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http://jmcc.editorialmanager.comfor online submission

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Heart Newsand viewsVolume 13, Number 2, 2005

www.ishrworld.org

the news Bulletin of the International Society

for heart research

In this issue:

� The Heart of the Matter,

by Inder S. Anand . . . . . . . . . . . . . 1

� President's Letter . . . . . . . . . . . . . 4

� Past Truth & Present Poetry,

by Richard J. Bing . . . . . . . . . . . . . 5

� Bridging the Gap, where

clinical and basic sciences

meet, by Karl T. Weber. . . . . . . . . 6

� 2005 Medals of Merit of

European Section . . . . . . . . . . . . . 7

� Report on New Orleans Meeting 8

� New Orleans, August 2005 . . . . . 9

� 2005 YIA Winner of the

American Section . . . . . . . . . . . . 10

9

the heart of the matter

7 12

new orleans,

Louisiana

August 2005

Osaka,japanDecember15-17, 2005

15

Tromso,

norway

June 2005

A Career inCardiovascular

research

Inder S. Anand, M.D.

Despite my eclectic interests andfairly regular change of place andresulting circumstance, research

on the effects of high altitude on thecardiovascular system has remained anenduring allure in my career. Initially, Iwas drawn to this field as a consequenceof the India-China war. In 1962, the Chinesearmy launched an attack in differentsectors of the Himalayan regions. TheGovernment of India, caught off guard, reacted in panic by hastily dispatchingseveral thousand soldiers to elevations of 3,500 to 5,000 meters above sea level.Woefully ill equipped, ill trained and unacclimatized for mountain warfare, thesesoldiers succumbed in massive numbers; still larger numbers developed amysterious illness within a few days of arriving at these altitudes, coughing upblood and unable to breath. It was only about a year later that it became clear thatthese men were developing high altitude pulmonary edema (HAPE), a conditionthat had hitherto been described only in case reports. As a doctor in training, I wascurious about this little known condition. When the mountaineering institute atManali was established as part of a strategy to prepare for any possible futureconfrontation in the mountains, I immediately joined to train as a mountaineer.

At the institute I developed an abiding fascination for the yak. I was intriguedwith their dexterity on the slopes and indifference to the rarified air. All expeditionsto Mount Everest had used the yak to haul heavy loads to camps over 6,000 meters.I learned that the yak belonged to the bovine family, and was in fact the first cousin

� Report on Tromsø Meeting . . . . 12� Report on Tartu Meeting . . . . . . 13

� Report on Perth Meeting . . . . . . 14

� Meetings Calendar . . . . . . . . . . . . 15

2

The news bulletin of the international society for heart research

of the cow. Nonetheless, cattle cannotsurvive at high altitude, developing brisketdisease with severe pulmonary hyper–tension and right heart failure. I could notfind an explanation as to why the yak is sototally adjusted to high altitude, while thecow has an adverse reaction. My intuitionprompted me to believe that perhaps thevital clue for comprehending mountainsickness lay in this distinction.

A scholarship to Oxford necessitated achange of focus, and I obtained a D.Philin physiology and acquired experience incardiology. By now I had developed akeen interest in heart failure. In 1984, Ireturned to England to study the role ofneurohormonal activation in heart failurewith Peter Harris. Although dormant, mydesire to understand the differences inresponse to altitude between the yak andthe cow still held my attention. I wasaware that Peter and his dear friend, theeminent pathologist, Donald Heath, hadfound that the camelids, like the llama inthe Andes, do not respond to hypobarichypoxia by vasoconstriction. I asked Peterif it was possible that the yak may havesimilar mechanisms of adaptation. Petersuggested we undertake to examine theconjecture. The initial studies at theWhipsnade Zoo, near London, confirmedthat the pulmonary artery pressure of theyak was indeed low.

The Heart of theMatter: A Career inCardiovascularResearch

In this issue of Heart News and Views, webegin a new series of autobiographical

articles entitled, “The Heart of the Matter:A Career in Cardiovascular Research”. Weare privileged to begin our series with thecontribution of Dr Inder S. Anand, Professorof Medicine at the University of MinnesotaMedical School and Director of the HeartFailure Program at the VA Medical Centerin Minneapolis, MN.Dr Anand was charged to provide anautobiographical account that must includespecific advice to young scientists interestedin pursuing a similar career path, and hehas graciously responded with a fascinatingaccount of his research experiences in thefield of high altitude physiology andmedicine. We are greatly indebted to DrAnand for setting such a high standard withthis initial installment in the series, andhope that you enjoy sharing the wisdom ofyour colleagues as they recount their storiesof a life lived in the pursuit of cardiovascularresearch.

Leslie Anderson Lobaugh, Ph.D.

The effects of high altitude on the cardiovascularsystem have remained an enduring allure in my career

Encouraged by the preliminary results, ateam comprising Peter Harris, DonaldHeath, David Williams, Roberto Ferrari,and myself was organized to go to theHimalayas to investigate the hemo–dynamics of the yak at 3,500 to 5,000meters. We were able to substantiate thatthe yak at those altitudes did not show anincrease in pulmonary arterial pressureand that the lack of hypoxic vasocon–striction was due to the absence ofvascular smooth muscle in the pulmonaryarterioles. Over the next ten years, wemade several expeditions to the region.The monks of the Tak Tok monastery, inthe village Shakti (4,500 m) where most ofour research was done, slowly warmed to

our presence. They brought to ourattention that the yak was not only animmediate relative of the cow but alsomated with the cow, the dzo being theprogeny. Like most crossbreeds the maledzo is sterile, while the female dzomo isvery fertile; she mates with the yak bull toproduce the stoll, and with the cow bull toproduce the gar. Soon we were able toshow that the lack of pulmonary vascularsmooth muscle, and consequently thehypoxic vasoconstrictive response, inthese crossbreeds is inherited as anautosomal dominant trait. After work on anumber of animal species in different partsof the world and over a number of years,it became obvious that animals indigenousto high altitude were adapted to hypobarichypoxia by developing biochemical,physiological and anatomical features thatwere genetic in nature, allowing thespecies to explore the environment to itsbest advantage.

It was now only natural to question ifhumans indigenous to high altitude hadalso adapted to hypoxia. In 1928, CarlosMonge described chronic mountainsickness (CMS) in Peru, a condition inwhich severe polycythemia develops insome individuals after a prolonged stay athigh altitude. Generally attributed to abreakdown in acclimatization, we won–dered whether it was no more than a

response to existing respiratory ailments.Most of the patients described by Mongewere, after all, heavy smokers and workedin mines. There were also more recentreports of Han Chinese migrants to Tibetdeveloping symptoms resembling CMS,which was not seen among Tibetans. Inthe summer of 1985 our team arrived in theTibetan city of Lhasa. We believed thatautopsy material would shed light on thepathogenesis of CMS and perhapsprovide evidence of adaptation in humans.

Dr Sui, the kindly Chinese pathologist inLhasa, anxious to help, would present useach day with the hearts and lungs ofinfants of Han origin who had died within

a few months of arrival from the plains ofChina to Lhasa (3,500 m). Upon exami–nation and reexamination of the autopsymaterial, we realized to our amazementthat we were observing a syndrome that,to our knowledge, had never been seen orreported. The condition affected mostlyinfants of Han origin who presented withcongestive heart failure within 2 monthsof being brought from low altitudes to livein Lhasa. The most striking feature wasright ventricular hypertrophy, and a dilatedpulmonary trunk. The ratio of the right toleft ventricular weight was 3 times that ofage matched Tibetan controls. Thepulmonary arterioles showed muscular–ization with development of a thickmuscular media. In contrast, the Tibetanage matched controls had thin walledpulmonary arteries and a single elasticlamina in the pulmonary arterioles. Clearly,unlike the Han infants, the Tibetan infantsappeared to be genetically adapted tohypoxia. We called this conditionsubacute infantile mountain sickness.

