Associations between birth weight and lung function in a Japanese adult population: The tohoku medical megabank community-based cohort study.

BACKGROUND: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation. METHODS: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants. RESULTS: Birth weight was positively associated with forced expiratory volume in 1 s (FEV1) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV1 of low birth-weight participants was not significant. CONCLUSIONS: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation.

Accuracy of Cardiac Output Measured by Fourth-Generation FloTrac and LiDCOrapid, and Their Characteristics Regarding Systemic Vascular Resistance in Patients Undergoing Cardiac Surgery.

OBJECTIVES: The clinical use of less-invasive devices that calculate the cardiac output from arterial pressure waveform is increasing. The authors aimed to evaluate the accuracy and characteristics of the systemic vascular resistance index (SVRI) of the cardiac index measured by 2 less-invasive devices, fourth-generation FloTrac (CIFT) and LiDCOrapid (CILR), compared with the intermittent thermodilution technique, using a pulmonary artery catheter (CITD). DESIGN: This was a prospective observational study. SETTING: This study was conducted at a single university hospital. PARTICIPANTS: Twenty-nine adult patients undergoing elective cardiac surgery. INTERVENTIONS: Elective cardiac surgery was used as an intervention. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, CIFT, CILR, and CITD, were measured after the induction of general anesthesia, at the start of cardiopulmonary bypass, after completion of weaning from cardiopulmonary bypass, 30 minutes after weaning, and at sternal closure (135 measurements in total). The CIFT and CILR had moderate correlations with CITD (r = 0.62 and 0.58, respectively). Compared with CITD, CIFT, and CILR had a bias of -0.73 and -0.61 L/min/m2, limit of agreement of -2.14-to-0.68 L/min/m2 and -2.42-to-1.20 L/min/m2, and percentage error of 39.9% and 51.2%, respectively. Subgroup analysis for evaluating SVRI characteristics showed that the percentage errors of CIFT and CILR were 33.9% and 54.5% in low SVRI (<1,200 dyne×s/cm5/m), 37.6% and 47.9% in moderate SVRI (1,200-1,800 dyne×s/cm5/m), 49.3% and 50.6% in high SVRI (>1,800 dyne·s/cm5/m2), respectively. CONCLUSIONS: The accuracy of CIFT or CILR was not clinically acceptable for cardiac surgery. Fourth-generation FloTrac was unreliable in high SVRI. LiDCOrapid was inaccurate across a broad range of SVRI, and minimally affected by SVRI.

Endoscopic Resection of a Pedunculated Cavernous Hemangioma of the Sigmoid Colon: A Case Report.

Hemangiomas are common benign tumors that usually occur on the head and neck in children. However, colonic hemangiomas are rare in clinical practice. Approximately 80% of colonic hemangiomas are of the cavernous type, and morphologically, ≥80% of colonic hemangiomas are sessile and semi-pedunculated. Notably, pedunculated colonic hemangiomas are rare. A 69-year-old woman presented with hematochezia and underwent colonoscopy, which revealed a soft pedunculated submucosal tumor (SMT) measuring 1.5 cm in diameter, in the sigmoid colon. The surface of the SMT resembled the surrounding normal colonic mucosa with regard to color and appearance, with multiple red patches. Narrow-band imaging revealed a few telangiectasias on the surface of the SMT. The lesion could not be definitively diagnosed based on endoscopic findings. Therefore, for more accurate diagnosis, the SMT was removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis. Histopathological examination of the specimen revealed a cavernous hemangioma with a negative resection margin. We report a case of a pedunculated cavernous hemangioma of the sigmoid colon removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis.

Microscopic polyangiitis masquerading as a pancreatic neoplasm with multiple lung metastases.

A 71-year-old man was admitted to our hospital with right lower abdominal pain. Blood analysis indicated severe inflammation, and abdominal CT revealed a pancreatic head tumour and multiple lung nodules. The level of a tumour marker was high. Pancreatic cancer with multiple lung metastases was suspected; however, because the mass was not detected via endoscopic ultrasonography, it was not biopsied. The serum creatinine level increased rapidly with a urine disorder, and myeloperoxidase-antineutrophil cytoplasmic antibody staining was positive. Severe rapidly progressive glomerulonephritis (RPGN) and microscopic polyangiitis were diagnosed, and high-dose glucocorticoid treatment was started. The patient's high fever returned to normal, and the serum creatinine level declined. Because the RPGN was severe, cyclophosphamide was administrated, and the glucocorticoid was tapered. The pancreatic tumour regressed, the lung nodules disappeared, and the tumour marker level normalised during the treatment. Renal function improved, and maintenance haemodialysis was avoided.

