Risk factors for persistent positive anticardiolipin antibodies in women with recurrent pregnancy loss.

Antiphospholipid syndrome (APS) is an established cause of recurrent pregnancy loss (RPL). It is necessary to detect persistently positive antiphospholipid antibodies to diagnose APS. This study aimed to explore risk factors for persistent anticardiolipin (aCL) positivity. Women with a history of RPL or with a history of one or more intrauterine fetal deaths after 10 weeks underwent examinations to determine the causes of RPL, including antiphospholipid antibodies. If aCL-IgG or aCL-IgM antibodies were positive, retests were performed at least 12 weeks apart. Risk factors for persistent aCL antibody positivity were retrospectively investigated. The number and percentage of cases above the 99th percentile were 74/2399 (3.1%) for aCL-IgG, and 81/2399 (3.5%) for aCL-IgM. Of the initially tested cases, 2.3% (56/2399) for aCL-IgG and 2.0% (46/2289) for aCL-IgM were ultimately positive above the 99th percentile in retests. Retest values after 12 weeks were significantly lower than the initial values for both IgG and IgM immunoglobulin classes. Initial aCL antibody titers were significantly higher in the persistent-positive group than in the transient-positive group for both IgG and IgM immunoglobulin classes. The cut-off values for predicting persistent positivity of aCL-IgG antibodies and aCL-IgM antibodies were 15 U/mL (99.1 percentile) and 11 U/mL (99.2 percentile), respectively. The only risk factor for persistently positive aCL antibodies is a high antibody titer during the initial test. When the aCL antibody titer in the initial test exceeds the cut-off value, therapeutic strategies can be defined in subsequent pregnancies without waiting for 12 weeks.

Public policy performance for social development: solar energy approach to assess technological outcome in Mexico City Metropolitan Area.

Mexico City Metropolitan Area (MCMA) is the most populated urban area in the country. In 2010, MCMA required 14.8% of total energy domestic demand, but greenhouse gas emissions accounted for 7.7% of domestic emissions. Mexico has massive renewable energy potential that could be harnessed through solar photovoltaic (PV) technology. The problem to explore is the relationship between local and federal public strategies in MCMA and their stance on energy transition concern, social empowerment, new technology appropriation, and the will to boost social development and urban sustainability. A public policy typology was conducted through instruments of State intervention approach, based on political agenda articulation and environmental local interactions. Social equality is encouraged by means of forthright funding and in-kind support and energy policies focus on non-renewable energy subsidies and electric transmission infrastructure investment. There is a lack of vision for using PV technology as a guiding axis for marginalized population development. It is essential to promote economic and political rearrangement in order to level and structure environmental governance. It is essential to understand people's representation about their own needs along with renewable energy.

Phylogeographic structure and karyotypic diversity of the Brazilian shrew mouse ( Blarinomys breviceps, Sigmodontinae) in the Atlantic Forest.

Blarinomys breviceps possesses cryptic and burrowing habits with poorly documented genetics and life history traits. Due to its rarity, only a few specimens and DNA sequences have been deposited in collections worldwide. Here, we present the most comprehensive cytogenetic and molecular characterization of this rare genus. Phylogenetic analyses based on partial cytochrome b sequences were performed, attempting to establish the relationships among individuals with distinct karyotypes along the geographic distribution of the genus in the Atlantic Forest. Classical and molecular cytogenetics, using banding patterns and FISH of telomeric and whole chromosome X-specific painting probes (obtained from the Akodontini Akodon cursor) were used to characterize and compare the chromosomal complements. Molecular phylogenetic analyses recovered 2 main geographically structured clades, northeastern and southeastern with pairwise sequence divergences among specimens varying between 4.9 and 8.4%. Eight distinct karyomorphs are described: (A) 2n = 52 (50A, XX), (B) 2n = 52 (48A, XY+2Bs), (C) 2n = 45 (42A, XY+1B), (D) 2n = 43 (37A, XX+4Bs), (E) 2n = 37 (34A, XY+1B), (F) 2n = 34 (32A, XX), (G) 2n = 31 (27A, XX+2Bs), (H) 2n = 28 (26A, XY), all with the same number of autosomal arms (FN(A) = 50). Variation of 0-4 supernumerary chromosomes (Bs) presenting heterogeneity in morphology and distribution of interstitial telomeric sequences (ITSs) is reported. ITSs are also found in some metacentric autosomes. The phylogeographic separation between 2 major lineages with high levels of genetic divergence, and the wide karyotypic diversity indicate that B. breviceps is a diverse group that warrants taxonomic re-evaluation.

