AFIP Wednesday Slide Conference - No. 24
March 17, 1999

Conference Moderator:
Dr. Corrie Brown, Diplomate, ACVP
Chairman, Department of Pathology
College of Veterinary Medicine
University of Georgia
Athens, Georgia 30602-7388
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Case I - E95481 (AFIP 2642606)

Signalment: Seven-year-old, breed unspecified, male horse.
History: In the course of epidemic control of glanders on a number of Turkish islands, 1,128 horses were examined using the intracutaneous mallein test. Thirty-five horses (3.1%) showed a positive reaction. Ten of these horses were killed, and glanders was confirmed in five cases by lesions and demonstration of Burkholderia mallei antigen.
Gross Pathology: Bloody, purulent exudate was found in the nasal cavity and paranasal sinuses. Beneath the exudate there were yellowish-white, firm, nodules which measured up to 3 mm in diameter. Larger foci were found, which tended to become confluent and ulcerated. The bases of the ulcers were granulated and had irregular borders. Identical lesions were found in the nostrils and upper lip.
Laboratory Results: Burkholderia mallei antigen was found in the mucous membrane of the nasal septum and the conchae by immunohistochemistry.
Contributor's Diagnosis and Comments: Acute inflammation of nasal mucous membranes with marked thrombosis of large venous vessels, infiltration of mucosa and submucosa with neutrophilic granulocytes and macrophages, and ulcers.

