Eosinophilic crystals as a distinctive morphologic feature of a hyaline droplet nephropathy in a mouse model of acute myelogenous leukaemia

Eosinophilic crystals have been described in the upper and lower respiratory tract, gall bladder, intrahepatic bile ducts and glandular stomach of different laboratory mice strains. They have been recently identified as chitinase-like (Ym1/Ym2) proteins. Here we describe the occurrence of eosinophilic crystals in the renal tubules of mice with experimentally induced acute myelogenous leukaemia. Fourteen FVB/N and 29 129Sv mice of both sexes, 8-10 weeks of age, were employed to establish a model of human acute myelogenous leukaemia. Nine mice that developed a widespread acute myelogenous leukaemia revealed the presence of eosinophilic crystals in renal tubules. The presence of eosinophilic crystals in the kidneys was constantly associated with a hyaline droplet nephropathy. Immunohistochemistry showed that the crystals and the hyaline droplets were composed of chitinase-like (Ym1/Ym2) proteins. Furthermore, immunoreactivity for Ym1/Ym2 proteins was also detected in the crystalline material stored in the cytoplasm of large macrophage-like cells or in extracellular localization within the leukaemic infiltrates. On the basis of our results we hypothesize that the detection of the Ym1/Ym2 proteins in the urine of mice might represent a feasible indicator of the burden and progression of the leukaemic condition in our murine model.     

Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice

Eosinophilic crystalline pneumonia is an idiopathic disease that occurs in many strains and stocks of mice, more commonly in strains on a C57BL/6 background. The disease occurs sporadically in most strains of mice and varies from mild and subclinical to severe and fulminating, sometimes resulting in respiratory distress and death. In this study, 94 aged male and female 129S4/SvJae mice were evaluated for eosinophilic crystalline pneumonia lesions. There was an 87% incidence, with females overrepresented. Histologically, there were multifocal to coalescing inflammatory infiltrates composed of numerous large eosinophilic macrophages and multinucleate cells admixed with eosinophils, neutrophils, lymphocytes, and plasma cells within alveolar and bronchiolar spaces, associated with refractile, brightly eosinophilic, angular crystals. Alveolar macrophages and multinucleate cells contained fine needlelike to rectangular intracytoplasmic crystalline material. Similar crystals were often free within alveoli and conducting airways, often associated with mucous metaplasia of bronchiolar epithelium. This disease may occur spontaneously or in concert with other pulmonary lesions, such as pulmonary adenomas, lymphoproliferative disease, allergic pulmonary disease, and parasitic or fungal infections. The characteristic crystals morphologically resemble Charcot-Leyden crystals, which represent eosinophil breakdown products in humans with eosinophil-related disease. However, crystals in eosinophilic crystalline pneumonia are composed predominantly of Ym1 protein, a chitinase-like protein associated with neutrophil granule products and secreted by activated macrophages. The function of Ym1 protein is not fully understood but is believed to be involved in host immune defense, eosinophil recruitment, and cell-cell and cell-matrix interactions consistent with tissue repair. The mechanism of induction of eosinophilic crystalline pneumonia with Ym1 crystal formation is unknown.     

Rhinosporidiosis in a cat.

A polypoid nasal mass from an adult cat was submitted for routine biopsy examination and was found to contain sporangia and sporangiospores consistent with Rhinosporidium seeberi. Inflammatory infiltrates were moderate and pyogranulomatous to lymphohistiocytic and were associated with hyperplasia of the transitional nasal epithelium. Apparently, this is the first reported case of rhinosporidiosis in a cat.     

Hematuria and extreme neutrophilic leukocytosis in a dog with renal tubular carcinoma

Renal tubular carcinoma was believed responsible for hematuria and extreme leukocytosis in a dog. Other paraneoplastic syndromes possibly associated with this neoplasm included fever, thoracolumbar hyperesthesia, and anemia attributable to myelophthisis. All clinical and clinicopathologic abnormalities resolved after unilateral nephrectomy. Neutrophil cytochemical stains were used to differentiate leukemoid reaction from myelocytic leukemia as the cause of the leukocytosis. The extreme leukocytosis in this dog may have been leukemoid reaction caused by production of colony-stimulating factor by the renal tubular carcinoma.     

