Gastroschisis is a defect of the umbilical ring: evidence from morphological evaluation of stillborn fetuses.

BACKGROUND: Gastroschisis (GS) is usually described as an abdominal wall defect, to the right of a normally inserted umbilical cord, without membraneous covering of the extruded organs. However, precise anatomical descriptions are lacking in the literature. Our aims were to provide evidence that allows reconsideration of its current definition, as well as an explanation for prenatal death, based on detailed observation of stillborn fetuses with GS and a review of the literature. METHODS: Prenatal studies, clinical examinations, and histological findings of five stillborn fetuses with isolated GS are described and photographic evidence is provided. RESULTS: In all five cases, the umbilical cord was only attached to the left side of the umbilical ring, while the right side remained uncovered, allowing evisceration of abdominal organs. Histological evidence of mucoid-like tissue at the free border of the ring suggests that at that site the cord was initially inserted and later detached. Characteristics of the umbilical ring, bowel dilatation, and autopsy findings of acute asphyxia strongly support compression of umbilical vessels as the cause of fetal death. CONCLUSIONS: Based on these findings, on the lack of evidence in the literature demonstrating full-thickness abdominal wall separating the defect from the umbilical cord, and on a critical review of the proposed mechanisms favoring the hypothesis of a defect separate from the umbilical ring, we propose that GS represents a failure in the normal attachment between umbilical cord and umbilical ring. The consistent clinical course of fetuses with prenatal demise suggests careful targeted monitoring during late gestation.

Novel invasive orthotopic bladder cancer model with high cathepsin B activity resembling human bladder cancer.

PURPOSE: We developed and characterized an orthotopic invasive bladder tumor model. MATERIAL AND METHODS: The MB49-I invasive bladder tumor cell line was obtained after 13 consecutive in vivo passages of primary tumor obtained by subcutaneous inoculation of MB49 bladder tumor cells in C57Bl/6J male mice. RESULTS: MB49-I tumor local invasiveness, tumor weight and spontaneous metastatic capacity were higher than in MB49 tumors. In MB49-I bladder tumors increased vimentin was observed, suggesting epithelial mesenchymal transition. In vitro the MB49-I cell line showed higher invasive properties associated with an increase in cathepsin B, metalloproteinase 9 and urokinase-type plasminogen activator proteolytic activities. Orthotopic bladder tumors induced by electrocautery of the bladder wall and subsequent instillation of MB49 and MB49-I bladder cancer cells generated superficial and invasive bladder tumors, respectively. CONCLUSIONS: The new murine bladder model described resembles human bladder disease, making it a useful tool for studying the molecular mechanisms of tumor progression and metastasis, and assaying antimetastatic and anti-invasive agents.

Tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas is associated with the degree of tumor progression.

PURPOSE: To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the "morphologically normal tissues" adjacent to them is associated with the degree of tumor progression. METHODS: Tumor and "normal tissues" were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and "normal tissues" and we investigated the existence of correlations between: (a) PA production in the tumor and "normal tissues", (b) different components of the PA system, and (c) PA system and the degree of tumor progression. RESULTS: (1) Total PA activity, u-PA activity and PAI-1 expression are significantly higher in tumor than in "normal tissues", whereas t-PA activity does not differ between them. (2) Total PA activity mainly correlates with u-PA activity in tumor tissues and similarly with u-PA and t-PA activities in "normal tissues". (3) There is a significant association between t-PA activity in tumor and "normal tissues" and the degree of tumor progression. CONCLUSIONS: "Morphologically normal tissues" adjacent to carcinomas present abnormal t-PA activity that is associated with the degree of tumor progression. Assaying of this activity could be useful as a predictive parameter.

Acephaly: further evidence for disruption but not for amniotic bands.

Complete absence of the fetal head in singleton pregnancies is a very rare defect; to our knowledge there are only 7 reported cases. Decapitation by amniotic bands has been considered as the most probable cause. However, in none of the described cases except one were amniotic bands, constriction rings, or other related findings observed, raising the possibility that mechanisms other than amputation by amniotic bands are involved. We present a further case of acephaly and discuss the role of amniotic bands and alternative mechanisms of decapitation and a possible sequence of events leading to acephaly.

Patterns of severe abdominal wall defects: insights into pathogenesis, delineation, and nomenclature.