Etiology: Burkholderia mallei (glanders).
Clinical and pathological findings in the case presented here, and in the other identified horses, indicated that lesions were restricted to the mucous membranes of the nasal cavity, its parasinuses, the nostrils, and the upper lips. The histological findings were characterized by acute inflammation; the lack of chronic features of inflammation, such as epithelioid cells, lymphocytes, and fibrous connective tissue was striking. Karyorrhexis, the previous "pathognostic" feature of a glanderous lesion, was not present. The study, which combined mallein testing with histopathology and immunohistochemistry, demonstrated the presence of Burkholderia mallei in horses and proved that glanders is endemic in certain parts of Turkey. There were no recent reports of infections in humans.
In experimental infections of the Syrian hamster with B. mallei, the inflammatory reaction is similar, at least in the nasal cavity (e.g. vasculitis). Concerning other organs, the natural equine cases cannot be compared due to the lack of lesions in corresponding organs in the horses. In the experimental case cited, a thorough study of the glanders bacillus was done. The study of the submitted case was limited to the identification of bacterial antigen in the natural cases of equine glanders by immunohistochemistry.
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Case 24-1. Low power view has necrosis and inflammation of nasal mucosa and thrombosis of nasal vessels. Larger thrombus demonstrates lines of Zahn (layers of fibrin, wbcs, platelets, RBCs, etc). Higher power view of vessel wall infiltrated and replaced by mostly degenerate neutrophils and fibrin. Lines of Zahn are seen more clearly on the left.
AFIP Diagnosis: Nasal conchae: Rhinitis, necrotizing, suppurative, diffuse, severe, with multiple thrombi and vasculitis, breed unspecified, equine.
Conference Note: Burkholderia mallei, the cause of glanders and farcy, is a small, aerobic, nonsporulating, gram-negative bacillus. It is an obligate parasite found principally in Asia, North Africa, and Eastern Europe. The bacterium primarily infects horses and donkeys, and the nasal sinuses, lungs, and skin of the extremities are the usual sites of involvement. The respiratory form of disease is commonly referred to as "glanders", while cutaneous disease is commonly known as "farcy". B. mallei is zoonotic, and humans become infected through contact with the organism in the laboratory or via infected animals. Infection in humans may cause acute, fatal pyemia or chronic granulomatous disease. Dogs and cats have also been infected. The disease was officially eradicated from the United States in 1937.
Infection in equidae usually occurs through ingestion or aspiration of material contaminated with the bacteria. Infection is spread by discharges of actively infected animals and subclinical carriers, often around feed bunks and watering troughs. Contamination of skin lesions and abrasions may also result in infection. After ingestion, bacteria invade the intestinal wall and localize in the lungs, skin, nasal mucosa, and other viscera. Humans and carnivores may be infected through ingestion of the organism, such as by consumption of contaminated horse meat, or by contact of mucous membranes with exudates containing the bacteria.
The severity of clinical signs and lesions in equidae is dependent upon the species infected and the virulence of the bacterial strain. Glanders is an acute, severe, systemic disease in donkeys and mules. The high mortality rate is usually due to bronchopneumonia. In horses, glanders is often chronic and may be subclinical. In all forms of the disease, pathological findings are characterized by poorly encapsulated pyogranulomas which spread locally or disseminate along lymphatics. In the nasal form, spreading nodular lesions occur which ulcerate the mucosa and may perforate the septum. A unilateral or bilateral, yellow, nasal discharge is frequently observed, and is highly infectious. Healed nasal ulcers may appear as stellate-shaped scars. In the cutaneous form, multiple, pyogranulomatous nodules occur along lymphatics which become enlarged and filled with purulent material, known as "farcy pipes"; rupture of the nodules, which contain tenacious exudate and organisms, frequently occurs. The pulmonary form is characterized by variable numbers of pyogranulomatous lesions scattered throughout the lung parenchyma; few pulmonary nodules are found in subclinical carriers, while more extensive lung involvement occurs in fatal cases. Regional lymph node involvement is common, and orchitis may occur.
Contributor: Institut of Veterinary Pathology, University of Munich, Veterinarstr. 13, Munich, Germany 80539.
1. Arun S, et al.: Equine glanders in Turkey. Vet Rec 144:255-258, 1999.
2. Alibasoglu M, et al.: Malleus-Ausbruch bei lowen im zoologischen garten Istanbul. Berl Munch Tierarztl Wschr 99:57-63, 1986.
3. Al-Izzi SA, et al.: In vitro susceptibility of Pseudomonas mallei to antimicrobial agents. Comp Immun Microbiol Infect Dis 12:5-8, 1989.
4. Al-Kafawi AA, et al.: Haematological changes in Arabian horses infected with glanders. Vet Rec 101:427, 1977.
5. Major Verma RA: Glanders in India with special reference to incidence and epidemiology. Indian Vet Journal 58:177-183, 1981.
6. Zubaidy AJ, et al.: Pathology of glanders in Iraq. Vet Pathol 15:566-568, 1978.
7. Jones TC, RD Hunt, King NW: Diseases caused by bacteria. In: Veterinary Pathology, 6th edition, pp. 450-451, Williams and Wilkins, Baltimore, MD, 1997.
8. Brown C: The respiratory system: Glanders. In: Equine Medicine and Surgery, Colahan PT, et al., eds., 5th ed., pp. 536-538, Mosby, Inc., St. Louis, MO, 1999.
9. Logas DB, Barbet JL: Integument: Diseases characterized by granulomatous draining nodules or masses. In: Equine Medicine and Surgery, Colahan PT, et al., eds., 5th ed., page 1886, Mosby Inc., St. Louis, MO, 1999.

Case II - 197072 (AFIP 2658217)

Signalment: Four-month-old, male, Saanen kid, caprine.

History: The kid was submitted for postmortem examination with a history of mild fever (40.8°C), mild dyspnea, and cough. Several other kids in the herd were showing similar clinical signs.
Gross Pathology: On postmortem examination, multifocal erosions were present on the oral mucosa of the hard and soft palate. Small amounts of blood-stained contents were found in the gastrointestinal tract, especially in the large intestine. In the respiratory tract, multifocal hemorrhage and ulceration of the laryngeal mucosa were present with flakes of mucopurulent discharge. The lungs were partially consolidated, especially the anteroventral lung lobes.