Effects of valsartan and amlodipine on home blood pressure and cardiovascular events in Japanese hypertensive patients: a subanalysis of the VART.

The Valsartan Amlodipine Randomized Trial (VART) was performed to compare the beneficial effects of valsartan and amlodipine on cardiovascular events in Japanese hypertensive patients. In this subanalysis of the VART, we assessed the relationship between home blood pressure (HBP) levels and cardiovascular events in the enrolled patients. We enrolled 1021 patients with mild-to-moderate hypertension in the VART. The participants were allocated randomly to either the valsartan group or the amlodipine group. The primary end point was a composite of all-cause death, sudden death, cerebrovascular events, cardiac events, vascular events and renal events. A total of 621 patients (valsartan group: 305 and amlodipine group: 316) completed the measurements of HBP (morning and evening) throughout the trial. Both the agents evenly and significantly lowered morning HBP and evening HBP throughout the trial. There was no significant difference in the primary end point between the two groups. However, we observed significant decreases in the left ventricular mass index and urinary albumin to creatinine ratio in the valsartan group but not in the amlodipine group. There were no significant differences in HBP levels and the main outcome of the cardiovascular events between the valsartan and amlodipine groups. However, in the valsartan group, significant improvements in left ventricular hypertrophy and microalbuminuria were observed.

Successful long-term management of adenomyosis associated with deep thrombosis by low-dose gonadotropin-releasing hormone agonist therapy.

We report the case of a patient with adenomyosis complicated by deep vein thrombosis in whom low-dose gonadotropin-releasing hormone agonist (GnRHa) therapy was useful as a uterus-conserving therapeutic option. The patient was a 34-year-old nulliparous woman who presented with edema and pain in the left lower leg. The patient had been treated with four cycles of GnRHa therapy for adenomyosis and repeatedly experienced chronic pelvic pain, dysmenorrhea and anemia due to hypermenorrhea. Leg venography confirmed deep vein thrombosis, and thrombolytic therapy was performed to eliminate symptoms. Because the patient strongly wanted to conserve the uterus, low-dose GnRHa therapy was initiated. The patient is currently taking 450 microg/day buserelin acetate nasally (regular dose: 900 microg/day), and estradiol levels have been maintained at 24-50 pg/ml. Anemia, leg numbness and chronic pelvic pain have dissipated, and the patient has not experienced estrogen deficiency symptoms for more than two years.

Identification of candidate genes involved in the radiosensitivity of esophageal cancer cells by microarray analysis.

Radiotherapy plays a key role in the control of tumor growth in esophageal cancer patients. To identify the patients who will benefit most from radiation therapy, it is important to know the genes that are involved in the radiosensitivity of esophageal cancer cells. Hence, we examined the global gene expression in radiosensitive and radioresistant esophageal squamous cell carcinoma cell lines. Radiosensitivities of 13 esophageal cancer cell lines were measured. RNA was extracted from each esophageal cancer cell line and a normal esophageal epithelial cell line, and the global gene expression profiles were analyzed using a 34 594-spot oligonucleotide microarray. In the clonogenic assay, one cell line (TE-11) was identified to be highly sensitive to radiation, while the other cell lines were found to be relatively radioresistant. We identified 71 candidate genes that were differentially expressed in TE-11 by microarray analysis. The up-regulated genes included CABPR, FABP5, DSC2, GPX2, NME, CBR3, DOCK8, and ABCC5, while the down-regulated genes included RPA1, LDOC1, NDN, and SKP1A. Our investigation provided comprehensive information on genes related to radiosensitivity of esophageal cancer cells; this information can serve as a basis for further functional studies.

Gene expression profiling of the response of esophageal carcinoma cells to cisplatin.

