease that is well known to be closely linked with sugar metaboljsm is diabetes. Although diabetes has now been shown to be a family of different disorders, all diabetics have one thing in common: abnormally high levels of glu cose in the blood. Moreover, in nearly all diabetics similar complications de velop, including heart disease, blind ness, cataracts, blood-vessel damage, nerve disorders and kidney damage. Is the high blood sugar by itself the cause

_ CARBON o OXYGEN

a-D-GLUCOSE

of diabetic complications? Many inves tigators tend to believe that it is and that tight control of blood sugar can pre vent, arrest and possibly even reverse the progress of these complications.

To understand what high blood sug ar does biochemists and physicians are asking how glucose damages cells at the molecular level. One possible mecha nism is that glucose combines with pro teins in the body, altering their configu ration and their function. Evidence of how this process might occur was re cently obtained by a number of groups, including Anthony Cerami and Ronald Koenig and their associates at Rockefel ler University and H. Franklin Bunn, Kenneth H. Gabbay and Paul M. Gal lop at the Harvard Medical School. These investigators found that glucose attaches itself, in a process not requiring enzymes, to the hemoglobin molecules of diabetic patients, thereby altering the electric charge and biochemical proper ties of the hemoglobin.

The idea that glucose can combine with amino acids and proteins is not new. For a while it was the subject of considerable research by biochem ists and food chemists. Aharon Katzir Katchalsky studied this reaction at the Hebrew University of Jerusalem for his doctoral degree, which he was awarded in 1938, and I continued on the same subject with him for my Ph.D. degree (also from Hebrew University) in 1950- 53. Food chemists had long known that the interaction of glucose and food pro teins, a reaction known as nonenzymatic browning because it proceeds without enzymes and turns the protein brown, causes a decrease in the digestibility and nutritive value of protein. Hematolo gists found some years ago that about 5 percent of the hemoglobin molecules of normal people contain nonenzymatical-

a-B-GLUCOSAMINE

AMINO SUGAR is glucosamine, a constituent of lobster shell, glycoprotein and the cell wall of fungi. In amino sugars one or more hydroxyl (-OH) groups of the sugar molecule are re placed by an amino, or nitrogen-containing, group. Here the amino group replaces the hydrox yl group on carbon No. 2 of the glucose molecule. More than 60 amino sugars are now known.

ly bound sugars. This attachment of sug ar molecules to proteins is a slow proc ess and does not normally happen to any great extent with proteins that are rapid ly broken down and resynthesized. Few sugar molecules are expected to attach themselves even to relatively stable pro teins such as hemoglobin. Diabetics, however, have so much glucose in their blood that their level of glucosylated hemoglobin molecules is two or three tiJ;Iles higher than the norm. Attempts are now being made to exploit this find ing clinically.

Red blood cells and their hemoglobin have a lifetime of about 120 days. Once glucose has become attached to the he moglobin it comes off slowly, so that the amount of glucosylated hemoglobin in the blood of a patient acts as an indica tor for the total blood-sugar concentra tion over the preceding few weeks. It is hence a better index than anything now available of how well controlled the pa tient's blood glucose has been over such a period.

Since glucose attaches to hemoglobin, it almost certainly attaches to other pro teins in the same way and may therefore change their properties and biological functions. The process may be particu larly damaging to proteins that are slow to be replaced, such as those in the lining. of blood vessels and in the insulating material around nerve cells. Cerami has recently demonstrated that a high con centration of glucose leads to the gluco sylation of proteins of the eye lens, both in vitro and in vivo, and to a sub sequent opacity of the protein matrix, mimicking the opacity seen in diabetic cataracts.

Biological Markers

Until recently it was not recognized that nature can employ sugars for the synthesis of highly specific compounds

e CARBON OXYGEN

o N I TROG E N o PHOSPHORUS o HYDROG EN

UR ID I N E D I PHOSPHATE GLUCOSE

that can act as carriers of biological in formation. This capability arises from the fact that a large number of struc tures can be formed from a small num ber of monomers. In other words, monosaccharides can serve as letters in a vocabulary of biological specificity, where the words are formed by varia tions in the nature of the sugars present, the type of linkage and the presence or absence of branch points. It is now known that the specificity of many natu ral polymers is written in terms of sug ars, not amino acids or nucleotides. This idea is not entirely novel, but it has only recently become well established.

In the 1920's it was still believed that the specific information in biological polymers was carried only by proteins. Between 1925 and 1937 Oswald T. Avery of the Rockefeller Institute, to gether with Michael Heidelberger and Walther F. Goebel, demonstrated that pure polysaccharides can carry specific immunological messages as antigens: substances that stimulate the produc tion of an antibody specific to them selves. Thus the highly purified Type III pneumococcus "specific soluble sub stance" was an antigen even though it did not have any of the properties of a protein. This substance was shown to be polysaccharide, consisting of repeating units of cellobiuronic acid (a disaccha ride of glucose and glucuronic acid).

The chemical basis of the antigenicity of polysaccharides was thoroughly clar ified through the application of highly sophisticated techniques developed by Heidelberger and Elvin A. Kabat of the Columbia University College of Physi cians and Surgeons, Walter T. J. Mor gan of the Lister Institute of Preventive Medicine in London and many others. Today it is well established that carbo hydrates are ideally suited for the for mation of specificity determinants that can be recognized by complementary

structures, which presumably are car bohydrate-binding proteins, on other cells or molecules.

The first indication that sugars serve as specificity determinants came from the discovery in 1941 by George K. Hirst in New York and by Ronald Hare in Toronto that the influenza virus caused red blood cells to agglutinate, or clump. The molecular basis of this phe nomenon was for a time obscure. Main ly as a result of the efforts of Alfred Gottschalk in Australia it was shown that the influenza virus binds to the red blood cell through sialic acid units on the cell surface. If the sialic acid is re moved from the cell surface by the en zyme neuraminidase, the influenza virus will no longer bind to the cell.

The role of carbohydrates in recogni tion has been best demonstrated in the control of the lifetime of glycoproteins in the circulatory system and their up take into the liver and of the uptake of lysosomal enzymes by cells. As often happens, these exciting discoveries orig inated with an unexpected observation, this one made in 1966 by G. Gilbert Ashwell of the National Institute of Ar thritis, Metabolism, and Digestive Dis eases and by Anatol G. Morell of the Albert Einstein College of Medicine in the course of an effort to understand the biological role of ceruloplasmin, a cop per-transport protein found in the blood serum of man and other animals. When Ashwell and Morell removed sialic acid from rabbit ceruloplasmin and rein jected the modified ceruloplasmin into the animals, it almost completely dis appeared from the circulatory system within 15 minutes. This was in striking contrast to the native glycoprotein, al most all of which remained in circula tion after the same length of time. Fur ther work has shown that with many serum glycoproteins the removal of ter minal sialic acid units to expose the un-

SUGAR NUCLEOTIDE, the first of more than 100 that have heen found, is uridine diphosphate glucose (UDP-glucose). It is the start ing compound for the biosynthesis of numerous other sugars. The general structure is that of a sugar in association with a nucleoside

(adenosine, guanosine, cytidine, uridine or deoxythymidine) and phos phorus in the form of phosphate. Here it is glucose, uridine and two phosphate groups. The nucleotide holds the sugar in an activated form for transformation to other sugars or transfer to acceptors.

102

We'll give you lift-off too! Welwyn Electric-one of North

England's pace-setter companies manufacture the hybrid circuits that make the Harrier jump-jet's brain tick. It's just one success story of the many you'll find in North England, a centre of excellence for scientific and engineering innovation ever since George Stephenson's locomotion No.1 took the world's first passenger train rumbling along a railroad track.

The North of England Development Council invites your company to consider an extension of operations or relocation in North England-recognised as the launch-pad for Europe-where

you'll find the right brains, plentiful and willing labour and the land to suit you (we also have factories off the peg, ready and waiting in a variety of sizes).

Ask first for our information pack and say whether you would also like to receive special in-depth studies on sectors such as Electronics, Scientific and Industrial Instruments or Pharmaceuticals.

Telex, telephone or write-and like Harrier we'll be ready for immediate take-off with a visit to you to fill in the background when ever you're ready for us.

North of England Development Council Bank House Carliol Square Newcastle upon Tyne NE1 6XE England

Telephone 0632 610036 Telex 537212

103

derlying galactose units results in the rapid removal of the modified glyco proteins from the circulatory system of experimental animals and their uptake by the parenchymal cells of the liver. The surface of such a cell contains a re ceptor specific for the binding of glyco proteins that lack sialic acid.

Galactose hence serves as a recogni tion marker that determines the survival time of many serum glycoproteins in the circulatory system of man, the rabbit and the mouse. In bird and reptile spe cies the recognition marker appears to be primarily acetylglucosamine. Clear ance systems in which fucose and man nose are the markers have also been found.

A particularly interesting marker is

1 . APPROACH

2 . B I ND I N G

LATENT AD E N Y LATE CYCLASE

3 . CON FORMAT IONAL CHANGE

mannose-6-phosphate, a sugar deriva tive that has recently been shown to act mainly in directing the intracellular traf fic of glycoprotein enzymes normally present in lysosomes. This finding had its origins in Neufeld's discovery that the enzyme deficiencies in cells from patients afflicted by mucopolysaccha ridoses such as Hurler's and Hunter's syndromes can be corrected by provid ing the cells with the missing enzymes. In 1974 she showed further that uptake into the cells depended on the presence in the enzymes of a carbohydrate-recog nition marker. In 1977 William S. Sly of the Washington University School of Medicine and Arnold Kaplan of the Saint Louis University School of Medi cine identified the recognition marker as

4. D ISSOCIAT IO N AND E NTRY

5 . P E N ETRAT I O N AND " ACT I VAT IO N " OF A S U B U N IT

6. ACT I VAT ION OF CYCLASE

ATP cAMP

ACTION OF GLYCOLIPID in binding the toxin of cholera bacteria is indicated. A glycolipid is a compound in which a sugar is linked to a lipid; here it is the ganglioside, or acidic glyco

lipid, known as GM b which is found in the plasma membrane of cells. A cholera toxin, consist ing of one A subunit (black) and five B subunits (white), approaches the plasma membrane of an intestinal mucosal cell (1), is hound by the GM 1 (2) and as a result is changed in con formation (3) in such a way that the A subunit is dissociated from the toxin and enters the mem brane (4). There the A subunit becomes activated (5) so that it is able to activate the adenylate cyclase system of the cell (6). The activation of the cyclase system causes the cell to secrete ex cess quantities of fluid, giving rise (as large numbers of cells become overactive) to the huge losses of liquid that often cause dehydration and death in cholera. If GM 1 is administered to the patient so that much of it is not associated with cells, it can bind the cholera toxin and inhib it the toxin's effect. Other gangliosides evidently inhibit similarly the action of other toxins.

104

a phosphorylated sugar unit: mannose- 6-phosphate. The function of the mark er is apparently to prevent the secretion of the enzymes from the cells and to direct them into the lysosomes. When the enzymes are supplied from the out side, it is this recognition signal that pro motes their binding to the cell surface; without binding they cannot enter the cells and reach the lysosomes.

By the covalent (electron-sharing) at tachment of carbohydrates to proteins or by a modification of the sugars in glycoproteins it may thereby be possible to control the proteins' lifetime in the circulation and to direct them to the liv er and perhaps also to other organs, as well as into lysosomes. Such techniques will have far-reaching uses for enzyme replacement therapy in cases of genetic disease and also for delivering drugs ac curately into target organs and cells.

Other Biological Roles

Sugars on cell surfaces also appear to determine the life span of circulating cells and their distribution in the body. This role was originally demonstrated in 1964 by Bertram M. Gesner and Victor Ginsburg of the National Institute of Arthritis, Metabolism, and Digestive Diseases. They found that radioactively labeled rat lymphocytes migrated to the spleen when they were reinjected into the animal. If before reinjection the sug ar fucose was removed from the surface of the cells by treatment with a specific glycosidase, the lymphocytes migrated to the liver instead, as if the fucose on the lymphocytes served as a "ZIP" code directing them where to go.

Old red blood cells - have less sialic acid on their surface than young ones, and so it has been postulated that the decrease of sialic acid is the signal re sponsible for the removal of the older red blood cells from the circulatory sys tem. This hypothesis seemed to be fur ther substantiated by the finding that when red blood cells are taken out of the circulation, and when the sialic acid is removed from their surface and they are reinjected into the blood, their life span is extremely short: only a couple of days out of the normal lifetime of 120. In spite of these striking correlations there is considerable doubt whether the re moval of sialic acid and the exposure of galactose units on the surface of the red blood cell are responsible for the remov al of senescent red cells from the blood under physiological conditions in vivo.

