Feline leukemia virus-induced erythroid aplasia: in vitro hemopoietic culture studies.

Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimately associated with macrophages. Kittens were inoculated with the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV) and sequential changes in marrow CFU determined. Erythroid aplasia, characterized by progressive non-regenerative anemia, lymphopenia, and a profound decrease in early and late CFUE but not CFUGM was induced by 3 to 5 weeks after FeLV-KT inoculation. The susceptibility of kittens to FeVL-induced erythroid aplasia was strongly age-related; neonatal kittens were most sensitive and substantial natural resistance developed by 4 weeks of age. The results demonstrate that FeLV-KT infection induced a rapid and selective suppression of erythroid progenitor cells and represents a suitable model of experimentally-induced acquired erythroid aplasia.

The tolerability and pharmacology of interleukin-6 administered in combination with GM-CSF or G-CSF in the rhesus monkey.

The tolerability and potential target organ toxicity of rhIL-6 administered subcutaneously (s.c.) with rhGM-CSF or rhG-CSF were investigated in healthy nonhuman primates. Fifteen Rhesus monkeys were randomized to receive one of the following five regimens: rhIL-6, rhGM-CSF, rhG-CSF, rhIL-6 and rhGM-CSF, or rhIL-6 and rhG-CSF. Each cytokine was administered s.c. once daily at 20 micrograms/kg/day for 30-31 days. Marked increases in blood leukocyte counts (predominantly neutrophils) were observed in the rhGM-CSF and rhG-CSF treatment groups, but only a mild trend toward increased WBCs was observed with rhIL-6 alone. Platelet counts increased 1.7- to 2.2-fold in the rhIL-6 and rhGM-CSF groups. All regimens were well tolerated. RhIL-6, alone or in combination with either CSF, had no significant toxic effects at the dosages tested. Minimal to moderate bone marrow hyperplasia was observed in all except rhIL-6-treated animals, which correlated well with peripheral blood increases in WBCs. RhIL-6-treated animals demonstrated increased fibrinogen concentrations and erythrocyte sedimentation rates, decreased serum albumin/globulin ratios, and increased serum alpha-2-macroglobulin concentrations. Increased synthesis of acute-phase proteins was not observed in the other groups. Combining rhIL-6 with rhGM-CSF or rhG-CSF may reduce the rhIL-6-mediated acute-phase response while maintaining the desirable hematopoietic effects of the stimulating factors.

Juvenile renal disease in related Standard Poodles.

Chronic renal failure was diagnosed in 6 young Standard Poodles from 2 related litters. Clinically, the disease was characterized by polydipsia, polyuria, anorexia, lethargy, vomiting, and bony deformities suggestive of fibrous osteodystrophy. Laboratory evaluation revealed azotemia and hypercholesterolemia in all 6 dogs and nonregenerative anemia in 3 dogs. Two dogs had hyperphosphatemia and another 2 were hypercalcemic. Isosthenuria and proteinuria were found in both dogs for which urinalyses were available. The kidneys were characterized pathologically by interstitial fibrosis, variable interstitial infiltrates of lymphocytes and plasma cells, tubular atrophy, tubular dilatation, tubular basement membrane mineralization, cystic glomerular atrophy, and immaturity of glomeruli, with inconspicuous capillary lumens.

Renal amyloidosis in related Abyssinian cats.

Renal amyloidosis was diagnosed in 8 related Abyssinian cats. The kidneys were characterized pathologically by medullary interstitial and glomerular amyloid deposition, interstitial fibrosis, and papillary necrosis. Amyloid deposits were birefringent under polarized light after Congo red staining, were thioflavine-T positive, and lost Congo red staining after permanganate oxidation. Four of the cats were evaluated clinically. Two of these cats were terminally uremic, with nonregenerative anemia, azotemia, hyperphosphatemia, metabolic acidosis, mild hyperglycemia, isosthenuria, proteinuria, cylindruria, and mild hematuria. The remaining 2 cats were only moderately azotemic. Three of the cats had severe gingivitis and all 4 cats had hyperproteinemia due to hyperglobulinemia.

Juvenile renal disease in Doberman Pinscher dogs.

Renal failure was diagnosed in 22 young Doberman Pinscher dogs. The clinical findings were anorexia, weight loss, vomiting, lethargy, polydipsia, polyuria, and dehydration. Laboratory findings were azotemia, hyperphosphatemia, lymphopenia, nonregenerative anemia, hypercholesterolemia, and proteinuria. The kidneys were characterized pathologically by glomerular sclerosis, cystic glomerular atrophy, tubular dilatation, tubular atrophy, mononuclear interstitial inflammation, interstitial fibrosis, interstitial mineralization, and hyperplasia of the collecting duct epithelium.

Flow cytometric and radioisotopic determinations of platelet survival time in normal cats and feline leukemia virus-infected cats.

