Uterine Artery Doppler Velocimetry During Mid-second Trimester to Predict Complications of Pregnancy Based on Unilateral or Bilateral Abnormalities

We performed this study to evaluate uterine artery Doppler velocimetry (UADV) measurement of unilateral or bilateral abnormalities as a predictor of complications in pregnancy during the mid-second trimester (20-24 weeks). We enrolled 1,090 pregnant women who had undergone UADV twice: once between the 20th and 24th week (1st stage) and again between the 28th and 32nd week (2nd stage) of pregnancy, and then delivered at Yonsei Medical Center. UADV was performed bilaterally. Follow-up UADV was performed between the 28th and 32nd week, and the frequencies of pregnancy-induced hypertension (PIH), fetal growth restriction (FGR), and preterm delivery (before 34 weeks of gestation) were determined. Chi-squared and t-tests were used where appropriate, with p < .05 considered significant. According to the results of UADV performed between 20-24 weeks of gestation, 825 women (75.7%) were included in the normal group, 196 (18.0%) in the unilateral abnormality group, and 69 (6.3%) in the bilateral abnormality group. The incidences of FGR were 8.0%, 10.2%, and 26.1%, and the incidences of PIH were 0.1%, 3.6%, and 14.5%, respectively. The incidence of PIH was significantly lower in the normal group. The incidences of preterm delivery were 2.2%, 5.6%, and 8.7%, respectively. PIH developed in 46.7% of patients with bilateral abnormal findings in both the 1st and 2nd stage tests, and developed in none of the patients with normal findings in both tests. Abnormal results found by UADV performed between the 20-24th weeks of pregnancy, such as high S/D ratios regardless of placental location and the presence of an early diastolic notch, were associated with significant increases in the incidences of intrauterine growth restriction (IUGR) and PIH. This was true for both bilateral and unilateral abnormalities. Abnormal findings in bilateral UADV during the second trimester especially warrant close follow up for the detection of subsequent development of pregnancy complications

Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model

INTRODUCTION: Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage (M2-Mϕ) population and are associated with poor prognosis in various cancers. In the present study, we attempted to assess whether M2-Mϕs derived from bone marrow stimulate the promotion and progression of mammary tumors. METHODS: 4T1 murine mammary carcinoma cells were injected either alone or coupled with M2-Mϕs into the mammary fat pads of syngeneic female Balb/C mice. M2-Mϕs were prepared by treating monocytes isolated from female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using an in vivo imaging system and the expression of cell proliferation-related, angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was immunohistochemically analyzed. To evaluate the effects of the crosstalk between 4T1 cells and M2-Mϕs on the secretion and mRNA expression of cytokines and the migration of monocytes, 4T1 cells and M2-Mϕs were co-cultured and cytokine antibody array, real-time RT-PCR, and trans-well migration assays were conducted. RESULTS: The co-injection of M2-Mϕs into the mammary fat pads of mice increased solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration of CD45(+ )leukocytes into tumor tissues. The proportions of Ki-67(+ )proliferating cells and the expression of hypoxia inducible factor-1α, vascular endothelial cell growth factor A, CD31, vascular endothelial cell growth factor C, and lymphatic vessel endothelial receptor-1 were increased significantly in the tumor tissues of mice co-injected with 4T1 cells and M2-Mϕs. The in vitro results revealed that the proliferation of 4T1 cells, the migration of monocytes, and the secretion of granulocyte colony-stimulating factor, IFNγ, IL-1α, IL-2, IL-16, IFNγ-induced protein-10, keratinocyte-derived chemokine, macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were increased when 4T1 cells were co-cultured with M2-Mϕs, as compared with when the 4T1 cells were cultured alone. CONCLUSION: The crosstalk between 4T1 cells and M2-Mϕs increased the production of cytokines, which may have induced immune cell infiltration into tumor tissues, tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby increasing solid tumor growth and lung metastasis

Familial Glucocorticoid Deficiency with a Point Mutation in the ACTH Receptor: A Case Report

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but no mineralocorticoid deficiency. We report a 2 month-old boy of nonconsanguineous parents, presented with hyperpigmentation. Physical examination showed diffuse dark skin of body including, oral mucosa, gum, hands, nails and scrotum. Laboratory evaluation revealed low serum cortisol (0.3 µg/dL), with very high plasma ACTH level (18,000 pg/mL), and serum cortisol level did not increase after ACTH stimulation test. Serum sodium, potassium, plasma renin activity, aldosterone and 17-hydroxyprogesterone were normal. Sequence analysis of the ACTH receptor (MC2R) gene showed a homozygous mutation of D103N. Diagnosis of FGD was made and treatment started with oral hydrocortisone

Improvement of Riboflavin Production Using Mineral Support in the Culture of Ashbya gossypii

