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At least 793 records · Page 44Linked to original sources
PubMed2006

Expression of vascular endothelial growth factor a, matrix metalloproteinase 9 and extravascular matrix patterns in iris and ciliary body melanomas.

PURPOSE: It was the aim of this study to assess the expression of vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase (MMP)-9 and extravascular matrix patterns (EMPs) in iris and ciliary body melanomas and their correlations with histopathologic parameters. METHODS: The study was conducted on 3 iris and 15 ciliary body melanomas. All tumors were subjected to immunohistochemical techniques for VEGF-A and MMP-9 expressions, the presence of EMPs was assessed, and routine paraffin sections were stained with hematoxylin-eosin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration and sclera invasion were analyzed using light microscopy. RESULTS: The mean patient age at the time of treatment was 43 years (range 19-69, median 39.5); 10 (55.6%) patients were males and 8 (44.4%) females. Histopathological cell types were spindle cells in 55.6%, mixed cells in 16.7%, and epithelioid cell types in 27.8% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 66.7 and 72.3% of the tumors, respectively. Microvascular loops and/or networks were seen in 33.4% of the tumors, with the remaining 66.7% of tumors displaying one or more of the other patterns. Metastatic disease developed in only 1 patient during follow-up. Tumor cell type, tumor size, mitotic rate, degree of pigmentation and EMPs were not correlated with metastasis. CONCLUSIONS: This study suggests that VEGF-A and MMP-9 were positive in the majority of iris and ciliary body melanomas. No correlation was found between VEGF-A and MMP-9 immunoreactivity and EMPs and occurrence of metastases in cases of anterior uveal melanoma.

Adult↗
PubMed1995

Lower body temperature in sleeping supine infants.

Night time rectal temperature recordings were made from 103 infants sleeping in their own home in different sleeping positions. In most cases sleeping position was verified by video monitoring throughout the night. In the period before an adult-like night time body temperature pattern appeared there was no significant effect of sleeping position upon night time body temperature, in line with previous reports. Once an adult-like night time temperature pattern appeared, infants sleeping supine reached significantly lower rectal temperatures than those sleeping prone or lateral. Babies sleeping supine moved significantly more during the night and were more likely to uncover their hands and arms. These findings suggest that supine sleepers are in a different physiological condition from those sleeping prone or lateral, which may be associated with their lower vulnerability to sudden unexpected infant death.

Body Temperature↗
PubMed1995

Patterns of failure following total body irradiation and bone marrow transplantation with or without a radiotherapy boost for advanced neuroblastoma.

PURPOSE: To evaluate the patterns of failure and outcome of patients undergoing high-dose chemotherapy, total body irradiation (TBI), and bone marrow transplantation (BMT) for advanced/relapsed pediatric neuroblastoma, with emphasis on the impact of a radiotherapy boost to primary and metastatic sites. METHODS AND MATERIALS: Between May 1986 and June 1993, 26 patients with advanced neuroblastoma underwent high-dose chemotherapy and TBI followed by BMT at our institution. The majority of patients were over the age of 2 years (73%) and were Stage IV at diagnosis (81%). Multiple metastatic sites were involved including bone (17), bone marrow (15), distant nodes (11), liver (5), lung (4) and brain (1). Twenty patients (77%) received cyclophosphamide (50 mg/kg x 4 days) and TBI as consolidation therapy. TBI was delivered to a total dose of 12 Gy given in 2 Gy twice daily (b.i.d.) fractions over the 3 days preceding bone marrow infusion. A local radiotherapy boost of 8-24 Gy was given to 13 out of 26 patients (50%) to the primary and/or metastatic sites immediately prior to or following induction chemotherapy according to physician judgement. Sites not amenable to a radiotherapy boost included the bone marrow, diffuse/bilateral lung involvement, and multiple bone metastases (> four sites). RESULTS: The actuarial overall survival of the 26 patients was 40.4% at 3 and 5 years, with a progression-free survival at 5 years of 38.5%. Six patients died of transplant-related toxicity (23%). The use of cyclophosphamide as high-dose consolidation chemotherapy was significantly better than other multidrug regimens used in terms of overall survival (p < 0.0001) and progression-free survival (p = 0.0004). The presence of liver involvement prior to BMT was a significant adverse prognostic factor by multivariate analysis. Of the 20 patients surviving the transplant, 10 (50%) underwent a local radiotherapy boost. The patterns of failure were as follows: 3 out of 10 "boost" patients failed overall, none in previous (old) sites of disease only, 1 in new sites only, and 2 in old and new sites; 6 out of 10 "no boost" patients failed overall, 4 in old sites only, none in new sites only, and 2 in old and new sites. There was a trend toward improved 5-year progression-free survival in patients surviving the transplant that received a boost (68% vs. 33%, p = 0.24). A failure analysis was also performed for each of the 59 initially involved sites, of which the majority (64%) were amenable to a radiotherapy boost. Overall, there is a trend toward less failure in sites amenable to a radiotherapy boost that were irradiated (1 out of 10) vs. those not irradiated (6 out of 28). Failure in the liver occurred in three out of four of the patients with liver involvement that did not receive boost radiotherapy, whereas all seven patients with distant nodal involvement were controlled without a boost. Long-term sequelae include learning difficulties (2), cataract formation (1), and hearing loss (2). Sequelae attributable to a radiotherapy boost occurred in only one patient who received whole brain radiotherapy and developed a cataract and learning difficulties. CONCLUSION: We have found an actuarial 5-year survival rate of 40.4% for patients with advanced neuroblastoma treated with BMT, which compares favorably with results of other published series. Disease recurrence following BMT was most common in previous sites of disease. The majority (64%) of these sites were amenable to a radiotherapy boost. An analysis of failure suggests that a low-dose radiotherapy boost improves control of these sites.

