Showing papers by "David A. Jackson published in 2005"
TL;DR: In vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin, which suggests a new mechanism of lymphangiogenesis.
Abstract: In the inflamed cornea, there is a parallel outgrowth of blood and lymphatic vessels into the normally avascular cornea. We tested whether adaptive and/or innate immune cells were actively involved in the genesis of new lymphatic vessels. Our results indicate that innate immune cells (CD11b+ macrophages, but not CD11c+ dendritic cells) physically contributed to lymphangiogenesis under pathological conditions and that bone marrow–derived CD11b+ macrophages expressed lymphatic endothelial markers such as LYVE-1 and Prox-1 under inflamed conditions in the corneal stromata of mice. Furthermore, blood vascular endothelial cells that expressed the Tie2 promoter did not contribute to newly formed lymphatic vessels under inflamed conditions. Our in vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin. The novel finding that CD11b+ macrophages are critical for the development of inflammation-dependent lymphangiogenesis in the eye suggests a new mechanism of lymphangiogenesis.
662 citations
TL;DR: Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied, and this work identifies the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers.
Abstract: The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers.
579 citations
TL;DR: It is suggested that when lymphangiogenesis is impaired, airway inflammation may lead to bronchial lymphedema and exaggerated airflow obstruction, and Correction of defective lymphang iogenesis may benefit the treatment of asthma and other inflammatory airway diseases.
Abstract: Edema occurs in asthma and other inflammatory diseases when the rate of plasma leakage from blood vessels exceeds the drainage through lymphatic vessels and other routes. It is unclear to what extent lymphatic vessels grow to compensate for increased leakage during inflammation and what drives the lymphangiogenesis that does occur. We addressed these issues in mouse models of (a) chronic respiratory tract infection with Mycoplasma pulmonis and (b) adenoviral transduction of airway epithelium with VEGF family growth factors. Blood vessel remodeling and lymphangiogenesis were both robust in infected airways. Inhibition of VEGFR-3 signaling completely prevented the growth of lymphatic vessels but not blood vessels. Lack of lymphatic growth exaggerated mucosal edema and reduced the hypertrophy of draining lymph nodes. Airway dendritic cells, macrophages, neutrophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D. Adenoviral delivery of either VEGF-C or VEGF-D evoked lymphangiogenesis without angiogenesis, whereas adenoviral VEGF had the opposite effect. After antibiotic treatment of the infection, inflammation and remodeling of blood vessels quickly subsided, but lymphatic vessels persisted. Together, these findings suggest that when lymphangiogenesis is impaired, airway inflammation may lead to bronchial lymphedema and exaggerated airflow obstruction. Correction of defective lymphangiogenesis may benefit the treatment of asthma and other inflammatory airway diseases.
566 citations
TL;DR: Patients undergoing a surgical procedure would be expected to derive net benefit from a mechanical compression method of thromboprophylaxis, irrespective of their absolute risk of venous thromboembolism.
Abstract: Objectives The objectives of this study were to assess the benefits in terms of reductions in the risks of deep vein thrombosis (DVT) and of pulmonary embolism (PE), and hazards in terms of major bleeding, of: (i) mechanical compression (graduated compression stockings, intermittent pneumatic compression, footpumps); (ii) oral anticoagulants; (iii) dextran; and (iv) regional anaesthesia (as an alternative to general anaesthesia) in surgical and medical patients. Search strategy The strategy involved a systematic search of electronic databases (MEDLINE, EMBASE, BIOSIS, Derwent), search of the Antithrombotic Trialists’ Collaboration database, contact with trialists and manufacturers, and scrutiny of bibliographies of identified papers and reviews of thromboprophylaxis. Selection criteria Properly randomised trials were selected, including those reported in a non-English language, with at least one unconfounded comparison of the effect of one of the methods under review versus control, or a direct comparison between different versions of a method, or a direct comparison between a pharmacological agent (dextran or an oral anticoagulant) and low molecular weight or unfractionated heparin. Trials were included only if systematic assessment of DVT by radiological methods was planned. Data collection and analysis All trials identified as fitting the selection criteria were independently assessed by at least two review authors for methodological quality and the numbers of patients with primary and secondary outcomes were recorded. The primary outcomes were DVT, PE and major bleeding events, and proximal venous thrombosis (PVT) and fatal PE were secondary outcomes. Trials were