The well-known A B O blood-group system was first described by Karl Land steiner of the Rockefeller Institute in 1900, but it was not until 1953 that Wal ter Morgan and Winifred Watkins of the Lister Institute demonstrated that the specificity of the major blood types is determined by sugars. For example, the difference between the blood types A and B lies in a single sugar unit that

3 �� • �� • �� •

��

MECHANISM OF ATTACHMENT of E. coli to a cell membrane, as is shown in the micrograph on page 9 1 , and its inhibition by free mannose is portrayed schematically. Bacteria approach a cell mem brane (1) in which a glycoprotein is embedded. Here mannose (black

1 06

•

dots), which is part of the glycoprotein, is recognized by binding sites on the E. coli. As a result the bacteria adhere to the host surface (2), initiating an infection. If free mannose is available, however, it binds to the bacteria first (3) and prevents them from attaching to the cell.

sticks out from the end of a carbohy drate chain of a glycoprotein or gly colipid on the surface of the red blood cell. In blood type A the determinant is acetylgalactosamine, in blood type B it is galactose. The two monosaccharides differ by only a small group of atoms, but that little difference is sometimes a matter of life and death, since using the wrong type of blood in a transfusion can have fatal results.

The enzymatic removal by specific glycosidases of a-linked acetylgalac tosamine from type A red blood cells or of a -linked galactose from type B red blood cells will convert both into type 0 cells. An effective conversion can, for example, be carried out by purified a galactosidase from coffee beans or soy beans, as was demonstrated in our labo ratory by Noam Harpaz and Harold Flowers. Such a conversion may be use ful clinically when type 0 cells of rare subtypes are needed for transfusion.

The sugars that determine the speci ficity of substances in the A B O blood group are distributed in the biological world in forms similar to those found in human beings. The substances are there fore also present in different mammals. Hence the red blood cells of the dog, the pig and the rabbit are invariably of type B and in some cases may also belong to type A. The ABO blood-group sub stances are present in birds and amphib ians and even in plants and bacteria.

Tamio Yamakawa of the University of Tokyo has recently suggested that dogs may possess a blood-group system specified by the sialic acid in red-blood cell glycolipids. Whereas all European dogs so far examined have glycolipids that incorporate acetylneuraminic acid, Yamakawa and his co-workers have shown that representative Japanese dogs such as the Kishu and Shiba breeds often have glycolylneuraminic acid in stead and that this occurrence is genet ically determined. Akita and Hokkaido dogs from northern Japan seem to be exceptional in having only acetylneur aminic acid in their red-blood-cell gly colipids. The origin of the Japanese dog is still controversial, but since the glyco lylneuraminic acid glycolipid is inherit ed as a dominant trait, the findings sug gest that the origins of the Akita and Hokkaido breeds are different from those of other Japanese dogs and that the Akita and Hokkaido breeds are re lated to European dogs.

Several toxins of bacteria and plants are now known to recognize carbo hydrate structures present in various classes of cell-surface molecules. In cluded are the cholera toxin and possi bly the tetanus toxin, which bind to cer tain glycolipids of the ganglioside type. Gangliosides are unique acidic glycolip ids that are selectively concentrated in the plasma membrane of cells.

W. E. van Heyningen of the Universi ty of Oxford showed in 1971 that gangli-

ntroducing instant motion ana ysis of high-speed events.

N o w w h e n y o u n e e d an a n a l ys i s of a h i g h - s pe e d p ro c e s s i n y o u r p l a n t , y o u d o n ' t h ave to c a l l i n a n o u t s i d e s pe c i a l i s t . You c a n f i l m i t yo u rs e l f .

T h e P o l a ro i d H i g h - S p e e d R e c o r d i n g S y s t e m fo r I n s t a n t M o t i o n A n a l y s i s t u r n s t h at f a s t act i o n i n to s l ow - m ot i o n p i c t u re s . It l et s y o u v i ew the p i c t u res in jus t 90 s e conds i n b ri l l i a n t c o l o r or b l ac k and w h i t e .

I f t h e re i s a n yt h i n g w ro n g , y o u c a n i m m e d i at e l y d i ag n os e t h e t ro u b l e . Yo u avo i d c o s t l y d ow n t i m e w h i l e w a i t i n g f o r a s pe c i a l i st t o a r r i v e . Aft e r y o u s h o o t , i f t h e re s u l t s are n o t w h at y o u n e e d , y o u c a n ad j u st t h e s e t- u p ( l i g h t s , l e n s , c a m e ra a n g l e , f r a m e s pe e d , e tc . ) a n d i m m e d i at e l y r e p e at t h e s h ot . T h e r e ' s n o w a i t i n g for f i l m t o b e d ev e l o pe d . O n c e y o u a r e s at i sf i e d w i t h t h e i n f o r m at i o n a n d h a v e t a k e n c o r re c t i v e act i o n , y o u c a n r e - s h oot f o r i n s t a n t a s s u r a n c e t h at e v e r yt h i n g i s w o r k i n g p r o p e r l y.

T h e s y s t e m c o n s i st s of a c a m e ra a n d a n a l y z e r. Both can be speed-controlled, g i v i n g y o u t h e m o s t v e r s at i l e s y s t e m fo r i n v e s t i g at i o n .

T h e c a m e r a , d e s i g n e d a n d m a n u fac t u red by M e k e l E n g i n e e r i n g , I n c , c a n t a k e m o t i o n p i c t u res at rat e s f r o m 4 to 300 f r a m e s p e r s e c o n d . It c a n s p re a d 1 0 s e c o n d s of ac t i o n o v e r as m u c h a s 2 V2 m i n u t e s o f f i l m , effe c t i v e l y s l o w i n g d ow n t h e m o t i o n b y 1 5 t i m e s .

