James A. Baker Institute for Animal Health * ** * * * i »» This report honors those whose generosity sustains the Institute's quality and independence, its high ideals of excellence and responsibility in the challenge and pursuit of truth. A Message from the Director N ineteen seventy-eight w as a banner year for the Jam es A. Baker Institute. Im por­ tant ad van ces w ere m ade in our research; a n ew record w as established in the num ber of scientific publications em anating from the Institute; im provem ents w ere m ade in our daily operations; and tw o capital projects w ere initiated that will enable us to broaden our research and explore new avenues in the area of disease prevention. The results of our research are described in the following reports by m em bers of the Institute's senior staff. Som e of our findings are im m ediately relevant to the health and w ell-being of dogs. O thers have general significance in respect to disease problem s not only of dogs but of food-producing anim als and m an himself. T he form al record of our research accom p lish m en ts is contain ed in ou r list of publications. M any of these rep orts have been published in leading scientific jou r­ nals. They provide visible evidence of our productivity and the quality of our research and account in large m easure for increased recognition of the Institute and new support in the form of grants, con tracts, and gifts. A laboratory rep ort, Infectious Canine Enteritis Caused by a Corona-like Virus: Current Status and Request for Information, w as published this year. A copy of this report can be obtained by writing to the Institute or by telephoning M rs. Florence H uth (607/277-3044). In June 1977 the Institute w as certified by the A m erican A ssociation for Laboratory Anim al C are. We are one of the few institutions in N ew York State to be so accredited. Five m em bers of our animal care staff w ere certified this year by the Am erican A ssociation for Laboratory Animal Science, bringing the total num ber to seven . Mr. M ichael C h ap m an and his associates are to be congratu lated for these achievem ents, w hich bring great credit to the Institute. Im p ortan t im p rovem en ts w ere m ade in ou r central w ashing and sterilization facility. These im provem ents will enable M rs. Elizabeth W heeler and Miss Julie Jordan to provide investigators with the scrupulously clean glassw are needed for tissue culture and our research with viruses. Two projects w ere initiated that will have a significant im pact on our future a c­ tivities. The A dele S. C olgate Tissue Culture Laboratory will be m odernized and furnished with new equipm ent needed for the propagation and attenuation of viruses and for research using the relatively new tools of som atic cell genetics. We are deeply grateful to the Surdna Foundation for their generous gift that m ade this im provem ent possible. The second project becam e a reality w hen the N ational C ancer Institute aw arded the Baker Institute a gran t of m ore than $400,000. These m onies, given in recognition of ou r basic research , will be used to construct a facility w here laboratory anim als can be h ou sed in a p roper en viron m en t in an area adjacen t to the existing building. N ew ap p roach es to disease prevention will result from research con d u cted in the new facility. Above: Neil H. McLain directs the Institute's day-to-day functions. Above right: Sandy Borow receiving a research partner citation on behalf of the Finger Lakes Kennel Club in recognition of their outstanding support Right: Ann W. Signore's secretarial responsibilities in­ clude correspondence and the preparation of laboratory reports. Service to the public continued not only in the publication of our research findings but also in the participation of ou r staff in m eetings and sem inars th rou gh ou t the country. A visible exam ple of our concern for the practical problem s of disease w as the isolation by Drs. Leland Carm ichael and M ax Appel of tw o viruses responsible for several outbreaks of canine infectious enteritis. Work on these viruses, the nutritional requirem ents of dogs, hip dysplasia, and other diseases continues, but additional support is needed. The accom panying figure illustrates our increasing dependence on grants and contracts from the N ational Institutes of H ealth (NIH). A lthough this support has grow n in recent years, the NIH is concerned m ainly w ith hum an diseases; therefore support from this source will be m ore difficult to obtain in the future. O ur ability to pursue m eaningful research on canine diseases will depend in large m easure on the finan­ cial support of foundations, kennel clubs, and individuals w ho share our interest in im proving the health of dogs. We face the future confident in the ability of our w ell-trained staff to m eet the challenges of our changing research, academ ic, and econom ic environm ent. At the Institute w e are particularly fortu nate in being served by an ad visory council that provides m oral support, expert advice, and scientific guidance. W ith the added ingredients of m aterial support and understan ding from those interested in the w elfare of d ogs, w e will m aintain the tradition of excellence and service th at has characterized the activities of the Institute during the tw enty-eight years of its existence. D irector is 200 Staff Administration Douglas D. McGregor, director: B .A ., M .D ., University of Western Ontario; D.Phil., Oxford University Neil H. McLain, administrative manager: A .B., Cornell Nancy D. Combs, administrative aide Florence C. Huth, secretary Audrey E. Lowes, secretary: A. A., Paul Smith's College Ann W. Signore, secretary: Cornell Douglas S. Robson, consultant in statistics: B .S ., M .A ., Iowa State University; Ph.D ., Cornell Laboratories Giralda Laboratories for Canine Infectious Diseases Leland E. Carm ichael, John M. Olin Professor of Virology: A .B., D.V. M., University of California; Ph.D ., Cornell Ricardo Flores-Castro, graduate research assistant: D.V. M ., Universidad Nacional Autonoma de Mexico Geoffrey J. Letchworth III, graduate research assistant: B .S ., Trinity College; D.V. M ., Cornell Roy V. Pollock, graduate research assistant: B .A ., Williams College; D.V. M ., Cornell Priscilla H. Dunham, laboratory technician Jean C. Joubert, laboratory technician Daynemouth Laboratory for Canine Nutrition Ben E. Sheffy, Caspary Professor of Nutrition: B.S., M .S., Ph.D., University of Wisconsin Marc H. Langweiler, graduate research assistant: B .S ., D.V. M ., Cornell Alma J. W illiams, laboratory technician: B.A ., University of Pennsylvania; M .S., Cornell Biochemistry Laboratory for the Study of Canine Hip Dysplasia George Lust, associate professor of biochemistry: B .S., University of Massachusetts; Ph.D ., Cornell David J. Dueland, graduate research assistant: B.A ., University of Colorado Wayne T. Beilm an, laboratory technician: M .S., Cornell Joseph J. Bertone, laboratory technician: B.S., Cornell Peter W. Farrell, laboratory technician: B .S., Cornell Hadley C. Stephenson Laboratory for Study of Canine Diseases Max J. G. Appel, professor of virology: D r.m ed.vet., University of Hannover; Ph.D ., Cornell Shaw -chien Tsai, graduate research assistant: D.V. M ., National Taiwan University; M .S., Auburn University Mary Beth Metzgar, laboratory technician: University of Evansville Oswald R. Jones Laboratory of Immunology Robin G. Bell, research associate: B.Sc., Australian National University; P h.D ., John Curtin School of Medical Research Lincoln S. Adams, laboratory technician: B .S., Hobart College, AALAS accreditation James E. Gerb, laboratory technician: B.S., Bethany College Microbiology Laboratory Douglas D. McGregor, professor of immunology: B. A ., M .D ., D.Phil. Thomas W. Jungi, postdoctoral associate: B.A ., Kantonsschule Wetzikon, Switzerland; M .S., University of Zurich; D.Phil., University of Basel Melissa C. Woan, postdoctoral associate: B.Ed., Taiwan Normal University; M .S., Ph.D ., University of Illinois Arris J. Chapman, laboratory technician: A. A .S., Carnegie College Richard King Mellon Laboratory for Electron M icroscopy Helen A. Greisen, research associate: B.S., M .S., Ph.D ., Cornell Colgate Division for Tissue Culture Frederick A. Hinman, laboratory technician: B.A ., Ithaca College Glassware Department Elizabeth C. Wheeler, supervisor Julie Ann Jordan, junior laboratory technician Animal Care Charles B. Bailor, animal technician Roy L. Barriere, animal technician: AALAS accreditation Michael J. Chapman, vivarium supervisor: AALAS accreditation Bernard L. Clark, research technician James M. Ebel, animal technician James C. Hardy, research technician: B.S., Cornell Ronald A. Hayes, animal technician: AALAS accreditation Gerald W. Hiller, animal technician: AALAS accreditation David L. Watkins, animal technician: A. A .S., State University of New York, AALAS accreditation James E. Young, animal technician: AALAS accreditation Maintenance Edson Wheeler, maintenance supervisor Arthur D. Howser, experimentalist Gerald G. Rice, mechanic John C. Howe, custodian Giralda Laboratories for Canine Infectious Diseases M uch of our effort this year w as directed tow ard identifying the canine viruses responsible for contagious gastroenteritis. Several outbreaks w ere reported in the United States in 1978, the first occurring in the spring. These outbreaks w ere characterized by occasional vom iting and diarrhea, som etim es hem orrhagic, and occasional deaths. A canine coronavirus (CCV) w as isolated from stool specim ens. C om m on features of the CCV infection w ere a loose, putrid orangish stool, lack of significant fever, and recovery after one to three w eeks of interm ittent diarrhea. Six strains of CCV w ere isolated in prim ary dog kidney cell cultures (Cornell R esearch Laboratory for D iseases of D ogs, Laboratory Report Series 2, no. 9, July 1978). A second agen t, a parvoviru s, w as observed by electron m icroscop y in stool speci­ m ens from dogs with a m ore severe form of contagious gastroenteritis. The par­ vovirus family includes a variety of viruses, am ong them the causal agent of feline p a n leu k o p en ia. O u tb reak s w h ere th e can in e p a rv o v iru s (C PV ) h as b een fou n d in great num bers in stool sam ples are characterized by severe vom iting, fever ( 1 0 3 105°F), a m arked decrease in circulating w hite blood cells (leukopenia), and d estru c­ tion of cells lining the intestinal tract. Rapid d eh yd ration m ay occur, especially in puppies, leading to death. Intestinal lesions are similar to those caused by the feline parvovirus (feline panleukem ia virus). Intranuclear inclusion bodies have been observed in som e cases. CPV app ears to be highly contagious, especially w here dogs are closely confined. A close antigenic relationship exists betw een the CPV and feline panleukopenia virus, suggesting reciprocal protective immunity. Current research on infectious canine viral gastroenteritis at the Institute, with Drs. Appel and G reisen, gives priority to developing m ethods for isolating, grow ing, and quantitating the viruses; developing serological procedures for diagnosis; defin­ ing the clinical and pathological m anifestations of disease; locating the principal grow th sites of each virus and determ ining the duration of viral shedding; charac­ terizing the im m une response; and developing appropriate im m unizing agents. O ur research continued on another disease, canine brucellosis. The extent of the problem of diagnosing brucellosis in the dog w as revealed in a review of diagnostic m ethods available. We m ade significant progress tow ard establishing reliable serological criteria for diagnosing the disease. We tested more than four thousand canine sera: samples subm itted to the laboratory and sam ples collected over three years from experim en­ tally infected beagles m aintained at the Institute. The results forced us to conclude that w hen used alone, none of the serological m eth od s in com m on use is adeq u ate to definitively d iagn ose brucellosis. Such a d iagn o sis can be m a d e only by isolating the cau sal a g e n t, B. canis, from the blood. H ow ever, by em ploying an im m