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Biomedical subjects

Simcha Yagel

Publications and source records attributed to Simcha Yagel.

At least 19 recordsLinked to original sources
PubMed2007

Fetal cardiomyopathy--in utero evaluation and clinical significance.

OBJECTIVE: To describe the prenatal diagnosis and outcome of fetal cardiomyopathy (CM). METHODS: The charts, photographs and videotapes of all fetuses with CM, who were assessed during pregnancy at two referral centers, were reviewed. RESULTS: The diagnosis of CM was established in 12 fetuses. All had structurally normal hearts, and all cases were diagnosed after 23 weeks of gestation, following normal early fetal echocardiogram. Three clusters of fetal CM appeared: Familial--two sib fetuses of a mother, who is a second generation of CM. Both had dilated CM and pathological findings were consistent with the diagnosis of endocardial fibroelastosis. Secondary--CM that was induced by another factor. Idiopathic--six cases of CM without an underlying specific etiology. Three women elected to terminate their pregnancy. Among the nine who delivered, four had a favorable outcome with normal cardiac function at the age of 1 month, in which three belonged to the secondary category, and five cases were complicated by fetal/infant death. CONCLUSIONS: CM may develop during fetal life and might be diagnosed by prenatal echocardiography. Normal cardiac findings in a midtrimester fetus do not exclude subsequent development of CM. Detailed prenatal sonographic examination may aid in determining the neonatal outcome.

Adult↗
PubMed2006

Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.

Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.

Angiogenesis Inducing Agents↗
PubMed2006

Diagnosis, surveillance, and treatment of the anemic fetus using middle cerebral artery peak systolic velocity measurement.

The in utero course of the anemic fetus has improved dramatically, owing to early diagnosis and cordocentesis transfusion. In utero invasive procedures such as amnio- and cordocentesis have become important modalities in the evaluation and treatment of anemic fetuses. However, they carry risks for both the mother and fetus. A valid and sensitive noninvasive means of following the anemic fetus is the evaluation of changes in the middle cerebral artery peak systolic flow velocity (MCA-PSV). This is a sensitive tool for both the evaluation of fetal anemia and response to treatment. Intracerebral vessels respond earliest to the fetal anemic state, and are readily accessible for ultrasound examination. We describe the methodology and evolving clinical applications of MCA-PSV measurement in the fetus, through an overview of the literature describing the development and application of MCA-PSV measurement in fetuses at risk of fetal anemia of various immune and nonimmune etiologies, illustrated by index cases from our center. MCA-PSV measurement is essential in the diagnosis, evaluation, and management of cases of fetal anemia. The use of this modality lessens the need for invasive procedures. The method is readily accessible and should be integrated into the repertoire of all obstetric ultrasound centers.

Anemia↗
PubMed2006

Prenatal sonographic diagnosis of congenital perineal skin tag: case report and review of the literature.

BACKGROUND: Skin tags, or acrochordons, are benign, soft, fleshy tumors that are composed of hyperplastic epidermis covering a dermal connective tissue stalk. METHODS: Case report of a congenital perineal skin tag that presented as a perineal tumor during second-trimester sonographic scan at 23 weeks' gestation. Literature review of the medical literature using Pubmed(R) and the search terms acrochordon, fibroepithelial polyp (FEP), and skin tag. RESULTS: Routine midtrimester targeted organ scanning at 23 weeks' gestation revealed a 5-mm hypoechogenic elongated mass in the perineal area of the fetus. The lesion progressed to twice that size by 36 weeks. Detailed anatomy scan of the fetus was unremarkable, and amniocentesis demonstrated normal karyotype. The mother developed spontaneous labor at 38 weeks' gestation and delivered a phenotypically normal girl with a round smooth mass in the perineal area. The lesion was removed; pathologic examination revealed a lipomatous skin tag. Literature review showed skin tags associated with different medical conditions. CONCLUSION: To the best of our knowledge, no prenatally diagnosed cases of this lesion on the fetal perineum have been published. In the present case, this was an innocuous finding.

Adult↗
PubMed2006

Three-dimensional power Doppler (3DPD) ultrasound in the diagnosis and follow-up of fetal vascular anomalies.