T h e Po l a ro i d a n a l y z e r g i ve s y o u a n o r m a l f o rw a r d s pe e d , fou r s l ow - m ot i o n s p e e d s , f r a m e - b y f r a m e a d v a n c e m e n t , sto p act i o n a n d i n s t a n t re p l ay. Yo u c o n t ro l a l l t h e s e s p e e d s w i t h a h a n d - h e l d c o n t r o l

Afte r e x p o s u re , t h e c o l o r o r b l ac k a n d w h i t e m o v i e c a s s ette i s i n s e rt e d i n t h e a n a l y z e r. T h e re i t d ev e l o p s a u t o m at i c a l l y i n 9 0 s e c o n d s a n d i s t h e n p roj e c t e d o n t h e

0 1 980 P o l a r o i d C o r p o r a t i o n · · P o l a r o l d " 1;

s c re e n Yo u s e e t h e re s u l t s immedia tely. A n d y o u c a n v i ew t h e p i c t u re s at a n y c o n v e n i e n t p l ac e .

T h i s s y s t e m l e t s y o u i n s t a n t l y t ro u b l e s h oot a n d s o l v e e n g i n e e r i n g , f a b r i c at i o n a n d p ro c e s s i n g p ro b l e m s t h at w o u l d o t h e rw i s e b e baffl i n g . I n v e st i g at e v i t al p o rt i o n s of a n a s s e m b l y l i n e to s e e w h at ' s c a u s i n g a h a n g - u p . A n a l yze a p l as t i c m o l d i n g o p e rat i o n to d i s c o v e r w h y p a rt s a r e d ef e c t i ve . O b s e rv e a c u t t i n g t o o l i n a m i l l i n g o r l a t h e o p e rat i o n to d et e r m i n e t o o l eff i c i e n c y. F i n d o u t i f a f a s t - m ov i n g p a rt i s b o u n c i n g e r rat i c a l l y a n d red u c i n g p ro d u c t i v i ty. T h e s e a n d a t h o u s a n d ot h e r h i g h - s p e e d eve n t s c a n be a n a l y z e d .

F o r m o re i n f o r m at i o n or a d e m o n s t rat i o n on y o u r own p re m i s e s , w r i t e to P o l a r o i d C o r p o r at i o n , D e pt . A 4 4 9 , 5 7 5 Te c h n o l o g y S q u a r e , C a m b r i d g e , M a s s . 021 3 9 . O r c a l l u s t o l l - f r e e f r o m t h e c o n t i n e nt a l U . S . : 8 0 0 - 2 2 5-1 61 8 . I n M a s s ac h u s e tt s , c a l l c o l l e c t : 61 7- 54 7-51 7 7

Po aroid I n stant Motion Analys i s

THE ATARI® PERSONAL COMPUTERS.

YOU SHOULD KNOW WHY SO MANY PEOPLE

ARE B UYING THEM. Computers helped to create big business and big

government . But they 've done very little for you . Until now. Now the computer revolution is ready to

come home . Thanks, in part , to Atari . We at Atari have made the computer easy to use and

adaptable to your needs . Whether you 're planning a new budge t , playing the stock marke t , or simply looking for a brighter chess partner.

An Atari Persor,al Computer puts yo u r mo ney to work for you .

Even professi onal managers who handle millions o f dollars are frequently unprofessi onal when i t comes to handling their own money.

Because they don't have the time or the to ols that are necessary for the j ob . That 's the best argument we know of for an Atari Personal Computer.

An Atari Personal Computer can help manage a stock portfolio . Assist in the preparation of taxes . Figure the best terms for a m ortgage . Keep an electronic record

of income and expenses . (So you'll know exactly what

can and can't afford . ) Or help y o u decide

mathe matically whether real estate

in Goldsboro is a better buy than

gold stock . An Atari

Personal Com t::;:::.iit puter is also an

excellent place for keeping records of all kinds . From stamp col lections to premium due dates . Think how unburdened your memory will feel when all these things are tucked into your computer's memory.

How to turn a s m a l l business into a big business .

receivable to inventory control . Yet they 're small enough to fit in a briefcase, so you can solve your problems at home or at the office .

Periphera l s aren't just a sideline at Atari .

Atari 's impressive array of advanced peripheral accessories allows your system to expand with your needs . As you write or run larger and larger programs you can increase the memory as well as the performance capabilities of your computer.

The most revo l utionary teacher's aid ever invented . One of the things that 's revolutionary

about the Atari Personal Computer is that it adj usts its teaching speed to your child .

If your child learns faster than other children our computer teaches faster.

If your child learns a little slower than other children our computer teaches a little slower.

Nobody gets bored . Perhaps more importantly, nobody gets lost .

An Atari Personal Computer has a voice that teaches , asks questions, and tells your child whether he or she has the right answer. If your child gets a wrong answer the

I g ATARI �@ I

Atari Personal C omputers are powerful enough to handle almost any kind of business application - from accounts � . (�.� :;. �'�l � ... I";'�;I!".JilIi��·.L��M��{"H; ;"�/�AI. "' • • "" ,..... �'-'I,��diJ-<t: ," 'q , '�"!':" ;:;.'f,':" '_"';i!}t'\ !� '" ,

�TA R I 400'"

• -

,...

, ,

All progrilms referred to or shown will be ilvaililble ilS preprogrilmmed cilrtridges or c dSSettes in 1980. or ilre eXilmples of progrilms which ciln be written in A tdri BASIC. A tilri reserves the right to modify programs or products without notice. *Prognms and peripherals not included.

computer doesn't have to move on to someone else ,

in o rder to save time . It waits for your child to answer the

question correctly. Atari has a wide

variety of these unique Talk & Teach ™ programs for kids at all grade levels , from primary

school to 12th grade . Atari also has programs for adults that let you

improve your abilities in everything from economics and accounting to supervisory skills and business communica tion. Atari's incredible Music Composer enlarges your creative ability through its own ability to play back every note that has been played on it - even in altered keys or temp o s .

Our enterta i n m ent p u t s your mind to work, not to sleep .

You 'll discover how much fun " smart " entertainment is when you try to outfox our computer in a game of chess . Or develop a levelheaded strategy while shooting off photon torpedoes in a game called Star Raiders. ™

personal computer on the market . You d o n 't have to know how to progra m it

to program i t . Just connect t h e computer i n t o a n y television set .

Then slip in one of Atari 's unique pre-programmed cart ridges . Or one of our cassette tapes . That 's all there is to it .

When you want to learn to write your own p ro grams , that 's easy t o o .