unodiffusion (ID) test that u ses a B. canis cell wall extract as antigen, one can judge field sam ples with 85-p ercen t accuracy. The diagnostic effort should include at least screening of sera by the rapid slideagglutination test (SAT). A negative result w ith this test is reliable, but a positive result is not. M ore than half of SAT-positive sera contain antibodies that crossreact with antigens shared by other organism s. Sera positive by the SAT always require additional study. A tw o -stag e screening of all SA T-positive sera is re co m ­ m en d ed . The tube agglutination test (TAT), w ith or w ithout the addition of 2-m ercap toeth an ol, is a valuable com p lem entary procedure. Fu rther analysis of SAT- and TAT-positive sera by ID tests provides the best chance for accurate diagnosis. This p roced u re is especially im p ortan t in chronically infected d ogs, w h ere a tte m p ts to isolate B. canis are often u n su ccessfu l. W e are n o w tryin g to isolate, sep arate, and purify B. can/s cell wall an tigen s to im p rove the specificity of ID tests for canine brucellosis. We continue to investigate the m echanism s w hereby the grow th of bovine herpesvirus-2 (m am m illitis virus) is restricted under various environm ental and physiological conditions. R esearch by Dr. Letchw orth has d em on strated that the virus can grow at skin tem peratu res but not at internal body tem p eratures. Reasons for this fact are becom ing apparent as we explore local cell-m ediated im m uneresponse m echanism s under controlled conditions. We observed diminished im ­ mune functions such as m onocyte chem otaxis, lym phocyte blastogenesis, and production of interferon at tem p eratures norm ally prevailing in the skin. Leland E. Carm ichael L eft: Canine p a r v o v ir u s , m a g n ifie d x 1 6 5 ,0 0 0 Daynemouth Laboratory for Canine Nutrition The D aynem outh Laboratory continued to study the role of vitam in E and selenium (Se) in canine nutrition. Earlier findings w ere substantiated: d ogs deficient in vitam in E and Se either did not respond or responded poorly to vaccination with distem per and infectious canine hepatitis vaccines. In vitro studies undertaken by Dr. L angw eiler revealed that this w eak resp on se w as associated w ith the p resen ce of a factor (or factors) in the serum of E-Se-deficient dogs that inhibits the proliferation of canine lym phocytes in cultures containing the phytom itogen PH A . Inhibition w as reversed by adding vitam in E to the diet or to the serum of deficient dogs. These studies continue as w e attem pt to isolate, purify, and identify the suppressor factor (or factors). Two other phenom ena w ere observed in E-Se-deficient dogs: derm atoses and retinal atrophy. Skin lesions developed in d ogs fed deficient diets that w ere high in polyunsaturated fats. Giving vitam in E or Se could prevent or delay the develop­ m en t of disease but w as less effective in anim als w ith established lesions. Dr. Riis dem onstrated a novel abnormality, central retinal atrophy, in E-Se-deficient dogs. H istological exam ination revealed the p resen ce of lipid d eposits in the retinal epithelium and degeneration of photoreceptors. The anim als w ere night-blind. In studies of lym phocytes from E-Se-sufficient dogs the addition of vitam in E to the diet in am ounts larger than published m inim um requirem ents significantly in­ creased the responsiveness of lym phocytes to m itogens. This observation has en­ couraged us to begin an investigation of the effects of vitam in E and Se supplem en­ tation on the response of puppies to distem per and infectious hepatitis vaccination. O ur nutrition research also addressed a practical question of dog breeders: Can vitam in C prevent or cure hip dysplasia? The vitam in C studies w ere undertaken in co llab oration w ith Dr. L u st a n d his asso ciates in th e B ioch em istry L ab o ra to ry for the Study of Canine H ip D ysplasia. D ogs can synthesize vitam in C in am ounts suffi­ cient to m eet their norm al m etabolic requirem ents. Labrador retrievers fed a diet lacking vitam in C m aintained constant levels of the vitam in in their plasm a and tissues and excreted an average of 0 .8 7 m g of vitam in C per kg of body w eight in their urine. Addition of 1 g of vitam in C per kg of body w eight per day to the diet increased the plasm a level of C but did not increase its concentration in tissues. Evidently, m uch of the vitam in C in the diet w as either m etabolized, excreted in the urine, or not ab sorb ed . M ost im p ortan t, d ietary vitam in C h ad no beneficial effect in p reven tin g the developm ent of hip dysplasia or the osteoarthritis associated with this disease. Likewise, im m une-response m echanism s w ere either not favorably affected or w ere depressed by vitam in C. Thus recom m endations that canine diets be supplem ented with vitam in C for the purpose of preventing hip dysplasia or im proving im m une responsiveness are not justified. Ben E. Sheffy Biochemistry Laboratory for the Study of Canine Hip Dysplasia Canine hip dysplasia is an inherited developm ental m alform ation of the coxofem oral joints. A characteristic feature of the disease is hip joint loosen ess, a term that is used synonym ously w ith joint laxity, subluxation, or m alarticulation. Joint looseness can be judged by m anipulating the fem oral head. Displacem ent of the fem oral head can also be dem onstrated by X -ray exam ination of the hip joint. O ur research this year centered on p ro­ viding a com prehensive description of hip joint laxity in Labrador retrievers that sh ow rad io lo g ical ev id en ce of hip dysplasia. We observed that loose joints contain an abnorm ally large am ount of synovial fluid. The accom panying table indicates that the volum e of synovial fluid is related to the degree of hip joint laxity as judged by m anipulation of the joint and radiological evidence of displacem ent of the fem oral head. Degree of Laxity N orm al Mild M oderate Severe Volume of Synovial Fluid (ml) 0.2 0.5 1.2 4.5 O ur exam ination of the relationship betw een synovial fluid volum e and hip