,gg/ml), penicillin (50 units/ml), and streptomycin (50 ,g/ml).Six to eight vessels were collected and subsequently processed for culture within 2 hr. and amphotericin B (2.5 sug/ml). During each wash, the vessel was clamped and the medium within the vessel was agitated gently by inverting the vessel four times. The pooled effluents containing the freed endothelial cells were distributed evenly among 75-cm2 glass or plastic petri dishes (10 ml per dish), and the cells were incubated at 370 in a humidified atmosphere of 5% CO2 in air. The medium was changed in all cultures every 3 days. For subculture, cells were treated briefly (1-2 min) with a calcium-and magnesium-free buffered saline containing trypsin (0.25%) and EDTA (0.05%). Released cells were seeded in new petri plates and the medium was changed 4-6 hr after the trypsin-EDTA treatment.Cultures established in this manner from calf aortae have been identified as endothelial by light and electron microscopic criteria, and the growth of the cells has been characterized. These data are described elsewheret.Endothelial cultures from human umbilical veins were derived by standard methods (1, 2), and human diploid fibroblast cultures were established from foreskins as described (13).Collagen Synthesis. Monolayers of primary cultures of endothelial cells (approximately 7 days after isolation, three to five cell generations in vitro) were incubated in a buffered balanced salt solution (14) supplemented with fetal bovine serum (10%), glucose (5 mg/ml), BME vitamins and amino acids (Gibco), glutamine (1 mM), ascorbic acid (50 ug/ml), 13-aminopropionitrile (50 jg/ml), and either [U-14C]proline (2 gCi/ml; 200 mCi/mmol) or [U-14C]lysine (1IuCi/ml; 342 mCi/mmol). After 48 hr the incubation medium and cell fractions were separated and calf skin collagen was added as carrier. Incorporation of total 14C into nondialyzable protein was determined after extensive dialysis against 0.1% sodium dodecyl sulfate in 0.1% sodium phosphate, pH 7.4 (NaDodSO4/PJ). 4-Hydroxy[14C]-proline was quantitated in this material by the method of Juva and Prockop (15). For gel chromatography and gel electrophoresis, the newly synthesized collagen in the medium was precipitated with ammonium sulfate (176 mg/ml). This ret E. Macarak, B. V. Howard, and N. A. Kefalides, manuscript submitted. 2361

Historical data are presented for neoplasms and related proliferative lesions from 1,170 Sprague-Dawley rats that served as controls in 9 carcinogenicity (2 year) studies conducted in the Safety Evaluation Facility of Ciba-Geigy Corporation, Summit, New Jersey. The most common neoplasm was pituitary adenoma, which occurred in 62.2% of the male and 84.7% of the female rats. Incidences of other neoplasms that occurred in more than 6.0% of the rats were, for males, benign pheochromocytoma (19.0%), cutaneous keratoacanthoma (7.9%), pancreatic islet cell adenoma (7.5%), benign testicular interstitial cell tumor (6.5%), and thyroid C-cell adenoma (6.5%). For females these incidences were mammary fibroadenoma (31.3%), mammary adenocarcinoma (16.8%), and mammary adenoma (6.5%). Focal cortical hypertrophy/cystic degeneration of the adrenal, a focal nonneoplastic lesion of zona fasciculata cells that often degenerate into large cysts, was present in 23.4% of all male and 82.7% of all female rats. Criteria for the differential diagnoses of selected neoplasms and related lesions are presented.

Abstract. Acute renal papillary necrosis occurred in five horses given normal therapeutic doses of phenylbutazone and deprived of water for 36 to 48 hours prior to euthanasia. Five horses given phenylbutazone alone and four horses subjected to water deprivation alone did not develop papillary necrosis. Urinalyses were normal prior to water deprivation, and also after water deprivation in the horses that did not receive phenylbutazone, but the waterdeprived, phenylbutazone-treated horses had many red blood cells, transitional epithelial cells, and large numbers of oxalate crystals in their urine.Ulceration of the alimentary tract was seen in more than 50% of these horses. Tongue ulceration was present in one of five horses given phenylbutazone and one of five horses which had phenylbutazone and water deprivation. Ulceration of the gastric mucosa was seen in two of the five phenylbutazone-treated horses, four of five horses with phenylbutazone treatment and water deprivation, and one of four horses with water deprivation alone. Severe colonic ulceration with perforation and peritonitis was present in one horse given phenylbutazone for three months. No other significant changes in the small or large intestine were seen in the other 13 horses.It generally has been thought that phenylbutazone is not toxic to horses [ 10, 151, although deaths have resulted from its use in man [ 15 I. Recently, however, severe adverse effects have been described in eight of ten ponies given normal therapeutic doses of phenylbutazone [20]. It was concluded that ponies were much more susceptible than horses to severe side effects during phenylbutazone treatment [3, 201. Ulceration of the alimentary canal is a relatively common side effect of phenylbutazone therapy in equidae [5, 6, 10, 20, 211 and other species [15, 191, and recently gastrointestinal protein loss has been reported in both horses and ponies [2 11. Although there is decreased urinary excretion of sodium and chloride [ 11, and raised blood urea nitrogen has been noted [20], no renal lesions have been described in any of these studies [l, 5, 6, 10, 20, 211. Renal papillary necrosis has been seen, however, in a series of 16 horses in which therapy with antiprostaglandin drugs, mostly phenylbutazone, was an almost constant feature, as was dehydration or impaired water intake [8]. The present study was undertaken to determine 603

Cartilage degeneration in osteoarthritis is initiated by a loss of proteoglycan. Intra-articular injection of papain causes a reversible loss of proteoglycan in rabbit knees. Rabbits were scanned with magnetic resonance imaging (MRI), using a 1.5T Signa superconducting magnet with 3 inch surface coil. Spin echo sequences were performed in the coronal and sagittal planes at 0, 24, 48, and 72 h after intra-articular injection of papain to obtain T1, proton density, and T2-weighted images. Cartilage proteoglycan content was measured biochemically and histochemically. Reduced articular cartilage thickness in the MR images of papain-treated knees corresponded to changes in cartilage proteoglycan content.

Abstract. Seven foals aged 18 days to 3% months had either single or multiple fullcircumference segments or long antimesenteric bands of necrotizing duodenitis, sharply delineated from adjacent viable duodenum. Perforation of the necrotic wall had occurred in all foals, leading to acute fibrinous peritonitis. On the mucosal surface severe, diffuse, acute inflammation and ulceration involved the anterior half of the duodenum. Two further foals, aged 28 and 30 days, had lesions that are believed to be a chronic form of this disease. Both foals had a thickened duodenal wall, with large areas of mucosa replaced by granulation tissue. In addition one had several strictures associated with firm adhesions between the duodenal serosa and adjacent structures, together with ascending cholangiohepatitis and pancreatitis. Eight foals had gastric ulcers that were considered to be of less significance than the duodenal lesions. No etiologic agent could be found by aerobic or anaerobic bacterial culturing, negative contrast electron microscopy for viruses, or immunofluorescence staining for equine herpesvirus 1, equine adenovirus, or equine coronavirus. The possible involvement of non-steroidal anti-inflammatory drugs is discussed.Perforating gastric ulcers have been described as uncommon lesions in foals [6]. Recently gastric ulceration has been described in foals as a clinical entity [5, 81 and either an associated duodenal perforating ulcer or duodenal ulceration with stricture was noted in some cases.We describe primary ulcerative duodenitis in foals, in its acute necrotizing, perforating form as well as in its chronic form with duodenal strictures. Case HistoriesCase histories are summarized in table I. Four foals came from one large breeding farm (farm A) in one season, while the other cases were the only foals affected on this farm and other large breeding farms with approximately 100 foals in the next season. Foals I , 5 , and 6 received phenylbutazone for lameness for a few days to a week before death. As part of the treatment for the terminal illness, foals I , 4, 5 , and 8 were given antibiotics and foals 1, 2, 4, 5 , 7, 8, and 9 were given flunixin meglumine. Abdominocentesis was done on foals 1, 2, 3, and 4. The fluid was yellow-green, contained 1,300 to 42,000 nucleated cells with wide variation between the proportions of lymphocytes and neutrophils, cells too degenerate to differentiate, and a variety of intracellular and extracellular bacteria. Foals 3, 4, 8, and 9 were euthanatized and foals 1. 2, 5 , 6, and 7 died.