There are several easy -to -learn programming lan guages and you can learn the most p opular one by simply listening to o ur step-by-step Talk & Teach cassette Invitation to Programming. ™

It pays to own an Atari . Now that you have a pretty good idea of what Atari

Personal C omputers can do, we think our suggested

Our games force you t o think quickly, analyze m oves starting price of under f 7 00 for the ATARI 4 00 * should and outwit your Zylon opponent s . Even our action sound reasonable . games like computer Basketball sharpen your reflexes . If you ' re one of those people who feels that a per-

What makes our computer games even more sana I computer is an extravagance in diffi cult fi nancial fun are the brilliant colors and true-to -life sounds . times , we 'd like to make one more point . In fact . A tari has more color variations , more sounds ATA RI® Difficult fi nancial times may be your best reason and more graphics capabilities than any other K I K for owning one .

PERSONAL COMPUTER SYSTEMS 1265 Borregas Ave . Dept . E, Sunnyvale, California 94086. Call toll-free 800- 5 3 8-8547 excluding

Hawaii and Alaska (in Calif. 800-672-1404) for the names of your nearest Atari retailers.

After 1/2 million owners, 6 billion miles and Motor Trends "Car of the Year" award, it stands alone.

T h e re ' s s o m e th i n g a b o u t b e i n g new. Eve ryo n e watches to s e e i f you ' l l work o u t .

B e l i eve u s , i t wa s n o d iffe r e n t w h e n C i t a t i o n w a s i n t r o d u ced . W e s a i d it was a w h o l e n ew k i n d of c o m p a ct ca r. A n d t h e n we h a d to p rove i t .

W e p u t C i t a t i o n to w o r k . B e co m i n g t h e m o s t s u ccessf u l n e w C h ev ro l et ever i n trod u c ed . A n d

n ow, a ft e r 1 - 1 /2 yea r s , i t's t h e b e s t- s e l l i n g f r o n t - w h e e l d rive i n A m e ri c a .

B u t t h e n , we fe l t s u re a b o u t C i t a t i o n f rom t h e sta rt . . . b e i n g so v e r s a t i l e . With i ts f r o n t- w h e e l d ri v e , roo m fo r fi v e , wa g o n - l i ke u ti l i ty, even h i d d e n sto r a g e s p a c e .

N ow, of c o u rse, you ' l l b e h e a ri n g a b o u t a l ot of f r o n t - w h e e l d rives

1981 CH EVY CITATION

osides of the brain bound cholera tox in and blocked its physiological effect. Later work by van Heyningen, by Lars Svennerholm and Jan Holmgren of the University of Goteborg and by Pedro Cuatrecasas of the Johns Hopkins Uni versity School of Medicine showed that the ganglioside G M 1 is the most effec tive inhibitor. A close correlation was found between the G M 1 content of in testinal mucosal cells from different spe cies and the amount of cholera toxin that was bound. There is also considera ble evidence that specific gangliosides can inhibit the action (;)f tetanus toxin and botulinum toxin. The existence on cells of specific carbohydrates showing a strong affinity with the toxins of viru lent organisms such as cholera and diph theria is of great medical importance, since it may be possible to protect against these diseases by the administra tion of suitable gangliosides.

The cell-surface sugars of ganglio sides serve for the attachment of other biologically active molecules. Promi nent among them is the potent antiviral agent interferon. The incubation of gan gliosides with interferon will inhibit in terferon's antiviral activity. Moreover, mouse cells that do not respond to treat ment with interferon become responsive after tlie incorporation of gangliosides into their surface membrane. These re sults indicate that gangliosides and in terferon can interact at the cell surface and that these complex carbohydrates may have a function in the antiviral ac tivity of interferon.

Cell Recognition

Cell-surface sugars serve as receptors for various other physiological and non physiological agents. Among them are lectins, which in binding to cells often give rise to agglutination. If they bind to lymphocytes, they induce cell growth and division, a phenomenon known as mitogenic stimulation.

Pronounced changes in cell-surface sugars are observed during the develop ment and differentiation of cells and on the transformation of normal cells into malignant ones. Many of the changes were originally detected with the aid of lectins. In particular the finding during the 1960's that malignant cells are much more readily agglutinated by lectins (such as wheat-germ agglutinin, conca navalin A and soybean agglutinin) than their normal counterparts focused the attention of many investigators on cell surface sugars. The excitement over these findings is waning, however, be cause it has proved to be extremely diffi cult to identify the structural changes that take place on the surface when normal cells become malignant. It has also not been possible to gain any insight into the physiological meaning of these changes. Moreover, the increased ag glutination by lectins is not a property

WE GUARANTEE WEALTH! -not riches , b ut a wealth of information ! -not a longer life , b ut a fuller one ! And if yo u a re not a l re a d y a b i rd watc he r , o u r magazi n e will open u p a whole n e w w o r l d for yo u filled w i t h song , col o r , g race a n d bea uty . B i m o n th l y , 96 page s , spa r k l i ng fact .filled articles , black & wh ite i l l u strati o n s , poetry , h u m o r , w h e re to , h o w to , when to ! The perfect gift for yo u rself and you r frie nd s ! W e g u a ra n t e e i t o r y o u r m o n e y ba c k ! S u bscribe toda y ! O n e yea r ( 6 i s s ue s ) $9. Add $2 .50 fore ign , U .S . f u n d s o n l y . Bird Watc h e r 's Digest , D e p t . SA , B o x 1 1 0, M a rietta , OH 45750. Visa /M a ster Charge m a y ca l l 800-848-9765 weekdays 9-5 .