Laboratory Results: Peste des petits ruminants was diagnosed by immunofluorescence, PCR, and AGPT.
Contributor's Diagnosis and Comments: Lung: Bronchopneumonia, subacute, diffuse, severe, with necrotizing bronchiolitis, type II pneumocyte hyperplasia, syncytial cells, and intranuclear and intracytoplasmic eosinophilic inclusions in airway epithelial cells.
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Case 24-2. Lung. Alveolar septa are thickened by hypertrophic type II pneumocytes, and alveoli are often filled with cellular debris and rare multinucleate giant syncytial cells bearing bright pink intranuclear and intracytoplasmic inclusions.
AFIP Diagnosis: Lung: Pneumonia, broncho-interstitial, necrotizing, subacute, diffuse, severe, with type II pneumocyte and bronchiolar epithelial hyperplasia, syncytial cells, and eosinophilic intranuclear and intracytoplasmic inclusion bodies, Saanen, caprine, etiology consistent with peste des petits ruminants virus.
Conference Note: Peste des petits ruminants (PPR), a contagious viral disease of sheep and goats, is similar clinically and pathologically to rinderpest in cattle and frequently manifests as diarrhea, stomatitis, oculonasal discharge, and pneumonia. The causative pathogen is a morbillivirus of the family Paramyxoviridae. In natural infections, the virus causes disease in goats and sheep, but not cattle or swine. Goats are considered to be more susceptible than sheep, but this is not always true. Morbilliviruses are important pathogens of humans and animals; in addition to PPR, classic members of this genus cause rinderpest in cattle, distemper in dogs, and measles in humans. Phocine and cetacean morbilliviruses have been described recently.
PPR is an economically important disease that was first reported in the Ivory Coast of Africa in 1942, and has since spread east to parts of Asia, including India and Pakistan. The African and Asian strains seem to be antigenically distinct. There is current concern that the virus may pose a serious threat to endangered wild goats and sheep in the Himalayas through contact with infected domestic sheep and goats. Transmission occurs by inhalation of aerosols from closely associated animals, by direct contact through licking and nuzzling, and occasionally through fomites such as water troughs and feed bunks recently used by infected animals.
Pathological changes associated with PPR include erosive stomatitis and enterocolitis, similar to that of rinderpest in cattle, and proliferative and necrotizing broncho-interstitial pneumonia. Lymphoid depletion or necrosis occurs in the spleen, Peyer's patches, and lymph nodes. In fatal cases, pneumonia may not be as severe in younger goats (less than 4 months) than in older animals (over 6-7 months), probably because young kids succumb to dehydration caused by diarrhea before pulmonary lesions can fully develop.
PPR-induced pneumonia shares several histologic features with the lung lesions of distemper in dogs and measles in humans. Broncho-interstitial pneumonia occurs, and characteristic large, multinucleate (syncytial) cells containing intracytoplasmic and intranuclear inclusions are found within alveoli and terminal bronchioles. Secondary bacterial infections are also common.
Contributor: Ministry of Agriculture and Rural Development, Veterinary Services, Kimron Veterinary Institute, PO Box 12, Beit Dagan, Israel 50250.
1. Taylor WP, Busaidy A, Barrett T: The epidemiology of peste des petits ruminant in Sultanate of Oman. Vet Microbiol 22:341-352, 1990.
2. Barker IK, Van Dreumel AA, Palmer N: The alimentary system. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th ed., vol. 2, page 162, Academic Press, San Diego, CA, 1993.
3. Kulkarni DD, et al.: Peste des petits ruminants in goats in India. Vet Rec 138:187-188, 1996.
4. Amjad H, et al.: Peste des petits ruminants in goats in Pakistan. Vet Rec 139:118-119, 1996.
5. Brown CC, Mariner JC, Olander HJ: An immunohistochemical study of the pneumonia caused by peste des petits ruminants virus. Vet Pathol 28:166-170, 1991.
6. Rossiter PB, Taylor WP: Peste des petits ruminants. In: Infectious Diseases of Livestock, Coetzer JA, Thomson GR, Tustin RC, eds., pp. 758-763, Oxford University Press, Cape Town, South Africa, 1994.
7. Jones TC, RD Hunt, NW King: Diseases caused by viruses. In: Veterinary Pathology, 6th edition, pp. 310-320, Williams and Wilkins, Baltimore, MD, 1997.

