Some viruses can accelerate the development of autoimmune diseases in certain individuals. In this issue, we discuss the hypothesis that certain viruses impair immune tolerance. As one example, we discuss the relationship between rheumatoid arthritis (RA) and Epstein-Barr virus (EBV). EBV is well known to be associated with African Burkitt′s B cell lymphoma, nasopharyngeal carcinoma and infectious mononucleosis. EBV has also been implicated in the pathogenesis of RA, based on indirect evidence, such as the presence of EBV particles in affected joint tissues, antigenic cross reactions between EBV and human proteins, and elevated humoral and cellular anti-EBV immune responses in patients. Since EBV plays an important role in polyclonal B cell activation, this virus might be associated with autoimmune dysfunction in patients with RA. We cloned the SAP/SH2D1A (signaling lymphocytic-activation molecule associated protein/Src homology 2 domain-containing protein) gene from peripheral leukocytes of patients with IgA nephropathy. SAP is essential for late B cell responsiveness, the development of long-term humoral immunity and the induction of cytotoxic T cells against EBV; it may also be involved in the regulation of the pathogenesis of RA. In the patients, expression of the SAP gene was decreased in the peripheral T cells that are thought to play critical roles, in conjunction with cytotoxic T cells and natural killer cells, in the elimination of EBV-infected B cells. Humanized mice (NOD/Shi-scid/IL-2Rãnull (NOG) mice transplanted with CD34+ hematopoietic stem cells) were inoculated with EBV and examined pathologically for signs of arthritis; erosive arthritis accompanied by synovial membrane proliferation, pannus formation and bone marrow edema were observed. These findings strongly suggest a causative role of EBV in RA.
In order to elucidate the molecular mechanism of neuroblastoma, differential screening of genes obtained from the cDNA libraries of favorable and unfavorable subsets of primary neuroblastomas (NBLs) has identified a novel gene. The novel gene BMCC1, which is preferably expressed in favorable neuroblastoma, was identified. BMCC1 acts as a pro-apoptotic protein in cells and the BCH domain possesses GAP activity. However, its real function has remained elusive. Yeast two-hybrid screening was used to identify proteins that interact with BMCC1. C-terminal amino acids of BMCC1, which includes the BCH domain, were used as baits in this screen. Subsequent analysis identified the translation elongation factor 1 alpha 1 (EF1A1) as a BMCC1-interacting partner. EF1A1 promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis and there is a possible functional implication for a shift in expression from eEF1A-1 to eEF1A-2 during neuronal development. Thus, EF1A may play a important role in neuronal development. Both GST pull-down assays and immunoprecipitation confirmed the physical interaction between BMCC1 and EF1A1. Immunofluorescence analysis revealed that EF1A1 co-localizes with BMCC1 in the cellular cytosol, which was further supported by cell fractionation and Western blotting. Overexpression of EF1A1 inhibited neurite extension in PC12 cells treated with NGF. Interestingly, knockdown of BMCC1 resulted in enhancement of NGF-induced neurite outgrowth, even in EF1A1-overexpressing PC12 cells. Downstream of the TrkA signaling, EF1A1 prolonged ERK phosphorylation. Furthermore, we demonstrated how the BMCC1/EF1A1 complex controls the differentiation of neuroblastoma cells. Taken together, the BMCC1/EF1A1 complex may play an important role in regulating differentiation of neuroblastomas through the NGF/TrkA signaling pathway.
We prepared three groups of female rats; streptozotocin-induced diabetic rats (STZ group), rats with physiological polyuria due to free ingestion of 5% sucrose solution (PU group) and age-matched control rats (C group), and investigated the voiding dysfunction during the early phase of the diabetes mellitus, by comparing various parameters after 1 and 4 weeks of treatment. Parameters examined were total voided volume, tidal voided volume (TV), bladder capacity (BC), based pressure (BP), maximum voiding pressure (PP), bladder opening pressure (BOP) and postvoid residual volume (PVR). TV and BC at 1 and 4 weeks were increased significantly in the STZ and PU groups, compared with the C group, but there were no significant differences in either of these parameters between the STZ and PU groups. PP in the PU group increased significantly compared with that in the C group at both 1 and 4 weeks, although PP decreased significantly in the STZ group at 4 weeks, compared with the C group. BOP and PP of the STZ group at 1 week were decreased significantly compared with the PU group. A large PVR was only observed in the STZ group at 4 weeks, and BP was decreased significantly compared with both the control and PU groups. These results suggest that the function of the autonomic nerve system was impaired at ∼1 week after the onset of diabetes mellitus, and that the inability to physiologically adapt to polyuria in the diabetic rats, due to the impaired autonomic function, induced voiding dysfunction during the early phase of the disease.
