Current eamments”EUGENE GARFIELD

lt.IsTITuTEFORSCientifiC INFORMATION*3501 MARKET ST., Philadelphia, pA 19104

The Most-Cited 1984 Life-SciencesArticles Highlight AIDS Research

&Number 49

In 1979 we began using two years of cita-tion data for our amual series identifyingthe articles most cited in the Science Cita-tion Indexm (SCW ). Our first two-yearstudy discussed the 1976 articles most citedin 1976 and 1977.1 Previously we countedonly the number of cites a paper receivedin the year it was published. Initially, wecategorized articles into life- or physical-scienees studies. Later we added othercategories such as chemistry.

Our intent in this series is twofold. An-nual citation-frequency anrdyses identify thepapers that attract immediate and widespreadattention in the science community. Thesepapers indicate new, active, or controver-sial research areas. In addition to pinpoint-ing the “hot” areas of research, this series

of essays can be used in trend analysis forscience policy and research administration.The year-to-year progress or decline inprominent research areas can be used as atype of general science indicator. The seriesalso shows how the research interests ofhigh-impact authors advance. It should benoted, however, that there are many incipi-ent fields where one may have to wait manyyears before observing significant publica-tion rates.

AIDS Research

In our series of most-cited life-sciencespapers, acquired imnmnodeficiency syn-drome (AIDS) research is an excellent il-lustration of the trend analysis feature. Whenthis series first began, AIDS research wasnonexistent. In fact, our study of 1976

December 8, 1986-r

life-sciences articles showed that the mostpopular new area of research concerned en-dorphins and enkephalins, the opiates foundprimarily in the brain and pituitary glands.Twenty percent of the 100 articles were con-

cerned with this topic. 1 I stressed new be-cause there were many other older fields thatwere more active but did not necessarilyproduce papers of high immediacy.

AIDS research did not appear in our an-nurd lists until we studied the 1982 papers.In that study six papers dealt with thk newdiseasez-quite a jump from the previousyear. These papers were all of a descriptivenature, dkcussing the immunological abnor-malities of homosexual men suffering fromAIDS. Kaposi’s sarcoma and Pneunrocysfiscan”niipneumonia were two of the principalopportunistic infections of AIDS patients.In contrast, that same year only six of thepapers concerned opiate receptors. Howev-er, by then we had identified dozens of re-search fronts for this now relatively ‘‘sta-ble” field. Indeed, some of the papers wehad identified in earlier years continued tobe well cited.

Reviewing this study’s Bibliography of the102 most-cited life-sciences papers, it isclear that by 1984 AIDS had developed in-to one of the most active areas of research.Most of the 23 AIDS-related papers have ad-vanced far beyond descriptions of the phys-

ical manifestations of this disease. By 1984scientists had established that AIDS iscaused by a virus that suppresses the imm-une system, leaving the victim open to at-tack by a range of opportunistic infections.

389

The virus works by depleting T-lympho-cytes, the agents mediating the cellular im-mune response. In addition, we now realizethat AIDS is not restricted to certain popula-tions, such as homosexual men and intra-venous drug abusers, but can be transmit-ted, at least occasionally, between womento men via heterosexual activity.

Monitoring future studies of the most-cited life-sciences articles will highlight thehigh-impact breakthroughs in AIDS re-

search. You might ask why this is necessaryconsidering the attention AIDS receivesfrom the general press. The point is that ourcitation analyses of the scientific literatureseem to mirror, with a few significant ex-ceptions, what has been repmted in the gen-eral press and in the science news sectionof general science journals such as Natureand Science. If this is true for such a visi-ble subject, then we hope and expect it isequally true for less visible areas.

While AIDS research dominates our listof 1984 articles, studies concerning onco-genes, antigen presentation, and signal-transduction research are also well repre-sented. Overall, the 102 articles in the Bib-liography garnered an average of 117 cita-

tions, 22 in 1984 and 95 in 1985.We used research fronts to categorize

these papers into broad subject areas. Re-search fronts develop as authors cite certainpapers to indicate the connection to theirown research. Papers that are frequentlycited together, or co-cited, identifi theshared features of current papers. In thisway the citing authors themselves categorizepapers into subject-related clusters of re-search. These co-citation groups help iden-tify research fronts. Of tie 102 papers in thisstudy, 90 are already core documents forISI@ research fronts.

Table 1 lists the 19 fronts that include atleast two papers from the Bibliography ascore dearnents. The size of a front is deter-mined by the number of published papersthat cite into it. For instance, the largestfront in this study is the “Role of phorbcd

ester receptor in activation of calcium mo-

bilization, phosphorylation of inositol, and

protein kinase C activity” (#85-0289), withover 1,600 citing papers and 58 core (cited)

papers, 9 of which are included in the Bib-liography. By comparison, the fronton the“Role of African-type retrovirus in epide-miology of AIDS and Kaposi’s sarcoma”

(#84-3901 ) is the smallest front, with 61papers. This research front was identifiedby a group of four core documents, two ofwhich are included in the Bibliography. Theother two were well cited but did not meetthe criterion for this study of having beenpublished in 1984.s,4

This latter research front is one of fivefrom Table 1 that deal with AIDS, comparedwith three from last year’s study.5 The sec-ond and third most-cited papers in the study,

both published in the same issue of Science,deal with AIDS. Mikulas Popovic, Lalmra-tory of Tumor Cell Biology, NationalCancer Institute (NCI), Bethesda; M.G.Samgadharan, Department of Cell Biology,Litton Bionetics, Inc., Kensington, Mary-land; and Elizabeth Read and Robert C.GaUo, also of NCI, developed a cell culturesystem from a human T-cell line that can

maintain growth even after being infectedby the AIDS virus. Previously, they couldnot get the AIDS virus to grow in culture

&cause it killed the cells that it infected. Thenew cell system allows the AIDS virus tobe produced in large quantities, making it

easier to analyze and elucidate the precisemechanism of activity of the AIDS virus. cThe paper describing this method is the thirdmost-cited paper in the Bibliography.

In the second most-cited paper, Gallo andcolleagues described how they used this cellsystem to grow large quantities of HTLV-

111, the virus that was detected in and iso-lated from patients who have AIDS or whoshow pre-AIDS symptoms. They conclud-

ed that the HTLV-111 virus is the causativeagent of AIDS. T Both of these papers arecore to the fronts concerning “Associationof human T-cell leukemia virus and otherretroviruses with leukemia-lymphoma,

AIDS, and related immune disorders”

390

Table 1: The 1984 and 1985 SCl@’/SSCP research fronts that include at least two of the 1984 most-cited life-sciences papers as core documents. A = research-front number. B = research-front m. C = number of 1984 most-citcd life-sciences papers included in the core of each research front, D= total number of core papers and 1984or 1985 citing papers for the year designated by the prefix in column A

A

84-017184-0319

84-1914

84-390184-499284-6753

85-017885-0208

850289

85-0647

85-0745851382285-1307

85-1677

85-1825

85-255385-2623

85-353885-6203

B

Clinical aspects and characterization of human T-cell subsetsPhospho~lation and calcium binding of phorlwl and inositol; stimulation of

protein-kinase releaseAssmiation of human T-cell leukemia virus and other retroviruses with leukemia-

Iymphoma, AIDS, and related immune disordersRole of African-ty~ retrovims in epidemiology of AIDS and Kaposi’s sarcomaIsolation and characterization of ANFIntracellular distribution and structure of the estrogen-receptor and other steroid-

horrnone receptorsMonoclinal antibody activation of T-cells and antigen-receptor gene expressionExpression of c-myc gene and other oncogenes causing hurnwr and mouse cell

cancersRole of phorbol ester receptor in activation of calcium mobilization,

phosphorylation of inositol, and protein kinase C activityAntilrcdies and antigens in response to disease, characterization of nuclear

RNAs, and nucleotide sequences for messenger RNA splicing in human genesImmunology, epidemiology, and virology of AIDS and HTLV-IIf virus infectionsCharacterization of rat and human nuclear estrogen receptorsBiological activity, receptor distribution, and the systemic and renal

hemodynamic effects of ANFRegulation, characterization, and expression of transcription-promoter genes in

viruses and human and non-human cellsEffects of leukemia vims and other retroviruses on human T-cells in patients

with leukemia and AIDSHTLV-111 antibcdy prevalence in epidemiology studies of AIDS in AfricaOncogenes and growtf-factor receptors and their roles in gene expression and

transformation in normal and cancer cellsCharacterization of MPTP neurotoxicity in dopamine neurons in parkinsonismEffects of platelet-derived growth factor, epidermal growth factors, phorbol

ester. and various viruses on the metabolism of inositol DhosDholiDids and. . .differentiation of various cells

(#84-1914) and “Effects of leukemia virusand other retroviruses on human T-cellsin patients with leukemia and AIDS”(#85-1825).

French and American Contributions

Last year we briefly discussed the contro-versy between AIDS researchers in the US

and France.5 Gallo and colleagues isolatedthe virus HTLV-111 and were credkd by thegeneral media as the discoverers of the causeof AIDS. It has since been shown that thisvirus is the same as the virus LAV,

discovered earlier by Luc Montagnier,Pasteur Institute, Paris, and colleagues.gThis priority controversy escalated when the

French team applied for a US patent inDecember 1983 for a test that detects anti-bodies to the AIDS virus. Four months later,in April 1984, the US team applied for a pat-ent for their own antibody test. The US

c

44

s

222

114

9

2

228

2

13

22

42

D

47/ 1,20658/1,119

41/608

4/6 112/108

5/86

39/74051/1,085

5S/1,632

341777

9/26817/3ou45/319

32/829

56/118

7/1477/607

16/1583/129

team’s application was approved in May1985, while the French patent applicationis still pending. A complex legal process hasbeen set in motion to sort out the compet-ing claims of both sides and decide who isthe true inventor of the blood test. Despitethis controversy, the 1986 Lasker Award hasrecognized the achievements of six scien-tists, including both Montagnier and Gallo,as well as Myron Essex, Department ofCancer Biology, Harvard School of PublicHealth, for their work in identifying thevirus that causes AIDS.9

While US research seems to be attractingthe most attention from the general mediain the US, AIDS research in France is very

highly regarded by the international com-munity of scientists, Of the five papers inthe Bibliography that are coauthored byscientists with French affiliations, four dealwith AIDS research. Montagnier and F.

391

Table 2: National locations of the institutional affdia-tions listed by authors in the Bibliography, accordingto total appeamnces (column A). B =numkr of paperscoauthored with researchers afftiiatcd with institutionsin other counmes. C = national locations of institutionslisted by coauthors.

country

us

UK

CanadaFranceSwitzerlandAustraliaJapanBelgiumIsraelFRGKenyaSwedenZaire

AB

79 17

13 6

64525242413222111110II

c

Australia, Belgium, Canada,FRG, France, Israel,Japan, Kenya, Switzerland,UK, Zaire

Israel, Kenya, Switzerland,us

ususUK, USFRG, USusUS, ZaireUK, USAustralia, USUK, US

Belgium, US

Barr&Sinoussi, also of the Pasteur Institute,are coauthors of these four papers. They alsocoauthored one of the papers on AIDS fromlast year. A Citarion Classic” commentaryby Barr& Sinoussi is currently in prepara-tion.

Author Aftliations

The 469 authors in this study are affiiatedwith institutions in 13 countries. Table 2provides the number of papers produced byauthors affiliated with institutions in each m-tion. US-affdiated authors appeared in 79papers, 17 of which were coauthored with

scientists affiliated with institutions of othernations, including Australia, Belgium,France, and the UK.

There are two articles in this study by au-thors affiliated with the Weizmarm Instituteof Science, Rehovot, Israel, as well as onearticle by authors affiliated with two insti-tutions in Zaire. These two countries werenot represented in last year’s studies of most-cited papers. Keep in mind, however, that

the cut-off point for papers included in theseessays is arbitrary. Ordy a few citatiotrs separate those selected from those omitted.

Table 3 lists the 108 institutions represent-ed in the Bibliography. Sixty-one of the in-

Table 3: Institutional affiliations hsted in papers in theBibliography in descending order of number ofappearances.

NIH, Bethesda, MDNC]

Bcrhesda, MD IIFrederick, MD 3

NIAIDClin. Ctr. 2NIADDKD 2NIMH I

Harvard Univ., MABoston sCambridge 5

Univ. California, CALos AngelesSan FranciscoBerkeleyLa Jolla

Lltron Bionet., Jnc,,Kensington, MD

Stanford Univ., CAAFRC, Cambridge, UK

Inst. Anim. Pbysiol.Unit Insect Neurophysiol.

Pharmacol.Unit Invertebrate Chem.

Physiol.Caltecb, Pasadena. CADana-Farb& Cancer Jnst., Boston, MAUniv. Cambridge, UKMfT, Cambridge, MAPasteur Inst., Paris, FranceUniv. Toronto, CanadaCDC, Atlanta, GAClaude Bernard Hosp., Paris, FranceCornell Univ. Med. CoIl., New York, NYGenentech, Inc., San Francisco,CAMere. Sloan-Kettering Cancer

Ctr., New York, NYOntarm Cancer inst.. Toronto, CanadaUniv. Texas, TX

DallasHouston

Walter Reed Army lnst. Res..Washington, DC

Waabington, DCWaker Reed Project,

Nawobi, KenyaAustralian Natl. Univ.,

Canberra, AustmliaBasel Univ., SwitzerlandCalifornia Biotcch, Inc.,

Mountain View, CAClin. Res. Inst. Montreal. CanadaHosp. Jnfant Dis.. Paris, FranceJmperial Cancer Res. Fund

Labs,, London, UKKobe Univ., JapanMRC, UK

Jmmunochem. Unit, OxfordSecretory Cntrl. Res. Grp.,

Liverpd

14

3

4411

22

I

21

21

11

Z2

13

10

7

65

55544433333

33

3

2

22

222

22

392

NY Hosp., NYNat]. Inst. Basic BioL, Okazski, JapanNew Engl, Deaconess Hosp., Boston, MAPrince Leopnld Inst. Trop.

Med., Antwerp, BelgiumSalk Inst. Biol. Stud., San Diego, CAUniv, Chicago, ILUniv. London, UKUniv. Med. Dent. New Jersey,

Newark, NJUniv, Pemsylvania, Philadelphia, PAVanderbilt Univ., NashviJle, TNWashington Univ., St. Louis, MOWeiznrann Inst. Sci., Rehovot, IsraelAddenbronke’s Hosp., Cambridge, UKAmerican Cancer Sm., New York, NYAnderlecht Hosp., Brussels, BelgiumBasel Inst, Jmmunol,, SwitzerlandBeth Israel Med. Ctr., New York, NYBiogen Inc,, Cambridge, MABiotech Res. Labs., Inc., RockviUe, MDBoston Univ., MABrugmann Hosp., Brussels, BelgiumCalifornia Dept. Hlth. ScW.,

Berkeley, CACedars-Sinai Med. Ctr., Los Angeles, CACetus Corp., Emeryville, CAColumbia Univ., New York, NYDartmouth Coil., Hanover, NHDept. Publ. Hlth. Trop. Med.,

Paris, FranceHokkaido Univ., Sappuro, JapanIndiana Univ., Blnumington, INInst. Cancer Res.: Royal Cancer

Hosp., Imndon, UKIntl, Agcy. Res. Cancer, Lyon, FranceJefferson Cnty. Dept. Publ.

Hlth., Birmingham, ALLiverponl Sch. Trop. Med., UKLudwig Inst. Cancer Res.,

Sydney, AustraliaMama Yemo Hosp., Kinshasa, ZaireMed. Coil. Virginia, Richmond, VAMerck Sharp & Dohme Res.

Labs., West Point, PA

2222

2222

2222111I11III1

I1111

111

11

II

111

Michael Reese Hosp., Chicago, ILMiyazaki Med. CoIl., JapanMonsanto Co., St. Louis, MON. London Bloud Transfusion

Ctr., Edgwdre, UKNY City Dept. Hlth,, NYNYU, NYNail, Inst. Biol. Stand., Lundon, UKNatl. Jewish Hosp. Res. Ctr., Denver, CONorth Shore Univ. Hosp., Manhasset, NYNorthwestern Univ., Evanston, ILOklahoma Med. Res. Fdn.,

Oklahoma City, OKOxford Univ., UKParis Univ., FrancePhilipps Univ., Marburg, FRGPitie-%fpctriere Hosp., Paris, FranceRice Univ., Houston, TXRoyal Mellmume Hosp., Parkville, AustraliaSaint Pierre Hosp., Brussels, BelgiumSaint-Luc Hosp., Brussels. BelgiumSanta Clara Valley Med. Ctr., San Jose, CASRJ Ml., Menfo Park, CASUNY, Stony Brook, NYTennessee Dept. Publ. Hlth., Nashville, TNTufts Univ., Boston, MAUniv. Anhvecp, BelgiumUniv. Cincinnati, OHUniv. Geneva, SwitzerlandUniv. Hlth. Sci., Bethesda, MDUniv. Kinshasa, ZaireUniv. LOuvain, BelgiumUniv. Liverpnnl, UKUniv. Melbuume, ParkviJle, AustraliaUniv. Miami, FLUniv. North Carolina, Chapel Hill, NCUniv. Pittsburgh, PAUniv. Rnchester, NYUniv. Southern California, Los Angeles, CAUniv. Virginia, Charlottesville, VAUniv. Wisconsin, Madison, WJUniv. Zurich, SwitzerlandUppsala Univ., SwedenVA Med. Ctr,, Palo Alto, CAWithington Hosp., Manchester, UK

1111

1111111

11111111111111I11111111111111111.

stitutions (56 percent) are located in the US,13 in the UK, 7 each in Belgium and France,4 each in Japan, Australia, and Switzerland,

and 3 in Canada. As mentioned earlier, twoinstitutions are from Zaire, while Israel, theFederal Republic of Germany, Kenya, andSweden each have one institution represent-ed in the Bibliography.

The number of multi-institutional studiesis growing significantly. It is neeessary tointerpret these figures carefully. It alsomakes the job of cataloging these studiesmore complex. Thus, while seven Belgianinstitutions are represented, there are onlythree papers involved.

Multiauthored Works

All but nine of the papers in the Bibliog-raphy have more than one author, Table 4shows the number of authors per paper. Fif-teen papers have two authors, 6 papers havethree authors, and 14 papers have four. Onepaper has 20 authors.

Eighty-five authors have more than onepaper listed in the Bibliography. Since AIDSresearch was so active in 1984, it is not sur-prising that the most prolific authors in ourstudy are AIDS researchers. Gallo coau-thored eight of the papers in the Bibliogra-phy, Samgadharan has six papers, whilePopovic has five papers in the study. M.M.

