Porencephaly in a Cynomolgus Monkey (Macaca Fascicularis)

Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis) aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish excavation with partial defects of the full thickness of the hemispheric wall, and it constituted open channels between the lateral ventricular system and arachnoid space. In addition, the bilateral occipital lobe was slightly atrophied. Histopathologically, fibrous gliosis was spread out around the excavation area and its periphery. In the roof tissue over the cavity, small round cells were arranged in the laminae. They seemed to be neural or glial precursor cells because they were positive for Musashi 1 and negative for NeuN and GFAP. In the area of fibrous gliosis, hemosiderin or lipofuscin were deposited in the macrophages, and activated astroglias were observed extensively around the excavation area

Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function

Atopic dermatitis-like skin lesions with IgE hyperproduction and pruritus in KFRS4/Kyo rats.

[Background]Rats showing spontaneous atopic dermatitis (AD)-like skin lesions were observed in the Kyoto Fancy Rat Stock 4 (KFRS4) strain breeding colony. [Objective]To establish the KFRS4 rat as a model of AD. [Methods]The clinical symptoms of AD-like skin lesions were assessed by scoring the degree of dermatitis and examining scratching behavior. The transepidermal water loss was measured to evaluate skin barrier function. Cells infiltrating the skin lesions were identified using histological and immunohistological analyses. IgE and cytokine levels were measured to examine immune status. An ointment treatment experiment was carried out to characterize dermatitis in the KFRS4 rats. [Results]Dermatitis initially appeared around 4 months of age and rapidly worsened from 6 to 8 months of age. The skin lesions accompanied scratching behavior and were predominantly observed in females. The increased transepidermal water loss indicated skin barrier dysfunction. Extensive infiltration of eosinophils, mast cells and lymphocytes was observed in the skin lesions. The plasma IgE level increased in accord with increasing severity of dermatitis. The Th2 and Th17 cytokine mRNA levels were significantly higher in the skin-draining lymph nodes than those in the non-skin-draining lymph nodes. It was demonstrated that betamethasone improved the symptoms of dermatitis. These findings demonstrated that dermatitis in the KFRS4 rats closely resembled that seen in human AD. [Conclusion]Female KFRS4 rats have the potential to serve as an animal model of human AD

Supplemental Material, DS1_TPX_10.1177_0192623318783957 - Comparison of Acute Gene Expression Profiles of Islet Cells Obtained via Laser Capture Microdissection between Alloxan- and Streptozotocin-treated Rats

<p>Supplemental Material, DS1_TPX_10.1177_0192623318783957 for Comparison of Acute Gene Expression Profiles of Islet Cells Obtained via Laser Capture Microdissection between Alloxan- and Streptozotocin-treated Rats by Yuki Kato, Yusaku Masago, Chiaki Kondo, Erika Yogo, Mikinori Torii, Atsuko Hishikawa, Takeshi Izawa, Mitsuru Kuwamura, and Jyoji Yamate in Toxicologic Pathology</p

Development of effective tumor immunotherapy using a novel dendritic cell–targeting Toll-like receptor ligand

<div><p>Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers. In murine experiments, most and significant inhibition of tumor growth and extended survival was observed in the group treated with the combination of h11c-activated DCs in combination with interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic myeloid-derived suppressor cells were significantly reduced by the combined treatment. Following the successful results in mice, the combined treatment was examined against canine cancers, which spontaneously generated like as those in human. The combined treatment elicited significant clinical responses against a nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment was also successful against a bone-metastasis of squamous cell carcinoma. In the successful cases, the marked increase of tumor-responding T cells and decrease of myeloid-derived suppressor cells and regulatory T cells was observed in their peripheral blood. Although the combined treatment permitted the growth of lung cancer of renal carcinoma-metastasis, the marked elevated and long-term maintaining of the tumor-responding T cells was observed in the patient dog. Overall, the combined treatment gave rise to emphatic amelioration in DC-based cancer therapy.</p></div

Effect of h11c on the surface molecules of DCs.

<p>DCs induced from BMCs of B6 mice were incubated with or without h11c. After incubation, the expression intensity of indicated costimulatory molecules and an antigen-presenting molecule was evaluated by FCM. (A) Representative FCM data are shown. The darker gray peaks indicate expression of surface molecules on DCs incubated with h11c. The lighter gray peaks indicate those on DCs incubated with PBS as a control. Vertical lines indicate MFI of each peak. (B) Expression intensity of surface molecules. The expression intensity of surface molecules was evaluated with MFI. Black bars indicate the expression intensity of the indicated molecules on the h11c-treated DCs. White bars indicate those of the PBS-treated DCs. Experiments were performed using five mice in each group. Results are expressed as mean ± SEM. * *p <0.01, *p <0.05.</p

Therapeutic and analytic results for case no. 1.

<p>(A) Tumor appearance before and after the 20th treatment (day 176). (B) Volume of the tumor after the start of treatment. The points indicated with arrows are when the analyses of the PB cells were performed. (C) Responses of T cells against tumor antigens. T cells were collected from PB on the days indicated by arrows in Fig 13B. The responses against own tumor lysate are shown in (a), and those against the lysate of an unrelated tumor are shown in (b). The protein concentration of the lysate in culture was 50 μg/ml. (D) Percentage of Treg and MDSC in the PB at the points indicated.</p