Imbalance of mononuclear cell infiltrates in the placental tissue from foetuses after spontaneous abortion versus therapeutic termination from 8th to 12th weeks of gestational age.

Placental macrophages (Hofbauer cells) are located close to trophoblastic cells and foetal capillaries, which make them perfect candidates for involvement in regulatory processes within the villous core. Their capacity of producing several cytokines and prostaglandin-synthesising enzymes, and expressing vascular endothelial growth factor, indicate a possible role in placental development and angiogenesis in order to support pregnancy. Common cells to Hofbauer macrophages sharing similar cell surface markers (HLA-A, -B, -C and leukocyte common antigen) have been reported in the stroma, decidua and amnion, indicating additional foetal protection. Yet this is not always the case. Most spontaneous abortions occur before 12 weeks' gestation, and most are due to chromosomal errors in the conceptus. Relatively few truly spontaneous abortions take place between 12 and 20 weeks' gestation. Thereafter, between 20 and 30 weeks, another type of premature spontaneous termination becomes prevalent, which is due to ascending infection. The numbers of cells expressing the various markers of the monocytemacrophage lineage change throughout pregnancy. In the present study, we investigated the immunohistochemical expression of mononuclear infiltrations in paraffin-embedded placentas, from foetuses after spontaneous abortion (8th, 10th and 12th weeks of gestational age), and those after therapeutic abortion at the same time, using a panel of monoclonal antibodies for the identification of leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), T lymphocytes (CD45RO/UCHL1), CD68 and CD14 cells. Immunologic factors in human reproductive failure are plausible mechanisms of infertility and spontaneous abortion. Approximately 25% of cases of premature ovarian failure appear to result from an autoimmune aetiology. Unfortunately, current therapeutic options for these women are limited to exogenous hormone or gamete substitution. Local inflammations at the sites of endometriosis implants are postulated to mediate the pain and reduced fecundability associated with this clinical syndrome. The recruitment of immune cells, particularly monocytes and T-cells, neovascularisation around foci of invading peritoneal lesions, and the possible development of antiendometrial autoantibodies support an immunologic basis of this disorder. To date, treatment of pain and infertility associated with endometriosis is primarily surgical, although immune-based adjuvants are theoretical possibilities for the future. Finally, although hypotheses supporting immunologic mechanisms of recurrent pregnancy loss have been popular over the past decade, most clinical investigations in this area do not provide compelling evidence for this position. Reputable specialists in reproductive medicine use experimental immunotherapies judiciously in selected cases of repetitive abortion. For example, the use of anticoagulation therapy can be beneficial in cases with documented antiphospholipid antibodies. At present, however, efficacious immunotherapy protocols for general application have not been established. Despite these caveats, continued strides in our understanding of human reproductive immunology should yield considerable future progress in this field. During the physiological changes that occur in the first and in the beginning of the second trimester of pregnancy, spiral arteries of the placental bed are converted into the uteroplacental arteries. The essence of this conversion consists of losing the muscular elements in the vessel walls, making them unable to respond to vasomotor influences. Cells that infiltrate the walls of spiral arteries and replace their normal elements are called migratory, non-villous or intermediate trophoblastic cells. Besides infiltrating and replacing the anatomic structures of spiral arteries, intermediate trophoblastic cells also penetrate into the lumina of these vessels forming endovascular plugs. These plugs are one of the reasons why early uteroplacental blood flow cannot be visualised, even with transvaginal ultrasound, during the first 12 weeks of gestation. In uncomplicated pregnancies, the endovascular trophoblast is bound to disappear by the end of the second trimester of pregnancy, but the literature on this topic is scarce. Here we describe the detection, isolation and characterisation of CD45RO-, L26- and CD68/CD14-positive cells from human early pregnancy deciduas. These cells were found in close vicinity to endometrial glands, with preference to the basal layer of the decidua. We conclude that (1) maternal cells, apparently CD45RO/UCHL1-positive cells, cross the maternofoetal barrier and participate in spontaneous (involuntary) abortions, and (2) a small proportion of maternal cells (approximately 30%), apparently CD68/CD14-positive cells, also cross the maternal-foetal barrier and cause growth delay and recurrent reproductive failure. Further investigation of involvement of the intercellular adhesion molecules 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin in leukocyte accumulation will be needed to support the passage of maternal cells to the foetus. The results were statistically significant (P<0.0001, Student's t-test).