BACKGROUND: During the last decade, descriptions of malformation complexes involving an abdominal wall defect (AWD) have repeatedly appeared in the literature, and there has been frequent confusion regarding nomenclature, definitions, and delineations. The aims of this work were to evaluate possible embryological relationships among AWD cases, review the related nomenclature, identify patterns involving AWDs, and stress the importance of complete clinical descriptions. METHODS Cases diagnosed as AWD complexes were selected from live--and stillborn infants of the Hospital Materno Infantil Ramón Sardá, Buenos Aires, and from the Laboratory of Perinatal Pathology, Buenos Aires, Argentina. They were sorted by the location of the AWD, the umbilical cord length, and the presence or absence of a persistent cloaca. The findings in 26 cases were described, according to proposed definitions. RESULTS: Three patterns could be identified: 1) the AWD involving the umbilical ring, a persistent or exstrophic cloaca, and a spinal cord anomaly; 2) the AWD extending laterally to the umbilical ring, severe unilateral limb defects, and same-sided agenesis of abdominal organs; and 3) the AWD not involving the umbilical ring, clefts, exencephaly, and amputations. Furthermore, overlapping among these patterns was observed, and possible involved mechanisms are discussed. CONCLUSIONS: The observed overlapping among patterns suggested that malformation complexes involving AWDs might not be independent conditions but rather belong to a common and broader spectrum of anomalies. Complete clinical descriptions, the avoidance of synonyms and generalizations, and strictly defined inclusion criteria are proposed for a better understanding of pathogenetic pathways in, and relationships among, AWD complexes.

Exogenous interferon-gamma alters murine inner cell mass and trophoblast development. Effect on the expression of ErbB1, ErbB4 and heparan sulfate proteoglycan (perlecan).

Implantation is a crucial event in human pregnancy. The participation of cytokines in the implantation process has been widely documented, although the role of many of these molecules is still a matter of controversy. In a previous report from our laboratory, we demonstrated that addition of interferon-gamma to the culture medium produces deleterious effects on mouse embryo development. In this study we investigated the effect of this cytokine on outgrowing embryo morphology and on the expression of epidermal growth factor receptors (ErbBs) and heparan sulfate proteoglycan (perlecan) in mouse embryos cultured in vitro. Morphological assessment of inner cell mass and trophoblast development was carried on in-situ fixed and stained outgrowths. Localization of ErbB1, ErbB4 and perlecan on pre- and peri-implantation embryos was investigated by immunocytochemistry. Addition of interferon-gamma produced a deleterious effect on both inner cell mass and trophoblast morphology. Immunostaining demonstrated that ErbB1, ErbB4 and perlecan are present on pre-implantation embryos and blastocysts; interferon-gamma altered the expression of ErbB4 and Perlecan at the blastocyst stage. We propose that the effects produced by this cytokine could be related to the altered acquisition of adhesion competence and low implantation rates observed in certain reproductive immunological disorders.

Reviewing old concepts at the start of a new millenium: growth restriction, adrenal hypoplasia, and thymomegaly in human anencephaly.

BACKGROUND: Anencephaly has been associated frequently with intrauterine growth retardation (IUGR), consistently with adrenal hypoplasia, and occasionally with an enlarged thymus. Few studies have analyzed the relationship between gestational age (GA), IUGR, associated anomalies and thymomegaly in anencephaly. The aims of our study were to evaluate this relationship and to highlight the usefulness of anencephaly as a model when investigating immune-endocrine interactions. METHODS: Fifty-two anencephalics' autopsies were reviewed retrospectively. Body weight, adrenal, and thymus weights were compared to prenatal, postnatal, and stillborn control values, and between associated and isolated anencephalic cases (presenting with and without other unrelated anomalies). Comparisons of adrenal and thymus weights were done by GA and by body weight. Thymus weight:body weight (TW:BW) ratios were compared to expected values. RESULTS: Anencephalics' body and adrenal weights were lower than their control values, whereas thymus weights did not differ. Body and thymus weights were twice as high in isolated than in associated anencephaly, whereas adrenal weights did not differ. Anencephalics TW:BW ratios were higher than their control values, higher in cases with IUGR, and higher in isolated rather than associated cases. When distributed by GA, thymus weights in anencephaly increased at a higher-than-expected rate. CONCLUSIONS: Our results suggest that adrenal hypoplasia is invariably present in anencephaly, and depending on an underdeveloped pituitary gland, seems to be independent of its etiology. On the contrary, IUGR mainly exists in associated cases and thymus enlargement mainly exists in isolated cases, suggesting a relationship with the underlying cause.

Inmunorregulación del crecimiento tumoral en un sistema murino / Immunoregulation of tumor growth in a murine model

Estudiamos la regulación del crecimiento tumoral y metastásico tanto por el propio tumor como por el sistema inmune, en un modelo murino. Sobrenadantes de cultivo de esplenocitos de portadores de tumor exacerban el crecimiento del propio tumor. Esta actividad desaparece luego de la cirugía tumoral pero con una cinética diferente dependendo de si el tumor es precoz o avanzado al tiempo de la cirugía. Las poblaciones esplénicas involucradas en la exacerbación varían durante el crecimiento del tumor mientras que las responsables de inducción de angiogénesis son siempre de naturaleza T. Con respecto de la autorregulación tumoral, encontramos que diferentes formas de antígenos tumorales (extractos tumorales, sobrenadantes de cultivo de células tumorales, células tumorales formolizadas) aumentan la diseminación metastásica, pero esta actividad está mediada por el sistema inmune del huésped. Por el contrario, sobrenadantes de cultivo de células tumorales no inducen exacerbación del tumor primario. Las células tumorales fueron tratadas con un modificador de membrana con la expectativa de alterar la respuesta inmune antitumoral