Riboflavin production in a culture of Ashbya gossypii was enhanced by adding mineral support with adsorbed soybean oil. When the support in an amount of 1 % to the amount of medium was added into the culture at agitation intensity corresponding to impeller rotation rate of 600 rpm, the attained riboflavin concentration was 2.5 g/L at the culture time of 4 days, i.e. 1.6 times higher than that in the culture without adding mineral support. Riboflavin yield coefficient based on consumed substrate was also 1.6-fold higher than that in the culture without mineral support. In order to investigate the effect of mineral support on the riboflavin production and mycelial morphology variation, intracellular oil droplets were investigated by staining mycelia with Nile red. The A. gossypii cells, growing in submerged culture using soybean oil as a carbon source, were found to form intracellular micro-lipid bodies. The oil droplets became bigger as the culture time increased, and then the riboflavin leakage began, whereas lipid bodies gradually disappeared. When the soybean oil adsorbed on mineral support was added to the culture, the diameter of A. gossypii mycelia was much thicker and more riboflavin crystals were accumulated than in the pool of culture without mineral support; and what is more, mycelial autolysis was delayed for 2 days due to the presence of mineral support

Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea

BACKGROUND AND PURPOSE Previous studies have examined the risk of stroke in patients with Parkinson disease (PD), but the incidence of PD onset among stroke patients and its risk according to severity of poststroke disabilities have scarcely been investigated. This study aims to determine whether the risk of PD is increased among stroke patients using a retrospective cohort with a large population-based database. METHODS We used data collected by the Korean National Health Insurance Service from 2010 to 2018 and examined 307,361 stroke patients and 380,917 sex- and age-matched individuals without stroke to uncover the incidence of PD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), and the risk of PD was compared according to presence and severity of disability. RESULTS During 4.31 years of follow-up, stroke patients had a 1.67 times higher risk of PD compared to individuals without stroke (adjusted HR = 1.67, 95% CI = 1.57-1.78). The risk of PD was greater among stroke patients with disabilities than among those without disabilities, even after adjustment for multiple covariates (adjusted HR = 1.72, 95% CI = 1.55-1.91; and adjusted HR = 1.66, 95% CI = 1.56-1.77, respectively). CONCLUSIONS Our study demonstrated an increased risk of PD among stroke patients. Health professionals need to pay careful attention to detecting movement disorders as clues for diagnosing PD

Right hydrothorax misconceived as atelectasis after left internal jugular vein catheterization -A case report-

Central vein catheterization is a common procedure for monitoring the central venous pressure, securing vascular access, administrating vasoactive drugs and removing air embolisms. However, many complications can occur, such as vessel injury, pneumothorax, hydrothorax, nerve injury, arrhythmia and infection at the insertion site. We encountered an unusual complication of a localized right hydrothorax that was initially misinterpreted as an atelectasis after left internal jugular vein catheterization and right lateral positioning for a left lower lobectomy

Transduction of the MPG-tagged fusion protein into mammalian cells and oocytes depends on amiloride-sensitive endocytic pathway

BACKGROUND: MPG is a cell-permeable peptide with proven efficiency to deliver macromolecular cargoes into cells. In this work, we examined the efficacy of MPG as an N-terminal tag in a fusion protein to deliver a protein cargo and its mechanism of transduction. RESULTS: We examined transduction of MPG-EGFP fusion protein by live imaging, flow cytometry, along with combination of cell biological and pharmacological methods. We show that MPG-EGFP fusion proteins efficiently enter various mammalian cells within a few minutes and are co-localized with FM4-64, a general marker of endosomes. The transduction of MPG-EGFP occurs rapidly and is inhibited at a low temperature. The entry of MPG-EGFP is inhibited by amiloride, but cytochalasin D and methyl-β-cyclodextrin did not inhibit the entry, suggesting that macropinocytosis is not involved in the transduction. Overexpression of a mutant form of dynamin partially reduced the transduction of MPG-EGFP. The partial blockade of MPG-EGFP transduction by a dynamin mutant is abolished by the treatment of amiloride. MPG-EGFP transduction is also observed in the mammalian oocytes. CONCLUSION: The results show that the transduction of MPG fusion protein utilizes endocytic pathway(s) which is amiloride-sensitive and partially dynamin-dependent. Collectively, the MPG fusion protein could be further developed as a novel tool of "protein therapeutics", with potentials to be used in various cell systems including mammalian oocytes

Whole genome sequence and analysis of the Marwari horse breed and its genetic origin

Background: The horse (Equus ferus caballus) is one of the earliest domesticated species and has played an important role in the development of human societies over the past 5,000 years. In this study, we characterized the genome of the Marwari horse, a rare breed with unique phenotypic characteristics, including inwardly turned ear tips. It is thought to have originated from the crossbreeding of local Indian ponies with Arabian horses beginning in the 12th century. Results: We generated 101 Gb (similar to 30 x coverage) of whole genome sequences from a Marwari horse using the Illumina HiSeq2000 sequencer. The sequences were mapped to the horse reference genome at a mapping rate of similar to 98% and with similar to 95% of the genome having at least 10 x coverage. A total of 5.9 million single nucleotide variations, 0.6 million small insertions or deletions, and 2,569 copy number variation blocks were identified. We confirmed a strong Arabian and Mongolian component in the Marwari genome. Novel variants from the Marwari sequences were annotated, and were found to be enriched in olfactory functions. Additionally, we suggest a potential functional genetic variant in the TSHZ1 gene (p.Ala344&gt;Val) associated with the inward-turning ear tip shape of the Marwari horses. Conclusions: Here, we present an analysis of the Marwari horse genome. This is the first genomic data for an Asian breed, and is an invaluable resource for future studies of genetic variation associated with phenotypes and diseases in horses.open1

Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy