Three dogs under 2 years of age with heartworm caval syndrome

Heartworm caval syndrome (CS) occurred in three dogs under 2 years of age. A 23-month-old dog was recovered by surgical and medical treatments, but the other 2 dogs (15 and 21 months old) died. Necropsy demonstrated 12 heartworms in the 15-month-old dog and 8 worms in the 21-month-old dog. Histopathologically, pulmonary arterial embolism caused by dead worms and thrombi were observed in these cases. The findings suggested that CS could develop regardless of canine age and worm burden if pulmonary arterial embolism related to worm death or thrombus formation were induced.     

Isolation of Salmonella from diarrheic feces of pigs

A survey of Salmonella was carried out in fecal samples of 887 pigs with diarrhea collected from 235 pig farms between April 1996 and March 2001. Salmonella was isolated from 84 feces (9.5%) of 887 pigs and from 45 (19.1%) of 235 farms. The higher prevalence was found in weaned pigs (12.4%) and fattening pigs (17.3%) than in sows (4.2%) and suckling pigs (4.5%). Isolation rates of S. Typhimurium were higher from weaned and fattening pigs than from the others. Therefore, risk of horizontal infection of S. Typhimurium will increase, if no adequate health managements are practiced when weaned and fattening pigs have diarrhea.     

Isolation and serological survey of Salmonella in pigs in Japan

A total of 267 fecal and serum samples collected from individual pigs reared on a Salmonella-positive farm were subjected to bacteriological and serological examinations of Salmonella. Salmonella was isolated from 47 pigs (17.6%) and prevalence of antibody to lipopolysaccharide (LPS) of S. Typhimurium, which was partly common to S. O4, 12: d: -, was observed in 90 pigs (33.7%). Salmonella was isolated from 26 (28.9%) of 90 antibody-positive pigs and 21 (11.9%) of 177 antibody-negative pigs. Twenty-one of 36 pigs (58.3%) positive for S. O4, 12: d: -, five of 10 pigs (50.0%) positive for S. Havana, and none for S. Anatum had antibodies. Thus, seropositive rates were higher than isolation-positive rates, and antibody prevalence was associated with serovars of the isolates. Then, we analyzed antibody prevalence among pigs on Japanese pig farms. The antibodies to LPS of S. Typhimurium were found in 195 of 1,498 pigs (13.0%) and in at least one serum sample on 35 of 52 farms (67.3%). Our results indicate that Salmonella does not seem to be so prevalent in pigs though it is widely prevalent among pig farms.     

Bacteriophage OP1, lytic for Xanthomonas oryzae pv. oryzae, changes its host range by duplication and deletion of the small domain in the deduced tail fiber gene

The entire genome of bacteriophage OP₁, lytic for Xanthomonas oryzae pv. oryzae causing bacterial leaf blight of rice, and the partial genomes of related phages were sequenced and analyzed. The OP₁ genome comprises double-stranded, 4785-bp long DNA with 51.1% G + C content. Fifty-nine open reading frames (ORFs) were detected. ORF25 had similarity with the tail fiber gene of phages, whose product is related to host specificity. The ORF25 regions were amplified from four host-range mutants (OP_1h, OP_1hC, OP_1h2, and OP_1h2C) by polymerase chain reaction, and their deduced amino acid sequences were compared. Three mutants (OP_1hC, OP_1h2, OP_1h2C) had duplications of a small domain in the N-terminal portion, although there were slight differences in the position of the duplicated sequences. One mutant OP_1h had substituted amino acids in the duplication region. New mutants isolated in the laboratory (OP_1hC and OP_1h2C from OP₁ and OP_1h2) acquired the ability to lyse strain N5874 belonging to phagovar (lysotype) C. However, they rapidly lost this lytic ability when incubated with other phagovars. This loss was always accompanied by a loss of the characteristic repeats, suggesting that the host range of OP₁-related phages changed mainly through duplication and deletion of a small domain in ORF25. The nucleotide sequence data reported are available in the DDBJ/EMBL/GenBank databases under the accession numbers AP008979, AB214312 to AB214316     

The role of primary germ tubes in the life cycle of Blumeria graminis: The primary germ tube is responsible for the suppression of resistance induction of a host plant cell