Inhibition of invasion by glycogen synthase kinase-3 beta inhibitors through dysregulation of actin re-organisation via down-regulation of WAVE2.

Cancer cell invasion is a critical phenomenon in cancer pathogenesis. Glycogen synthase kinase-3ß (GSK-3ß) has been reported to regulate cancer cell invasion both negatively and positively. Thus, the net effect of GSK-3ß on invasion is unclear. In this report, we showed that GSK-3ß inhibitors induced dysregulation of the actin cytoskeleton and functional insufficiency of focal adhesion, which resulted in suppressed invasion. In addition, WAVE2, an essential molecule for actin fibre branching, was down-regulated after GSK-3ß inhibition. Collectively, we propose that the WAVE2-actin cytoskeleton axis is an important target of GSK-3ß inhibitors in cancer cell invasion.

Cell-based assay of nongenomic actions of progestins revealed inhibitory G protein coupling to membrane progestin receptor α (mPRα).

Previously, we established cell lines stably producing goldfish membrane progestin receptor α (goldfish mPRα) proteins, which mediate steroidal nongenomic actions. In this study, we transfected these cell lines (MDA-MD-231) with cDNAs encoding a recombinant luciferase gene (GloSensor). These cells can be used for monitoring the effects of ligands that bind to mPR by means of luminescence, the intensity of which reflects intracellular cyclic adenosine monophosphate (cAMP) levels. Luminescence intensity of the cells increased significantly when cells were treated with forskolin, strong activator of adenylyl cyclase. Then, we established a strategy to measure changes in luminescence that correlated with the actions of the ligands. The actions of ligands were measurable by the prevention of stimulation caused by forskolin after ligand stimulation. The studies using these cell lines indicated that cAMP concentrations were decreased specifically by the mPR ligands 17α,20ß-dihydroxy-4-pregnen-3-one, diethylstilbestrol and progesterone. Furthermore, pertussis toxin inhibited the decrease in cAMP levels caused by mPR ligands. These results support evidence from previous results that mPRα is coupled to an inhibitory G protein.

Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal-responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor-1α mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on their expression of choriocarcinoma cells.

AIM: We studied the effect of pre-eclampsia sera on the expression of placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), metal-responsive transcription factor-1 (MTF-1), heme oxygenase 1 (HO-1) and hypoxia inducible factor-1α (HIF-1α) mRNAs in JEG-3 cells (trophoblast-derived cells) and placenta from pre-eclampsia patients to investigate pre-eclampsia pathophysiology. MATERIAL AND METHODS: Placenta and serum samples were taken from pre-eclampsia and normal pregnancy patients. JEG-3 cells were cultured with pre-eclampsia and normal pregnant sera in 24-well tissue culture plates. RNA was purified from placental trophoblast cells and JEG-3 cells 24 h after incubation. The expression of mRNA was measured using real-time polymerase chain reaction. RESULTS: The expression of sFlt-1 mRNA increased, and that of PlGF and HO-1 mRNA decreased in JEG-3 cells after incubation with pre-eclampsia sera. The expression of PlGF mRNA decreased, and that of sFlt-1mRNA increased in pre-eclampsia placenta. The expression of MTF-1 and HO-1 mRNA decreased. A correlation was found between PlGF mRNA expression and the expression of MTF-1 and HIF-1α mRNA. A correlation between sFlt-1 and HIF-1α mRNA expression was also found. CONCLUSION: Changes in PlGF mRNA expression in pre-eclampsia placenta may relate to serum factors and the expression of MTF-1 and HIF-α mRNA. Changes in sFlt-1mRNA expression may relate to serum factors and the expression of HIF-α mRNA. We suggest that serum factors play a role in PlGF and sFlt-1 expression in pre-eclampsia placenta.

Relationship between Toll-like receptor-4 and mPGES-1 gene expression in local lesions of endometriosis patients.

PROBLEM: Toll-like receptors (TLRs) are innate immune receptors that mediate the pattern recognition of, and response toward, pathogens and host-derived danger signals. We reported that cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) mRNA were expressed in cases of endometriosis. The relationship between COX-2, mPGES-1, and TLR4 in endometriotic lesions has yet to be determined. METHOD OF STUDY: Endometriosis samples were obtained from 37 patients with endometrial cysts. Endometrial tissues were obtained from patients undergoing surgical procedures for benign gynecological conditions. COX-2, mPGES-1, and TLR4 mRNA expressions were examined by real-time quantitative reverse transcription PCR (qRT-PCR) and mPGES-1, and TLR4 protein localization was examined by immunohistochemistry. RESULTS: TLR4 proteins were mostly located to the glandular epithelium. The immunoreactivities of TLR4 and mPGES-1 from endometriosis lesions were significantly higher than those in eutopic endometrium in the proliferative phase. The expression levels of mPGES-1 mRNA in peritoneal endometriosis were higher than those in eutopic endometrium in the proliferative phase. The expression of TLR4 mRNA correlates with that of mPGES-1 mRNA and not with that of COX-2 in endometriotic lesions. CONCLUSION: Relationship between TLR4 and mPGES-1 mRNA in endometriotic lesions indicate that innate immunity may play an important role in the pathogenesis of endometriosis.

Effect on the production of soluble endoglin from human choriocarcinoma cells by preeclampsia sera.

PROBLEM: The soluble endoglin (sEng) is an antiangiogenic protein that may inhibit TGF-ß1 signaling and endothelial nitric oxide synthase activation in endothelial cells. The levels of sEng increased in sera obtained from preeclampsia. The factors that increase the sEng in preeclampsia have not been known well. To investigate the factors that may increase sEng in preeclampsia, we examined the effect of preeclampsia sera on the production of sEng from human choriocarcinoma (JEG-3) cells. METHODS: Serum samples were taken from women with normal pregnancy and from those with preeclampsia. JEG-3 cells were cultured with serum for 24 hrs, and the sEng levels in supernatants and expression of sEng and Hemo oxygenase-1 (HO-1) mRNA in cells were measured. RESULTS: The addition of preeclampsia sera into JEG-3 cells led to increased release of sEng and expression of Eng mRNA. Preeclampsia sera inhibited the expression of HO-1 mRNA in JEG-3 cells. CONCLUSION: The results suggest that preeclampsia sera may increase the protein production of sEng and mRNA expression of Eng from JEG-3 cells like trophoblast without hypoxia and that in addition to hypoxia, preeclampsia sera may play a role of high level of serum sEng in preeclampsia patients. Decreased HO-1 activity may relate to increased sEng release.

Effects of anti-ß2-glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line.

AIM: Anti-ß2-glycoprotein I (anti-ß2-GPI) antibody has been detected in cases of recurrent abortion and intrauterine death. Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) are growth factors that accelerate villous proliferation. Soluble VEGF receptor-1 (sVEGFR1) is a soluble receptor for PlGF and suppresses the function of PlGF. In order to study the pathological mechanism of anti-ß2-GPI antibody, we evaluated the effects of anti-ß2-GPI antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cells. METHODS: The sera were taken from six anti-ß2-GPI antibody-positive and six anti-ß2-GPI antibody-negative patients with recurrent miscarriages. Choriocarcinoma cells (JEG-3) were cultured in 24-well plates. After each serum and isolated immunoglobulin G (IgG) were added to the culture medium, the PlGF, VEGF and sVEGFR1 in the culture medium were measured by ELISA 24 h later. When the isolated IgG was added to culture medium, only the levels of PlGF were measured. RESULTS: The anti-ß2-GPI antibody-positive sera and isolated IgG significantly suppressed the production of PlGF from JEG-3 cells more strongly than the anti-ß2-GPI antibody-negative sera. The suppressive effects were not changed by serum inactivation. There was no significant difference in the values of the XTT assay and the production of VEGF and sVEGFR1 between the antibody-positive and antibody-negative sera. CONCLUSIONS: Anti-ß2-GPI antibody-positive sera and IgG suppress the production of PlGF from JEG-3 cells. We suggest that the anti-ß2-GPI antibodies may suppress PlGF production from trophoblasts and cause the failure of placenta formation and function.

O-[18F]fluoromethyl-L-tyrosine is a potential tracer for monitoring tumour response to chemotherapy using PET: an initial comparative in vivo study with deoxyglucose and thymidine.

PURPOSE: To compare the utility of a new artificial amino acid, O-[18F]fluoromethyl-L-tyrosine ([18F]FMT), for monitoring cancer chemotherapy with deoxyglucose and thymidine. METHODS: [18F]FMT, [14C]deoxyglucose ([14C]DG) and [6-3H]thymidine ([3H]Thd) were applied in this study. A 2.5 mg/kg dose of mitomycin (MMC) was administered to AH272 rat hepatoma-bearing Donryu rats. Tumour uptake of each tracer was measured just before (baseline) and on days 1, 3, 5 and 7 after the MMC administration, 1 h after a mixture of [18F]FMT, [14C]DG and [3H]Thd had been injected, and was shown as DURs (% injected dose/gram tissue normalised for the rat body weight). Dual-tracer macroautoradiographs with [18F]FMT and [14C]DG were also prepared. RESULTS: The tumour uptake for each tracer decreased earlier than did the tumour size. DURs (mean+/-SD) at baseline and on days 1, 3, 5 and 7 were as follows: [18F]FMT: 4.68+/-0.72, 3.34+/-0.66, 3.13+/-0.72, 3.42+/-0.45, 3.01+/-0.32; [14C]DG: 3.26+/-0.40, 3.09+/-0.55, 3.01+/-0.97, 2.28+/-0.35, 1.70+/-0.72; and [3H]Thd: 2.23+/-0.46, 1.54+/-0.45, 1.28+/-0.37, 1.35+/-0.20, 0.94+/-0.12. Decrease in [18F]FMT uptake compared with baseline was significant from day 1 (p<0.01), and the decrease in [3H]Thd uptake was also significant on day 1 (p<0.05) and days 3-7 (p<0.01). However, decrease in [14C]DG uptake was only significant from day 5 (p<0.01). Macroautoradiography suggested that the influence of inflammatory cells on the accumulation of [18F]FMT in tumours is smaller than that on the accumulation of [14C]DG. CONCLUSION: [18F]FMT uptake shows a rapid and sensitive response to chemotherapy, comparable to that of [3H]Thd, suggesting that it may be applied as a powerful tracer for monitoring of proliferative activity after cancer chemotherapy using PET.

An experimental study on O-[18F]fluoromethyl-L-tyrosine for differentiation between tumor and inflammatory tissues.

OBJECTIVE: O-[18F]fluoromethyl-L-tyrosine (18F-FMT) is a recently developed tumor-detecting agent with simple preparation and high radiochemical yields. The aim of this study was to assess the potency of 18F-FMT for differentiating tumor and inflammatory tissues using an animal model with an implanted tumor and experimentally induced inflammatory foci. METHODS: An ascites hepatoma cell line, AH109A, turpentine oil and Staphylococcus aureus were inoculated subcutaneously into Donryu rats as a tumor model, aseptic inflammation model and bacterial infection model, respectively. The biodistribution of radioactivity was assessed in rats at 5, 10, 30, 60, and 120 min after injection with 18F-FMT. Dual tracer whole-body and macro autoradiographies were performed 60 min after injection with a mixture of 18F-FMT and 2-deoxy-D-[1-14C]glucose (14C-DG). RESULTS: Tumor uptake of 18F-FMT was on average 1.27% injected dose per gram of tissue (%ID/g) and 1.43% ID/g at 30 min and 60 min, respectively and significantly higher than that in other normal tissues, except the pancreas (3.48% ID/g at 60 min). The uptakes in the aseptic and bacterial inflammatory tissues were very low and were not different from those of the background tissues. Dual tracer whole-body and macro autoradiographic studies showed that tumor uptake of 18F-FMT was clearly higher than uptake by the other tissues, while 18F-FMT accumulated much less both in aseptic and bacterial inflammatory tissues. In contrast, the 14C-DG images showed high accumulations not only in tumors but also in aseptic and bacterial inflammatory tissues. CONCLUSION: 18F-FMT seems to be a promissing tracer for the differentiation between tumor and inflammation because of higher specificity to tumor.