Mathematic s and Humor John Allen Paulos In an i l l u m in a t i n g and enter taining b o o k , P a u l o s u s e s catas trophe theory t o plot t h e course of a j o k e or the proce s s of a c rea tive thought i n mathe m a t ic a l ly graphic t e r m s . Paulo s's work has been reported i n Th e New York Ti m es and i n an Essay in Ti m e which c o m m e n t e d : 'With Dr. P a u los's breakthrou g h , Americans m a y h a v e the m e a n s t o r e c o v e r the capac i t y t o spot baloney no matter h ow it i s s l i c e d . "

I l l u s t rated $12 . 95

Unive rsity of CHICAGO Press

� . . - - - - - - - - - - - . - - - . - . - - - - - . . �

! Sp<zak S<znnan ! i lik" a 1)iplomat ! = • W h a t sort of p e o p l e need to l e a r n a set y o u r o w n pace test i n g y o u r s e l f , cor· •

• • fore i g n l a n g u a g e as q u i c k l y a n d effect ive- r e c t i n g e r r o r s , re i n f o r c i n g a c c u r a t e Iy a s p o s s i b l e ? Fore i g n se rv i c e p e r so n n e l , res p o n s e s . • • t h a t ' s w h o . T he F S l ' s Prog r a m m ed G e r m a n C o u r s e

I I N o w you c a n m a k e a start o n . l e a r n i n g c o m e s i n t w o v o l Li mes: You m a y o r d e r o n e • to s p e a k G e r m a n w i t h t h e s

a m e mat e - or both c o u rses: • r i a l s u sed by t h e U . S . Depa r t m e n t of 0 Vol u m e I. Prog r a m med i ntrod uction to • • State - t h e Fore i g n Serv i c e I n s t i) u t e ' s G e r m a n , 9 c a s s e t t e s , 1 2 h o u r s a n d

I Progra m m e d I n trod u c tion to Germ a n a n d 647·pa g e t e x t , $ 1 1 5. • B a s i c Course, Con tinued. , :J Vol ume I I . B a s i c Course, C o n t i n u e d • • T h e F S I spent t h o u s a n d s of d o l l a rs a n d ( M ore Advanced) 8 c a s s e t t e s , 8 ';' I • m a n y years deve l o p i n g t h ese m a t e r i a l s h o u r s a n d a 333· p a g e t e x t , $ 9 8 . f o r u s e by m e m b e r s o f A m e r i c a ' s ( N ew York State res i d e n t s a d d a p . • •

• d i p l o m a t i c cor p s , Today peo p l e i n a l l p r o p r i a t e s a l e s t a x . ) • w a l k s of l i f e w h o need to l e a r n to s p e a k a

Yo u r c asse ttes are s h i p ped to y o u in h a n d . • •

fore i g n l a n g u a g e are t u r n i n g to t h i s s o m e l i b ra ry b i n d e r s , o u t s t a n d i n g a u d i o cassette p r o g r a m ,

• • T h e F o re i g n Service I n s t i t u t e ' s G e r m a n T O O R D E R , J U ST C L I P T H I S A D a n d m a i l •

Course is by far t h e most e f f e c t i v e way to w i t h your n a m e and a d d re s s , and a check • l e a r n G e r m a n at y o u r conve n i e n c e a n d at or money order. Or c h a r g e to your cred i t • • y o u r own pace. It c o n s i s t s of a s e r i e s of card ( A m e r i c a n E x p r e s s , V I SA , M a s t e r

I • t a p e cassettes and accom p a n y i n g text· C h a r g e , D i ners C l u b) by e n c l o s i n g c a rd boo k , You s i m p l y f o l l o w t h e s p o k e n a n d n u m b e r, e x p i r a t i o n d a t e , a n d y o u r • I .

w r i t t e n i n st r u c t i o n s , l i s t e n i n g a n d l e a r n · S i g n at u re. • i n g . By t h e end of t h e cou rse y o � ' 1 1 f i n d T h e Foreign Service I n s t i t u t e ' s G e r m a n

• • y o u r s e l f l e a r n i n g a n d s p e a k i n g e n t i re l y i n

course Is uncon d i t i o n a l l y g u a ra nteed. Try

• G e r m a n ! A n a t i v e G e r m a n s p e a k e r, c l e a r l y

i t for t h ree weeks. I f y o u ' re not c o n v i n ced I recorded o n t h e cassettes, prov i d e s an ex· i t's m e m o s t c o n ve n i e n t a n d m o st p a i n l es s I I

ce l l e n t m o d e l to h e l p you deve l o p y o u r way t o l e a r n G e r m a n , ret u r n i t a n d we ' l l reo

s k i l l s , f u n d every p e n n y y o u p a i d ! Order today ! • • ThiS co urse turns your c a s s e t t e pla yer

blJ . • I n t o a "tea ching m a c h i n e " W i t h I t s U n ! ' A u d i o F o r u m '" ", .

I q u e " p ro g r a m m e d " l e a r n i n g met h o d , you Dept. 8 0 0 • ® 1 45 Ea st, 49th 5t. • � .UPWft.�aDL � New York, N . Y . 1 00 1 7 .' .. ,.�, _ • • .... r ...,. . . (21 2) 753·1 783 •

�- . - - - . - - - - - - - - - - - - - - - - - - . . . � 1 1 3

#1 in a series ofreports on newtechnology fromXerox A bout a year ago, Xerox introduced the E thernet

network - a pioneering new development that ma kes it poss ible to link different office mach ines into a s ingle network tha t 's reliab le, flexible and eas ily expanda b le.

The fo llo wing are some n otes explain ing the tech n o log ica l underpin n ings of th is development. They a re con trib uted by Xerox research scientist Da vid B oggs.

The E thernet system was designed to meet several ra ther ambitious obj ectives .

F i r s t , it had to allow many users wi thin a given organization to access the same data . N ex t , it had to a l l o w the organization the economies that come fro m reso urce shar i n g ; that i s , if several people could share the same information processing equipment , i t would cut down on the amount and expense of hardware neede d . I n a ddition, t h e resulting n e twork h a d to be flex i b l e ; users had to be able to change components easily so the network could grow smoo thly as new capability was neede d . Finally, it had to have maximum reliability - a system based on the notion of shared information would look pre tty silly if users couldn't get a t the information because the network was broken.

1 1 4

Collision Detection The E thernet network uses a coaxial cable

to connect various pieces of information equip ment. I nformation travels over the cable in p ackets which are sent from one machine to ano ther.

A key problem in any system of this type is how to control access to the cable : what are the rules determining when a piece of equipment can talk? E therne t 's method resembles the unwritten rules used by people at a p a r ty to decide who gets to tell the next sto ry.

While someone is speaki n g , everyone else w a i t s . When the current speaker stops, those who w a n t to say something pause, and then l aunch into their speeches . If they co llide with each other ( hear someone else talking, too ) , they all stop and wait to start up again. Eventually one p a uses the shortest time and starts talking so soon that everyone else hears hi m and waits.

