The inhibitory effect of AMP-activated protein kinase (AMPK) on chemokine and prostaglandin production in human endometrial stromal cells.

BACKGROUND: To investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1ß in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR). METHODS: Endometrial specimens were obtained and cultured. We examined the effects of IL-1ß, IL-1 ra and AICAR on the production of IL-8, MCP-1, PGE2 and PGF2α in human ESCs. The phosphorylations of AMPK, IκB, 4EBP-1, p70S6K and S6 ribosomal protein were analyzed by Western immunoblotting. RESULTS: Following stimulation by IL-1ß, the production of IL-8, MCP-1, PGE2 and PGF2α showed significant increases, and these increases were suppressed by AICAR. The expression of cyclooxygenase-2 (COX-2) induced by IL-1ß and suppressed by AICAR. The phosphorylation of IκB, 4EBP-1, p70S6K and S6 ribosomal protein were inhibited via an AMPK-dependent signal transduction. CONCLUSIONS: The production of IL-8, MCP-1, PGE2 and PGF2α induced by IL-1ß in ESCs were involved in the negative regulatory mechanisms of AMPK. The substances that activate AMPK may be promising agents for the treatment of pathological problems such as dysmenorrhea.

Effect of the Propionylation Method on the Deformability under Thermal Pressure of Block-Shaped Wood.

Converting wood waste into thermoplastic materials is an attractive means of increasing its utilization because complex three-dimensional molded products can easily be obtained by press molding wood with thermoplasticity. Chemical modification, especially esterification, is a promising method for imparting thermoplasticity to wood. In this study, we produced multiple propionylated wood specimens using several propionylation methods and elucidated the factors affecting the deformability of the wood. Regardless of the method, all of the propionylated wood samples showed deformability in the tangential direction. However, in the longitudinal direction, not only the degree of propionylation but also the propionylation method had a significant influence on the deformability. The flow in the tangential direction occurred under a relatively low pressure, whereas the flow in the longitudinal direction occurred under higher pressure. The chemical composition and motility of each sample were evaluated using solid-state NMR measurements. With some propionylation methods, decomposition of the cellulose main chain occurred during the reaction, which had a dominant effect on the deformability of the wood in the longitudinal direction. These results indicate that the deformability of wood can be controlled by the appropriate selection of a propionylation method and its treatment conditions.

Solid-state NMR study on changes of phosphate and proton species in metal pyrophosphate composite (MP2 O7 -MO2 ) ceramics.

In order to investigate the effects of composite production and the role of the counter cation for metal phosphate conductors, changes in the solid-state nuclear magnetic resonance (NMR) spectra and magnetic relaxation times caused by the removal of volatile products and water washing were examined for various metal pyrophosphate (MP2 O7 -MO2 ; M = Sn, Si, Ti, and Zr). Acidic species could be detected by 1 H MAS NMR spectra for all the composites except ZrP2 O7 -ZrO2 that had the lowest conductivity. The 31 P DD-MAS NMR spectra for MP2 O7 -MO2 composites showed different signal patterns depending on the counter cations participating in the ion exchange as a result of different microstructures. Combinational analysis of 31 P DD-MAS and 31 P CP-MAS NMR spectra of the composites indicated that protonic bulk phosphates were observed at slightly lower fields than non-protonic bulk phosphates in all of the MP2 O7 -MO2 composites. After water washing, the acidic species and the protonic bulk phosphates of MP2 O7 -MO2 composites disappeared or were reduced to trace amounts. The T1 H values of the water-washed composites lengthened because of removal of orthophosphoric acid, although the T1 P values remained almost unchanged. The results of the solid-state NMR studies suggest that the protonic bulk phosphates of MP2 O7 -MO2 composites do not generally distribute in the bulk but exist in the interface between excess H3 PO4 and the bulk. Copyright © 2016 John Wiley & Sons, Ltd.

Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report and survey of related literature.

Primary large-cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen.

