Biomedical subjects

J Heemskerk

Publications and source records attributed to J Heemskerk.

12 recordsLinked to original sources

PubMed2006

Advantages of advanced laparoscopic systems.

BACKGROUND: Conventional laparoscopy offers great benefits to our patients, but suffers from major technical drawbacks. Advanced laparoscopic systems are being developed addressing some of these drawbacks. METHODS: We performed a training-box based study, performing laparoscopic tasks using conventional laparoscopy and advanced laparoscopic systems in order to assess the influence of these technical drawbacks in order to predict where the biggest advantages of newly developed surgical systems can be expected. RESULTS: The most significant technical drawbacks were two-dimensional vision, disturbed eye-hand target axis and (possibly to a lesser extent) the rigid instruments with a limited five degrees of freedom. CONCLUSION: Major advances in advanced laparoscopy might only be expected using console-based robot-arm manipulated systems like the daVinci surgical system, or a combination of a high-quality 3-dimensional vision system, restoration of the eye-hand-target axis and the use of an advanced handheld instrument offering seven degrees of freedom such as the Radius surgical system.

Adult↗

PubMed2005

Challenges and opportunities in clinical trials for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.

Child↗

PubMed2000

Mesenchymal/epithelial induction mediates olfactory pathway formation.

In the olfactory pathway, as in the limbs, branchial arches, and heart, mesenchymal/epithelial induction, mediated by retinoic acid (RA), FGF8, sonic hedgehog (shh), and the BMPs, defines patterning, morphogenesis, and differentiation. Neuronal differentiation in the olfactory epithelium and directed growth of axons in the nascent olfactory nerve depend critically upon this inductive interaction. When RA, FGF8, shh, or BMP signaling is disrupted, distinct aspects of olfactory pathway patterning and differentiation are compromised. Thus, a cellular and molecular mechanism that facilitates musculoskeletal and vascular development elsewhere in the embryo has been adapted to guide the differentiation of the olfactory pathway in the developing forebrain.

Animals↗

PubMed1999

Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin.

Ventral midline cells in the neural tube have distinct properties at different rostrocaudal levels, apparently in response to differential signalling by axial mesoderm. Floor plate cells are induced by sonic hedgehog (SHH) secreted from the notochord whereas ventral midline cells of the rostral diencephalon (RDVM cells) appear to be induced by the dual actions of SHH and bone morphogenetic protein 7 (BMP7) from prechordal mesoderm. We have examined the cellular and molecular events that govern the program of differentiation of RDVM cells under the influence of the axial mesoderm. By fate mapping, we show that prospective RDVM cells migrate rostrally within the neural plate, passing over rostral notochord before establishing register with prechordal mesoderm at stage 7. Despite the co-expression of SHH and BMP7 by rostral notochord, prospective RDVM cells appear to be specified initially as caudal ventral midline neurectodermal cells and to acquire RDVM properties only at stage 7. We provide evidence that the signalling properties of axial mesoderm over this period are regulated by the BMP antagonist, chordin. Chordin is expressed throughout the axial mesoderm as it extends, but is downregulated in prechordal mesoderm coincident with the onset of RDVM cell differentiation. Addition of chordin to conjugate explant cultures of prechordal mesoderm and neural tissue prevents the rostralization of ventral midline cells by prechordal mesoderm. Chordin may thus act to refine the patterning of the ventral midline along the rostrocaudal axis.

Animals↗

PubMed1997

Linking Frizzled and Wnt signaling in Drosophila development.

Drosophila Frizzled-2 (Dfz2) has been identified as a putative fly Wingless (Wg) receptor. Although Dfz2 shows significant homology with Fz, a protein that operates in the mechanisms that establish planar polarity in Drosophila epithelia, any clear evidence for an involvement by Fz in a Wnt signaling pathway has hitherto been absent. Here we describe the planar polarity phenotypes of loss-of-function and overexpression of Fz in the developing Drosophila eye and find it almost identical to the loss-of-function or overexpression of Dishevelled (Dsh - a protein operating in Wnt second messenger systems). In addition, we show that overexpression of Shaggy (Sgg - another component of the Wnt pathway) in the eye also causes a phenotype similar to Fz and Dsh. To test further the link between planar polarity and Wnt signaling we misexpressed Wg in the developing eye and found it had a potent polarizing effect in the retinal epithelium. Since the overexpression of Fz in the developing eye gave a phenotype consistent with activating the Wnt pathway, we tested overexpression of Fz in the developing embryonic ectoderm and found that it phenocopied overexpression of Wg. To check that Fz was indeed able to activate a Wnt pathway we overexpressed it in Drosophila tissue culture cells and observed the characteristic phosphorylation of Dsh that occurs in response to Wnt signaling. Taken together our results significantly strengthen the case for Fz acting in a Wnt signaling pathway in Drosophila.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord.