Case III - M37 (AFIP 2648323)

Signalment: 18-month-old, female, European, shorthair cat.
History: An outdoor, unvaccinated cat was presented with a five day history of fever (40oC) and anorexia associated with the onset of diffuse swelling of the right mammary gland. The mammary glands were firm, painful, and focally ulcerated. All four limbs were severely edematous. The health status declined rapidly, and the animal was euthanatized. A necropsy was not performed.
Gross Pathology: See clinical description above.
Laboratory Results: None.
Contributor's Diagnoses and Comments:
1. Dermatitis, hyperplastic, ulcerative, chronic, with intracytoplasmic eosinophilic inclusion bodies (feline poxvirus).
2. Mastitis and panniculitis, pyogranulomatous, necrotizing, chronic-active, with intranuclear inclusion bodies.
Lesions typical of epidermotropic poxvirus infection were present, i.e. epidermal hyperplasia, ballooning degeneration of keratinocytes, and presence of numerous, variably-sized, intracytoplasmic eosinophilic bodies. Ultrastructurally, these inclusions were made up of large (300-450 nm) mature virions within a protein-rich material ("A-type inclusions"). Early viral particles were scattered within the cytoplasm.
The epidermal ulceration was associated with severe, deep, pyogranulomatous, necrotizing panniculitis and mastitis. Within this inflammatory process, nuclei of reactive histiocytes and fibroblastic cells were enlarged and contained basophilic to amphophilic intranuclear inclusion bodies. The inclusions occasionally filled the nucleus, which was delineated by a thin rim of chromatin. These nuclear changes suggest a viral infection such as herpesvirus. Ultrastructural studies are on-going to determine their nature.
The Poxviridae are highly epitheliotropic DNA viruses causing cutaneous and systemic disease in birds, wild and domestic mammals, and humans. Feline poxvirus infection, first reported in 1978, is recognized with increasing frequency in Europe, usually in the autumn. Cats are thought to become infected through bites sustained during hunting of wild rodents, which are considered to be the natural reservoir. Transmission of poxviruses from rodents to man through the domestic cat may become of zoonotic significance, particularly since the cessation of smallpox vaccination. Cat-related human poxvirus infections have been reported, including one with a fatal outcome in an immunosuppressed patient.

About 50% of infected cats develop a single, cutaneous, bite-like, ulceration on the head, neck, forelimbs or paws. Secondary skin lesions develop 4 to 16 days later and consist of multiple (more than 10), firm, 2 to 3 mm nodules, enlarging over 2 to 3 days to form up to 2 cm ulcerated papules. Oral mucosal ulcerations and systemic signs are uncommon. Most cats recover in 1 to 2 months; however, death has been reported in cats with evidence of feline leukemia virus infection and in cats treated with glucocorticoids. In this case, the cat developed systemic signs leading to euthanasia. Although no laboratory work-up was done (such as FeLV and FIV testing), the rapid health deterioration and the probable dual viral infection suggest an immunodeficient status.
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Case 24-3. Haired skin. The dermis and subcutis beneath a thickened epidermis is expanded by edema and infiltrating inflammatory cells which surround and separate normal dermal elements. High power of the epidermis illustrates multiple brightly eosinophilic intracytoplasmic inclusions within keratinocytes, multifocal neutrophilci infiltrates, and parakeratotic hyperkeratosis.
Case 24-3. Several intracytoplasmic inclusions within a degenerating cell contain multiple electron dense dumbell shaped virions characteristic of poxvirus.
AFIP Diagnosis: Haired skin: Dermatitis, proliferative and necrotizing, diffuse, moderate, with neutrophilic, histiocytic, hemorrhagic, and fibrinous panniculitis, necrotizing vasculitis, and eosinophilic intracytoplasmic epithelial, fibroblastic, and histiocytic inclusions, Domestic Shorthair, feline.
Conference Note: Conference participants generally agreed with the histopathologic findings described by the contributor. However, attendees did not identify intranuclear viral inclusions within histiocytes and fibroblasts. Rather, participants interpreted the nuclear structures as prominent nucleoli or clumped chromatin associated with degenerative or reactive changes. Viral particles were not identified within nuclei in ultrastructural studies performed by the contributor subsequent to the submission of the case to the Wednesday Slide Conference; the contributor subsequently interpreted the nuclear changes as degenerative.
Contributor: Laboratoires Pfizer, BP 159, 37401 - Amboise Cédex, France.
1. Bennett M, et al.: Poxvirus infection in the domestic cat: Some clinical and epidemiological observations. Vet Record 118:387-390, 1986.
2. Eis-Hübinger AM, et al.: Fatal cowpox-like virus infection transmitted by cat. Lancet 336:880, 1990.
3. Gaskell RM, et al.: Natural and experimental pox virus infection in the domestic cat. Vet Record 112:164-170, 1983.
4. Nowotny N: The domestic cat: A possible transmitter of viruses from rodents to man. Lancet 343:921, 1994.
5. Thomsett LR, Baxby D, Denham EMH: Cowpox in the domestic cat. Vet Record 103:567, 1978.
6. Stolz W: Characteristic but unfamiliar the cowpox infection, transmitted by a domestic cat. Dermatology 193:140-143, 1996.
7. Yager J, Scott D: The skin and appendages. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th ed., vol. 1, pp. 633-635, Academic Press, San Diego, CA, 1993.
8. Nowotny N: [Serologic studies of domestic cats for potential human pathogenic virus infections from wild rodents]. Zentralb Hyg Umweltmed 198:452-461, 1996.
9. Czerny CP, et al.: Characterization of a cowpox-like orthopoxvirus which had caused a lethal infection in man. Arch Virol Suppl 13:13-24, 1997.

Case IV - TAMU 1998 2 (AFIP 2641894)

Signalment: Yearling, male white-tailed deer (Odocoileus virginianus).
History: The deer was admitted with a 7-10 day history of lethargy and anorexia. No diagnosis was made; however, the deer broke with a watery diarrhea. Pieces of what were interpreted to be sloughed mucosa were passed in the feces. The animal was not febrile and was euthanized in extremis.
Gross Pathology: Ascites (200 ml of clear fluid) and intestinal serosal petechiae were noted. There was a fibrinous cast in the terminal half of the small intestines, the cecum, rectum and spiral colon.
Laboratory Results:
1. WBC: 1100
2. Total protein: 3.5 g/dl
Tests for bovine viral diarrhea virus, Salmonella sp., and Clostridium sp. (specifically for Clostridium difficile and its toxin) were negative. PCR of the spleen for malignant catarrhal fever (MCF) was positive.
Contributor's Diagnosis and Comments: Acute necrotizing enterocolitis.

Etiology: Malignant Catarrhal Fever (MCF).
This deer was raised in captivity on a sheep farm, an epidemiologic feature of histories of US cattle affected with MCF. In addition to laboratory tests, further support for the MCF diagnosis was provided by histology. There was vasculitis of several organs and lymphoblastic infiltration of the choroid plexus (without encephalitis and vasculitis of the brain; see figure 4 of Wobeser reference). The hemogram also suggested a viral infection.
The etiologic agent for endemic MCF of the US has not been isolated, and it is presumed to be a herpesvirus. Herpesvirus particles have been seen in tissues from naturally occurring disease. In the US, cattle affected with MCF typically have anterior uveitis, a mucopurulent oculonasal discharge, muzzle and oral erosions, and a high fever. Diarrhea is also described with this disease. "Milky eye" (anterior uveitis) and a progressive CNS syndrome with fever and a variety of lesions and signs are described in MCF affected deer on exotic game ranches in Texas, but there is variability to the syndrome seen (see references).
This deer's clinical disease is similar to that described for white-tailed deer. The enterocolitis is typical of that seen with severe viral enteritis, and using one's imagination, there are numerous "herpesvirus-like" inclusions in enterocytes. Lesions of MCF in Asian deer species are different and sometimes suggest that the agent of MCF may be oncogenic.
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Case 24-4. Small intestine. Thickened, blunted villi are expanded by abundant lymphocytes, macrophages, and fewer eosinophils. The hypertrophic, vacuolated endothelium of a small arteriole is infiltrated by lymphocytes and neutrophils.
AFIP Diagnosis: Small intestine and colon: Enterocolitis, subacute, diffuse, severe, with follicular lymphoid depletion, transmural edema, crypt abscesses, and crypt necrosis, loss, and regeneration, white-tailed deer (Odocoileus virginianus), cervid.
Conference Note: Malignant catarrhal fever (MCF) is a systemic, frequently fatal, viral disease of cattle and various other ruminants. Two forms of the disease occur which are clinicopathologically similar, but epidemiologically distinct. One form occurs in susceptible animals that commingle with wildebeest (a member of the subfamily Alcephaline), and is known as wildebeest derived-MCF; the causative agent is alcelaphine herpesvirus-1 and is foreign to the United States. The second form, endemic in the US, occurs in animals in contact with sheep. Sheep-associated MCF is caused by ovine herpesvirus-2 (OHV-2), a g-herpesvirus. It shares genetic and biological characteristics with alcelaphine herpesvirus-1 and herpesvirus saimiri.10
