Pathological analysis of batch safety testing of veterinary vaccines using small laboratory animals     

Kasumi Sudo  Mariko Ochiai  Naoyuki Aihara  Noriyuki Horiuchi  Atsushi Yamamoto  Sachiko Matsumoto  Koji Oishi 《Journal of toxicologic pathology》2021,34(2):137

Batch safety tests (BSTs) of veterinary vaccines are conducted using small laboratory animals to assure the safety of vaccines according to several criteria, including clinical signs and change in body weight. Although the latter is used as an evaluation index in BSTs, there have been no reports on the internal changes that affect body weight during the test period. Therefore, we analyzed BST via pathological examination of the tested animals. Here, BSTs were performed for 176 batches using mice and 126 batches using of guinea pigs. Most of the gross findings could be classified into four lesion types (nodules, adhesions, ascites, no apparent signs), with only one vaccine inducing lesions that could not be classified into any of these four types. Histopathological examination revealed that the reactions caused by BST were pyogenic and/or granulomatous inflammation. Nodular or adhesive lesions comprised more severe pyogenic granulomatous inflammation than ascites or cases with no apparent gross lesions. These nodular or adhesive lesions were more frequently induced by vaccines that contained an adjuvant than by vaccines that did not contain an adjuvant. The cases with “exceptional” gross findings histologically presented severe necrosis of the hematopoietic system. Additional testing showed that these “exceptional” lesions were induced when a specific type of light liquid paraffin was injected along with other vaccine additives. Our results show that body weight loss and/or lesions during BST were induced by proinflammatory properties of the tested vaccines and that BST is a sensitive method for detecting unexpected effects of vaccine components.  相似文献   

Expression of P-glycoprotein and breast cancer resistance protein in three cases of canine lymphoma showing drug resistance     

Sachiko HYOKAI  Hiroyo TANAKA  Noriyuki AIHARA  Junichi KAMIIE 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2021,83(3):473

In canine lymphoma, drug resistance is the major factor hindering treatment. In this study, we performed immunohistochemical examination of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which are considered as transporters related to multidrug resistance in three recurrent canine lymphomas. All cases were negative for both transporters before anticancer drug administration, but became positive after this administration. The expression was confirmed in capillary endothelial cells, such as in brain capillaries acting as the blood-brain barrier (BBB). It is suggested that both transporters expressed on capillary endothelial cells in lymphoma tissue may inhibit the spread of anticancer drugs into tumor tissues from blood, the same as the BBB. Therefore, capillary endothelial cells could act as a blood-tumor barrier, which might be involved in drug resistance in canine lymphoma.  相似文献   

Involvement of a host erythrocyte sialic acid content in Babesia bovis infection     

Takabatake N  Okamura M  Yokoyama N  Okubo K  Ikehara Y  Igarashi I 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2007,69(10):999-1004

Host sialic acid (SA) has recently been suggested to play an important role in erythrocyte (RBC) infection by Babesia spp. The present study attempted to further determine the specific type of SAs important in the RBC invasion. Bovine RBC was found to bear abundant alpha2-3-linked SA residues but not alpha2-6-linked SA in nature, confirmed by flow cytometric analysis of the neuraminidase (Nm)-treated RBCs. Lectin-blot analyses revealed the removal of alpha2-3-linked SAs from the 97-, 33-, and 31-kDa bands by the Nm treatment. Addition of the Nm-treated RBCs into an in vitro culture of B. bovis resulted in a decreased population of the parasitized RBCs. The thin smear samples from the cultures were then observed under a confocal laser scanning microscope after staining with the alpha2-3-linked SA-specific lectin: a selective invasion of B. bovis was found only in the intact RBCs bearing the SAs, but not in the desialylated RBCs. Furthermore, a significant reduction of the parasitized RBCs was also observed in the culture supplemented with exogenous 3'-sialyllactose containing the alpha2-3-linked SAs. However, the complete inhibition of parasite proliferation was not achieved in the culture. These findings indicate that while the alpha2-3-linked SA-dependent pathway is needed for highly efficient invasion of host RBCs by B. bovis, there might also be other potential alternative pathways.  相似文献   

Characterization of Elicitor-inducible Tobacco Genes Isolated by Differential Hybridization     

Daigo TAKEMOTO  Noriyuki DOKE  Kazuhito KAWAKITA 《Journal of General Plant Pathology》2001,67(2):89-96

Inducible responses in plants against pathogen attack play a major role in resistance to disease. The defense responses are mostly associated with the expression of various kinds of inducible genes. We employed differential hybridization to isolate elicitor-inducible genes (EIGs) of tobacco (Nicotiana tabacum cv. Samsun NN) using the tobacco-fungal elicitor system. A cDNA library was constructed from tobacco leaves treated for 12 hr with hyphal wall components (HWC) prepared from Phytophthora infestans, and six EIGs were identified. Expression of all EIGs was induced after inoculation with the soybean pathogen Pseudomonas syringae pv. glycinea (nonpathogenic on tobacco) or treatment with salicylic acid, and a variety of expression patterns of EIG mRNAs was observed. Sequence analysis of EIG cDNAs revealed similarities to genes for SAR8.2 (EIG-B39 and EIG-D14), glycine-rich protein (EIG-G7), extensin (EIG-I30), acyltransferase (EIG-I24) and unknown protein (EIG-J7). Possible roles of EIG products in disease resistance are discussed. Received 30 August 2000/ Accepted in revised form 30 November 2000  相似文献   

Induction of Systemic Resistance in Cucumber against Several Diseases by Plant Growth-promoting Fungi: lignification and Superoxide Generation   总被引：11，自引：0，他引：11  

Nobuyo Koike  Mitsuro Hyakumachi  Koji Kageyama  Shinji Tsuyumu  Noriyuki Doke 《European journal of plant pathology / European Foundation for Plant Pathology》2001,107(5):523-533

Five fungal isolates (Trichoderma, Fusarium, Penicillium, Phoma and a sterile fungus) from zoysiagrass rhizosphere that promote plant growth were tested for their ability to induce systemic resistance in cucumber plants against Colletotrichum orbiculare. Roots of cucumber plants were treated with these fungal isolates using barley grain inocula (BGI), mycelial inocula (MI) or culture filtrate (CF). Most isolate/inoculum form combinations significantly reduced the disease except BGI of Trichoderma. These fungal isolates were also evaluated for induction of systemic resistance against bacterial angular leaf spot and Fusarium wilt by treatment with BGI. Penicillium, Phoma and the sterile fungus significantly reduced the disease incidence of bacterial angular leaf spot. Phoma and sterile fungus protected plants significantly against Fusarium wilt. Roots treated with CFs of these fungal isolates induced lignification at Colletotrichum penetration points indicating the presence of an elicitor in the CFs. The elicitor activity of CFs was evaluated by the chemiluminescence assay using tobacco callus and cucumber fruit disks. The CFs of all isolates elicited conspicuous superoxide generation. The chemiluminescence activity of the CF of Penicillium was extremely high, and its intensity was almost 100-fold higher than that of other isolates. The chemiluminescence activity was not lost following treatment with protease or autoclaving or after removal of lipid. The MW 12,000 dialyzed CF fraction was highly effective in eliciting chemiluminescence activity. Chemiluminescence emission from cucumber fruit disks treated with Penicillium was the same as that obtained from tobacco callus, except that the lipid fraction also showed a high activity. Both the MW 12,000 fraction and the lipid fraction induced lignification in the epidermal tissues of cucumber hypocotyls.  相似文献   

Effects of propofol-sevoflurane anesthesia on the maternal and fetal hemodynamics blood gases, and uterine activity in pregnant goats   总被引：2，自引：0，他引：2  

Setoyama K  Shinzato T  Misumi K  Fujiki M  Sakamoto H 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2003,65(10):1075-1081

To determine the effects of propofol and sevoflurane on hemodynamics, acid-base balance and uterine activity in pregnant animals, a prospective experimental study was designed by use of ten pregnant goats. Propofol was intravenously administered at a bolus dose of 5 mg/kg and then infused a rate of 0.3 mg/kg/min for 5 min. Following the induction, the animals were incrementally inhaled 2.7 and 4.1% of end-tidal concentration of sevoflurane each for 30 min, and then recovered. The maternal and fetal heart rate (HR), arterial blood pressure (BP) and acid-base balance, the intrauterine pressure (IUP), and the uterine blood flow (UBF) were measured. Following the pre-anesthetic data, the parameters were measured 7 times throughout the anesthetic and recovering periods. The propofol infusion induced 1.37 times of HR increase and produced decrease in PO(2) and a relevant metabolic acidemia in the mother, with no effect in the fetus. Sevoflurane reduced BP in the fetus from 30 (2.7%) to 60 (4.1%) min of inhalation. The uterine contractions disappeared throughout sevoflurane inhalation, and then recurred within 15 min after the cessation of sevoflurane. Propofol injection increases HR, and induces a moderate hypoxemia and metabolic acidemia associated with the suppressed ventilation for pregnant goats, with less effect on the fetal hemodinamics. Sevoflurane causes minimal change in maternal hemodynamics, but induces significant hypotension in the fetus and reduction of uterine activity. These data may be useful in making anesthetic choices combined with analgesia for Caesarian section in goats.  相似文献   

