Search

Immunoglobulin A (IgA) pemphigus, also known as intercellular IgA dermatosis, is a rare autoimmune bullous disease presenting with IgA anti‐keratinocyte cell surface autoantibodies. Concomitant lymphoproliferative disorders have been reported in IgA pemphigus, including IgA monoclonal gammopathy of undetermined significance and IgA type multiple myeloma (MM). A 35‐year‐old Japanese woman with a 3‐year history of pruritic papulovesicles on her lower legs and trunk was referred to our department. Histopathological examination revealed acantholytic blisters, and results of both direct and indirect immunofluorescence were negative. Direct and indirect immunofluorescence were still negative 3 years and 7 months later. Approximately 7 years after her first visit, the patient was re‐referred to us because of disease exacerbation. Histopathological findings revealed subcorneal blistering with acantholysis, in which neutrophil‐dominant inflammatory cells were present. Indirect immunofluorescence was positive for IgA on the epidermal cell surface and both desmoglein (Dsg) 1/3 and (Dsc) desmocollin 1–3 enzyme‐linked immunosorbent assays (ELISAs) for IgA were positive. The histological findings and positive Dsc1 IgA ELISA led to the diagnosis of subcorneal pustular dermatosis (SPD)‐type IgA pemphigus. Further examination revealed hyper‐IgA globulinemia, increased serum IgA‐κ protein, and increased plasma cells in the bone marrow, enabling the diagnosis of IgA type MM. Daratumumab, lenalidomide, and dexamethasone (DLd) therapy was effective for both the MM and the skin lesions, resulting in negative results on Dsg1/3 and Dsc1‐3 IgA ELISAs. The association between IgA pemphigus and IgA type multiple myeloma remains unclear, and only seven cases including the present case have been reported. Literature review revealed associations between SPD‐type and IgA κ chain in IgA pemphigus and MM, and that in most cases the onset or diagnosis of MM was simultaneous or occurred after the diagnosis of IgA pemphigus. Therefore, clinicians should be aware of the development of multiple myeloma during the clinical course of patients with SPD‐type IgA pemphigus. [ABSTRACT FROM AUTHOR]

Background: Factor V (FV) deficiency is a monogenic inherited coagulation disorder considered to be an ideal indication for gene therapy. To investigate the possibility of therapeutic application of genome editing, we generated induced pluripotent stem cells (iPSCs) from a FV‐deficient patient and repaired the mutation of factor V gene (F5) using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9). Methods: The patient's peripheral blood mononuclear cells were reprogrammed for iPSCs. The targeting vector was designed with homology arms against F5 containing the corrected sequence. Cas9 ribonucleoprotein (RNP) complex and targeting vector were electroporated into iPSCs. Gene‐edited iPSCs were differentiated into hepatocyte‐like cells (HLCs). Results: The mutation of F5 in patient‐derived iPSCs was repaired by CRISPR/Cas9. In concentrated culture supernatants of patient‐derived iPS‐HLCs, neither FV antigen nor activity was detected, while in those of gene‐corrected iPS‐HLCs, FV antigen and specific activity were 67.0 ± 13.1 ng/mL and 173.2 ± 41.1 U/mg, respectively. Conclusions: We successfully repaired the mutation of F5 using the CRISPR/Cas9 and confirmed the recovery of FV activity with gene‐corrected iPS‐HLCs. Gene‐edited iPSCs are promising for elucidating the pathophysiology as well as for a modality of gene therapy. [ABSTRACT FROM AUTHOR]

The hepatocyte paraffin 1 (Hep Par 1) antibody is widely used as a hepatocyte marker, recognizing carbamoyl phosphate synthetase 1 (CPS1), an essential component of the urea cycle. Various missense, nonsense, and frameshift mutations occur in the CPS1 gene. In neonatal patients with homozygous CPS1 deficiency (CPS1D), urea cycle defects with resulting severe hyperammonemia can be fatal, though liver transplantation provides a complete cure for CPS1D. We performed Hep Par 1 immunostaining in the explanted livers of 10 liver transplant patients with CPS1D. Seven were negative for Hep Par 1 in the hepatocytes and the other three showed normal diffuse granular cytoplasmic staining. As expected, all three Hep Par 1-positive patients had at least one missense mutation, and all four patients who had only nonsense or frameshift mutations were Hep Par 1-negative. The other three patients were unexpectedly negative for Hep Par 1, even though each had one missense mutation. These results suggest that CPS1D can be related to the loss of Hep Par 1 reactivity due to the loss of protein production, a one amino acid substitution resulting in an abortive protein product, or both. Hep Par 1 immunohistochemistry can be used as a simple method to confirm CPS1D. [ABSTRACT FROM AUTHOR]

Multinodular and vacuolating neuronal tumors (MVNT) have been referred to as distinctive neuronal tumors whose characteristic features include multiple nodules localized in the subcortical white matter. MVNT are composed of vacuolating dysplastic neurons reactive to HuC/HuD. A significant overexpression of alpha-internexin (INA) limited to the stroma of nodules was reported in one tumor. Since genetic analyses have failed to demonstrate any consistent alterations, the nosological position as well as the nature of MVNT, namely, neoplastic or dysplastic, remains unclear. We herein present another example of MVNT involving the amygdala and anterior hippocampus in a 41-year-old man. In addition to the nodular lesions described earlier, we found INA-positive ribbon-like lesions that replaced neuropil and extended along the hippocampal gray matter. We also identified dysplastic neurons infiltrating into the CA4 hilus of the hippocampus. Intense INA expression was present in the stroma as well as the cytoplasmic membrane of dysplastic neurons and their processes. While the invasiveness suggested a neoplasm, a relatively restrictive, either nodular or ribbon-like growth pattern with INApositive abnormal neuropil suggested a hamartoma. Such quasi-tumors should be accommodated in the World Health Organization classification of tumors of the central nervous system, as are dysembryoplastic neuroepithelial tumor and Lhermitte-Duclos disease. [ABSTRACT FROM AUTHOR]

The effects of microwave roasting on phospholipids in soybeans were investigated in relation to moisture. Whole soybeans at different moistures (9.6, 38.2, and 51.9%) were roasted by exposure to microwaves at a frequency of 2,450 MHz. During microwave treatments, the lower the moisture content, the higher was the internal temperature in soybeans at the end of microwave roasting. Total lipids were extracted from the beans after microwave treatment, and the phospholipids were separated with thin-layer chromatography. Phosphatidylcholine was the principal phospholipid in the extracted lipids from all unroasted and roasted bean samples. After microwave roasting, phospholipids containing an amino group, especially phosphatidylethanolamine, decreased substantially ( P<0.05) in lower-moisture soybeans. However, increasing the moisture content depressed a rise in the internal temperature of soybeans and prevented a reduction in phospholipids and/or polyunsaturated fatty acids in the phospholipids. Based on the changes in the composition and fatty acid distribution of phospholipids in soybeans during microwave roasting, it is necessary to consider the moisture content in soybeans when roasting in a microwave oven. [ABSTRACT FROM AUTHOR]