Human duty in fetal loss: A study of fetal research on hematopoiesis

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Practical appraisal to ethics in fetal death: a case of anasarca

La respuesta humana hacia la muerte de un serquerido difiere en las distintas sociedades, religiones,culturas y razas, y se pone de manifiesto en unaserie de ceremonias y observancias. Dado que elexamen post-mortem puede resultar ofensivo paraalgunos grupos, la determinación de la necesidad deuna autopsia se debe basar tanto en la ética como enlos principios legales. La ética es “la ciencia quetrata de la naturaleza humana y de los fundamentosde las obligaciones morales; la ciencia de los debereshumanos” Aunque es responsabilidad de la sociedady deber del examinador médico o del juez deinstrucción solicitar la investigación de la muertedesde el punto de vista médico-legal, el establecimientode una política dogmática tiende a crearconfrontaciones en lugar de cumplir las obligacionesestatutarias. El enfoque de objeción a una autopsiadebe hacer hincapié en los valores de “respeto,compasión, amabilidad y cortesía por encima delmínimo requerido por cualquier política o directriz”

Human response to the death of a loved onevaries among different societies, religions, cultures,and races through a series of ceremonies andobservances. Since postmortem examination maybe offensive to some of these groups, thedetermination of the need for autopsy should bebased on ethical as well as legal principles. Ethics isthe “science which treats of human nature and thegrounds of moral obligation; the science of humanduty”. Although it is the responsibility of societyand the duty of a medical examiner/coroner toprovide medicolegal death investigation,establishing dogmatic policy is apt to createconfrontation rather than fulfillment of statutoryobligations. The approach to an objection toautopsy should stress values of “respect,compassion, kindness and courtesy beyond theminimum required by any policy or guideline”

NCL-CD30 staining of epithelial cells in the basal germinative layer of the epidermis and epithelial buds during foetal skin development.

The fact that the CD30 molecule can mediate signals for cell proliferation or apoptosis prompted us to perform a systematic investigation of CD30 antigen expression in embryonal tissues during proliferation and differentiation stages. We first targeted the foetal human intestinal cryptae cells with positive results. The epidermis is a dynamic epithelium that is constantly renewed throughout life. The basal layer, attached to the basement membrane, contains the dividing cells of the skin and as cells move up from this layer they undergo differentiation, ending in the formation of a terminally differentiated anucleate cell called squame. It is intriguing to find out if cells in the basal layer can express the CD30 antigen. We investigated the immunohistochemical expression of CD30 antigen in 15 paraffin-embedded tissue samples representing epidermis and epidermal buds from foetuses after spontaneous abortion in the 8th, 10th and 12th weeks of gestation, respectively, using the monoclonal antibody NCL-CD30. A Northern blotting analysis was additionally performed. The results showed that: (1) the epithelial cells of the epidermis in the developing skin express the CD30 antigen; (2) CD30 expression in these epithelial cells is higher in cases of hormonal administration than in normal gestation; (3) a similar positive reaction involved the epidermal buds associated with the development of the skin appendages. Northern blots of tissue sections using a CD30 cDNA probe detected mRNAs of the same molecular mass and variety similarly to those in the positive control cell line HUT 102.

Distribution of somatostatin in pancreatic ductal adenocarcinoma remodels the normal pattern of the protein during foetal pancreatic development: an immunohistochemical analysis.

AIM: To determine the immunoreactivity of somatostatin during the development of the human fetal pancreas and pancreatic ductal adenocarcinoma, given that, somatostatin-positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. METHODS: Tissue sections from 15 pancreatic fetal specimens, and an equal number of ductal adenocarcinoma specimens were assessed. RESULTS: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly different from the relevant density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (P1=0.021 P2=0.001, P3<0.0001, P4=0.003 respectively). The above values were estimated from the 8th to 10th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (P5=0.16) and pure ductal type (P6=0.65). CONCLUSION: The immunostaining for somatostatin identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, (initially considered as pure ductal tumors), and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of somatostatin and analogues as monotherapy in pancreatic cancer management.

Immunohistochemical characterization of human fetal pancreas and pancreatic ductal adenocarcinoma. A study of somatostatin antibody NCL-SOMATOp