When a piece of equipment wants to use the E thernet cable , i t l istens first to hear if any o ther station is talking . When i t hears silence on the cable, the station starts talking, b u t it also l istens . I f i t hears o ther stations sending too , i t s t o p s , as do the o ther stations. Then it waits a

random amount of time , on the order of micro seconds, and tries again. The more times a station collides, the longer, on the average, it waits before trying again.

I n the technical literature , this technique is called carrier-sense multiple-access with col lision detection. I t is a modification of a me thod developed by researchers at the University of Hawaii and fur ther refined by my colleague Dr. Robert Metcalfe . As long as the interval during which stations elbow each other for control of the cable is short relative to the interval during which the winner uses the cable, it is very efficient. Just as important, i t requires no central

Cl Cl

control - there is no distinguished station to break or become overloaded.

The System With the foregoing problems solved,

. E thernet was ready for introduction. It consists of a few relatively simple components:

Ether. This is the cable referred to earlier. S ince it consists of j ust copper and p lastic, its reliab ility is high and its cost is low.

Tr ansceiver s . These are small boxes that insert and extract bits of informa tion as they pass by on the cab l e . Controller s . These a r e large scale inte grated circuit chips which enable all sorts of equipment, fr om communicating type writers to mainfr ame computers, regardless of the manufacturer, to connect to the E therne t . The resulting system is n o t only fast ( tr ans

mitting millions of bits of information per second ) , it's essentially modular in design. I t's l argely because of this modul arity that E thernet succeeds in mee ting its objectives of economy, reliability and expandabil i ty.

The system is economical simply because it enables users to share b o th equipment and information, cutting down on hardware costs. It is reliable because control of the system is distributed over many pieces of conm1Unicating equipment, instead of being vested in a single central controller where a single piece of mal functioning equipment can i nm10bilize an entire system. And Ethernet is expandable because it readily accepts new pieces of infor-

,. mation processing equipment. This enables an organization to plug in new machines gradu ally, as its needs dicta te, or as

technology develops new and better one s .

About The Author David Boggs is one of the inventors of

E thernet . He is a member of the research staff of the Computer S cience Laboratory at Xerox's P alo Alto Research Center.

He holds a B achelor's degree in Electrical Engineer ing from P rince ton University and a Master's degree from S tanford University, where he is currently pursuing a P h . D .

XEROX XEROX ® J nd Ethl'rnCI 3 rt' trademarks of XEROX CORPORATION.

1 1 5

1 1 6

SOME SERIOUS N OTES ON MOVING.

By Victor Borge

When you move , make sure your mail arrives at your new address right after you do .

The key is this: Notify everyone who regularly sends you mail one full month before you move .

Your Post Office or Postman can supply you with free Change-of-Address Kits to make no tifying even easier.

One last serious note . Use your new ZIP Code .

Don't make your mail come looking for you . (� J Notify everyone a month before you move . � ®

©uSPS 1980

shared by all malignant cells, so that the early hopes of employing lectins to iden tify and perhaps to attack such cells se lectively have faded.

Cell-surface sugars participate in fer tilization in mammals, sea urchins, pro tozoa and algae. Cellular association in slime molds is mediated by the interac tion of carbohydrate-binding proteins on one cell with specific oligosaccharide receptors on another cell. Thus differen tiation in slime molds from a vegetative (single cell) form to a cohesive (aggre gated) form is accompanied by the ap pearance of both cell-surface lectins and specific glycoproteins. Moreover, sim ple sugars such - as galactose and acetyl galactosamine inhibit the aggregation of cells in this system.

In recent years it has been demon strated that cell-surface saccharides act as receptors not only for viruses but also for bacteria. This finding is proba bly the best-documented example of a specific cell-cell interaction mediated by carbohydrates. It is a phenomenon of great importance, since the adher ence of bacteria to tissue surfaces is the initial event in a bacterial infection. Work done in our laboratory and else where has demonstrated that bacteria such as Escherichia coli and Salmonel la typhim u rium adhere to epithelial cells and to scavenging white blood cells through units of mannose on the surface of such cells. This carbohydrate-specific interaction is mediated by a mannose specific lectin present on the surface of the bacteria. The lectin has been isolat ed from E. coli by Yuval Eshdat of our department. In collaboration with Da vid Mirelman of our department and Moshe Aronson and Itzhak Ofek of Tel Aviv University we have also found that colonization of the urinary tract of mice infected with E. coli can be mark edly diminished by the administration of methyl a -mannoside, a sugar that ef fectively inhibits the mannose-specific adherence of the bacteria to epithelial cells. Further studies of the sugars on cell surfaces that act as receptors for bacteria may lead to the design of im proved inhibitors of adherence. Such in hibitors might serve to prevent bacterial infection by blocking its first step, the adherence of the invading organism to the epithelial surfaces of the host.

To sum up, carbohydrates are found in wide variety, and many of them are extremely complex. They perform nu merous tasks in living organisms; most important, like nucleic acids and pro teins, they seem to serve as information al molecules. Determining more about these compounds and establishing in de tail their chemical structure and confor mation wil l not only result in a deeper understanding of what life is but also make it possible to combat more effec tively ',arious diseases, such as those caused by genetic defects or infectious agents.

toda y 's quartz timepieces is revealed. Most m aj o r com pa n i es wo u l d rat h e r

h a v e t h e s e facts re m a i n sec ret, b u t o n e l itt l e - k n ow n c o m p a n y d e c i d ed t o s h ow its ge n i u s to t h e wo r l d .

To effe c t i v e l y c o m p e t e i n w o r l d m a rkets a n d w h e n l ac k i n g i n necessary tec h n o l ogy, m a n y m a j o r c o m pa n i es have t u rned to s m a l l e r m o re d y n a m i c co m pa n i e s to b u i l d t h e i r p rod u c t s . So m e t i m e s t h e p rod u ct i s b u i lt t o t h e s p e c s of t h e m aj o r c o m p a n y . B u t m o re often t h a n not, t h e o n l y u n i q u e p a rts a re a l a be l a n d d i ffe r e n t o w n e r ' s m a n u a l . T h i s p ract i c e i s q u ite p reva l e n t i n t h e d i gital watch i n d u stry.

O n e company t h a t h a s been t h e rea l sou rce be h i n d p rod ucts i nt rod u ced i n the U . S. b y compan ies l i ke Mattei , Timex and Texas I nstr u m e nts, is Olym pos Elec tro n i c Co . , a l so known as Otro n .

O l y m pos E l ectro n i c n o w w a n t s t h e wo r l d to k n ow i t s n a m e a n d ge n i u s . W e feel l u c ky t o b e sel ected t o b r i n g t h i s sto ry t o you .

Normal Time

Dual Time Zone

Dual 24 Hour Alarms

Stopwatch

WE : 9 1 2 : 5 6 3'-1

WE :9 �i��!��:�4 1 1 : 5 6 3 '-1 hour tlme; model

12 selection (24 hr. '--___ -J shownl. a One o; two loud 6: 3 0 - I alarms set for

;. 6:30 am.

0 0 1 2 hr. chrono, nn . n n n n split and lap tim· U U ' U U u u ing, with 1l100

'--___ \....J sec. precision.

Hourly . n n the hour G Chimes on Chime ' U U with confir· mation. .��1

r ht [3 12 or 24 hr

Ll hl g ' O ' 3 U 2 S count down, g for I " count up E.enlng Ilmer. Viewing

O l y m pos E l ectro n i c C o . is n o w i n trod u c i n g p rod u ct s i nto t h i s c o u n t ry u nd e r its own t rade n a m e -Ot ro n . We a re i nt rod u c i n g o n e of t h e fi rst Ot ron p rod u cts i nto t h e U . S .

1 2 o r 2 4 H O U R D U A L T I M E , D U A L ALA RM C H RONOG RA P H T h e fi rst product we sel ected i s t h e

A l a r m C h ro n o X watc h . I t m a y be t h e m o s t a d v a n c e d Q u a rtz t i m e p i ece i n t h e w o r l d t o d a y f o r u n d e r $200.

We k n ow of n o ot h e r watc h t h at com b i n e s t h e s e u n i q u e feat u res a n d d e s i g n . It h a s both a 2 n d t i m e z o n e c a pa b i l ity a n d a 2 n d sepa rate a l a r m . I t c o m e s i n e i t h e r 1 2 o r 24 h o u r versi o n . These feat u res a re j u st t h e begi n n i ng . Co m pa re t h i s watc h feat u re -for-feat u re aga i n st a n y ot h e r in t h e wo r l d . We be l i eve you w i l l be c o n v i n ced t h at t h e re is not a better watc h d o l l a r-for d o l l a r a n yw h e r e .

T E ST E D TO 1 00 F E E T O F WAT E R T h ree y e a r s a g o , t h e re w e r e n o

d i gi t a l water resistant a l a r m watc h e s . Today t h ey e x i st i n s o m e m o re a d v a n c ed m od e l s , b u t c o s t $ 1 00, $ 2 00 or more. Our Alarm C h ro n o X i s s u b m e r s i b l e t o 1 00 feet o f wate r . Its u n i q u e a l a r m e m i t s s o u n d r i g h t t h r u t h e sta i n l e s s steel c a s e . T h e O-ri n g c o n st ructi o n a n d roc k h a rd m i n e ra l gl ass lens p rov i d e a l o c k tight seal aga i n st water to 1 00 feet - i t ' s g u a ra nteed .

T H I N N E SS A N D B O L D MASC U L I N E D E S I G N

T h e A l a rm C h ro n o X i s a co m bi n a t i o n of bo l d m a sc u l i n e d e s i g n a n d j u st t h e r i g h t d e g r e e of t h i n n e s s . N o sac r i f i c e i n fu n c t i o n o r m a sc u l i n ity, t h e Ch ro n o X m e a s u res 8 . 9 m m f r o m t h e top of its m i n e r a l g l ass l e n s to t h e b a c k of its sta i n l e s s s t e e l c a s e . T h at' s 1 . 6 m m t h i n n e r t h a n t h e p opu l a r Se i ko A l a r m C h ro n o g ra p h , 2 . 1 m m t h i n n e r t h a n t h e C i t i z e n a n d 3 . 1 m m th i n n e r t h a n Texas I n st r u m e nts . Yet Alarm C h ro n o X has t h e sa m e b o l d d e s i g n of eac h . The Sei ko se l l s fo r $250; t h e C i t i z e n fo r $ 2 00; a n d t h e T . I . fo r $ 1 2 5 . . . What does Ot ro n k n ow t h a t th ese ot h e r c o m pa n i es d o n ' t ?

U N S U R PASS E D Q U A L I T Y A N D ACC U RACY FOR U N D E R $70

Sta i n l ess ste e l case, a n d fi n e l y wove n m e s h b r a c e l e t , m i n e ra l g l a s s l e n s , wate r res i st a n t t o 1 00 feet a n d q u a rtz acc u racy to ± 5 sec o n d s per m o n t h . T h a t ' s q u a l ity a n d a c c u racy fou n d o n l y i n watc h e s cost i n g $200 o r m o r e . T h e A l a r m C h ro n o X se l l s fo r $69 . 9 5 i n sta i n l e s s steel case a n d $ 7 9 . 9 5 i n go l d w i t h 3 m i c ro n s of r e a l g o l d o v e r sta i n l e s s . Com p a re feat u res a n d p r i c e f o r you rse l f before you ca l l to o r d e r .

O R D E R TO L L F R E E AT N O- R I S K T h e A l a r m C h ro n o X i s offered w i t h a

1 5 d ay n o - r i s k t r i a l p e r i od . If d u ri n g 1 5 d ays, you fi n d t h e A l a r m C h ro n o X n ot to yo u r l i ki n g ret u r n it for a p ro m pt re fu n d of yo u r p u rc h ase p r i c e .

I n t h e u n l i ke l y eve nt t h at a n yt h i n g s h o u l d go w ro n g after t h e t r i a l p e r i o d , yo u r A l a r m C h ro n o X i s b a c k e d b y a fu l l year w a r r a n ty t h r u Ot ro n ' s Service by m a i l repa i r fac i l ity in t h i s c o u n t r y .

To o r d e r yo u r A l a r m C h ro n o X fi l l o u t t h e order fo rm b e l o w a n d s e n d it w i t h c h e c k o r m o n ey o r d e r to u s . F o r fa ster serv i c e , c red i t c a rd c u st o m e rs c a l l To l l F ree 1 -800- 5 2 7 - 7066 . Do n ' t w a i t - order today to i n s u re gett i n g a watch of t h i s q u a l ity, w i t h t h e se fu n ct i o n s , at t h i s price .

1 1 7