A prostate fibromyxoid sarcoma with smooth muscle differentiation in a F344xBNF1 rat

This report describes a spontaneous prostate fibromyxoid sarcoma with smooth muscle differentiation in an approximately 136-week-old intact male F344xBNF1 rat on a diet study for 2 weeks. At necropsy, the prostate was markedly distorted and enlarged by a firm white multinodular mass (6.0 × 4.5 × 3.5 cm). Histopathologically, the mass consisted of solid sheets of interlacing mesenchymal spindle cells with indistinct cell borders. Nuclei were separated by variable amounts of hyaline to fibrillar eosinophilic and/or myxomatous material. The extracellular myxomatous material tended to form whorls and stained positively with alcian blue. The mass stained strongly with Masson trichrome and vimentin throughout. Approximately 5% of the neoplastic cells were positive for smooth muscle actin, and none stained for desmin and pancytokeratin. To the authors' knowledge, this fibromyxoid sarcoma with smooth muscle differentiation is the first such described prostatic sarcoma in a rat.     

Listeriosis in a raccoon dog (Nyctereutes procyonoides) associated with canine distemper

A wild raccoon dog (Nyctereutes procyonoides) that manifested severe illness and died was examined. Necropsy revealed severe emaciation, systemic icterus and petechial hemorrhages on the mucous membranes. Histopathologically, necroses were seen in the liver and brain stem associated with meningitis. Eosinophilic intranuclear inclusion bodies were observed in the spleen and intestinal mucosa, and eosinophilic intracytoplasmic inclusion bodies were seen in transitional epithelium in the bladder. Listeria monocytogenes 4b was isolated from the liver, spleen, kidneys and lungs, and the pathogen was also detected in the liver and brain stem immunohistopathologically. The disease was diagnosed as listeriosis associated with canine distemper virus infection in a raccoon dog.     

乳牛肾淀粉样变病超微结构和免疫组织化学的研究

对临床尸检一例乳牛肾淀粉样变病进行了组织与超微病理学和免疫组织化学的研究。结果提示其淀粉样蛋白为无分枝、平行或非平行排列的微丝,主要沉积在肾小球和小血管周围。在肾小球,系膜区沉积最为严重,其次为肾小球毛细血管基膜。生物素-亲和素免疫过氧化物酶(ABC)染色结果显示,抗淀粉样蛋白A(AA)反应阳性颗粒沉积于肾小球和肾的小血管壁上,其抗AA阳性反应提示本病为继发性淀粉样肾病。     

Hyalinizing pancreatic adenocarcinoma in six dogs

Exocrine pancreatic carcinoma is a particularly malignant neoplasm of the dog. Clinical and pathologic findings of an unusual variant of exocrine pancreatic neoplasia termed hyalinizing pancreatic adenocarcinoma were evaluated in 6 dogs. On microscopic examination, neoplasms were composed of tubules and acini of epithelial cells, with bright eosinophilic granular apical cytoplasm. Tubular lumina and tumor stroma contained abundant hyaline material that resembled amyloid. The hyaline material was not congophilic, and tumor cells and hyaline material were immunohistochemically negative for amyloid A, immunoglobulin light chains (kappa and lambda), amylin (islet amyloid polypeptide), laminin, and alpha(1)-antitrypsin. Two patients survived longer than 15 months after diagnosis; one of these dogs was untreated and had grossly evident metastasis at the time of diagnosis. The deaths of the other 4 dogs occurred as a result of poor recovery after partial pancreatectomy or in association with other concurrent life-threatening conditions. Two dogs were diagnosed with panniculitis, a condition rarely associated with pancreatic disease. Further evaluation is needed to determine the composition and biologic significance of intratumor hyaline material. Studies that associate exocrine pancreatic carcinoma grade and histologic subtype with prognostic outcomes in the dog are warranted such that appropriate therapy can be elected.     

