Identification of a mammalian vesicular polyamine transporter

Spermine and spermidine act as neuromodulators upon binding to the extracellular site(s) of various ionotropic receptors, such as N-methyl-d-aspartate receptors. To gain access to the receptors, polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Although vesicular storage is mediated in an ATP-dependent, reserpine-sensitive fashion, the transporter responsible for this process remains unknown. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine by exchange of H+. SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes. These results indicated that SLC18B1 encodes a vesicular polyamine transporter (VPAT)

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Pasteurella multocida pneumonia with hemoptysis: A case report

Pasteurella multocida, which colonizes upper respiratory and digestive tracts, is a leading cause of respiratory diseases in many host species. Here, we describe a case of P. multocida pneumonia with hemoptysis. A 72-year-old female diagnosed with bronchiectasis with a 36-year history presented with a worsened infiltrative and granular shadow in the lower right lobe and lingular segment. Bronchial lavage fluid culturing suggested Pasteurella pneumonia. P. multocida was confirmed by 16S rRNA sequencing. The patient was readmitted to our hospital because of hemoptysis, and she was treated successfully with antibiotic therapy. The possibility of P. multocida infection must be considered in patients who own pets

Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP

灌流指標に対する大和当帰葉茶・当帰葉湯手浴の急性効果の評価

departmental bulletin pape

Crescentic glomerulonephritis associated with syphilis: a case report and review of the literature

Abstract Background Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. Case presentation A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. Conclusions Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone