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Type 1 diabetes mellitus (T1DM) accounts for 5-10% of diabetes and results from the destruction of the β-cells of the pancreas. Patients with T1DM become dependent on insulin for survival, [...], Impaired revascularization of transplanted islets is a critical problem that leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are known to aid neovascularization, we aimed to enhance islet engraftment by cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or without (islet-only group) human cord blood-derived EPCs, were transplanted into diabetic nude mice. The islet-EPC group reached euglycemia by ~11 days posttransplantation, whereas the islet-only group did not. Also, the islet-EPC group had a higher serum porcine insulin level than the islet-only group. Islets from the islet-EPC group were more rapidly revascularized at the early period of transplantation without increment of final capillary density at the fully revascularized graft. Enhanced revascularization rate in the islet-EPC group was mainly attributed to stinmlating vascular endothelial growth factor-A production from the graft. The rapid revascularization by EPC cotransplantation led to better graft perfusion and recovery from hypoxia. EPC cotransplantation was also associated with greater β-cell proliferation, probably by more basement membrane production and hepatocyte growth factor secretion. In conclusion, cotransplantation of EPCs and islets induces better islet engraftment by enhancing the rate of graft revascnlarization. These findings might provide a directly applicable tool to enhance the efficacy of islet transplantation in clinical practice. Diabetes 61:866-876, 2012

Caring for a pregnant woman is both an enormous privilege and a weighty responsibility. To meet these demands, ob/gyns must constantly keep up with new innovations in their specialty and [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.06.033 Byline: Chan-Wook Park, Joong Shin Park, Soon-Sup Shim, Jong Kwan Jun, Bo Hyun Yoon, Roberto Romero Abstract: The purpose of this study was to determine if an elevated concentration of soluble fms-like tyrosine kinase-1(sFlt-1) in maternal plasma and amniotic fluid is a risk factor for the subsequent development of preeclampsia. Author Affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, and Laboratory of Fetal Medicine Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea Article History: Received 2 March 2005; Revised 10 May 2005; Accepted 7 June 2005 Article Note: (footnote) This study was supported by a grant 01-PJ1-PG1-01CH07-0002 from the 2001 Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea. Presented at the Twenty-Fifth Annual Meeting of the Society for Maternal Fetal Medicine, February 7-12, 2005, Reno, Nev.

Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

Increased amounts of an enzyme called matrix metalloproteinase-8 in the amniotic fluid of pregnant women is a strong risk factor for premature birth. This measurement could be done whenever a pregnant woman has an amniocentesis for genetic reasons.

Increased amounts of an enzyme called matrix metalloproteinase-8 in the amniotic fluid of pregnant women may be a marker for funisitis. Funisitis is an inflammation of the umbilical cord, which is a sign of inflammation in the fetus.

Pregnant women whose membranes rupture prematurely are likely to deliver prematurely if they have less amniotic fluid than normal. This was the conclusion of a study of 129 pregnant women with premature rupture of membranes who had amniocentesis.

Examination of tissue samples of the placenta shortly after birth can identify newborn babies who may have a serious condition called fetal inflammatory response syndrome. The analysis can identify inflammation of the umbilical cord, which may be a marker of intrauterine infection.

The polymerase chain reaction (PCR) may identify many cases of intra-uterine infection that biological cultures miss. In a study of 154 pregnant women with premature rupture of fetal membranes, biological culture missed 40% of the women who were infected with the bacterium Ureaplasma urealyticum.

Elevated levels of interleukin-6 in cervical fluid may be a sign that a pregnant woman has a uterine infection and will go into labor prematurely. Interleukin-6 is an immune system protein that increases during infection.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1067/mob.2000.104207 Byline: Bo Hyun Yoon (a)(f), Roberto Romero, Joong Shin Park (a)(f), Chong Jai Kim (b)(f), Seung Hyup Kim (c), Jung Hwan Choi (d), Tai Ryoon Han (e) Abstract: The aim of this study was to determine whether fetal exposure to intra-amniotic inflammation and a systemic fetal inflammatory response (funisitis) are associated with the development of cerebral palsy at the age of 3 years. Author Affiliation: (a) Departments of Obstetrics and Gynecology, Seoul, Korea (b) Departments of Obstetrics and Pathology, Seoul, Korea (c) Diagnostic Radiology, Seoul, Korea (d) Pediatncs, Seoul, Korea (e) Rehabilitation Medicine, Seoul, Korea (f) Seoul National University College of Medicine and the Laboratory of Fetal Medicine Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea Article History: Received 17 May 1999; Revised 2 August 1999; Accepted 2 November 1999 Article Note: (footnote) * Supported by grant 03-96-050 from Seoul National University Hospital Research Fund, grant of KISTEP (Korea Institute of Science & Technology Evaluation and Planning), and grant 97-04-03-08-01-3 from the Korea Science and Engineenng Foundatton., ** Presented at the Nineteenth Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, California, January 18-23, 1999.

Oligohydramnios appears to be a sign of an inflammation in the uterus, according to a study of 59 pregnant women with premature rupture of membranes. This condition occurs in pregnant women when there is not enough amniotic fluid around the baby.

