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1.
Praxis (Bern 1994) ; 101(3): 195-8, 2012 Feb 01.
Article in German | MEDLINE | ID: mdl-22294306

ABSTRACT

A woman, who consumed the recommended daily doses of Relaxane® and Hova® over several months was found to have elevated liver enzymes. A liver biopsy showed histologic changes consistent with primary biliary cirrhosis. After stopping treatment with Relaxane® and Hova® we observed a decline of the increased liver enzymes to normal levels two months later. A second biopsy of the liver three months later showed a clear decline of the initial histologic changes.


Subject(s)
Chemical and Drug Induced Liver Injury/diagnosis , Liver Cirrhosis, Biliary/diagnosis , Phytotherapy/adverse effects , Plant Extracts/toxicity , Aged , Biopsy , Chemical and Drug Induced Liver Injury/pathology , Diagnosis, Differential , Female , Humans , Humulus , Liver/pathology , Liver Cirrhosis, Biliary/pathology , Liver Function Tests , Plant Extracts/administration & dosage , Valerian
3.
Kidney Int ; 72(12): 1520-6, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17960139

ABSTRACT

Joubert syndrome (JS) is an autosomal recessive disorder, consisting of mental retardation, cerebellar vermis aplasia, an irregular breathing pattern, and retinal degeneration. Nephronophthisis (NPHP) is found in 17-27% of these patients, which was designated JS type B. Mutations in four separate genes (AHI1, NPHP1, CEP290/NPHP6, and MKS3) are linked to JS. However, missense mutations in a new ciliary gene (RPGRIP1L) were found in type B patients. We analyzed a cohort of 56 patients with JS type B who were negative for mutations in three (AHI1, NPHP1, and CEP290/NPHP6) of the four genes previously linked to the syndrome. The 26 exons encoding RPGRIP1L were analyzed by means of PCR amplification, CEL I endonuclease digestion, and subsequent sequencing. Using this approach, four different mutations in the RPGRIP1L gene in five different families were identified and three were found to be novel mutations. Additionally, we verified that missense mutations are responsible for JS type B and cluster in exon 15 of the RPGRIP1L gene. Our studies confirm that a T615P mutation represents the most common mutation in the RPGRIP1L gene causing disease in about 8-10% of JS type B patients negative for NPHP1, NPHP6, or AHI1 mutations.


Subject(s)
Cerebellar Diseases/genetics , Eye Diseases/genetics , Kidney Diseases, Cystic/genetics , Proteins/genetics , Adult , Child , Cytoskeletal Proteins , DNA Mutational Analysis , Family Health , Female , Genetic Linkage , Humans , Male , Pedigree , Point Mutation , Syndrome
5.
Oncogene ; 26(23): 3440-9, 2007 May 17.
Article in English | MEDLINE | ID: mdl-17130827

ABSTRACT

Inactivation of the HRPT2 gene encoding parafibromin was recently linked to the familial hyperparathyroidism-jaw tumor syndrome. Patients with this syndrome carry an increased risk of parathyroid and renal tumors. To determine the relevance of HRPT2 for sporadic renal tumors, clear cell, papillary and chromophobe renal cell carcinomas as well as oncocytomas and Wilms tumors were analysed for HRPT2 gene alterations. Loss of heterozygosity (LOH) of HRPT2 was found in seven of 56 (12.5%) clear cell, three of 14 (21%) papillary, six of 10 (60%) chromophobe renal cell carcinomas, three of eight (38%) oncocytomas and four of 10 (40%) Wilms tumors. In addition, two novel HRPT2 point mutations, causing K34Q and R292K changes in parafibromin, were detected in one clear cell carcinoma and one Wilms tumor, respectively. These tumors displayed LOH of the remaining wild-type allele, but interestingly no von Hippel-Lindau (VHL) mutation. Functional analysis revealed that the K34Q mutant species of parafibromin is, unlike wild-type protein, defective in suppressing cyclin D1 expression in vivo. Taken together, these results suggest that renal cancer-associated mutations in parafibromin occur in the absence of VHL mutation, which in turn may contribute to constitutively elevated cyclin D1 expression and abnormal cell proliferation.