Cisplatin is the most common chemotherapeutic agent used in esophageal cancer. However, sensitivity to cisplatin varies greatly between patients. It is important to identify the gene(s) that are related to the sensitivity to cisplatin in esophageal cancer patients. The IC50 for cisplatin was measured for 15 esophageal cancer cell lines (TE1-5, TE8-15, KYSE140, and KYSE150). RNA was extracted from each of these cell lines and a normal esophageal epithelial cell line, namely, Het1A, and gene expression profiles were analyzed using an oligonucleotide microarray consisting of 34 594 genes. TE4 was highly resistant and TE12, 14, and 15 were sensitive to cisplatin. Thirty-seven genes were differentially expressed in the cisplatin-resistant esophageal cancer cell line. Our investigation provides a list of candidate genes that may be associated with resistance to cisplatin in esophageal cancer cells, which may serve as a basis for additional functional studies.

Relationship between expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in esophageal carcinoma cell lines.

5-Fluorouracil (5-FU) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC). Gene expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), has recently been investigated in order to predict the 5-FU sensitivity of several cancers. We examined the relationship between such gene expression and 5-FU sensitivity in 25 ESCC cell lines. TS, DPD, TP and OPRT mRNA levels were assessed by real-time polymerase chain reaction. The 50% inhibitory concentrations (IC50) of 5-FU in 25 ESCC cell lines were determined by cell proliferation assay. IC50 values for 5-FU ranged from 1.00 to 39.81 micromol/L. There were significant positive correlations between IC50 and TS mRNA expression (R(2) = 0.5781, P < 0.0001) and DPD mRNA expression (R(2) = 0.3573, P = 0.0016). There were no correlations between IC50 and TP or OPRT mRNA expression. TS and DPD mRNA expression levels may be useful indicators in predicting the anti-tumor activity of 5-FU in ESCC.

Collective mode properties in a paired fullerene-ion plasma.

A pair-ion plasma without electrons consisting of C60+ and C60- is generated through the processes of electron-impact ionization, electron attachment, and magnetic filtering. Properties of electrostatic modes propagating along magnetic-field lines are experimentally investigated by externally exciting them with two types of electrodes. It is found that four kinds of wave modes exist and a frequency spectrum of phase lag between the density fluctuations of C60+ and C60- is unique in comparison with ordinary electron-ion plasmas. One of the modes is an ion acoustic wave which is divided into two branches at around the ion cyclotron frequency in the presence of a backwardlike mode joining them. The phase lag of the ion acoustic wave strongly depends on the frequency, while those for the other ion plasma and intermediate-frequency waves are constant at pi independent of the frequency.

Proteome analysis of human placentae: pre-eclampsia versus normal pregnancy.

Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to obtain placental proteome maps. The identified protein spots (ca. 60% of the total) on the proteome maps included several pregnancy-related proteins (PRPs). Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to pre-eclampsia revealed three immunopositive spots that appeared to correspond to dynactin p-50, a protein related to cell turn-over. The rate of positivity for dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre-eclamptic women than in 58 normally pregnant women. These results indicate that dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.

Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma.

NDRG1 (N-myc downstream regulated gene-1) was reported to be necessary for p53-mediated apoptosis and to be regulated by PTEN (phosphatase and tensin homolog). In several cancers, it was suggested to be a tumor suppressor gene. Its significance in esophageal squamous cell carcinoma (ESCC) has not been studied. The objective of this study was to clarify the relation between clinicopathological and biologic factors in esophageal carcinoma and to determine the prognostic significance of the expression of NDRG1. Expression of NDRG1 mRNA was quantified by real-time reverse transcription polymerase chain reaction using a Lightcycler in 47 esophageal ESCC specimens. The data were analyzed with reference to clinicopathological factors. Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0-I vs. II-IV; P = 0.0027) and local tumor invasion (T1-2 vs. T3-4; P = 0.0136). Patients who had low NDRG1 mRNA expression had a significantly shorter survival after surgery compared with patients who had high NDRG1 mRNA expression (log-rank test, P = 0.0478). Impaired NDRG1 expression may lead to more aggressive invasion of ESCC.

Cerebral hemodynamics in Moyamoya disease: correlation between perfusion-weighted MR imaging and cerebral angiography.