393

Table 4 The number of authors per paper for the 1984life-sciences articles most cited in the sCp,1984-1985.

Number Number Number Numberof Uf of Uf

Authurs Papers Authors Papers

20 I 9 319 1 8 217 1 7 815 2 6 1214 3 5 1613 1 4 1412 1 3 611 4 2 1510 3 I 9

Davis also coauthored five papers. In addi-tion to Montagnier and Barr6-Sinoussi, men-tioned earlier, five other authors wrote fourpapers each: M.J. Berridge, J.C. Cher-mann, L.E. Hood, R.F. Irvine, and T.W.Mak.

The 102 papers in the Bibliography werepublished in the 21 journals listed in Table5. As is usual in these studies, almost 60 per-cent of the papers were published in Nature(31 papers), Science (16 papers), or Cell(11 papers). Table 5 also includes 1984 im-pact factors, calculated by dividing the 1984citations to 1982 and 1983 articles publishedin a journal by the number of articles pub-

lished by that journal in those two years. Fora more extensive discussion of high-impactjournals, see my recent paper in Annals ofInternal Medicine. 10

Signal-Transduction StudiesTwo of the top five most-cited articles

were published in Nature. Both deal withsignal transduction, a field that is growingrapidly. Cell behavior is governed by signal-ing systems that transduce external signalsfrom hormones, growth factors, or neuro-transmitters into certain types of internalsignals, known as second messengers. Thesesecond messengers control cellular pro-cesses, such as metabolism, secretion, con-traction, and cell growth. One signal-trans-duction system uses inositol phospholipidsas part of the transduction mechanism. Theinositol phospholipid called phosphatidylino-

sitol 4, 5-bisphosphate is hydrolyzed todiacylglycerol and inositol trisphosphate. II

Table 5: The 2 I Journals represented in the I!st of 1984life-sciences papers most cited in the SCP1984-1985. The numbers in parentheses are the 1984impact factors for the journals, (The 1984 impact fac-tor equals the number of 1984 citations recewed bythe 1982-1983 anicles in a journal divided by thenumber of articles published by the journal during thatsame period. ) Data were taken from the JCR” Thefigures at the right indicate the number of papers fromeach journal that appear in the list.

Numberof

Journal Papers

Nature (10.3) 31Science (8.2) 16CeO (16.2) IIN. Engl. J. Med. (16.0) 8Pmt. Nat. Acad, Sci. USA (9.0) 7Lancet (9.4) 6J, Biol. Chem. (6. I ) 5Binchem. Biophys. Res, Cormnun. (3 .0) 3Biochem. J. (3.4) 2Nucl. Acid Res. (6,0) 2Acts Biuchim. Biophys. (2.5) IAnn. lntem, Med. (8.2) 1Ann. Trop. Med. Parasitnl. (1.1) IAnnu. Rev. Immunol. (17.1) 1Brain Res. (2.8) 1Ca-A Cancer J. Clin. (3.3) 1FEBS Lett. (3.0) 1J, Clin. Invest. (6.1) 1J. Immunol. (6,3) IMicrobiol. Rev. (18.8) 1Rev. Infec. Dis. (2.5) 1

Yasutomi Nishizuka, Department of Bio-

chemistry, School of Medicine, Kobe Uni-versity, Japan, reviewed the studies estab-

lishing diacylgl ycerol as a second messen-ger that activates protein kinase C, an en-zyme that regulates a wide variety of cellfunctions and proliferation. Nishizuka pro-posed that protein kinase C is a prime tar-get for the actions of tumor-promoting phor-bol esters. II This field is attracting a greatdeal of attention because an imbalance ofprotein kinase C activity may be responsi-ble for normal cells becoming cancerous.Nishizuka’s review article was cited over500 times, making it the most-cited 1984life-sciences article.

In another highly cited signal-transductionstudy, Michael J. Berridge, Department ofZoology, University of Cambridge, pro-poses that inositol trisphosphate is releasedinto the cytoplasm to function as a secondmessenger for mobilizing intracellular cal-

394

cium. 12 Cited over 350 times, Berridge’sreview paper is the fifth most-cited paperin this study, Berridge is writing a surveyof this research area for the 1S1Atlas of Sci-ence@: Pharmacology, which will be pub-lished in 1987. Berridge, along with Mon-tagnier, mentioned earlier, and Desir6 Col-Ien, Center for Thrombosis and VascularResearch, University of Louvain, Belgium,are the recipients of the annual award of theLouis Jeantet Foundation for Medicine. Thisaward, established in 1983, supports the on-going research efforts of scientists in West-ern Europe. 13

Both of these papers are core to ‘‘Phos-phorylation and calcium binding of phorboland inositol; stimulation of protein-kinase

release” (#84-03 19) and research front#85-0289, mentioned earlier as the largestfront in our study.

Oncogene StudiesCertainareasof research have been prom-

inent in these citation-frequency studies overthe past few years. One such area is thestudy of oncogenes, normally unexpressedgenes that, when activated, can producetumors in cell culture. Walter Bodmer, Im-perial Cancer Research Fund, London, UK,believes that oncogenes are simply alterednormal genes that now have this additionaltumor-producing capability. 14

Ten papers in the Bibliography involveoncogene investigations. The fourth most-cited paper, by J. Downward, ProteinChemistry Laboratory, Imperial Cancer Re-search Fund, and colleagues, found that eachof six peptides derived from the humanepidermal growth factor (EGF) receptor issimilar to a part of the sequence of the on-cogene v-erb-11 transforming protein. Thesestudies are important bwause the mechanismby which the oncogene transforms cells mayinvolve a protein with functions similar tothose of EGF during cell growth. Abnor-mal expression of an EGF-like protein maylead to uncontrolled growth by tumorcells. 1AThis paper was cited 115 times in1984 and 249 times in 1985, and it is core

to the research front on ‘‘Oncogenes andgrowth-factor receptors and their roles in

gene expression and transformation in nor-mal and cancer cells” (#85-2623).

Another active area of research here andin past studies concerns antigen presentation.Eleven of the 39 core papers in ‘‘Monocli-nal antibody activation of T-cells and anti-gen-receptor gene expression” (#85-0178)are in this study. These papers investigateT-cell receptors and their role in the cellularimmune response. Scientists are trying toestablish a structural model of the T-cellreceptor that explains how it functions in an-tigen recognition. For example, scientistsare studying how T-cell receptors dktinguishbetween an antigen normally present in thebody (’‘self” antigen) and a foreign antigenthat may pose a danger to the body (’‘non-self” antigen).

Yueh-hsiu Chien and colleagues, Depart-ment of Medical Microbiology, School ofMedicine, Stanford University, California,

studied a T-cell receptor gene and found thatpart of its sequence closely resembles partof the genetic sequence of immtmoglobulirrs,

those proteins involved in the humoral im-mune response. Chien and colleagues pro-pose that it is this section of the T-cell recep-tor gene that is involved in antigen recogni-tion. 15Published in Nature, this paper wascited about 100 times in 1984 and 1985.

A new area of research not previouslyrepresented in these annual studies concernsthe atrird natriuretic factor (ANF), a hor-mone released by the atrium of the heart.ANF inhibits reabsorption of sodium by therenal tubules of the kidney, thereby promot-ing both diuresis, an increased excretion ofurine, and natriuresis, the excessive loss ofcations such as sodium in the urine.

ANF is a small polypeptide hormone de-rived from a 126-amino acid precursor.Kenji Kangawa and Hisayuki Matsuo, De-partment of Biochemistry, Miyazaki Medi-cal College, Japan, extracted a 28-aminoacid peptide that they labeled a-human atrialnatriuretic pdypeptide (cAANP). This pep-tide elicits diuretic and natriuretic activities

395

and is thought to represent the principaJ ac-tive molecule of ANF. lb One of eightpapers in this study investigating ANF, thispaper was cited about 130 times in 1984 and1985.

All eight papers on this topic are core tothe front on “Biological activity, receptordistribution, and the systemic and renal he-modynarnic effects of ANF” (#85-1307),which attracted over 300 published papersin 1985. Monitoring the release of ANFcould play a role in understanding disordersrelated to salt and water imbrdance. How-ever, since this hormone has only recentlybeen identified, more information about

ANF must be accumulated before the ther-apeutic potential of this peptide hormone canbe ascertained. The subject of ANF will rdsobe covered in the 1987 ISIAtlas of Science:phU9’??UCOiOgy. h wfll be diSCUSSed by JOhtl

H. Laragh, Hypertension Center, Cornell

University Medical College, New York, acoauthor of the first paper in the Bibliog-raphy. 17

Conclusion

While this list of 102 papers representsonly a fraction of the important research oc-curring in 1984, it does give excellent ex-

amples of those newer areas of research thatwere the most active. These amualcitation-frequency studies help us monitorthe progress made from year to year. Thescientific community is engaged in a con-tinuing quest to understand phenomena suchas AIDS, oncogenes, antigen presentation,and ANF. Each new discovery opens upnew areas of knowledge. New informationtechnologies help us exploit this knowledgeso rapidly that we often lose track of theshort history involved. In the paat, we wotddnot have considered five years much timeto wait for a progress report on a new field.Today, changes are produced in five yearsthat might have required an entire genera-tion in the past. Many different teams work-ing in parallel produce solutions to problemsby a catrdytic process that social scientistsneed to study more carefully.

