The aim of this study was to clarify the regulatory effects of epithelial kinetics on indigenous bacterial proliferation in the large intestine. The lifespan, migration speed and proliferation rate of crypt epithelial cells in the initial 20% of the colon (proximal colon) and the 50% of the colon (middle colon) in bromodeoxyuridine-administrated rats were histoplanimetrically and chronologically compared. The proximal colon possessed well-developed mucosal folds and a large amount of indigenous bacteria which filled the crypt lumen, whereas no folds or bacteria were found to occupy the crypt lumen in the middle colon. The cell lifespans were 32.2, 42.5 and 33.6 hr in the apical and the basal parts of the mucosal folds of the proximal colon, and in the middle colon, respectively. The migration speeds were 4.2, 2.1 and 3.3 μm/hr, respectively, while the appearance frequencies of proliferating cell nuclear antigen (PCNA)-positive crypt epithelial cells were 35.0, 24.6 and 33.8%. These findings suggest that the lifespan was shortened and the migration speed increased in the most luminal mucosa of colon, contributing to the elimination of the adhered bacteria from the most luminal mucosa. By contrast, the elongation of the lifespan and deceleration of the migration of epithelial cells in the basal parts of the mucosal folds might contribute to reliable settlement of indigenous bacteria, resulting in the maintenance of a large amount of indigenous bacteria in the lumen of the proximal colon.
The thoracic duct drains lymph from the caudal part of the body to the venous system. The visualization of the thoracic duct is important for diagnosis of chylothorax, which may be caused by the damage of the duct. However, it is not easy to visualize the thoracic duct by injecting dyes and/or contrast media into peripheral lymph nodes and mesenteric lymphatics. In the present study, we examined whether the thoracic duct can be visualized by injecting dyes and contrast media directly into the testicular parenchyma. Under deep pentobarbital anesthesia, 14 male Japanese White rabbits were percutaneously injected with dyes (India ink or methylene blue) or contrast media (iohexol 240, 300, or LipiodolTM) into the testicular parenchyma. Then, we grossly observed the stained thoracic duct or took radiographs and CT images of the duct. In all cases with dyes injections, the thoracic duct was successfully visualized. We observed stained lymphatic vessels from the testis to the duct. In case of contrast media injections, the thoracic duct was visualized with X-ray and CT imaging, when 1.5-2.0 ml per one testis of iohexol 240 at 37°C were injected into the right or both testes. The duct was most clearly visible, 3-5 min after the injections. The results show that the thoracic duct is reliably visualized simply by injecting dyes or contrast media into the testicular parenchyma. Our visualization method may also be applicable to the diagnosis of chylothorax in male animals.
We dissected the hindlimb of a female western lowland gorilla and determined the muscle dimensions (mass, fascicle length, and physiological cross-sectional area: PCSA). Comparisons of the muscle parameters of the measured gorilla with corresponding reported human data demonstrated that the triceps surae muscles were larger and had more capacity to generate force than the other muscle groups in both species, but this tendency was more prominent in the human, probably as an adaptation to strong toe-off during bipedal walking. On the other hand, PCSAs of the extrinsic pedal digital flexors and digiti minimi muscles were larger in the western lowland gorilla, suggesting that the foot, particularly the fifth toe, has a relatively high grasping capability in the lowland gorilla.
We investigated 66 Erysipelothrix rhusiopathiae strains isolated from pigs affected with swine erysipelas in Japan from 1994 to 2001 for serotype, pathogenicity towards mice, protection in vaccinated mice and antimicrobial susceptibility. Most of the isolates (84.8%) were serotype 1 or 2. For the first time, strains belonging to serotype 21 were isolated from cases of septicemia. Fifty isolates (75.8%) were highly virulent, 12 isolates (18.2%) were weakly virulent and 4 isolates were avirulent strains. All the mice vaccinated with the Koganei 65-0.15 vaccine strain survived challenge exposure with 50 highly virulent isolates. Six isolates (9.1%) grew on TPB-T80 agar containing 0.02% of acriflavine, and this was identical to the growth of the vaccine strain. Forty-seven isolates (71.2%) were resistant to oxytetracycline. The number of strains resistant to oxytetracycline among field isolates increased rapidly each year. Tylosin-resistant strains were also isolated (6.1%). These results suggest that certain characteristics, particularly antimicrobial susceptibility of E. rhusiopathiae isolates, change yearly in the field. Therefore, further investigation of the characteristics of E. rhusiopathiae field isolates is necessary.
Campylobacter jejuni is a major cause of food borne pathogens in humans and a major reservoir for this pathogen is poultry. The C. jejuni in broilers was investigated from in the caeca of broilers. Twenty broiler/flock samples from 7 flocks were assessed. The average prevalence of C. jejuni was 65% in the broiler flocks. The adhesion and invasion ability of 48 strains of C. jejuni on INT 407 were studied. The adhesion and invasion ability of 48 Campylobacter isolates from caecal contents were analyzed with Human embryonic intestine (INT-407) cells being used as a gentamicin resistance assay. The caecal isolates exhibited a wide range of adherence and invasion ability. There was a significant correlation (p<0.01) between the adherence and the invasion ability of the Campylobacter isolates. Each of the virulence-associated genes: dnaJ, cadF, pldA and ciaB was detected by polymerase chain reaction from 100, 76, 31 and 41% of the Campylobacter strains, respectively. All of four virulence-associated genes were detected in 11 isolates. However, there was unclear association between the invasion ability and the presence of virulence-associated genes in this experiment, suggesting that more genes may be involved in the invasion process.
Slime factor production and antibiotic resistance of 67 Enterococcus faecalis strains isolated from chicken arthritis were investigated in this study. Slime factor productions of enterococci were found as 59.7%. The antibiotic resistances were investigated by testing gentamycin, penicillin, streptomycin, vancomycin, danofloxacin, and enrofloxacin. The resistance rates were found as 62.68%, 76.11%, 67.16%, 13.43%, 47.76%, 43.28%, respectively. For slime factor positive enterococci, the antibiotic resistance rates were found as follows respectively; 82.50%, 87.50%, 92.50%, 17.50%, 72.50%, and 60.00%. In conclusion; the slime factor might play a role as a colonization factor for chicken arthritis and slime factor positive enterococci were found to be more resistant to these antibiotics. The resistance rates between slime factor positive and negative enterococci against the tested antibiotics except for vancomycin were found statistically significant (p<0.05).
The fragile histidine triad (FHIT) gene is a tumor-associated gene, and aberrant FHIT gene and protein expression have been described in many types of human tumors. Furthermore, it has been reported that FHIT gene inactivation is induced by hypermethylation of 5' CpG islands in the gene or by genomic deletion around the open reading frame (ORF). In this study, we explored the aberrations in the canine FHIT gene and Fhit protein expression and assessed the methylation status and genomic deletions by using 5 canine lymphoma cell lines. We found that the decrease in the expression of the Fhit protein in canine lymphoma cell lines was similar to that in human tumors. The expression of the wild-type FHIT transcript was reduced in all 5 cell lines. However, we could not confirm the involvement of aberrant methylation events in the 5' CpG islands of the canine FHIT gene. We were able to identify homozygous or heterozygous deletions in the canine FHIT genes in all 5 cell lines. Moreover, a widespread genomic deletion of the FHIT gene, which included the ORF region, was detected in 1 cell line. In the present study, we detected aberrations in the FHIT gene and Fhit protein expression in all 5 canine lymphoma cell lines, and this phenomenon might be an important factor in promoting canine lymphoma.
We present a clinical overview of a dog with acute onset of Hepatozoon canis infection. A stray female beagle dog of unknown age was referred to Kagoshima University showing anemia. Blood tests revealed the presence of anemia, thrombocytopenia, hyperproteinemia, polyclonal gammopathy, hypoalbuminemia, and elevated creatine kinase and alkaline phosphatase activities. In addition, capsule-like organisms were detected in the cytoplasm of approximately 50% of neutrophils in blood smears. H. canis infection was confirmed by polymerase chain reaction and DNA sequencing analyses. Amplified DNA fragments revealed 100% identity to the 18S ribosomal RNA gene of H. canis. The clinical symptoms improved after the administration of antibiotics. Hepatozoonosis in dogs is rare, but veterinarians should be alert to its possible acute onset.