Changes in expression and localization of GPRC5B and RARalpha in the placenta and yolk sac during middle to late gestation in mice

The mRNA expression of GPRC5B, an orphan G protein-coupled receptor, is induced by retinoic acid (RA). Because RA plays critical roles in embryonic development, reproductive functions, metabolism and homeostasis, GPRC5B is also considered crucial in these physiological events. We investigated the changes in expression of GPRC5B and RA receptor (RAR) alpha mRNAs and immunohistochemical localization of their proteins in the murine placenta and yolk sac at 13.5, 15.5 and 17.5 days post coitus. Stable levels of GPRC5B and RARalpha mRNAs were detected in the placenta and yolk sac. In the placenta, GPRC5B was present in maternal and fetal vascular endothelial cells, stromal cells, fibroblast-like cells and glycogen cells. A strong reaction to RARalpha was detected in maternal and fetal vascular endothelial cells and stromal cells. The levels of GPRC5B and RARalpha proteins in maternal and fetal vascular endothelial cells decreased with gestation. In the yolk sac, GPRC5B and RARalpha proteins were detected in vascular endothelial cells, but their levels did not change during the gestation period. These findings indicate that GPRC5B is involved in RA-dependent morphogenesis/angiogenesis and regulation of extracellular matrix synthesis in the murine placenta and yolk sac.     

Pathology of morbillivirus infection in striped dolphins (Stenella coeruleoalba) from Valencia and Murcia, Spain.

During the summer and fall of 1990 hundreds of striped dolphins (Stenella coeruleoalba) died in the Spanish Mediterranean as a result of morbillivirus infection. A pathological investigation was carried out on dolphins from Valencia and Murcia which were among the first to die in the epizootic. The dolphins were in poor body condition and pneumonia was the main necropsy finding. Microscopic lung lesions characterized by necrosis of bronchial and bronchiolar epithelium and infiltration of alveoli with macrophages, lymphocytes, neutrophils and multinucleated syncytia were seen in most dolphins. Cytoplasmic and nuclear eosinophilic viral inclusions were present in bronchial and bronchiolar epithelium and in syncytia. Focal granulomatous inflammation associated with nematodes was also present. Brain lesions included diffuse degeneration and necrosis of neurons, microgliosis, perivascular cuffing, formation of syncytia and focal demyelination. Cytoplasmic and nuclear eosinophilic inclusions were present in neurons and glial cells. There was severe lymphoid necrosis and depletion of spleen and lymph nodes and syncytia also occurred in lymph nodes. Biliary and transitional epithelium contained nuclear and cytoplasmic eosinophilic inclusions. Immunoperoxidase staining using monoclonal antibodies to phocine distemper virus confirmed the presence of morbillivirus antigens in lung and brain. The distribution and severity of lesions in striped dolphins are similar to those of distemper in seals, harbor porpoises and terrestrial mammals. The formation of syncytia in the lung and brain may be a useful pathological indicator of morbillivirus infection and may be used in the investigation of pinniped and cetacean strandings in North America.     

Small intestine adenocarcinoma in conjunction with multiple adenomas causing acute colic in a horse.

An 11-year-old Andalusian stallion developed marked signs of colic associated with an acute small intestine obstruction. Exploratory laparotomy revealed a distal jejunum full-thickness wall induration and multiple small adherent intraluminal masses. Fifteen centimeters of jejunum, including the induration, and several intraluminal masses were resected. Histologic examination revealed an adenocarcinoma and multiple polypoid adenomas. The horse was discharged, and no complications were reported 12 months postoperatively. Colic was considered secondary to partial jejunal lumen obstruction by the adenocarcinoma. Adenocarcinoma recurrence or transformation from remaining adenomas into an adenocarcinoma is still a major risk.     

Accumulation of 2,8 dihydroxyadenine in bovine liver, kidneys, and lymph nodes

A variety of tissues from 20 cattle slaughtered at federally inspected facilities contained abundant light green to greenish-yellow material. Gross lesions were most common in the liver and hepatic lymph nodes. Less frequent lesions were present in the mediastinal, renal, intercostal, and gastric lymph nodes. The material was most prominent in the portal triads, and in the medullary sinuses of the lymph nodes, at times occupying up to one half of the nodal mass. Renal calculi were present in one animal. Histologically, the condition was characterized by the intracytoplasmic accumulation of innumerable brown, acicular crystals in hepatocytes, macrophages, and renal tubular epithelial cells. Less frequent large aggregates of extracellular crystals were found in the lumens of renal tubules and in portal triads. Crystals were highly birefringent when examined using polarized light. The crystals were identified as 2,8 dihydroxyadenine using X-ray diffraction, electron diffraction, infrared spectroscopy, and mass spectrometry. In mammals, adenine is normally converted to adenylate by the enzyme adenine phosphoribosyltransferase. When adenine phosphoribosyltransferase is absent, deficient, or inhibited, adenine is oxidized to 2,8 dihydroxyadenine, which is extremely insoluble at physiological pH. In human beings, an autosomal recessive disease known as 2,8 dihydroxyadeninuria is caused by a deficiency of adenine phosphoribosyltransferase.     

