PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner

Objectives: Details of the histogenesis of salivary gland tumors are largely unknown. The oncogenic role of PLAG1 in the salivary gland has been demonstrated in vivo. Herein, we demonstrate the roles of PLAG1 in the acinar and ductal cells of normal human salivary glands in an attempt to clarify the early events that occur during the histogenesis of salivary gland tumors. Methods: Normal salivary gland cells with acinar- (NS-SV-AC) and ductal- (NS-SV-DC) phenotypes were transfected with PLAG1 plasmid DNA. Subsequently, the PLAG1 overexpressed and mock cells were examined by cell proliferation, transwell migration, and salisphere formation assays. The expression levels of salivary and pluripotent stem cell markers and differentiation markers were evaluated by quantitative real-time polymerase chain reaction and immunofluorescence. Alterations in transcriptional expressions were investigated via cap analysis of gene expression with gene-enrichment and functional annotation analysis. Results: PLAG1 promoted cell proliferation and transwell migration in the acinar and ductal cells, and markedly enhanced the stemness profiles and luminal cell-like profiles in acinar cells; the stemness profiles were partially increased in the ductal cells. Conclusion: PLAG1 enhanced the stemness profiles in the acinar cells of normal human salivary glands in a cell type-specific manner. Thus, it may be involved in salivary gland tumorigenesis by increasing the stemness character of the normal salivary gland cells

Phospholipase D Family Member 4, a Transmembrane Glycoprotein with No Phospholipase D Activity, Expression in Spleen and Early Postnatal Microglia

BACKGROUND: Phospholipase D (PLD) catalyzes conversion of phosphatidylcholine into choline and phosphatidic acid, leading to a variety of intracellular signal transduction events. Two classical PLDs, PLD1 and PLD2, contain phosphatidylinositide-binding PX and PH domains and two conserved His-x-Lys-(x)(4)-Asp (HKD) motifs, which are critical for PLD activity. PLD4 officially belongs to the PLD family, because it possesses two HKD motifs. However, it lacks PX and PH domains and has a putative transmembrane domain instead. Nevertheless, little is known regarding expression, structure, and function of PLD4. METHODOLOGY/PRINCIPAL FINDINGS: PLD4 was analyzed in terms of expression, structure, and function. Expression was analyzed in developing mouse brains and non-neuronal tissues using microarray, in situ hybridization, immunohistochemistry, and immunocytochemistry. Structure was evaluated using bioinformatics analysis of protein domains, biochemical analyses of transmembrane property, and enzymatic deglycosylation. PLD activity was examined by choline release and transphosphatidylation assays. Results demonstrated low to modest, but characteristic, PLD4 mRNA expression in a subset of cells preferentially localized around white matter regions, including the corpus callosum and cerebellar white matter, during the first postnatal week. These PLD4 mRNA-expressing cells were identified as Iba1-positive microglia. In non-neuronal tissues, PLD4 mRNA expression was widespread, but predominantly distributed in the spleen. Intense PLD4 expression was detected around the marginal zone of the splenic red pulp, and splenic PLD4 protein recovered from subcellular membrane fractions was highly N-glycosylated. PLD4 was heterologously expressed in cell lines and localized in the endoplasmic reticulum and Golgi apparatus. Moreover, heterologously expressed PLD4 proteins did not exhibit PLD enzymatic activity. CONCLUSIONS/SIGNIFICANCE: Results showed that PLD4 is a non-PLD, HKD motif-carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and Golgi apparatus. The spatiotemporally restricted expression patterns suggested that PLD4 might play a role in common function(s) among microglia during early postnatal brain development and splenic marginal zone cells

Group A Streptococcal Toxic Shock Syndrome after a Routine Gynecological Procedure

Streptococcal toxic shock syndrome (STSS) is a life-threatening illness mainly caused by invasive group A Streptococcus (GAS) infection. Herein, we report a case of a postmenopausal woman who developed STSS from an ascending vaginal GAS infection after cytocervical sampling. The patient complained of vaginal discharge, for which she underwent gynecological examination with vaginal sampling. The following day, there was onset of diarrhea and vomiting. After 7 days, she was admitted to our hospital with septic shock. Necrotizing enterocolitis was suspected and surgical intervention was performed; however, the patient was diagnosed with primary peritonitis and antibiotics were initiated. On day 2, GAS was suspected by blood cultures, and antibiotics were changed in consideration of STSS. On day 4, GAS was confirmed in blood, ascitic fluid, and vaginal swab specimens, and STSS caused by an ascending vaginal GAS infection was diagnosed. This case report indicates that STSS could occur following cytocervical sampling for vaginal discharge. If a woman has unexplained septic shock, especially with gastroenteritis symptoms, STSS should be considered as a differential diagnosis

A Nationwide Hospital Claims Database Analysis of Real-World Patterns of Laxative Use for Opioid-Induced Constipation in Japanese Patients with Cancer

Abstract Introduction Opioid-induced constipation (OIC) is one of the most common side effects in patients with cancer treated with opioid analgesics. The actual use of laxatives for OIC in Japan remains unelucidated. This study aimed to investigate the real-world patterns of laxative use for patients with cancer who newly initiated opioid analgesic therapy. Methods We used a Japanese nationwide hospital claims database (January 2018–December 2019). Patients with cancer newly receiving opioid analgesic therapy were included and classified on the basis of opioid classes (weak or strong) and route of administration (oral or transdermal) at initiation. The patients were divided into two groups on the basis of whether they received early medication (starting laxatives within 3 days after initiating opioid analgesic therapy), and patterns of laxative use were analyzed. Results There were 26,939 eligible patients, with 50.7% of them initiated with strong opioids. The proportion of patients who received early medication was 25.0% for weak opioids and 57.3% for strong opioids. Osmotic laxatives were most frequently used as first-line therapy in the early medication group (oral weak opioids: 12.3%, oral strong opioids: 29.4%, transdermal strong opioids: 12.8%). Stimulant laxatives were frequently used as first-line therapy, to the same extent or more than osmotic laxatives in the non-early medication group (oral weak opioids: 13.7%, oral strong opioids: 7.7%, transdermal strong opioids: 15.1%). Peripherally acting μ-opioid receptor antagonists were the second most frequently used in the early medication group for those on oral strong opioids (9.4%). Conclusion This study demonstrated for the first time that the patterns of laxative use for OIC in Japanese patients with cancer were different, depending on the opioid types at initiation and the timing of laxative medication

The correlation of significant <i>r</i>² values (fdr = 0.05, <i>r</i>²>0.2) between two sample sets and two gene pools.

<p>(a) core collection (Ca) vs plus trees in Kanto Breeding Region (Ka), (b) core collection (Pacific Ocean side (Cp) vs Japan Sea side (Cj)), c) plus trees in Kanto Breeding Region (Pacific Ocean side (Kp) vs Japan Sea side (Kj)). The solid line represents linear correlation, and the dashed line represents line of identity. ρ is the spearman’s correlation coefficient.</p

Summary of models and number of significant loci at a nominal 1% level.

<p>Summary of models and number of significant loci at a nominal 1% level.</p

Frequency distributions of membership in the clusters defined by the reference population for <i>C. japonica</i>.

<p>(a) natural population (n = 181). Black bar represents the reference samples for STRUCTURE analysis. Q>0.8 indicates reference samples for Pacific Ocean side, while Q<0.2 those for Japan Sea side. (b) core collection (n = 456), (c) plus tree individuals in Kanto Breeding region (n = 367).</p