A Patient with Systemic Lupus Erythematosus Complicated by Neurological Symptoms of Toluene Poisoning

We report a patient with systemic lupus erythematosus complicated by toluene poisoning. She had erythema, alopecia, arthralgia, and various neurological symptoms. Laboratory findings showed leukocytopenia, low levels of complements, and anti-dsDNA antibody. However, normal interleukin-6 level and IgG index of cerebrospinal fluid and brain magnetic resonance imaging and single photon emission computed tomography findings suggested that her neurological symptoms were caused by metabolic disorder but not neuropsychiatric systemic lupus erythematosus. Erythema, alopecia, and arthralgia improved rapidly after administration of prednisolone and tacrolimus, whereas neurological symptoms improved only gradually. Because of a history of exposure to toluene, her neurological symptoms were considered to be due to toluene poisoning. The differentiation of toluene poisoning from neuropsychiatric systemic lupus erythematosus based on symptoms is difficult because both induce various neuropsychiatric disorders. Laboratory findings of cerebrospinal fluid, radiological findings, and medical interview were useful for differentiation of toluene poisoning from neuropsychiatric systemic lupus erythematosus

Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma

Background: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary phase in hepatocellular carcinoma (HCC). Methods: A retrospective analysis of 22 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was performed. Enhancement ratios (ERs) and expression levels of the organic anion transporter (OATP) 1B3 protein were examined. Results: Gd-EOB-DTPA accumulated in the hepatobiliary phase in 6 of the 22 cases. All 6 Gd-EOB-DTPA-positive cases were moderately differentiated HCC, but 11 other moderately differentiated HCCs did not show Gd-EOB-DTPA uptake. Histopathologically, 4 Gd-EOB-DTPA-positive HCCs and 5 Gd-EOB-DTPA-negative HCCs produced bile. HCCs with Gd-EOB-DTPA uptake overexpressed OATP1B3 compared with HCCs without Gd-EOB-DTPA uptake, and OATP1B3 levels were significantly correlated with ERs (r = 0.91, P < 0.0001). Conclusions: Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production

Generation of congenic mouse strains by introducing the virus-resistant genes, Mx1 and Oas1b, of feral mouse-derived inbred strain MSM/Ms into the common strain C57BL/6J

Mx1 (Myxovirus resistance protein) and Oas1b (Oligoadenylate synthetase-1), induced by type 1 interferon (IFN), play a role in early antiviral innate immunity by inhibiting the replication of viruses. In mice, Mx1 and Oas1b confer resistance to the infection of orthomyxoviruses including influenza viruses and flaviviruses including West Nile viruses, respectively. Laboratory mice have been used to study the mechanisms of the pathogenesis of these virus infections; however, it is possible that they are not a suitable model system to study these viruses, since most of the inbred laboratory mouse strains lack both genes. It has been reported that feral mouse-derived inbred strains show resistance to the infection of these viruses due to the presence of intact both genes. In this study, we generated congenic strains in which the Mx or Oas locus of the MSM/Ms (MSM) mouce was introduced to the most widely used mouse strain, C57BL/6J (B6). B6.MSM-Mx mice showed resistance to the infection of influenza virus but not of West Nile virus. On the other hand, B6.MSM-Oas mice showed resistance to the infection of West Nile virus but not of influenza virus. Our results indicate that Mx1 and Oas1b show highly antiviral specificity in mice possessing the same genetic background. Therefore, these congenic mice are useful for not only infection study but also investigation of host defense mechanism to these viruses

Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study

Abstract Background Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD. Methods This single centre, retrospective nested case–control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups’ patient characteristics. Results We studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs. Conclusions JAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients

Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected].

BACKGROUND: Acute/subacute interstitial pneumonia in dermatomyositis (DM-A/SIP) is a disease associated with a poor prognosis that resists treatment with glucocorticosteroids (GC) and progresses rapidly in a period of weeks to months to death. We retrospectively studied outcomes, prognostic factors, and their relations with survival rate in patients with DM-A/SIP treated with early cyclosporine A (CSA)/GC combination therapy and 2-hour postdose blood concentration monitoring. METHODS: This study comprised 32 DM-A/SIP patients who were simultaneously treated with CSA and prednisolone. Clinical and laboratory findings were compared between those who died due to DM-A/SIP and those surviving 24 weeks after beginning of therapy. Prognostic factors were extracted, and their relations with the survival rate were evaluated. RESULTS: Of the 32 DM-A/SIP patients, 25 survived, 5 died of DM-A/SIP, and 2 died of infections. In those who died due to DM-A/SIP, ferritin level and the alveolar-arterial oxygen gradient were significantly increased compared with the survivors (P<0.001 and P = 0.002, respectively). Multivariate analyses showed that ferritin and alveolar-arterial oxygen gradient were independent prognostic factors of poor outcome. The survival rate 24 weeks after beginning of treatment was significantly lower in those with a ferritin level of ≥ 600 ng/ml and alveolar-arterial oxygen gradient of ≥ 45 Torr (P<0.001 and P<0.001, respectively). All patients with both prognostic factors died, and the outcome was significantly poorer in these patients than in those with one or neither of the prognostic factors (P<0.001). CONCLUSIONS: We identified pre-treatment high serum ferritin level and high alveolar-arterial oxygen gradient as poor prognostic factors in DM-A/SIP patients undergoing early CSA/GC combination therapy and showed that the outcomes were poor in patients with both factors

Infection of a Japanese Patient by Genotype 4 Hepatitis E Virus While Traveling in Vietnam

Cases of imported hepatitis E in industrialized countries infected with a genotype 1 hepatitis E virus (HEV) have been identified. We report a 56-year-old Japanese man who acquired infection with a genotype 4 HEV with 98.8% identity to a Vietnamese isolate after ingestion of uncooked shellfish while traveling in Vietnam

Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study.

Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).The median serum LIGHT level was 119 (16-335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL-6 level was 14.7 (2.4-154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6-335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16-164.2] pg/ml) (P = 0.02). The serum IL-6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4-259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP