Nude rats as a model of natural Pneumocystis carinii pneumonia: sequential morphological study of lung lesions.

A spontaneous infection with Pneumocystis carinii (P.c.) caused enzootic fatal pneumonia in a long-term experiment with athymic Rowett Nude (Han:RNU rnu/rnu) and New Zealand Nude (Han:NZNU rnuN/rnuN) rats. In order to reproduce the infection and to characterize the early pathogenesis of lung lesions, 13 young athymic Han:RNU and Han:NZNU rats from P.c.-free breeding colonies were housed together in one room with chronically P.c.-infected rats. They were killed after 8, 12, 16, 20 or 24 weeks, and their lungs were examined for P.c. infection by means of light microscopy, immunohistochemistry and transmission electron microscopy. Lung lesions progressed from a mild interstitial pneumonia with scattered alveolar macrophages (8 weeks) to a severe diffuse interstitial pneumonia with widespread areas of distended alveoli, filled with foamy material. In all lungs, P.c. antigen was detected immunohistochemically, developing from small intra-alveolar aggregations of organisms into large multifocal clusters. Ultrastructurally, P.c. trophozoites and cysts were seen attached to type I pneumocytes and lying free in the alveolar lumen. Chronic severe P.c. pneumonia (20 and 24 weeks) was characterized by masses of P.c. trophozoites in the alveoli and alveolar walls, extensive proliferation of type II pneumocytes and interstitial fibrosis. The easy and consistent horizontal transmission of spontaneous P.c. pneumonia to previously non-infected athymic Han:RNU and Han:NZNU rats and the similarity of the disease to human infection demonstrate both rat strains to be excellent models for studying pulmonary pneumocystosis of immunodeficient human patients.

Intestinal lesions in experimental phocine distemper: light microscopy, immunohistochemistry and electron microscopy.

The involvement of the intestinal mucosa and of the gut-associated lymphoid tissue in phocine distemper was studied in six severely diseased harbour seals 11 to 16 days after experimental infection. Five seals exhibited a mild or moderate enteritis in the small or large intestine. In all the seals, a moderate to severe depletion of submucosal lymphoid follicles was found. Likewise, antigen of phocine distemper virus (PDV) was demonstrated immunohistochemically in the intestinal wall of all the seals. Most antigen was found in the submucosal lymphoid follicles, followed by the crypt epithelium and follicle-associated epithelium (FAE). Ultrastructurally, intracytoplasmic tubular structures were detected in the FAE and interpreted as morbilliviral nucleocapsids. The results indicate a direct cytopathogenic effect of PDV on intestinal lymphoid and epithelial cells and suggest an important role of the intestinal tract in phocine distemper and, by analogy, in other morbillivirus infections as a regular site of virus replication, virus shedding and immunosuppression.

Lewis rats of the inbred strain LEW/Han: life expectancy, spectrum and incidence of spontaneous neoplasms.

Although Lewis rats are frequently used in biomedical research, little is known about their life-data and spontaneous pathology. Therefore, it was the aim of this study to determine the life expectancy, spectrum and incidence of spontaneous neoplasms of the inbred rat strain LEW/Han. A total of 629 LEW/Han rats (305 females and 324 males) from a specified pathogen-free breeding colony were kept from weaning up to their natural death under defined environmental conditions. A complete histological examination was performed on all organs and macroscopically altered tissues of all animals which died during the first three years of the study. These were 296 female (98%) and 213 male (66%) rats. The mean lifespan of the females (27.7 +/- 5.1 months) was significantly shorter than that of the males (32.5 +/- 6.6 months). In both sexes, the lifespan was mainly determined by the occurrence of neoplasms. Of the large spectrum of 52 histologically different tumour types, the highest incidences were observed for adenomas of the pituitary gland and adenomas/adenocarcinomas of the adrenal cortex in both sexes, mammary gland tumours and endometrial carcinomas in females, and C-cell adenomas/adenocarcinomas of the thyroid gland and tumours of the haemopoietic system in males. Of these, the high incidences of tumours of the haemopoietic system in males (27.7%) and of endometrial carcinomas in females (45.2%) should be considered as characteristic features of the strain.

An improved technique for visually controlled pinealectomy in the rat.

An improved method for pinealectomizing rats and other small laboratory rodents is described which avoids bleeding and allows excision of the organ under exact visual control. After removing a small piece of the skull dorsal to the confluence of the transverse and dorsal sagittal sinuses, the latter is ligated and cut. The underlying pineal gland is then exposed and may be excised reliably without damage to the gland tissue or to adjacent brain structures. Intra- and post-operative complications are extremely rare.

[Infection with Bacillus piliformis (Tyzzer's disease) in foals]. / Infektion mit Bacillus piliformis (Tyzzer's disease) beim Fohlen.

Tyzzer's disease, caused by Bacillus piliformis and characterized by a multifocal, necrotizing hepatitis was diagnosed in a 25 days old, male, German warmblood foal. The animal was submitted to the clinic of horses because of colic symptoms and a severe depression. Upon arrival it was comatose, recumbent and showed opisthotonos. Due to a severe, metabolic acidosis and a rapid progression of the disease, the foal was euthanatized. In immediately formalin-fixed tissue samples Bacillus piliformis was detected in the cytoplasma of hepatocytes by different histological techniques (Giemsa stain, silver impregnation technique by Warthin-Starry, immunohistology). This case is discussed within a literature review.

History and pathology of an enzootic Pneumocystis carinii pneumonia in athymic Han:RNU and Han:NZNU rats.

A report is given on the history and pathology of an enzootic outbreak of spontaneous Pneumocystis carinii pneumonia (PCP) that occurred in a colony of male and female athymic Han:RNU rnu/rnu and Han:NZNU rnuN/rnuN rats maintained in a longevity study from weaning up to their natural death. The rats were obtained from specified pathogen free (SPF) breeding colonies and were kept in a barrier type animal quarter with standardized housing conditions. Groups of heterozygous, euthymic littermates in the same room remained unaffected. First cases of PCP were observed simultaneously in both stocks and both sexes when the rats were 15 to 18 months old. During the following 18 months, most of the animals developed pneumonia. Shortly prior to death the animals showed dyspnea and cachexia. Gross examination revealed focal or diffuse pulmonary consolidation. Histologically, characteristic lung lesions consisted of an interstitial pneumonia with perivascular and peribronchiolar infiltrations and with clusters of foamy macrophages within single or groups of alveoli. Most prominent in moderate and severe infections was an amorphous, honey-combed eosinophilic material within enlarged alveolar spaces. The diagnosis was based on the histological identification of Pneumocystis carinii (Pc) cysts in lung sections stained with Grocott's methenamine silver and was confirmed immunohistochemically. The evaluation of all evidence leads to the conclusion that Pc was introduced into the experimental colony by care-takers. The high incidence of PCP and its resemblance to human PCP indicate the suitability of athymic Han:RNU and Han:NZNU rats as natural models for this disease.

Total suppression of spontaneous endometrial carcinoma in BDII/Han rats by melengestrol acetate.

Female virgin BDII/Han rats develop spontaneous endometrial carcinoma (EC) in incidences up to 90%. Our objective was to determine whether lifelong administration of the progestin melengestrol acetate (MGA) would suppress those tumors. Four groups of 20 rats aged 24-28 days were employed Group I animals were untreated controls. Groups II, III, and IV were fed 0.1, 0.2, and 0.4 mg MGA/kg daily in their diet during their lifetimes. All treated groups were free from EC during their lifetimes with an increased lifespan up to 30%. The controls, in contrast, had an EC incidence of 85%. Histologically, with one exception all tumors were classified as adenocarcinoma. While most of the control rats died from EC, nearly all animals of groups II and III died from age-related diseases. Rats in group IV showed side effects due to the glucocorticoid properties of MGA. Besides alopecia and obesity an acceleration of chronic progressive nephrosis was observed. The study establishes the validity of the prophylactic approach to spontaneous hormone-dependent cancers in a rat tumor model.

Progression of renal failure in the Han: SPRD polycystic kidney rat.

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with incomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of progression have not been elucidated. To identify some pathogenetic factors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalapril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 animals per group) S-urea at age 150 days was consistently above 300 mg/dl, while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In castrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-211) compared to sham-operated male Han: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uninephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not significantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170; 140-195 in non-enalapril controls), although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S-urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to some extent. Uninephrectomy accelerates renal failure in the rat, but not in humans. On the other hand, in contrast to human ADPKD the renin system is suppressed in the rat model and ACE inhibition does not affect the course of renal failure.