Adrenal Gland Neoplasms↗
PubMed1999

Getting a-head of the organizer: anterior-posterior patterning of the forebrain.

The molecular mechanisms that drive the development of embryonic tissues are being uncovered rapidly. One such fascinating example is the development of the forebrain, the most anterior part of the nervous system. In this review, we will discuss the mechanisms that induce the formation of the forebrain in multiple vertebrate systems, placing emphasis on a recent article published by Grinblat et al. ((1)) Using zebrafish as a model system, these authors combine elegant embryological manipulations with the use of early markers of the presumptive forebrain, to show that initial induction and patterning of this tissue occurs near the onset of gastrulation. In addition, their results confirm observations made in other systems that planar signals, those traveling in the plane of the ectoderm, are involved in forebrain induction and patterning.

Animals↗
PubMed2004

Early requirement for fgf8 function during hindbrain pattern formation in zebrafish.

Fibroblast growth factor (FGF) signaling is required for normal development of the vertebrate brain, including the isthmus and caudal regions of the hindbrain. Recent work in zebrafish has identified a requirement for the combination of fgf3 and fgf8 functions in specification of rhombomeres 5 and 6 (r5, r6), when evaluated at mid- and late somitogenesis stages. However, when examined earlier in development, during early somitogenesis stages, FGF8 alone is required to initiate r5 and r6 development. Both a mutation in fgf8 and injection of fgf8-targeted antisense morpholino-modified oligonucleotides result in suppression of genes normally expressed in r5 and r6 by the one- to two-somite stage. This expression recovers by the six-somite stage, and we propose that this recovery is a response to activation of fgf3 and to delayed accumulation of fgf8. These data demonstrate an early, nonredundant requirement for fgf8 function in hindbrain patterning.

Animals↗
PubMed2000

The nudel protease of Drosophila is required for eggshell biogenesis in addition to embryonic patterning.

The dorsoventral axis of the Drosophila embryo is defined by a ventral signal that arises within the perivitelline space, an extracellular compartment between the embryo plasma membrane and the vitelline membrane layer of the eggshell. Production of the ventral signal requires four members of the serine protease family, including a large modular protein with a protease domain encoded by the nudel gene. Here we provide evidence that the Nudel protease has an integral role in eggshell biogenesis. Mutations in nudel that disrupt Nudel protease function produce eggs having vitelline membranes that are abnormally permeable to the dye neutral red. Permeability varies among mutant nudel alleles but correlates with levels of Nudel protease catalytic activity and function in embryonic dorsoventral patterning. These mutations also block cross-linking of vitelline membrane proteins that normally occurs upon egg activation, just prior to fertilization. In addition, Nudel protease autoactivation temporally coincides with vitelline membrane cross-linking and can be triggered in mature eggs in vitro by conditions that lead to egg activation. We discuss how the Nudel protease might be involved in both eggshell biogenesis and embryonic patterning.

Animals↗
PubMed2000

Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation.

In the mature thymus, thymocyte maturation depends on interactions with different thymic epithelial subtypes in a three-dimensional thymic architecture. However, the molecular mechanisms that generate these epithelial subtypes are not well understood. Evidence is accumulating that during fetal thymus development, epithelial cells differentiate by successive interactions with differentiating thymocytes. This review presents fetal thymus development as a process of organogenesis, the main function of which is to promote thymic epithelial cell differentiation and the generation of a functional thymic microenvironment. In this model, endoderm-derived epithelial cells are the driving force in generating the thymic primordium, with hematopoietic cells providing later signals that organize and pattern the developing thymus.

Body Patterning↗
PubMed2004

Pattern formation: a focus on notch in butterfly eyespots.

New observations of early and dynamic expression of Notch in developing lepidopteran wings suggests that this signalling pathway may function in defining the central focus that will specify the butterfly eyespot colour pattern.

Animals↗
PubMed2005

Normal patterning of the coronary capillary plexus is dependent on the correct transmural gradient of FGF expression in the myocardium.

The formation of the coronary vessel system is vital for heart development, an essential step of which is the establishment of a capillary plexus that displays a density gradient across the myocardial wall, being higher on the epicardial than the endocardial side. This gradient in capillary plexus formation develops concurrently with transmural gradients of myocardium-derived growth factors, including FGFs. To test the role of the FGF expression gradient in patterning the nascent capillary plexus, an ectopic FGF-over-expressing site was created in the ventricular myocardial wall in the quail embryo via retroviral infection from E2-2.5, thus abolishing the transmural gradient of FGFs. In FGF virus-infected regions of the ventricular myocardium, the capillary density across the transmural axis shifted away from that in control hearts at E7. This FGF-induced change in vessel patterning was more profound at E12, with the middle zone becoming the most vascularized. An up-regulation of FGFR-1 and VEGFR-2 in epicardial and subepicardial cells adjacent to FGF virus-infected myocardium was also detected, indicating a paracrine effect on induction of vascular signaling components in coronary precursors. These results suggest that correct transmural patterning of coronary vessels requires the correct transmural expression of FGF and, therefore, FGF may act as a template for coronary vessel patterning.

Animals↗
PubMed1998

Localized requirements for windbeutel and pipe reveal a dorsoventral prepattern within the follicular epithelium of the Drosophila ovary.

Establishment of dorsoventral polarity within the Drosophila embryo requires extraembryonic positional information generated during oogenesis. The genes windbeutel, pipe, and nudel are required within the somatic follicle cells of the ovary for production of this spatial cue. Using a novel follicle cell marker system, we have directly evaluated the effect of mutant follicle cell clones on the embryonic dorsoventral pattern. We find no spatially localized requirement for nudel activity. In contrast, windbeutel and pipe are required only within a restricted ventral region of the follicular epithelium. This ventral region can determine lateral embryonic cell fates nonautonomously, indicating that spatial information originating ventrally is subsequently refined, perhaps via diffusion, to yield the gradient of positional information that determines the embryonic dorsoventral pattern.

Animals↗
PubMed2000

Elegant hypothesis and inelegant fact in developmental biology.

The relationship between theoretical and experimental approaches to the problem of pattern generation during embryonic development has often been uneasy. This stems at least in part from the different emphases that have typically been used in the two approaches. The spectacular success of modern genetic techniques in uncovering developmental mechanisms has led to a widespread belief that theory is no longer very relevant. However, recent examples of data-driven modelling point to new roles for theoretical approaches in exploring important issues such as the robustness and evolution of pattern-forming mechanisms.

Animals↗
PubMed2002

From head to tail: links between the segmentation clock and antero-posterior patterning of the embryo.

Periodic production of somites along the anteroposterior axis of the vertebrate body involves a molecular oscillator, the 'segmentation clock', which can be visualized through the periodic activation of genes linked to the Notch pathway. Recent findings show that oscillations initiate at gastrula stages and point to a role for FGF signaling in positioning the segmental boundaries. This clock also controls aspects of spatio-temporal Hox gene activation thus ensuring a perfect match between segment boundary position and future regional identity of the somites.

Animals↗
PubMed2003

Vertebrate development: taming the nodal waves.

Recent results have provided evidence that regulatory loops operating in vertebrate embryos between the developmental signalling factors Nodal and Lefty may provide a real example of the kind of reaction-diffusion process long predicted to be a mechanism of pattern formation.

Animals↗
PubMed2006

Transcriptional regulation of Dictyostelium pattern formation.

On starvation, Dictyostelium cells form a terminally differentiated structure, known as the fruiting body, which comprises stalk and spore cells. Their precursors--prestalk and prespore cells--are spatially separated and accessible in a migratory structure known as the slug. This simplicity and manipulability has made Dictyostelium attractive to both experimental and theoretical developmental biologists. However, this outward simplicity conceals a surprising degree of developmental sophistication. Multiple prestalk subtypes are formed and undertake a co-ordinated series of morphogenetic cell movements to generate the fruiting body. This review describes recent advances in understanding the signalling pathways that generate prestalk-cell heterogeneity, focusing on the roles of the prestalk-cell inducer differentiation-inducing factor-1 (DIF-1), the tip inducer cAMP and the transcription factors that mediate their actions; these include signal transducer and activator of transcription (STAT) proteins, basic leucine zipper (bZIP) proteins and a Myb protein of a class previously described only in plants.

