Anti-DNA antibodies cross-reactive with ß2-glycoprotein I induce monocyte tissue factor through the TLR9 pathway.

Antibodies specific for cardiolipin (CL)-ß2-glycoprotein I (ß2GPI) are known to induce tissue factor (TF) expression by monocytes and endothelial cells which leads to a prothrombotic state in antiphospholipid syndrome (APS), but the mechanism is not fully elucidated. Previously, we reported that the mouse monoclonal anti-CL-ß2GPI antibody WB-6 cross-reacts with DNA, enters monocytes via binding to cell surface DNA, and induces TF expression. The current study aimed to identify the intracellular signaling pathways involved in this process. The binding of WB-6 to CL-ß2GPI or DNA, and endocytosis was not prevented by chloroquine, but pre-treatment of the cells with chloroquine significantly suppressed TF expression. TLR9 inhibitory oligodeoxynucleotide also suppressed the WB-6-induced TF expression, suggesting a pivotal role of the TLR9 pathway in TF production. Serum antibodies obtained from a patient with APS accompanying systemic lupus erythematosus (SLE) bound to both CL-ß2GPI and DNA, and induced TF in normal monocytes. This effect was suppressed by chloroquine, and abolished by removal of the DNA-binding activity. These results suggest that induction of TF expression results from TLR9 activation by DNA which was internalized together with cross-reactive antibodies produced in secondary APS accompanying SLE.

ß-Lactamase-non-producing ampicillin-resistant Haemophilus influenzae is acquiring multidrug resistance.

BACKGROUND: Haemophilus influenzae strains with reduced susceptibilities to antimicrobial agents have emerged in Japan. Here, we aimed to investigate H. influenzae non-susceptibility to ß-lactams and non-ß-lactams. METHODS: A total of 260 H. influenzae isolates from patients in 2013-2016 were analysed. Antimicrobial susceptibilities were assessed by determining the minimum inhibitory concentration. Additionally, isolates with reduced susceptibility were analysed by both genetic and statistical methods. RESULTS: ß-Lactamase-non-producing ampicillin-resistant H. influenzae (BLNAR) strains increased significantly and accounted for more than 50% of all isolates from 2014. Additionally, the proportion of quinolone-low-susceptibility isolates increased significantly (P<0.05). Among these, three quinolone-non-susceptible isolates showed minimum inhibitory concentrations higher than the susceptibility breakpoint of levofloxacin. Moreover, one of the three isolates showing multidrug resistance was resistant to macrolides, ß-lactams, and quinolones. Low susceptibilities to non-ß-lactams were significantly associated with BLNAR. CONCLUSIONS: The present study indicates that BLNAR strains are increasing and tend to show multidrug resistance. Additionally, multidrug-resistant H. influenzae (MDRHI) has emerged. To prevent the further spread of MDRHI, the proportions of BLNAR strains should be evaluated.

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization.

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study.

Parastomal hernia repair with the Sugarbaker technique using e-PTFE mesh.

PURPOSES: Although surgery is commonly used to treat parastomal hernia, it is very difficult and has shown poor results. Recently, repair with prosthetic materials has been thought to be a more promising method. METHODS: The Sugarbaker technique with e-PTFE mesh (Dualmesh®) performed via open surgery was adopted for seven patients with parastomal hernia. Two of them were recurrent cases. Three of the patients experienced incarceration of the intestine and recovered conservatively before surgery. The median age of the patients at the parastomal hernia repair was 77.6 years old (range 37.7-84.7). RESULTS: The median operative time was 211 min (range 147-256). The median hernia size was 28 cm2 (range 7.5-60 cm2). The median amount of blood loss during the operation was 158 g (range 0-370 g). Surgical site infection was not observed. The postoperative median hospital stay was 17 days (range 13-40) and the median follow-up was 2.4 years (range 1.0-3.7). During the follow-up period, we did not observe recurrence or readmission. CONCLUSIONS: The surgical results were satisfactory with minimal morbidity and no recurrences. The Sugarbaker technique for parastomal repair using e-PTFE mesh may be suitable as a standard method for treating parastomal hernia.

Hyalinizing spindle cell tumor with giant rosettes of the omentum.

We report the first case of a hyalinizing spindle cell tumor with giant rosettes of the omentum. The mesenchymal tumor arises from a multiplication of fibroblastic cells containing large rosette-like structures composed of a central collagen core surrounded by plump oval to spindle tumor cells. A 38-year-old woman exhibited the symptom of abdominal pain in the right side, with a correlated sensation of a mass in the same area. A tumor consisting of both solid and cystic cytologic features was subsequently diagnosed, on the right side of the uterus. Her serum level of CA-125 was only slightly elevated. Surgical intervention indicated that the tumor originated from lower pole of the omentum and the histological diagnosis was hyalinizing spindle cell tumor with giant rosettes. The metastatic potential of this type of tumor is considered similar to that of the metastatic low-grade fibromyxoid sarcoma, which indicated the need for careful clinical follow up of this case.