*****

My thanks to Lisa Holland, KarenMaguire, and Pat Taylor for their help inthe preparation of this essay. 019961s1

REFRRENCE.S

1. Gartleld E. The 1976 articles most cited in 1976 and 1977. Part 1, Life sciences. Emays of min@mation scientist. PhiSadelphia: 1S1 Press, 1981. Vol. 4. p. 8 I-99.

2. ---------- The 1982 articles merst cited in 1982 and 1983. 1. Life sciences.Ifrid., 1985. Vol. 7. p. 353-65.

3. Pape J W, Liautaud B, Thomas F, Mathurin J-R, St. Amand M-M A, Borwy M, Peaa V,Pampfdte M, Larnehe A C & Johnson W D. Characteristics of the squired imnmrmdeticierccysyndrome (AIDS) in Haiti. N. .Qrg/. J. Med. 309:945-50, 1983.

4. Bygbjerg I C. Letter to editor. (AIDS in a Danish surgeon. Zaire, 1976.) Lzmcer 1:925, 1983.5. Garfield E. The 1983 articles most cited in 1983 and 1984. 1. Life aciencm. CurrerU Con/erus

(47): 3-18, 25 November 1985. (Reprinted in: Essays of an infonrration scienri.w ghostwriting nrrdother essays. Pfritadelphia: 1S1 Press, 1985. Vol. 8. p. 444-59. )

6. Popovic M, Sarrrgarfharmr M G, Read E & Gaffo R C. Detection, ianlation, and continuousproduction of cytopathic retrovimaea (HTLV-111) from patients with AIDS and pre-AIDS. Science224:497-560 1984.

7. Gafto R C, Satahrrddlrr S Z, Popovic M, Shearer G M, Kaplan M, Hayrw B F, Pafker T J,Redtield R, Oleake J, Safai B, White G, Foster P & Markham P D. Frequent deteetion andisolation of cytopathic retroviruses (HTLV-IIf) from patienta with .43DS and at risk for AIDS.Science 224:5(X)-3, 1984.

S. Barr&Sinousai F, Chermann J C, Rey F, Nugeyre M T, Charrraret % GIIIeat J, ~USUet c,Axter-Btin C, V&zinet-Brmt F, Rorrz50ax C, Rozenbaurn W & Montagnter L. Isolation of aT-lymphotropic retrovirus from a patient at risk for squired immune deficiency syndrome (AIDS).Srience 220:S68-71, 1983.

9. Schmeck H M. AIDS resrarch rivats share a major award.New York limes 23 September 1986. p. Cl; C3.

396

10. Garfield E. Which medical jnurnrds hzve the greatest impact? Ann. In/em, ?&f. 105(2):313-20, 1986.11, NfshJzuka Y. The role of protein kinase C in cell surface signaf transduction and nmrnur promotion,

Nature 308:693-8, 1984.12. BerrJdge M J. Innzitol trisphnsphatc and dizcylglycerol as second mesamrgers.

Biochem. J. 220:345-60, 1984.13, Louis &?arrtetFoundation for MadIcbre. Press release. 24 January 1986, 1 p,14. Dawnward J, Yardsn Y, Mzyea E, Scrace G, Tatty N, Stackwell P, Ullr’ich A, Schlesinger J &

Watefileld M D. Close similarity of epidermzl growth factor receptor and v-erb-B oncogene proteinsequences. Nature 307:521-7, 1984,

15. Chien Y-h, Gtwtcdgne N R J, Kavater J, Lee N E & Davis M M. Somztic recombhxition in a murineT-cd receptor gene, Nature 309:322-6, 1984.

16. Kangawa K & Matauo H. purification and complete amino acid sequence of a-human atrial natriureticpnlypcptide (a-MNP). Biochem. Biophys. Res, Comrnun. 118:131-9, 1984.

17. Atloa S A, Kteinert H D, Csmargo M J, JrumazewJcz A, Seafey J E, L-m@ J H, Schfflhg J w,LawicldJ A, Johnson L K & Maack T. purification, sequencing and syntfresis of natriuretic andvasnactive rat aerial peptide. Nature 309:717-9, 1984.

Bibliography: The 1984 tife-zciences articles most cited in the SCP, 1984-1985, Article.v are listed in alphabeticorder by fwst author. The authors’ affiliations foffow each citation. Cnde numbers indicate the 1984 and 1985SCI/SSCF research-front specizfries for which these are core pzpera. A = 1984 citations, B = 1985 citations,C= total. D =bibliogrzphic data.

ABC

15 94 109

g 54 62

9 56 65

33 320 353

0 220 220

11 66 77

0 70 70

22 86 108

33 100 133

D

Atlsa S A, Kleinert H D, Carrmrga M J, Jamrazewicz A, S4ey J E, Larzgfr J H,Schifffng J W, Lewicki J A, Jobnsnn L K & Masck T. purification, sequencing andsynthesis of nztriuretic and vasnzctive rat atrizi peptide. Nature 309:717-9, 1984. CornellUniv. Med. COIL, Hypertension Ctr, md Dept. Physiol., New York, NY; CafifomiaBiotcch. Inc., Mountain View, CA. 85-1307

Benjamin D C, Berzofsky J A, East I J, Grrrd F R N, Harmrmr C, Leach S J,Margolfmh E, Mfchael J G, Miffer A, Prsger E M, ReichIJrr M, SercarzE E, Smith-GiU S J, Tndd P E & Wilamr A C. The antigenic structure of pmtcins: a reappraisal..4rrrru. Rev, hmnuacd. 2:67-101, 1984. Univ. Virginia, Dept. Microbiol., Charlottesville,VA; NfH, NC1 and NMDDKD, Bethesda, MD; Indiana Univ., Dept. Chem., Blnam-ington, IN; Narf. Jewish Hozp. Res. Ctr., Denver, CO; Univ. Melbourne, Ruszcll Grim-wade Sch. Binchem., Parkvifle, Austrafia; Northwestern Univ., Dept. Biachem., Molcc.Biol., Cell BIO1,, Evanston, IL; Univ. Cincinnati, Dept. Microbiol. Imrnunol., OH; Univ.California, Dept. Microbiol,, Los Angeles and Dept. Bhchem,, Berkeley, CA; OklahomaMed. Res. Fdn., Arthritis Jmmunol. Lab., Oklahoma City, OK. 85-1308

BergetS M. Are U4 small nuclear ribnnucleoproteins involved in pcdyadenylation? Nafure309:179-82, 1984. Rice Univ., Dept. Biacbem., Houston, TX. 85-2329

k-ridge M J. fnositol trisphosphate and dmcylglycerol as second messengers. Biochem. J.220:345-60, 1984. Univ. Cambridge, Dept. Zocd.; AFRC, Unit Insect Neurophysiol.Phzmlacol., UK. 84-0319, 85-0289

Berridge M J & Irviie R F. Jnositol trisphosphate, a novel aecmrd meszenger in cellularsignal tcanaduceion. Nature 312:315-21, 1984. Univ. Cambridge, Dept. h].; AFRC,Unit foaect Neurophysiol. Phamrzcnl. and Inst. Anim. Physiol., UK. 85-0289

Bokoch G M, Katada T, NoctJmp J K, Ui M & Gtisn A G. Purification and propertiesof h inhib]tnry guanine nucleotide-bmdirrg regulatory compnnent of adenylats cyclase.J. Biol. Chart. 259:356&7, 1984, Univ. Texas, Hhfr. Sci, Ctr., Dallas, TX; HokkaidoUniv., Fat. Phanm Sci., Sapporo, Japan. 85-2866

Broder S & Gaflo R C. A pztbngenic retrovirus (HTLV-111) lied to AJDS. IV. Eng/. J.Med. 311:1292-7, 1984. NIH, NCI, Bethesda, MD. 85-3258

Brun-Vezirret F, Barre-SJnouasi F, Saimot A G, Chcfatnl D, Montagnfer L, Rouzioux C,Kfatzmamr D, Rozenbarrm W, GlrrckrrrannJ C & Chermamr J C. Detection of IgGantitmdies to Iymphadenopatby-associated vims in patients with AIDS or lymphadenopathysyndrome. L@acet 1:1253-6, 1984. Claude Bernard Hosp., Microbiol. -Virol. Lab. andInst. Med. Tmp. Epidemiol,; Pzateur fnst., Dept. Virol,; Dept. Publ. Hlth. Trop. Med.,Jmmunol.-Nephrol. Lab.; Pitie-Salpetriere Hosp., Paris, France. 84-1914, 85-1825

Burgess G M, Gaeffrey P P, McKfnney J S, Berrfdge M J, Irvfne R F & Putney J W.The second messenger linking receptor activation to irrtemzf Ca relezse in liver. Nature309:63-6, 1984. Med. CoIl. Virginia, Dept. Pfrarmacnl., Richmond, VA; Univ. Cam-bridge, Dept. Zool.; AFRC, Unit Invertebrate Chem. Physiol. and Inst. Anirm Physiol.,UK. 84-0319, 85-0289

397

ABC34 97 131

16 48 64

10 71 81

6 61 67

23 76 W

4 85 89

10 62 72

26 62 88

26 96 122

8 54 62

64 111 175

49 111 I&l

16 136 152

115 249 364

19 55 74

DCampiA J, Gray H E, Pardee A B, Dean M & Sonenshein G E. Cell-cycle control of

c-myc but not c-ra.r expression is lost following chemical transformation, Cell 36:241-7,1984. Harvard Univ., Med. Sch.; Dana-Farber Cancer Jrrst., DIV. CeJf Growth Regulat.;Boston Univ., Med. Sch., Buston, MA. 85-0208

Card M C, Campbell R D, Bentley D R & Porter R R. A molecular nrsp of the humanrmrjor histucompatibiJity complex class JJJ region linking complement genes C4, C2 andfactor B. Nlzmre 307:237-41, 1984. MRC, hnmuncxhem. Unit; Oxford Univ,, Dept.Bicxhem., UK. 85-0638

Cheirrgsong-Poprrv R, Weiss R A, Dafgfeish A, Tedder R S, Shmraorr D C, JefTries D J,Ferns R B, Brigg.s E M, Weller 1 V D, Mittorr S, Adfer M W, Fartfdng C, LawrenceA G, Grur.ard B G, Weher J, Harris J R W, PincfrJrrgA J, Craske J & Barbara J AJ. Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS-riskpatients in Britain, J.uncet 2:477-80, 1984. Jnst. Cancer Res,: Roysl Cancer Hosp.,Chester Bcatty Rcs, Inst.; Univ, London, Middlcscx Hosp. Med. Sch., St, Stephen’sHosp. Med. Sch., and St. Mary’s Hosp. Med. Sch., London; Withington Hosp., Labs.Regional Virus and Publ. Hlth,, Manchester; N. London Blund Transfusion Ctr.,Ekfgware, UK.