subdivided into those that had assessed a method as the only means of thromboprophylaxis (‘monotherapy’) and those that had assessed the effects of adding a method to another form of thromboprophylaxis (‘adjunctive therapy’). Main results Mechanical compression methods reduced the risk of DVT by about two-thirds when used as monotherapy and by about half when added to a pharmacological method. These benefits were similar irrespective of the particular method used (graduated compression stockings, intermittent pneumatic compression or footpumps) and similar in each of the surgical groups studied. Mechanical methods reduced the risk of PVT by about half and the risk of PE by two-fifths. Oral anticoagulants, when used as monotherapy, reduced the risk of DVT and of PVT by about half, and this protective effect appeared similar in each of the surgical groups studied. There was an apparently large four-fifths reduction in the role of PE, but not only was the magnitude of this reduction statistically uncertain, but also pulmonary embolism was reported by a minority of trials, so it may be subject to selection bias. Oral anticoagulant regimens approximately doubled the risk of major bleeding. Oral anticoagulant regimens appeared less effective at preventing DVT than heparin regimens [64% (standard error [SE] 8) greater risk of DVT], although were associated with less major bleeding [35% (10) risk reduction for major bleeds]. Dextran reduced the risk of DVT and of PVT by about half, again irrespective of the type of surgery, but too few studies had reported PE to provide reliable estimates of effect on this outcome. Dextran appeared to be less effective at preventing DVT than the heparin regimens studied. Dextran was associated with an increased risk of bleeding, but too few bleeds had occurred for the size of this excess risk to be estimated reliably. Compared with general anaesthesia, regional anaesthesia reduced the risk of DVT by about half, and this benefit appeared similar in each of the surgical settings studied. Regional anaesthesia was associated with less major bleeding than general anaesthesia. Conclusion In the absence of a clear contraindication (such as severe peripheral arterial disease), patients undergoing a surgical procedure would be expected to derive net benefit from a mechanical compression method of thromboprophylaxis (such as graduated compression stockings), irrespective of their absolute risk of venous thromboembolism. Patients who are considered to be at particularly high risk of venous thromboembolism may also benefit from a pharmacological thromboprophylactic agent, but since oral anticoagulant and dextran regimens appear less effective at preventing DVT than standard low-dose unfractionated heparin or low molecular weight heparin regimens, they may be less suitable for patients at high risk of venous thromboembolism, even though they are associated with less bleeding. Whenever feasible, the use of regional anaesthesia as an alternative to general anaesthesia may also provide additional protection against venous thromboembolism. There is little information on the prevention of venous thromboembolism among high-risk medical patients (such as those with stroke), so further randomised trials in this area would be helpful.
282 citations
TL;DR: The results suggest that td1 functions in the inflorescence to limit meristem size, and suggest that the CLAVATA signaling pathway is conserved in monocots.
Abstract: Development in higher plants depends on the activity of meristems, formative regions that continuously initiate new organs at their flanks. Meristems must maintain a balance between stem cell renewal and organ initiation. In fasciated mutants, organ initiation fails to keep pace with meristem proliferation. The thick tassel dwarf1 (td1) mutation of maize affects both male and female inflorescence development. The female inflorescence, which results in the ear, is fasciated, with extra rows of kernels. The male inflorescence, or tassel, shows an increase in spikelet density. Floral meristems are also affected in td1 mutants; for example, male florets have an increase in stamen number. These results suggest that td1 functions in the inflorescence to limit meristem size. In addition, td1 mutants are slightly shorter than normal siblings, indicating that td1 also plays a role in vegetative development. td1 encodes a leucine-rich repeat receptor-like kinase (LRR-RLK) that is a putative ortholog of the Arabidopsis CLAVATA1 protein. These results complement previous work showing that fasciated ear2 encodes a CLAVATA2-like protein, and suggest that the CLAVATA signaling pathway is conserved in monocots. td1 maps in the vicinity of quantitative trait loci that affect seed row number, spikelet density and plant height. We discuss the possible selection pressures on td1 during maize domestication.
262 citations
TL;DR: In a mouse cornea assay, IGF-1 and IGF-2 induce lymphangiogenesis as detected with LYVE-1, a specific marker for lymphatic endothelium, suggesting that these factors are likely to contribute to lymphatic metastasis.
