Key Clinical Message Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.
Abstract Background and Aims Anti-glomerular basement membrane (GBM) glomerulonephritis (GN), characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is a well-known antimalarial drug. In addition, it has immunomodulatory, anti-inflammatory, and autophagy inhibitory effects and its recognized in the treatment of autoimmune disease such as SLE. However, its effect for anti-GBM GN is unknown. In this study, we investigated the effect of HCQ against anti-GBM GN in rats. Method 7 week old male, WKY rats were induced by the administration of anti-GBM serum (50μg/rat). We administered either HCQ (50mg/kg) or vehicle (Phosphate-buffered saline) from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, hematuria. Urine was collected for 24 hours on day 1, 3, 5, and 7. Rats were sacrificed on day 7 after induction of anti-GBM GN. Renal histological changes were assessed by PAS staining, and Masson trichrome stain, and macrophage was assessed by ED-1 stain. Mitogen-Activated Protein Kinase (MAPK) was evaluated by western blotting (WB) and inflammatory cytokines were evaluated by ELISA using urine. Results HCQ treatment suppressed renal function decline. Histologically, extracellular and intracellular cells were increased from day 1, fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM GN had high levels of interferon-α, interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α. These changes were significantly suppressed by HCQ. In addition, HCQ suppressed phosphorylation of JNK/p38 MAPK. Conclusion Our study showed that HCQ could attenuate anti-GBM GN and have an anti-inflammatory effect by inhibiting JNK/p38 MAPK activation. HCQ may have therapeutic potential in anti-GBM GN.
The pathogenesis of nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and nonsyndromic cleft palate only (NSCP) may be associated with genetic factors. Although some predisposing genes/loci have been reported, their attributable risk is too small to be clinically meaningful. To clarify the genetic causes and mechanisms of NSCL±P or NSCP, we conducted mutation analysis of target genes using a next-generation sequencing (NGS) approach.The target genes, IRF6, WNT5A, WNT9B, TP63, MSX1, TFAP2A, PAX9, DLX3, DLX4, and MN1, were selected based on previous reports of potential associations with the development of NSCL±P or NSCP from genome-wide association studies and candidate gene analyses. Mutation analysis was conducted using NGS on 74 Japanese trios (patient and parents) and 18 Japanese patients only families.We detected single-nucleotide variants (SNVs) for 7 genes: IRF6, DLX4, WNT5A, TFAP2A, WNT9B, TP63, and PAX9. The SNVs found on IRF6 and DLX4 were missense mutations, whereas those identified on WNT5A, TFAP2A, WNT9B, TP63, and PAX9 were rare variants in the noncoding region; no de novo mutation was identified in the trio samples. The amino acid change on DLX4 was detected within the highly conserved homeodomain and was predicted to have a deleterious impact on the protein function by in silico analysis.The DLX4 missense mutation c.359C>T (Pro120Leu) was found in 1 Japanese patient with NSCL±P and was located in the homeodomain region. This mutation likely plays a role in the development of NSCL±P in the Japanese population.
Abstract Mutations in proline‐rich transmembrane protein 2 ( PRRT2 ) cause paroxysmal kinesigenic dyskinesia (PKD). Recently, we reported that a Prrt2 mutation exacerbated L‐dopa‐induced motor deficits in mice, suggesting that the basal ganglia might contribute to PKD pathology. Here, we demonstrated that the Prrt2 mutation enhanced depolarization stimuli‐induced extracellular dopamine levels in the mouse striatum, which were attenuated by repeated stimulation. L‐dopa administration maintained high dopamine levels in Prrt2 ‐KI mice even during repetitive stimuli but did not affect dopamine levels in wild‐type mice. Thus, the enhanced and prolonged responsiveness of dopamine release in nigrostriatal dopaminergic neurons to sequential excitation may be partially implicated in Prrt2‐related dyskinesia.
Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, represents a relatively new disease entity. MACF is categorized as a benign ovarian tumor. However, due to a limited number of case reports, its clinical and pathological features and optimum management remains largely undetermined. Herein, we report on a rare case of MACF that grew rapidly in size and was diagnosed on detailed pathological examination. A 44-year-old Japanese woman, who detected a myoma-like lesion 1-year earlier, was referred to our hospital when the follow-up examination demonstrated that the mass had increased in size. Magnetic resonance imaging revealed a T1 isointense and T2 hyperintense tumor (11 cm in diameter) in the right pelvic cavity. Laparoscopy confirmed the presence of a right ovarian tumor and laparoscopic right adnexectomy was performed. The tumor cells consisted of dense cellular proliferations of spindle fibroblast-like cells without significant cytological atypia. The mitotic activity index was estimated at >15 mitotic figures per 10 high-power fields. Reticulin staining and FOXL2 mutation analysis excluded the possibility of an adult granulosa cell tumor, and the patient was diagnosed with a MACF of the ovary. To the best of our knowledge, we are the first to report on a case of rapid growth of a MACF of the ovary during follow-up. When an increase in the size of a solid ovarian mass is detected, a MACF should be considered as a differential diagnosis.
