Determinant factors of postoperative recurrence of endometriosis: difference between endometrioma and pain.

OBJECTIVE: Although the postoperative use of hormonal treatment for endometriosis is recommended in the European Society of Human Reproduction and Embryology guidelines to prevent the recurrence of endometriosis-associated dysmenorrhoea, hormonal treatment may not be necessary for all patients who undergo surgical treatment for endometriosis. The aim of this study was to clarify the determinant factors that predict the recurrence of endometriosis after surgery in order to develop personalized hormonal treatment recommendations. Factors associated with the recurrence of endometrioma and pain were investigated independently to identify the likelihood of recurrence in each individual patient. STUDY DESIGN: Between 2008 and 2013, 352 patients underwent surgery and were diagnosed with endometriosis based on pathological findings at the study hospital. Among these patients, 191 experienced a recurrence of endometrioma in the absence of pre- or postoperative hormonal treatment. Various clinical factors such as pre-operative pain, intra-operative findings and postoperative improvement of pain were compared between patients who experienced recurrence after surgery and those who did not. RESULTS: The cumulative 5-year recurrence rate of endometrioma was 28.7% among the 191 patients who did not undergo pre- or postoperative hormonal treatment. Significant differences were detected in maximum tumour diameter, revised American Society for Reproductive Medicine score (r-ASRM score), operative time and operative blood loss between patients in the recurrent endometrioma group and the non-recurrent endometrioma group; only the r-ASRM score was significantly correlated with recurrence of endometrioma in the multivariate analysis. The cumulative 5-year rate of persistent/recurrent pain was 33.4%. There were significant differences in the postoperative improvement of pain between the persistent/recurrent pain group and the non-recurrent pain group according to the univariate and multivariate analyses. CONCLUSION: This study suggests that the risk factors for recurrence of endometrioma differ from the risk factors for recurrence of pain. The use of postoperative hormonal treatment should be considered based on the dominant risk factors and needs of each patient.

Gastric adenocarcinoma of fundic gland type (chief cell predominant type) with unique endoscopic appearance curatively treated by endoscopic submucosal resection.

Gastric adenocarcinoma of fundic gland type [chief cell predominant type; (GA-FD-CCP)] is a rare gastric cancer variant arising from non-atrophic mucosa without Helicobacter pylori infection in the upper third portion of the stomach. GA-FD-CCP originates deep in the mucosal layer; hence, endoscopic lesion detection is often difficult at an early stage because of a minimal change in the mucosal surface. Here we present a 66-year-old man with an early stage of GA-FD-CCP showing characteristic endoscopic features. Esophagogastroduodenoscopy demonstrated a flat, slightly reddish area with black pigment dispersion and irregular micro-surface structure at the gastric fornix. The tumor was resected by endoscopic submucosal dissection and was pathologically diagnosed as GA-FD-CCP. Prussian blue staining revealed that the black pigment was a hemosiderin deposition. We reported a rare case of successfully treated GA-FD-CCP with black pigmentation that aided in early lesion detection.

Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.

BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.

Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells.

Interleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-gamma on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [(125)I]-labelled IL-17. The activation of nuclear factor-kappa B (NF-kappa B), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-gamma induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-gamma for 24 h enhanced [(125)I]-labelled IL-17-binding by 2.4-fold. IL-17 rapidly induced the phosphorylation and degradation of I kappa B alpha molecules, and the combination of IL-17 and IFN-gamma induced a marked increase in NF-kappa B DNA-binding activity as early as 1.5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-gamma synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-gamma might play an important role in the inflammatory responses in the intestinal mucosa.

Rhodium complex-catalyzed reaction of isonitriles with carbonyl compounds: catalytic synthesis of pyrroles.

[figure: see text] Low-valent rhodium complexes are efficient catalysts for the activation of alpha-C-H bond of isonitriles. Addition of isonitriles to carbonyl compounds proceeds under mild and neutral conditions to give the corresponding alpha,beta-unsaturated formamides. Catalytic synthesis of pyrroles can be performed by cyclocondensation of isonitriles with 1,3-dicarbonyl compounds.

Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells.

BACKGROUND: Bile acids have been shown to exhibit varying degrees of cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the aim of the present study is to investigate the mechanisms underlying the cytotoxicity of HDCA. METHODS: The intestinal cell lines IEC-6 and Caco-2 cells were used. The cytotoxicities of various bile acids were evaluated using the MTS assay; their cytolytic effects were measured using the LDH release assay. The induction of apoptosis was determined by the specific figure changes in the cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis induced by the bile acids was measured using an ELISA assay. RESULTS: The bile acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis, depending on their hydrophobic properties. On the other hand, HDCA induced strong cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing monolayer cells. CONCLUSIONS: These results strongly suggest that HDCA induces cytotoxicity through its ability to induce apoptosis rather than its detergent effect.

