Publications by authors named "Jaco Hagoort"

Objectives: Down syndrome (DS) is associated with airway abnormalities including a narrowed trachea. It is uncertain whether this narrowed trachea in DS is a consequence of deviant fetal development or an acquired disorder following endotracheal intubation after birth. This study aimed to compare the tracheal morphology in DS and non-DS fetuses using microfocus computed tomography (micro-CT).

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Over the last few years, fetal postmortem microfocus computed tomography (micro-CT) imaging has increased in popularity for both diagnostic and research purposes. Micro-CT imaging could be a substitute for autopsy, particularly in very early gestation fetuses for whom autopsy can be technically challenging and is often unaccepted by parents. This article provides an overview of the latest research in fetal postmortem micro-CT imaging with a focus on diagnostic accuracy, endovascular staining approaches, placental studies and the reversibility of staining.

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Evolutionary responses to selection for bipedalism and childbirth have shaped the human pelvis, a structure that differs substantially from that in apes. Morphology related to these factors is present by birth, yet the developmental-genetic mechanisms governing pelvic shape remain largely unknown. Here, we pinpoint and characterize a key gestational window when human-specific pelvic morphology becomes recognizable, as the ilium and the entire pelvis acquire traits essential for human walking and birth.

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To increase our understanding of the etiology of specific neurological disorders (e.g., Duane syndrome, glossoptosis in Pierre Robin sequence), proper knowledge of anatomy and embryology of cranial nerves is necessary.

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Due to advancements in ultrasound techniques, the focus of antenatal ultrasound screening is moving towards the first trimester of pregnancy. The early first trimester however remains in part, a 'black box', due to the size of the developing embryo and the limitations of contemporary scanning techniques. Therefore there is a need for images of early anatomical developmental to improve our understanding of this area.

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Using serial block-face scanning electron microscopy, we report on the internal 3D structures of the brown planthopper, (Hemiptera: Delphacidae) at nanometer resolution for the first time. Within the reconstructed organs and tissues, we found many novel and fascinating internal structures in the planthopper such as naturally occurring three four-way rings connecting adjacent spiracles to facilitate efficient gas exchange, and fungal endosymbionts in a single huge insect cell occupying 22% of the abdomen volume to enable the insect to live on plant sap. To understand the muscle and stylet movement during phloem sap-sucking, the cephalic skeleton and muscles were reconstructed in feeding nymphs.

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The size and growth patterns of the components of the human embryonic heart have remained largely undefined. To provide these data, three-dimensional heart models were generated from immunohistochemically stained sections of ten human embryonic hearts ranging from Carnegie stage 10 to 23. Fifty-eight key structures were annotated and volumetrically assessed.

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This data article presents datasets associated with the research article entitled "The immunological architecture of granulomatous inflammation in central nervous system tuberculosis'' (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-dimensional (3D) models.

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Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma.

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Mitchell-Riley syndrome (MRS) is caused by recessive mutations in the regulatory factor X6 gene () and is characterised by pancreatic hypoplasia and neonatal diabetes. To determine why individuals with MRS specifically lack pancreatic endocrine cells, we micro-CT imaged a 12-week-old foetus homozygous for the nonsense mutation c.1129C>T, which revealed loss of the pancreas body and tail.

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Organogenesis is a complex coordinated process of cell proliferation, growth, migration, and apoptosis. Differential growth rates, particularly during cardiogenesis, play a role in establishing morphology. Studies using stereological and cell sorting methods derive averages of morphogenetic parameters for an organ.

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The fibro-muscular architecture of the urogenital triangle remains contentious. Reasons are small size of the constituting structures and poor visibility with most imaging methods. We reinvestigated the area in serial sections of three males (21-38 years old) of the American and Chinese Visible Human Projects and two 26-week-old male fetuses, and compared the findings with earlier observations in females.

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Congenital muscle diseases, such as myopathies or dystrophies, occur relatively frequently, with estimated incidences of up to 4.7 per 100 000 newborns. To diagnose congenital diseases in the early stages of pregnancy, and to interpret the results of increasingly advanced in utero imaging techniques, a profound knowledge of normal human morphological development of the locomotor system and the nervous system is necessary.

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The pelvic floor guards the passage of the pelvic organs to the exterior. The near-epidemic prevalence of incontinence in women continues to generate interest in the functional anatomy of the pelvic floor. However, due to its complex architecture and poor accessibility, the classical 'dissectional' approach has been unable to come up with a satisfactory description, so that many aspects of its anatomy continue to raise debate.

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Current knowledge about human development is based on the description of a limited number of embryonic specimens published in original articles and textbooks, often more than 100 years ago. It is exceedingly difficult to verify this knowledge, given the restricted availability of human embryos. We created a three-dimensional digital atlas and database spanning the first 2 months of human development, based on analysis of nearly 15,000 histological sections of the renowned Carnegie Collection of human embryonic specimens.

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Background: Pelvic-floor anatomy is usually studied by artifact-prone dissection or imaging, which requires prior anatomical knowledge. We used the serial-section approach to settle contentious issues and an interactive 3D-pdf to make the results widely accessible.

Method: 3D reconstructions of undeformed thin serial anatomical sections of 4 females and 2 males (21-35y) of the Chinese Visible Human database.

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MicroRNAs (miRNAs) regulate many aspects of cellular function and their deregulation has been implicated in heart disease. MiRNA-30c is differentially expressed in the heart during the progression towards heart failure and in vitro studies hint to its importance in cellular physiology. As little is known about the in vivo function of miRNA-30c in the heart, we generated transgenic mice that specifically overexpress miRNA-30c in cardiomyocytes.

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Organ development is a complex spatial process in which local differences in cell proliferation rate play a key role. Understanding this role requires the measurement of the length of the cell cycle at every position of the three-dimensional (3D) structure. This measurement can be accomplished by exposing the developing embryo to two different thymidine analogues for two different durations immediately followed by tissue fixation.

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Knowledge of complex morphogenetic processes that occur during embryonic development is essential for understanding anatomy and to get insight in the pathogenesis of congenital malformations. Understanding these processes can be facilitated by using a three-dimensional (3D) developmental series of human embryos, which we aim to create in this project. Digital images of serial sections of 34 human embryos of the Carnegie Collection between Carnegie stages 7 (15-17 days) and 23 (56-60 days) are used to create 3D reconstructions of different organ systems.

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Interpretation of the results of anatomical and embryological studies relies heavily on proper visualization of complex morphogenetic processes and patterns of gene expression in a three-dimensional (3D) context. However, reconstruction of complete 3D datasets is time consuming and often researchers study only a few sections. To help in understanding the resulting 2D data we developed a program (TRACTS) that places such arbitrary histological sections into a high-resolution 3D model of the developing heart.

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Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A.

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Molecular imaging, which is the three-dimensional (3D) visualization of gene expression patterns, is indispensable for the study of the function of genes in cardiac development. The instrumentation, as well as the development of specific contrast agents for molecular imaging, has shown spectacular advances in the last decade. In this review, the spatial resolutions, contrast agents, and applications of these imaging methods in the field of cardiac embryology are discussed.

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In this communication we discuss the formation of the synchronously contracting chambered heart from a peristaltically contracting linear heart tube. It is proposed that members of the T-box family of transcription factors play a crucial role in the formation of the building plan of the formed heart. Tbx5 may confer venoarterial polarity to the heart tube, whereas Tbx2 initially and Tbx3 in later developmental stages prevent the cardiac inflow tract, atrioventricular region, outflow tract, as well as the cardiac inner curvatures from chamber differentiation.

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Objective: The molecular mechanisms that regulate the formation of the conduction system are poorly understood. We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS).

Methods: The patterns of expression of Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular chamber-type myocardium in the developing heart, were analyzed in mice by in situ hybridization and three-dimensional reconstruction analysis.

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