The purpose of this article was to investigate the effects of sedatives and general anesthetics, such as tiletamine-zolazepam, medetomidine, and isoflurane on the short ERG protocol. Six healthy mongrel dogs were assessed by a convenient short ERG protocol with the owners' consent. The amplitudes of a-wave and b-wave, as well as the implicit time of ERG under different anesthesia statuses, were recorded and analyzed. The amplitudes of ERG waves were not significantly different between tiletamine-zolazepam and medetomidine groups, except in b-wave after 5 min dark adaptation (140 ± 42 μV in tiletamine-zolazepam and 101 ± 32 μV in medetomidine, p<0.01). The amplitude of ERG recorded in isoflurane (5 ± 3 μV of a-wave and 12 ± 6 μV of b-wave under light adaptation; 41 ± 19 μV of b-wave after 1 min dark adaptation; 28 ± 15 μV of a-wave and 58 ± 32 μV of b-wave after 5 min dark adaptation) were significantly different from tiletamine-zolazepam (8 ± 2 μV of a-wave and 24 ± 9 μV of b-wave under light adaptation; 117 ± 44 μV of b-wave after 1 min dark adaptation; 59 ± 18 μV of a-wave and 140 ± 42 μV of b-wave after 5 min dark adaptation), except in a-wave after 1 min dark adaptation (39 ± 13 μV in tiletamine-zolazepam and 34 ± 17 μV in isoflurane). Comment-General anesthesia had significantly lower amplitudes in the dark-adapted group compared with the sedation group. Therefore, tiletamine-zolazepam is a desirable choice for the short ERG protocol in dogs.
A 4-year-old spayed female domestic shorthair cat was presented to us for swelling of all foot pads. The skin lesions were histopathologically diagnosed as suppurative pyogranulomatous panniculitis. The lesions did not respond to cephalexin, prednisolone or itraconazole. However, complete resolution of the skin lesions was obtained with doxycycline. A littermate living in the same household developed similar skin lesions that were also successfully treated with doxycycline. Polymerase chain reaction analysis detected the 16S ribosomal RNA gene of Nocardia spp. in DNA extracted from lesion pus, and direct nucleotide sequencing analysis revealed 100% homology with Nocardia elegans. We diagnosed this case as nocardiosis.
The purposes of this study were to determine the tissue distribution of canine adrenomedullin (AM) and to determine whether increased canine AM mRNA expression is associated with congestive heart failure (CHF) due to mitral regurgitation (MR). Canine AM mRNA expression was detectable in various normal tissues, including cardiovascular tissues. In addition, the AM mRNA expression in the left atrium of dogs with MR was significantly higher than that in normal subjects. In conclusion, AM is a potential neurohumoral factor in dogs with CHF due to MR.
A 10-year-old Japanese domestic cat was presented with anorexia and weight loss. Severe anemia and thrombocytopenia were detected. Abdominal radiography and ultrasonography revealed the presence of multiple masses in the spleen. Cytological analyses of the masses revealed several atypical histiocytic cells and considerable hemophagocytosis. A splenectomy was performed, and the mass was diagnosed as histiocytic sarcoma on the basis of histopathological, cytochemical and immunohistochemical analyses. Further, abnormal hemophagocytosis was observed in the bone marrow. The cat was administered prednisolone and lomustine, and it survived for 107 days after admission. An autopsy revealed the presence of neoplastic histiocytic cells in the bone marrow, liver, pancreatic lymph node and glomeruli. This is the first case of histiocytic sarcoma in a cat to be reported in Japan.
A 7-month-old Holstein heifer presented with posterior paresis and megaesophagus. At post mortem examination, a nodular tumor was found attached to the thoracic wall and the eighth to eleventh thoracic vertebrae, adjacent to the left posterior pulmonary lobe. The tumor was diagnosed as rhabdomyosarcoma by histology. This is a very rare case of spinal infiltration of rhabdomyosarcoma in cattle.