Subject(s)
Allelic Imbalance/genetics , Kidney Neoplasms/genetics , Mutation/genetics , Tumor Suppressor Proteins/genetics , Aged , Aged, 80 and over , Alleles , Base Sequence , Chromosomes, Human, Pair 1/genetics , Female , Heterozygote , Humans , Lysine/genetics , Male , Middle Aged
6.
Klin Padiatr ; 217(5): 300-3, 2005.
Article in English | MEDLINE | ID: mdl-16167280

ABSTRACT

We report on a phenotypically male newborn with 45,X/46,X,dic(Y)-mosaicism. Right-sided inguinal hernia was surgically corrected. Histological examination of the tissue revealed an ambiguously differentiated gonad on this side. The clinical, cytogenetic, and histological results are described and the prognosis and clinical management of these patients are discussed.


Subject(s)
Gonadal Dysgenesis, Mixed/genetics , Mosaicism , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Karyotyping , Male , Phenotype , Prognosis
7.
Am J Physiol Regul Integr Comp Physiol ; 287(6): R1505-16, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15345472

ABSTRACT

Physiological cholestasis linked to immature hepatobiliary transport systems for organic anions occurs in rat and human neonates. In utero, the placenta facilitates vectorial transfer of certain fetal-derived solutes to the maternal circulation for elimination. We compared the ontogenesis of organic anion transporters in the placenta and the fetal liver of the rat to assess their relative abundance throughout gestation and to determine whether the placenta compensates for the late maturation of transporters in the developing liver. The mRNA of members of the organic anion transporting polypeptide (Oatp) superfamily, the multidrug resistance protein (Mrp) family, one organic anion transporter (OAT), and the bile acid carriers Na(+)-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) was quantified by real-time PCR. The most abundant placental transporters were Oatp4a1, whose mRNA increased 10-fold during gestation, and Mrp1. Mrp1 immunolocalized predominantly to epithelial cells of the endoplacental yolk sac, suggesting an excretory role that sequesters fetal-derived solutes in the yolk sac cavity, and faintly to the basal syncytiotrophoblast surface. The mRNA levels of Oatp2b1, Mrp3, and Bsep in the placenta exceeded those in the fetal liver until day 20 of gestation, suggesting that the fetus relies on placental clearance of substrates when expression in the developing liver is low. Mrp3 immunolocalized to the epithelium of the endoplacental yolk sac and less abundantly in the labyrinth zone and endothelium of the maternal arteries. The placental expression of Oatp1a1, Oatp1a4, Oatp1a5, Oatp1b2, Oat, Ntcp, Mrp2, and Mrp6 was low.


Subject(s)
Gene Expression Regulation, Developmental/genetics , Liver/embryology , Organic Anion Transporters/genetics , Placenta/physiology , Animals , Base Sequence , DNA Primers , Female , Fetal Development/genetics , Gestational Age , Liver/physiology , Polymerase Chain Reaction , Pregnancy , RNA, Messenger/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction
9.
Neuropediatrics ; 33(2): 57-62, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12075484

ABSTRACT

We describe a girl with intrauterine growth retardation, congenital cataracts, mild dysmorphic features and joint contractures. MRI performed at 1 week and 6 months, demonstrated postnatal cerebral and cerebellar atrophy and loss of white matter. The patient died at 10 months. Post-mortem examination revealed ovarian dysgenesis. There was normal development of neuronal and axonal structures, but lack of myelination in brainstem and cerebellum. Subcortical and deep white matter of the cerebral hemispheres were largely destroyed (cavitated), with preserved, but unmyelinated axons in other brain areas. These findings are compatible with a severe leukodystrophic process of pre- or perinatal onset. The exact pathogenesis is not known.


Subject(s)
Brain/abnormalities , Brain/pathology , Ovary/abnormalities , Abnormalities, Multiple , Disease Progression , Fatal Outcome , Female , Humans , Infant, Newborn , Magnetic Resonance Imaging
10.
J Clin Endocrinol Metab ; 87(4): 1856-63, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11932330

ABSTRACT

Organic anion-transporting polypeptides (OATPs) are a family of multispecific carriers that mediate the sodium-independent transport of steroid hormone and conjugates, drugs, and numerous anionic endogenous substrates. We investigated whether members of the OATP gene family could mediate fetal-maternal transfer of anionic steroid conjugates in the human placenta. OATP-B (gene symbol SLC21A9) was isolated from a placenta cDNA library. An antiserum to OATP-B detected an 85-kDa protein in basal but not apical syncytiotrophoblast membranes. Immunohistochemistry of first-, second-, and third-trimester placenta showed staining in the cytotrophoblast membranes and at the basal surface of the syncytiotrophoblast. Trophoblasts that reacted with an antibody to Ki-67, a proliferation-associated antigen, expressed lower levels of OATP-B. OATP-B mRNA levels were measured in isolated trophoblasts under culture conditions that promoted syncytia formation. Real-time quantitative PCR estimated an 8-fold increase in OATP-B expression on differentiation to syncytia. The uptake of [(3)H]estrone-3-sulfate, a substrate for OATP-B, was measured in basal syncytiotrophoblast membrane vesicles. Transport was saturable and partially inhibited by pregnenolone sulfate, a progesterone precursor. Pregnenolone sulfate also partially inhibited OATP-B-mediated transport of estrone-3-sulfate in an oocyte expression system. These findings suggest a physiological role for OATP-B in the placental uptake of fetal-derived sulfated steroids.


Subject(s)
Estrone/analogs & derivatives , Organic Anion Transporters/metabolism , Placenta/metabolism , Biological Transport/drug effects , Biological Transport/physiology , Cells, Cultured , Estrone/antagonists & inhibitors , Estrone/pharmacokinetics , Female , Giant Cells/physiology , Humans , Oocytes/metabolism , Organic Anion Transporters/genetics , Organic Anion Transporters/physiology , Pregnancy , Pregnenolone/pharmacology , RNA, Messenger/metabolism , Trophoblasts/metabolism
11.
Ultrasound Obstet Gynecol ; 19(1): 92-8, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11851976

ABSTRACT

Skeletal dysplasias, a heterogeneous group of bone growth disorders, can be detected by routine prenatal ultrasound examination. As it is difficult to make a specific diagnosis, prediction of prognosis is of importance for obstetric management. In order to specify diagnosis, radiological, pathological and molecular genetic examination are often required. Our report describes two cases of thanatophoric dysplasia with different fetal sonographic findings. The classical classification of type I and II seems to be ambiguous as, in both cases, the same mutation in the fibroblast growth factor receptor 3 gene was found. The importance of comprehensive multidisciplinary assessment is emphasized.


Subject(s)
Fetal Diseases/diagnostic imaging , Thanatophoric Dysplasia/diagnostic imaging , Ultrasonography, Prenatal , Adult , Female , Fetal Diseases/genetics , Fibroblast Growth Factor 3 , Fibroblast Growth Factors , Humans , Mutation , Pregnancy , Proto-Oncogene Proteins , Receptors, Growth Factor/genetics , Thanatophoric Dysplasia/genetics
12.
Eur J Pediatr Surg ; 12(6): 429-31, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12548500

ABSTRACT

Intestinal pseudoobstruction may be part of a paraneoplastic syndrome. We report a teenage girl with ganglioneuroblastoma who presented with severe constipation. The intestinal pseudoobstruction was presumed to be due to inflammation of the myenteric plexus with destruction of the ganglion cells caused by antineuronal nuclear antibodies (ANNA or Anti-Hu).


Subject(s)
Ganglioneuroblastoma/complications , Intestinal Neoplasms/complications , Intestinal Pseudo-Obstruction/etiology , Paraneoplastic Syndromes/diagnosis , Adolescent , Constipation/etiology , Female , Ganglioneuroblastoma/pathology , Ganglioneuroblastoma/surgery , Humans , Intestinal Neoplasms/pathology , Intestinal Neoplasms/surgery , Intestinal Pseudo-Obstruction/surgery , Myenteric Plexus/physiopathology , Neoplasm Recurrence, Local , Palliative Care
13.
Am J Obstet Gynecol ; 185(5): 1265-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11717670

ABSTRACT

A case report of hemolytic uremic syndrome with placental involvement in 2 of 3 consecutive pregnancies highlights the impact on the fetal placental compartment and the importance of diligent antenatal care in subsequent pregnancies.


Subject(s)
Hemolytic-Uremic Syndrome/complications , Placenta/blood supply , Pregnancy Complications , Thrombosis/embryology , Thrombosis/etiology , Adult , Female , Humans , Maternal-Fetal Exchange , Pregnancy , Recurrence
14.
Onkologie ; 24(4): 368-72, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11574765

ABSTRACT

BACKGROUND: Inflammatory myofibroblastic tumors (IMT) represent a spectrum of neoplasms that occur in the mesentery and retroperitoneum and less frequently in the mediastinum of children and young adults. Transformation into inflammatory fibrosarcoma and metastases are rare. CASE REPORT: We report the case of a 16-year-old patient with an inflammatory myofibroblastic tumor of the mesentery with mediastinal metastases. Partial remission was obtained by chemotherapy with ifosfamide, dactinomycine, and vincristine. Two months later, relapse with infiltration of the meninges developed, and the patient died. CONCLUSION: This case demonstrates unusual features of an IMT: presentation with metastases, excellent response to chemotherapy, dissemination to the CNS.


Subject(s)
Mediastinal Neoplasms/diagnosis , Meningeal Neoplasms/secondary , Mesentery , Neoplasms, Muscle Tissue/secondary , Peritoneal Neoplasms/diagnosis , Adolescent , Biopsy , Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Diagnosis, Differential , Humans , Male , Mediastinal Neoplasms/pathology , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/pathology , Meninges/pathology , Mesentery/pathology , Neoplasms, Muscle Tissue/diagnosis , Neoplasms, Muscle Tissue/pathology , Peritoneal Neoplasms/pathology , Spinal Cord Compression/diagnosis , Spinal Cord Compression/pathology , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/secondary , Tomography, X-Ray Computed
15.
Acta Obstet Gynecol Scand ; 80(9): 840-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11531636

ABSTRACT

BACKGROUND: To determine interleukin-6 and interleukin-8 levels in amniotic fluid, retroplacental blood and maternal serum and relate these values with cervical dilatation in term labor. METHODS: Prospective study. n=78 healthy women undergoing term cesarean section, divided into four groups: controls, n=42, (elective cesarean section; no contractions, membrane rupture or cervical dilatation); latent labor, n=12, (latent phase labor; cervix <2 cm dilated); established labor, n=12, (active labor, cervix 2-5 cm); advanced labor, n=12, (active labor, cervix >5 cm). Interleukin-6 and interleukin-8 were determined by ELISA (pg/ml), placenta and placental bed biopsy examined histopathologically, and amniotic fluid also microbiologically. Results were expressed as median and ranges or mean and standard deviations, as appropriate. For statistical analysis, Mann-Whitney U-tests or Kruskal-Wallis tests were used as applicable (Statview 4.5). Power and linear regression analyses were performed. p<0.05 was considered significant, p<0.001 highly significant. RESULTS: Compared with controls, IL-6 and IL-8 increased significantly with cervical dilatation in all compartments tested for almost all labor groups (p<0.05 to p<0.0001). Significant changes were also seen between latent and advanced labor groups in some compartments (p<0.05), but not between established and advanced labor groups. Intrauterine infection was excluded in any of the patients clinically and on histopathological or microbiological analysis of placentae and amniotic fluid. CONCLUSIONS: In term labor without intraamniotic infection, interleukin-6 and interleukin-8 at the fetomaternal interface and in maternal serum rise significantly with cervical dilatation. These cytokines could be used as markers of active labor if vaginal examination is not applicable.


Subject(s)
Interleukin-6/analysis , Interleukin-8/analysis , Labor Stage, First/physiology , Labor, Obstetric/physiology , Adolescent , Adult , Amniotic Fluid/chemistry , Biomarkers/analysis , Cross-Sectional Studies , Female , Humans , Interleukin-6/blood , Interleukin-8/blood , Pregnancy , Prospective Studies
16.
Z Geburtshilfe Neonatol ; 205(4): 152-5, 2001.
Article in German | MEDLINE | ID: mdl-11570196

ABSTRACT

INTRODUCTION: 1-2% of all twin pregnancies are complicated by premature contractions, leading to premature rupture of membranes before 26 weeks of pregnancy. In this situation, a decision is required to either actively induce premature delivery or to initiate expectant management. Maternal and fetal risks regarding perinatal mortality and morbidity and the benefits of pregnancy prolongation have to be weighted against each other. CASE REPORT: We present delayed deliveries of two I-Parae with dichorionic twin pregnancies, achieved by in vitro fertilisation. In both cases, spontaneous membrane rupture and miscarriage of the leading fetus occurred prior to 20 gestational weeks. As signs of infection were missing initially, we adopted a conservative, expectant management. In both cases, the pregnancies could be prolonged to more than 30 weeks' gestation. DISCUSSION: In the absence of additional risk factors, expectant, conservative management of multiple pregnancies after loss of one fetus can lead to pregnancy prolongation of 91 and 96 days, respectively. The gained gestational age of the remaining fetus and the healthy mother-child pairs are discussed under perinatal, economical and psychological aspects.