Animals↗
PubMed2006

From clusters to stripes: the developmental origins of adult cerebellar compartmentation.

Many aspects of the adult cerebellum are organized into parasagittal stripes, including several types of neurons and prominent afferent and efferent projections. Purkinje cells are the best-studied example of parasagittal organization in the cerebellum and, in particular, zebrin II/aldolase C is the stereotypical molecular marker of Purkinje cell stripe heterogeneity in the adult. Zebrin II is a member of the so-called 'late-onset' class of parasagittal markers, which are first expressed shortly after the birth of the mouse and do not reach maturity until 2-3 weeks postnatal. In contrast, 'early-onset' pattern markers are expressed in ordered Purkinje cell clusters in the embryonic cerebellum but become expressed homogeneously shortly after birth. The approximately 10 day temporal gap between the patterned expression of early and late markers has impeded the identification of putative genealogical relationships between clusters and stripes. This review will describe Purkinje cell patterns and their transitions, and critically discuss the evidence for genealogical relationships between early and late patterns.

Animals↗
PubMed2003

Normal and abnormal dental development.

Teeth are vertebrate organs that arise from complex and progressive interactions between an ectoderm, the oral epithelium and an underlying mesenchyme. During their early development, tooth germs exhibit many morphological and molecular similarities with other developing epithelial appendages, such as hair follicles, mammary and salivary glands, lungs, kidneys, etc. The developing mouse tooth germ, which is an experimentally accessible model for organogenesis, provides a powerful tool for elucidating the molecular mechanisms that control the development of these organs. Dentition patterning also provides a unique model for understanding how different shapes of teeth arise in different regions of the jaws. We review here the main signalling networks mediating the epithelial-mesenchymal interactions involved in tooth morphogenesis and patterning.

Animals↗
PubMed2006

Signal dynamics in Sonic hedgehog tissue patterning.

During development, secreted signaling factors, called morphogens, instruct cells to adopt specific mature phenotypes. However, the mechanisms that morphogen systems employ to establish a precise concentration gradient for patterning tissue architecture are highly complex and are typically analyzed only at long times after secretion (i.e. steady state). We have developed a theoretical model that analyzes dynamically how the intricate transport and signal transduction mechanisms of a model morphogen, Sonic hedgehog (Shh), cooperate in modular fashion to regulate tissue patterning in the neural tube. Consistent with numerous recent studies, the model elucidates how the dynamics of gradient formation can be a key determinant of cell response. In addition, this work yields several novel insights into how different transport mechanisms or ;modules' control pattern formation. The model predicts that slowing the transport of a morphogen, such as by lipid modification of the ligand Shh, by ligand binding to proteoglycans, or by the moderate upregulation of dedicated transport molecules like Dispatched, can actually increase the signaling range of the morphogen by concentrating it near the secretion source. Furthermore, several transcriptional targets of Shh, such as Patched and Hedgehog-interacting protein, significantly limit its signaling range by slowing transport and promoting ligand degradation. This modeling approach elucidates how individual modular elements that operate dynamically at various times during patterning can shape a tissue pattern.

Animals↗
PubMed1977

Proportional regulation of body form and cortical organelle pattern in the ciliate Dileptus.

Morphometric and ultrastructural studies of shape and pattern regulation were performed on Dileptus anser. In this ciliate 2 body regions can be distinguished: proboscis and trunk. When a large portion of the trunk is excised, shape regulation occurs and the proper proboscis/trunk ratio is restored through elongation of the remnant of the trunk and shortening of the proboscis. When there is nothing but proboscis left, the trunk is formed from the proximal portion of proboscis and again the right proportion is restored. Regulation of the ciliary pattern is based mainly on resorption of some ciliary elements. The resorption of somatic ciliature is especially intense within narrowing regions, where otherwise overcrowding of cilia would occur. The resorption of oral ciliature was found to occur within an area located at the apex of the proboscis. Oral structures when damaged by cutting may be repaired in situ. Changes in the microfibrillar system of the cell were found during regulation of shape of the posterior region of the cell, as well as during regulation of size of oral structures. Regulatory processes in Dileptus are compared to those known for other ciliates, and possible differences between the regulation of shape and the regulation of pattern are discussed.

Animals↗