joint laxity led to som e astonishing findings. We observed that the hip joint becam e tigh ter w h en th e synovial fluid is rem o v ed . In d eed , som e d ysp lastic joints sh ow ed norm al laxity w hen the fluid w as aspirated through a needle inserted into the joint space. R em oving the fluid apparently creates a vacuum that prevents displacem ent of the fem oral head. In circum stances w here the joint rem ained abnorm ally loose after fluid w as rem oved , w e found that the round ligam ent w as stretched and sw ollen . These findings encourage speculation about the processes underlying the develop­ m ent of hip dysplasia. A n increase in synovial fluid in the hip joint m ight allow the fem oral h ead to m ove m ore freely, setting in train processes that result in the d estru ctio n of tissu e an d th e d ev e lo p m e n t of o steo arth ritis. T h ese p ro ce sse s o ccu r in dogs genetically p red isp osed to the disease. H ow this genetic m akeup is exp ressed in the structure and function of the hip joint and w hat factors favor the accum ulation of synovial fluid in dysplastic joints are the subjects of continuing studies. George Lust Hadley C. Stephenson Laboratory for Study of Canine Diseases Infectious enteritis in dogs has been ascribed to at least tw o viruses, a canine corona virus (CCV) and a canine parvovirus (CPV). Several outbreaks of gastroen­ teritis linked to infection by CCV w ere reported in the U nited States this year, and CPV w as isolated from dogs with diarrhea, fever, and leukopenia. In light of these reports, we are undertaking a thorough study of canine viru s-in d u ced enteritis. O ur im m ediate objectives are to ascertain the prevalence of infection, the m ode of spread of CCV and CPV, the persistence of these viruses in infected dogs, and the im m une-response m echanism s associated with recovery from infection. We m ust define the dim ensions of the problem in order to develop effective vaccines for disease prevention. D istem per, of cou rse, is far m ore serious than viral enteritis. Effective vaccines against distem per are widely used, yet cases continue to be reported. A m ajor problem has been the difficulty of accurately diagnosing distem per w hen its only sign is encephalitis. D iagnosis often dep en d s on the results of serological tests. We recently identified a specific antibody to canine distem per virus (CDV) in the IgM fraction of serum up to three weeks after vaccination or up to three m onths after infection with virulent CDV. W e are now trying to develop sensitive m ethods to m easure this antibody so that we can provide a practical and reliable test for diagnosing distemper. W e are also investigating the role of cell-m ediated im m unity in host resistance to d istem p er. L a b o ra to ry te sts h av e sh o w n th a t a p articu lar class of ly m p h o cy te s (Tc) can kill C D V -in fected cells in an im m u n ologically specific w ay. W e also fou n d th at o th er ly m p h o cy te s ca n kill in fected ta rg e t cells by a m ech an ism th a t d o es n o t d ep en d o n th e sh arp d eg re e of reco g n itio n req u ired by Tc. T h ese “ n atu ral killer cells" are p resen t even in d ogs th at have n ever been exp osed to CDV. A different m ech an ism of p rotection involving interferon could be im p ortan t in m a n y viru s in fection s, in clu d in g d istem per. E x p erim en ts u n d ertak en by Dr. Tsai indicate that dogs can produce interferon in response to stim ulation by a synthetic polynucleotide or infection with N ew castle disease virus. We are now producing large am ounts of canine interferon to use in ascertaining the part played by inter­ feron in resistance to CDV. There have been tw o reports in the scientific literature that claim ed a relationship betw een dog ow nership and multiple sclerosis. A lthough the supporting evidence is w eak, the m atter is of deep con cern to dog ow n ers. Therefore w e h ave undertaken an epidem iological and serological study of the response of hum ans to the m ore com m on canine viruses. M ax J. G. Appel Oswald R. Jones Laboratory of Immunology Intestinal parasites are responsible for som e of the m ost com m on and debilitating diseases in anim als and h u m an s. O ur research is d irected to p reven tin g such diseases by d eveloping effective vaccin es. A n ecessary step is to identify antigens th at ca n in d u ce an im m u n e re sp o n se . It also is im p o rta n t to identify stag es in th e life cycle of parasites that are vulnerable to attack by antibodies or cells. The problem has been studied in rats infected w ith Trichinella spiralis, the parasite responsible for trichinosis. W e h a v e sh o w n th a t e x p o su re to eith er th e larval o r ad u lt stag es of T. spiralis can p rotect anim als again st infection. The im m unity ind u ced by larvae is effective m ainly against larvae, and th at indu ced by adult w orm s is effective against the adult. H ow ever, both respon ses are exp ressed in the expulsion of w orm s from the small intestine. This finding suggests the existence of at least tw o antigens that can induce a protective response. Two other responses have been identified by im m unizing with defined stages in the life cycle of T. spiralis: o n e re sp o n se im p airs re p ro d u ctio n by fem ale w o rm s an d another (rapid expulsion) prevents the establishm ent of larvae in their intestinal niche. These processes act synergistically to produce a high level of resistance. Knowledge of im m une processes gives us only the skeleton of a response pattern; understanding the m echanism s of these processes provides the flesh necessary for full com p reh en sion . W e are analyzing the m ech an ism s responsible for each of the fo u r d efen se re sp o n se s id en tified in an im als im m u n ized ag ain st T. spiralis. O ur studies so far have focused on rapid expulsion. This dram atic response can result within a few hours in the expulsion of up to 90 p ercen t of the w orm s in a challenge inoculum . In experim ents using parabiotic rats w e dem onstrated that rapid expulsion is an im m