Subject(s)
Abortion, Spontaneous , Fetal Membranes, Premature Rupture/therapy , Pregnancy, Multiple , Abortion, Spontaneous/pathology , Adult , Female , Fertilization in Vitro , Fetal Membranes, Premature Rupture/pathology , Humans , Infant, Newborn , Obstetric Labor, Premature/pathology , Obstetric Labor, Premature/therapy , Placenta/pathology , Pregnancy , Pregnancy Trimester, Second , Tocolysis , Twins
17.
J Cereb Blood Flow Metab ; 21(7): 857-64, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435798

ABSTRACT

There is increasing evidence that erythropoietin (Epo) has a protective function in cerebral ischemia. When used for treatment, high Epo plasma levels associated with increases in blood viscosity, however, may counteract beneficial effects of Epo in brain ischemia. The authors generated two transgenic mouse lines that overexpress human Epo preferentially, but not exclusively, in neuronal cells. In mouse line tg21, a fourfold increase of Epo protein level was found in brain only, whereas line tg6 showed a dramatic increase of cerebral and systemic transgene expression resulting in hematocrit levels of 80%. Cerebral blood flow (CBF), as determined by bolus tracking magnetic resonance imaging, was not altered in the tg6 line. The time-to-peak interval for the tracer, however, increased approximately threefold in polyglobulic tg6 mice. Immunohistochemical analysis revealed an increase in dilated vessels in tg6 mice, providing an explanation for unaltered CBF in polyglobulic animals. Permanent occlusion of the middle cerebral artery (pMCAO) led to similar perfusion deficits in wild-type, tg6, and tg21 mice. Compared with wild-type controls, infarct volumes were not significantly smaller (22%) in tg21 animals 24 hours after pMCAO, but were 49% enlarged (P < 0.05) in polyglobulic tg6 mice. In the latter animals, elevated numbers of Mac-1 immunoreactive cells in infarcted tissue suggested that leukocyte infiltration contributed to enlarged infarct volume. The current results indicate that moderately increased brain levels of Epo in tg21 transgenic mice were not sufficient to provide significant tissue protection after pMCAO. The results with tg6 mice indicate that systemic chronic treatment with Epo associated with elevated hematocrit might deteriorate outcome after stroke either because of the elevated hematocrit or other chronic effects.


Subject(s)
Cerebral Infarction/pathology , Erythropoietin/genetics , Gene Expression , Animals , Blood Flow Velocity , Blood Viscosity , Brain/blood supply , Brain/metabolism , Brain/pathology , Brain Ischemia/metabolism , CD11 Antigens/analysis , Cerebral Infarction/metabolism , Endothelium, Vascular/chemistry , Erythropoietin/physiology , Hematocrit , Humans , Laminin/analysis , Macrophages/pathology , Magnetic Resonance Imaging , Male , Mice , Mice, Transgenic , Middle Cerebral Artery/surgery , Monocytes/pathology , Neurons/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Vascular Cell Adhesion Molecule-1/analysis
18.
Obstet Gynecol ; 97(4): 505-9, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11275018

ABSTRACT

OBJECTIVE: To estimate the incidence and lethality of placental maturation defect, and to determine the impact of the pattern of placental dysfunction on the risk of recurrent stillbirth or maternal disease in later life. METHODS: Questionnaire and archival analysis of fetal deaths from placental dysfunction at 32-42 weeks (1975-1995 in Zurich), classified as chronic (parenchyma loss) or acute (maturation defect of the terminal chorionic villi). Population survey of 17,415 consecutive unselected singleton placentas (1994-1998 in Berlin). RESULTS: Of the 71 stillbirths, 34 were due to parenchyma loss and 37 to maturation defect. Parenchyma loss predominated in the first pregnancy (73.5% compared with 43.2%; P <.05). The risks of recurrent stillbirth and subsequent childlessness did not differ between the two groups. Eleven percent of mothers whose placenta had maturation defect had diabetes in the index pregnancy; none of the other women in the group developed diabetes over the 5-20-year observation period. In the population survey, incidence of maturation defect was 5.7%, and was associated with fetal death in 2.3% of cases. Normal placentas were associated with fetal death in 0.033%. CONCLUSION: Placental maturation defect can be a cause of fetal hypoxia. Although the risk of stillbirth is 70-fold that of a normal placenta, few affected fetuses actually die. The risk of recurrent stillbirth is tenfold above baseline and occurs mostly after 35 weeks' gestation.


Subject(s)
Fetal Death/epidemiology , Fetal Death/etiology , Placenta/physiopathology , Adult , Female , Humans , Incidence , Infant, Newborn , Placenta/pathology , Pregnancy , Recurrence , Surveys and Questionnaires , Switzerland/epidemiology
19.
Anticancer Res ; 21(5): 3253-9, 2001.
Article in English | MEDLINE | ID: mdl-11848480

ABSTRACT

BACKGROUND: The aim of this study was to develop and characterize a mouse xenograft model for the hypercalcemic-type of small cell carcinoma of the ovary (HTSCCO). PATIENTS AND METHODS: Tumor fragments were removed from a patient and cultured in six subsequent generations of nude mice. Histology, comparative genomic hybridization (CGH), electron microscopy and serum calcium levels were investigated. RESULTS: Morphology remained the same from the primary tumor of the patient through the 6th passage in the mouse. Serum calcium levels were significantly higher in the tumor-bearing mice compared to controls. CGH of the HTSCCO did not show evidence of a close relationship to either a germ cell tumor or an epithelial ovarian cancer. CONCLUSION: Some evidence was provided that the HTSCCO is an inhomogeneous tumor that is neither related to a germ cell tumor nor to an epithelial ovarian cancer, but is a distinct tumor entity.


Subject(s)
Carcinoma, Small Cell/pathology , Hypercalcemia/pathology , Ovarian Neoplasms/pathology , Tumor Cells, Cultured , Adult , Animals , Calcium/blood , Carcinoma, Small Cell/blood , Carcinoma, Small Cell/genetics , Cell Division/physiology , Chromosome Aberrations , Female , Humans , Hypercalcemia/blood , Hypercalcemia/genetics , Mice , Mice, Nude , Microscopy, Electron , Neoplasm Transplantation , Nucleic Acid Hybridization , Ovarian Neoplasms/blood , Ovarian Neoplasms/genetics , Transplantation, Heterologous
20.
Angiogenesis ; 4(1): 79-84, 2001.
Article in English | MEDLINE | ID: mdl-11824382

ABSTRACT

The rapidly growing chorionic villi of the human placenta characteristically show constant blood vessel growth and differentiation. In contrast, the underlying decidua reveals tissue remodeling without apparent angiogenesis. Using the chick chorioallantoic membrane (CAM) assay, we found marked inhibition of angiogenesis by the feto-maternal interface tissue derived from nine human placentas obtained minutes after delivery. Inhibition was prevented by the addition of monensin, which blocks the release of synthesized cell products, and was markedly reduced by drying or freezing the tissue before the assay. Histology, combined with statistical analysis of the constituent cell types, correlated inhibition of angiogenesis with the number of fetally-derived extravillous trophoblasts in the feto-maternal interface tissue. Electron microscopy revealed endothelial cell damage in preexisting small (but not large) CAM vessels. We conclude that decidual tissue inhibited angiogenesis by releasing a water soluble factor which was under apparent constant production by vaible trophoblast on the CAM. The extravillous trophoblast population resembles tumor cells in its migratory and invasive properties but, in contrast to tumor induced angiogenesis, it is angiostatic, perhaps to counteract angiogenic proteins leaking from the intervillous space which could be detrimental to the maternal organism if active.


Subject(s)
Neovascularization, Physiologic , Placenta/blood supply , Allantois/blood supply , Allantois/drug effects , Allantois/ultrastructure , Animals , Chick Embryo , Chorion/blood supply , Chorion/drug effects , Chorion/ultrastructure , Chorionic Villi/blood supply , Chorionic Villi/drug effects , Chorionic Villi/physiology , Chorionic Villi/ultrastructure , Decidua/blood supply , Decidua/drug effects , Decidua/physiology , Decidua/ultrastructure , Female , Humans , In Vitro Techniques , Maternal-Fetal Exchange/physiology , Microscopy, Electron , Monensin/pharmacology , Neovascularization, Physiologic/drug effects , Placenta/drug effects , Placenta/physiology , Pregnancy
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