Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings

Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention.     

Seasonal variations in the incidence of pine wilt and infestation by its vector, Monochamus alternatus, near the northern limit of the disease in Japan

During the last few decades, pine wilt disease has spread to cool-climate regions in Japan and, more recently, the potential risk of it spreading into the European midwest has also become a concern. In a coastal pine stand (84.7?ha) in Akita, near the northern limit of pine wilt disease in Japan, we investigated seasonal variations in the incidence of damage caused by the disease to trees and oviposition by the disease’s insect vector, Monochamus alternatus, during a two-year period. Foliage discoloration occurred throughout each year, and its seasonal variation showed a bimodal pattern in Pinus thunbergii (a higher peak in May–June and a smaller peak in October) and a clear peak in June in P. densiflora, which differed from the patterns in seasonal variation seen for warm-climate regions. Oviposition scars by M. alternatus were found in 40–45% of the trees damaged each year. The percentage of trees that had oviposition scars was higher in P. thunbergii than in P. densiflora. This appeared to reflect the difference in seasonal discoloration pattern between the two species. Analysis of the oviposition risk showed that trees that exhibited discoloration starting between July and October had a significantly higher risk or significantly higher oviposition scar densities, particularly for those that became discolored between August and September (2.5–14.6-fold higher risk than during other months). Oviposition scar densities per damaged tree were similar within the period of higher oviposition risk. Considering both oviposition risks and scar densities, we concluded that trees with discoloration that become apparent between July and October are important targets for preventing the spread of pine wilt disease in Akita.     

Proceedings of the 2013 Joint JSTP/NTP Satellite Symposium

The first joint Japanese Society of Toxicologic Pathology (JSTP) and National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held on January 29^th at Okura Frontier Hotel in Tsukuba, Ibaraki, Japan, in advance of the JSTP’s 29^th Annual Meeting. The goal of this Symposium was to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, select images that were used for audience voting or discussion, and the voting results. Some lesions and topics covered during the symposium include: treatment-related atypical hepatocellular foci of cellular alteration in B6C3F1 mice; purulent ventriculoencephalitis in a young BALB/c mouse; a subcutaneous malignant schwannoma in a RccHan:WIST rat; spontaneous nasal septum hyalinosis/eosinophilic substance in B6C3F1 mice; a rare pancreatic ductal cell adenoma in a young Lewis rat; eosinophilic crystalline pneumonia in a transgenic mouse model; hyaline glomerulopathy in two female ddY mice; treatment-related intrahepatic erythrocytes in B6C3F1 mice; treatment-related subendothelial hepatocytes in B6C3F1 mice; spontaneous thyroid follicular cell vacuolar degeneration in a cynomolgus monkey; congenital hepatic fibrosis in a 1-year-old cat; a spontaneous adenocarcinoma of the middle ear in a young Crl:CD(SD) rat; and finally a series of cases illustrating some differences between cholangiofibrosis and cholangiocarcinoma in Sprague Dawley and F344 rats.     

分步型流域“降雨-流出”过程数值模拟方法的研究

流域地表流出的计算是水文学的一个重要研究课题。本研究以黄土高原北部的六道沟流域为流域模型,在确定试验流域地形和土壤物理性质的基础上,利用运动波理论和拟河道网开发分布型流域的"降雨-径流"过程的数值计算方法,对观测流量数值模拟结果的分析表明,该计算方法适用于北部黄土高原的实际,研究结论为该区域的地表水资源的推求提供了一种有效的数值计算方法。     

Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan: possible spread of the mutant allele in the Japanese domestic cat population

GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disease caused by simultaneous deficiencies of acid beta-hexosaminidase (Hex) A and Hex B due to an abnormality of beta-subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. In the present study, a retrospective diagnosis was performed in 2 previous suspected cases of feline Sandhoff-like disease using a DNA test to detect the causative mutation identified previously in 4 cats in 2 other families of Japanese domestic cats. Enzymic analysis was also performed using stored leukocytes and plasma collected from the subject families in order to investigate the usefulness of enzymic diagnosis and genotyping of carriers. The DNA test suggested that the 2 cases were homozygous recessive for the mutation. Consequently, 6 cats homozygous for the same mutation have been found in 4 separate locations of Japan, suggesting that this mutant allele may be spread widely in the Japanese domestic cat populations. In enzymic analysis, Hex A and Hex B activities in leukocytes and plasma measured using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide as a substrate were negligible in affected cats, compared with those in normal and carrier cats. However, there was a wide overlap in enzyme activity between normal and carrier cats. Therefore, it was concluded that enzymic analysis is useful for diagnosis of affected cats, but is not acceptable for genotyping of carriers.     

Arrangement of cortical microtubules in compression wood tracheids of Taxus cuspidata visualized by confocal laser microscopy

Cortical microtubules (MTs) in differentiating compression wood tracheids of Taxus cuspidata stems were visualized by confocal laser microscopy. They were oriented obliquely at an angle of about 45° to the tracheid axis during formation of the secondary wall. Artificial inclination altered the pattern of alignment of MTs. Banding MTs were helically oriented late during the formation of the secondary walls. These results indicate that MTs might control the orientation and localized deposition of cellulose microfibrils in the secondary walls of compression wood tracheids.Part of this report was presented at the 46th annual meeting of the Japan Wood Research Society, Kumamoto, April 1996     

Soybean meal can partially replace enzyme-treated fish meal in the diet of juvenile Pacific bluefin tuna <Emphasis Type="Italic">Thunnus orientalis</Emphasis>

This study was carried out to investigate whether expensive enzyme-treated fish meal (EFM) can be partially replaced by soybean meal (SM) or enzyme-treated SM (ESM) without compromising the growth of captive-raised Pacific bluefin tuna (PBT) juveniles. Five fish diets were tested: EFM (control) and EFM in which 10 or 20% of the EFM was replaced with either ESM or SM (ESM₁₀, ESM₂₀, SM₁₀ and SM₂₀, respectively). The respective diets were provided to 28-day-old PBT juveniles (mean body weight approx. 0.38 g) stocked randomly in 15-m³ tanks (276 juveniles per tank; two tanks per treatment) for 12 days. The final mean body weight of PBT juveniles on diets EFM, SM₁₀, and SM₂₀ was significantly higher than that of juveniles on diet ESM₂₀. Although daily feeding rate was significantly higher in the ESM and SM groups, feed efficiency (FE) was significantly higher in the EFM group; there was no significant difference between juveniles fed diets EFM and SM₁₀. Protein and phosphorus retention efficiency were significantly lower in the ESM₂₀, and ESM₂₀ and EFM groups, respectively. Phosphorus discharge was significantly lower in the SM groups. The results demonstrate that 10% SM (11% EFM replacement) can be included in EFM without compromising the growth performance of PBT juveniles.     

Development of a monoclonal antibody for the detection of anti-canine CD20 chimeric antigen receptor expression on canine CD20 chimeric antigen receptor-transduced T cells

Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.     

Tetrodotoxin--distribution and accumulation in aquatic organisms, and cases of human intoxication

Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue.