Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.     

Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33

To investigate the role of interleukin (IL)-33 in rheumatoid arthritis (RA) patients, we measured the serum levels of IL-33 in RA patients before and after the administration of etanercept. Twenty-four patients with RA were treated with etanercept. Clinical and laboratory examinations, including serum levels of C-reactive protein (CRP) and hemoglobin (Hb); white blood cell (WBC) and red blood cell (RBC) counts; and the Disease Activity Score of 28 joints including CRP (DAS28-CRP), were performed at the baseline and at 3 and 6 months after the initial treatment with etanercept. The mean serum IL-33 levels had decreased significantly at 3 and 6 months after the initial treatment with etanercept. Serum IL-33 levels showed a significant correlation with the number of tender joints, CRP, DAS28-CRP, and the WBC count, and an inverse correlation with the RBC count and Hb level. These findings indicated that the decrease of serum IL-33 levels was a novel function of etanercept, shown for the first time in this study. Measurement of serum levels of IL-33 may become a useful control marker for RA treatment.     

Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

Murine colon carcinoma cells engineered to produce human interleukin-2 induce tumor-specific anti-tumor response

Murine colon carcinoma cells (colon 26) transduced by a retrovirus vector with the human interleukin-2 (IL-2) cDNA were studied for their tumorigenicity. Although cell growth in vitro was not affected by integration of the IL-2 gene, s.c. tumors of IL-2-producing colon 26 cells (H2) in syngeneic mice regressed spontaneously after producing small masses. Histological examination of the sites of tumor rejection revealed predominant infiltration of macrophages around the tumor necrotic mass. Subsequent challenge with parent colon 26 cells, but not with Meth A cells (fibrosarcoma of the same genetic background), did not result in tumor formation in mice which had been protected against H2 cells. Inoculation of H2 cells into syngeneic nude mice resulted in tumors with a retarded growth rate. Taken together, T cell-dependent, tumor-specific immunity is obtained by local IL-2 secretion around colon tumors, and this experimental animal model gives us a clue(s) for investigating host anti-tumor responses by cytokine production. © 1996 Wiley-Liss, Inc.     

Spontaneous reconstruction of the canine hypogastric nerve over a long period after removing half of its length

Spontaneous reconstruction of the sympathetic pathway projecting to the seminal tract after serious injury has not been well understood. Multiple cross-innervation mechanisms from the spinal cord via the hypogastric nerve to the seminal tract have been demonstrated currently. This study was undertaken to explore long-term spontaneous reconstruction of the canine hypogastric nerve (HGN), which controls ejaculation, after removing half of its length. Further, the study tried to identify the crossed-pathway(s) reconstructed. Responses of the vas deferens/epididymis and bladder neck to electrical stimulation of the lumbar splanchnic nerve (LSN) or the HGN were examined. In six dogs whose hypogastric nerve was injured bilaterally as described above 4 years before, corresponding to more than 20 years in human, nine (43%) and 13 (57%) of the 21 LSNs stimulated elicited elevation of vasal and bladder neck pressure, respectively. By combining re-transection of a HGN, the following pathways to the vas deferens/epididymis were identified to have been reconstructed: (1) to the ipsilateral was deferens/epididymis without crossing to the other side; (2) to the contralateral vas deferens/epididymis by crossing to the other side at the caudal mesenteric plexus (CMP); (3) to the contralateral vas deferens/epididymis by crossing to the other side from the ipsilateral HGN at the commissural branches between the right and left pelvic plexuses (CBPP); and (4) to the ipsilateral vas deferens/epididymis by crossing twice at the CMP to the other side and at the CBPP again from the contralateral HGN to the ipsilateral side. The similar patterns of reconstruction were also observed in the bladder neck. The above results indicate that the sympathetic pathways via the HGN to the canine seminal tract can be reconstructed spontaneously in a high rate over a long period after serious injuries and that their cross-innervation system can be repaired.