Couples that exhibit balanced translocation represent 2~5% of all cases of habitual abortion. Balanced translocation does not have any effect on phenotypic features. However, balanced translocation likely causes the formation of an unbalanced gamete during meiosis, resulting in abortion. Although reciprocal translocation and Robertsonian translocation are both categorized as balanced translocation events, the two have different impacts on the rate of successful pregnancy with live infants. Chromosomal karyotype analysis provides important personal information, and is a potent predictor of the patient's outcome. In this study, we attempted to clarify the background of chromosomal abnormalities, which were observed as the etiologic examinations for habitual abortion from 2001 to 2010 in Nihon University Itabashi Hospital. We identified 12 normal variants and 9 balanced translocation events in 401 patients. Of 8 patients with reciprocal translocation, 3 patients were male and 5 were female. One patient with Robertsonian translocation was female. Females could be more likely to exhibit balanced translocation than males. Since only one case of Robertsonian translocation was found among the balanced translocation events, it might be difficult for patients with reciprocal translocation to produce live infants. We must carefully consider the comprehensive management of translocation carriers, including genetic counseling.
Purpose: The purpose of this study was to investigate the efficacy and quality of postoperative analgesia by adding continuous femoral nerve block with ropivacaine (CFNB) to continuous epidural analgesia with ropivacaine (CEPA) for bilateral total knee arthroplasty (B-TKA). Methods: Thirty patients undergoing B-TKA in our hospital were included in this study. Postoperative pain intensities were recorded using visual analog pain scale (VAS) scores (0-100 mm) up to 48 hr after B-TKA, both at rest and during movement, following CEPA and CFNB in one leg (CFNB side). Analgesic effects and side effects on the CFNB and non-CFNB sides were compared in the same patient. Results: VAS scores were sig-nificantly different between the CFNB and non-CFNB sides (p < 0.001-0.05) both at rest and during movement. Supplemental analgesics, in the form of rectal suppositories and intramuscular injections, were used to reduce postoperative pain on the non-CFNB side. All patients complained of pain postoperatively only on the non-CFNB side. Six patients experienced nausea and another 6 experienced numbness of the leg as side effects. Conclusions: The present study indicates that CEPA combined with CFNB for analgesia following B-TKA could be a more suitable analgesic method than CEPA alone to reduce postoperative pain, both at rest and during movement, with few side effects.
We report a case of rectal perforation after internal hemorrhoidectomy. A 58-year-old man diagnosed with fourth degree hemorrhoids, based on Goligher“s classification, underwent surgery using the procedure for prolapse and hemorrhoids (PPH). On postoperative day 2, he complained of abdominal pain and a fever. We diagnosed rectal perforation because gastrographin enema showed leakage from the lower rectum to the abdominal cavity, and we performed emergency colostomy. PPH is used extensively as a surgical approach for the treatment of internal hemorrhoids. However, we must recognize that severe and critical complications are rarely caused by not skilled technique.
A 30-year-old man was referred to our hospital for endoscopic removal of dentures that had accidentally been aspirated. Chest CT scan revealed the dentures in the right intermediate bronchus. Endoscopic removal was not possible, and thus surgical removal was performed. The dentures were removed via a longitudinal incision in the right intermediate bronchus. Closure of the incision was accomplished with 3-0 PDS-II, and the suture line was reinforced by fibrin glue. The postoperative course was uneventful, and the patient was discharged on postoperative day 9.
Spontaneous pneumomediastinum (SPM) is a rare condition and a benign self-limited disorder that usually occurs in young men without remarkable factor or disease. We experienced a 14-year-old boy with SPM complaining of gradual onset of chest pain while playing with his dog. He was hospitalized and treated conservatively, and his symptoms resolved 4 days post-admission. We should recognize SPM as one of the causes of chest pain in young men.