Our objective was to evaluate the effects of a reservoir-type calcitriol (5 mg/animal) transdermal patch on plasma calcitriol and calcium (Ca) concentrations in dairy cattle. A group of six heifers received three different types of patches: an encapsulated reservoir solution containing calcitriol alone (CAL), calcitriol with dodecylamine (CAL+D), or vehicle (CONT). The patches were applied to the skin of the tail for duration of 2 days at intervals of at least 3 weeks. Cattle that received CAL or CAL+D showed significant increases in plasma calcitriol and Ca concentrations on day 2 and days 2 and 3, respectively. The areas under the plasma concentration-time curve (AUC) values for plasma calcitriol and Ca in the CAL and CAL+D groups increased significantly compared to the CONT group. The data of this study describe evidence of measurable transdermal absorption of exogenous calcitriol from a patch and its sufficient biological action to elevate plasma Ca concentrations.
The purpose of this study was to investigate the pathology of zymosan-induced arthritis in the SKG mouse model of rheumatoid arthritis in humans, and to validate this model as a reliable drug screening system. To achieve this purpose, methotrexate (1 or 10 mg/kg, once daily) or vehicle only was administered intraperitoneally to SKG mice with zymosan-induced arthritis. Histologically, this arthritis was characterized by the presence of granulation tissue rich in granulocytes. Methotrexate suppressed the development of arthritis in ankle and wrist joints in both clinical and histological studies. These results indicated that methotrexate has not only prophylactic, but also therapeutic effects on zymosan-induced arthritis developed in SKG mice and may thus be a promising control agent for drug research in the SKG mouse model of rheumatoid arthritis.
For chronic kidney disease patients with renal anemia, recombinant human erythropoietin (rHuEPO) is a very effective drug; however, the treatment regime is troublesome, requiring multiple administrations each week. In the present study, we examined the efficiency of hydroxyapatite (HAp) as a drug delivery carrier for the sustained release of erythropoietin (EPO) to reduce the frequency of administration. Spray-dried HAp microparticles, formed from zinc-containing HAp (Zn-HAp) and Zn-HAp calcined at 400°C, were used as carriers of EPO, and five Zn-HAp formulation samples incorporating EPO were prepared; no formulation, poly-L-lactic acid (PLA) formulation, zinc (Zn) formulation, Zn/PLA formulation, and calcined/Zn/PLA formulation. ICR mice were administered these samples or commercial rHuEPO (Epogin) as a control from dorsal neck subcutaneous, and hematological and histopathological analyses, including enzyme-linked immunosorbent assay for plasma EPO concentration, were performed. An increase in the blood EPO level was detected on days 3 and 8 post-administration. Peak hematopoiesis was delayed and higher hematological values were obtained on day 14 post-administration with no serious adverse reactions compared with the control. The Zn/PLA formulation sample was found to be most effective in reducing the initial peak while sustaining the delayed release of EPO. In conclusion, the Zn-HAp formulation samples were considered to be useful carriers for the sustained release of EPO, and the Zn/PLA formulation appears to be the most effective of five Zn-HAp formulation samples in sustaining EPO release.
In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.
The success of immunological method for the control of ticks depend on the use of potential key antigens as tick vaccine candidates. Chitinase is induced by ecdysteroids to degrade the older chitin at the time of molting. Previously, we cloned a gene encoding 113 kDa protein (CHT1) of Haemaphysalis longicornis, and identified the CHT1 as a protein of chitinase (You et al. 2003). In this study, the recombinant CHT1 (rCHT1) expressed in Escherichia coli was used to immunize mice. The mice were challenge-infested with ticks at different developmental stages of the same species. The rCHT1 stimulated a specific protective anti-tick immune response in the mice as evidenced by the significant longer feeding periods in the larval ticks and significant difference in the egg weights. The molting periods in the ticks fed on the rCHT1-immunized mice tended to be longer than those of the controls. Nymphal ticks fed on the rCHT1-immunized mice showed lower molting rate (76.7%) compared to 96.7% for the control. These results demonstrated that the rCHT1-immunized mice sera implicated on molting step, suggesting that the rCHT1 might be a useful vaccine candidate antigen for biological control of the tick.