When the conidia of Blumeria graminis f. sp. hordei (Bgh) are inoculated on barley coleoptile cells they produce short germ tubes called primary germ tubes (PGTs) about 2 h after inoculation. We evaluated the positive role of a PGT in inducing accessibility of the host cell under the germ tube. When an appressorium (APP) penetrated the same cell on which a PGT was present, the ratio of haustorium formation (penetration efficiency) was significantly higher than when an APP penetrated the cell adjacent to the one on which a PGT was present. When an APP penetrated the cell laterally adjacent to the one on which a PGT was present we killed the cell under the PGT by puncturing it with a microneedle and then investigated the penetration efficiency of the cell adjacent to the dead cell. As a control we killed the cell longitudinally adjacent to the one on which a PGT was present and investigated the penetration efficiency of the laterally adjacent cell. The results showed that the penetration efficiency of the former was significantly lower than that of the latter. This suggests that some accessibility factor might transfer from a cell on which a PGT is present to a laterally adjacent cell. The existence of a conidium body but not a PGT was not effective for induced accessibility of the host cell. Moreover, when a Bgh germling was removed 6 h after inoculation and another germling was transferred to the same cell, the penetration efficiency was significantly higher than that of control. As a control, a Bgh germling was transferred to a cell on which no germling was present. These results suggest that the existence of PGT is effective for induced accessibility of a host cell when penetrated by Bgh. However, it is unclear whether or not a PGT secretes some substance(s) which suppresses the resistance induction of a host cell.     

Age and growth of alfonsino Beryx splendens from the Kanto District, central Japan, based on growth increments on otoliths

ABSTRACT:   Age and growth of alfonsino Beryx splendens (Lowe) were studied using counts of presumed daily incremental growth rings on the transverse section of otoliths of fish collected from the Kanto District, central Japan. Microstructural growth increments were observed from the core to the outermost margin of the broadest of approximately 50 branches formed on the surface of an otolith. Of 98 otoliths examined, 46 were readable. The number of increments and fish lengths ranged from 448 (218 mm fork length [FL]) to 3701 (411 mm FL). The ages of these fish were estimated to be 1 year, 2 months and 10 years, 2 months, respectively, assuming that an increment was formed daily. The von Bertalanffy growth equation combined for males and females was expressed as follows: L _t  = 542 {1 −  exp  [−0.133( t  + 2.00)]}, where L _t is fork length (mm) at yearly age t . The results of the present study were compared with those of other researchers who had studied alfonsino from central Japan.     

Responses to the Standard for Exchange of Nonclinical Data (SEND) in non-US countries

The Standard for the Exchange of Nonclinical Data (SEND), adopted by the US FDA, is part of a set of regulations and guidances requiring the submission of standardized electronic study data for nonclinical and clinical data submissions. SEND is the nonclinical implementation of SDTM (Study Data Tabulation Model), the standard electronic format for clinical regulatory submissions to FDA. SEND, SDTM, and the associated Controlled Terminology have been developed by CDISC (Clinical Data Interchange Standards Consortium). In order to successfully implement SEND, interdisciplinary contributions between sponsors and CROs, need a model for task allocation. This is being undertaken by the Pharmaceutical Users Software Exchange (PhUSE). Because SEND is currently the preferred submission format of the US FDA only and will become required by it starting in December 2016, only American academic societies and companies are actively involved. An exception to this is the INHAND initiative, which leads the way in standardizing terminology for toxicological pathology. On the other hand, international globalization of other clinical and nonclinical practices is not feasible because there are substantial differences between the US and non-US countries in CRO involvement in drug development. Thus, non-US countries must consider and develop approaches to SEND that meet their needs. This paper summarizes the activities of the major organizations involved in SEND development and implementation, discusses the effective use of SEND, and details a compliance scheme (research material of the Showa University School of Medicine) illustrating how pharmaceutical companies can complete a large amount of work up to an FDA application with the effective utilization of CROs and solution providers.     

The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma

Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels have been reported to exacerbate human tumor progression. The role of SET in canine melanoma, however, has not been understood. Here, we investigated the potential therapeutic role for SET inhibitors in canine melanoma. The expression of SET protein was observed in 6 canine melanoma cell lines. We used CMeC-1 cells (primary origin) and CMeC-2 cells (metastatic origin) to generate cell lines stably expressing SET-targeting shRNAs. Knockdown of SET expression in CMeC-2, but not in CMeC-1, leads to decreased cell proliferation, invasion and colony formation. Phosphorylation level of p70 S6 kinase was decreased by SET knockdown in CMeC-2, suggesting the involvement of mTOR (mammalian target of rapamycin)/p70 S6 kinase signaling. The SET inhibitors, OP449 and FTY720, more effectively killed CMeC-2 than CMeC-1. We observed PP2A activation in CMeC-2 treated with OP449 and FTY720. These results demonstrated the potential therapeutic application of SET inhibitors for canine melanoma.