OBJECTIVE: This study was undertaken to examine the value of 3-dimensional power Doppler (3DPD) ultrasound imaging in diagnosis and follow-up of fetal vascular anomalies. STUDY DESIGN: In 174 women undergoing early second-trimester targeted organ scanning, followed by a midtrimester second scan in a university hospital setting, 3DPD was applied to the fetal intra-abdominal and intrathoracic vessels. RESULTS: In 137 of 174 fetuses (75%) in the earlier scan, and in 164 of 174 fetuses (95%) in the later scan, 3DPD ultrasound successfully visualized the fetal vessels. In an additional 9 cases, anomalous vascularity was identified: fetal intra-abdominal umbilical vein varix (2), persistent right umbilical vein (1), agenesis of ductus venosus (2), eventration of diaphragm (1), parenchymal and vascular lung anomaly (1), sacrococcygeal teratoma (1), and chorioangioma (1). 3DPD improved diagnostic precision, aided our understanding of anomalous structure, and added information on the vascular volume of lesions in some cases. CONCLUSION: 3DPD improved ultrasound visualization of the fetal vessels of the abdomen and thorax in normal and anomalous cases.

Blood Vessels↗
PubMed2006

The shadow of the intrauterine device.

OBJECTIVE: An intrauterine device (IUD) is a highly effective and prevalent form of birth control with a low failure rate. It is not without complications, including irregular bleeding and pelvic pain, perforation, expulsion, and pregnancy. Investigation of the symptomatic patient and routine follow-up of asymptomatic women with IUDs include transvaginal ultrasonography to rule out IUD malposition and other complications. Three-dimensional ultrasonography (3DUS) has been shown to have added value in imaging the pelvic organs, including the uterus. However, even with 3DUS, the operator may encounter difficulty in imaging the IUD in its entirety, because of variability in both echogenicity and exact location. METHODS: More than 30 women undergoing IUD placement evaluation, including routine examinations and cases of suspected pregnancy, irregular bleeding, infection, and pelvic pain, were evaluated with 3DUS and volume contrast imaging in the C plane (VCI-C), which visualized acoustic shadows of the IUDs, facilitating identification of the intrauterine position and type of the device. RESULTS: Four examples are presented from women undergoing evaluation of IUD placement in whom 2-dimensional ultrasonography failed to visualize the device satisfactorily. Volume contrast imaging in the C plane allowed visualization of the acoustic shadows of the IUDs, thereby providing more exact imaging of the type of device as well as aiding in locating the IUD. In a woman with irregular bleeding, a bicornuate uterus with pregnancy in 1 horn and a bowed T-type IUD in the contralateral horn were diagnosed with VCI-C. CONCLUSIONS: We conclude from these shadow images that VCI-C is a useful modality in cases of difficult visualization of the IUD; VCI-C visualization of the acoustic shadow of the IUD may provide an adjunctive approach.

Female↗
PubMed2005

The CD85J/leukocyte inhibitory receptor-1 distinguishes between conformed and beta 2-microglobulin-free HLA-G molecules.

For a proper development of the placenta, maternal NK cells should not attack the fetal extravillous cytotrophoblast cells. This inhibition of maternal NK cells is partially mediated via the nonclassical MHC class I molecule HLA-G. Recently, we demonstrated that HLA-G forms disulfide-linked high molecular complexes on the surface of transfected cells. In the present study, we demonstrate that HLA-G must associate with beta(2)m for its interaction with CD85J/leukocyte Ig-like receptor-1 (LIR-1). Although HLA-G free H chain complexes are expressed on the surface, they are not recognized and possibly interfere with CD85J/LIR-1 and HLA-G interaction. The formation of these complexes on the cell surface might represent a novel mechanism developed specifically by the HLA-G protein aimed to control the efficiency of the CD85J/LIR-1-mediated inhibition. We also show that endogenous HLA-G complexes are expressed on the cell surface. These findings provide novel insights into the delicate interaction between extravillous cytotrophoblast cells and NK cells in the decidua.

Antigens, CD↗
PubMed2005

Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum.

Growth factor signalling has important modulatory roles in the process of human follicular growth, oocyte maturation and corpus luteum (CL) formation. Recently, Sprouty-2, an inhibitor of receptor tyrosine kinase (RTK) signalling pathway was advocated as a marker of oocyte competence in the bovine ovary. We sought to study Sprouty-2 expression and regulation in the human ovary. RT-PCR was used to detect Sprouty-2 mRNA in human granulosa-lutein cells (GLC) collected from follicular aspiration of IVF patients. The effect of epidermal and fibroblast growth factors (EGF and FGF) on Sprouty-2 mRNA expression in GLC was studied using quantitative real-time PCR. Immunohistochemistry was performed on cultured GLC, human CL and stimulated rat ovary sections. Sprouty-2 mRNA was expressed in human GLC. EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC. The Sprouty protein was localized to GLC of early and late human CL but not to the theca cell layer. Immunostaining of developing rat CL confirmed the temporal and spatial expression of Sprouty in humans. The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation.

