Palmoplantar pustulosis and pustulotic arthro-osteitis associated with multiple venous occlusion: A case report and literature review.

Pustulotic arthro-osteitis (PAO) is a rare chronic inflammatory arthropathy associated with palmoplantar pustulosis. The pathogenesis of PAO remains unclear. The most common musculoskeletal involvement in PAO is ossification of the sternoclavicular joints. A combination of parietal inflammation and hyperostosis-induced mechanical compression in this region is hypothesized to contribute to multiple venous thrombosis. Here, we present a 66-year-old man with PAO-associated multiple venous occlusion who was successfully treated with guselkumab. We also discuss its clinical manifestation and cause by reviewing the literature.

Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

BACKGROUND: The risk factors associated with the development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD) are still unclear. The aim of the present study was to identify such risk factors in NAFLD patients who developed HCC. METHODS: Between April 2000 and -December 2016, a total of 182 patients with NAFLD were enrolled in this study; of these, only 22 patients had HCC. To identify risk factors, univariate and multivariate analyses were performed. To identify risk factors other than the degree of fibrosis, propensity matched analysis adjusted by the NAFLD fibrosis score (NFS) was carried out on 44 patients. Multivariate and survival analyses were also performed in HCC patients. RESULTS: In 182 patients, multivariate analysis highlighted the NFS (OR 2.275; p < 0.001) and hypertension (OR 5.868; p = 0.037) as independent factors that were significantly associated with the development of HCC. After adjustment for the NFS, multivariate analysis identified diabetic retinopathy (OR 8.654; p = 0.017) as an independent factor that was significantly associated with the development of HCC. For predicting the development of HCC, the area under the receiver operating characteristic curve of diabetic retinopathy was significantly higher than that of diabetes (0.731 vs. 0.615; p < 0.001). In patients with HCC, multivariate analysis indicated that the NFS were significantly associated with diabetic retinopathy. CONCLUSIONS: Diabetic retinopathy as well as liver fibrosis is a risk factor that associates with the development of HCC in NAFLD patients. Therefore, NAFLD patients with diabetic retinopathy should undergo careful screening for HCC.

Altered expression of microRNAs in patients with pouchitis after restorative proctocolectomy.

BACKGROUND AND PURPOSE: Pouchitis is the most common long-term complication of restorative proctocolectomy with ileal pouch-anal anastomosis. We investigated alterations in the expression of microRNAs, noncoding RNAs that act as potent negative regulators of gene expression, in pouchitis. METHODS: The subjects of this study were 16 patients with diagnosed pouchitis and 48 patients without pouchitis after restorative proctocolectomy, performed for ulcerative colitis. Total RNA was extracted from biopsies and microRNAs were quantified using a real-time polymerase chain reaction. RESULTS: The expression of microRNA 21 and 223 was higher, whereas that of microRNA 192 and 196a was lower, in the inflamed mucosa from the pouchitis patients than in the mucosa from the non-pouchitis patients. The levels of 14 microRNAs were significantly lower in the mucosa from the pouchitis patients, than in the non-inflamed proximal ileal mucosal samples. The expression of microRNA 192 was remarkably reduced in pouchitis. A significant negative correlation was found between microRNA 192 and interleukin 17 receptor A mRNA levels. CONCLUSIONS: Significant alteration in miRNA expression in line with inflammatory bowel disease was evident in the mucosa from the pouchitis patients. Interleukin 17 receptor A may be involved in the pathogenesis of pouchitis through the downregulation of microRNA 192.

Delayed-onset enzootic bovine leukosis possibly caused by superinfection with bovine leukemia virus mutated in the pol gene.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), to which animals are most susceptible at 4-8 years of age. In this study, we examined tumor cells associated with EBL in an 18-year-old cow to reveal that the cells carried at least two different copies of the virus, one of which was predicted to encode a reverse transcriptase (RT) lacking ribonuclease H activity and no integrase. Such a deficient enzyme may exhibit a dominant negative effect on the wild-type RT and cause insufficient viral replication, resulting in delayed tumor development in this cow.

