Ultrastructure of the early human implantation in vitro

Four hatched human blastocysts obtained after in-vitro fertilizationand development were placed on monolayer cell cultures of humanendometrial epithelium, and subsequently examined by transmissionelectron microscopy. All four blastocysts became adherent tothe monolayer and three implanted and exhibited outgrowth oftheir trophoblastic cells. During implantation the blastocystsdifferentiated into mural and polar trophoblastic cells, andembryonic cells including endodermal cells. The endometrialcells were displaced and stacked into a multilayer at the peripheryof the implantation sites, allowing the trophoblastic cellsto come in contact with the culture dish. The endometrial cellsdisplayed local exo- or endo-cytosis where they contacted thetrophoblastic cells. The trophoblastic cells were not observedto be phagocytosing endometrial cells. These observations suggestthat human blastocysts portray an intrusive type of implantationduring the initial stages.     

Expression analysis of ataxin-7 mRNA and protein in human brain: evidence for a widespread distribution and focal protein accumulation

Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG-trinucleotide repeat in the coding region of the SCA7 gene. The expansion is translated into an extended polyglutamine stretch in the protein ataxin-7, a protein of unknown function. By Northern blot analysis expression of ataxin-7 was detected in numerous regions of human brain and some peripheral tissues. It is unknown, however, if ataxin-7 is enriched at sites of the SCA7 pathology. We studied the regional and cellular expression pattern of ataxin-7 at the mRNA level by in situ hybridization histochemistry in normal human brain. Furthermore we used a monoclonal and two polyclonal antibodies raised against the normal ataxin-7 to establish the distribution of this protein in brain, retina and peripheral organs. At the mRNA level ataxin-7 was preferentially expressed in neurons; the regional distribution reflected neuronal packing density. Ataxin-7 immunoreactivity (IR) was similarly widely expressed. In most neurons, ataxin-7 IR was preferentially localized to the cytoplasmatic compartment although some nuclear ataxin-7 IR was detected in most neurons. A more intense and more prominently nuclear ataxin-7 IR was observed in neurons of the pons and the inferior olive, brain regions severly affected by the disease, suggesting that the subcellular localization and abundance of ataxin-7 is regulated in a regionally specific way. Since neurons displaying more intense and more prominently nuclear ataxin-7 IR belonged to the class of susceptible cells in SCA7, an enrichment of normal ataxin-7 in the nuclear compartment may contribute to neurodegeneration. However not all sites of SCA7 pathology displayed a strong cytoplasmatic and nuclear immunoreactivity.     

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

Untersuchungen zur Expression von Galectin-3 im Schilddrüsengewebe und in Follikelzelltumoren der Schilddrüse Kritische Bewertung einer m?glichen pr?operativen differenzialdiagnostischen Nutzung Kritische Bewertung einer m?glichen pr?operativen differenzialdiagnostischen Nutzung

Galectin-3 geh?rt zu einer Gruppe endogener Lektine mit Affinit?t zu beta-galaktosidhaltigen Glykokonjugaten (Galectin-1– 4 bzw. 1–7). Es ist in zahlreichen Geweben nachgewiesen und im Zusammenhang mit Tumorwachstum, Dedifferenzierung und Metastasierung untersucht worden. Nur wenige Untersuchungen besch?ftigten sich bislang mit dem Nachweis von Galectin-3 in Tumoren der Schilddrüse und mit der m?glichen differenzialdiagnostischen Bedeutung. Wir haben aus dem eigenen fortlaufenden operativen Untersuchungsgut insgesamt 118 Schilddrüsentumoren mit einem monoklonalen Antik?rper gegen Galectin-3 untersucht und die Pr?parate vergleichend unter Anwendung eines semiquantitativen Score zur Erfassung von Unterschieden der Expression ausgewertet. Normales Schilddrüsengewebe, nod?s-hyperplastisches Gewebe und Gewebe mit Funktionssteigerung sind für Galectin-3 weitgehend negativ. Adenome mit typischem zytologischem Befund sind überwiegend negativ, k?nnen aber herdf?rmig in Einzelzellen oder Follikelgruppen positiv reagieren. Papill?re Karzinome zeigen fast durchweg eine ausgepr?gte Galectin-3-Expression. Bei follikul?ren Karzinomen sowie oxyphilen Adenomen und Karzinomen sind die Befunde jedoch sehr uneinheitlich, und es finden sich neben positiven auch Galectin-3-negative Tumoren. Die follikul?re Variante des papill?ren Karzinoms ist mit der Galectin-3-Reaktion zuverl?ssig erfassbar. Die mit Galectin-3 erhobenen Befunde müssen jedoch bei der Beurteilung der Dignit?t von Tumorl?sionen der Schilddrüse u. E. mit kritischer Zurückhaltung und unter Einbeziehung bekannter histologischer Malignit?tskriterien bewertet werden.     

Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: Relevance for mental disorders

Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood. GluA1‐containing AMPA receptors, which are located predominantly on hippocampal neurons, are the primary molecular determinants of synaptic plasticity. We investigated here the consequences of the inducible deletion of GluA1 AMPA receptors in glutamatergic neurons during late adolescence. We generated mutant mice with a tamoxifen‐inducible deletion of GluA1 under the control of the CamKII promoter for temporally and spatially restricted gene manipulation. GluA1 ablation during late adolescence induced cognitive impairments, but also marked hyperlocomotion and sensorimotor gating deficits. Unlike the global genetic deletion of GluA1, inducible GluA1 ablation during late adolescence resulted in normal sociability. Deletion of GluA1 induced redistribution of GluA2 subunits, suggesting AMPA receptor trafficking deficits. Mutant animals showed increased hippocampal NMDA receptor expression and no change in striatal dopamine concentration. Our data provide new insight into the role of deficient AMPA receptors specifically during late adolescence in inducing several cognitive and behavioral alterations with possible relevance for neuropsychiatric disorders. © 2013 Wiley Periodicals, Inc.     

Gehirn,Nerven

Ohne Zusammenfassung     

Intrauterine fertilization capsules—A clinical trial

Treatment of 26 women with tubal infertility was attempted using intrauterine capsules loaded with oocytes and spermatozoa. The stimulation protocol was as used for in vitro fertilization and embryo transfer and consisted of short-term use of Buserelin, human menopausal gonadotropin, and human chorionic gonadotropin. Oocytes were collected by ultrasonically guided transvaginal aspiration, and spermatozoa were prepared by swim-up technique. The gametes were placed in agar capsules 4 hr after oocyte collection, and the capsules were introduced to the uterine fundus using an insertion tube and piston from an intrauterine device. Six complete capsules and parts of two other capsules were expelled. None of the women became pregnant, compared with a pregnancy rate of 21% per aspiration following in vitro fertilization and embryo transfer during the same period.     

Hypercapnea and hypoxia challenge tests in infants at risk for sudden infant death syndrome

Infants who have almost died of sudden infant death syndrome (SIDS) and infants who are siblings of SIDS victims constitute groups at increased risk for SIDS. Management dilemmas are common among physicians caring for these infants. To assess the usefulness of hypoxia (17% oxygen) and hypercapnea (3% carbon dioxide) challenge tests as predictors of outcome, we reviewed the records of 102 infants who underwent these tests. During hypoxia tests, we found that periodic breathing and respiratory pauses frequently developed among the infants in these high-risk groups, but also developed among control infants. During hypercapnea testing, some infants failed to increase their minute ventilation (usually measured by volume of breath X breaths per minute), but control infants showed this poor response just as often as high-risk infants. Our findings suggest that hypoxia and hypercapnea stress tests are of limited usefulness in planning management of infants at risk for SIDS.