X-linked lymphoproliferative disease type 1 (XLP1) is a rare monogenic immune dysregulation disorder caused by a deficiency of a signaling lymphocyte activation molecule-associated protein (SAP). ...While many patients with XLP1 present with fatal hemophagocytic lymphohistiocytosis upon Epstein Barr virus (EBV) infection, a small fraction present with limbic encephalitis in the absence of EBV infection. It is poorly understood why SAP deficiency may cause limbic encephalitis in XLP1.
A 12-year-old boy presented with seizures, changes in personality, memory loss, and cognitive deficits during treatment for interstitial pneumonia. A diagnosis of limbic encephalitis was made. Despite treatment against CD8+ T cell-mediated autoimmunity with intravenous methylprednisolone, dexamethasone, intravenous immunoglobulin, plasma exchange, cyclosporine, weekly etoposide, mycophenolate mofetil, and adalimumab, encephalitis progressed until the patient died after one month of treatment intitiation. Post-mortem genetic testing revealed a de novo SH2D1A truncating mutation. Tests for EBV infection were negative. Initial spinal fluid revealed markedly elevated protein levels, mild pleocytosis, and elevation of two chemokines (C-X-C motif chemokine ligand CXCL 10 and CXCL 13). Moreover, initial spinal fluid was tested positive for anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) autoantibody.
In XLP1-associated limbic encephalitis, anti-AMPAR autoantibody production by the dysregulated immune system due to SAP deficiency might be a pathogenic mechanism of central nervous system manifestations. In addition to the standard treatment for XLP1, targeted treatment against B-cell-mediated immunity might be indicated for patients with XLP1-associated limbic encephalitis.
Background
Yolk sac tumor (YST) is a germ cell tumor that is generally associated with good prognosis in children. It has been recently reported that vaginal YSTs can be cured using chemotherapy ...alone. Thus, minimal invasiveness and function preservation are pre-requisites for surgical approaches. Herein, we report a case of vaginal YST that was resected in a function-preserving manner using a unique combination of surgical approaches.
Case presentation
In a 9-month-old Asian female infant, a vaginal tumor was detected while investigating for vaginal bleeding. The patient was referred to our hospital, and the tumor was diagnosed as a YST after incisional biopsy. Six courses of carboplatin-based chemotherapy were administered. Contrary to the findings in previous reports, the tumor was chemo-resistant and surgical resection was required for the residual tumor. During surgery, we utilized laparoscopic and endoscopic procedures to ensure tumor-free surgical margins at the cervix, rectum, and lateral wall of the vagina. Additionally, the posterior sagittal approach was used to easily resect the tumor, and the vagina was reconstructed leaving only inconspicuous scars in the intergluteal cleft. No complications occurred postoperatively. Pathological examination of the surgical specimen revealed tumor-free surgical margins. The patient received four cycles of intensified chemotherapy before and after the surgery. The patient has been disease-free for 6 months now.
Conclusions
Our combination of laparo/endoscopic and posterior sagittal approach ensured a tumor-free macroscopic surgical margin with easier, cosmetically pleasing vaginal reconstruction, while preserving the anorectal and urinary functions. We believe that this approach could be utilized not only for vaginal YST, but also for any vaginal tumor, especially those arising from the posterior or lateral wall.
The efficacy of tandem HDCT against high‐risk neuroblastoma has been reported; however, an optimal regimen remains to be established. In this paper, we report our experience using tandem HDCT ...comprising the MEC and BuMel regimens in patients with high‐risk neuroblastoma. We retrospectively analyzed four patients with stage M high‐risk neuroblastoma who received HDCT with MEC followed by BuMel combined with autologous stem cell rescue. Although none of their metastatic lesions had disappeared after induction chemotherapy, three patients showed a CR after tandem HDCT. Gastrointestinal mucosal injuries and renal dysfunction were observed as non‐hematologic adverse events of grade 3 or higher. Gastrointestinal mucosal injuries were observed in all four patients following the first HDCT and in one patient following the second HDCT and were treated with parenteral nutrition and analgesics. One patient experienced renal dysfunction during the first HDCT, which was alleviated by sufficient hydration and diuretics and resulted in the reduction of melphalan dosage for the second HDCT. SOS was not observed in any patient. The HDCT regimens examined in this study were observed to be feasible and did not result in any life‐threatening adverse events. Our findings indicate that tandem HDCT comprising MEC and BuMel is a potentially effective regimen for patients with high‐risk neuroblastoma, including for those who respond poorly to induction chemotherapy, although additional studies in a larger population should be conducted to verify any long‐term outcomes and toxicity.
Human rck/p54, a product of the gene cloned at the breakpoint of t(11; 14) (q23;q32) chromosomal translocation on 11q23 in B‐cell lymphoma, is a member of the DEAD‐box RNA helicase family. Here, the ...crystal structure of Nc‐rck/p54, the N‐terminal core domain of rck/p54, revealed that the P‐loop in motif I formed a closed conformation, which was induced by Asn131, a residue unique to the RCK subfamily. It appears that ATP does not bind to the P‐loop. The results of dynamic light scattering revealed to ATP‐induced conformational change of rck/p54. It was demonstrated that free rck/p54 is a distended molecule in solution, and that the approach between N‐terminal core and C‐terminal domains for ATP binding would be essential when unwinding RNA. The results from helicase assay using electron micrograph, ATP hydrolytic and luciferase assay showed that c‐myc IRES RNA, whose secondary structure regulates IRES‐dependant translation, was unwound by rck/p54 and indicated that it is a good substrate for rck/p54. Over‐expression of rck/p54 in HeLa cells caused growth inhibition and cell cycle arrest at G2/M with down‐regulation of c‐myc expression. These findings altogether suggest that rck/p54 may affect the IRES‐dependent translation of c‐myc even in the cells.
The RCK gene was cloned on the basis of the t(11;14)(q23;q32) chromosome translocation observed in human B‐cell lymphoma cell line RC‐K8. This gene was found to be overexpressed in various kinds of ...tumours. The gene product, rck/p54, consisting of 472 amino‐acid residues with molecular weight 53.2 kDa, belongs to the family of DEAD‐box RNA helicases. Its ATP‐dependent RNA‐unwinding activity toward c‐myc RNA molecules in vitro has recently been demonstrated. In the present study, limited proteolysis experiments of rck/p54 were used to truncate the N‐terminal domain (residues 1–288; 31.8 kDa) of rck/p54, leading to successful crystallization of Nc‐rck/p54, i.e. the N‐terminal core domain (residues 70–288; 24.5 kDa) of rck/p54. Crystals of Nc‐rck/p54 were grown to a size suitable for X‐ray structure analysis using polyethylene glycol 3350 as the precipitant. The crystal belongs to the orthorhombic space group P212121, with unit‐cell parameters a = 65.5, b = 73.1, c = 84.8 Å, and diffracts X‐rays to beyond 2.0 Å resolution.
BACKGROUNDX-linked lymphoproliferative disease type 1 (XLP1) is a rare monogenic immune dysregulation disorder caused by a deficiency of a signaling lymphocyte activation molecule-associated protein ...(SAP). While many patients with XLP1 present with fatal hemophagocytic lymphohistiocytosis upon Epstein Barr virus (EBV) infection, a small fraction present with limbic encephalitis in the absence of EBV infection. It is poorly understood why SAP deficiency may cause limbic encephalitis in XLP1. CASEA 12-year-old boy presented with seizures, changes in personality, memory loss, and cognitive deficits during treatment for interstitial pneumonia. A diagnosis of limbic encephalitis was made. Despite treatment against CD8+ T cell-mediated autoimmunity with intravenous methylprednisolone, dexamethasone, intravenous immunoglobulin, plasma exchange, cyclosporine, weekly etoposide, mycophenolate mofetil, and adalimumab, encephalitis progressed until the patient died after one month of treatment intitiation. Post-mortem genetic testing revealed a de novo SH2D1A truncating mutation. Tests for EBV infection were negative. Initial spinal fluid revealed markedly elevated protein levels, mild pleocytosis, and elevation of two chemokines (C-X-C motif chemokine ligand CXCL 10 and CXCL 13). Moreover, initial spinal fluid was tested positive for anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) autoantibody. DISCUSSIONIn XLP1-associated limbic encephalitis, anti-AMPAR autoantibody production by the dysregulated immune system due to SAP deficiency might be a pathogenic mechanism of central nervous system manifestations. In addition to the standard treatment for XLP1, targeted treatment against B-cell-mediated immunity might be indicated for patients with XLP1-associated limbic encephalitis.
PDF