This study demonstrates the potential usefulness of a flow cytometric technique to measure platelet survival time in cats utilizing autologous platelets labeled in vitro with fluorescein isothiocyanate (FITC). When compared with a 51Cr method, no significant differences in estimated survival times were found. Both the 51Cr and FITC-labeling procedures induced similar changes in platelet shape and collagen-induced aggregation. Platelets labeled with FITC had significantly greater volumes compared with those of glutaraldehyde-fixed platelets. These changes were primarily related to the platelet centrifugation and washing procedures rather than the labels themselves. This novel technique potentially has wide applicability to cell circulation time studies as flow cytometry equipment becomes more readily available. Problems with the technique are discussed. In a preliminary study of the platelet survival time in feline leukemia virus (FeLV)-infected cats, two of three cats had significantly reduced survival times using both flow cytometric and radioisotopic methods. These data suggest increased platelet turnover in FeLV-infected cats.

Simian adenoviral pneumonia.

In the past 6 years we have encountered 26 cases of fatal adenoviral pneumonia in six species of simian primates. O these, 22 animals were between 11 and 38 days old at the time of death, and pneumonia was the primary clinical disease. The spectrum of clinical disease varied from peracute fatal disease to inapparent disease with seroconversion. In one outbreak involving 4 infants housed together in an isolation unit, simian virus 11 was isolated from 3 of the infants and seroconversion occurred in all 4. At necropsy the lungs were voluminous, with firm gray areas of consolidation. On histopathologic examination, severe patchy necrotizing alveolitis and bronchiolitis were present. Variable edema and hyaline membrane formation, alveolar epithelial hyperplasia, and secondary bacterial pneumonia were also seen. Large basophilic intranuclear inclusions were present in bronchiolar and alveolar epithelial cells in all 26 cases. In 4 of 8 cases examined ultrastructurally typical intranuclear paracrystalline arrays of adenoviral virions were demonstrated. Intranuclear inclusion bodies were also observed occasionally in bile duct and pancreatic duct epithelium. Simian adenoviral pneumonia can be a spontaneous disease problem in laboratory-reared primates and offers excellent potential as an animal model of human adenoviral pneumonia.

Renal pathology of catheterized baboons (Papio cynocephalus).

Renal disease was found at necropsy in 27 of 60 catheterized baboons (Papio cynocephalus). Primary diagnoses were infarcts in eight baboons, septic embolic nephritis in four, and mesangioproliferative glomerulonephritis in 15. Infarcts and septic embolic nephritis are multifocal renal diseases; mesangioproliferative glomerulonephritis is diffuse, progressive and often accompanied by severe proteinuria, hypoalbuminemia (less than 3 g/dl), and generalized edema. Five of the 15 baboons with glomerulonephritis also developed uremia and died of renal failure. Ten baboons with glomerulonephritis were given microbiological examination during their clinical course. Bacteria were isolated from the peripheral blood of eight baboons and from the catheter itself in two. The organisms isolated (in decreasing order of frequency) were Herellea sp., Streptococcus sp., Klebsiella sp., Staphylococcus sp., and Providencia sp. Prospective immunofluorescence studies were done on frozen sections from six catheterized baboons with glomerulonephritis and two uncatheterized controls. There were granular deposits of IgG in all six, IgM in five, C3 in four, and IgA and C4 in two. In the controls, only trace amounts of IgM were seen in one animal. The amount of IgG deposited in th glomeruli correlated with the severity of the glomerulonephritis. Bacterial antigens were found by immunofluorescence in glomeruli of three of five baboons examined. Glomerulonephritis in these baboons seems to be immunologically mediated, and in origin, pathogenesis and morphologic expression resembles shunt nephritis in humans with infected indwelling shunts and catheters.

Spontaneous mesangioproliferative glomerulonephritis in pigtailed macaques (Macaca nemestrina).

Mesangioproliferative glomerulonephritis was found in 28 of 113 pigtailed macaques (Macaca nemestrina) that died in 1977. In five it was considered severe enough to cause significant renal dysfunction; in two of these it was the cause of death. The basic lesion was a proliferation of mesangial cells and deposition of mesangial matrix in the mesangial stalk, resulting in various degrees of stalk expansion and increased lobulation of the glomerular tuft. Preliminary immunofluorescence and ultrastructural studies suggests the pathogenesis of the lesion may involve deposition of antigen-IgM immune complexes in the mesangial region.

A quantitative one-dimensional magnetic resonance imaging technique in adjuvant arthritis: the assessment of disease progression and indomethacin efficacy.

OBJECTIVE: To demonstrate the use of a one-dimensional proton (1H) nuclear magnetic resonance (NMR) imaging technique to noninvasively monitor the progression of adjuvant arthritis and its response to indomethacin treatment in Lewis rat leg joints. METHODS: The total hydrogen content of a defined volume of the joint was quantitated at selected time points. The differences in proton T2 relaxation times allowed for characterization and quantitative separation of the fluid (relatively long T2) and nonfluid (relatively short T2) components of hydrogen content in the defined volume. The estimates of hydrogen content of both long and short T2 tissue components were used to assess the severity of the disease and its regression with indomethacin treatment. RESULTS: A progressive increase of the 2 components of hydrogen content in saline treated arthritic rats is consistent with histological examinations. After 19 days of treatment, 0.1 mg/kg/day and 0.5 mg/kg/day of indomethacin reduced the fluid component (primarily from inflammatory edema) in arthritic leg joints by 39 and 77% respectively, compared to the saline treated arthritic rats. The higher dose of indomethacin also significantly reduced the nonfluid component (primarily from cellular content) suggesting a reduced influx of inflammatory cells into the affected areas. The paw volume measurements, radiologic changes, and histopathology also showed the regression of adjuvant arthritis on treatment. CONCLUSION: The study demonstrated that the NMR method has the sensitivity required to assess the treatment efficacy in adjuvant arthritis and suggests its possible utility in early diagnosis and monitoring of therapy in clinical arthritis on human extremities.