Adolescent↗
PubMed2005

Fibroblast growth factor-10 and fibroblast growth factor receptors 1-4: expression and peptide localization in human decidua and placenta.

The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4) are expressed in human decidual and placental tissues. We analyzed the expression of FGF-10 and FGFRs 1-4 in 1st, 2nd and 3rd trimester placentas, as well as in decidua. RT-PCR and immunohistochemistry were employed to study mRNA and protein expression. FGF-10 was expressed by decidual cells and by cytotrophoblasts of the cytotrophoblast columns during all three trimesters. FGFR 1-4 were expressed in the placenta but not in the decidua. Placental expression of FGFRs was temporally regulated: In 1st trimester placentas, FGFR 1-4 were expressed by Hofbauer cells, FGFR-1 and FGFR-4 were expressed in cytotrophoblast columns, and the latter was also expressed by syncytiotrophoblasts. Similar expression was seen in 2nd trimester placentas with additional expression of FGFR-1 in blood vessel walls. The expression of FGFR-1 and FGFR-4 in the 3rd trimester was comparable to that seen in the 2nd trimester. The expression of FGF-10, FGFR-1 and FGFR-4 in the maternal-fetal interphase suggests their role in decidual-trophoblast interaction. The abundance of FGFR expression in Hofbauer cells implies that mesenchymal-trophoblast interaction is important for regulation of villous development.

Decidua↗
PubMed2005

Spatiotemporal expression of heparanase during human and rodent ovarian folliculogenesis.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs), major components of the basement membrane (BM) and extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound molecules, including basic fibroblast growth factor (FGF2). Structural and functional development of the corpus luteum (CL) involves tissue remodeling, active angiogenesis, and steroid production. Heparanase-induced ECM and BM breakdown as well as FGF2-stimulated endothelial proliferation may have an important role in the regulation of luteal function. Heparanase mRNA was detected by reverse-transcription-polymerase chain reaction in granulosa cells recovered from follicular fluid of in vitro fertilization patients. Using sulfate-labeled ECM, heparanase enzymatic activity was determined in human luteinized granulosa cells. Employing immunohistochemistry, heparanase protein was localized predominantly in the theca interna cell layer of the mature antral follicle, whereas in human corpora lutea, both luteinized granulosa and theca cells were immunostained for heparanase. During luteolysis, heparanase was identified in macrophages surrounding the forming corpus albicans. In serially sectioned ovaries from unstimulated rats as well as from eCG-treated rats, expression of heparanase was noted exclusively in the ovarian steroid-producing interstitial tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in lutein cells of the forming corpora lutea. Temporal expression of heparanase in granulosa cells during the luteal phase and in macrophages during luteal regression supports the hypothesis that heparanase plays a role in human ovarian ECM remodeling and may potentiate cellular migration and growth factor bioavailability.

Adolescent↗
PubMed2004

Utero-ovarian morphology and blood flow after tubal ligation by the Pomeroy technique.

OBJECTIVES: The objectives of this study were to evaluate ovarian sonographic morphology and pelvic blood flow in patients who had undergone bilateral tubal ligation by the Pomeroy technique. DESIGN: Twenty women who had undergone bilateral tubal ligation during cesarean section by the Pomeroy techniques were compared to 20 matched controls who had undergone cesarean section alone. Ovarian morphology as well as ovarian and uterine pulsatility index (PI), resistance index and peak systolic velocity were evaluated using transvaginal sonography and Doppler velocimetry. RESULTS: Patients post tubal ligation by the Pomeroy technique were found to have a significantly higher rate of polycystic appearance of the ovaries (60% vs. 5%; p < 0.005). Six patients (30%) had post tubal ligation symptoms, as compared to none of the controls. Five of the six symptomatic tubal ligation patients (83%) had ovarian polycystic appearance, which was not significantly different than asymptomatic patients. Ovarian artery PI was significantly higher in symptomatic patients (2.7 +/- 1.9) compared to asymptomatic patients (1.5 +/- 0.9) (p < 0.05). CONCLUSIONS: We therefore conclude that patients post bilateral tubal ligation by the Pomeroy technique may acquire an ovarian polycystic appearance and increased ovarian PI, which may be associated with a tendency to develop post tubal ligation symptoms.