Abstract: Lymphangiogenesis is an important process that contributes to the spread of cancer. Here we show that insulin-like growth factors 1 (IGF-1) and 2 (IGF-2) induce lymphangiogenesis in vivo. In a mouse cornea assay, IGF-1 and IGF-2 induce lymphangiogenesis as detected with LYVE-1, a specific marker for lymphatic endothelium. Interestingly, IGF-1-induced lymphangiogenesis could not be blocked by a soluble vascular endothelial growth factor receptor 3, suggesting that the vascular endothelial growth factor receptor 3-signaling pathway is not required for IGF-induced lymphangiogenesis. In vitro, IGF-1 and IGF-2 significantly stimulated proliferation and migration of primary lymphatic endothelial cells. IGF-1 and IGF-2 induced phosphorylation of intracellular signaling components, such as Akt, Src, and extracellular signal-regulated kinase in lymphatic endothelial cells. Immunohistochemistry, RT-PCR, and Affymetrix GeneChip microarray analysis showed that the receptors for IGFs are present in lymphatic endothelium. Together, our findings suggest that IGFs might act as direct lymphangiogenic factors, although any indirect roles in the induction of lymphangiogenesis cannot be excluded. Because members of the IGF ligand and receptor families are widely expressed in various types of solid tumors, our findings suggest that these factors are likely to contribute to lymphatic metastasis.
231 citations
TL;DR: Progress in elucidating the developmental mechanisms in each of these plants may contribute greatly to the understanding of the evolution of development in higher plants.
Abstract: Inflorescences and flowers in the grass species have characteristic structures that are distinct from those in eudicots. Owing to the availability of genetic tools and their genome sequences, rice and maize have become model plants for the grasses and for the monocots in general. Recent studies have provided much insight into the genetic control of inflorescence and flower development in grasses, especially in rice and maize. Progress in elucidating the developmental mechanisms in each of these plants may contribute greatly to our understanding of the evolution of development in higher plants.
208 citations
TL;DR: It is shown that the KNOX homeodomain (HD) is necessary and sufficient for intercellular trafficking, identifying a novel function for the HD as the minimal sequence required for trafficking of KN1 and its associated mRNA.
Abstract: Cell-to-cell trafficking of regulatory proteins is a novel mechanism for communication during cell fate specification in plants. Although several developmental proteins traffic cell-to-cell, no signals that are both necessary and sufficient for this function in developmental proteins have been described. We developed a novel trafficking assay using trichome rescue in Arabidopsis. Fusion to KNOTTED1 (KN1) conferred gain-of-trafficking function to the cell-autonomous GLABROUS1 (GL1) protein. We show that the KNOX homeodomain (HD) is necessary and sufficient for intercellular trafficking, identifying a novel function for the HD as the minimal sequence required for trafficking of KN1 and its associated mRNA.
161 citations
TL;DR: The results challenge the view that leukocyte trafficking is regulated solely by selective recruitment of pre-existing chemokine receptor-positive cells from peripheral blood, by providing an alternative explanation based on aberrant lymphocyte retention and compromised lymphatic return.
Abstract: According to the current model for tissue-specific homing, specificity is conferred by the selective recruitment of lymphocyte populations from peripheral blood, based on their expression of chemokine and adhesion receptors (endothelial selection). In this study, we provide evidence for an alternative stromal induction mechanism that operates in chronic inflammation. We show that the human rheumatoid synovial microenvironment directly induces functional inflammatory (CCR5 and CXCR3) and constitutive (CCR7 and CXCR4) chemokine receptors on infiltrating CD4(+) T cells. Expression of the corresponding inflammatory chemokine ligands (CCL5 and CXCL11) was confined to stromal areas in the synovium. However, expression of the constitutive ligands (CCL19 and CXCL12) was inappropriately high on both vascular and lymphatic endothelium, suggesting that the vascular to lymphatic chemokine gradient involved in lymphatic recirculation becomes subverted in the rheumatoid synovium. These results challenge the view that leukocyte trafficking is regulated solely by selective recruitment of pre-existing chemokine receptor-positive cells from peripheral blood, by providing an alternative explanation based on aberrant lymphocyte retention and compromised lymphatic return.
112 citations
TL;DR: The dissemination of cancer cells through the lymphatics may occur by invasion of peripheral cancer cells into the adjacent normal lymphatics, or through shunts eventually produced at the invading tumour front as a consequence of active angiogenesis and lymphangiogenesis.