Congenital toxoplasmosis from a mother with type 2 diabetes mellitus: a case report.

A 33-year-old woman with type 2 diabetes mellitus (DM) was suspected of being primarily infected with Toxoplasma gondii at 12 weeks of gestation (GW). Although acetylspiramycin was started at 17 GW, the T. gondii DNA gene was detected in the amniotic fluid at 18 GW. Chemotherapy was changed to pyrimethamine plus sulfadiazine from 20 GW, but was changed back to acetylspiramycin after 2 weeks because of vomiting. Acetylspiramycin was continued until her delivery. DM was controlled well during the pregnancy. An asymptomatic male baby was born by cesarean section at 37 GW, and was treated with acetylspiramycin for 4 weeks because the polymerase chain reaction results of umbilical cord blood were positive. He has developed normally until the present, that is, 6 months of age. Herein, we describe a case report in which symptomatic congenital toxoplasmosis was avoided in a pregnant woman with an immunosuppressive risk due to prompt chemotherapy.

Recurrent immature teratoma of the ovary with long-term disease-free interval.

Grade 3 immature teratoma of the ovary is rare and has a poor prognosis due to early recurrence. This report describes a case of grade 3 immature teratoma of the ovary that recurred 16 years after the last treatment. The patient underwent abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, pelvic-para-aortic lymphadenectomy, and adjuvant chemotherapy under the diagnosis of grade 3 immature teratoma of the ovary when she was 15 years old, and complete remission was achieved. Sixteen years after the initial treatment, the tumor relapsed in her liver and pleura. She was treated by 10 courses of tri-weekly paclitaxel and carboplatin, and was alive with stable disease for 12 months after the disease relapse. After 1 year, the tumor progressed, and she died 16 months after the relapse. This is the first report of grade 3 immature teratoma of the ovary that relapsed more than 5 years after the prior treatment.

Retrospective analysis of outcomes of secondary debulking surgery for recurrent epithelial ovarian cancer with favorable prognostic factors.

AIM: Ovarian cancer is the second most common gynecological malignancy, yet it has the highest case-fatality ratio of all gynecologic malignancies. Surgery followed by combination platinum-taxane chemotherapy is the standard approach to the management of primary epithelial ovarian cancer. However, standard treatment of patients with recurrent ovarian cancer remains poorly defined. Secondary cytoreductive surgery (SDS) at the time of relapse has been proposed as a means of improving the prognosis of recurrent ovarian cancer patients with a treatment-free interval of at least 6 months. METHODS: In the present study, we retrospectively collected 16 patients with recurrent epithelial ovarian cancer who might benefit most from SDS and evaluated the impact of SDS on the outcomes for this highly select patient group. RESULTS: We found that SDS led to excellent outcomes, with a 73.1% 8-year overall survival rate after initial treatment, a 67.9% 5-year overall survival rate after prior SDS, and a 31.3% 5-year progression-free survival rate after prior SDS. Although the findings were not significant, these results suggest that repeated SDS might improve outcomes for this patient group. CONCLUSION: The present study may provide a platform for discussion of the impact of aggressive or repeated SDS on the survival of patients with recurrent epithelial ovarian cancer and favorable prognostic factors. Further multi-institutional studies with larger number of patients are mandatory to confirm the present findings.

Solid-state NMR study of dopant effects on the chemical properties of Mg-, In-, and Al-doped SnP2 O7.

The effects of doped low-valence cations on the properties of the SnP2 O7 proton conductor at ambient temperature are investigated from changes in solid-state NMR spectra and nuclear magnetic relaxation times. Although the T1 H values increased with decreasing acidity as a result of cation exchange, the (1)H chemical shifts moved to lower field in Al- and In-doped materials compared with undoped ones. Furthermore, the shifts changed to higher field in Mg-doped materials, suggesting the existence of different protonic species in those materials. The bulk phosphate chemical shifts in the (31)P dipolar-decoupling MAS NMR spectra were very similar, regardless of the nature and amount of the doping species. On the other hand, by (1)H/(31)P cross-polarization MAS NMR, P2O7 signals interacting with an interstitial proton [Q(1)(proton)] were observed in all the undoped and doped SnP2 O7, while acidic P-OH-type phosphate signals [Q(1)(acid)] were additionally observed in the Mg-doped conductor. The different affinity of the proton with the dopants and phosphates caused lower conductivity and larger activation energy in the Mg-doped materials, compared with those in the In- and Al-doped materials.

Endometriosis of the perineum.

Endometriosis of the perineum and vulva is extremely rare, with the most common site being episiotomy scars. We report here a case of spontaneously developing perineal endometriosis successfully treated with local excision. A 39-year-old woman was admitted complaining of a painful vulvar lump with cyclic swelling. She had first noticed the mass 7 years before, and it had gradually increased in size. Gynecological examination showed a walnut-size, painful, subcutaneous mass in the left perineum. Magnetic resonance imaging revealed a multilobular cystic mass with inner hemorrhage, suggesting vulvar endometriosis. The patient was treated by local excision of the vulvar mass, and complete excision was achieved. The pathological diagnosis of the excised tissue was endometriosis. The patient is well without evidence of disease 5 months following the local excision. Spontaneous perineal and vulvar endometriosis is extremely rare. However, any lesion that evolves in response to the menstrual cycle should be considered endometriosis.

Coexistence of Ovarian Endometrioma and Ovarian Pregnancy: A Case Report.

Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a 34-year-old Japanese woman with a life-threatening hemoperitoneum in the first trimester coexisting with ovarian endometrioma and ovarian pregnancy. The patient was hospitalized in our department for acute hypogastric pain and massive hemoperitoneum during pregnancy. She had a history of miscarriage at eight weeks of gestation one year prior. Her serum beta-human chorionic gonadotropin (hCG) level was >2,000 mIU/mL. Also, a transvaginal ultrasound showed an empty uterus, an intact right ovary, an inhomogeneous left ovary, and a massive hemoperitoneum. An exploratory laparoscopy revealed a rupture of the left ovarian endometrioma, a left corpus luteal cyst, and intraperitoneal bleeding of approximately 1,200 mL. However, no ectopic lesions were observed. Microscopic examination revealed an endometriotic cyst with decidual changes in the stroma, a corpus luteal cyst, and chorionic villi with hemorrhage. Serum beta-hCG levels became negative on the 27th postoperative day. The postoperative course was uneventful. This case shows that, in addition to the differential diagnosis of ovarian pregnancy from ovarian endometrioma, clinicians should consider the coexistence of both conditions.

Prophylactic oophorectomy and aromatase inhibitors for premenopausal deep angiomyxoma: A case report and literature review.

Deep angiomyxoma is a rare, infiltrative, hormone-dependent, benign-mesenchymal neoplasm that occurs in the deep soft tissues of the perineal regions. In total, 33% females with newly diagnosed deep angiomyxoma will typically relapse within 5 years after the standard treatment of radical resection. Postoperative hormone therapy is frequently administered to prevent recurrence, but the role of prophylactic oophorectomy in premenopausal women remain to be fully elucidated. In the present report, a 42-year-old Japanese woman was referred for a refractory Bartholin's cyst that is 14 cm in diameter. Based on the results of imaging (unenhanced CT and MRI) and histopathology, deep angiomyxoma was suspected, but no definitive diagnosis was possible. Tumor resection and bilateral salpingo-oophorectomy were performed before the postoperative diagnosis was confirmed to be deep angiomyxoma. The patient received an aromatase inhibitor (2.5 mg letrozole daily) as adjuvant hormonal therapy. There was no evidence of recurrence at the 1-year postoperative follow-up. In conclusion, prophylactic oophorectomy and postoperative adjuvant therapy with aromatase inhibitors may be a promising treatment option for deep angiomyxoma to optimize the outcome of surgical treatment. Long-term follow-up is required to monitor for the late and/or local recurrence of deep angiomyxoma and possible adverse effects of adjuvant hormonal therapy.