BACKGROUND AND PURPOSE: In Moyamoya disease, the relationship between cerebral hemodynamics and angiographic findings has not been fully evaluated. The purpose of this study is to evaluate hemodynamics in Moyamoya disease with perfusion-weighted MR imaging (PWI) and cerebral angiography. METHODS: Twenty patients with Moyamoya disease were the subjects. Mean transit time (MTT) derived from PWI was calculated in the medial frontal lobes, the posterior frontal lobes, the occipital lobes, and the basal ganglia. From the angiographies, we classified the degrees of internal carotid artery (ICA) and posterior cerebral artery (PCA) stenoses as well as the degrees of Moyamoya vessels and leptomeningeal anastomosis (LMA). MTT in each region was compared with the angiographic findings. RESULTS: MTT positively correlated with the degree of ICA stenosis in the medial frontal (P < .01), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of PCA stenosis in the medial frontal (P < .001), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of Moyamoya vessels in the medial frontal (P < .05) and posterior frontal (P < .01) lobes. A multivariate analysis revealed that ICA and PCA stenoses and Moyamoya vessels were independent factors that prolonged MTT. CONCLUSION: Both ICA and PCA stenoses may influence overall cerebral perfusion in Moyamoya disease. The development of Moyamoya vessels may indicate hemodynamic impairment.

Malignant mixed müllerian tumor of primary mesenteric origin.

Malignant mixed müllerian tumor (MMMT) is a rare tumor. A literature search revealed very few reports on MMMT, especially those arising in the peritoneum. We recently encountered an MMMT of primary mesenteric origin associated with left fallopian tube cancer. There have been no previous reports about its occurrence in the mesentery. When cases of peritoneal MMMT were reviewed, the disease was found to be associated with synchronous or metachronous gynecologic tumors of müllerian duct origin (ie, ovarian tumors, primary serous carcinoma of the peritoneum, fallopian tube cancer, endometrial cancer, and adenocarcinoma of the cervix) in 12 out of 32 patients (37.5%). Peritoneal MMMT are frequently associated with gynecologic tumors.

Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance and pulmonary complication in thoracic esophagectomy patients.

SUMMARY: In spite of improvements in surgical technique and perioperative care, severe lung complication remains as the leading cause of morbidity in thoracic esophageal cancer patients who undergo esophagectomy. The purpose of this study was to evaluate the safety and effectiveness of postoperative drug therapy using low dose dopamine, gabexate mesilate, and ulinastatin on postoperative lung complication in esophageal cancer patients. Sixty-one patients operated for esophageal cancer from 1996 to 2000 were treated postoperatively with low dose dopamine (300 microg/kg/h), gabexate mesilate (80 mg/h), and ulinastatin (300 000 unit/day) as a study group. Seventy-four patients operated from 1987 to 1994 served as an historical control group. Various preoperative and perioperative medical parameters and water balance were analyzed. Postoperative pulmonary complications were observed in 26 patients (35.1%) in the control group and three patients (4.9%) in the study group, respectively (P < 0.0001). Preoperative and perioperative variables were not significantly different between the groups. Water balance from operation to postoperative day 3 in the study group was significantly lower than the control group. Postoperative use of low dose dopamine, gabexate mesilate, and ulinastatin significantly reduced pulmonary complications after esophagectomy. This may be partly attributable to negative water balance during the early postoperative days.

Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy.

BACKGROUND: Impaired regeneration and dysfunction of the cirrhotic liver following partial hepatectomy (PHx) are the most serious risk factors for postoperative liver failure. AIMS: Using naked hepatocyte growth factor (HGF) plasmid by the electroporation (EP) in vivo method, we investigated HGF for its role and mechanism of proliferation and restoration of liver mass in cirrhotic mice following PHx. ANIMALS: Eight week old female mice were used. METHODS: HGF plasmid 50 micro g was injected intramuscularly and transferred by EP in vivo once a week for three weeks. After establishment of carbon tetrachloride induced cirrhosis, mice underwent PHx. The HGF treated group was given naked HGF plasmid four days before PHx, and additional HGF was given once a week until they were killed, while a control group was given only empty plasmid. Mice were killed 2, 4, 10, and 14 days after PHx. Morphological and functional restoration of the liver were examined, as well as activation of mitogen activated protein kinase (MAPK) and mRNA levels of HGF activator (HGFA). RESULTS: The HGF treated group demonstrated a continuous threefold increase in HGF levels in plasma. Therapy with HGF in cirrhotic PHx resulted in effective liver regeneration via restoration of HGFA and activation of MAPK p44/p42, accelerated normalisation of liver function, and increased collagen degradation. CONCLUSIONS: HGF gene therapy by in vivo EP may be useful for hepatic resection in cirrhotic livers by stimulating liver proliferative and collagenolytic capacities, as well as accelerating functional recovery.

Serum adenosine deaminase activity and its isoenzyme pattern in women with normal pregnancies.

Adenosine deaminase (ADA) is a purine enzyme which is essential for the proliferation, maturation and function of lymphoid cells, and congenital deficiency of this enzyme is associated with severe combined immunodeficiency disease. The activity of ADA has changed in diseases characterized by the alteration of cell-mediated immunity such as rheumatoid arthritis, systemic lupus erythematosus and tuberculosis, so ADA has been considered as a nonspecific marker of cell-mediated immunity. In this study we examined changes in serum total ADA activity and the patterns of two ADA isoenzymes, ADA1 and ADA2 in normal pregnant women, and evaluated the possible role of the alteration of cell-mediated immunity during normal pregnancy as causes of changes in ADA activity. We measured serum activities of total ADA, ADA1 and ADA2 in normal pregnant women in the third trimester (n=24) and age-matched healthy nonpregnant women (n=24). Peripheral blood lymphocytes and monocytes were also measured. In normal pregnant women, serum total ADA activity averaged 10.5 +/- 0.5 U/L, which was significantly lower than in nonpregnant women (14.0 +/- 0.5 U/L ) (p<0.05), and mean serum ADA2 activity also significantly reduced that of nonpregnant women (p<0.05). There was no significant difference in ADA1 activity in normal pregnant and nonpregnant women. The decrease in total ADA activity was accompanied by the decrease in lymphocyte count. These results suggest that reduced serum total ADA activity reflects decrease in ADA2 activity, and which may be in part associated with depressed cell-mediated immunity during normal pregnancy.

Changes in the proportion of T helper 1 and T helper 2 cells in cord blood after premature rupture of membranes.

This study investigated changes in the proportion of T helper (Th)1 and Th2 cells in cord blood after premature rupture of membranes (PROM), and evaluate the effects of PROM on the intrauterine fetal immune status. The proportion of CD3-positive T cells secreting interferon (IFN)-gamma as an index of Th1 cells, and interleukin (IL)-4 as an index of Th2 cells in cord blood of 12 newborns with and without PROM, were analyzed by flow cytometry. In cord blood of newborns with PROM, the proportion of IFN-gamma secreting cells significantly increased, and the proportion of IL-4 secreting cells was rather high but not significantly higher than that of newborns without PROM. These changes eventually caused a shift in the Th1/Th2 ratio to Th1 dominance in PROM. There was no significant correlation between the proportion of IFN-gamma secreting cells and the duration of PROM before the onset of labor. These results suggest that the increase in the proportion of IFN-gamma secreting cells after PROM, which eventually cause the Th1/Th2 ratios to show the Th1 predominance, may reflect in part intrauterine fetal immune responses to PROM.

Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells.

To determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF) and related compounds on the growth of leukemic cells, human myeloid leukemic cells (HL-60) were exposed to bovine lactoferrin (bLF) and proteolytic hydrolysates of bLF. Pepsin hydrolysates of bLF showed a greater growth suppressive effect than tryptic hydrolysates or mature bLF. Four peptides with proliferation inhibition activity were purified from pepsin hydrolysates by ion-exchange chromatography, reverse-phase HPLC, and gel-filtration. All peptides were from the N-terminal end, in a region where lactoferricin B (Lfcin B), an antibacterial peptide, is located. Among the four peptides, peptide 1 (pep1) was found to exhibit highest activity and corresponded to residues 17 to 38 of bLF, with a molecular weight of 2753.88. The IC50 value of this peptide was 6.3 micrograms/ml. Three other peptides were less active and corresponded to sequences 1 to 16 and 45 to 48, linked by disulfide-bridge (pep2, molecular mass of 2430.13), 1 to 15 and 45 to 46 linked by disulfide bridge (pep3, molecular mass of 2017,92) and from residues 1 to 13 (pep4, molecular mass of 1558.73). Cell proliferation inhibition activity of the peptides was thought to be due to induction of apoptosis, which was evaluated by DNA ladder formation, DNA fragmentation, enhanced expression of phosphatidyl serine, and morphological changes. The IC50 values of the three peptides were confirmed using synthetic peptides and were consistent with those of purified peptides.