Abstract: Aims/Methods: Normal and malignant pulmonary and endometrial tissues were analysed for lymphatic vessels to assess the process of lymphangiogenesis and its role at these sites, using specific immunostaining for LYVE-1 and the panendothelial marker CD31. Results: Lymphatics were clearly demonstrated in some normal tissues (myometrium, bronchial submucosa, and intestinal submucosa), but not in others (endometrium and alveolar tissue). LYVE-1 positive lymphatic vessels were detected at the tumour periphery of endometrial and lung carcinomas, but not within the main tumour mass. Double staining for LYVE-1 and the MIB1 proliferation marker revealed a higher proliferation index in lymphatic endothelial cells at the invading front of endometrial carcinomas, compared with myometrial areas distal to the tumour. Lung and endometrial carcinomas did not have an intratumorous lymphatic network. Conclusions: Although lymphangiogenesis may occur at the invading tumour front, incorporated lymphatics do not survive. Therefore, the dissemination of cancer cells through the lymphatics may occur by invasion of peripheral cancer cells into the adjacent normal lymphatics, or through shunts eventually produced at the invading tumour front as a consequence of active angiogenesis and lymphangiogenesis.
104 citations
TL;DR: The results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease.
Abstract: The presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the vascular endothelial growth factor-D (VEGF-D), its receptor VEGF-receptor-3 (VEGFR-3) and the lymphatic endothelium-specific hyaluronan receptor LYVE-1 in a panel of 19 primary human ductal pancreatic tumors and 10 normal pancreas specimens. We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D. Compared to normal human pancreas, pancreatic cancer tissue showed overexpression of VEGF-D and VEGFR-3 in conjunction with a high lymphatic vascularization as determined by immunohistochemistry and in situ hybridization. Tumors derived from VEGF-D-overexpressing cells had a higher microvessel density compared to their mock-controls, as determined based on CD31 immunohistochemistry. Importantly, these tumors also revealed a significant induction of intra- and peritumoral lymphatics, as judged from immunohistochemical detection of LYVE-1 expression. This was associated with a significant increase in lymphatic vessel invasion by tumor cells and an increased rate of lymphatic metastases, as indicated by pan-cytokeratin reactive cells in lymph nodes. Our results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease.
TL;DR: An influenza B virus plasmid-based rescue system was used to introduce site-specific mutations, previously observed in neuraminidase (NA) inhibitor-resistant viruses, into the NA protein of six recombinant viruses, which displayed increased resistance to zanamvir, oseltamivir and peramivIR, with certain viruses displaying cross-resistance to all three drugs.
Abstract: Objectives and methods: An influenza B virus plasmid-based rescue system was used to introduce site-specific mutations, previously observed in neuraminidase (NA) inhibitor-resistant viruses, into the NA protein of six recombinant viruses. Three mutations observed only among in vitro selected zanamivir-resistant influenza A mutants were introduced into the B/Beijing/1/87 virus NA protein, to change residue E116 to glycine, alanine or aspartic acid. Residue E116 was also mutated to valine, a mutation found in the clinic among oseltamivir-resistant viruses. An arginine to lysine change at position 291 (292 N2 numbering) mimicked that seen frequently in influenza A N2 clinical isolates resistant to oseltamivir. Similarly, an arginine to lysine change at position 149 (152 in N2 numbering) was made to reproduce the change found in the only reported zanamivir-resistant clinical isolate of influenza B virus. In vitro selection and prolonged treatment in the clinic leads to resistance pathways that require compensatory mutations in the haemagglutinin gene, but these appear not to be important for mutants isolated from immunocompetent patients. The reverse genetics system was therefore used to generate mutants containing only the NA mutation. Results and conclusions: With the exception of a virus containing the E116G mutation, mutant viruses were attenuated to different levels in comparison with wild-type virus. This attenuation was a result of altered NA activity or stability depending on the introduced mutation. Mutant viruses displayed increased resistance to zanamivir, oseltamivir and peramivir, with certain viruses displaying cross-resistance to all three drugs.
TL;DR: Detecting tumor lymphatic vessel proliferation is another step in the understanding of tumor biology, and the targeting of lymphatic growth may be of potential therapeutic benefit in selected patients with head and neck squamous cell carcinoma.