Medium- and long-chain fatty acids differentially modulate interleukin-8 secretion in human fetal intestinal epithelial cells.

The primary therapeutic effects of enteral nutrition in patients with Crohn's disease have been reported previously. Although the quantity and type of fat in enteral nutrition are considered to be important, it is unclear how fat modulates mucosal inflammatory responses in the intestine. In the present study, we evaluated the effects of medium-chain and long-chain fatty acids (MCFA and LCFA) on interleukin (IL)-8 secretion in a fetal intestinal epithelial cell line, intestine-407 cells. IL-8 expression was evaluated at the protein and mRNA levels. The activation of nuclear factor-kappaB was assessed with an electrophoretic gel mobility shift assay. The addition of oleic acid (LCFA) micelles, but not octanoic acid (MCFA) micelles, weakly but significantly enhanced basal IL-8 secretion in the intestine-407 cells. The addition of MCFA (5 mmol/L) induced a 40% increase in IL-1beta-induced IL-8 secretion and a 35% increase in tumor necrosis factor (TNF)-alpha-induced IL-8 secretion, respectively. The addition of LCFA (5 mmol/L) induced a 140% increase in IL-1beta-induced IL-8 secretion and a 110% increase in TNF-alpha-induced IL-8 secretion, respectively. These responses were also observed at the mRNA levels. The electrophoretic gel mobility shift assay indicated that both MCFA and LCFA enhanced IL-1beta- and TNF-alpha-induced nuclear factor-kappaB activation. We demonstrated the proinflammatory activities of MCFA and especially LCFA. It is likely that medium-chain triglycerides may be more suitable than long-chain triglycerides as an energy source in enteral diets in the treatment of patients with Crohn's disease.

Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in human pancreatic periacinar myofibroblasts.

BACKGROUND & AIMS: We have previously isolated and characterized human pancreatic periacinar myofibroblasts. In this study, to define the role of these cells in the pathogenesis of acute pancreatitis, we investigated chemokine expression in them. METHODS: Secretion of chemokines (interleukin [IL]-8, monocyte chemoattractant protein [MCP]-1, RANTES, and MIP [macrophage inflammatory protein]-1alpha) was evaluated by ELISA, Northern blotting, and nuclear run-on assays. The activation of NF-kappaB and NF-IL6 was assessed by an electrophoretic gel mobility shift assay. RESULTS: IL-8 and MCP-1 secretion was rapidly induced by both IL-1beta and tumor necrosis factor (TNF)-alpha. RANTES secretion was induced more slowly and was induced mainly by TNF-alpha. However, MIP-1alpha secretion was not induced by any stimuli. These responses were also observed at the messenger RNA level, and they were accompanied by an increase in transcriptional rate. The increase in transcriptional activation of chemokine genes correlated with the NF-kappaB and NF-IL6 activation. Furthermore, a blockade of NF-kappaB activation by PDTC and TPCK markedly reduced the IL-1beta- or TNF-alpha-induced chemokine gene expression. CONCLUSIONS: Chemokine secretion is differentially regulated in pancreatic periacinar myofibroblasts, suggesting a role for these cells in mediating the infiltration and accumulation of inflammatory cells in the pancreas.

The expression of chemokine genes correlates with nuclear factor-kappaB activation in human pancreatic cancer cell lines.

Chemokines may regulate the process of immune cell infiltration that is often found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and RANTES (regulated on activation, normal T cell expressed and secreted)] in human pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear factor-kappaB (NF-kappaB) and NF-IL6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was not detected in all cells. The addition of IL-1beta and tumor necrosis factor (TNF)-alpha strongly enhanced IL-8, MCP-1, and RANTES secretion; these responses were observed at the mRNA level as well as at the protein level. IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB in PANC-1 cells, and the increase in chemokine mRNA expression correlated with NF-kappaB activation. The activation of NF-IL6 was modest. A blockade of NF-kappaB activation by TPCK markedly reduced the IL-1beta- and TNF-alpha-induced chemokine gene expression. Our findings indicate that chemokines are produced by pancreatic cancer cells, and suggest that these factors may contribute to the accumulation of tumor-associated immune cells. In addition, the transcriptional activation of chemokine genes in pancreatic cancer cells may be closely associated with NF-kappaB activation.

Low-valent ruthenium and iridium hydride complexes as alternatives to Lewis acid and base catalysts.