unological response; it cannot be ascribed m erely to a change in the norm al function of the intestine. Parabiotic rats are anim als that are surgically united and hence share a com m on blood circulation. Rapid expulsion can be transferred from one parabiont to another under these unusual conditions only w h en the intestine of the u nim m unized p artn er is subject to a secon d stim ulus. This stim u lu s is p ro v id e d by T. spiralis o r by th e antigen ically differen t p arasite Heligmosomoides polygyrus. This finding and m ore recent observations suggest that rapid expulsion involves tw o distinct p rocesses: an im m unological p rocess in w hich either antibodies or cells are involved and a process that depends on irritation of the intestine and has no im m unological basis. We are continuing to study this fascinating phenom enon with a view to identifying both the im m unological com ponent and the nature of the nonspecific stim ulus required for the full exp ression of this defense. Robin G . Bell Above: Thomas W. Jungi measuring the influence of infec­ tion on macrophage function Above right: The microbiology wing of the Institute, which houses modern laboratories for virus research Right: Melissa C. Woan preparing tissue culture medium Microbiology Laboratory O ur research on m echanism s of acquired resistance to infection continued with the goal of ascertaining how im m une animals recognize infectious agents and eliminate th em from the body. T hese p ro cesses have been studied in rats infected w ith Listeria monocytogenes, a bacterium know n for its capacity to survive and grow in m ac­ rop h ages. M any organ ism s are p h ag ocy tosed and killed in m acro p h ages, but som e can su rvive an d grow in this p otentially hostile en v iro n m en t. L. monocytogenes is a w ell-studied exam ple; others include the tubercle bacillus and the bacteria that cause brucellosis and typhoid fever. But the m acrophages of im m une anim als can kill th ese organ ism s or limit their g ro w th , th ereb y arrestin g th e p rog ressio n of disease. This defense reaction dep en d s for its full exp ression on the activity of T lym phoctyes, w hich are form ed as part of the anim al's im m une response to infection. O ur research and that of others have show n that L. monocytogenes can stim ulate the production of activated T cells in the lym ph nodes or spleen of infected anim als. These specifically sensitized lym phocytes m igrate to centers of infection, w here they are stim ulated by microbial antigens to release a variety of m olecules that have pow erful effects on m acrophages. Som e attract m acrophages and m ove lym pho­ cy tes to th e reaction site; o th ers en h an ce th e cap acity of m a cro p h a g e s to kill in gested organism s. A m ajor goal of our research is to understand how these im portant processes operate, for only with this know ledge can w e expect to im prove the capacity of anim als to defend them selves against a variety of infectious agen ts. The problem is being studied in rats, w here inbred strains can be used to ascertain the role of genetic factors in the interaction of T cells and m acrophages. T hom as W. Jungi Recovery from m any viral infections depends on the host's capacity to destroy infected cells. M acrophages and several classes of lym phocytes can recognize and kill cells th at h arb o r viru s a n d e x p re ss viral an tig en s on th eir su rface. But the relative im portance of each of these types of protective cells has not yet been determ ined, nor have the conditions been defined that favor the production of protective cells. The problem has been studied in ham sters and rabbits infected with vaccinia virus, the vaccine agent used to protect hum ans against sm allpox. M ethods w ere de­ veloped for m easuring the protective capacity of various types of cytotoxic effector cells. O ur data indicate that infection with a low dose of vaccinia virus stim ulates a cell-m ediated im m une response in w hich lym phocytes of the T cell class operate as specific m ediators of cytotoxicity. In con trast, infection with a large dose of virus stim ulates the form ation of both cytotoxic T cells and "n atu ral killer cells." The latter are p resen t in the tissues of norm al, nonim m u n ized subjects as well as in the tissues of im m une anim als. Further studies are under w ay to ascertain the part played by various types of cytotoxic cells in resisting infection. Melissa C. Woan Richard King Mellon Laboratory for Electron Microscopy O steoarthritis, often associated w ith canine hip dysplasia, is a m ajor cau se of discom fort and loss of function in affected anim als. A s part of our investigation of this disease w e are using the electron m icroscope to study the ultrastructural m orphology of the synovial m em brane from the joints of dysplastic dogs. Earlier studies w ith the light m icroscope show ed that a layer of cells on the surface of the m em b ran e facing the joint cavity thickens and form s fingerlike p rojections (villi) that protrude into the joint space. U sing the electron m icroscope, w e identified tw o distinct cell types in this region of the m em brane. The m ost conspicuous w as a fibroblast that has an extensive n et­ w ork of internal m em branes, the endoplasm ic reticulum . These cells m ay be the source of hyaluronic acid, found in high con cen tration in synovial fluid. The su g g es­ tion is based on the know ledge th at cells w ith a w ell-d evelop ed endoplasm ic reticulum often secrete large am ounts of protein, and the suspicion that hyaluronic acid is secreted in a similar way. The second cell type had the structural ch aracteris­ tics of a m acrop hage and w as found in sm aller num bers in the m em brane. The p u rp o se of ou r stu d y is to determ ine the relative num b ers of these tw o cell types in the norm al synovial m em brane and in the m em branes of diseased joints. By d ocu­ m enting th ese relationships and studying other chan ges in the m em b ran e, we expect to gain insight into pathogenic m echanism s underlying the developm ent of osteoarthritis. The