Abstract: Objective To examine the relationship between intratumoral lymphatic vessel density and clinical and pathological variables in patients with head and neck squamous cell carcinoma. Design Archived paraffin-embedded biopsy specimens were sectioned and stained with hematoxylin-eosin and anti–LYVE-1 antibody, a highly specific marker for lymphatic endothelium. Tumor grade, infiltrating margin, inflammatory infiltrate, and percentage of tumor necrosis were noted and lymphatic vessel density measured using Chalkley point counting. Setting Tertiary care center at a university hospital. Patients A total of 168 previously untreated patients with advanced squamous cell carcinoma (73, larynx; 62, oropharynx; and 33, hypopharynx) treated with primary radiation (with or without planned neck dissection) and salvage surgery from 1992 to 1999. Interventions Measurement of intratumoral lymphatic vessel density in pretreatment tissue biopsy specimen. Main Outcome Measures Disease-free and disease-specific survival, tumor occurrence, and nodal status. Results In patients with laryngeal carcinoma there was a significant relationship between the presence of intratumoral lymphatics and nodal metastases at presentation ( P = .02) and poorly differentiated tumor grade ( P = .02). Patients with high lymphatic vessel density also had a significantly worse disease-specific survival ( P = .03). However, this difference was not significant with multivariate analysis. No significant relationship existed between the presence of intratumoral lymphatics and any of the clinical or pathological variables in oropharyngeal and hypopharyngeal carcinoma. Conclusions In this patient sample, the development of intratumoral lymphatics in laryngeal carcinoma, but not in oropharyngeal or hypopharyngeal carcinoma, is associated with a spread of the tumor to regional lymph nodes. Detecting tumor lymphatic vessel proliferation is another step in the understanding of tumor biology, and the targeting of lymphatic growth may be of potential therapeutic benefit in selected patients with head and neck squamous cell carcinoma.
TL;DR: A noninvasive imaging technique was developed to characterize the delivery as well as interstitial transport of a macromolecular agent, albumin-GdDTPA, in the MCF-7 human breast cancer model in vivo, using magnetic resonance imaging.
Abstract: Noninvasive imaging techniques to image and characterize delivery and transport of macromolecules through the extracellular matrix (ECM) and supporting stroma of a tumor are necessary to develop treatments that alter the porosity and integrity of the ECM for improved delivery of therapeutic agents and to understand factors which influence and control delivery, movement, and clearance of macromolecules. In this study, a noninvasive imaging technique was developed to characterize the delivery as well as interstitial transport of a macromolecular agent, albumin-GdDTPA, in the MCF-7 human breast cancer model in vivo, using magnetic resonance imaging. The transport parameters derived included vascular volume, permeability surface area product, macromolecular fluid exudate volume, and drainage and pooling rates. Immunohistochemical staining for the lymphatic endothelial marker LYVE-1 was done to determine the contribution of lymphatics to the macromolecular drainage. Distinct pooling and draining regions were detected in the tumors using magnetic resonance imaging. A few lymphatic vessels positively stained for LYVE-1 were also detected although these were primarily collapsed and tenuous suggesting that lymphatic drainage played a minimal role, and that the bulk of drainage was due to convective transport through the ECM in this tumor model.
TL;DR: In this article, a mouse model of spontaneous secondary lymphangiogenesis in the normally avascular cornea was presented. But the authors did not consider the effect of deletion in the gene encoding the cytoskeletal protein destrin.
Abstract: Lymphangiogenesis, the formation of new lymphatic vessels, is important for tumor metastasis and induction of immunity to peripheral antigens including organ transplants. We herein describe a novel mouse model of spontaneous, secondary lymphangiogenesis in the normally avascular cornea. corn1 mice, which suffer from a deletion in the gene encoding the cytoskeletal protein destrin, develop hemangiogenesis as well as spontaneous outgrowth of LYVE-1+++/CD31+ lymphatic vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is delayed in onset, is less intense, and regresses earlier compared with hemangiogenesis. Moreover, the lymphangiogenesis is preceded only by a mild recruitment of CD45+ inflammatory cells into the cornea. In contrast to mice with inflammation-induced hem- and lymphangiogenesis, corn1 mice do not develop breakdown of the blood-aqueous barrier. Finally, in this novel mouse model, a blocking anti-VEGFR3 antibody significantly inhibited not only lymph- but also hemangiogenesis. In summary, destrin deletion has differential effects on spontaneous hem- and lymphangiogenesis in the normally avascular cornea and represents a novel mouse model to study the mechanisms of lymphangiogenesis and to test the antihem- and antilymphangiogenic properties of known or new antiangiogenic agents.