Ultrastructure of Dirofilaria immitis microfilaria(Mf) was imaged through scanning and transmission electron microscopies. Transverse annular striations covered all over the surface of the whole body. Two small pores on the cephalic disk and the mouth-like cavity at a ventral side of the first striation next to the cephalic disk were observed. A single triangular hook was projected from the upper palate. The excretory pore was observed at the 80th annulus from the anterior end, and the anal pore at the 90th annulus from the posterior end. The both pores were located at the ventral side of the body. This study first demonstrated that a large number of nuclear column cells were distributed in the body cavity. These cells were spherical and about 1 μm in diameter. Each of the cells contained a spherical nucleus and was connected to each other by micro-strings that were running radially. Many flattened muscle cells were located at the inside of the hypodermis of the whole body. The tail contained only a single longitudinal muscle cell.
Kaposiform hemangioendothelioma is a rare human vascular neoplasm. In veterinary medicine this tumor type was only recognized in the dog. Here we describe an unusual case arising in the urinary bladder of a Holstein-Friesian adult cow. Histologically the tumor presented a nodular proliferation of spindle cells, forming angular slits, often containing extravasated erythrocytes. Peripherically, well-formed vascular channels were seen. These cells were positive to vimentin and to factor VIII-related antigen by immunohistochemical stain. Based on its characteristics, it was classified as kaposiform hemangioendothelioma and as far as we know, it is the first case described in cattle.
Inhibition of cardiac hypertrophy leads to a significant reduction in cardiovascular mortality and morbidity. Quercetin is by far the most abundant flavonoid and believed to ameliorate cardiovascular disease. Therefore, we investigated whether quercetin supplementation could attenuate the development of cardiac hypertrophy induced by pressure overload. Three weeks after suprarenal transverse abdominal aortic constriction, heart to body weight (HW/BW) ratio increased compared to the sham group (3.40 ± 0.06 mg/g versus 2.83 ± 0.02 mg/g, P<0.001). The quercetin administered group showed complete inhibition of cardiac hypertrophy (2.85 ± 0.01 mg/g, P<0.001). Malonyldialdehyde production induced by pressure overload was suppressed by quercetin. The activities of extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase, Akt and GSK-3β were significantly increased with pressure overload and attenuated by quercetin treatment. We conclude that quercetin appears to block the development of cardiac hypertrophy induced by pressure overload in rats and that these effects may be mediated through reduced oxidant status and inhibition of ERK1/2, p38 MAP kinase, Akt and GSK-3β activities.
The aims of this study were to confirm whether commercial acetated Ringer's solution, which contains 28 mM of sodium acetate, is superior to commercial lactated Ringer's solution in alkalizing effects in calves with experimentally induced metabolic acidosis. Twenty calves with experimentally induced mild acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The acetated Ringer's solution induced a significantly greater increase in venous HCO3- and base excess concentrations than the other fluids during the early phases of extracellular fluid replacement in mild metabolic acidosis. Therefore, the alkalizing effect of commercial acetated Ringer's solution is superior to commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic acidosis in calves.
We surveyed the prevalence of Leptospira spp. from 2005 to 2008 in wild boars and deer in Japan using polymerase chain reaction. Leptospiral flaB was detected in the kidneys of wild boars (positive ratio, 15.2%; 22 of 145) from 9 prefectures and a deer (1.1%; 1 of 94) from 1 prefecture in Japan. There was no annual change in the prevalence of positive animals during the investigation period (chi-squared test, p=0.94) or in the prevalence in male and female wild boars in the 2007 to 2008 season (Fisher's exact test, P=0.45). The Leptospira species harbored by these animals were deduced to be L. interrogans (from 22 animals) and L. borgpetersenii (from 1 animal).
Stray dogs are a public health risk factor when canine rabies is endemic. The Rabies Prevention Law has introduced measures to control stray dogs, but many dogs are still captured in Japan. In order to estimate the immune status of stray dogs for the purposes of risk management, we conducted a serological survey at the Hyogo Prefecture Animal Well-being Center. Only 27.7% of dogs brought into the Center (n=166) had protective immune status. This result suggests that there is the potential for reintroduction of canine rabies into stray dogs, leading to endemic rabies and its transmission to humans. Continued removal of stray dogs, education on rabies prevention and vaccination of dogs therefore remain important public health issues.
