No abstract

SUMMARY Introducing avidin‐biotin complex ELISA for anti‐DNA antibody, the mechanism of in vitro production of anti‐ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL‐6‐IL‐6R loop was studied in patients with systemic lupus crythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti‐ssDN A antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density cenlrifugation responded to rIL‐6 to produce IgG and IgG anti‐ssDNA antibody. rIL‐2 and rIL‐4 had lesser effects on the differentiation of low density B cells. In fact, IL‐6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti‐IL‐6R MoAb, MT18, which did not inhibit IL‐6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL‐6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL‐6. Thus, endogenous IL‐6 produced by high density B cells bound to the IL‐6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti‐IL‐6 or anti‐IL‐6R MoAb (PM1). which inhibited IL‐6 binding, both inhibited IgG anti‐ssDNA antibody as well as total IgG production by SLE B cells in a dose‐dependent manner. These results suggest that interruption of the autocrine IL‐6 loop would be of therapeutic value in SLE.

Kiyotsugu takuma 14 , Kazuma Yamakawa 15 & the Japanese Association for Acute Medicine (JAAM) Sepsis prognostication in intensive care Unit and emergency Room (Spice) (JAAM Spice) Study Group* Systemic inflammatory response syndrome (SIRS) reportedly has a low performance for distinguishing infection from non-infection. We explored the distribution of the patients diagnosed by SIRS (SIRS patients) or a quick sequential organ failure assessment (qSOFA) (qSOFA patients) and confirmed the performance of the both for predicting ultimate infection after hospital admission. We retrospectively analyzed the data from a multicenter prospective study. When emergency physicians suspected infection, SIRS or the qSOFA were applied. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the SIRS and qSOFA for predicting established infection. A total of 1,045 patients were eligible for this study. The SIRS patients accounted for 91.6% of qSOFA patients and they showed a higher rate of final infection than that of non-SIRS patients irrespective of the qSOFA diagnosis. The AUCs for predicting infection with SIRS and a qSOFA were 0.647 and 0.582, respectively. The SIRS significantly predicted an ultimate infection (AUC, 0.675; p = 0.018) in patients who met the SIRS and qSOFA simultaneously. In conclusion, the SIRS patients included almost all qSofA patients. SiRS showed a better performance for predicting infection for qSofA in those who met both definitions. Since the announcement of the third international consensus definitions for sepsis and septic shock (Sepsis-3), much debate has been had on the accuracy of the quick sequential organ failure assessment (qSOFA) score for predicting mortality due to sepsis compared with the systemic inflammatory response syndrome (SIRS)

In lightly anesthetized pigs during uncontrolled hemorrhagic shock, infusion with 4 degrees C lactated Ringer's solution (which seems to be feasible in the clinical setting) decreases the core temperature rapidly and prolongs survival.

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.