Showing papers by "David A. Jackson published in 2001"
TL;DR: The occurrence and biological significance of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice are established and VEGF-C is identified as a molecular link between tumor lymphang iogenesis and metastasis.
Abstract: Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (lymphangiogenesis) and the presence of intratumoral lymphatic vessels have been controversial. Using a novel marker for lymphatic endothelium, LYVE-1, we demonstrate here the occurrence of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice. Vascular endothelial growth factor (VEGF)-C overexpression in breast cancer cells potently increased intratumoral lymphangiogenesis, resulting in significantly enhanced metastasis to regional lymph nodes and to lungs. The degree of tumor lymphangiogenesis was highly correlated with the extent of lymph node and lung metastases. These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis.
1,671 citations
TL;DR: It is demonstrated that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread and could be blocked with an antibody specific for V EGF-D.
Abstract: Metastasis to local lymph nodes via the lymphatic vessels is a common step in the spread of solid tumors. To investigate the molecular mechanisms underlying the spread of cancer by the lymphatics, we examined the ability of vascular endothelial growth factor (VEGF)-D, a ligand for the lymphatic growth factor receptor VEGFR-3/Flt-4, to induce formation of lymphatics in a mouse tumor model. Staining with markers specific for lymphatic endothelium demonstrated that VEGF-D induced the formation of lymphatics within tumors. Moreover, expression of VEGF-D in tumor cells led to spread of the tumor to lymph nodes, whereas expression of VEGF, an angiogenic growth factor which activates VEGFR-2 but not VEGFR-3, did not. VEGF-D also promoted tumor angiogenesis and growth. Lymphatic spread induced by VEGF-D could be blocked with an antibody specific for VEGF-D. This study demonstrates that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread.
1,203 citations
TL;DR: It is demonstrated that VEGF‐C‐induced lymphangiogenesis mediates tumour cell dissemination and the formation of lymph node metastases.
Abstract: Metastasis is a frequent and lethal complication of cancer. Vascular endothelial growth factor-C (VEGF-C) is a recently described lymphangiogenic factor. Increased expression of VEGF-C in primary tumours correlates with dissemination of tumour cells to regional lymph nodes. However, a direct role for VEGF-C in tumour lymphangiogenesis and subsequent metastasis has yet to be demonstrated. Here we report the establishment of transgenic mice in which VEGF-C expression, driven by the rat insulin promoter (Rip), is targeted to beta-cells of the endocrine pancreas. In contrast to wild-type mice, which lack peri-insular lymphatics, RipVEGF-C transgenics develop an extensive network of lymphatics around the islets of Langerhans. These mice were crossed with Rip1Tag2 mice, which develop pancreatic beta-cell tumours that are neither lymphangiogenic nor metastatic. Double-transgenic mice formed tumours surrounded by well developed lymphatics, which frequently contained tumour cell masses of beta-cell origin. These mice frequently developed pancreatic lymph node metastases. Our findings demonstrate that VEGF-C-induced lymphangiogenesis mediates tumour cell dissemination and the formation of lymph node metastases.
942 citations
TL;DR: It is shown that a soluble form of VEGFR-3 is a potent inhibitor of Vascular endothelial growth factor (VEGF)-C and VEGF-D signaling, and when expressed in the skin of transgenic mice, it inhibits fetal lymphangiogenesis and induces a regression of already formed lymphatic vessels, though the blood vasculature remains normal.
Abstract: The lymphatic vasculature transports extravasated tissue fluid, macromolecules and cells back into the blood circulation. Recent reports have focused on the molecular mechanisms regulating the lymphatic vessels. Vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to stimulate lymphangiogenesis and their receptor, VEGFR-3, has been linked to human hereditary lymphedema. Here we show that a soluble form of VEGFR-3 is a potent inhibitor of VEGF-C/VEGF-D signaling, and when expressed in the skin of transgenic mice, it inhibits fetal lymphangiogenesis and induces a regression of already formed lymphatic vessels, though the blood vasculature remains normal. Transgenic mice develop a lymphedema-like phenotype characterized by swelling of feet, edema and dermal fibrosis. They survive the neonatal period in spite of a virtually complete lack of lymphatic vessels in several tissues, and later show regeneration of the lymphatic vasculature, indicating that induction of lymphatic regeneration may also be possible in humans.
769 citations
TL;DR: It is shown that mouse LYVE-1 both binds and internalizes hyaluronan in transfected 293T fibroblasts in vitro and demonstrated using immunoelectron microscopy that it is distributed equally among the luminal and abluminal surfaces of lymphatic vessels in vivo.
452 citations
TL;DR: The recent discovery of a new HA receptor, LYVE-1 (lymphatic vessel endothelial HA receptor), expressed predominantly in lymphatic vessels, highlights another aspect of HA biology: its continuous transit through the lymphatic system and its potential involvement in lymph node homing by CD44+ leukocytes and tumor cells.
322 citations
TL;DR: Findings provide evidence that the CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms.
Abstract: The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To understand how this regulation is achieved, we isolated a novel mutant of maize, fasciated ear2 (fea2), which causes a massive overproliferation of the ear inflorescence meristem and a more modest effect on floral meristem size and organ number. We cloned the fea2 gene using transposon tagging, and it encodes a membrane localized leucine-rich repeat receptor-like protein that is most closely related to CLAVATA2 from Arabidopsis. These findings provide evidence that the CLAVATA pathway for regulation of meristem size is functionally conserved throughout the angiosperms. A possible connection of fea2 to the control of crop yields is discussed.
293 citations
TL;DR: The expression pattern of human sialoadhesin was found to be similar to that of the mouse receptor, being absent from monocytes and other peripheral blood leukocytes, but expressed strongly by tissue macrophages in the spleen, lymph node, bone marrow, liver, colon, and lungs.
289 citations
TL;DR: VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis, which has significant implications in the planning of gene therapy using these growth factors.
Abstract: — The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VEGFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57Bl6 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet–endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors.
237 citations
TL;DR: It was concluded that with the above procedure, OCT could quantitatively monitor the mineral changes in a caries lesion on a longitudinal basis.
Abstract: A method for quantitative assessment of dental caries using optical coherence tomography (OCT) was demonstrated. Development of caries lesions in 15 bovine teeth, by demineralization in acidic buffer solution, was quantitatively assessed daily for 3 days, using OCT. An OCT system which can collect A-scans (depth versus reflectivity curve), B-scans (longitudinal images) and C-scans (transverse images at constant depth) was used. While the B- and C-scans qualitatively described the lesion detected, the A-scan which showed the depth (mm) resolved reflectivity (dB) of the tooth tissue was used for the quantitative analysis. After a simple normalization procedure to determine the actual depth the light travelled into the tooth tissue, the area (R) under the A-scan was quantified as a measure of the degree of reflectivity of the tissue. The result showed that R (dB mm) decreased with increasing demineralization time. The percentage reflectivity loss (R%) in demineralized tissue, which related to the amount of mineral loss, was also calculated, and it was observed that R% increased with increasing demineralization time. It was concluded that with the above procedure, OCT could quantitatively monitor the mineral changes in a caries lesion on a longitudinal basis.
132 citations
Journal Article•
TL;DR: In this article, the authors show that with suitable optics in the arm of a Michelson interferometer, orthogonal Galvo-scanning mirrors build a sampling function in the form of Newton rings when the two interferometers arms are matched.
Abstract: We show that, with suitable optics in the arm of a Michelson interferometer, orthogonal galvo-scanning mirrors build a sampling function in the form of Newton rings when the two interferometer arms are matched. Using a low-coherence source, one can obtain transversal depth-resolved images. A fast display procedure using a storage oscilloscope was devised based on this method.