TL;DR: It is demonstrated that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination.
Abstract: This study was undertaken to determine the highly sensitive method for detecting tumour lymphatic vessels in all the fields of each slide (LV), lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI) and to compare them with other prognostic parameters using immunohistochemical staining with polyclonal (PCAB) and monoclonal antibodies (MCAB) to the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and the pan-endothelial marker factorVIII in a series of 67 human breast cancers. In all LYVE-1-stained sections, LV (some of which contained red blood cells) were frequently found localised in extralobular stroma, dermis, connective tissue stroma and adjacent to artery and vein, but were rare within the intralobular stroma or the tumour body (3/67 cases) or areas of widespread invasion. In contrast small blood vessels were observed in intra- and extralobular stroma in the factor VIII-stained sections. Quantitation of vessel numbers revealed that LYVE-1/PCAB detected a significantly larger number of LV than either H&E or LYVE-1/MCAB (P<0.0001). LYVE-1/PCAB detected LVI in 25/67 cases (37.3%) and their presence was significantly associated with both lymph node metastasis (χ2=4.698, P=0.0248) and unfavourable overall survival (OS) (P=0.0453), while not relapse- free survival (RFS) (P=0.2948). LMVD had no influence for RFS and OS (P=0.4879, P=0.1463, respectively). Our study demonstrates that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination.
TL;DR: eOCT appears to be effective in assessing rat ONH, allowing detailed structural analysis of the multilayered ONH structure, and is suggested as a novel method for the detection of early changes in the ONH in glaucoma.
Abstract: Aim: To investigate en face optical coherence tomography (eOCT) and its use as an effective objective technique for assessing changes in the glaucomatous rat optic nerve head (ONH) in vivo, and compare it with confocal scanning laser ophthalmoscopy (cSLO). Methods: 18 Dark Agouti (DA) rats with surgically induced ocular hypertension were imaged with eOCT and cSLO at regular intervals. Assessment included three dimensional (3D) topographic reconstructions, intensity z-profile plots, a new method of depth analysis to define a “multilayered” structure, and scleral canal measurements, in relation to the degree of intraocular pressure (IOP) exposure. Results: The increased depth resolution of the eOCT compared to the cSLO was apparent in all methods of analysis, with better discrimination of tissue planes. This was validated histologically. eOCT demonstrated several significant changes in imaged rat ONH which correlated with IOP exposure, including the area of ONH (p Conclusion: eOCT appears to be effective in assessing rat ONH, allowing detailed structural analysis of the multilayered ONH structure. As far as the authors are aware, this is the first report of scleral canal expansion in a rat model. They suggest eOCT as a novel method for the detection of early changes in the ONH in glaucoma.
TL;DR: In this article, an extensometer based on fiber Bragg gratings (FBG) was used for the monitoring of the relative displacement between two adjacent buildings with individual foundations located in an earthquake-prone area.
Abstract: We report on an extensometer based on fibre Bragg gratings (FBG) which offers a relatively large and high dynamic range for the monitoring of the relative displacement between two adjacent buildings with individual foundations located in an earthquake-prone area. The sensor consists of a sensing FBG subjected to strain and a reference FBG. The fibre containing the strain-sensing FBG is directly surface mounted onto the walls of both buildings, with the fixations ~1 m apart. A large range of ±20 mm is achieved by desensitization through a tilt of the fibre axis with respect to the displacement vector (~6° away from the normal). The sensor is illuminated by a broadband source (SLD with λ0 = 815 nm) and the reflected signal is monitored directly by a CCD-based optical spectrum analyser. The recorded spectra are curve-fitted to two Gaussian distribution functions on a PC. A precision of 36 µm displacement with an integration time of 3 ms has been achieved.
TL;DR: In this article, the hadronic branching ratios of the Z{sup 0} boson into heavy quarks were measured using a multi-tag technique using the SLC Large Detector experiment at SLAC between 1996 and 1998.