Aspergillus niger pulmonary infection in a dog     

Kim SH  Yong HC  Yoon JH  Youn HY  Yoshioka N  Kano R  Hasegawa A 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2003,65(10):1139-1140

A 6-month-old male golden retriever was presented with fever, bloody-watery diarrhea and mild cough. Parvovirus and Isospora canis infection was confirmed and successfully treated. Two weeks later, the dog had severe cough and mucopurulent nasal discharge. Aspergillus niger was cultured from endotracheal washings on blood agar at 37 degrees C. Treatment with itraconazole for about 10 weeks resolved the clinical signs.  相似文献   

Effects of milrinone on hemodynamics and regional blood flow in the hypoxic dog   总被引：2，自引：0，他引：2  

Setoyama K  Ota H  Miura N  Fujiki M  Misumi K  Sakamoto H 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2002,64(6):499-503

Milrinone, a therapeutic agent for acute congestive heart failure, has both inotropic and vasodilatory effects, but investigations of these effects of milrinone were almost all conducted under normoxia, and few reports have investigated how milrinone affects the hemodynamics and redistribution of regional blood flow under severe hypoxia. By using colored microspheres, we investigated how milrinone affects hemodynamics and the redistribution of regional blood flow under severe hypoxia. Twelve healthy mongrel dogs were divided into 2 groups. The milrinone group was infused with milrinone cumulatively at 25, 75 and 250 microg/kg for 5 min each. The intact group was infused with saline instead of milrinone. We measured the hemodynamics and cerebrum, cerebellum and kidney blood flow in both groups. Both groups were inspired with 10% oxygen. Milrinone induced significant decrease in mean pulmonary artery and pulmonary vascular resistance, compared with the intact group. In both groups slight decreases in mean arterial pressure, systemic vascular resistance and double-product were seen. In regional blood flow, milrinone-induced increases in blood flow were seen in the cerebrum, cerebellum, and especially in the kidneys. Milrinone's vasodilatory effects were sufficient even under hypoxia. And milrinone increased regional blood flow slightly in the cerebrum and cerebellum, and significantly in the kidneys. These results suggested that milrinone protects against hypoxia-induced organ damage especially in the kidneys. In addition, milrinone is very potent in improving severe congested hemodynamics which complicates hypoxic pulmonary vasoconstriction.  相似文献   

Cranial features of the spotted seal, Phoca largha, in the Nemuro Strait, considering age effects     

Mizuno AW  Ohtaishi N 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2002,64(2):137-144

Cranial features (development, individual variation, and sexual dimorphism) were examined from the 23 metrical characters and 2 nonmetrical characters (the degree of closure of the 9 cranial sutures and the presence of sagittal crest) in the two spotted seal specimen groups at the Nemuro Strait, Hokkaido. One specimen group was incidentally taken in the salmon trap nets between 1982 and 1983 (n = 70), and the other was randomly sampled by damage control kill between 1997 and 1998 (n = 82). The development of morphometrical characters of skulls ceased at 5.6, 10.7, 7.9, and 11.9 yr. old, for 1982-83 male, 1982-83 female, 1997-98 male and 1997-98 female, respectively. The sutures were half ankylosed till approximately 10 yr. old in both sexes. The sagittal crest began from about 5 yr. old in male. Individual variation of skull was large in the feeding, breathing, and facial-expression apparatus. On the other hand, the variation of braincase, and skull concerning to the movement of head/neck tended to be small. Only 1997-98 specimens exhibited a sexual dimorphism in skull characters except for the braincase, whereas the dimorphism was not found in 1982-83 specimens. We could not detect the significant difference between two specimen groups, although there were a few differences in characters related to the rostrum and mandible.  相似文献   

Polymorphisms and the antiviral property of porcine Mx1 protein   总被引：9，自引：0，他引：9  

Asano A  Ko JH  Morozumi T  Hamashima N  Watanabe T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2002,64(12):1085-1089

We determined the cDNA sequences of the type I interferon-inducible proteins, pig Mx1 from PK(15) and LLC-PK1 cells, and compared the antiviral activities of both Mx proteins, including Mx1 polymorphisms against vesicular stomatitis virus (VSV). Mx1 cDNA derived from PK(15) cells had an 11 bp-deletion in the 3' end of the coding region, and was estimated to encode 8 amino acid substitutions and a 23 amino acid extension compared to that from LLC-PK1 cells. VSV replication was inhibited in the 3T3 cells expressing Mx1 mRNA after the cDNA was transfected. However, the efficiency of this inhibition was not different between the cells expressing Mx1 mRNA from both PK and LLC. These results indicate that pig Mx1 protein confers resistance to VSV.  相似文献