Feline leukemia virus-induced thrombocytopenia and macrothrombocytosis in cats.

The Kawakami-Theilen strain of feline leukemia virus (FeLV-KT), an exogenous anemia-inducing retrovirus, induced significant macrothrombocytosis and thrombocytopenia during acute infections of cats. The geometric mean platelet volumes of both freshly isolated fixed platelets and ethylenediamine tetraacetic acid-sphered platelets from infected cats were increased, but the ratio of fresh-fixed to ethylenediamine tetraacetic acid-sphered platelet volumes, an estimate of ethylenediamine tetraacetic acid-induced isovolumetric shape change, was normal. Total plasma membrane increased as the platelet volumes increased in FeLV-KT-infected cats, but estimated surface connected canalicular system surface area did not. Platelet concentrations were decreased 2 to 6 weeks after inoculation, but marked macrothrombocytosis resulted in a trend toward increased platelet mass on weeks 5 and 6 after inoculation. Thus, FeLV-KT-induced macrothrombocytosis may serve as a model of impaired platelet volume regulation. The platelet volume and platelet membrane surface area abnormalities found suggest that this model would allow studies of the megakaryocyte/platelet axis, particularly in the area of membrane formation and territorial demarcation.

Renal disease in the pigtailed macaque (Macaca nemestrina).

Spontaneous renal disease in the pigtailed macaque was evaluated in a prospective study of 20 apparently healthy monkeys that were killed and a retrospective study of 674 monkeys that died of spontaneous disease. Many apparently normal pigtailed macaques have a mesangioproliferative glomerulonephritis of slight to moderate severity. Deposition of immunoglobulin, particularly IgM, was common in renal glomeruli and did not seem to correlate with renal disease. Glomerulonephritis was found in 14% of the adult monkeys that died of spontaneous disease; in 4.2% it was severe enough to have caused renal failure. Tubular nephrosis was the most common renal lesion (22.6% of adults) and was usually a nephrotoxicity resulting from treatment of diarrhea with nephrotoxic antibiotics. Other lesions found were incidental or were secondary to disease processes in other organs. Pigtailed macaques that have been in our colony at least six months have a higher incidence of renal disease than is reported elsewhere in Old World monkeys.

Familial renal amyloidosis in Abyssinian cats.

Medullary and glomerular amyloidosis, papillary necrosis, and secondary interstitial disease were diagnosed in eight related adult Abyssinian cats from two catteries. The lesions were similar to those in two unrelated mongrel cats with renal amyloidosis. Ultrastructurally, the patterns of amyloid deposition were as described in other species, although medullary deposition predominated. Potassium permanganate oxidation blocked Congo red staining of the deposits suggesting that they contained amyloid A protein (secondary amyloid). The disease may be a model of familial secondary amyloidosis and offers an opportunity to study the pathogenesis of both amyloid deposition and papillary necrosis. The histochemical characteristics of feline renal amyloid require careful attention to technique. Section thickness affects Congo red affinity and both dichroism as well as birefringence should be considered when interpreting staining reactions. Thioflavine-T may be the preferred stain for identification of small deposits of amyloid. Variation in section thickness markedly affected the degree of potassium permanganate oxidation.

Experimental nasopharyngitis and pneumonia caused by Chlamydia trachomatis in infant baboons: histopathologic comparison with a case in a human infant.

Three infant male baboons were inoculated with a strain of CHLAMYDIA TRACHOMATIS ISOLATED FROM A HUMAN INFANT WITH PNEUMONITIS. One baboon, inoculated by intratracheal, nasopharyngeal, and oropharyngeal seeding, had rales, radiographic evidence of pneumonia, persistent nasopharyngeal C. trachomatis infection, and a four-fold rise in titer of antibody. At sacrifice 24 days after inoculation, nasopharynx, trachea, airways, and lung yielded C. trachomatis, and epithelial inclusions were seen by light and immunofluorescent microscopy. Histopathologic changes noted were nearly identical to those in a lung biopsy specimen from a human infant and pneumonitis and nasopharyngeal C. trachomatis. The second baboon was inoculated by tracheal seeding and maintained nasopharyngeal C. trachomatis until killed 30 days later. Autopsy revealed nasopharyngitis and patchy mild pneumonitis. The third baboon was inoculated by nasopharyngeal seeding and maintained nasopharyngeal C. trachomatis for 49 days. Both of the latter baboons seroconverted. Infant baboons appear to be useful animal models for C. trachomatis nasopharyngitis and pneumonia.