The discovery of a new chemical reaction often leads to new applications and new chemical principles. Low-valent ruthenium and iridium hydride complexes are highly useful redox Lewis acid and base catalysts. Nitriles are activated by these catalysts and undergo reactions with either nucleophiles or electrophiles under neutral conditions. Hydration of nitriles, esterification of nitriles with alcohols, and amidation of nitriles with amines can be performed catalytically together with formation of ammonia. The catalytic reactions of pronucleophiles such as nitriles and carbonyl compounds with electrophiles such as alkenes, alkynes, carbonyl compounds, imines, and nitriles take place generally.

Secretion of complement components of the alternative pathway (C3 and factor B) by the human alveolar type II epithelial cell line A549.

The complement system participates in the local immune system of the lung. In this study, we investigated the secretion of complement components of the alternative pathway (C3 and factor B) in the alveolar type II epithelial cell line A549. The levels of C3 and factor B protein in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). The C3 and factor B mRNA expression was assessed by reverse transcription polymerase chain reaction (RT-PCR). The addition of interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha induced a dose- and time-dependent increase in C3 and factor B secretion. The addition of IL-6 or interferon (IFN)-gamma also induced a weak but significant increase in C3 and factor B secretion. These responses at the protein level were also observed at the mRNA level. Furthermore, the combination of IL-1beta plus TNF-alpha induced a marked increase in C3 and factor B secretion. Similarly, IL-6 and IFN-gamma potently enhanced IL-1beta- or TNF-alpha-induced C3 and factor B secretion, respectively. In this study, we demonstrated C3 and factor B secretion in A549 cells, and showed that the proinflammatory cytokines, IL-1beta, IL-6, TNF-alpha and IFN-gamma, acted as potent inducers of C3 and factor B secretion. It is likely that alveolar type II epithelial cells are the local sites of complement biosynthesis, and that various cytokines act as regulators of this local immune protection system.

Transforming growth factor-beta1 acts as a potent inhibitor of complement C3 biosynthesis in human pancreatic cancer cell lines.

In this study, we attempted to determine how transforming growth factor (TGF)-beta1 affects complement C3 secretion in the pancreatic cancer cell lines PANC-1 and BxPC-3. We also compared the responses in C3 secretion with those in interleukin (IL)-8 secretion. The C3 and IL-8 expression was evaluated at the protein and messenger RNA (mRNA) levels. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-1beta and tumor necrosis factor (TNF)-alpha both induced a marked increase in C3 and IL-8 secretion. However, TGF-beta1 potently decreased the IL-1beta- and TNF-alpha-induced C3 secretion, whereas the IL-8 secretion was weakly but significantly enhanced. These responses were also observed at the mRNA level. In PANC-1 cells, IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB, and TGF-beta1 enhanced this activation slightly. The induction of Fos protein has been reported to be required for the inhibitory action of TGF-beta1, and the translocation of Fos protein into the nucleus was associated with TGF-beta1 stimulation in PANC-1 cells. Our results suggest that TGF-beta1 may act as a potent inhibitor of C3 secretion in pancreatic cancer cell lines under inflammatory conditions. This action of TGF-beta1 did not correlate with NF-kappaB activation, but associated with the translocation of Fos protein into the nucleus.

Counter-regulatory effect of sodium butyrate on tumour necrosis factor-alpha (TNF-alpha)-induced complement C3 and factor B biosynthesis in human intestinal epithelial cells.

The various biological activities of butyrate have been well documented. In this study, we tested the effects of butyrate on TNF-alpha-induced complement C3 and factor B biosynthesis in human intestinal epithelial cells. The biosynthesis of C3, factor B and IL-8 was evaluated at the protein and mRNA levels. To evaluate transcriptional activation, the nuclear run-on assay was performed. The transcription factor-DNA binding activity was assessed by an electrophoretic gel mobility shift assay (EMSA). In the intestinal epithelial cell lines HT-29, T84 and Caco-2, sodium butyrate enhanced TNF-alpha-induced C3 secretion, but suppressed TNF-alpha-induced factor B and IL-8 secretion. Nuclear run-on assay revealed that transcriptional regulatory mechanisms are involved in the effects of sodium butyrate. The EMSAs indicated that sodium butyrate suppressed TNF-alpha-induced nuclear factor (NF)-kappaB- and activation protein (AP)-1-DNA binding activity, but enhanced TNF-alpha-induced activation of CCAAT/enhancer-binding protein (C/EBP)beta (NF-IL-6)-DNA binding activity. Sodium butyrate induced a counter-regulatory effect on TNF-alpha-induced C3 and factor B biosynthesis in human intestinal epithelial cells. Butyrate action has been discussed with its activity to induce histone hyperacetylation, but its counter-regulatory effect on complement biosynthesis may be closely associated with the modulation of transcription factor activation.