01 Jan 2001
TL;DR: In this paper, the authors reported a search for the flavor-changing neutral current decay with the Belle detector at the KEKB storage ring, and observed the decay process with a branching fraction.
Abstract: We report a search for the flavor-changing neutral current decay $B\ensuremath{\rightarrow}{K}^{(*)}{l}^{+}{l}^{\ensuremath{-}}$ using a $29.1{\mathrm{fb}}^{\ensuremath{-}1}$ data sample accumulated at the $\ensuremath{\Upsilon}(4S)$ resonance with the Belle detector at the KEKB ${e}^{+}{e}^{\ensuremath{-}}$ storage ring. We observe the decay process $B\ensuremath{\rightarrow}{\mathrm{Kl}}^{+}{l}^{\ensuremath{-}}(l\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}e,\ensuremath{\mu})$, for the first time, with a branching fraction of $B(B\ensuremath{\rightarrow}{\mathrm{Kl}}^{+}{l}^{\ensuremath{-}})\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}({0.75}_{\ensuremath{-}0.21}^{+0.25}\ifmmode\pm\else\textpm\fi{}0.09)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}$.
Journal Article•
TL;DR: The penalty in terms of performance reduction introduced into the optical coherence tomograph when integrated with a confocal receiver and the signal-to-noise ratio analysis for the different confocal Receiver configurations are presented.
Abstract: A fiberized optical coherence tomographic (OCT) system is modified to produce a confocal image similar to that produced by a scanning laser ophthalmoscope. Two possible configurations are presented, one that can deliver either an OCT or a confocal image and another that is capable of producing both the OCT and the confocal images simultaneously. Using the later configuration, we demonstrate such images from the retina in the living eye. The penalty in terms of performance reduction introduced into the optical coherence tomograph when integrated with a confocal receiver and the signal-to-noise ratio analysis for the different confocal receiver configurations are presented.
TL;DR: The application of en-face OCT imaging to produce topography and perform area and volume measurements of the optic nerve is illustrated for the first time.
Abstract: A special imaging instrument was developed which can acquire optical coherence tomography (OCT) en-face images from the eye fundus, and simultaneously a confocal image. Using this instrument we illustrate for the first time the application of en-face OCT imaging to produce topography and perform area and volume measurements of the optic nerve. The procedure is compared with the topography, area and volume measurements using a confocal scanning laser ophthalmoscope.
Journal Article•
TL;DR: Novel markers for lymphatic endothelial cells have been identified and their availability has revolutionized research in this field and their use to study tumour lymphangiogenesis is reviewed.
Abstract: The capacity of malignant tumours to metastasize to distant tissues presents a huge problem for the treatment of cancers using conventional surgical and cytotoxic drug therapies. One of the main routes for tumour spread is via the lymphatic vessels, an important conduit for tumours such as breast, lung and gastrointestinal tract that frequently colonize regional lymph nodes. In comparison with the vasculature however, little is known about the biology of tumour lymphatics, tumour lymphangiogenesis or the mechanisms that regulate entry and subsequent migration of tumour cells within lymphatic vessels. This situation has persisted because of the lack of specific molecular markers with which to visualize even normal lymphatics within tissues or to isolate lymphatic endothelial cells for in vitro experimental analysis. Just recently however, novel markers for lymphatic endothelial cells have been identified and their availability has revolutionized research in this field. In this article we highlight the main characteristics of these markers and review recent progress in their use to study tumour lymphangiogenesis.
01 Jan 2001
TL;DR: In this paper, the authors studied radiative B meson decays into higher kaonic resonances decaying into a two-body or three-body final state, using a data sample of 21.3 fb$^{-1}$ recorded at the $Upsilon(4S)$ resonance with the Belle detector at KEKB.
Abstract: We have studied radiative B meson decays into higher kaonic resonances decaying into a two-body or three-body final state, using a data sample of 21.3 fb$^{-1}$ recorded at the $\Upsilon(4S)$ resonance with the Belle detector at KEKB. For the two-body final state, we extract the $B \to K_2^{*}(1430)^0 \gamma$ component from an analysis of the helicity angle distribution, and obtain ${\cal B}(B^0 \to K_2^{*}(1430)^0 \gamma) = (1.26\pm 0.66\pm 0.10)\times 10^{-5}$. For the three-body final state, we observe a $B \to K\pi\pi\gamma$ signal that is consistent with a mixture of $B \to K^* \pi \gamma$ and $B \to K \rho \gamma$. This is the first time that $B \to K^* \pi \gamma$ and $B \to K \rho \gamma$ have been observed separately. We find their branching fractions to be ${\cal B}(B \to K^* \pi \gamma; M_{K^*\pi}<2.0 GeV/c^2) = (5.6\pm 1.1\pm 0.9)\times 10^{-5}$ and ${\cal B}(B \to K \rho \gamma; M_{K\rho} < 2.0 GeV/c^2) = (6.5\pm 1.7^{+1.1}_{1.2})\times 10^{-5}$, respectively.
TL;DR: In this paper, a remote fiber-ized low-coherence interferometric sensor has been used to measure the refractive index of air, which can be used for industrial applications where materials degradation prevents the use of conventional gas and humidity sensors.
Abstract: A remote fiberised low-coherence interferometric sensor has been used to measure the refractive index of air. The relative humidity, temperature, pressure or carbon dioxide content may be determined from the measurement of the refractive index of air if the values of the other parameters are known. The sensor works linearly, for example, over the full range of humidity and does not suffer from aging or hysteresis. This maintenance-free sensor has a relative accuracy of 1.6% with a fast response time. The relative sensitivity of the sensor to changes in the values of the other parameters influencing the refractive index of air has also been deduced. The sensor is designed primarily for industrial applications where conventional electronic sensors cannot be used in environments where materials degradation prevents the use of conventional gas and humidity sensors.
TL;DR: In this paper, a Mach-Zehnder unbalanced LiNbO3 integrated modulator with independent control of the phase of each arm is incorporated into the reference arm of a low coherence interferometer set-up.
TL;DR: Developmental biologists seek to explain the generation of complex three-dimensional organisms from the starting point of a single cell and its genetic complement.
Abstract: Developmental biologists seek to explain the generation of complex three-dimensional organisms from the starting point of a single cell and its genetic complement. During this incredible transformation, different cell fates rarely are specified intrinsically; rather, the fates of individual cells or
TL;DR: In this paper, the series combination of an AOTF and a frequency-modulated MZI was used to achieve a minimum strain resolution of 2.23 ne Hz-1/2 at a frequency of 10 kHz.
Abstract: We report a new concept for interrogating and multiplexing large numbers of fibre Bragg grating sensors for dynamic measurands. The series combination of an AOTF and a frequency-modulated MZI forms the basis of a system, which allows simultaneous interrogation of eight sensors, and near-simultaneous interrogation of 64. A minimum strain resolution of 2.23 ne Hz-1/2 at a frequency of 10 kHz was achieved.
01 Jan 2001
TL;DR: In this article, the series combination of an AOTF and a frequency-modulated MZI was used to achieve a minimum strain resolution of 2,23 ne Hz -1/2 at a frequency of 10 kHz.
Abstract: We report a new concept for interrogating and multiplexing large numbers of fibre Bragg grating sensors for dynamic measurands. The series combination of an AOTF and a frequency-modulated MZI forms the basis of a system, which allows simultaneous interrogation of eight sensors, and near-simultaneous interrogation of 64. A minimum strain resolution of 2,23 ne Hz -1/2 at a frequency of 10 kHz was achieved.
04 May 2001
TL;DR: En face optical coherence tomography (OCT) as mentioned in this paper is OCT in the standard fundus image perspective of the retina, which incorporates all of the cross-sectional information of conventional sagittal (B-scan) OCT but provides a full field view.
Abstract: En face optical coherence tomography (OCT) (face-to-face, from French – opposite) is OCT in the standard fundus image perspective of the retina. It incorporates all of the cross-sectional information of conventional sagittal (B-scan) OCT but provides a full field view. En face is the viewpoint captured by ophthalmoscopes, fundus cameras, fluorescein and ICG angiograms, and microperimetry (Fig. 3.1)
TL;DR: In this article, a fiberoptic system based upon fiber Fabry-Perot strain sensors, capable of measuring deformations and modes of vibration of a composite panel, is presented.
Abstract: A fibre-optic system based upon fibre Fabry-Perot strain sensors, capable of measuring deformations and modes of vibration of a composite panel, is presented. Wavelength-division signal demultiplexing allows for the simultaneous interrogation of the strain sensors.
01 Jan 2001
Patent•
19 Mar 2001
TL;DR: In this paper, a maize gene, gene product, and regulatory regions were used to manipulate meristem growth, inflorescence development and arrangement, and ultimately to improve yield of plants.
Abstract: The invention relates to the isolation and characterization of a novel maize gene (fae2) responsible for meristem proliferation and inflorescence development. The novel gene, gene product, and regulatory regions may be used to manipulate meristem growth, inflorescence development and arrangement, and ultimately to improve yield of plants. The invention includes the novel gene and protein product as well as the use of the same for temporal and spatial expression in transgenic plants to enhance kernel development, alter plant morphology and increase yield in plants.
23 May 2001
TL;DR: In this paper, the authors considered a configuration that allows simultaneous display of the confocal signal and the OCT signal, which requires a separate confocal channel in the system, and discussed the noise sources in the two channels.
Abstract: An OCT system is built around a confocal optical receiver by adding a reference beam to the beam returned from the target tissue to the photodetector. The amount of light collected by the OCT receiver (both signal and background signal) depends on the parameters of the confocal receiver. We are interested in a configuration that allows the simultaneous display of the confocal signal and the OCT signal, which requires a separate confocal channel in the system. In this case, the S/N performance is different in the two channels and depends on the optical configuration used. The paper discusses the noise sources in the two channels. S/N ratios are numerically evaluated for cases of experimental interest. As far as the penetration depth in OCT is concerned, a value of 20 optical depths was considered achievable in previous reports if only the shot noise was considered. We correct this value by taking into account the excess photon noise and the limitations imposed by the safety power limits. Multiple scattering determines an increase in noise via the excess photon noise term.
23 May 2001
TL;DR: It is shown that an instrument with adjustable depth resolution is especially useful for the en-face OCT technology, and images with a similar aspect to those produced by a scanning laser ophthalmoscope can now be obtained in real time using the OCT principle.
Abstract: Two instruments are now available for high depth resolution imaging of the retina. A scanning laser ophthalmoscope is a confocal instruments which can achieve no more than 0.3 mm depth resolution. A longitudinal OCT instrument uses a superluminescent diode which determines a depth resolution better than 20 microns. There is a gap in depth resolution between the two technologies. Therefore, different OCT configurations and low coherence sources are investigated to produce a choice of depth resolutions, and to cover the gap between the old confocal technology and the new OCT imaging method. We show that an instrument with adjustable depth resolution is especially useful for the en-face OCT technology. Such an instrument can bring additional benefits to the investigation process, where different requirements must be met. For instance, a poor depth resolution is required in the process of positioning the patient's eye prior to investigation. A good depth resolution is however necessary when imaging small details inside the eye. The utility of the OCT en-face imaging with adjustable coherence length for diagnostic is illustrated by images taken from the eye of a volunteer. Images with a similar aspect to those produced by a scanning laser ophthalmoscope can now be obtained in real time using the OCT principle.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.