Calcium/calmodulin-dependent kinase inhibitor induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells.

KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells. We investigated the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of KN-93, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.

A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells.

The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand (initially described as a ligand for the peripheral benzodiazepine receptor), induces apoptosis in some lines of human tumor cells. We investigated the effect of PK11195 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of PK11195, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of PK11195. In contrast, the nonsite selective ligand diazepam has a little effect on these cells. Cell cycle analysis indicated that exposure to PK11195 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that PK11195 may serve as a therapeutic agent for the treatment of choriocarcinoma.

Parallel factor (PARAFAC) kernel analysis of temperature- and composition-dependent NMR spectra of poly(lactic acid) nanocomposites.

The parallel factor (PARAFAC) kernel matrix to analyze a sample system stimulated by more than one type of perturbation is described. PARAFAC kernel is a quantitative representation of the synchronicity and asynchronicity observed within the PARAFAC score matrices generated by carrying out two-dimensional (2D) correlation analyses. Thus, kernel matrix representation provides more intuitively understandable interpretation to the conventional PARAFAC trilinear model. In this study, the utility of PARAFAC kernel is demonstrated by the study of poly(lactic acid)-nanocomposite undergoing a structural change depending on the temperature as well as the clay content in the sample. Seemingly complicated variation of nuclear magnetic resonance (NMR) spectra induced by the change in the temperature and clay content are readily analyzed by the multiple-perturbation 2D correlation spectroscopy and PARAFAC kernel. PARAFAC kernel revealed that crystalline and amorphous structures of the PLA substantially undergo thermal deformation, and these variations are also influenced by the presence of the clay.

Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells.

A membrane-targeted, lipophilic ether lipid of synthetic phospholipid analog, erucylphosphocholine (ErPC), induces apoptosis in some lines of human tumor cells. We investigated the effect of ErPC in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of ErPC, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that BeWo cells were sensitive to the growth inhibitory effect of ErPC. Cell cycle analysis indicated that exposure to ErPC decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine and by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that ErPC may serve as a therapeutic agent for the treatment of choriocarcinoma.

Effects of bufalin on the proliferation of human choriocarcinoma cells.

OBJECTIVE: Bufalin is a traditional Chinese medicine, and it induces apoptosis in some lines of human tumor cells. METHODS: We investigated the effect of bufalin in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of bufalin, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. RESULTS: An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that BeWo cells were sensitive to the growth inhibitory effect of bufalin. Cell cycle analysis indicated that exposure to bufalin decreased the proportion of cells in the synthesis phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. CONCLUSIONS: These results suggest that bufalin may serve as a therapeutic agent for the treatment of choriocarcinoma.

Rapid Benzylation of Wood Powder without Heating.

Converting wood waste into thermoplastic materials is an attractive means of increasing its utilization. A promising method for imparting thermoplasticity to wood is chemical modification, in which the hydroxyl groups in wood are substituted with benzyl groups. In the common method, wood powder is first treated with a highly concentrated aqueous NaOH solution, and then reacted with a benzylation reagent by heating for a long time under stirring. In this study, a 50% aqueous tetra-n-butylphosphonium hydroxide solution was used for the pretreatment of wood powder. This modified alkaline treatment enhanced the efficiency of the subsequent benzylation reaction, which could be conducted without heating over a shorter time. The effects of various conditions on the efficiency of the benzylation reaction were evaluated. Both the alkali pretreatment and the subsequent benzylation required only ~5-10 min of stirring without heating to obtain benzylated wood with a similar degree of benzylation as that achieved by the common method. The chemical structure of the benzylated wood powder was characterized by Fourier-transform infrared and solid-state NMR spectroscopies, and its thermal softening characteristics were evaluated by thermomechanical analysis. Finally, a translucent film could be obtained by hot-pressing the benzylated wood powder.