electron m icroscop y laboratory also collaborated w ith other laboratories in the Institute in studies of canine distem per encephalitis and viral-induced gastroen­ teritis of dogs. Indeed, our finding tw o distinct viruses in fecal specim ens w as an early indication that m ore than one virus w as responsible for the outbreaks of gastroenteritis described elsew here in this report. O ne of these viruses had the structural characteristics of a corona virus; the other was a parvovirus. These studies continue as part of the Institute's effort to define these diseases and develop practical m ethods for their prevention. Helen A. Greisen Advisory Council Dr. Richard M. Johnson Dwight D. Eisenhower Professor of Neurology Johns Hopkins University Mr. John A. Lafore, Jr. Past president, American Kennel Club Hon. Gary A. Lee Congressional representative from New York State Dr. Irwin H. Lepow Chairman, Department of Medicine School of Medicine University of Connecticut Dr. Robert R. M arshak Dean, School of Veterinary Medicine University of Pennsylvania Mr. John M. Olin Honorary chairman, Board of Directors Olin Corporation Dr. Neil W. Pieper M rs. Richard M. Scaife Acknowledgments Your interest in the Jam es A. Baker Institute for A nim al H ealth, expressed by your gift, enables us to carry out our d ay-to-d ay m ission. W ith your support we can respond swiftly to opportunities as they arise and im prove the quality of anim al health. Your gift earns the Institute's deepest thanks. In appreciation for their exceptional interest in the Institute, w e should like to exp ress our gratitude to Mr. an d M rs. G ay lo rd D onnelley, M rs. Priscilla M axw ell E n d ico tt, Mr. Jo h n M . O lin, Mr. W illiam F. Stifel, and Mr. Robert W. W oodruff. Friends Dr. Sheldon B. Adler Miss Mildred Allen Miss Rosemarie T. Antonelli Mrs. Stevens Baird Mrs. Dudley Baker Mrs. Barbara Barty-King Mrs. Janet Baynton Mr. and Mrs. Stephen D. Bechtel Mr. and Mrs. Daniel Bennett Mrs. Mona Berger Mr. and Mrs. Walter A. Berry Ms. Wendy H. Bicknell Mrs. Paula T. Bliss Mrs. Patricia Boe Rev. and Mrs. Hans Boehringer Mr. and Mrs. Philip G. Bond Mr. and Mrs. Fred Bondi, Jr. Mr. and Mrs. Albert C. Bostwick Mrs. Marjorie Brandt Dr. and Mrs. Eben Breed Mr. Donald R. Brenneman Mr. and Mrs. William C. Brockschmidt Mr. Alanson C. Brown III Mrs. Frederick D. Brown Mr. and Mrs. George A. Burpee (in honor of Dr. Isidor Yasgur) Ms. Mary V. 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Wadsworth Mrs. Christine Wallace Ms. Terry Walters Mrs. Roberta L. Walton Mr. and Mrs. Harwood Warriner (in honor of Dr. Martin Fremont) Mrs. F. Carrington Weems Mr. Robert G. Wehle Mrs. Carolyn R. Wilson Dr. and Mrs. William W. Wimer III Mr. Dayle Wong Mr. Robert W. Woodruff Research Partners The designation research partner w as established eight years ago to h on or a gift of $250 or m ore a year. T h ose w h o h a v e m a d e a gift of $ 2 ,5 0 0 are in d icated by L. T. (lifetim e re se a rch p a rtn e r). The n a m e s of the research p artners are inscribed on a perm an ent plaque in the library of the Institute, as are those of our founders and longtime supporters. Dr. George R. Alfson Dr. Alan C. Baum (L.T.) Dr. Gary M. Baum (L.T.) Dr. Albert M. Beck Dr. Jack Bloch Dr. Dorothy E. Bradley (L.T.) Dr. and Mrs. Donald F. Buckley Dr. and Mrs. Kenneth W. Chamberlain, Jr. Dr. Robert E. Clark Dr. Clarence C. Combs, Jr. Dr. Margaret Combs Dr. and Mrs. William P. 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Levine Dr. Leonard R. Levine Dr. George Levy Dr. Anson C. Lewis Dr. Bertram Lewis Dr. Gilbert Lewis Dr. Jordan Lewis Dr. Norman F. Lewis Dr. Joseph J. Libra Dr. and Mrs. Bernard Lipman Dr. Alan A. Livingston Dr. Jeanne Newbecker Logue Dr. Robert A. Lopez Dr. Joan Peterson Lorenzen Dr. Jay Luger Dr. Seymour Lustig Dr. Donald R. Lynch Dr. Robert E. Lynk Dr. Alexander D. MacCallum Dr. Janet Meade MacCallum Dr. John F. McCarthy Dr. W. Kenneth McKersie Dr. Homer F. McMurray Dr. and Mrs. Edward A. Majilton Dr. and Mrs. Wilber C. Maker Dr. and Mrs. Robert V. Manning Dr. Donald B. Martin Dr. John J. Martin Dr. Robert S. Martin Dr. George E. Maurice Dr. Ronald F. Mayhew Dr. Warren W. Mead, Jr. Dr. James L. Meiczinger Dr. Morton Meisels Dr. and Mrs. Raphael Meisels Dr. Edward C. Melby, Jr. Dr. Henry C. Melius Dr. Thomas W. Melius, Jr. Dr. Alan S. Meyer Dr. Louis W. Mick Dr. and Mrs. Donald E. Mielke Dr. Robert K. Milkey Dr. Eugene G. Miller Dr. Michael H. 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Schuerger Dr. Alvin F. Schwartz Dr. Victor J. Schwartz Dr. and Mrs. Stephen H. Schwirck Dr. Wilbur R Schwobel Dr. Daniel W. Scott Dr. George H. Scott Dr. Alec C. Sears Dr. Frank A. Serra Dr. Joseph C. Shaffer Dr. Martin P. Shapiro Colonel Louis L. Shook Dr. Joseph G. Shute Dr. M. Christine Sidler Dr. Eric W. Simmons Dr. Norman Simon Dr. Norman E. Skinner Dr. Alcott L. Smith Dr. Arthur L. Smith Dr. Avery L. Smith Dr. Ernest K. Smith Dr. Lewis L. Smith Dr. Glen D. Snell, Jr. Dr. Brian Sorrell Dr. Hermann B. Stein Dr. John V. Steiner Dr. Edward F. Steinfeldt Dr. Alfred C. Steinhoff Dr. Edward W. Stewart Dr. Phillip B. Stewart Dr. Robert S. Stoll Dr. and Mrs. Garland D. Stone Dr. Richard L. Stone Dr. John J. Strickler Dr. Joseph Stuart Dr. Hugh P. Studdert Dr. William A. Sumner Dr. Johanna Asmus Sutorius Dr. John C. Sweatman Dr. Emanuel Tarlow Dr. and Mrs. Donald O. Taylor Dr. Robert D. Taylor, Jr. Dr. Theodore F. Taylor Dr. and Mrs. Joseph A. Thomas Dr. Robert W. Thomas Dr. Frederic B. 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Ziegler Dr. and Mrs. Irving Zimmerman Dr. Manuel Zimmerman Dr. Theodore Zimmerman Dr. William E. Zitek Dr. William J. Zontine Dr. Carl L. Zymet Clubs Allentown Dog Training Club, Inc.* American Bouvier des Flandres Club, Inc. American Boxer Club, Inc.* American Maltese Association, Inc.* American Sealyham Terrier Club Annapolis Kennel Club, Inc.* Australian Shepherd Club of Southern California, Inc. Back Mountain Kennel Club* Baltimore County Kennel Club, Inc.J Boxer Club of Long Island, Inc.* Bronx County Kennel Club California Collie Clan, Inc.* Catonsville Kennel Club, Inc.* Central Florida Kennel Club* Central Ohio Kennel Clubt Charles River Dog Training Club, Inc. Cheshire Kennel Club Cleveland Collie Club Collie Club of America, Inc.$ Collie Club of Central New York, Inc. Collie Club of Kentucky, Inc.* Contra Costa County Kennel Club, Inc. Detroit German Shepherd Obedience Training Clubt Devon Dog Show Association, Inc.t Dog Owners' Training Club of Maryland, Inc. 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Somerset Hills Kennel Club* South Texas Obedience Club Spartanburg Kennel Clubt Sussex Hills Kennel Club, Inc. Tappan Zee German Shepherd Dog Club, Inc.* Trenton Kennel Club* Tri-county Old English Sheepdog Club Upper Marlboro Kennel Club* Waukesha Kennel Club, Inc.* Westchester Kennel Club* West Highland White Terrier Club of America* Worcester County Kennel Club, Inc.:} •Gave $ 1 0 0 -$ 4 9 9 since January 1, 1978. tG a v e $ 5 0 0 -$ 9 9 9 since January 1, 1978. JG a v e $1,000 or m ore since January 1, 1978. Veterinary Associations Capital District Veterinary Medical Society Chautauqua County Veterinary Medical Society (in memory of Mr. Egil Jensen and Mrs. Wilford Sanderson) Hudson Valley Veterinary Medical Society, Inc. Long Island Veterinary Medical Association (in memory of Dr. Murray Lerner) Westchester-Rockland Veterinary Medical Association Women's Auxiliary to the Long Island Veterinary Medical Association Women's Auxiliary to the New York State Veterinary Medical Society Women's Auxiliary to the Veterinary Medical Association of New York City, Inc. Foundations and Trusts Albert C. Bostwick Foundation American Irish Setter Foundation C.A.L. Foundation Geraldine Rockefeller Dodge Foundation, Inc. Gaylord Donnelley Foundation Walter Kendall Trust Kroc Foundation Lakeside Foundation Louise Foundation James A. Macdonald Foundation John M. Olin Foundation Dr. J. E. Salsbury Foundation Surdna Foundation, Inc. Walnut Hall Foundation In Memoriam Dr. Peter I. Amsher Mr. William C. Baron Ms. Helen M. Bascom Dr. William Boardman Dr. William D. Clark Mrs. Helen E. Fleischmann Dr. Rudolph Frohlich, Jr. Mr. Edgar A. Giles Mr. E. Roland Harriman Mr. Egil Jensen Dr. Murray M. Lerner Mr. John M cLeod, Sr. Mr. Milton Muller Mr. Irving Newman Mr. John Neylon Ms. Alice Hannah Patterson Mr. Wilford Sanderson Companies Biozyme Medical Laboratories, Inc. Burns-Biotec Laboratories Division (Chromalloy Pharmaceutical, Inc.) Burroughs Wellcome and Company, Inc. Corning Glass Works Fort Dodge Laboratories, Inc. Gaines Dog Research Center General Foods Corporation Hoffman-LaRoche, Inc. Norden Laboratories Pfizer, Inc. Pitman-Moore Company Veterinaria AG, Zurich Publications Publications for the first ten years are listed in the Institute report for 1960. Those for each year thereafter appear in the annual report for that year. Since 1960, articles have been num bered con secu tively. S om e of th e follow ing p u b lication s h av e b een listed in a p rev io u s y ear's re p o rt as in press. They are repeated this year, w ith their original num bers, to record full bibliographic details. Articles com pleted during the past year are those num bered 431 to 459. 394 Jungi,T. W.: 1978. Evaluation of various filter membranes for Boyden-type leukocyte migration studies. ]. Immunol. Methods, 2 1 :3 7 3 —82. 395 Jungi, T. W., and McGregor, D. D .:1978. Impaired chemotactic responsiveness of macrophages from gnotobiotic rats. Infect. Immunity, 19:553—61. 396 Jungi, T. W., and McGregor, D. D .: 1978. Activated lymphocytes trigger lymphoblast extravasation. Cell. Immunol., 38:76 —83. 402 Lust, G .,a n d Miller, D. R .: 1978. Metabolic changes in cartilage from young dogs with degenerative joint disease. In The aetiopathogenesis of osteoarthrosis. Edited by G. Nuki. Pitman Medical Press, London. 403 Lust, G ., Farrell, P. W., and Sheffy, B. E .: 1978. Development of degenerative hip joint disease in young dogs. In Models for osteoarthrosis. Edited by G. Nuki. Pitman Medical Press, London. 413 Lefford, M. J ., and McGregor, D. D .: 1978. The lymphocyte mediators of delayed hypersensitivity: The early phase cells. Immunology, 3 4 :5 8 1 -9 0 . 428 Sheffy, B. E.: 1978. Nutrition and nutritional disorders. In Symposium on canine pediatrics. The Veterinary Clinics of North America, Vol. 8. W. B. Saunders, Philadelphia. 431 Appel, M .: 1978. Reversion to virulence of attenuated canine distemper virus in vivo and in vitro J Gen Virol., 4 1 :3 8 5 -3 9 3 . 432 Appel, M ., and Bemis, D. A .: 1978. The canine contagious respiratory disease complex (kennel cough). Cornell Vet., 68 (suppl. 7): 70 - 75. 433 Banta, C. A ., Clem ens, E. T., Krinsky, M. M ., and Sheffy, B. E. Sites of organic acid production and patterns of digesta m ovem ent in the gastrointestinal tract of dogs. ]. Nutr. In press. 434 Bell, R. G. Undernutrition, infection and immunity. The role of parasites. Papua New Guinea Med. ]. In press. 435 Bell, R. G ., McGregor, D. D ., and Despommier, D. D. Trichinella spiralis: Multiple, phase-specific, anti-parasite responses mediate the intestinal component of protective immunity in the rat. Exp. Parasitol. In press. 436 Carmichael, L. E.: 1978. Infectious canine enteritis caused by a corona-like virus: Current status and request for information. Cornell Research Laboratory for Diseases of Dogs, Lab. Rep., ser. 2, no. 9. 437 Carm ichael, L. E ., and M edic, B. L. S.: 1978. Small-plaque variant of canine herpesvirus with reduced pathogenicity for newborn pups. Infect. Immunity, 2 0 :1 0 8 -1 4 . 438 Flores-Castro, R ., and Carmichael, L. E.: 1978. Canine brucellosis: Current status of methods for diagnosis. Cornell Vet., 68 (suppl. 7): 7 6 —88. 439 Jungi, T. W., and McGregor, D. D .: 1978. Allogeneic restriction of acquired antimicrobial resistance in the rat. ]. Immunol., 121:449—55. 440 Jungi, T. W., and McGregor, D. D .: 1978. Allogeneic restriction of antimicrobial resistance and delayedtype hypersensitivity. Abstract. Annual Reunion of the Swiss Society for Allergology and Immunology. 441 Jungi, T. W., and McGregor, D. D .: 1978. Allogeneic restriction of the delayed inflammatory reaction in the rat. ]. Immunol., 121:456 —63. 