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volume 13, number 2, 2005

Regardless of my responsibilities as acardiologist in Chandigarh, the questionof whether humans indigenous to highaltitude were adapted never receded frommy mind. In 1988, chance gave me yetanother opportunity to find the answer. Acall from the army headquarters informedme that they were unable to comprehenda strange epidemic that was bedevilingtheir personnel at the Siachin Glacier (5,000to 6,500 m). The next six weeks were spentinvestigating these patients, who evi–denced a remarkable pathophysiology ofheart failure. Healthy soldiers, after ten totwenty weeks of being stationed ataltitudes of 5,000 to 6,500 meters, startedto develop a syndrome: insidious in onset,with gradual increase in shortness of breathand edema leading to gross anasarca.ECG and echocardiography showed rightventricular hypertrophy and dilatation butnormal LV structure and function. Hemo–dynamics confirmed moderate pulmonaryhypertension. All the abnormalitiesreverted to normal within 12-16 weeks oftransfer to sea level. I decided to call thissyndrome adult subacute mountainsickness, because it bore all the charac–teristics of subacute infantile mountainsickness. Both the infantile and adultvariety could be considered the humancounterpart to brisket disease in cattle.

To continue our work on mountainsickness, we established a permanentlaboratory in Leh (3,500 m). Here we foundthat the pulmonary arterioles of nativeLadakhi highlanders, who had died

accidentally, lacked vascular smoothmuscle, much like those of the yak. Takentogether, the rarity of the syndrome inTibetan infants and Ladakhi adults, andthe absence of vascular muscle in nativeLadakhis, strongly suggested thathumans indigenous to high altitude havealso adapted to hypobaric hypoxia.

The whole pleasure of research is not what has beenfound but what it might lead to, a light cast beyond itself

At the end of my venture across theterrain of high altitude medicine, there isa deep sense of gratitude in knowing that,by making the classification of mountainsickness more comprehensive, we havemade a contribution to the understandingof the impact of altitude on humans andanimals. However, over and above all,there is the feeling of immense fulfillmentin the education garnered and the lessonslearned. I offer these in the hope thatyoung scientists may find somethingtherein to assist them on their journey. AsEinstein said, “your generation must putmy generation to shame”.

� I recognize that at every juncture in myendeavor in scientific research, providingthe momentum was one or anotherfortuitous opportunity. Nevertheless, fora set of circumstances to be identified asopportune, the determining factor is reallythe disposition of the mind. It is the alertreasoned mind that grasps an indication,thereby creating the ‘lucky chance’.� Experience also bears out the impor–

tance of intuition. If I had abandoned myhunch on observing the yak functioningat high altitude, perhaps we would neverhave engaged in this exploration. Logic isindeed crucial for developing andvalidating any theory, however it isintuition that is the guide to discovery.� The role of worthy mentors cannot beoverstated. Peter Harris and Donald Heathbrought to our research their admirableerudition and inherent rapidity of thought,affording guidance and an indispensablecorrective against any tendency towardsmental lethargy.� A hypothesis, while needed to directobservation and design experimentation,should never impede the ability to remainopen to all probability. An attitude todiscover rather than to prove engendershumility to be sensitive to alternateopinion. If we had not listened to Dr Sui,

a critical aspect of our research wouldhave been lost.� Popular know how and belief warrantsrespect. Common knowledge in the fieldis fed by observations that have enduredtime. The monks were, after all, the sourceof the crucial information on thecrossbreeds.� The whole pleasure of research is notwhat has been found but what it mightlead to, a light cast beyond itself. It wasthe animal data that urged us to study thehumans at high altitude.� In the final analysis, scientific researchis not only for stimulating the reasonedmind to scrutinize and explain phenom–ena, it is as much a dedication of spirit tounravel the truth in the service of wisdomand beauty. The resolve to defy the manychallenges this entails can only be sus–tained by an unwavering passion for thecalling. Science is a jealous lover cravingabsolute commitment of time and ardor.

Inder S. Anand, M.D.

Minneapolis, MN �

The author with Donald Heath (middle) andPeter Harris in La Paz, Bolivia in 1988,during an expedition to study pulmonaryartery pressures in new born infants.

4

president 's letter

Dear Reader,

s you know, August is holiday time in Italy. Being 100% Italian, I began myAholiday two weeks early and I am writing this letter while relaxing in Boca di Magraby the sea. My thoughts have turned to an earlier visit by Tom Ruigrok and his family.We went out on my boat, and I still have the memory of a Dutch professor baskingin the shade of the caves on a fantastic stretch of Ligurian coast called Le Rocce Rosse,while every Italian was fighting to get more sunshine! Time goes by so fast, and I onlyhope that we will be able to repeat this experience.

Because I am on holiday, instead of giving you an official report of ISHR business Ithought that I would tell you a little about the history of Bologna, and thus tempt you to attend the 2007 World Congresswhich will be held there.

The University of Bologna was founded in 1088. It is the oldest universityin the western world, and has influenced the entire history of EuropeanUniversities. Throughout history, Bologna has been an important centrefor learning in many fields of study: methodology, logic, judicial andtheological sciences during the Middle Ages, and medicine, physics andmathematics during and after the Renaissance. Bologna produced majorcontributors to these areas of knowledge, including such scholars asAldrovandi, Malpighi, Marsili, and Galvani. The University has also hadteachers of the highest caliber, among them Carducci, who received theNobel Prize for Literature in 1906. Thanks to Carducci, the University ofBologna virtually symbolised the new Italian culture.

Bologna is the chief town in Emilia Romagna. You must pass through itwhen going from the north to the south of Italy. The town began as anEtruscan centre, then Gallic, and finally it became a Roman colony. Thewonders of Bologna are the arches and towers throughout the city.Bologna is considered La Mecca for food, and it is best know for Tortellini,Parmesan Cheese and an enormous variety of sausages – Mortadella beingthe most famous. However, for the Italians it is the city of homemade freshpasta, and if you visit Bologna you will be able to meet the families that stillproduce it. Lambrusco is the local wine. Bologna has a population ofaround 500,000, and a famous international airport that connects it tocities worldwide.

I hope that you will forgive me for such an informal letter, but I promise that I will be back again soon with more “official”ISHR business. Tom, please be assured that Le Rocce Rosse are still there, and that my new boat has a roof to provideshade.

Roberto Ferrari

the news bulletin of the international society for heart research

The Neptune fountain andthe Basilica di San Petronio

in Bologna

5

Richard J. Bing

Past truth & present poetry

(continued on page 9)

volume 13, number 2, 2005

29. Kohler, Milstein, and

Monoclonal AntibodiesWITH the advent of molecularbiology and immunology, anew era of medical therapy

has arrived. The discovery of monoclonalantibodies by Köhler and Milstein in 1975brought closer the dream of Paul Ehrlichof a magic bullet, a therapy which targetsa specific cause of a disease. Today clinicaltrials with monoclonal antibodies haveshown promise for breast cancer usingbevacizumab against the angiogenicvascular endothelial growth factor and oftrastuzimab or herceptin, a monoclonalantibody against HER-2, a surface cellprotein that transmits signals controllingcell growth and cell division. In lung andcolorectal cancer, clinical trials haveshown the potential value of the mono–clonal antibody bevacizumab. In cardio–logy, daclizumab, a humanized mono–clonal antibody against the interleukin-2receptor, appears to be an effectiveprophylactic agent against acute cellularrejection of cardiac transplants. Mono–clonal antibodies have had an equal impacton methodology. This includes theseparation of individual cell types withspecific surface markers, the diagnosis oflymphoid and myeloid malignancies,tissue typing, serotyping of micro–organisms, among others.

The key to Köhler and Milstein’ssuccess lies in the fusion of cells; theyfused mouse myeloma tumor cells tospleen cells derived from a mouse whichpreviously had been immunized, usingSendai Virus to accomplish fusion. Laterpolyethylene glycol or addition of a strongelectric field were used. Köhler andMilstein were lucky because they chosenormal antibody producing cells from amouse that had already been activated byimmunization. Activated cells fuse 100times better than non-activated cells. Inaddition, their hybrid cells were stableand continued to produce antibodies.Hybridomas were selected out in a tissueculture medium which did not supportgrowth of the parental cell types. Bysuccessive dilution or by plating out,

single clones could be established inwhich all the antibodies produced wereidentical, had the same Ig class andallotype, and the same structure, affinityand specificity for a given epitope.

While Milstein and Köhler’s hybrid–omas were fusions from mouse cells,human clonal antibodies can now beconstructed by using recombinant DNAtechnology; this can entail chimericconstructs in which the mouse domainsare spliced onto human genes, resultingin antibodies which are less immunogenicin humans.

Who were Georges Jean Franz Köhlerand César Milstein? Köhler was born in1946 in Munich and died in 1995 ofmyocardial failure when he was only 48years old. He studied biology at theUniversity of Freiburg and in 1971 went tothe Basel Institute of Immunology wherehe obtained his Ph.D. In 1974 Köhlermoved to England for a 2-year post–doctoral fellowship to work with Milsteinin the medical research council laboratoryin Cambridge. César Milstein was born inArgentina in 1927, the son of Europeanimmigrants. He obtained his Ph.D. inArgentina, as he writes “with no economicsupport.” He then moved to the depart–ment of biochemistry in Cambridge, thenreturned to Argentina, and then moved

permanently to Cambridge to work withFred Sanger, the head of the division ofprotein chemistry. Upon the advice ofSanger, he switched from biochemistry toimmunology and began to work on thefusion of two myeloma cell cultures. Itwas then that Köhler joined him and thiscooperation led to the production ofhybridomas. Instead of hybridizing twomyelomas, they hybridized a myelomaand an antibody producing cell. The twomen had met first at a lecture Milsteingave in Basel, and their cooperation led towork which changed immunology. AsMilstein wrote in his obituary of Köhler:“We both concluded that it was thiscombination of knowing how to fuse cellsand wanting specific myelomas that led tothe substitution of one fusion partner forspleen cells of an immunized animal.”

It was, so Milstein reported, the speedat which everything happened which wasso remarkable. The paper in Nature wassubmitted when Köhler had been in thelaboratory for just one year. But the journalagreed to publish the report only oncondition that it be condensed to anabbreviated letter format. This misjudg–ment of great advances by editorialreviewers is all too common. How difficultit is to cross the barrier from obscurity torecognition! Government agencies alsofailed to appreciate the potential of thediscovery and no patents were appliedfor. After finishing his second year as apostdoctoral fellow in Cambridge, Köhlerreturned in 1976 to the Institute in Baseland hence to Freiburg as Director of a MaxPlanck Institute. He left it to others tocommercially exploit monoclonal anti–bodies, which became a billion dollarbusiness.

Köhler’s tenacity to learn and hisapproach to difficult situations wasshown in Cambridge when he foundhimself living in a house with a piano anddecided to learn to play. He refused totake piano lessons, so he bought the

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the news bulletin of the international society for heart research

All' s well that

ends well

bridging the gap. where clinical and basic sciences meet

by Karl. T. Weber, M.d.

THE many lakes and rivers ofManitoba make it a popularvacationland. It is one of Canada’s

three Prairie Provinces - Alberta andSaskatchewan are the others - and thepolar bear capital of the world. Daffodilsdotted the landscape on the plains ofManitoba as spring had finally arrived inlate May.

Fester and Tess Pearson were recentlymarried in Vita, located in rural south–eastern Manitoba not far from the RedRiver. They dropped out of high schoolto raise their twin boys, James and John,born on Thursday, May 22, 1947. Jameswas born 7 lbs, 8 oz and appeared vigorousand active. By comparison, John weighedonly 5 lbs, 5 oz and was frail and weak.Breastfeeding both boys would bedifficult for Tess, given her scant supplyof breast milk. Pediatrician Dr Medwicksuggested Tess reserve breastfeeding forJohn; James would receive formula sheprepared. The boys were discharged homeon Thursday, June 5. It was time for theboys’ feeding when Tess said, “Fester,go fetch some water for James’ formula.”Fester grabbed a bucket and went outback as Tess breastfed John. Finding anempty rain barrel after the recent dry spell,Fester ambled down the gully to the well.His right arm applied rapid, repetitive up-and-down action on the pump handleuntil the bucket was full. He rushed backto the house, hoping his responsivenesswould please Tess. He had plans for themafter the boys were asleep.

At 1 month of age, John was growingnicely despite his seemingly weakdisposition at birth; James, on the otherhand, now seemed listless and his lipswere gray. Perhaps it was the dimcandlelight that lit the house. The nextmorning was bright and sunny. Tess roseearly to change John’s diaper and fed him.She then aroused James, who had a bluishdiscoloration of his lips, fingers, and toes.Tess became quite frightened and

immediately awoke Fester. “Fetch myfather!” she exclaimed. “We need to go tothe doctor. James is ill.” Within the hourthey had driven to the hospital in Vita.

Practitioner Dr Hutchins learned thatJames had been the larger and healthierof the two at birth. He inquired as towhether either boy had recently beensick. Diarrhea, perhaps? Except for thepresent spell and perhaps some list–lessness, James had not been ill. Johnwas well. “This bluish discoloration, orcyanosis, could be due to a hole in James’heart,” he reported. “Congenital heartdisease, it’s called. We must obtain achest x-ray.” The x-ray revealed James’heart to be of normal size and there wasno suggestion of cardiovascular mal–formation. Nonetheless, Dr Hutchinsmet with the Pearsons and recommendedJames be admitted for observation. Laterthat day, Dr Hutchins looked in on Jamesin the nursery. He was receiving O

2, but

his cyanosis persisted. The followingday, James was released, no longerdiscolored and his strength restored.After only a few days at home, Jamesagain turned blue. He was readmitted tothe hospital, where he once againrecovered.

Rain finally appeared on Tuesday, July1. Evenings were now warmer and thewood-burning stove no longer needed.The next morning Tess woke James to findhim with a third episode of cyanosis.However, on this occasion the cyanosiswas so generalized and intense that whenDr Hutchins saw James he referred thePearsons back to Dr Medwick. Thatevening, Tess made provisions to takethe train to Winnipeg. John would remainbehind and stay with Tess’s mother, Mary,who would feed him with milk from Bessie,Tess’ cow.

Upon their arrival in Winnipeg onThursday, James’ cyanosis was barelyperceptible. Additionally, Dr Medwickcould find no evidence of heart or lungdisease. He was perplexed as to the causeof James’ intermittent cyanosis. “Isuggest the next time James has an episodeyou call me straightaway. I will catch thefirst train to Vita and examine James.” Afrustrated Fester and worried Tessreturned home that day to find Tess’ father,George, pacing the pavement, his anxietyevident. “John has turned blue, and yourmother is fit to be tied,” he reported. Upontheir arrival at the Barnett farm, Tess foundJohn to be cyanotic. “Fester, telephoneDr Medwick in Winnipeg and ask him tocome to Vita. Tell him James appears to befine while John is now the one who isblue.” Medwick arrived on Saturdaymorning.

What is your diagnosis?

