Spontaneous B-cell lymphoma in the cranial mediastinal lymph node of an aged male C57BL/6J mouse.

B-cell lymphoma is generally observed in the spleen, mesenteric lymph nodes, and Peyer's patches in aged mice and rarely appears in other organs. Herein, we report a case of spontaneous B-cell lymphoma originating from the cranial mediastinal lymph node in a male 75-week-old C57BL/6J mouse. Macroscopically, a white mass was found at the base of the heart with no connection to the thymus.

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats.

In drug development, assessment of non-clinical peripheral neurotoxicity is important to ensure human safety. Clarifying the pathological features and mechanisms of toxicity enables the management of safety risks in humans by estimating the degree of risk and proposing monitoring strategies. Published guidelines for peripheral neurotoxicity assessment do not provide detailed information on which endpoints should be monitored preferentially and how the results should be integrated and discussed.

Karnovsky's fixative prevents artifacts appearing as vacuolation derived from tissue processing in kidneys treated with antisense oligonucleotide.

Antisense oligonucleotide (ASO) therapies have been identified as a new treatment modality for intractable diseases. In kidneys treated with ASOs, vacuoles, in addition to basophilic granules, are often observed in the proximal tubules. Some reports have described that these vacuoles are likely to be a secondary phenomenon resulting from the extraction of ASOs during tissue processing.

Spontaneous ovarian choriocarcinoma in a young ICR mouse.

This paper describes the spontaneous ovarian choriocarcinoma observed in a young female Crl:CD1 (ICR) mouse. The mouse was sacrificed at 8 weeks of age after oral administration of a compound for 2 weeks. The left ovary was found to be cystically enlarged with dark red hemorrhaging.

Spontaneous hyaline glomerulopathy in a young Slc:ICR mouse.

Hyaline glomerulopathy is a type of glomerular lesion that occurs in aging mice. Spontaneous hyaline glomerulopathy is rare in young mice. Here, we report spontaneous hyaline glomerulopathy in a young adult (15-week-old) ICR mouse.

Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism.

The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6.

Gene expression profiling in the lungs of phenylhydrazine-treated rats: the contribution of pro-inflammatory response and endothelial dysfunction to acute thrombosis.

Pulmonary thrombosis is a life-threatening disorder caused by various risk factors. We previously reported that phenylhydrazine (PHZ) induces acute thrombosis in the rat lung, with regional stasis in the alveolar capillaries as a trigger, and subsequent hemostatic disruption is involved as an accelerator in the pathogenesis of this condition. In this study, we examined the other possible pathogenesis, particularly endothelial dysfunction in the lungs of PHZ-treated rats using gene expression profiling.

Hematological and morphological investigation of thrombogenic mechanisms in the lungs of phenylhydrazine-treated rats.

Abnormality in hematological condition including hemolytic disorders has been suggested one of the risk factor of pulmonary thrombosis. We previously reported that phenylhydrazine (PHZ) could induce acute thrombosis in the rat lung. In this study, time-related hematological and histopathological changes were evaluated in PHZ-treated rats to reveal the pathogenesis of pulmonary thrombosis in hemolytic condition.

Gene expression in livers of BALB/C and C57BL/6J mice fed a high-fat diet.

We previously demonstrated that high-fat diet (HFD)-induced hepatic lipid accumulation is more severe in BALB/c mice than in C57BL/6J (B6) mice. To understand the changes in liver metabolism, we studied blood chemistry, gene expression, and histopathological changes of the liver in nine-week HFD-fed BALB/c and B6 mice and one- or four-week HFD-fed BALB/c mice. Serum total cholesterol and triglyceride levels were significantly increased in all HFD-fed groups, and one- and four-week HFD-fed BALB/c groups, respectively.

Spontaneous amphophilic focus in the liver of a young Sprague-Dawley rat.

Altered hepatocellular focus was histopathologically observed in the liver of a 6-week-old Sprague-Dawley rat. The hepatocytes within this lesion had diffusely eosinophilic cytoplasm with scattered basophilia and slightly enlarged nuclei with prominent nucleoli. Based on these cytological characteristics, the lesion of these hepatocytes was classified as an amphophilic focus.

Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat, an animal model of the metabolic syndrome.

SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks.

A Hepatocellular Adenoma in a Diet-induced Obese Mouse.

A hepatic nodule was noted in a C57BL/6J mouse with diet-induced obesity at 53 weeks of age. Macroscopically, a protruding yellowish white nodule was observed on the visceral surface of the left lateral lobe. Light microscopy demonstrated clear demarcation from the compressed adjacent parenchyma, with loss of the distinct lobular pattern.

Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats.

Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying pharmacology and hepatotoxicology, Fischer 344 male rats were dosed with 300 mg/kg/day of fenofibrate for 14 days and the urine and plasma were analyzed on days 2 and 14.

Evaluation of gene expression related to hepatic cell maturation and differentiation in a chemically induced mouse hepatoblastoma cell line.

The MHB-2 cell line, established from a mouse hepatoblastoma (HB), was subjected to the reverse transcriptase-polymerase chain reaction (RT-PCR) for evaluation of gene expression related to cell differentiation. RNAs for c-kit, CD34, thy-1, albumin, cytokeratin (CK) 8, 18 and 19 could be detected, but expression of alpha-fetoprotein, glucose-6-phosphatase, tyrosine aminotransferase and CK7 was not observed. MHB-2 cells were positive for CK8/18 but negative for c-kit, CD34, thy-1 and albumin on protein level.

Histopathological characterization of the skeletal myopathy in rasH2 mice carrying human prototype c-Ha-ras gene.

A skeletal myopathy is found in approximately 100% of rasH2 mice. To confirm detailed features of the rasH2 skeletal myopathy, the biceps femoris, diaphragm, triceps brachii, gastrocnemial (types I and II fiber-mixed muscles) and soleus muscle (type I fiber-dominant muscle) obtained from male rasH2 and non-transgenic littermates aged 10-13 and 34 weeks were examined. Variations in the muscle fiber size, early-scattered degeneration/necrosis and regeneration of muscle fibers were detected in 10-13-week-old rasH2 mice.

One-step RT-PCR without initial RNA isolation sStep for laser-microdissected tissue sample.

One-step RT-PCR procedure without initial RNA extraction step is tested for laser microdissected tissue sample. Unfixed cryosections of liver and kidney tissue of male SD rats were cut using laser microdissection system and directly used as templates for RT-PCR study. To check the sensitivity, 5, 25, 125, and 625 hepatocytes were cut and put in PCR-tube.

Immunohistochemical localization of transforming growth factor alpha in regenerating rat liver.

Immunohistochemical localization of TGF-alpha and cell proliferation kinetics during liver regeneration after two-thirds partial hepatectomy (PH) were investigated. Twenty-four to 72 hr after PH, appreciable increase in the number of TGF-alpha-positive hepatocytes was observed in zones 1 and 2. At the peak at 36 hr, almost all positive cells were stained in their nuclei.

Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.

Skeletal myopathy was found in almost all-transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle fiber size, centrally placed nuclei, regenerating fibers, and interstitial fibrosis were evident; hyalinization and necrosis were sometimes observed in the skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory changes in the skeletal muscle or abnormality of adjacent peripheral nerve were not observed.