Propósito: La somatostatina es una hormona peptídica gastrointestinal que inhibe el crecimiento delcáncer pancreático, como atestigua un número creciente de informes. Sin embargo, no siempre es así. Conobjeto de aclarar la controversia planeamos la identificación de somatostatina durante el desarrollo del tejidopancreático embrionario humano y en el adenocarcinoma pancreático, considerando que las células quecontienen somatostaina existen tanto en el epitelio ductal pancreático primitivo como en el carcinomapancreático.• Métodos: Muestras de tejido de páncreas fetal (n=15) y de adenocarcinoma pancreático ductal (n=15) sevaloraron analizando la expresión de somatostatina por métodos inmunohistoquímicos.• Resultados: El epitelio ductal exocrino primitivo normal y el epitelio endocrino mostraron un aumentoclaramente significativo de la expresión de somatostatina cuando se compararon con la cantidad existente enlos tejidos pancreático mixto, ductal-endocrino y de tipo ductal puro (p1=0,021, p2=0,001, p3<0,0001 yp4=0,003, respectivamente) durante la 5ª a la 10ª semanas. No se encontró una diferencia estadísticamentesignificativa de la expresión de somatostatina entre el tejido acinar que rodea a los islotes y los tejidos mixto(p5=0,16) y ductal puro (p6=0,65) entre la 13ª y la 24ª semanas.• Conclusiones: Las células del cáncer pancreático pueden expresar somatostatina siguiendo un modeloque reproduce la expresión normal del péptido en las células δ del páncreas durante la organogénesisembrionaria. Una nueva opción potencialmente adyuvante de la terapéutica del cáncer pancreático se debedirigir hacia la somatostatina y sus análogos

Purpose: Somatostatin is a gastrointestinal peptide hormone that inhibits growth of pancreatic cancer as reported by an increasing body of evidence. Yet this is not always the case. To clarify the controversy we aimed to identify the expression of somatostatin in developing human embryonic pancreatic tissue and pancreatic adenocarcinoma given that somatostatin positive cells were shown either into primitive pancreatic ductal epithelium or into pancreatic carcinoma. • Methods: Tissue sections representing pancreatic fetal specimens (n=15) and ductal pancreatic adenocarcinoma specimens (n=15) were assessed using immunohistochemical methods for somatostatin expression. • Results: Normal primitive exocrine ductal epithelium and endocrine epithelium showed a definite, statistically significant, higher expression of somatostatin over neoplastic pancreatic tissue of mixed (ductalendocrine) and pure ductal type (p1=0.021, p2=0.001, p3<0.0001, and p4=0.003 respectively) during the 8th to the 10th week. No statistically significant differential expression of somatostatin in the mantle zone of the islets over neoplastic tissue of mixed (p5=0.16) and pure ductal type (p6=0.65), from the 13th to the 24th week was demonstrated. • Conclusion: Pancreatic cancer cells can express somatostatin in a model that reproduces the normal expression of the peptide by δ-cells during embryonal organogenesis. Therapy aimed at pancreatic cancer must be targeted to somatostatin and analogues as potential adjuvant novel option

Post transplantation human herpes virus-8 unrelated primary effusion lymphoma of the peritoneal cavity in a HIV-negative female

El linfoma de derrame primario (PEL) es una forma individualizada recientemente de linfoma no hodgkiniano(clasificación de la OMS), que se desarrolla principalmente en varones infectados con HIV, más frecuentementehomosexuales, en estadios avanzados de la enfermedad (recuento total de linfocitos CD+ 100-200/µl).Ocasionalmente aparece en otros estados de inmunosupresión (como durante el período de trasplante de órganossólidos) e incluso, aunque muy rara vez, en pacientes inmunocompetentes. Desde un punto de vista patogénico,el PEL se ha relacionado con el herpesvirus asociado al sarcoma de Kaposi (también llamado herpesvirus8 humano y HHV 8) y antecedentes clínicos de sarcoma de Kaposi. La frecuencia relativamente baja de la enfermedad,la ausencia de una casuística que permita una mejor caracterización y su desenlace desfavorable,apoyan la necesidad de profundizar en su conocimiento. Presentamos aquí los hallazgos clínico-biológicos deun paciente negativo para HIV, que fue diagnosticado de PEL peritoneal, originado en células T y no asociadoa HHV 8, cinco años después de un trasplante renal

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin lymphoma (WHOclassification), developing mainly in HIV-infected males, more frequently homosexual, in advanced stages ofthe disease (total CD4+ lymphocyte count below 100-200/µl). Occasionally, it appears in otherimmunosupressive states (such as solid organs transplantation period) and even, although very rarely, inimmunocompetent patients. From a pathogenic point of view, PEL has been related to Kaposi's sarcomaassociated herpes virus (also named human herpesvirus 8, HHV 8) and to clinical antecedents of Kaposi'ssarcoma. The relatively low frequency of this disease, the absence of a wide casuisticsts allowing a bettercharacterization, and its unfavourable outcome, support the need of a deeper knowledge. We present here theclinico-biological findings of a HIV-negative patient, who was diagnosed of peritoneal PEL, of T cell origin,and not HHV 8-associated, five years after renal transplantation