Pathology of infectious diarrhea of infant rats (IDIR) induced by an antigenically distinct rotavirus.

Suckling rats were inoculated with a group B rotavirus to determine the progression of the morphologic changes induced in the intestine by this virus. Several changes were observed by light microscopy 1 day after viral inoculation: shortening of small intestinal villi, villous epithelial necrosis, and villous epithelial syncytia. The lesions were most often present in the distal small intestine, although other small intestinal segments were affected to a lesser degree. By day 3 post-inoculation, epithelial necrosis, and syncytia were no longer present; however, the villous epithelium was disorganized and irregularly vacuolated, and intestinal crypt epithelium was hyperplastic. Alterations in villous height to crypt depth ratios were present in portions of the small intestine for the remainder of the 12-day study period. Epithelial syncytia appeared to form by the breakdown of the lateral interdigitating membranes of the absorptive villous epithelium. Viral particles, abundant in the syncytia, appeared to form from amorphous or reticular arrays of viral precursor material. Group B rotaviral antigens, as detected by indirect immunofluorescence, were present in large amounts in the small intestinal villous epithelium only on the first day after viral inoculation. These studies show that two important diagnostic features of group B rotaviral infections of rats, epithelial syncytia and viral antigen as determined by immunofluorescence, are present only on the first day of disease. These findings should be taken into consideration when attempting to diagnose disease induced by this agent.

Infectious diarrhea of infant rats produced by a rotavirus-like agent.

During the investigation of an outbreak of diarrhea in suckling rats, a virus morphologically identical to but antigenically distinct from rotaviruses was identified. The disease was characterized clinically by erythema and cracking and bleeding of the perianal skin associated with the excretion of poorly formed fecal pellets, liquid, and gas. Light microscopy-observable changes consisted of small intestinal villous atrophy, villous epithelial necrosis, and villous epithelial syncytial cell formation. The cytoplasm of the epithelial syncytial cells contained large numbers of 80-nm viral particles that were often associated with reticular aggregates of electron-dense material. Viral infection principally involved the luminal one-fourth to one-third of the intestinal villi as determined by indirect immunofluorescence. This rotavirus-like agent contained 11 double-stranded RNA segments; however, the migration pattern of these segments in polyacrylamide gels differed from the electrophoretic pattern which is characteristic of the typical rotaviruses. The agent had a buoyant density in CsCl of 1.36 to 1.4 g/cm3 and was labile at pH 3 and at 56 degrees C; however, infectivity of viral inocula was not altered by extensive treatment with ether or by pH 5 buffers. This disease, which we have named infectious diarrhea of infant rats, is the first recognized viral diarrhea of rats and appears to be a good model for the study of the recently recognized group of atypical rotaviruses.

Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues.

Chemotherapeutic use of anthracycline antibiotics is limited by their cardiotoxic effects. A potential solution to this problem is the development of anthracycline analogues retaining antitumor efficacy but without cardiac toxicity. An isolated perfused rabbit heart model was used to compare the nature and extent of early ultrastructural effects on the myocyte of three anthracycline analogues purported to have lesser cardiotoxicity than Adriamycin (doxorubicin). Seventeen rabbit hearts were perfused with oxygenated Krebs-Ringer bicarbonate buffer at 39 degrees C containing either Adriamycin (4 mg/L), daunomycin (10.6 mg/L), aclacinomycin (8 mg/L), or rubidazone (17.6 mg/L). For comparison, three hearts each were exposed to phosphoramide mustard (14.7 mg or 25 mg/L) or 4-hydroperoxy cyclophosphamide (24 mg or 17 mg/L), two active congeners of cyclophosphamide, an agent interacting with DNA differently than the anthracyclines and which is known to be cardiotoxic in high dose. Two hearts were exposed to dactinomycin (0.1 mg or 0.2 mg/L) which intercalates with DNA in a manner similar to the anthracyclines but which is not cardiotoxic. Ten control hearts were perfused with oxygenated buffer solution only. Light microscopic study disclosed no differences between treated and control hearts. Electron microscopic examination showed a striking and distinctive clumping of nuclear chromatin with clearing of chromatin from the nuclear membrane in all anthracycline treated hearts but in no hearts treated with 4-hydroperoxy cyclophosphamide, phosphoramide Mustard, dactinomycin, or control hearts. The nuclear effects of the four anthracycline analogues were indistinguishable. Thus, all anthracycline analogues studied produced acute nuclear alterations which were distinctive from the changes produced by other DNA interactive chemotherapeutic agents. The relationship of the distinctive anthracycline nuclear changes to the late cardiomyopathy requires further definition.