Localization of canine, feline, and mouse renal membrane proteins

Immunohistochemistry allows the localization of proteins to specific regions of the nephron. This article reports the identification and localization of proteins in situ within normal canine, feline, and mouse kidney by immunohistochemistry; maps their distribution; and compares results to previously reported findings in other species. The proteins investigated are aquaporin 1, aquaporin 2, calbindin D-28k, glutathione S-transferase-α, and Tamm-Horsfall protein. Aquaporins are integral membrane proteins involved in water transport across cell membranes. Calbindin D-28k is involved in renal calcium metabolism. Glutathione S-transferase-α is a protein that aids in detoxification and drug metabolism. The role of Tamm-Horsfall protein is not fully understood. Proposed functions include inhibition of calcium crystallization and reduction of bacterial urinary tract infection. The authors' findings in the dog are similar to those in other species: Specifically, the authors localize aquaporin 1 to the proximal convoluted tubule epithelium, vasa recta endothelium, and descending thin limbs; aquaporin 2 to collecting duct epithelium; and calbindin D-28k within distal convoluted tubule epithelium. Glutathione S-transferase-α has variable expression and is found in only the renal transitional epithelium in some individuals, in only the proximal straight tubules in others, or in both locations in others. Tamm-Horsfall protein localizes to thick ascending limb epithelium. These findings are similar in the cat, with the exception that aquaporin 1 is located in glomerular podocytes, in addition to proximal convoluted tubule epithelium, and glutathione S-transferase-α is found solely within the proximal convoluted tubule within all kidney samples examined. The mouse kidney is almost identical to the dog but expresses glutathione S-transferase-α in the glomeruli only.     

Semen characteristics of goats with subacute, acute and chronic besnoitiosis

A study on the semen obtained from breeding goats suffering from mild to severe chronic besnoitiosis revealed marked changes in semen volume, colour, density, concentration, mass and individual motility and percentage live. There were also many neutrophils and spermatozoa with primary and secondary defects, including missing tails and deformed heads and tails. The observed changes were considered to be severe enough to account for the infertility observed in the flock. Sections of testes obtained for histopathology were characterised by massive blockage of the pampiniform plexus, degeneration of the germinal epithelium, tubular necrosis with an inflammatory infiltrate and, in some cases, accumulation of haemosiderin-like material in the tunica vaginalis.     

Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to para-dichlorobenzene for two years

Carcinogenicity and chronic toxicity of para-dichlorobenzene (p-DCB) were examined by exposing 50 BDF1 mice and 50 F344 rats of both sexes by inhalation to p-DCB vapor at a target concentration of 0 (control), 20, 75 or 300 ppm for 6 hr/day, 5 days/week and 2 years. Incidences of hepatocellular carcinomas, hepatoblastomas and hepatic histiocytic sarcomas in the 300 ppm-exposed male mice, and hepatocellular adenomas and carcinomas and hepatoblastomas in the 300 ppm-exposed female mice were increased. An increase in the incidences of most of those liver tumors was dose-related. No increase in tumor incidence was found in any p-DCB-exposed rat of either sex. Centrilobular hypertrophy of hepatocytes and papillary mineralization and pelvic urothelial hyperplasia of the kidney were noted in the 300 ppm-exposed male rats. Treatment- and age-related increases in incidences of the eosinophilic globules of the respiratory and olfactory epithelia in female rats and incidences of the respiratory metaplasia of the nasal gland epithelium in mice and rats and the olfactory epithelium in mice were noted. The nasal lesion was the most sensitive endpoint of chronic inhalation toxicity. Induction of the mouse hepatocarcinogenicity and lack of the rat nephrocarcinogenicity found in the present study were compared with the mouse liver tumors and the rat renal tumors reported by the NTP gavage study, and discussed in light of the estimated p-DCB uptake into the body through the inhalation and the oral administration.     