White-tailed deer are experimentally susceptible to both forms of MCF, and several natural infections have been reported. Compared to cattle, the disease in deer is more acute, infected animals may have fewer clinical signs prior to death, the lesions are more hemorrhagic, and there is increased visceral involvement. In deer, gastrointestinal and myocardial lesions are prominent; these are seen less frequently in cattle succumbing to MCF.
Several findings described by the contributor are consistent with previous reports of sheep-associated MCF in deer: a history of close association with sheep; clinical signs of lethargy, anorexia, and watery diarrhea; lymphoblastic infiltration of the choroid plexus; and the results of the laboratory tests. Like the contributor, all participants identified severe necrotizing enterocolitis. In some sections, there is mild necrotizing vasculitis affecting some medium-sized arterioles in the submucosa and serosa. However, participants did not identify fibrinoid degeneration of vessels, prominent perivascular inflammatory infiltrates, or proliferation of lymphoblastic cells in the mucosa or submucosa; these histologic features have been used to distinguish sheep-associated MCF from other infectious agents with similar clinicopathological presentations, especially other viral etiologies. Conference participants considered bluetongue, epizootic hemorrhagic disease, bovine viral diarrhea, and colibacillosis in the differential diagnosis for the intestinal lesions.
Contributor: Texas A&M University, Department of Veterinary Pathobiology, College of Veterinary Medicine, College Station, TX 77843-4467.
1. Blake JE, Nielson NO, Heuschele WP: Lymphoproliferation in captive wild ruminants affected with malignant catarrhal fever: 25 cases (1977-1985). J Amer Vet Med Assoc 196:1141-1143, 1990.
2. Clark K, Adams LG: Viral particles associated with malignant catarrhal fever in deer. Amer J Vet Res 37:837-840, 1976.
3. Clark K, Robinson RM, Marburger RG, Jones LP, Orchard JM: Malignant catarrhal fever in Texas cervids. J Wildl Dis 6:376-383, 1970.
4. Clark K, Robinson RM, Weishuhn LL: Further observations on malignant catarrhal fever in Texas deer. J Wildl Dis 8:72-74, 1972.
5. Liggitt HD, DeMartini JC: The pathomorphology of malignant catarrhal fever. I. Generalized lymphoid vasculitis. Vet Pathol 17:58-72, 1980.
6. Liggitt HD, DeMartini JC: The pathomorphology of malignant catarrhal fever. II. Multisystemic epithelial lesions. Vet Pathol 17:73-83, 1980.
7. Liggitt HD, DeMartini JC, McChesney AE, Pierson RE, Storz J: Experimental transmission of malignant catarrhal fever in cattle: Gross and histopathologic changes. Amer J Vet Res 39:1249-1257, 1978.
8. Wobeser G, Majka JA, Mills JHL: A disease resembling malignant catarrhal fever in captive white-tailed deer in Saskatchewan. Can Vet Journal 14:106-109, 1973.
9. Brown CC, Bloss LL: An epizootic of malignant catarrhal fever in a large captive herd of white-tailed deer (Odocoileus virginianus). J Wildl Dis 28:301-305, 1992.
10. Schock A, Collins RA, Reid HW: Phenotype, growth regulation and cytokine transcription in ovine herpesvirus-2 (OHV-2)-infected bovine T-cell lines. Vet Immunol Immunopathol 66:67-81, 1998.
Course Coordinator:
Ed Stevens, DVM
Captain, United States Army
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.
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