Small-Cell Carcinoma of the Uterine Cervix Discovered With Quadriplegia Caused by Cervical Spine Metastasis.

Small-cell carcinoma of the uterine cervix is a rare and aggressive tumor, and the prognosis is poor compared with those of squamous cell carcinoma and adenocarcinoma of the uterine cervix, even when discovered at an earlier stage. We treated a patient with progressive small-cell carcinoma of the uterine cervix that metastasized to the cervical spine. The patient, a 73-year-old woman, presented with the symptom of numbness in her limbs. As she had difficulty moving her limbs (ie, quadriplegia), she was carried to an emergency room. A metastatic cervical spine tumor from the uterine cervical cancer was revealed by a computed tomography scan, and the patient was then transferred to our hospital's neurosurgery department for treatment. We performed a resection of the cervical spine tumor and fixation of the spinal bone. Because the patient's performance status was 4 and she remained bedridden 24 h/day, we could not perform systemic chemotherapy. We thus provided palliative care, including palliative radiotherapy, pain control, and rehabilitation to improve her limbs' functioning. The patient died of the uterine cancer within approx. 6 months after the initiation of treatment. There is no established treatment for small-cell carcinoma as a gynecological lesion. For patients with progressive uterine cancer, the optimal treatments, including palliative care, must be determined.

Port-site implantation of parasitic leiomyoma after laparoscopic myomectomy and its histopathology.

Although parasitic leiomyoma could be spontaneous or iatrogenic in origin, port-site implantation of parasitic leiomyoma is an iatrogenic benign sequela of laparoscopic surgery. A 30-year-old, primigravida Japanese woman was referred after unresponsiveness to preoperative gonadotropin-releasing hormone for intramural fibroids. Magnetic resonance imaging showed multiple intramural fibroids and left ovarian endometrioma with no malignant features. Laparoscopic myomectomy with power morcellation and ovarian cystectomy were performed, followed by treatment with a combined oral contraceptive. Seven years after the primary surgery, she underwent abdominal myomectomy for a port-site, and peritoneal recurrence of the leiomyoma and intramural leiomyomas was detected. Microscopic examination revealed that resected specimens from the port-site demonstrated leiomyoma with lesser cell density and more prominent hyalinization than those from the uterus. Therefore, clinicians should counsel patients regarding the risks and benefits of laparoscopy with morcellation versus laparotomy. Further development of techniques for uterine tissues extraction is warranted.

Variable temperature solid-state NMR spectral and relaxation analyses of the impregnation of polyethylene glycol (PEG) into coniferous wood.

To investigate the behaviours of polyethylene glycol (PEG) and its interaction with biomass constituents in coniferous wood (Japanese cypress), variable temperature solid-state NMR spectra and relaxation times were measured from 20-80 °C. Signal intensities in the 1H and 13C PST-MAS NMR spectra changed depending on both the measurement temperature and the melting point of the impregnated PEG. In the 13C CP-MAS NMR spectra with increasing temperature, although the signal intensities of biomass constituents slightly decreased, signal intensities of PEG molecules in the cypress maximized at 80 °C. PEG impregnation into cypress decreased the T 1H values at 80 °C for short to medium chain PEG in the liquid phase while it decreased T 1H values at ambient temperature for long chain PEG in the solid phase because the interactions of PEG molecules and the biomass constituents of coniferous wood were different for different chain lengths of the PEG. These variable temperature measurements of both solid-state NMR spectra and relaxation time indicated that impregnation of longer chain PEG molecules produced higher hydrophobicity because of the increased steric hinderance of PEG attached to carbohydrates. The variable temperature measurements also showed that long chain PEG molecules were restricted to the lumen while short to medium chain length PEG molecules infiltrated into the intercellular region of the cell wall in addition to the lumen. These results obtained from the variable temperature NMR measurements were also supported by ATR-IR spectroscopy analyses.