Histopathology of incidental findings in cynomolgus monkeys ( macaca fascicularis ) used in toxicity studies

The purpose of our publication is to widely communicate pictures of spontaneous findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is commonly seen in the general organs. The frequency and severity of these lesions may be influenced by the administration of drugs with an effect on the immune system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is also frequently seen in cynomolgus monkeys, and it is caused mainly by a Helicobacter pylori infection. Various degrees of brown pigments are observed in various organs, and it is possible to distinguish the material of the pigments by its morphological features and site. A focal/segmental glomerular lesion is occasionally seen in a section of the kidney, and the minimal lesion has no influence on the urinalysis. We showed the common glomerular lesions in HE-stained sections, as well as in PAM- or PAS-stained sections, for understanding the details. Young and pubertal monkeys are usually used in toxicity studies; therefore, understanding various maturation stages of the genital system is important. In particular, the female genital system needs to be understood in the morphology, because their cyclic changes are different from other laboratory animals. Thus, we present the normal features of the cyclic changes of the female genital organs. Furthermore, we provide more information on spontaneous findings in cynomolgus monkeys for exact diagnoses in toxicity studies.     

Cloning of the feline GADD45 cDNA and analysis of its mutation in feline lymphoma cell lines

Growth arrest and DNA damage-inducible protein 45 (GADD45) plays an important role in suppressing multistep carcinogenesis. In this report, we describe the isolation of the complete wild-type feline GADD45 cDNA from feline tissues. Expression of feline GADD45 mRNA was detected in the liver, spleen, kidney, lung, and testis. The predicted amino acid sequences encoded by the full-length feline GADD45 cDNA display sequence homology with those from other vertebrates, and as in the case of human GADD45, cell growth suppression was observed by ectopic expression of feline GADD45. However, no mutations were detected by sequence analysis of feline GADD45 in several feline lymphoma cell lines, indicating that the GADD45 mutation might be uncommon in feline oncogenesis.     

Geographical distribution of vampire bat-related cattle rabies in Brazil

Seventy-seven rabies virus (RV) isolates originating from Brazilian cattle were genetically characterized. Partial nucleoprotein gene sequences of these isolates were phylogenetically and geographically analyzed. Cattle isolates, which clustered with the vampire bat-related RV group, were further subdivided into nine genetic subgroups. These subgroups were distributed widely in lowland regions, with some subgroups separated from each other by mountain ranges. In addition, separation of the groups in mountainous regions was correlated with altitude. These results indicate that cattle rabies is derived from several regionally-defined variants, which suggests that its geographical distribution is related to that of the vampire bat population.     

Recurrence analysis of intraoperative acridine orange-photodynamic therapy for dogs with intranasal tumors

Intraoperative acridine orange-photodynamic therapy (AO-PDT) and cribriform plate irradiation are used to treat canine intranasal tumors. The purpose of this study was to evaluate the effects of AO-PDT on intranasal tumors and the recurrence rate of tumors after this treatment. Treatments with AO-PDT were performed on 38 dogs through a narrow window of the dorsal nasal cavity. The median progression-free interval was 12 mo and recurrence was detected in 21 dogs. Based on computed tomography, recurrence in 16 dogs was biased to the following areas: lateral (n = 10), medial (n = 2), ventral (n = 0), rostral (n = 0), and caudal (n = 8). Side effects were mild and included subcutaneous emphysema and rhinitis. The median survival time was 24 mo. Although AO-PDT with cribriform irradiation is an effective treatment for intranasal tumors, AO-PDT techniques should be improved to treat the nasal cavity more uniformly and thoroughly.     

Identification of a novel gene (Apq1) from the indica rice cultivar ‘Habataki’ that improves the quality of grains produced under high temperature stress

The appearance of brown rice grown under high temperature conditions is an important characteristic for improvement in Japanese rice breeding programs. We performed a QTL analysis of the appearance quality of brown rice using chromosome segment substitution lines of the indica cultivar ‘Habataki’ in the ‘Koshihikari’ genetic background. A line carrying a ‘Habataki’ segment on chromosome 7 showed a high percentage of perfect grains produced under high temperature conditions during the ripening period. To verify the role of this segment, and to narrow down the region containing the useful allele, substitution mapping was performed using multiple paired lines. As a result, the chromosomal location of a gene that we named Appearance quality of brown rice 1 (Apq1) was delimited to a 48-kb region. In addition, we developed an Apq1-near isogenic line (NIL) to evaluate the effect of Apq1 on various agronomic traits. Under high temperature conditions during the ripening period, the Apq1-NIL produced significantly higher percentages of perfect grains than ‘Koshihikari’. Other agronomic traits, including yield and palatability, were similar between the Apq1-NIL and ‘Koshihikari’. Therefore, the ‘Habataki’ allele of Apq1 will be useful in breeding programs aimed at improving the quality of grains ripened under high temperature conditions.     

Occurrence of boscalid resistance in cucumber powdery mildew in Japan and molecular characterization of the iron–sulfur protein of succinate dehydrogenase of the causal fungus

A total of 74 mass isolates of cucumber powdery mildew fungus (Podosphaera xanthii) were collected from commercial greenhouses with a history of boscalid use in Ibaraki Prefecture, Japan, and tested in a leaf disk assay for their sensitivity to boscalid. The mildew development of 40 of 74 isolates and five sensitive reference isolates on the disks was completely suppressed at 5 μg boscalid/ml. The minimum inhibitory concentrations (MIC) for the remaining 34 isolates were 50 μg/ml or higher, and 21 of these isolates also grew well at 500 μg/ml. Six single-spore isolates were resistant to boscalid with MIC values higher than 500 μg/ml; four of these were moderately resistant (MR), and two were very highly resistant (VHR) isolates. The growth of MR isolates was almost completely suppressed at 500 μg/ml, whereas two VHR isolates grew vigorously at 500 μg/ml. In foliar inoculation tests of potted cucumber plants, the efficacy of boscalid (500 μg/ml) against both MR and VHR isolates was very low. Partial DNA fragment of the iron–sulphur protein subunit (SdhB) gene of succinate dehydrogenase was PCR-amplified from five sensitive and five resistant isolates and directly sequenced, revealing that VHR isolates possess a substitution from a highly conserved histidine (CAT) to tyrosine (TAT) in a third cysteine-rich center of a putative SdhB, whereas MR isolates so far have not been found to have such substitution in SdhB.     

Effect of multiple oral dosing of fluconazole on the pharmacokinetics of cyclosporine in healthy beagles

Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a four-period crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC(0-12) and C(max) values for treatment B were significantly higher than those for the other treatments. In particular, the AUC(0-12) of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.     

Effect of electric field in conditioned aversion response

The aim of the present study was to estimate whether rat sense exogenous electric field (EF) including one used in our previous studies. Employing a conditioned place aversion response paradigm based on an aversive behavior against light environment, alteration in both voluntary behavior of Wistar rat to a 50 Hz sinusoidal EF was examined. Following conditioning without EF, the times spent in white place in rats was significantly shortened (P<0.05). While, such changes were not shown in rats conditioned with EF. Thus, it was considered that the aversion response to light environment was interfered by exposure to EF. An interference in recognition of brightness via EF induced effect to visual system or in learning system via direct effect to central nerve system was considerable as a factor for EF-induced effect. In addition, it was remained that rat possibly sense exposure to EF as preferable. In order to confirm which factor functioned, further studies are needed.     

Genetic analysis of phosphoprotein and matrix protein of rabies viruses isolated in Brazil

To investigate the genetic characteristics of phosphoprotein (P) and matrix protein (M) genes of variable rabies virus (RV) prevalent in Brazil, the authors genetically characterized the P and M genes from 30 Brazilian RV field isolates. Phylogenetic analysis based on the P and M genes revealed the presence of six RV variants that consisted primarily of three insectivorous bats, the vampire bat, dog and fox in Brazil. Specific amino acid substitutions corresponding to these phylogenetic lineages were observed, with Asp(42) and Glu(62) in the P protein found to be characteristic of Brazilian chiroptera- and carnivora-related RVs, respectively. Amino acid sequence motifs predicted to associate with a viral function in the P and M proteins were conserved among Brazilian RV variants.