Sertoli cell tumour with Call-Exner-like bodies in a dog

An histological diagnosis of Sertoli cell tumour and concurrent seminoma was formulated after complete resection of the right testicle in a 8-year-old Doberman. The unusual histological feature of abundant eosinophilic material with a extracellular location forming the Call-Exner-like bodies is reported.     

J亚群禽白血病病毒引发蛋鸡多种肿瘤类型的病理分析

本试验对J亚群禽白血病病毒引发商品蛋鸡发生多种肿瘤进行了详细的病理学观察。尸检10只病死鸡,其中髓细胞性白血病占8/10,表现肝脾明显肿大,被膜下可见弥散的灰白色结节,组织学观察发现几乎所有组织均见典型髓细胞样瘤细胞增生。其中5/10病例表现有其他类型肿瘤,包括血管瘤、纤维瘤、脂肪肉瘤。用ALV-J特异性引物H5/H7进行PCR确诊该鸡群感染了ALV-J。     

Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome.

Fibrotic degeneration was examined in the kidneys of ICR-derived glomerulonephritis (ICGN) mice, a novel inbred mouse line with a hereditary nephrotic syndrome of unknown etiology considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we histochemically revealed changes in accumulation of extracellular matrix (ECM) components and in localization of integrins, cellular receptors for ECM, in the kidneys of ICGN mice with the progression of renal failure. Excessive accumulation of basement membrane (laminin and collagen IV) and interstitial (type III collagen) ECM components were demonstrated in the glomeruli and tubulointerstitum of ICGN mice. Marked deposition of type I collagen and tenascin was seen only in the glomeruli of ICGN mice but not in those of ICR mice as normal controls. Increased expression of integrin alpha1-, alpha2-, alpha5- and beta1-subunits in glomeruli with fibrotic degeneration and abnormal distribution of alpha6-subunit were noted in the kidneys of ICGN mice. Excessive laminin, a ligand of alpha6beta1-integrin, was demonstrated on the tubular basement membrane, but alpha6-subunit diffusely disappeared on the basal side of the tubular epithelial cells. We presumed that abnormal integrin expression in renal tubules causes epithelial cell detachment, and consequently tubular nephropathy, and results in disorder of ECM metabolism causing excessive accumulation of ECM components in the kidneys of ICGN mice.     

Acidophilic macrophage pneumonia in laboratory mice

Acidophilic macrophage pneumonia, characterized by an accumulation of characteristic crystalloid-laden alveolar macrophages, was seen in 30/7,500 NMRI, 7/600 T x HT, 2/100 C57BL and in no cases of 1,500 CBA and 1,100 BALB/c mice. Histologically, there was a focal accumulation of large numbers of eosinophilic macrophages, generally associated with granulocytes. Macrophages could be mononucleate or multinucleate and had a crystalline cytoplasm. Free-lying crystals were sometimes observed. Ultrastructurally, macrophages had a cytoplasmic accumulation of needle-shaped and rhomboidal crystals, often showing a clear lattice structure with a repeat of 3-5 nm. The crystalloid inclusions may be derived from the breakdown products of granulocytes and appear similar to inclusions in macrophages in other parts of the hematopoietic system. That these inclusions are probably derived from eosinophils is based on the appearance within macrophages of structures resembling eosinophil granules at various stages of degradation and the similarity between the lattice repeat of the crystalloids and that of the crystalline core of the eosinophil granule. The crystalloid inclusions may be related to the Charcot-Leyden crystals found in human beings.     

Post mortem studies on infertile buffalo bulls: testicular histology

Testicular tissues of 22 buffalo bulls (Bubalus bubalis) which suffered from three types of infertility were examined histologically. Nine bulls with no sexual libido showed underdeveloped seminiferous tubules; five of them also had various forms of germinal tissue hypoplasia (bilaterally complete, partial or incomplete) and in the other four the seminiferous tubules showed developed layers of germinal epithelium but no complete spermiogenesis. Among 11 bulls which had always produced poor quality semen one suffered from incomplete bilateral testicular hypoplasia and two had simple testicular degeneration; five showed marked testicular degeneration associated with fibrosis of intertubular spaces, and in three there was intertubular fibrosis and tubular stasis. In two bulls in which the quality of semen had deteriorated one showed bilateral partial testicular hypoplasia and the other had bilateral testicular degeneration with unilateral intertubular fibrosis and tubular stasis.