The carrier rates of Complex Vertebral Malformation (CVM) in 9 Holstein dairy herds in Hokkaido, number of usages of CVM carrier semen for breeding and gene frequencies of CVM carriers were measured. The mean CVM carrier rates of 140 cows from 4 herds in 1994 and 315 cows from 5 herds in 2003 were 10.8%(range 4.7-30.0%) and 5.1%(range 0.0-6.1%), respectively. The rate of use of CVM carrier semen in the Hokkaido district was 5.6% in 2002. The gene frequencies calculated from CVM carriers among the 315 cows and number of CVM carrier semen samples used were 0.032 and 0.028, and the occurrence of homozygous CVM in 2003 was estimated to be 0.1% in the local districts of Hokkaido, Japan.
The effects of the time period between canine epididymis removal and cooling on post-thaw caudal epididymal sperm quality were investigated. Sperm recovered from the epididymis stored for 6 hr at 4 or 20°C exhibited similar motility. However, when the epididymis was stored for 12 hr or longer at 20°C, sperm motility was significantly lower than that at 4°C (p<0.01). The post-thawed qualities of sperm recovered from the caudal epididymides that had been stored at 20°C for 0 or 6 hr and then at 4°C for 24 hr after removal were not significantly different. Therefore, leaving the canine epididymis at 20°C for up to 6 hr after its removal may have little effect on the post-thaw quality of recovered caudal epididymal sperm.
Thioacetamide (TA) is a potent hepatotoxicant known to affect liver metabolism, inhibit mRNA transport and induce immune suppression. The genetic mechanism underlining this biological toxic compound is well understood using microarray technology. Thus, we used high-throughput rat genome oligonucleotide microarrays containing approximately 22,000 genes to investigate the genetic components of TA-related cytotoxicity in WB-F344 rat liver epithelial (WB-F344) cells. We treated cells with TA (two concentrations over five time periods, ranging from 1 to 24 hr), isolated total RNA at 1, 3, 6, 12 and 24 hr following TA treatment and hybridized the RNA to microarrays. Clustering analysis distinguished two groups of genes, early (1 and 3 hr) and late (6, 12 and 24 hr) phase genes. In total, 2,129 and 2,348 differentially-expressed genes were identified following treatment with low and high concentrations of TA, respectively. A common set of 1,229 genes that were differentially expressed following treatment with both low (1,000 μM) and high (10,000 μM) concentrations of TA had similar expression patterns. Interestingly, 1,410 genes at the low concentration and 1,858 genes at the high concentration were differentially expressed in the early phases, suggesting that these genes associated with the early response to TA may be useful as early markers of hepatotoxicity.
A chromatographic strip assay was developed for rapid detection of serum antibodies to non-structural protein of foot-and-mouth disease virus. The assay was based on Escherichia coli-expressed 3ABC non-structural protein and an immunochromatographic technique, which shortened the detection time to about one hour. The sensitivity of the assay was determined to be 96.8% for infected pigs; its specificity was 100% for naïve pigs and 98.8% for vaccinated pigs. In the experimentally infected pigs, anti-3ABC antibodies were detectable from eight days post-infection until the end of the study, 34 days post-infection. The performance of this assay was comparable to that of two commercial ELISA kits, Ceditest FMDV-NS and UBI FMDV NS EIA, and was better than that of CHEKIT FMD-3ABC po. Given its advantages of instant testing and quantitative measurement, this assay has potential as a useful tool for rapid on-farm diagnosis of foot-and-mouth disease.
Bovine viral diarrhea virus 2 (BVDV-2) strains are divided into cytopathic and non-cytopathic biotypes based on the ablity to induce cytopathic effects in cultured cells. The mechanism of cytopathogenicity of BVDV-2 is not well understood. We examined cytopathogenesis in MDBK cells resulting from BVDV-2 infections by microscopic examinations and microarray analysis. We found that BVDV-2 activates endoplasmic reticulum (ER) stress signaling pathways that contribute to apoptosis of infected cells. We also monitored the expression of ER stress marker gene by RT-PCR during BVDV-2 infection and demonstrated that infection of MDBK cells with a cytopathic strain of BVDV-2 induces glucose-regulated protein 78 expression. Infection with BVDV-2 also induces DNA-damage-inducible transcript 3 expression and downregulates the lectin-galactoside-binding soluble 1 level. These results show that cytopathic strains of BVDV-2 induce an ER stress response resulting in apoptosis.