Chiba K, Trevor A & Caatagrrolf N. Metahulism of the neurotoxic tertia~ amme, M~P,by brain monuamine oxi&se. Biochem. Biop/rys. Res. Conrrnun. 120:574-8, 1984, Univ.California, Depts. Pharmscol. and Pharrrr, Chem., San Francisco, CA. 85-3538

Cfden Y-h, Gascoigne N R J, Kavaler J, Lee N E & Davis M M. Somstic recombinationin a murine T-cell receptor gene. Mzrure 309:322-6, 1984. Stanford Univ,, Sch. Med.,CA. 85-0178

Chien Y-h, Becker D M, Lmdsten T, Okarnrrra M, Cohen D I & Davis M M. A thirdtyp of murine T-cell receptor gene. Nature 312:31-5, 1984, Stanford Univ., Sch. Med.,CA. 85-0178

Cbrrrch G M & Gilbert W. Genomic squencing. Proc. Mm. .4cad. Sci. .5S4 81:1991-5,1984, Harvard Univ., Biol. Labs.; Biogen Jnc., Crmrbridge, MA.

Cbrrneck N, Somet J, Taefmmr H, Mascart-Lemone F, De Bruyere M, Vandepecre P,Dasnoy J, Marcefi.r L, Larny M, Jonas C, EyckrrrarraL, Nnel H, Vanbaeverbeek M &Brrtzler J-P. Acquired imrrtunodeticiency syndrome in Afncsrr patients. N. Engl. J. Med.310:492-7, 1984. Saint Pierre Hnsp., Div. Jnfect. Dk.; Saint-Luc Hosp., Dcpts. Med.,Hernatol., Virol., and Pathol.; Brugrnann Hosp., Dept. Med.; Anderlecht Hosp., Dept.Med., Brussels; Inst. Trop. Dis., Dept. Med., Antwerp, Belgium. 84-3901, 85-2553

Cuchet C, Gill G N, Meisenhelder J, Cuoper J A & Hrmter T. C-kins.se phosphorylatesthe epiderrnal growth factor receptor and reduces its epiderrnel growth factor-stimulatedtyrosine protein kinmc activity. J. Bid. Chem. 259:2553-8, 1984. Univ. CaJiforrria, SanDiego, Sch. Med., La Jolla; Salk Inst. Biol. Stud., Labs. Mokc. Biol. and Virol., SanDiegn, CA. 850289

Corcoran L M, Adarns J M, Drmrr A R & Cory S. Mmirre T-iymphoenas in which thecellular myc oncogene has been activatal by retrovird insertion. Cel[ 37:113-22, 1984.Royal Melbuume Hosp., WaJter and Eliza Hall Jnst. Med. Res. rmd Melbuume TumorBiol, Unit, ParkviJle; Ludwig Inst. Cancer Res., Sydney, Australii. 85-0208

Currmr J W, Lawrence D N, JalYe H, Kaplan J E, Zyla L D, Charnberbrnd M,Weinstein R, Lui K-J, Schonberger L B, Spira T J, Afexarrder W J, Swinger G,Armrrarm A, Solomon S, Auerbach D, Mildvarr D, Stoneburner R, Jaaurr J M,Haverkos H W & Evatt B L. Acquired imnrmrudeficiency syndrome (AJDS) associatedwith transfusions. N. Engl. J. Med. 310:69-75, 1984. CDC, AJDS Prog,, Atfanta, GA;Michael Rear Hosp., Dept. Intern. Med., Cbicagn, IL; NY City Dept. Hlth.; Beth IsraelMed. Ctr., NY; Tennessee Dept. Publ. Hlth., Nashville, TN; Jefferson Cnty. Dept. Publ.Hlth., Birmingham, AL; Univ. California, Med. Ctr., San Francisco, CA. 84-1914,854745

Currie M G, GeUer D M, Cole B R, Siegel N R, Fok K F, Adams S P, Eubanks S R,GaJhrppi G R & F%eedJemarrP. purification and sequence snaJysis of bioactive atria] peF-tides (atrlopcptins). Science 223:67-9, 1984. Washington Univ., Sch. Med.; MonsantoCo., Molcc. Biol. Dept., St. Louis, MO. 84-4992, g5-1307

Dmareffo C A. Interleukin- 1, Rev. @c. Dis. 6:51-95, 1984. Tufts Univ., Sch. Med.,Boston, MA, 85-1379

Downward J, Yarden Y, Mayea E, Scrace G, Totty N, Sttrckwell P, Ulfrich A,ScMesafnger J & WaterField M D. Close similarity of epidennrd growth factor receptorand v-erb-B oncogene protein sequences. Namre 307:521-7, 1984. Jmpcrid Cancer Res.Fund, Protein Chem. Lab., London, UK; Weizmann Inst. Sci,, Dept. Chem. Jnmrunol.,Rehovot, Israel; Genentcch Inc., San Fmrrciscn, CA, 84-1033, 85-2623

Emersurr B M & Felaenfeld G. Sp+xitic factor conferring nuclease hypersensitivity at the 5end of the chicken adult 6-globin gene. Proc. Nat. Acad. $ci. USA 81:95-9, 1984. NIH,NIADDKD, Bethesda, MD. 854540

—.

398

ABC D49 125 174 Fmrci A S, Maeher A M, Longo D L, Lane H C, Rcmk A H, Maarrr H & Gelmann E

P. Acquired immurrodeficiency syndrome: epidemiologic, clinical, immunologic, andtherapeutic considerations. Am, Intern. Med. 100:92-106, 1984, NIH, Clin. Ctr,,Bethesda, MD. 85-5383

12 57 69 Feorino P M, Kalyrmaramarr V S, Haverkoa H W, Cabrarfilla C D, Wartield D T,Jaffe H W, Harrison A K, Gottlieb M S, Goldtirrger D, Chermarrn J-C, Barre-Sinorraai F, Spira T T, McDmrgal J S, Curran J W, Montagrrier L, Murphy F A &Francia D P. Lymphadenopathy associated virus infection of a blond donor-recipient pairwith acquired immmmdeticiency syndrome. Scierrce 225:69-72, 1984. CDC, Ctr, Infect.Dis., Atlanta, GA; Univ. California, Sch. Med.; Cedars-Sinai Med. Ctr,, Los Angeles,CA; Pasteur Inst., Dept. Virol., Paris, France. 85-1825

21 49 70 Fkrer-Moore J & Stroud R M. Amphipathic analysis and possible formation of the ionchannel in an acetylcholine receptor. Proc. Nat. ,4cad. Sci. USA 81:155-9, 1984. Univ.California, Sch. Med., San Francisco, CA, 85-1426

19 76 95 Fung M C, Hapel A J, Ymer S, Cohen D R, Johnson R M, Campbell H D & Young 1G. Molecular cloning nf cDNA for murirre interleukirr-3. Nature 307:233-7, 1984,Australian Natl. Univ., John Curtin Sch. Med. Res., Canberra, Australia. 85-3101

1I5 404 519 Gallo R C, Salabuddhr S Z, Popcwic M, Shearer G M, Kaplan M, Hayrrea B F, PalkerT J, Redffeld R, Oleske J, Safai B, White G, Foster P & Markham P D. Frequentdetection and isolation of cytopathic retroviruses (HTLV-Iff) from patients with AIDS andat risk for AIDS, Science 224: 50f-3, 1984, NIH, NCI, Bethesda; Litton Bionet., Inc.,Dept. Cell Biol., Kensington, MD; North Shore Univ. Hosp., Div. Infect. Dis.,Manhasset; Mere. Sloan-Kettering Cancer Ctr., Dermatnl. Serv., New York, NY; DukeUniv., Sch. Mcd,, Durham; Univ. North Carnlina, Dcpt. Med., Chapel Hill, NC; WakerReed Army Inst. Res., Dept. Virus Dis., Washingron, DC; Univ, Med. Dent. NewJersey, Div, Allergy, Immurrol. Infect. Dis, Newark, NJ. g4- 1914, 85-1825

9 643 69 Gaacoigne N R J, Cfden Y-h, Becker D M, Kavaler J & Davis M M. Genomic organiza-tion and sequence of T-cell receptor (J-chain constant- and joining-region genes. Nrrrure310:387-91, 1984. Stanford Univ., Sch. Med., CA. g5-0178

17 136 153 (Msnan A G. G-proteins and dual control of adenyktte cyclase. Cell 36:577-9, 1984, Univ.Texas, Hkh. Sci, Ctr, and Southwestern Grad. Sch., Dallas, TX.

4 73 77 Goedert J J, Biggar R J, Winn D M, Greene M H, Mann D L, GaJlo R C,%rrrgadfraran M G, Weiaa S H, Grossman R J, Boshrer A J, Strong D M & BlattnerW A. Determinants of retrovirus (HTLV-Iff) antibody and immunrrdeticiency conditions inhomosexual men, lxrrrcef 2:711-6, 1984. NIH, NC1; Univ. Hkh. Sci., Uniformed Serv.,Bethesda; Litton Bionet,, Inc., Dept. Cell Biol., Kensington; Biotech Res. Labs,, Inc,,Rockville, MD. g5-1825

3 74 77 Greenberg M E & ZifT E B. Stimulation of 3T3 cells induces transcription of the c-josproto-oncogene. Narure 31 I :433-8, 1984. NYU, Med. Ctr., NY, 85-0208

1 66 67 Groopman J E, Sofahuddin S Z, Sarrrgaefharan M G, Markham P D, Gmrda M, SliikiA & Gallo R C. HTLV-111 in saliva of people with AIDS-related complex and healthyhomosexual men at risk for AIDS. Science 226:447-9, 1984. New Engl. Deaconess Hosp.,Dept. Mcd,, Boston, MA; NIH, NCI, Bethesda and Frederich Litton Bionet,, Inc,, Dept,Cell Biol., Kensington, MD. 85-6135

4 77 81 Halfiwell B & Gutteridge J M C. Oxygen toxicity, oxygen radicals, transition metals anddisease. Biochern. J. 219:1-14, 1984. Univ. London, King’s CoIl.; Natl. Inst. Biol.Stand., London, UK. 85-2053

12 58 70 Haaeltine W A, Sodmaki J, Pafarca R, Brigga D, Perkins D & Wong-Staal F. Structureof 3’ terminal region of type II human T Iymphotropic virus: evidence for new codingregion. Science 225:419-21, 1984, Harvard Univ., Med. Sch. and Sch. Publ. Hlth.; Dana-Farber Cancer Inst., Boston, MA; NIH, NCI, Bctfresda, MD. 85-1825

10 59 69 Hay R, Bofmi P & Gasaer S. How mitochondria import proteins. ,4cta Biochim, Biop/rys,779:65-87, 1984. Eiasel Univ., Biocenter, Switzerland. 85-6398

67 133 2(w3 Hedrick S M, Nielsen E A, Kavaler J, Cohen D I & Davis M M. Sequence relationshipsbetween putative T-ceii receptor polypeptides and immunoglobulins. Nature 308:153-8,1984. NIH, NIAID, Bethesda, MD; Stanford Univ., Sch. Med., CA. 84-0171, 85t3178

58 133 191 Hedrick S M, Cohen D I, Nielsen E A & Davis M M. Isolation of cDNA clones encndingT cell-specific membrane-associated proteins. Nature 308:149-53, 1984. NIH, NIAID,Bethesda, MD; Stanford Univ., Sch. Med., CA. 84-0171, 85-0178

5 73 78 Heikfdla R E, Marrzino L, Cabbat F S & Duvoisin R C. Protcctinn against thedopamirrergic neurotoxicity of 1-methyl-4-phenyl-l ,2,5,6-tetrahydropyridirre by monoamineoxidasc irrfribitors, Nature 311:467-9, 1984. Univ. Med. Dent. New Jersey, Dept,Neumi., Newark; Rutgers Univ., Med. Sch., Piacaraway, NJ. 85-3538

8 92 ICS3 Heldin C-H & Watermark B. Growth factors: mccfranism of action and relation to on-cogenes. Cell 37:9-20, 1984. Uppsafa Univ., Depts. Med. Physiol. Chem. and Pathol.,Sweden.

399

ABC D19 67 86 Iwashita S & Fox C F. Epidemral growth factor and potent phorbol tumor promoters in-

duce epidermal growth factor receptor phosphorylation in a similar but distinctively dif-ferent manner in human epidermoid carcinoma A431 cells. J. BioL Chern. 259:2559-67,1984. Univ. California, Dept. Microbiol. and Molec. Biol. Inst., Los Angeles, CA.85-0289

51 I40 191 Jnaeph S K, Thonma A P. Williams R J, Irvine R F & Williamsrm J R. myo-Inositol1,4,5-trisphosphate: a second messenger for the hormonal mobilization of intracellularCal+ ,n liver. J. Bid. Chem. 259:3077-81, 1984, Umv. Pennsylvania, Sch. Md,

Philadelphia, PA; AFRC, Inst. Anim, Physiol., Cambridge, UK. 84-0319, 85-028934 95 129 Kmrgawa K & Mafarro H. purification and complete amino acid sequence of a-human

atrial natriuretic pnlypeptide (cr-hANP). Biochem. Biophys. Res. Comrrrun. 1I8:131 -9,1984. M1yazaki Med. COO., Dept. Binchem., Japan. 84-4992, 85-1307

19 65 84 Kruhr M, Hasliiger A, Holtgreve H, Richards R 1, Krauter P, Weatphaf H M & BeatoM. Characterization of DNA sequences through which cadmium and glucncorticoid hor-mones induce human metaflothionein -flA gene. Nature 308:513-9, 1984. Univ. SouthernCalifornia, Sch. Med., Los Angeles, CA; Australian Natl. Univ., Res. Sch. Biolog. Sci.,Canberra, Australia; Ph]lipps Umv., Physiol. Chem, hrst,, Marburg, FRG. 85-1677

20 81 101 Kaufman J F, Arrffray C, Korman A J, Shackelford D A & Stromhrger J. The class ffmolecules of the human and murine major histocompatihifity complex, Ccl/ 36:1-13, 1984Basel Inst. Inrmunol.. Switzerland: Harvard Univ.. Dem. Binchem. Molec. Biol.. Cam-bridge, MA. 85-7037

31 122 153 King W J & Greene G L. Monnclonaf antibodies lncafize cestrogen receptor in the nucleiof target cells. Nafure 307:745-7, 1984. Univ. Chicago, Ben May Lab. Cancer Res., IL.84-6753, 85-0822

15 79 94 Klatzmamr D, Barre-Sinorsssi F, Nugeyre M T, Daugcret C, Vibner E, Griaeelfi C,Brmr-Vezinet F, Ronzioux C, Gluckrnarr J C, Cherrmurrr J-C & Montagcrier L. Selcx-tive tropism of lymphadenoparhy assnciatcd virus (LAV) for helper-inducer T lym-phocytes, Science 225:59-63, 1984. Paris Univ., UER Pitie-Safpetriere; Pasteur Inst.,Dept. Virol.; Hosp. Infant Dis., Dept. Pe&at.; Claude Bernard Hosp., Virol, Lab., Paris,France. 85-1825

28 108 136 Kordc M. Compilation and arrafysis of sequences upstream from the translational start sitein eukmyotic mRNAs. IVUCLAcid Res. 12:857-72, 1984. Univ. Pittsburgh, Dept. Biol.Sci., PA.

13 62 75 Langaton J W, Forno L S, Rebert C S & Irwin 1. Selective nigral tnxicity after systemicadministration of 1-methyl-4-phenyl- 1,2,5,6-tetrahydropyrine (MPTP) in the squirrelmonkey. Bmin Res. 292:390-4, 1984. Santa Clara Valley Med. Ctr., Dept. Neurol., Sanlose; Stanford Univ., Sch. Med.; Vet. Admin. Med. Ctr., Dept. Patbol., Pafo Alto; SRfIntl., Menlo Park, CA. 84-3825, 85-3538

11 105 116 Levy J A, Hoffman A D, Kramer S M, Landis J A, Shmabukrrro J M & Osfdro L S.Isolation of lymphneytopattic retroviruses from San Franciaco patients with AIDS. Science225:840-2, 1984. Univ, California, Scb, Med., San Francisco; California Dcpt, Hlth.Serv., Viral Rickettsial Dis. Lab., Berkeley, CA. 85-1825

7 59 66 Lewis R A & ArMen K F. The biologically active leukotrienes: biosynthesis, metabolism,receptors, functions, and pharmacology. 1. C/in. Invesr, 73:889-97, 1984. Harvard Univ.,Med. Sch. and Brigham and Women’s Hosp., EWston, MA. 85-1368

15 67 82 Macara I G, Marinetti G V & Bafduzzi P C. Transforming protein of avian sarcoma virusUR2 is associated with phosphatidylinositol kinasc activity: possible role in tumorigenesis.Pmt. Mr. Acad. .Sci. USA 81:2728-32, 1984. Univ. Rnchester, Sch. Med. Dent.. NY.85-6203

13 56 69 Maki M, Takayarmgi R, Miacmo K S, Parrdey K N, Tibbetts C & Inagemri T. Structureof rat atria] natriuretic factor precursor deduced from cDNA sequence. Narure 309:7224,1984. Vanderbilt Univ., Sch. Med., Nashville, TN. 85-1307

10 59 69 Maffxsen M, Mirnwd K, MJr?fsnesa S, Kronenberg M, Govermarr J, Wrrrkapiller T,Prystowsky M B, YoaWI Y, Fitch F, Mak T W & Hnod L. Mouse T cell antigenreceptor: structure and organization of constant and joining gene segments encndirrg the dpolypeptide. Cell 37:1101-10, 1984. Caftech, Div. Biol,, Pasadena, CA; Univ. Chicago.Dept. Pathol., IL; Univ. Toronto, Ontario Cancer Inst., Crmada. 850178

4 67 71 Markey S P, Jobannessen J N, Chirreh C C, Burma R S & Herketrhmn M A. In-traneuronal generation of a pyridirrium metabnlite may cauae drug-induced parkinsonism.Nature 311:464-7, 1984. NIH, NIMH, Bethesda, MD. 85-3538

14 55 69 Marquardt H, Hunkapiller M W, Hood L E & Todaro G J. Rat rrarrsfnrming growthfactor typ 1: structure and relation to epidemud growth factor. Science 223:1079-82,1984. NIH, NCI, Frederick, MD; Caltech, Div, Biol., Paaadena, CA. 85-1294

19 46 65 McGhuda W, Levine M S, Hctfen E, Krrrniwa A & G&ring W J. A con$med DNA se-quence in homneotic genes of the Drosophila An[ema@ia and bithorax complexes.Nature 308:428-33, 1984. Basel Univ., Biocenter, Switzerland. 84-2344, 8543374

400

ABC7 69 76

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14 62 76

13 53 66

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18 61 79

27 53 80

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89 326 415

19 68 87

II 62 73

10 69 79

DMcGrath J P, Capon D J, Goeddel D V & LevirmorI A D. Comparative biochemical

properties of normal and activated human me p21 protein. Nature 310:644-9, 19t34,Genentech, Inc., Dept. Molec. Biol,, San Francisco, CA. 85-0208

Melton D A, Krieg P A, Rebaglfati M R, Mmdatis T, Zhtn K & Green M R. Efficientin vitro synthesis of biologically active RNA snd RNA hybridization probes from plasmidscontaining a bacteriophage SP6 promoter. Nucl. Acid Res. 12:7035-56, 1984. HarvardUniv., Dept. Biochem. Molec, Biol,, Cambridge, MA, 85-7714

Merion R M, White D J G, Tbfru S, Evans D B & Cahre R Y. Cyclosporine: tive yearsexperience in cadaveric renal transplantation. IV. .EngL J. Med. 310:148-54, 1984. Univ,Cambridge, Depts. Surg, and Patbol.; Addenbrooke’s Hosp., UK. 85-2493

Meuer S C, Hussey R E, Fahbi M, Fox D, Acuto O, Fitzgerald K A, Hodgdon J C,Protentis J P, !lchlavsman S F & Rehdrers E L. An alternative pathway of T-cell ac-tivation: a timctional role for the 50 kd T 11 shmp erythrocyte receptnr protein, Cell36:897-906, 1984. Dana-Farber Cancer Inst,, Div. Tumor Inununol,; Harvard Univ.,Med. Sch., Boston, MA.

Meuer S C, Hnaaey R E, Cantrell D A, Ho@don J C, Sehlossman S F, Srrdth K A &Reinhera E L. Triggering of the T3-TI antigen-receptor complex results in clonal T-cellproliferation through an interleukin 2-deptndent autocrine pathwsy. Proc, Nut. ,4crrd. Sci.USA 81:1509-13, 1984. Dana-Farber Cancer Inst., Div. Tumor Inzmunol.; Harvard Univ.,Med. Sch., Boston, MA; Dartmouth COO., Med. Sch., Hanover, NH, 85-3696

Mfaorro K S, Fukurrd H, Grammer R T & Irragami T. Rat atrial natriuretic factor com-plete amino acid sequence and dkultide linkage essential for biological activity, Biochem.Biophys. Res. Conrmun, 119:524-9, 1984. Vanderbilt Univ., Sch. Med., Nashville, TN,85-1307

Murray H W, Rubfn B Y, Maaur H & Roberta R B. Impaired production of Iymphokinesand imrnunc (gamma) interferon in the acquired imnumodeticiency syndrome. N. Engl, J.Med. 310:883-9, 1984. Cornell Univ. Med. COIL, Dept. Med.; NY Hosp.; Sloan-Kettering Inst. Cane-s Res., New York, NY; NIH, Clin. Ctr., Bethesda, MD. 84-2324

NishJmrka Y. The role of protein kinase C in cell surface signal transduction and NIIIOU1

promotion, Nature 308:693-8, 1984, Kobc Univ., Sch. Med.; Natf. Inst. Basic Biol.,Dept. CeU BioL, Okazaki, Japan. 84-0319, 85-0289

NBhuuka Y. Turnover of inositol phospholids and signal transduction. Science225:1365-70, 1984. Kobe Univ., sch. Med.; NatL Inst. Basic Biol., Okazski, Japan,

Padgett R A, Konarska M M, Grabowsfd P J, Hardy S F & Sharp P A. lariat RNA’sas intermediates and products in the splicing of rneasenger RNA precursors. Science225:898-903, 1984. MIT, Ctr. Cancer Res. and Dept. Binl., Cambridge, MA; SUNY,Stony Brook, NY. 85-0&t7

Parker C S & Topol J. A Drosophila RNA prdymerase ff transcription factor binds to theregulatory site of an hsp 70 gene. Cc// 37:273-83, 1984. Caltech, Div, Chem,, Pasadena,CA. 85-1677

Petersen O H & Maruyruna Y. Calcium-activated potassium channels and their role insecretion. Ntz[ure 307:693-6, 1984. Univ, Liverpool, Physiol. Lab.; MRC, sccreto~CntrL Rea. Grp., Liverpool, UK, 84-8516, 85-0215

Picard D & Schafllrer W. A lymphocyte-specific enhancer in the mouse imrnunoglobulin xgene. Nature 307:80-2, 1984, Univ. Zurich, Molec. Biol. Inst. II, Switzerland.

Piot P, Taebnan H, Minlangu K B, Mbendi N, Ndangf K, Kalambayi K, Bridta C,Qrdmt T C, Febraod FM, Wobirt O, Mazeba P, Stevens W, Mitchell S & McCormfckJ B. @uired immunodeficiency syndrome in a heterosexual population in Zaire. Larcet2:65-9, 1984, Inst. Trop. Med.; Univ. Antwerp, Belgium; Manra Yemo Hosp.; Univ,Xinshasa, Univ. Hosp., Zaire; NIH, NIAID, Bethesda, MD; CDC, Ctr. Infect. Dk.,Atlanta, GA. 84-3901, 85-2553

Popovic M, Sarngadbaran M G, Read E & Gallo R C. Detection, isolation, and con-tinuous production of cytopatfic retroviruscs (HTLV-JJI) from patients with AIDS and pre-AJDS. Science 224:497-500, 1984. NIH, NC1, Bethesda; Litton Bionet., Inc., Dept. CellBiol., Kensington, MD. 84-1914, 85-1825

Prentki M, Biden T J, Janjic D, Irvine R F, Berridge M J & Wolfhefm C B. Rapidmobilization of Ca2 + from rat insulinoms microsomes by inositol- 1,4,5-trisphosphate.Nature 309:562-4, 1984. Univ. Geneva, Med. Biochem. Inst., Switzerland; AFRC, Inst.Anim. Physiol. and Unit Insect Neurophysiol. Phmmscol.; Univ. Cambridge, Dept. Zrml.,UK. 85-0289

Quesada JR, Reuben J, Mantdng J T, Hersh E M & Guttermart J U. Alpha interferonfor induction of remission in hairy-cell leukemia. N, Engl. J. Med. 310: )5-8, 19&t. Univ.Texas, M.D. Anderson Hosp. Tumor Inst., Houston, TX. 854129

Rnsenberg S A, Grbrrrn E A, McGrogarr M, Doyle M, Kawasaki E, Koths K & MarkD F. Biologicaf activity of recombinant human intcrleukin-2 produced in ficlwichia coli.Science 223:1412-5, 1984. NIH, NC], Bethesda, MD; Cetus Corp., Emczyville, CA.85-6121

401

ABC4 78 82

20 96 116

20 71 91

4 81 85

79 250 329

58 158 216

20 46 66

17 83 la-r

10 54 64

17 63 80

85664

28 84 112

DRrrskin B, Krainer A R, Maniatis T & Green M R. Excision of an intact intron as a

novel lariat structure during pre-mRNA splicing in vitro. Cc// 38:317-31, 1984. HarvardUniv., Dept. Bioehem. Molec. Biol., Cambridge, MA. 854647

Safai B, GroopmmsJ E, Popovic M, Schupbach J, Sarngadharan M G, Arnett K,Sliski A & Gallo R C. Serocpidemiological studies of human T-lymphotropic retrovimstype 111in acquired irnmunodeficiency syndrome. Lmcer I: 1438-40, 1984. Mere. Sloan-Kettering Cancer Ctr., New York, NY; Litton Bionet., Inc., Dept. Cell Biol., Kensington;NIH. NCI, Bethesda, MD; New Engl. -Lkaconess Hosp., Dept, Med., Boston, MA,84-1914, 85-1825

%sito H, Kram D M, Takagaki Y, Hayday A C, Eisen H N & Tonegawa S. Completeprimary structure of a hetemdimeric T-cell receptor deduced from cDNA sequences.Nature 309:757-62, 1984. MIT, Ctr. Cancer Res. and Dept. Biol., Cambridge, MA.84-0171, 85-0178