442 Jungi, T. W., and McGregor, D. D. Dissociation of macrophage accumulation and local chemotactic activity in inflammatory sites. International Congress of Inflammation, Bologna. In press. 443 Jungi, T. W., and McGregor, D. D .: 1978. Evidence that Listeria-activated T cells provoke lymphoblast extravasation non-specifically. Abstract. Annual Reunion of the Swiss Society for Allergology and Im­ munology. 444 Kostiala, A. A. I., Lefford, M. J ., and McGregor, D. D. Immunological memory in tuberculosis. 2. Mediators of protective immunity, delayed hypersensitivity and macrophage migration inhibition in central lymph. Cell. Immunol. In press. 445 Lust, G ., Farrell, P. W., and Beilm an, W. T.: 1978. A tentative mechanism for development of osteoar­ thritis in dogs with hip dysplasia. Abstract. Proceedings of symposium: Studies in joint disease. London Hospital Medical College. 446 Lust, G ., Farrell, P. W., Sheffy, B. E ., and VanVleck, L. D .: 1978. An improved procedure for genetic selection against hip dysplasia in dogs. Cornell Vet., 68 (suppl. 7 ):4 1 —47. 447 McGregor, D. D ., Crum , E. D ., Jungi, T. W., and Bell, R. G. Transfer of immunity against Listeria monocytogenes by positively selected T cells. Infect. Immunity. In press. 448 Miller, D. R ., and Lust, G. Accumulation of procollagen in the degenerative articular cartilage of dogs with osteoarthritis. Biochim. Biophys. Acta. In press. 449 Nuki, G ., Pritchard, H. D ., Henderson, W. J ., and Lust, G .: 1978. Articular cartilage mineralization and inorganic pyrophosphate metabolism in chondrocytes. Europ. J. Rheumatol. Inflammation, 1:105—14. 450 Sheffy, B. E ., and Schultz, R. D .: 1977. 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Ways of Giving In establishing the Institute, of w hich the Cornell R esearch Laboratory for D iseases of D ogs is an im portant part, the Cornell U niversity Board of Trustees authorized the Treasurer's Office of Cornell U niversity to act as custodian of all funds given in support of the Institute. As a donor, you are thus assured your gift will achieve the m axim um benefit. There are m any w ays you can give to advance the w ork of the Institute. Som e of these opportunities offer substantial incom e tax and estate tax benefits. C h eck s. All checks should be m ade payable to Cornell U niversity and m ailed to: Office of the D irector Jam es A. Baker Institute for Animal Health Cornell University Ithaca, N ew York 14853 for the uses and purposes of the Cornell Research Laboratory for D iseases of Dogs. A ppreciated stocks. Selling appreciated stocks is alm ost certain to increase your taxes. You gain m axim um tax benefits by giving the stocks to Cornell outright and deducting their full current m arket value as a charitable contribution, thus avoiding capital gains tax. The transaction can be com pleted with m axim um speed and at low est cost by following these steps: 1. D ecide w h a t secu rities y o u w an t to give an d take th e certificate to y o u r bank o r broker. 2. Inform your bank or broker that you w ant to m ake a gift of these shares or securities to Cornell University for the Institute. 3. Instruct your bank or broker to telephone the Office of University Investm ents, at 607/277-0 022. 4. W rite a note to the Director, Jam es A. Baker Institute for Animal H ealth, Cornell University, Ithaca, N ew York 14853, including the nam e of your bank or broker and the form and size of your gift. D ep reciated stocks. You get m axim um benefit from a gift of stocks that have gone dow n in value by selling them and giving the cash proceeds to Cornell. This w ay you get the capital loss allow ance and a charitable contribution deduction for the total am ount of your gift. Instruct you r bank or broker to sell particular shares or securities for your account and send the proceeds as a gift to Cornell for the Jam es A. Baker Institute for Animal H ealth. B eq u ests. C haritable bequests provide substantial estate tax benefits. T hey can be m ad e in m any form s: gifts of land or buildings, securities, personal property, or cash. The U niversity counsel of Cornell U niversity suggests the follow ing provision in m aking a bequest for dog research : “ I hereby give, devise, and bequeath [description of property] to C ornell University, an educational corporation located at Ithaca, N ew York, for the uses and purposes of the Cornell Research Laboratory for Diseases of D ogs." D eferred giving — incom e-producing trusts. An incom e-producing trust enables you to m ake a m eaningful gift to the Institute, gain spendable incom e for life, and derive im p ortan t tax benefits. A beneficiary m ay be nam ed to receive this incom e, too. The Institute can offer three plans: the Pooled Life Incom e Fund for gifts of $5,000 or m ore, the A nnuity Trust, and the U nitrust for gifts of $50,000 or m ore. Currently each plan supports an incom e of about 7 percent a year. Financial planning involving deferred gifts is a highly com plex subject requiring exp ert advice from y o u r a tto rn e y an d o th e r sp ecialists. If yo u are in terested in this w ay of su p p o rtin g the Jam es A . B aker Institute for A nim al H ealth, please notify the director, w ho will m ake arrangem ents for you to receive m ore specific inform ation. Financial Situation To assu re d o n o rs th a t th eir fu n d s will su stain an d a d v an ce re se a rch on d o g s n o w an d in th e fu tu re, the Cornell U niversity Board of Trustees m ade a provision for disposal of excess incom e as follows: “The Institute's incom e is in excess of its operating exp en se, and the balance of the funds is ad d ed to the Institute's E n d o w m en t." July 1, 1977, to June 30, 1978 Funds Available Gifts and earnings budgeted State of N ew York general support State of N ew York dog license fees Federal grants $208,855 122,587 144,000 254,781 $730,223 Expenditures Salaries Operational costs $607,240 211,566 $818,806 Reserves used to balance budget $ 88,583 Research that involves species other than dogs is supported by other sources. Office of University Publications 279 4.5M BP