[In vitro activities of 23 antimicrobial agents against 4,993 gram-positive and gram-negative bacterial strains isolated from multicenter of Japan during 1994--in vitro susceptibility surveillance.Levofloxacin-Surveillance Group].

In a surveillance study conducted during 1994 at 24 medical institutes from different geographical areas of Japan, the susceptibility of clinical isolates to twenty three comparative agents, such as ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefaclor, cefotiam, cefdinir, cefclidin, ceftazidime, cefpirome, imipenem, aztreonam, vancomycin, minocycline, chloramphenicol, clarithromycin, sulfamethoxazole/trimethoprim, amikacin, and gentamicin, were tested by the standard broth micro-dilution method. A total of 4,993 isolates tested in this study included Streptococcus pneumoniae, methicillin susceptible Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), coagllase negative streptococci (CNS), Enterococcus faecalis, Enterococcus faecium, Enterobactericeae, Pseudomonas aeruginosa from patients with urinary tract infections or respiratory tract infections, and Haemophilus influenzae. For MSSA, S. pneumoniae, Enterobacteriaceae, and H. influenzae, more than 70% of the isolates was susceptible to fluoloquinolones. However, resistance occurred in more than 50% of MRSA and P. aeruginosa isolated from UTI. Fluoroquinolones were found to be effective against high level penicillin-resistant S. pneumoniae, the third generation cephem-resistant Enterobacteriaceae and ampicillin-resistant H. influenzae.

Primary gastric Burkitt's lymphoma presenting with c-myc gene rearrangement.

A 54-year-old man with primary gastric Burkitt's lymphoma is described. He was evaluated for appetite loss and intermittent midepigastric pain. Upper gastroduodenal endoscopy detected an ulcer in the lesser curvature of the body, and biopsy specimens revealed infiltration of medium-sized lymphoblasts with "starry sky" macrophages. The infiltrated cells were positive for a B-cell marker. Abdominal computed tomography scan demonstrated marked enlargement of the gastric wall, but no enlargement of lymph nodes. These findings led us to diagnose primary gastric Burkitt's lymphoma. The patient responded dramatically to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but 6 months after his initial admission, the disease recurred in the stomach and bone marrow. Lymphoblastic cells were positive for B-cell markers (CD 10, 19, 20, and human leukocyte antigen [HLA]-DR) and showed an abnormal karyotype, 47, XY, t(8;14)(q24;q32), +12. In these cells, the Epstein-Barr virus genome was detected by polymerase chain reaction. Southern blot analysis revealed rearrangement of Ig heavy and light chain genes. In addition, c-myc gene rearrangement was detected. Eight months after the beginning of chemotherapy, the patient died of central nervous system involvement. To our knowledge, this is the first description of a genetic analysis of primary gastric Burkitt's lymphoma.

[Evaluation of the number of clones and the degree of nucleotide diversity of the HCV genome by FSSA (fluorescence single strand conformation polymorphism and sequence analysis) in patients with chronic active hepatitis C receiving interferon therapy].

We evaluated the number of clones and the degree of nucleotide diversity in the HVR of the HCV genome in patients with chronic active hepatitis C who were treated with IFN (interferon). We could not obtain the nucleotide sequence per se of the HCV genome but were able to evaluate the degree of diversity in the nucleotide sequence of the HCV genome using FSSA. Nonresponders to IFN therapy showed significant diversity in the nucleotide sequence, even if their number of HCV clones are small. Responders showed little diversity in the nucleotide sequence, which suggests that their viral clones were composed of populations with less variability in the HVR. IFN therapy had more impact on diversity in the nucleotide sequence than on the number of HCV clones.

[Markedly elevated serum fructosamine in a non-diabetic patient with IgA-kappa type multiple myeloma].

We reported a non-diabetic patient with IgA-kappa multiple myeloma whose serum fructosamine value was markedly elevated. The M-protein from this patient was shown to be conjugated to serum albumin confirmed by immunoelectrophoresis and immunofixation. The fructosamine activity was shown in the high molecular weight fraction by S-300 superfine gel chromatography. Although serum fructosamine values of other three non-diabetic patients with IgA type multiple myeloma were elevated, patients with IgG type multiple myeloma and primary macroglobulinemia had low or normal serum fructosamine values. These findings suggested that glycation of monoclonal IgA of multiple myeloma was much more increased than that of other types of immunoglobulins and monoclonal IgA in this patient was conjugated to serum albumin resulting in the elevated serum fructosamine.