Abstract: We measure the hadronic branching ratios of the Z{sup 0} boson into heavy quarks: R{sub b}={gamma}{sub Z{sup 0}}{sub {yields}}{sub bb}/{gamma}{sub Z{sup 0}}{sub {yields}}{sub hadrons} and R{sub c}={gamma}{sub Z{sup 0}}{sub {yields}}{sub cc}/{gamma}{sub Z{sup 0}}{sub {yields}}{sub hadrons} using a multitag technique. The measurement was performed using about 400 000 hadronic Z{sup 0} events recorded in the SLC Large Detector experiment at SLAC between 1996 and 1998. The small and stable SLAC Linear Collider beam spot and the CCD-based vertex detector were used to reconstruct bottom and charm hadron decay vertices with high efficiency and purity, which enables us to measure most efficiencies from data. We obtain, R{sub b}=0.21604{+-}0.00098(stat.){+-}0.00073(syst.){+-}0.00012(R{sub c}) and, R{sub c}=0.1744{+-}0.0031(stat.){+-}0.0020(syst.){+-}0.0006(R{sub b})
TL;DR: The 1918 'Spanish' flu that killed 20–50 million people has been recreated from its gene sequence and is shown to be a nasty beast.
Abstract: The 1918 'Spanish' flu that killed 20–50 million people has been recreated from its gene sequence. The virus truly is a nasty beast.
Journal Article•
14 Feb 2005
TL;DR: In this paper, a dual OCT system working at 850 nm was devised and demonstrated the capability of the method by simultaneously acquiring images from the optic nerve and fovea of a volunteer.
Abstract: By dividing both the object and reference beam in an OCT interferometer, two independent OCT imaging channels are assembled. The depth scanning proceeds simultaneously in the two OCT channels and from the same range, however a differential optical path difference can be introduced between the two channels. In this way, two simultaneous images are generated where the depth differs in each pixel by the differential optical path difference. A dual OCT system working at 850 nm was devised and we demonstrate the capability of the method by simultaneously acquiring images from the optic nerve and fovea of a volunteer. The configuration devised insures a strict pixel to pixel correspondence between the two images irrespective of the axial eye movements while the depth difference between the corresponding pixels is exactly the differential optical path difference. The images are collected by fast en-face scanning (T-scan) which allows both B-scan and C-scan acquisition.
01 Jan 2005
TL;DR: The intercellular movement of homeodomain proteins, a family of homeotic proteins, can be explained by the recent discovery of cell-to-cell trafficking of proteins or RNAs.
Abstract: Homeotic proteins have pivotal roles during the development of both plant and animals. Many homeotic proteins exert control over cell fate in cells where their genes are not expressed, i.e., in a non-cell autonomous manner. Cell-to-cell communication, which delivers critical information for position-dependent specification of cell fate, is an essential biological process in multicellular organisms. In plants, there are two pathways for intercellular communication that have been identified: the ligand/receptor-mediated apoplastic pathway and the plasmodesmata-mediated symplasmic pathway. Regulatory proteins and RNAs traffic symplasmically via plasmodesmata and play a critical role in intercellular communication. Thus, the non-cell autonomous function of homeotic proteins can be explained by the recent discovery of cell-to-cell trafficking of proteins or RNAs. This article specifically focuses on understanding the intercellular movement of homeodomain proteins, a family of homeotic proteins.
TL;DR: A unique instrument which acquires and displays simultaneously an Optical Coherence Tomography (OCT) and an indocyanine green fluorescence image (ICGF) is reported using a previously described ophthalmic OCT/confocal imaging system.
Abstract: The authors report preliminary clinical results using a unique instrument which acquires and displays simultaneously an Optical Coherence Tomography (OCT) and an indocyanine green fluorescence image (ICGF). The two images are produced by two channels, an OCT and a confocal channel tuned to the ICG fluorescence spectrum. The system is based on our previously described ophthalmic OCT/confocal imaging system, where the same source is used to produce the OCT image and excite fluorescence in the ICG dye. The system is compact and assembled on a chin rest and it enables the clinician to visualise the same area of the eye fundus in terms of both en-face OCT slices and ICG angiograms, displayed side by side. The images are collected by fast T-scanning (en-face) which are then used to build B-scan or C-scan images. We present images of a variety of choroidal neovascular membranes, and lesions suspected of harboring choroidal neovascular membranes.