Saito H, Krasrz D M, Takagaki Y, Hayday A C, Eisen H N & Tocregawa S. A thirdrearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature 312:36-40,1984. MfT, Ctr. Cancer Res. and Dept. Biol., Cambridge, MA. 8543178

%rngadharrrn M G, Popnvic M, Bruch L, Schupbach J & Gallo R C. Antibwhes reac-tive with human T-lymphotropic retrovimses (HTLV-Tffl in the serum of patlems withAIDS. Science 224:506-8, 1984. Litton Bionet., Inc., Dept. Cell Biol., Kensington; NIH,NC], Bethesda, MD. 84-1914, 85-1825

Schrrpbach J, Popnvic M, Gilden R V, Gonda M A, $arngadharan M G & Gallo R C.Serological analysis of a subgroup of human T-lymphotropic retrovimses (HTLV-ffI)associated with AIDS. Science 224:503-5, 1984. NIH, NCI, Bethesda and Frederick; Lit-ton Bionet., Inc., Dept. Cell Biol., Kensington, MD. 84-1914, 85-1825

Scott G B, Buck B E, Leterman J G, Bloum F L & Parks W P. Acquired inmmncdefi-ciency syndrome in infants. h’ .Eng/. J. Med. 310:76-81, 1984. Univ. Miami, Sch. Med.,FL. 84-0752, 85-0745

Seidah N G, LrczrrreC, Chretien M, Tbibault G, Garcia R, Cantin M, GenestJ, NuttR F, Brady S F, Lyle T A, Paleveda W J, Colton C D, Ciccarone T M & Veber D F.Amino acid sequence of homologous rat atrial pcptides: natr’iuretic activity of native andsynthetic forms. Proc’. Nat. A-ad. Sm USA 81:2640’$, 1984. Clin. Res. Inst. Montreal,Protein Pituitary Hormone Lab. and MRC Grp. Hypertension, Canads; Merck Sharp &Dahme Res. Labs., West Point, PA. 85-1307

Silverherg E. Cancer statistics, 1984. Ca-A Cancer J. ChrI. 34:7-23, 1984. AmericanCancer Sm., Dept. Epidemiol. Statist., New York, NY.

Siu G, Clark S P, Yushikai Y, Mafiin M, Yanagi Y, Strauss E, Mak T W & HundL. The human T cell antigen receptor is enccded by variable, diversity. and joining genesegments that rearrange to generate a complete V-gene. Cell 37:393-401, 1984. Cakech,Div. Biol., Pasadena, CA; Umv. Toronto, Dept. Med. Biophys.; OntarioCancerlnst.,Canada. 85-0178

Siu G, Kronenherg M, Strauss E, Haars R, Mak T W & Hued L. The stmcture, rear-rangement and expression of D gene segments of the murine T cell antigen receptor.Narure 3 I I :34--50, 1984. Cakech, Div. Biol., Pasadena, CA; Columbia Univ.. Coil.Physns. Surgs., New York, NY; Univ. Toronto, Dept. Med. Biophys.; Ontario Cancerfnst., Canada. 854178

Skmson D J, deKernion J B, Verma I M & Cline M J. Expression of cellular oncogenesin human malignancies. Science 224:256-62, 1984. Univ. California, Ctr. Hlth. Sci. ~ LosAngeles; Safk Inst. Biol. Stud., San Diego, CA. 85-7317

15 56 71 Smith D H, Wellde B T, Sabwa C L, Reardon M J & Huekmeyer W T. A complementfixation test for visceral Ieishrnaniasis using homologous parasite antigen IL Am. Trop.Med. Parmiro/ 78:495-5(X), 1984. Liverponl Sch. Trop. Med., Dcpt. Trop. Mc&, UK;Wslter Reed Project, Nairobi, Kenya; Walter Reed Army Inst. Res., Wash@on, DC.

7 87 94 SodrUSki J G, Rosen C A & Haseltine W A. Tram-acting transcriptlonaf activation of thelong terminal repeat of humun T lympbotropic viruses in infected cells. Science225:381-5, 1984. Dana-Farber Cancer Inst.; Harvard Univ., Med. Sch. and Sch. Publ.Hlth., Buston, MA. 85-1825

30 95 125 Srsgirnoto Y, Whitman M, Carstley L C & Erikaun R L. Evidence that the Rous sarcomavirus transforming gene product phosphorylates phospha:idylinositol and diacylgl ycerol,Proc. Nar. Acad. .Sci. USA 81:2117-21, 1984. Harvard Univ., Depts. Cell. Dcv. Biol. andBiochem. Molec. Biol., Cambridge, MA. 85-6203

22 43 65 Taub R, Moukfirrg C, Battey J, Murphy W, Vaaicek T, Lenoir G M & Leder P. Ac-tivation and somatic mutation of the translmatcd c-myc gene in Burkitt Iymphoma cells.Cc// 36:339-48, 1984. Harvard Univ., Med. Sch., Bnston, MA; hf. Agcy. Res. Cancer,Lyon, France.

23 46 69 Tbibasdt G, Garcia R, Cantin M, Genest J, Laaure C, Seidab N G & Cfrretien M.Primary structure of a high M, form of rat atrial natnuretic factor. ~EBS Qtr.

402

A

10

17

20

18

55

11

27

11

70

BC

54 64

145 162

78 98

63 81

96 151

129 140

105 132

57 68

176 246

D167:352-6, 1984. Clin. Res. Inst. Montreal, MRC Grp. Hypertension and Labs. Biochem.Molec, Nerrroendocrinol., Canada. 85-1307

Thomaa A P, Alexander J & Wiifhmraun J R. Relationship between mositol polyphosphateproduction and the increase of cytosolic free Ca2+ induced by vasopressin in isolatedhepatmytes. J. Biol. Chem, 259:5574-84, 1984. Univ. Pennsylvania, Sch. Med.,PhJadelphia, PA. 85-0289

Ulfrich A, Corraaena L, Hayfffek J S, Dull T J, Gray A, Tam A W, Lee J, Yarden Y,Lihermamr T A, ScMednger J, Downward J, Mayea E L V, Whittle N, WatertleldM D & Seeburg P H. Hrmrarr epiderrnai growth factor receptor cDNA sequence andakrant expression of the amplified gene in A431 epiderrrroid carcinoma cells. Nature309:418-25, 1984, Genentech, Inc., Dept. Molcc. Biol., San Francisco, CA; WeizrrrannInst. Sci., Dept. Chem. Irrmrunol., Rehovot, Israel; Imperial Cancer Res. Fund, ProteinChem. Lab,, London, UK. 85-2623

Urrarme E R, Beller D 1, Lu C Y & Allen P M. AnIigen presentation: comments on itsregulation and mechanism. J, hrrrnrmo/. 132:1-5, 1984, Harvard Univ., Med. Sch.,Boston, MA.

Varr de Werf F, Ludhruok P A, Bergmarm S R, Tiefenhrmrn A J, Fox K A A, deGeeat H, Veratraete M, Cohen D & S&d B E. Coronary rhrombcdysis with tissue-typepiasnrinogen activator in patienta with evolving mycardial irrfsrction. N, .ErrgL J. Med.310:609-13, 1984. Washington Univ., Sch. Med., St. Louis, MO; Univ. Lorrvain,Belgium. g5-0829

Vikner E, Rouzioux C, Brun F V, Flacher A, Chermann J C, Barre-Mmouaai F,Grrzengei C, Darrgrret C, Mardgne P, Griacefif C & Morrtaguier L. Isolation of newlymphotropic retrovirus from two sibiings with hemophilia B, one with AIDS. Izrrrcet1:753-7, 1984, Hosp. Chdd. Dis., Pediat, Irmnunol. Hematol. Unit; Pasteur Inst., Dept,Virol,; Claude Bernard Hosp., Cent. Virol, Lab., Paris, Frmrce. 84-1914, 85-i 825

Walker G C. Mutagenesis and inducible responses to deoxyribonucleic acid damage inEscherichiu crrli. Mkrobiol. Rev. 48:60-93, 1984. MIT, Dept. Biol., Cambridge, MA,85-0730

Wefahona W V, Liebermnn M E & Gorskf J. Nuciear localization of urrrrccupiedoesrrogen receptors. Mrfrwe 307:747-9, 1984. Univ. Wisconsin, Depts. Biocbem., HurrrarrOncol,, and Arrirm Sci., Madison, WI. 84-6753, 85-0822

Yammmka M, Greenberg B, Johrraon L, Seifhamer J, Brewer M, Frkdernarm ‘1’, MillerJ, Atlas S, I.aragh J, Lewkid J & Fiddea J. Cloning and sequence analysis of thecDNA for the rat atrial natriuretic factor precursor. Nature 309:719-22, 1984. CsfifomiaBiotcchnol, Inc., Mmrntain View, CA; Cornell Univ. Med. COIL, Hypertension Ctr.; NYHosp., New York, NY. 85-1307

Yanagi Y, Yaafdkaf Y, Leggett K, Clark S P, Afekaander I & Mak T W. A humT<eil-s~ific cDNA cione enccdes a protein having extensive homology toirnrnunoglobulinchains. Narure 308:145-9, i984. Ontario Cancer Inst.; Univ. Toronto,Dept. Med. Biophys., Canada. 84-0i71, 85-0178

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