Adult↗
PubMed2004

Novel APC-like properties of human NK cells directly regulate T cell activation.

Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane-enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell-mediated cytotoxicity and specific ligand recognition by cell surface-activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell-activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2-deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell-activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.

Antigen-Presenting Cells↗
PubMed2004

The role of magnetic resonance imaging in the evaluation of isolated mild ventriculomegaly.

OBJECTIVE: Isolated mild ventriculomegaly is defined as dilatation of the lateral ventricle from 10 to 15 mm, with no other structural abnormalities observed at the time of diagnosis. Its reported frequency is between 1 per 50 and 1 per 700 deliveries. There are no universal recommendations for evaluation of isolated mild ventriculomegaly. Targeted sonography, karyotype analysis, and viral antigen testing, particularly for cytomegalovirus, are most often used for further investigation of this finding. We studied the role of magnetic resonance imaging as part of the prenatal evaluation of isolated mild ventriculomegaly. METHODS: Thirty-six pregnant women were referred to 2 Hadassah hospitals between 1999 and 2002 for evaluation of isolated mild ventriculomegaly. They underwent targeted sonography to exclude other anomalies, genetic amniocentesis for fetal karyotype, and serologic cytomegalovirus tests. Mild ventriculomegaly was the only pathologic finding diagnosed. Fetal brain magnetic resonance imaging was performed to evaluate the correlation between sonographic and magnetic resonance imaging findings and the additional contribution of magnetic resonance imaging in evaluating isolated mild ventriculomegaly. RESULTS: Thirty-six magnetic resonance imaging studies were performed. All tests were adequate for evaluation. In 3 (8.3%) of 36 cases, magnetic resonance imaging showed additional findings: in a severely obese woman, ventricular dilatation up to 18 mm and periventricular cystic lesions with abnormal sulcation suggestive of diffuse parenchymal abnormality were diagnosed, and in 2 cases, bleeding in germinal centers was found. On subsequent sonographic examination, no other finding but isolated mild ventriculomegaly was diagnosed. In the remaining 33 women (91.7%), magnetic resonance imaging studies correlated well with sonographic findings. Further sonographic follow-up in this subgroup failed to reveal any other pathologic findings. CONCLUSIONS: Our study supports the view that magnetic resonance imaging should be considered as part of the evaluation of isolated mild ventriculomegaly, especially when objective difficulties preclude detailed sonographic examination.

Fetal Diseases↗
PubMed2003

Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function.

The nonclassical class I MHC molecule HLA-G is selectively expressed on extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. HLA-G can inhibit the killing mediated by NK cells via interaction with the inhibitory NK cell receptor, leukocyte Ig-like receptor-1 (LIR-1). Comparison of the sequence of the HLA-G molecule to other class I MHC proteins revealed two unique cysteine residues located in positions 42 and 147. Mutating these cysteine residues resulted in a dramatic decrease in LIR-1 Ig binding. Accordingly, the mutated HLA-G transfectants were less effective in the inhibition of NK killing and RBL/LIR-1 induced serotonin release. Immunoprecipitation experiments demonstrated the involvement of the cysteine residues in the formation of HLA-G protein oligomers on the cell surface. The cysteine residue located at position 42 is shown to be critical for the expression of such complexes. These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells.

Amino Acid Sequence↗
PubMed2003

CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells.

In the maternal decidua, natural killer (NK) cells, characterized by lack of CD16, are found in direct contact with the fetal extravillous trophoblasts (EVTs). It is yet unknown which factors contribute to the specific homing of this unique NK subset to the decidua. In this study we analyze the chemokine receptor repertoire on various NK populations derived from the peripheral blood and decidua. We show that CXCR4 and CXCR3 receptors are preferentially expressed on CD16- NK subsets derived either from the peripheral blood or the decidua and that these receptors are involved in migration of all NK subsets to their ligands. We further demonstrate in vivo that invading EVTs that eventually perform endovascular invasion express CXCL12, the ligand for CXCR4, but not ligands for CXCR3. Indeed, specific accumulation of the CD16- NK cells at the expense of CD16+ cells was observed only when in vitro migration was performed with ligands for CXCR4. Finally, incubation of the peripheral blood CD16- NK cells with cytokines present in the decidua, especially interleukin 15 (IL-15), resulted in the expression of chemokine receptor repertoire similar to that observed on decidual NK cells, suggesting an additional important regulatory effect of local decidual cytokines.

Blood Vessels↗