Since the Pearson’s visit to clinic andduring the train ride to Vita on July 4th, DrMedwick considered various possibilities.He was prepared to address them. Parentsand grandparents had not taken ill whileJames had become cyanotic on severaloccasions and now so had John.

Cyanosis, the presence of 5 g/dL ormore of reduced hemoglobin in capillaries,may be subdivided into central and

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Volume 13, Number 2, 2005

peripheral types. In the central type, thereis either arterial blood desaturation or anabnormal hemoglobin derivative. Mucousmembranes and skin are both affectedand discolored. Peripheral cyanosis isdue to either a slowing of blood flow or anabnormally large degree of O

2 extraction

from normally saturated arterial blood.Causes of peripheral cyanosis includegeneralized vasoconstriction, low cardiacoutput associated with blood loss,cardiogenic shock, or venous occlusion.James did not have any of these. Twoother things argued against peripheralcyanosis: it was generalized; and did notimprove on supplemental O

2.

Medwick found John to be drowsy andhis skin, lips, hands, and toes had a bluishdiscoloration but there was no evidenceof cardiopulmonary disease. From hisdoctor’s bag Medwick pulled out a testtube and syringe. He withdrew bloodfrom John. It was chocolate-colored! Evenwhen he swirled the tube and its blood,mixing it with ambient oxygen, thechocolate color remained. This furtherruled out reduced hemoglobin due tohypoxemia and entities such as congenitalheart disease with a right-to-left shunt orintermittent respiratory airway obstruc–tion. He then removed a vial from his bag;it contained a solution of methylene blue.He administered 0.5 cc intravenously andwithin the hour John’s cyanosis dis–appeared. The diagnosis was now made:methemoglobinemia.

The question that now challengedMedwick was why the twins had devel–oped methemoglobinemia (metHb). Thefact that James recovered in the hospitaland on the train to Winnipeg could alsobe explained by his removal from anoffending agent in the environment.Aniline dyes from blankets or waxcrayons? Aniline derivatives, such asphenacetin? None seemed likely. Nitrates?But from where? Well water? He wouldhave to search the premises.

The well at the Barnett’s had beendrilled last year and was well constructed.Nevertheless, Medwick took a sample for

subsequent examination. Over at thePearson’s decrepit farmhouse Medwickrequested “show me where you obtainyour drinking water.” Tess took him outback to the rain barrel, which was filledwith water after the recent rain. “Whenthe barrel is empty, Fester fetches waterfrom our well,” she remarked. “With thedrought we had these past weeks, James’formula was prepared with well water.”The well was old, in poor repair, andsituated in a gully downstream from thePearson’s house, Bessie’s small barn, andthe outhouse. Medwick could onlyimagine the high nitrogenous concen–tration that had accumulated undergroundfrom human and animal waste. This mustbe the source of nitrates as he took asample. “Let’s see Bessie,” he askedTess. They found the old cow drinkingwater from her trough. “Where does thiswater come from?” he asked. “Rain watermostly. But with the drought, Fester filledit with well water.” Medwick noted“ruminants, like cows and sheep, have arumen filled with bacteria that can convertnitrates to more toxic nitrites. Monogastricanimals, like pigs and chickens, have norumen and the nitrate they consume iseliminated in urine. So the milk Johnreceived from Bessie must have been high

in nitrites and nitrates. Newborn infantshave little acid in their stomach and thebacteria present converts nitrates tonitrites. Let me have a sample of Bessie’smilk for analysis.”

“This is all so fascinating,” said Tess.“Maybe Bessie has nitrate poisoning andthat’s why she seems so run down andwhy her milk production is so scanty.Should we check her for cyanosis?”Medwick beamed at the idea. Sure enough,when he lifted Bessie’s upper lip toexamine her mucous membranes, therewas the telltale bluish discoloration.

That night, Tess called over to herhusband dozing in a chair. “Fester, I’vebeen thinkin’. I’m going back to highschool this fall to get my diploma. MaybeI could go on to the university and becomea veterinarian.” She paused a moment.“By the way, Fester, go fetch rain waterfor James’ formula. And take your time.I have a headache.”

Abridged from: Weber KT. All’s well thatends well. Cardiovasc Res 1999; 41: 5-8.

Karl T. Weber, M.D. �

During the European Section meeting in Tromsø, the Medal of Merit was awardedfor the third time. The Medal was given to Bernard Swynghedauw (Paris, France) and

Ernesto Carafoli (Padova, Italy) for their outstanding contributions to cardiovascularresearch. The laudatio’s were delivered by Jean-Jacques Mercadier and Fabio Di Lisa,

respectively.

medal of merit of the european section

From right to left:Jean-Jacques

Mercadier,Bernard

Swynghedauw,Ernesto Carafoli and

Fabio Di Lisa

8

the news bulletin of the international society for heart research

1

2

3

report on the XXVII annualmeeting of the american section

(may 12-15, 2005; New orleans, louisiana)

HAVING arrived in the culturally rich city of New Orleans to attend the 27thannual meeting of the American Section of the International Society for

Heart Research we were greeted by an abundance of both sunshine and heat (twoentities not associated with Scottish summers!). Although the good weather wasa more than adequate reward for the long trek across the Atlantic the best wasyet to come as we were treated to a fantastic meeting full of numerouseducational and social highlights.

A stimulating forum, compiled by theexceptional conference committee,commenced with an inspirational lecturefrom Prof. Louis J. Ignarro, a Nobel laureatefrom the University of California, LosAngeles. Prof. Ignarro’s talk describednitric oxide (NO) as a unique signallingmolecule and illustrated how exercise canenhance the beneficial effect of NO onthe cardiovascular system, a belief heappears to hold steadfast as evidencedby an entertaining collection of slidesdocumenting his triumphs as a marathonparticipant. His seminar also describedhis successful path to achieving thecoveted Nobel Prize and served to dispelsome of the mystique surrounding theaward ceremony, which proved to be ofgreat interest to both senior and juniorinvestigators alike.

The high quality of Prof. Ignarro’slecture proved not to be an isolated event,as it was followed by a series of excellenteducational speakers all of whom arehighly accomplished in the field of cardio–vascular research. Amongst them wereDr Edward Frohlich, who delivered theexcellent ‘Janice Pfeffer DistinguishedLecture’ on left ventricular hypertrophy,and Dr Eric Olson (2005 OutstandingInvestigator) who gave an elegant speechon transcriptional control of heartdevelopment and disease.

The 16 symposia, which were presentedthroughout the course of the meeting,encompassed a wide spectrum of cardio–vascular research and were well receivedby a diverse audience. The conferencealso showcased 150 posters of an

extremely high standard in the form of twoevening poster sessions, the abstracts ofwhich were published in the JMCC 38(5),2005.

The extravagant Grand Ballroom of theFairmont Hotel was the setting for thebanquet dinner on the penultimate day ofthe conference. A winning combinationof mouth-watering cuisine, an abundanceof wine, and live entertainment providedby one of the finest local jazz bands provedto be the makings of a highly enjoyablenight. The informality of the eveningallowed the participants to indulge in an‘uninhibited’ environment, which extend–ed to the buzzing Bourbon St. after dinner,and the acquisition of an assortment oftraditional Mardi Gras beads. The eveningwas also highlighted by the announce–ment of the winner of the prestigiousyoung investigator award, Dr Asa B.Gustafsson from the Scripps ResearchInstitute, for her talk on the contributionof Bnip3 to myocardial ischaemia/reperfusion injury and autophagy.

As research students we thoroughlyenjoyed the meeting and revelled in theopportunity to converse with so manydistinguished and experienced scientists.In our opinion, meetings such as these areideal opportunities to amalgamate seniorand junior scientists, facilitating theexchange of both ideas and experience,and thus more post-graduate studentsshould be encouraged by their super–visory teams to attend.. Finally, the meetingwas both an educational and socialtriumph, which was thoroughly enjoyedby all participants, and all in all an event

1. (From left to right) Keynote lecturer Louis J.Ignarro, and Dennis B. McNamara, Krishna C.Agrawal and Patrice Delafontaine (membersof the local organizing committee).2. On May 12, 'The First International Sympo–sium on The Role of Mitochondria in CardiacDysfunction' was organized by Jim Downey,Peipei Ping, Keith Garlid and Roberta Gottlieb.The meeting was followed by a Mississippidinner cruise aboard the John JamesAudubon. From l. to r.: Jim Downey (taking acat nap after a strenuous day), Yoshica Kunoand Nataliya Solenkova (all from Mobile, AL).3. The writers of this report and their super–visors during the banquet. From l. to r.: ShiangYong Lim, Kathleen A. Kane (Glasgow), SarahK. Walsh and Cherry L. Wainwright (Aberdeen).

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which the organising committee shouldbe very proud of.

Sarah K. Walsh, B.Sc. (Aberdeen, UK),

Shiang Yong Lim, M.Pharm. (Glasgow,UK) �

During the banquetÅsa B. Gustafsson (La Jolla, CA)received the Young Investigator

Award from Donald M. Bers,Chairman of the YIA Committee.

score of a piece by Chopin and began toteach himself to play. Apparently he wasable step by step to play this work. Köhler’sdeath was a terrible loss for humanity, forscience, and for his family. As Milsteinwrote, “Once I told him that we were beingblamed for our alleged failure to take apatent. His comment was ‘we are notbusiness men, we are scientists’.” Howtimes have changed!

ReferencesGoldsby RA, Kindt TJ, Osborne BA.Immunoglobulins: Structure and Function (pp.104-113). In: Kuby Immunology (4th Ed.).New York: WH Freeman & Co, 2000.

Hampton T. Monoclonal antibody therapiesshine in breast cancer clinical trials. JAMA2005; 293: 2985-2989.

Hengartner H, Secher D. In Memoriam:Georges Jean Franz Köhler, April 17, 1946 –March 3, 1995. Biol Chem Hoppe-Seyler 1995;376: 521-522.

Hershberger RE, Starling RC, Eisen HJ, et al.Daclizumab to prevent rejection after cardiactransplantation. N Eng J Med 2005; 352:2705-2713.

Hosenpud JD. Immunosuppression in cardiactransplantation. N Eng J Med 2005; 352:2749-2750.

Köhler G. Derivation and diversification ofmonoclonal antibodies (pp. 228-243). In:Frängsmyr T, Lindsten J (Eds.) Physiology orMedicine 1981-1990: Nobel Lectures.Singapore: World Scientific, 1993.

Köhler G. Curriculum Vitae. Taken from:http://nobelprize.org/medicine/laureates/1984/kohler-cv.html on July 6, 2005.

Köhler G, Milstein C. Continuous cultures offused cells secreting antibody of predefinedspecificity. Nature 1975; 256: 495-497.

Köhler G, Milstein C. Derivaton of specificantibody-producing tissue culture and tumorlines by cell fusion. Eur J Immunol 1976; 6:511-519.

Koprowski H, Steplewski Z, Herlyn D, et al.Study of antibodies against human melanomaproduced by somatic cell hybrids. Proc NatlAcad Sci USA 1978; 75: 3405-3409.

Roitt I. Immunochemical techniques (pp. 105-127). In: Essential Immunology (8th Ed.).Oxford: Blackwell Scientific Publishers, 1994.

Wigzell H. The Nobel Prize for Physiology orMedicine. In: Les Prix Nobel: 1984. Stockholm-Sweden: Almqvist & Wiksell International,1985.

Melchers F. Obituary: Georges Köhler (1946-1995). Nature 1995; 374: 498.

Milstein C. Georges Jean Franz Köhler – apersonal tribute. Immunology Today 1996;17: 103.

Richard J. Bing, M.D. �

(continued from page 5)

Kohler, milstein, and

monoclonal antibodies

New OrleansAugust 2005

Jim Downey, Ph.D.

I was asked to write a short note abouthurricane Katrina. Thankfully, Mobile

received only wind damage from Katrina’sfury as the city is mostly on high ground.Since the storm came ashore 100 miles fromMobile, we felt that we would escape; infact, we experienced a strong hurricane withmany trees down and power outages all overthe city. My electricity came back on 4 daysafter the storm and most Mobilians hadsome property damage. For those that werecloser to the sea the storm was equivalent toa tsunami as a 10-meter wall of water surgedover the beach along 100 miles of the GulfCoast. All structures near the water wereravaged from Mobile Bay to New Orleans.The civil defense here is good; all low-lyingareas were evacuated prior to the storm sothe loss of life was minimal. Even so, somepeople either failed to obey the evacuationor were unable to leave and several hundredpeople died. That number surely will rise asthey drain New Orleans.

My university in Mobile was only lightlydamaged and we were back in operationwithin a week of the storm. Those in NewOrleans were not so lucky. People evacuatedthe city and then were unable to return dueto the flooding. Many people were scattered,and employers, friends, and even their

families have had trouble locating them. TheAmerican Physiological society hasmaintained a bulletin board to exchangemessages between displaced physiologists.Tulane and LSU physiology faculty haveturned up in California, Mississippi, Georgia,Arkansas, Texas and even Guatemala. Theywill not be able to return to their homes anytime soon. LSU plans to hold medical schoolclasses at a Baton Rouge campus whileTulane students will probably resume theirclasses in Houston, Texas.

Mobile is flooded with evacuees whohave no homes to return to. Those that arefortunate are renting apartments and hotelrooms while those of less means still live inshelters. The government has been simplyoverwhelmed and a clear plan has not yetemerged from them. Private charities haveled the way for much of the recovery,foremost among them the American RedCross. Donations to them will go directly toKatrina’s victims. http://www.redcross.org/

Most of our members have been to a NewOrleans meeting as it is one of the greatestvenues in the world. Fortunately, the FrenchQuarter was not flooded and most of the citythat we knew remains intact. New Orleanswill recover and be better than ever. Restassured you will be able to enjoy many moremeetings in the Big Easy.

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the news bulletin of the international society for heart research

IT was a great honor to receive the 2005 Young Investigator Award at the XXVII Annual Meeting of the American Section in New Orleans for my work on the

mitochondrial pro-apoptotic protein Bnip3 in ischemia/reperfusion injury. I amoriginally from Stockholm, Sweden, and came to the United States to study atthe University of California, San Diego, where I completed my Ph.D. in theDepartment of Pharmacology in 2001. I moved to the Scripps Research Instituteto do my postdoctoral training with Dr Roberta A. Gottlieb, where I recently madethe transition to faculty. Our laboratory is interested in the process by which cellsself-destruct, and we are currently most interested in the mitochondrial alterationsthat develop during ischemia/reperfusion (I/R). My research has focused onelucidating the role of Bnip3 in I/R injury.

Cell Death in Ischemia/ReperfusionCardiovascular disease is the leading

cause of death in North America and ispredicted to become more prevalent asour population ages. Cardiovasculardisease can be initiated by multiple factors,but in recent years it has become apparentthat a major contributing factor is the lossof myocardial cells. Cell death can occurin a destructive, uncontrolled manner vianecrosis or by the highly regulatedprocess of apoptosis. Until recently, theloss of myocytes was attributed tonecrosis; however, it is now clear thatapoptosis may play an important role inthe pathogenesis of a variety of cardio–vascular diseases. Importantly, cardiac

myocytes are terminally differentiated;once destroyed they are not replaced.Consequently, with fewer myocytes, theability of the myocardium to sustaincontractile function is reduced.

Mitochondria and Bcl-2 Family ofProteins

The mitochondria play a key role inapoptosis. They provide the energynecessary for the completion of apop–tosis and release important pro-apop–totic factors such as cytochrome c intothe cytosol. The Bcl-2 family proteins areimportant regulators of the mitochondrialpathway of apoptosis in the cardio–vascular system. This family consists of

both pro- and anti-apoptotic members.Bnip3 is a pro-apoptotic member of theBcl-2 family and is primarily localized tothe mitochondria. Although Bnip3 mRNAcan be detected in multiple organs, itsphysiological function is unknown. Wehave found high levels of basal expressionof Bnip3 in the adult myocardium,indicating that Bnip3 is maintained in aninactive state by an unknown mechanismin the absence of death stimuli.

Contribution of Bnip3 to I/R InjuryWe have established a technique of

TAT protein transduction into isolatedperfused hearts where linkage of the 11-amino acid transduction domain of HIVTAT to a protein allows it to be readilytransduced into cells in the heart(Reference). To investigate whether Bnip3plays a role in mediating I/R injury in therat heart, we generated a TAT-fusion

Contribution of Bnip3 tomyocardial ischemia/reperfusioninjury and autophagy

Figure 1. Effect of TAT-Bnip3∆TM transduction on I/R injury. Rat hearts were perfused with TAT-proteins for 15 min and thensubjected to 30 min of global ischemia followed by reperfusion for 15 min (for superoxide production) or 120 min (for infarct size).A. Creatine kinase activity in the coronary effluent was measured for 15 min before ischemia and for the first 15 min of reperfusion

(n=8, * p<0.05). B. Infarct size was determined by TTC staining (n=4, *p<0.05). C. Superoxide levels were assessed bymeasuring dihydroethidium (DHE) conversion to ethidium (n=4, *p<0.05 vs. control, **p<0.05 vs. I/R+TAT-β-gal).

Åsa B. Gustafsson, Ph.D.

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volume 13, number 2, 2005

protein encoding the carboxyl terminaltransmembrane deletion mutant of Bnip3(TAT-Bnip3∆TM) which has been shownto act as a dominant negative to blockBnip3-induced cell death. Perfusion withTAT-Bnip3∆TM significantly reducedboth creatine kinase release and infarctsize in hearts subjected to 30 min of globalischemia and 120 min of reperfusioncompared to TAT-β-gal (Figure 1). I/Rinjury is associated with increasedproduction of reactive oxygen species(ROS), such as superoxide anion,hydrogen peroxide, and hydroxyl radical.To assess whether the cardioprotectiveeffects of TAT-Bnip3∆TM could beattributed to a reduction in the productionof ROS, superoxide generation wasmeasured in heart slices obtained after 30min of ischemia and 15 min of reperfusion.Using dihydroethidium staining to detectsuperoxide production, we found thatTAT-Bnip3∆TM attenuated superoxideproduction after I/R, suggesting thatincreased ROS production is partly due to

activated Bnip3 in I/R hearts (Figure 1).Perfusion with TAT-Bnip3∆TM beforeischemia also improved functionalrecovery after I/R compared with TAT-β-gal perfused hearts. Moreover, we foundthat hearts perfused with TAT-Bnip3∆TMexhibited reduced cytochrome c and AIFrelease after I/R, and that addition ofrecombinant Bnip3 to mitochondriaisolated from the rat heart resulted in therelease of cytochrome c and AIF.

Ischemia/Reperfusion Results inBnip3-Mediated Induction ofAutophagy

Autophagy plays an important role incellular homeostasis and is the processby which cells recycle cytoplasm anddispose of excess or damaged organ–elles. Since several studies have linkeddysfunctional mitochondria with up–regulation of autophagy, we speculatedthat Bnip3-induced mitochondrial damagein I/R might lead to induction of autophagyin cardiac myocytes. A characteristic ofautophagy is the recruitment of themicrotubule-associated protein lightchain 3 (LC3) to autophagic vesicles,which can be detected as punctatepatterns of LC3-GFP. We found thatcontrol cells transiently transfected with

Figure 2. A. HL-1 cells were transfected with LC3-GFP and vector or Bnip3∆TM prior to simulated I/R (sI/R). After 2 h of ischemia and 90 min of reperfusion, the extent of autophagy was assessed by analyzing staining patterns of LC3-GFP. Thepercentage of diffuse vs. punctate LC3-GFP-positive cells per condition is shown as the mean ± S.E.M. of three independent

experiments. Simulated I/R caused upregulation of autophagy, which was significantly reduced by overexpression of Bnip3∆TM(p<0.05). B. HL-1 cells were transfected with LC3-GFP and pcDNA3.1, Bnip3, or Bnip3∆TM. After 48 h, the extent of

autophagy was assessed by analyzing staining patterns of LC3-GFP. Overexpression of Bnip3 in cardiac myocytes significantlyinduced autophagy (*p<0.05 vs. control). The percentage of diffuse vs. punctate LC3-GFP-positive cells per condition

is shown as the mean ± S.E.M. of three independent experiments.

LC3-GFP showed predominantly a diffusedistribution of green fluorescence,whereas I/R resulted in an increasedpunctate pattern (Figure 2). Moreover, I/R-induced autophagy was significantlyreduced by overexpression of Bnip3∆TM,whereas overexpression of Bnip3 led toincreased induction of autophagy in theabsence of I/R (Figure 2).

Conclusions and Future DirectionTaken together, these findings implicate

Bnip3 as a major contributor to myocardialinjury by causing mitochondrial dys–function. Moreover, I/R leads to Bnip3-mediated upregulation of autophagy. Weare currently investigating the molecularmechanism(s) of Bnip3 activation whichleads to mitochondrial dysfunction andupregulation of autophagy in cardiacmyocytes.

ReferenceGustafsson ÅB, Sayen MR, Williams SD,Crow MT and Gottlieb RA. TAT proteintransduction into isolated perfused hearts.Circulation 2002; 106: 735-739.

Åsa B. Gustafsson, Ph.D.La Jolla, CA

agustafs@scripps.edu �

Åsa B. Gustafsson (La Jolla, CA) was thewinner of the Young Investigator Award atthe XXVII American Section Meeting(New Orleans, Louisiana; May 12-15,

2005).

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the news bulletin of the international society for heart research

Report on the xxv EuropeanSection meeting(june 21-25, 2005; Tromso, Norway)

While the European Union debates how far to expand itsreaches to the east, the European Section of the ISHR

made the bold and daring move to expand its meeting venues tothe far north. As an American, I was excited to hear that thisyear’s meeting would be closer to the state of Alaska than toRome. My only previous European Section meeting was theoutstanding 2002 congress in Szeged, Hungary, and I was veryinterested in attending another. For years I have followed theresearch of my northern Norwegians colleagues, and I haveenjoyed hearing stories of fjords, white nights, and seal physiologyfrom Terje Larsen and others when they venture out from Tromsøto attend meetings closer to the equator. So when I saw that the2005 meeting was in Tromsø, I simply had to go.

Tromsø is a small city (population62,000) on an island situated betweenfiords and mountain peaks at almost 70degree latitude, 400 km north of the ArticCircle. From here the great Norwegian’sarctic explorers Fridtjof Nansen and RoaldAmundsen took off on their daringexpeditions to the North over 100 yearsago. It is home of the University ofTromsø, which is the northern-mostuniversity in the world. (Tromsø is alsohome to the northern-most beer breweryand cathedral!) It has an excellent medicalschool, and an active program in “articresearch” involving the physiology andbehavior of the local wildlife, particularlyreindeer and seals.

When making our travel plans, we sawthat there were several flights a daybetween Oslo and Tromsø, however, withthe encouragement of Terje, we decidedto travel by boat. We flew to Bodø, 450km south of Tromsø, and took the local“steamer” Hurtigruten up through the

snow capped fiords. The trip took 24hours and made several stops at isolatedvillages to drop off goods and exchangepassengers. It was the longest day of theyear, with beautiful sun-lit views all nightlong and a side trip to Troll’s Fjord full oftrolls

The local organizers must be com–mended for putting together an out–standing scientific and social program,and for attracting a first-rate collection ofsubmitted abstracts. The meeting washeld in a beautiful facility at the University.There were two parallel sessions, withposters stationed between the two lecturehalls, which forced lots of positiveinteraction among participants at thebreaks. The social program started withan opening reception at an architecturallyintriguing refurbished old warehouse onthe water front. We stayed at the receptionquite late. I have attended many eveningsocial events at scientific meetings, andthey all have a natural ending when it isdark and one feels the natural desire tosleep. This was not the case in the whiteand almost sunny nights in Tromsø: I feltlike I could have socialized all night long.

On a subsequent evening there was abarbeque dinner, which was a realadventure. About 400 of us were loadedonto a fast boat that took the scenic routeout to the beautiful island of Sommarøy,where we dined on reindeer meat andwonderful fish. From the island one reallyhad the feeling of being north: to the westwas Greenland, Iceland was to thesouthwest, and Alaska was only a fewthousand kilometers across the North Pole

1

2

1. Judge Nick Severs (London, UK) isscrutinizing one of the posters.2. Friederike Cuello (London, UK) wasthe recipient of the 2005 ISHR-ES /SERVIER Research Fellowship.From left to right: Drs Stefano Corda(SERVIER, Paris), Friederike Cuello andFabio Di Lisa (President of the EuropeanSection).

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The Gala dinner was full of surprises,from a concert performance by thevirtuoso flutist and editor Tom Ruigrok,to the lecture on the benefits of cod liveroil. We were all fortunate to receivevolumes of complimentary samples of fishoil capsules from the sponsor of themeeting, Fri Flyt, and we had a verythorough and hilarious lecture on thebenefits of cod liver oil from a local expert.I know that the economy of Norway isbooming due to the export of high pricedcrude oil, however what I really envy istheir production of cod liver oil. Since themeeting I have been taking Norwegianfish oil supplements, and I have greatlyimproved bodily functions that I did notpreviously know I even possessed!

All together, it was an outstandingscientific meeting and a great culturalexperience. We left Tromsø with thestrong desire to return. Perhaps it is timefor the European Section of the ISHR tomake another bold move, and hold a“Skiing Under the Aurora Borealis”meeting in Tromsø in January, with 24hour darkness?

William C. Stanley, Ph.D.,

Margaret Chwascinska-Sharel

Cleveland, USA

Report on the Nordic-BalticMeeting on Cellular Bioenergetics:Mitochondria in Myocytes -

Methodological Aspects andDysfunction in CardiovascularDisease(June 15-21, 2005; Tartu, Estonia)

The meeting, organised by theNetwork of the research institutions

of Nordic and Baltic countries, andsupported by the European Section ofthe ISHR and the Research Council ofNorway, was held as a postgraduatesummer school in the Centre ofMolecular and Clinical Medicine,Faculty of Medicine, University of Tartu.

Michiel ten Hove (Oxford, UK)received the Young InvestigatorAward from Fabio Di Lisa.

1

2

3

1-3. Excursion to Sommarøy(Photographer: Nancy Bundt).2. From left to right: Ole Mjøs

(Tromsø, Norway), Lionel Opie(Cape Town, South Africa) and Gary

Lopaschuk (Alberta, Canada).More photo’s can be seen at

www.betterhearts.net.

(continued on page 15)

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the news bulletin of the international society for heart research

GREETINGS FROM PERTH, AUSTRALIA:XXIX ANNUAL SCIENTIFIC MEETING ofthe AUSTRALASIAN SECTION(AUGUST 5-8, 2005)

The XXIX Annual Scientific Meeting of the Australasian Section was recentlyheld in conjunction with The Cardiac Society of Australia & New Zealand

(CSANZ) in Perth, Western Australia, a beautiful city lavished with Mediterranean-like climate and unique landscape. CSANZ is a clinical society composed ofcardiologists, cardiac surgeons, trainees, nurses and other allied professionals.More than 1800 participants, including overseas CSANZ and ISHR membersfrom Germany, France, UK, USA, China, Japan, Taiwan, Malaysia, Indonesia,Singapore and New Zealand made the conference a busy and exciting occasionfor the ISHR to contribute significantly to the design of the combined scientificprogram.

Dr Elizabeth Nabel (Maryland, USA)presented the CSANZ’s 2005 R.T. HallLecture on “Genetic Medicine andCardiovascular Disease”. Based on herexperience and clinical success, Dr Nabelemphasised in her excellent presentationthat clinical breakthroughs can only arisewith close interplay between originalclinical observations, laboratory science,and subsequent clinical trials, ofteninvolving numerous iterations back andforth with the laboratory. This set a perfectscene and provided justification forISHR’s joint meeting with CSANZ.

Symposia highlights included: Molec–ular Biology of Cardiac Failure; Signal–ling Mechanisms in Cardioprotection;Cardiac Myocyte Signalling in AdaptiveGrowth, Hypertrophy & Failure; Sex,Steroids & Angiotensin Peptides -Trophic Effects; Atherosclerosis andInflammation; Cardiac Oxygen Signal–ling in Stress & Survival; MetabolicSyndrome, Diabetes & the Heart; and Atthe Heart of Function & Dysfunction. Inaddition, ISHR ran two “Leading EdgeResearch Techniques & ResourceWorkshops”: Proteomics & Genomics-Practice and Possibilities, and AssessingCardiac Function - Meeting the In VivoChallenge.

As in previous meetings, there was alsoa strong focus on research students.

Outstanding oral presentations were madeby the four finalists in the ISHR StudentPrize Symposium: Edna Lekgabe (Mel–bourne, Australia), Sharon Tsang (HongKong, China), Iwan Alban Williams(Sydney, Australia), and the winner, EnzoPorrello (Melbourne, Australia), whosetalk was entitled “Evidence suggestive ofan angiotensin II-dependent cardio–myocyte cull in neonatal hypertrophicheart rat”. The popular Poster, Wine andCheese session provided a relaxedatmosphere for animated discussions andcontemplation on the work presented.The Best Student Poster Prize wasawarded to Freya Sheeran (Melbourne,Australia) for her presentation of“Respiratory chain functional defectsunderlying mitochondrial complex-1activity in human heart failure”, and theHigh Commendation Poster Prize went toLu (Karen) Fang (Melbourne, Australia)who presented: “Gender affects remodel–ling and healing post acute myocardialinfarct in mice”.

On behalf of all the delegates I wouldlike to acknowledge and sincerely thankDr Salvatore Pepe (Australasian SectionPresident), A/Prof. Lea Delbridge (Secre–tary) and Dr Xiao-Jun Du (Treasurer) forall the hard work they put into organisinga great program. Sincere appreciation alsogoes to Drs Leonard Arnolda, PeterThompson, Richmond Jeremy, KenHossack, and the CSANZ OrganisingCommittees for enabling a successful jointmeeting. Indeed this success sets theprecedence for the next joint meeting withCSANZ (4-6 August, 2006) to be held inCanberra, Australia’s capital. For thosewho love wine (we all know the cardio–vascular benefits!), the Canberra regionscool climate wines are now receiving inter–national recognition. With 140 vineyardswith more that 30 cellar doors, most ofwhich are only 30 minutes from the city, besure to allow extra days to explore! TheAustralasian Section invites you to joinus!