Comparative studies of human UDP-glucuronosyltransferase 1A8 and 1A9 proximal promoters using single base substitutions.

  The nucleotide sequences of the proximal promoters of UDP-glucuronosyltransferase (UGT) 1A8 and 1A9 genes are very similar. However, UGT1A8 and 1A9 are mainly expressed in extra-hepatic and hepatic cells, respectively. Using mutants of UGT1A8 and 1A9 proximal promoters, we revealed their critical differences in terms of promoter activity and the role of the T-repeat region (T-region) conserved in both promoters. In extra-hepatic cells, Caco2, the activity of UGT1A9 proximal promoter increased to 73.4 ± 8.5% of that of the UGT1A8 proximal promoter with only 4 base changes: -160C, -152A, -62T, and -59G. The derivatives of the T-region showed that this region is not necessary for promoter activity, but the length of T repeats influences the activity somewhat. Therefore, the cause of the low activity of the UGT1A9 proximal promoter may be not only 4 base changes, but also the truncation of T repeats. From these results, the UGT1A9 proximal promoter was assumed to change into the non-active form from the original sequence, and this might be one of the reasons for the tissue-specific expression of UGT1A9.

An NA-deficient 2009 pandemic H1N1 influenza virus mutant can efficiently replicate in cultured cells.

We identified a novel neuraminidase (NA)-deficient virus that was a 2009 pandemic influenza H1N1 virus mutant. The mutant virus had a deletion of 1,009 nt in the NA gene and lacked an enzymatic domain. Although the yield of the NA-deficient virus was limited, it formed large plaques when applied to MDCK cell cultures, indicating that the virus was able to spread to adjacent cells. Furthermore, the NA-deficient virus was eluted from chicken erythrocytes at 37 °C, even in the presence of the antiviral drug peramivir. Spread of this NA-deficient virus may pose a potential threat to anti-influenza therapies.

L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus.

The bovine leukemia virus (BLV) Tax protein is believed to play a crucial role in leukemogenesis by the virus. BLV usually causes asymptomatic infections in cattle, but only one-third develop persistent lymphocytosis that rarely progress after a long incubation period to lymphoid tumors, namely enzootic bovine leucosis (EBL). In the present study, we demonstrated that the BLV tax genes could be divided into two alleles and developed multiplex PCR detecting an L233P mutation of the Tax protein. Then, in order to define the relationship between the Tax protein and leukemogenicity, we examined 360 tumor samples randomly collected from dairy or breeding cattle in Japan, of which Tax proteins were categorized, for age at the time of diagnosis of EBL. The ages of 288 animals (80.0%) associated with L233-Tax and those of 70 animals (19.4%) with P233-Tax individually followed log-normal distributions. Only the two earliest cases (0.6%) with L233-Tax disobeyed the log-normal distribution. These findings suggest that the animals affected by EBL were infected with the virus at a particular point in life, probably less than a few months after birth. Median age of those with P233-Tax was 22 months older than that with L233-Tax and geometric means exhibited a significant difference (P<0.01). It is also quite unlikely that viruses carrying the particular Tax protein infect older cattle. Here, we conclude that BLV could be divided into two categories on the basis of amino acid at position 233 of the Tax protein, which strongly correlated with leukemogenicity.

Phylogenetic analyses of pandemic influenza A (H1N1) virus in university students at Tobetsu, Hokkaido, Japan.

Pandemic influenza H1N1 virus (A[H1N1]pdm09) emerged in 2009. To determine the phylogeography of A(H1N1)pdm09 in a single population, 70 strains of the virus were isolated from university students or trainee doctors at Tobetsu, Hokkaido, Japan, between September and December 2009. The nucleotide sequences of the HA1 region of the HA genes and described phylogenetic relationships of the strains circulating among them were analyzed. It was found that the 70 isolates could be phylogenetically separated into three groups and that two epidemics were caused by different groups of the virus. The three groups were also distinguishable from each other by three amino acid changes: A197T, S203T and Q293H. The substitution of S203T, which is located in the antigenic site, suggests antigenic drift of the virus.