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The systemic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Appetite, body weight, and the presence of vomiting and/or diarrhea were monitored throughout the study. Renal function was monitored by measuring serum blood urea nitrogen (RUN) and creatinine concentrations, urine specific gravity, and creatinine clearance before each treatment. Electrocardiograms and echocardiograms were also done before each treatment. The cats were killed 3 weeks after the last treatment, and complete necropsies were performed. Partial or complete anorexia occurred in all cats with significant weight loss occurring after a cumulative doxorubicin dose of 150 mg/m2 BSA. Mild vomiting and diarrhea that required no treatment also occurred sporadically in all cats. Echocardiographic changes consistent with doxorubicin-induced cardiomyopathy occurred in four cats after cumulative doses of 170 to 240 mg/m2 BSA. Clinical heart disease and electrocardiographic changes were not observed. Subsequent histological examination revealed myocyte vacuolization and myocytolysis in all six hearts. Renal dysfunction, characterized by increasing azotemia with progressively more dilute urine, was detected in two cats. Mean creatinine clearance values also decreased significantly throughout the study. At necropsy, all cats had histological evidence of renal

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A ganglioside fraction isolated from pooled intestines from newborn to 4-week-old piglets, which we previously partially characterized and showed to specifically inhibit the binding of porcine rotavirus (OSU strain) to host cells (M. D. Rolsma, H. B. Gelberg, and M. S. Kuhlenschmidt, J. Virol. 68:258–268, 1994), was further purified and found to contain two major monosialogangliosides. Each ganglioside was purified to apparent homogeneity, and their carbohydrate structure was examined by high-pH anion-exchange chromatography coupled with pulsed amperometric detection and fast atom bombardment mass spectroscopy. Both gangliosides possessed a sialyllactose oligosaccharide moiety characteristic of GM3gangliosides. Compositional analyses indicated that each ganglioside was composed of sialic acid, galactose, glucose, and sphingosine in approximately a 1:1:1:1 molar ratio. Each ganglioside differed, however, in the type of sialic acid residue it contained. AnN-glycolylneuraminic acid (NeuGc) moiety was found in the more polar porcine GM3, whereas the less polar GM3 species contained N-acetylneuraminic acid (NeuAc). Both NeuGcGM3 and NeuAcGM3 displayed dose-dependent inhibition of virus binding to host cells. NeuGcGM3 was approximately two to three times more effective than NeuAcGM3 in blocking virus binding. Inhibition of binding occurred with as little as 400 pmol of NeuGcGM3/50 ng of virus (∼2 × 107virions) and 2 × 106 cells/ml. Fifty percent inhibition of binding was achieved with 0.64 and 1.5 μM NeuGcGM3 and NeuAcGM3, respectively. The free oligosaccharides 3′- and 6′-sialyllactose inhibited binding 50% at millimolar concentrations, which were nearly 1,000 times the concentration of intact gangliosides required for the same degree of inhibition. Direct binding of infectious, triple-layer rotavirus particles, but not noninfectious, double-layered rotavirus particles, to NeuGcGM3 and NeuAcGM3 was demonstrated by using a thin-layer chromatographic overlay assay. NeuGcGM3and NeuAcGM3 inhibited virus infectivity of MA-104 cells by 50% at concentrations of 3.97 and 9.84 μM, respectively. NeuGcGM3 (700 nmol/g [dry weight] of intestine) was found to be the predominant enterocyte ganglioside (comprising 75% of the total lipid-bound sialic acid) in neonatal piglets, followed by NeuAcGM3 (200 nmol/g [dry weight] of intestine). NeuGcGM3 and NeuAcGM3 together comprised nearly 100% of the lipid-bound sialic acid in the neonatal intestine, but their quantities rapidly diminished during the first 5 weeks of life. These data support the hypothesis that porcine NeuGcGM3 and NeuAcGM3 are physiologically relevant receptors for porcine rotavirus (OSU strain). Further support for this hypothesis was obtained from virus binding studies using mutant or neuraminidase-treated cell lines. Lec-2 cells, a mutant clone of CHO cells characterized by a 90% reduction in sialyllation of its glycoconjugates, bound less than 5% of the virus compared to control cell binding. In contrast, Lec-1 cells, a mutant CHO clone characterized by a deficiency in glycosylation of N-linked oligosaccharides, still bound rotavirus. Furthermore, exogenous addition of NeuGcGM3 to the Lec-2 mutant cells restored their ability to bind rotavirus in amounts equivalent to that of their parent (CHO) cell line. In the virus-permissive MA-104 cell line, NeuGcGM3 was also able to partially restore rotavirus infectivity in neuraminidase-treated cells. These data suggest that gangliosides play a major role in recognition of host cells by porcine rotavirus (OSU strain).

Th e morphologic cha nges in idiopathic epilepsy ar e largely conside red to be the result of epileptic attacks, but th e lesio ns them selves may ca use seizures . Similar lesion s are also indu ced by hypoxic cond itions.s-' In so me cases , the seiz ure activity and th e conseq uent ischemi c events may play a role in the development oflesion s occurr ing in status epilepticus;' howe ver , in ano ther stud y on experime ntal epilepsy, the strict control of blood pressure and oxygen ten sion has not been a ble to prevent th e formation of brain lesion s." On ce produ ced , th e lesions may become an epileptoge nic focus, resulting in extensive brain dam age.' Pythi osis in th e hor se is usuall y a local subcutaneous infection, o ften accompanied by cutaneo us ulceration and fistul ou s tracts. It is cha rac terized by the presen ce of exuberant gran ulation tissue containi ng granular yellow or yellow-gray cores called " leeches" or " kunke rs." ? Eosi no phils are the most com mon inflamma to ry cell, and the cores consist of degen erat ing or necrotic eos inophilic debri s. A mark ed gra nulom atou s reac tio n usually is present around th e cores.' Recently, two cases ofequine enteric pyth iosi s were describ ed .':' In both cases , there was a steno tic jej una l mass th at consis ted of den se fibrou s connective tissue, contai ning granulomas or necroti c cores that were surro unded by gra nulomato us inflammati on . In one case , va riably int en se infiltrates of eosino phils were present. ' We describe a case of equine enteric pythi osis in which eosino phils were the pred om inant inflammat ory cell. ReferencesA 7-year-old Arabian geld ing was presented to th e U niversity of Illinois Veteri nary Teaching Hospital with a 36-hou r history of colic th at failed to respond to medical treatment. Rectal palp at ion revealed colonic im pactio n. Large bowel tym pa ny develop ed , and the horse was taken to surgery. A ventral midline laparot om y revealed three ab no rmal ities: an impacti on of the diaphragmati c flexur e, gastric and large bowel tympan y, and a mid-j ejunal intramural soft tissue mass. After correcting the tympan y and colonic obstructio n, approx ima tely 42 ern of th e jejunum, including th e mass, were removed and an anas to mosis perform ed. T he hor se recovered un event fully and was doing well, wit h no furt her episodes of colic, 1.5 years after surgery .T he jej un al mass was nodular , in tra mural, measur ed 3 x 4 x 5 em, and occ upied 320 0 of th e intestina l circum ference . T he overlying mu co sa was ulcerated with green-bro wn fibri llar mat erial th at adh ered to th e ulcerated surface . Histologica lly there was focally extensive mu cosal ulcerati on ove rlying mu ltip le irr egularl y shaped , 2-to 7-m m diam eter intra m uscular nodules. T he nodules consisted of a central core of gra nular eos ino philic debris (predo mi na ntly necrot ic eosi no phils) surro unded by degenerat ing eos ino phils and neut rophils with a few macroph ages and an occasiona l mu ltinucl...