Helen Kiriazis, Ph.D.

Melbourne, Australia �

Oral and poster presentationfinalists (from l. to r.):Iwan Williams, Sharon Tsang,Edna Lekgabe, Lu (Karen) Fangand Enzo Porrello (winner of theprize for the best oralpresentation).

15

ISHR MEETINGS CALENDAR

� December 15-17, 2005. XXII Japanese Section Meeting - To Clarify our Current Standpoint and our Goal in the Heart

Research Field. Osaka, Japan. Inquiries: Dr M. Hori, Osaka University, Graduate School of Medicine, Dept of Internal Medicine and

Therapeutics, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan. Tel. +81 6 6879 3631; Fax +81 6 6879 3639; E-mail mhori@medone.med.osaka-

u.ac.jp; Website www2.convention.co.jp/22ishr-japan/

� January 12-14, 2006. Joint Annual Meeting of the Indian Section and the IACS. Chennai, India. Inquiries: Dr Suresh

Kumar, Institute of Cardiovascular Diseases, Madras Medical Mission, Chennai 600 037, India. Tel. +91 44 26565961 / 26561801 / 26565991;

Fax +91 44 26565859 / 26565510; E-mail icvddoctors@dishnetdsl.net

� June 14-17, 2006. XXVI European Section Meeting. Manchester, UK. Inquiries: Scientific Secretariat: Mrs R. Poulton,

The University of Manchester, Room 1.302, Stopford Building, Oxford Road, Manchester M13 9PT, UK. Tel. +44 161 275 1628; E-mail

rpoulton@fs1.scg.man.ac.uk Meeting Secretariat: The University of Manchester, ConferCare, Barnes Wallis Building, Sackville Street,

Manchester M60 1QD. Tel. +44 161 306 4068; E-mail mcc.reg@umist.ac.uk; Website www.meeting.co.uk/confercare/ishr2006

� June 14-16, 2006. XXVIII American Section Meeting. Toronto, Canada. Inquiries: Dr P. Liu, Heart & Stroke/Richard Lewar

Centre of Excellence, University of Toronto, Rm 78A, 150 College Street, FitzGerald Building, Toronto, Ontario M5S 3E2. Tel. +1 416 946

8543; Fax +1 416 946 7545; E-mail hsrlcentre.excellence@utoronto.ca; Website www.ishr2006.com

� September 2-6, 2006. World Congress of Cardiology. Barcelona, Spain. Inquiries: E-mail congress@escardio.org; Website

www.worldcardio2006.org

� November 12-15, 2006. Scientific Sessions of the American Heart Association. Chicago, IL. Inquiries: Website

www.americanheart.org

� June 22-26, 2007. XIX World Congress of the ISHR. Bologna, Italy. Inquiries: Dr R. Ferrari, Department of Cardiology,

University Hospital of Ferrara, Corso Giovecca 203, 44100 Ferrara, Italy. E-mail info@ishr-italy2007.org; Website www.ishr-italy2007.org

volume 13, number 2, 2005

A number of senior scientists fromAustralia, Czech Republic, Denmark,Estonia, Finland, France, Germany, Italy,Lithuania, Norway, Slovak Republik andUK, and PhD students from Nordic andBaltic countries exchanged their researchresults and scientific ideas. A wide rangeof topics was addressed, including Mito–chondrial respiratory chain, its regulationand pathological alterations, Compart–mentalization of the energy metabolism,Mathematic modeling of bioenergeticprocesses, Role of mitochondria inintracellular signalling, Alterations inskeletal muscles in conditions of heartdisease, Role of mitochondria in the celldeath process, and Methods of studyingof the normal and altered functions of themitochondria. A significant part of themeeting was devoted to discussing thenewest methodological approaches in thefield of cellular bioenergetics, withpractical instructions in different labo–ratories.

The format, scientific content andtechnological merits of the meeting werehighly appreciated by the PhD students

and lecturers. The participants alsoenjoyed the informal meetings andsightseeing tours in Tartu and itssurroundings that helped us to recoverafter rather demanding and intensiveworkdays. It was a general understandingthat the meeting was a great success infavor of establishing the academic andresearch Network between the Nordicand Baltic countries and of its integrationinto the European research area. Themeeting was accepted as a part of thecurrent academic PhD study programs inthe participating Institutions.

After finishing their work in Tartu, manyPhD students and lecturers attended theXXV European Section Meeting inTromsø, Norway. Those attending bothmeetings were pleased to discover thatthe scientific program of Tartu’s meetingfairly complemented the content of thesession The Multifaceted Mitochondria:from Protection to Aging held in Tromsø.

Enn Seppet, M.D., Ph.D.

Tartu, Estonia �

Satellite Meeting in

Tartu, Estonia(continued from page 13)

16

HEART NEWS AND VIEWSis the official News Bulletin of theInternational Society for HeartResearch and is published everyfourth month.

EditorT.J.C. RuigrokUtrecht, The NetherlandsE-mail t.j.c.ruigrok@xs4all.nl

Deputy EditorL. Anderson LobaughDurham, NC, USAE-mail llobaugh@nc.rr.com

Editorial BoardR.A. AltschuldColumbus, OH, USAM. AvkiranLondon, UKSecretary General and TreasurerG. BaxterLondon, UKEuropean SectionR. BolliLouisville, KY, USAPresident-ElectT. IzumiKanagawa, JapanJapanese SectionH. KiriazisMelbourne, AustraliaAustralasian SectionX.Y. LiBeijing, ChinaChinese SectionA. MattiazziLa Plata, ArgentinaLatin American SectionE. MurphyDurham, NC, USAAmerican SectionT. RavingerovaBratislava, Slovak RepublicA.-M.L. SeymourHull, UKN. TakedaTokyo, JapanK.K. TalwarChandigarh, IndiaIndian SectionR.A. WalshCleveland, OH, USAEditor-in-Chief, JMCCK.T. WeberMemphis, TN, USA

Desk EditorB.J. WardLondon, UK

Editorial OfficeMarkt 133961 BC Wijk bij DuurstedeThe Netherlands.Tel.: +31 343 597 555Fax: +31 343 597 510

the news bulletin of the international society for heart research

HEART NEWS AND VIEWSis published thanks to

an educational grant from Servier

a private French pharmaceutical company committed to therapeutic advances in cardiovascular medicine as

well as other key therapeutic areas. We have successfullydeveloped products in the field of cardiovascular diseases(ischemic heart disease, hypertension, and heart failure),

as well as in other major therapeutic fields. A number of landmark studies like PROGRESS, EUROPA, PREAMI,ADVANCE, HYVET, and BEAUTIFUL are, or have been,

conducted with our support.

The dynamism of our research is ensured by consistentallocation of as much as over 25% of the annual turnover

of the Group to search for new molecules and develop their therapeutic applications.

Servier is also the founding father of The European

Cardiologist Journal by

Fax and Dialogues in

Cardiovascular Medicine,

a quarterly publication with a worldwide circulation edited by Roberto FERRARI

and David J. HEARSE.

Dialogues discusses in acomprehensive way issuesfrom the cutting edge of basic research and clinical cardiology.

The forthcoming issue, devoted to ACUTE CORONARY SYNDROMES

will feature articles by:

M. Valgimigli, P. Serruys, et al; S. K. James, L. Wallentin, et al; M. Bertrand;

A. Menozzi and D. Ardissino

Acute Coronary Syndromes

Volume 10 • Number 3

2005

For further information on Dialogues in Cardiovascular Medicine please contact:

Dr Elena Louette - Servier International192 avenue Charles de Gaulle - 92578 Neuilly-sur-Seine Cedex - France

or webmaster@servier.com