Tubo-Ovarian Abscess Occurring 16 Years After Supracervical Hysterectomy

Background: Supracervical hysterectomy is seldom performed and there are few reports of tubo-ovarian abscess (TOA) after supracervical hysterectomy. Case: The case of a 49-year-old woman with a right TOA is reported. This patient had received a supracervical hysterectomy 16 years earlier due to rupture of the uterus. At this admission, she presented with complaints of lower abdominal pain and fever. Bimanual and transvaginal ultrasound examinations demonstrated a tender mass in the right adnexal region. Laparotomy, pathologic examination and microbiologic study confirmed the diagnosis of right TOA. Conclusion: After supracervical hysterectomy, patients may develop endocervicitis, parametritis and/or TOA. This series may be a subtype of ascending infections in the female genital tract

Dental Calculus Stimulates Interleukin-1beta Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes

Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1beta. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1beta precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1beta, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1beta secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1beta secretion by ELISA. We found that calculus induced IL-1beta secretion in both human PMNs and PBMCs. Calculus also induced IL-1beta in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1beta induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1beta transcription. To analyze the effect of the inorganic structure, we baked calculus at 250 degrees C for 1 h. This baked calculus failed to induce pro-IL-1beta transcription. However, it did induce IL-1beta secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1beta in mouse macrophages, and baked calculus induced IL-1beta in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1beta secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in the activation of NLRP3 inflammasome

Partitioning and Chemical Environments of Minor Elements in Individual Large Benthic Foraminifera Cultured in Temperature-Controlled Tanks

Because reef-dwelling large benthic foraminifera (LBF) tests, which is composed of high-magnesium calcite, are the common components of modern reef sediments, and ancient reef carbonate rocks, they can provide a continuous record of the paleoenvironment of reef sediments. Evaluation of the responses of the minor element concentrations (Mg, Sr, Na, P, and S) of individual tests to ambient temperature and LBF growth modes was conducted with two cultured species, Calcarina gaudichaudii and Amphisorus kudakajimensis. The elements were assessed as tracers of temperature, salinity, nutrient concentration, and calcification rate. The Mg content of C. gaudichaudii and the Sr content of both species were controlled by temperature. It can be confirmed that the Mg of individual tests of C. gaudichaudii is a useful paleothermometer. There was a large biological modulation of Na, P, and S incorporation. In situ XANES analysis revealed that both inorganic and organic species contributed to the P and S content of LBF tests. We observed five sulfur components with variable oxidation states

Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin

The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2−/− mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2−/− lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2−/− and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2−/− fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2−/− mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF

Unilateral Ovarian Abscess Caused by Salmonella

Background: Patients with unilateral ovarian abscesses due to Salmonella are rare. Case report: A 48-year-old woman with a left ovarian abscess caused by Salmonella group O7 is reported. Conclusion: In our patient, the ovary may have been seeded hematogenously by salmonellae and may have evolved into a local infection

Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice

MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFN gamma, naive Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFN gamma and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells

Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia

金沢大学大学院医学系研究科　We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of 125I-LDL were 0.5 ± 0.3 ng/mg protein (mean ± SEM), 14 ± 8 and 8 ± 6 ng/mg protein per 6 h (four normal cells; 44 ± 3, 386 ± 32, and 1,335 ± 214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of 12:5I-LDL were 6 ± 2, 29 ± 8, and 90 ± 32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed ~46% of the normal activities of receptor. ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [14C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 μg/ml. However, at 0.05 μg/ml of ML-236 B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 μg/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and heterozygote, sterol synthesis was inhibited even after preincubation. These results suggest that (a) the inhibitory effect of ML-236B is overcome in homozygote cells by their high intracellular levels of HMG-CoA reductase and (b) that a higher dose of ML-236B may be required to lower serum cholesterol levels in FH homozygotes than in heterozygotes