Elevated levels of interleukin-6 in umbilical cord blood may indicate an increased risk of bronchopulmonary dysplasia in premature babies. Premature babies are at risk for this lung disease and the finding of increased interleukin-6 levels in a study of 203 babies indicates the disease follows an inflammatory response.

Invasion of the amniotic cavity by Ureaplasma urealyticum provokes a significant inflammatory response in pregnant women with prematurely ruptured fetal membranes. Researchers measured inflammatory mediators in the amniotic fluid and postpartum umbilical cord blood in 120 pregnant women. Isolated Ureaplasma urealyticum microorganism invasion in the absence of other organisms was detected in 21% of women with ruptured membranes, and was associated with elevated amniotic fluid leukocyte, tumor necrosis factor, and interleukin 1-beta levels and a higher level of interleukin-6 in the umbilical cord blood. These changes are consistent with a defensive inflammatory response.

An increased fetal plasma cortisol level in a pregnant woman with preterm rupture of membranes may predict the spontaneous onset of labor. Researchers analyzed fetal blood samples in 51 pregnant women whose fetal membranes had ruptured prematurely, but who were not in labor. The average fetal cortisol level in women who spontaneously began labor within one week of rupture was 8.35 micrograms/deciliter (mcg/dL), but only 4.75 mcg/dL in women who did not begin labor. There was no significant difference in fetal dehydroepiandrosterone levels.

Byline: Bo Hyun Yoon, Roberto Romero, Jong Kwan Jun, Eli Maymon, Ricardo Gomez, Moshe Mazor, Joong Shin Park Keywords: Parturition; cortisol; dehydroepiandrosterone sulfate; interleukin-6; premature rupture of the membranes; prematurity; chorioamnionitis; preterm labor Abstract: Objective: The role of steroid hormones in the control of human parturition has been a subject of debate. Activation of the fetal hypothalamic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens, specifically, dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cortisol and dehydroepiandrosterone sulfate and the onset of preterm labor in patients with preterm premature rupture of the membranes. Study Design: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Corticosteroids had not been administered before fetal blood sampling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonparametric statistics and survival analysis. Results: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentesis had a significantly higher median level of fetal plasma cortisol but not of dehydroepiandrosterone sulfate than those delivered after 7 days (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] [mu]g/dL vs median 4.75 [3.0 to 10.4] [mu]g/dL, P < .0001; for fetal plasma dehydroepiandrosterone sulfate: median 154.4 [8.6 to 333.8] [mu]g/dL vs median 194.6 [96.7 to 402.5] [mu]g/dL, P = .09). (2) The cordocentesis-to-delivery interval was significantly shorter in patients with a fetal plasma cortisol value of [greater than or equal to]7 [mu]g/dL (derived by receiver-operating characteristic curve analysis) than in those with fetal cortisol Author Affiliation: Seoul, Korea Article Note: (footnote) [star] From the Department of Obstetrics and Gynecology, College of Medicine, Seoul National University., [star][star] Supported by grant No. 97-04-03-08-01-3 from the Korea Science and Engineering Foundation (KOSEF)., a Drs Romero, Maymon, Gomez, and Mazor have participated as private citizens, not as agents of the US government or any of the universities to which they hold appointments., aa Reprint requests: Bo Hyun Yoon, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, 110-744, Korea., acents 0002-9378/98 $5.00 + 0 6/6/92970

Necrotizing funisitis (NF) is defined as the presence of an arc (i.e., crescent/band/ring/halos) of infiltrated neutrophils and/or associated debris in Wharton's jelly (WJ) of umbilical-cord (UC). However, no information exists about the comparison in intra-amniotic inflammatory-response (IAIR) and inflammation in extra-placental membranes between the presence and absence of NF in the context of inflammation in WJ among spontaneous preterm births (PTBs). The objective of current study is to examine this issue.

No information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2010.01.056 Byline: JoonHo Lee (a), Joong Shin Park (a), Errol R. Norwitz (b), Byoung Jae Kim (a), Chan-Wook Park (a), Jong Kwan Jun (a), Hee Chul Syn (a) Keywords: Albumin; amniotic fluid; antenatal corticosteroids; lumican; prothrombin fragment 2; surface-enhanced laser desorption/ionization time-of-flight mass spectrometry; transthyretin Abstract: We sought to examine changes in the intraamniotic proteomic environment after the administration of antenatal corticosteroids to women with impending preterm delivery. Author Affiliation: (a) Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (b) Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT Article History: Received 22 November 2009; Revised 9 January 2010; Accepted 19 January 2010 Article Note: (footnote) The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community., This study was supported by Grant no. 04-2008-0170 from the Seoul National University Hospital Research Fund., Cite this article as: Lee J, Park JS, Norwitz ER, et al. Identification and characterization of proteins in amniotic fluid that are differentially expressed before and after antenatal corticosteroid administration. Am J Obstet Gynecol 2010;202:388.e1-10.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.07.006 Byline: Si Eun Lee, Roberto Romero, Hanna Jung, Chan-Wook Park, Joong Shin Park, Bo Hyun Yoon Keywords: amniotic fluid; C-reactive protein; cord blood; fetal inflammatory response syndrome; intraamniotic inflammation Abstract: Intraamniotic inflammation is a risk factor for adverse pregnancy and neonatal outcome, regardless of the presence or absence of a positive amniotic fluid (AF) culture. The purpose of this study was to determine whether the intensity of a fetal inflammatory response (FIR) differs between cases of intraamniotic inflammation with microbiologically proven infection and cases with negative AF cultures. Author Affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea. Article Note: (footnote) Cite this article as: Lee SE, Romero R, Jung H, Park C-W, Park JS, Yoon BH. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2007;197:294.e1-294.e6. , Supported by grant R01-2006-000-10607-0 from the Korea Science and Engineering Foundation, funded by the Korean government (Ministry of Science and Technology).

In sacrococcygeal teratoma, the presence of high‐output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N‐terminal pro‐B‐type natriuretic peptide [NT‐pro‐BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT‐pro‐BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3/cm, elevated NT‐pro‐BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

This study was aimed at evaluating changes in CYP3A activity following and during pregnancy by analyzing metabolic markers for CYP3A activity, which can help avoid unnecessary drug exposure and invasive sampling.

On page 12 of the September 15, 2005 special technology issue, in the article 'Technical innovation in clinical obstetrics,' Drs. Park and Norwitz state that 'elevated amniotic fluid levels of [...]

Early graft loss in islet transplantation means that a large amount of donor islets is required. Endothelial cells and endothelial colony-forming cells (ECFCs) have been reported to improve instant blood-mediated inflammatory reaction (IBMIR) in vitro. In this study, we examined if ECFC-coated porcine islets would prevent early graft loss in vivo. Human ECFCs were prepared from cord blood and cocultured with islets to make composite grafts. Diabetic nude mice underwent intraportal transplantation. Blood glucose levels were monitored, and morphological examination of the grafts along with analysis of the components of IBMIR and inflammatory reaction were performed with the liver tissues. The ECFC-coated islets significantly decreased blood glucose levels immediately after transplantation compared to the uncoated islets. Composite ECFC islet grafts were observed in the liver sections, associated with a more insulin+area compared to that of the uncoated group within 48 h after transplantation. Deposition of CD41a, C5b-9, and CD11b+cells was also decreased in the ECFC-coated group. Expression of porcine HMGB1 and mouse TNF-α was increased in the transplantated groups compared to the sham operation group, with a trend of a decreasing trend across the uncoated group, the ECFC-coated group, and the sham group. We demonstrated that the composite ECFC porcine islets transplanted into the portal vein of nude mice improved early graft loss and IBMIR in vivo.

AbstractThe objective of the present study was to determine whether angiotensinogen G(?6)A polymorphism is associated with the elevation of blood pressure (BP) in the hypertensive disorders of pregnancy in Korean population. The subjects included 201 cases with the hypertensive disorders of pregnancy and 160 healthy controls. The medical records of subjects were reviewed. Cases were classified into the four subtypes (transient hypertension, preeclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension) by the diagnostic criteria suggested by the National High Blood Pressure Education Program Working Group. Cases were also divided into the high and low BP group by the elevation of BP (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(?6)A polymorphism was determined by restriction fragment length polymorphism. Frequencies of AA genotype were significantly higher in the high than in the low BP group in the preeclampsia, superimposed preeclampsia, and the combined group (N= 201), suggesting that the angiotensinogen G(?6)A allele was significantly associated with the elevation of BP in the hypertensive disorders of pregnancy among South Korean women. The present findings imply that the elevation of BP can serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.

Forceps delivery remains an important part of the obstetric armamentarium. When applied by practitioners skilled in their use, forceps delivery can quickly and safely deliver a fetus at risk. Unfortunately, forceps can also be an instrument of harm for the women or her infant. This is particularly true of rotational forceps. The goal of this monograph is to review in detail the indications, contraindications, technique, as well as risks and complications of forceps delivery, with particular attention to rotational forceps. We conclude by asking the question: Should rotational forceps be abandoned altogether?

The response of pituitary gonadotropes to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of gene expression. Several factors are known to affect expression of the mouse GnRHR (mGnRHR) gene, including GnRH and activin. We have previously shown that activin augments GnRH-mediated transcriptional activation of mGnRHR gene, and that region −387/−308 appears to be necessary to mediate this effect. This region contains two overlapping cis-regulatory elements of interest: GnRHR activating sequence (GRAS) and a putative SMAD-binding element (SBE). This study investigates the role of these elements and their cognate transcription factors in transactivation of the mGnRHR gene. Transfection studies confirm the presence of GnRH- and activin-response elements within −387/−308 of mGnRHR gene promoter. Competition electrophoretic mobility shift assay experiments using −335/−312 as probe and αT3–1 nuclear extract or SMAD, Jun, and Fos proteins demonstrate direct binding of AP-1 (Fos/Jun) protein complexes to −327/−322 and SMAD proteins to −329/−328. Further transfection studies using mutant constructs of these cis-regulatory elements confirm that both are functionally important. These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGnRHR gene.