The differentiation of distinct cell types in the ventral neural tube depends on local inductive signals from the notochord. We have isolated a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh) from zebrafish and rat, termed vhh-1. vhh-1 is expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme. Each of these cell groups has floor plate inducing activity, suggesting that the vhh-1 gene may encode a floor plate-inducing molecule. Widespread expression of rat vhh-1 in frog embryos leads to ectopic floor plate differentiation in the neural tube. In vitro tests for the signaling functions of vhh-1 demonstrate that COS cells expressing the rat vhh-1 gene induce floor plate and motor neuron differentiation in neural plate explants. vhh-1 may, therefore, contribute to the floor plate and motor neuron inducing activities of the notochord.

Amino Acid Sequence↗

PubMed1994

Drosophila hedgehog acts as a morphogen in cellular patterning.

The patterning of cell types in embryogenesis is specified by signals emanating from specialized organizer regions. We demonstrate that engrailed-expressing cells in the Drosophila epidermis have organizer properties. These cells influence the pattern of cell type differentiation across the segment. We show that this function is mediated by the hedgehog (hh) gene. The results of modulating the levels of hh in the embryo suggest that hh acts as a morphogen, specifying distinct cell fates by a concentration-dependent mechanism. We present a model that integrates the role of hh with that of the wingless signal in establishing the segmental array of cell type diversity.

Animals↗

PubMed1994

The making of a maggot: patterning the Drosophila embryonic epidermis.

Cell fates are instructed by signals emitted from specialized cell populations called organizers. The study of epidermal patterning in Drosophila is contributing novel insights concerning the establishment and action of such organizers. Juxtaposed rows of cells express either the wingless or hedgehog signaling molecules and thereby act as organizers of segment pattern. These signals mediate a mutually re-enforcing interaction between the two rows of cells to sustain organizer function. In a distinct and subsequent phase, wingless and hedgehog act to specify the fates of cells.

Animals↗

PubMed1991

Multiple modes of engrailed regulation in the progression towards cell fate determination.

The engrailed gene product of Drosophila specifies the fate of a subset of cells in each segment. Our studies of engrailed regulation suggest that fate determination is an elaborate, multistep process. At the time in embryogenesis when the engrailed-dependent cell fate is probably determined, four modes of control act in an overlapping progression to govern engrailed expression. After activation by pair-rule genes, both an extracellular signal, wingless, and autoregulation are required for engrailed expression. Autoregulation graduates to wingless independence, but is transient, and is superseded by an engrailed-independent mode of maintenance.

Animals↗

PubMed1990

Molecular and cellular interactions responsible for intrasegmental patterning during Drosophila embryogenesis.

The elaboration of pattern within insect segments is a well-studied example of cellular patterning during development. This process requires that each cell develop appropriately for its position. Experimental embryology suggests that intercellular communication plays a key role in imparting positional information to cells. Drosophila genetics has identified numerous genes whose activity is required for patterning within segments, and whose molecular genetic analyses suggest they constitute and control cell communication circuits. Particular genes are expressed or required by cells that will follow distinct developmental pathways, and some appear to confer or interpret intercellular signals. Other patterning genes are ubiquitously required and may provide the machinery through which the signals are transmitted.

Animals↗

PubMed1983

DNA sequence changes in an upstream DNase I-hypersensitive region are correlated with reduced gene expression.

Previous experiments have identified a region that is required for the expression of the Drosophila glue protein gene Sgs-4 and is located 300-500 base pairs upstream from the structural gene. The chromatin in this region changes conformation and becomes hypersensitive to DNase I digestion when the gene becomes active, a change that apparently induces additional conformational changes near the site of transcription initiation. To learn more about the DNA sequence requirements for the function of this region, we analyzed three naturally occurring Sgs-4 under-producers. In two of these strains, a single base pair change within the hypersensitive region is correlated with a 50% reduction in the amount of Sgs-4 RNA produced. Another strain, which has multiple 5' lesions, is severely reduced in Sgs-4 expression and in the DNase hypersensitivity of the upstream region. Several of the sequence changes in this extreme underproducer lie near hypersensitive sites, suggesting that they inhibit the appearance of the normal DNase hypersensitive conformation.

Animals↗

PubMedDate not supplied

Tunga penetrans. A case report and review of the literature.

Tungiasis is an infection caused by infestation of Tunga Penetrans into the epidermis. Although, at the moment, presentation of this condition seems rare in Europe and Northern America, tungiasis is highly endemic in other parts of the world. We describe a case of Tunga Penetrans infection in the foot of a 22-year old Dutch female returning from Kenya, and present a review of the literature. Now that intercontinental travel is increasing, physicians in other parts of the world will be expected to recognize and treat this exotic infection. Knowledge of human tungiasis is mandatory in order to recognize the symptoms, achieve correct diagnosis and ensure adequate medical treatment to our patients.

Adult↗