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G Cox

Publications and source records attributed to G Cox.

At least 37 records · Page 2Linked to original sources
PubMed2001

Computer-generated, three-dimensional reconstruction of histological parallel serial sections displaying microvascular and glandular structures in human endometrium.

This paper describes a technique to develop high-resolution three-dimensional (3D) images of microvasculature structures in curettage, hysterectomy or endometrial resection biopsies using parallel histological serial sections. Employing a labelled streptavidin-biotin-alkaline phosphatase (LSAB(+)) method and visualising by using DAB(+) with the primary antibody, mouse anti human Q-Bend-10, the images were directly digitised from a light microscope into the KS400 Universal Image Processing and Analysis software via a CCD colour camera; binary images of the structures were created and the binary images were exported into VoxBlast 3D rendering software to view still and rotating 3D images on a computer monitor. This in turn enabled hard copies of the full sequence to be printed.

Endometrium↗
PubMed2001

Visualization of meiotic events in intact living anthers by means of two-photon microscopy.

In this paper we describe the application of two-photon microscopy (2 PM) to the study of meiosis in plants. Fresh, unfixed anthers of Agapanthus umbelatus were briefly incubated on a minimal medium containing the DNA fluorophore DAPI. DAPI incorporation took place in about 30 min and nuclei and other DNA-containing organelles kept their fluorescence for more than 24 h. Using PM it was possible to optically section the whole, unfixed anthers to a depth of approximately 200 microm. This was up to the mid sagital section and into the sporogenic tissue. Several meiotic figures were observed with unparalleled resolution. Sequences of nuclear dynamics and division were occasionally observed in the surrounding tissues and epidermal layer of cells. However we could not optimize the procedures up to the level of observing the dynamics of division on the meiotic nuclei as well. We hypothesize that either (1) meiotic cells are sensitive to the reasonably high excitation levels of infrared light needed to attain such penetration in the tissue, or (2) that our incubation procedures are not sufficiently non-invasive for meiosis to remain unperturbed. To the best of our knowledge this is the first report on direct observation of living meiotic cells in plants and establishes the potential of 2 PM for intact organ research.

Indoles↗
PubMed2001

Measurement of thin coatings in the confocal microscope.

The use of the confocal microscope for measurement of the thickness of thin transparent coatings, such as the varnish layer on compact discs, is described. The relationship between true and apparent thickness varies in a non-linear fashion, but intensity profiles show a good correspondence with calculated profiles. This provides the basis of a nomogram for prediction of coating thickness.

Journal Article↗
PubMed2001

A biological staging model for operable non-small cell lung cancer.

BACKGROUND: Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system. Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets. Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC. METHODS: A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken. Immunohistochemical analysis was performed on paraffin embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers. RESULTS: Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)), and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74)) were independent prognostic factors. Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73)) or neither (HR 4.43 (2.29-8.57)) of these markers. EGFR expression correlated with tumour cell MMP-9 expression (p<0.001). Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)). CONCLUSION: Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient. The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.

Adult↗
PubMed2001

Increased detection of interleukin-5 in sputum by addition of protease inhibitors.

The measurement of interleukin (IL)-5 in sputum is problematic, with interfering factors affecting immunoassay. The authors investigated whether sputum proteases could be acting as interfering factors by studying the effect of protease inhibitors (PI) on sputum IL-5 measurement. Induced sputa from 20 subjects with asthma were divided into aliquots, processed with and without protease inhibitors (in low and high concentrations) and the levels of IL-5 (spiked and endogenous) measured by enzyme immunoassay were compared. The concentration of sputum IL-5 was significantly increased by PI, with median (interquartile range) levels processed with no, low and high PI concentrations being 0 (0), 41.8 (75.6) and 66.1 (124.4) pg x mL(-1), respectively. There was also a significant increase in percentage recovery of spiked IL-5. Although high concentrations of PI reduced cell viability, there was no effect on total or differential cell counts and low concentrations of PI had no effect on cell counts or viability. Levels of endogenous interleukin-5 in sputum of asthmatic subjects can be significantly increased by the addition of protease inhibitors, and samples which would be regarded as negative for interleukin-5 without protease inhibitors may instead have considerable amounts of interleukin-5 detected.

Asthma↗
PubMed2001

Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas.

Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheochromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A-->G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34--36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.

Adrenal Gland Neoplasms↗
PubMed2000

Fluorescent pigments in corals are photoprotective.

All reef-forming corals depend on the photosynthesis performed by their algal symbiont, and such corals are therefore restricted to the photic zone. The intensity of light in this zone declines over several orders of magnitude--from high and damaging levels at the surface to extreme shade conditions at the lower limit. The ability of corals to tolerate this range implies effective mechanisms for light acclimation and adaptation. Here we show that the fluorescent pigments (FPs) of corals provide a photobiological system for regulating the light environment of coral host tissue. Previous studies have suggested that under low light, FPs may enhance light availability. We now report that in excessive sunlight FPs are photoprotective; they achieve this by dissipating excess energy at wavelengths of low photosynthetic activity, as well as by reflecting of visible and infrared light by FP-containing chromatophores. We also show that FPs enhance the resistance to mass bleaching of corals during periods of heat stress, which has implications for the effect of environmental stress on the diversity of reef-building corals, such as enhanced survival of a broad range of corals allowing maintenance of habitat diversity.

Animals↗
PubMed2000

Does immunointensity account for the differences in prognostic significance of Bcl-2 expression in non-small cell lung cancer?

Bcl-2 is an oncogenic protein that plays a central role in apoptosis. The association of Bcl-2 expression and prognosis in non-small cell lung cancer (NSCLC) is unclear, with some studies showing improved outcome whilst others show no survival advantage. We evaluated 178 surgically resected NSCLC specimens for Bcl-2 and p53 immunoexpression. Bcl-2 staining was present in 34.9% of cases (weakly staining 24.2%, strongly staining 10.7%), nuclear p53 in 43. 3% and cytoplasmic p53 in 10.7%. There was no association between p53 and survival. Bcl-2 immunoexpression correlated with improved outcome (p=0.04). A sub-group of strongly Bcl-2 staining cases had a poor survival compared to those that stained weakly (p=0.01). The strongly staining cases had a similar survival to negative cases. Immunointensity may therefore account for the disparity in results regarding the prognostic significance of Bcl-2 demonstrated in previous studies.

Adult↗
PubMed2000

A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease.

BACKGROUND: Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. A prospective randomized, controlled trial comparing limited thoracotomy (open lung biopsy) and thoracoscopy for lung biopsy was done. METHODS: Ambulatory patients with a clinical diagnosis of diffuse interstitial lung disease were randomized to thoracoscopy or limited thoracotomy. Data on postoperative pain, narcotic requirements, operating room time, adequacy of biopsy, duration of chest tube drainage, length of hospital stay, spirometry, and complications were collected. RESULTS: A total of 42 randomized patients underwent lung biopsy (thoracoscopy 20, thoracotomy 22). The two study groups were comparable with respect to age, gender, corticosteroid use, and preoperative spirometry. Visual analog scale pain scores were nearly identical in the two groups (p = 0.397). Total morphine dose was 50.8 +/- 27.3 mg in the thoracoscopy group and 52.5 +/- 25.6 mg in the thoracotomy group (p = 0.86). Spirometry (FEV1) values in the two groups were not significantly different on postoperative days 1, 2, 14, and 28 (p = 0.665). Duration of operation was similar in both groups (thoracoscopy 40 +/- 30 minutes, thoracotomy 37 +/- 15 minutes; p = 0.67). The thoracoscopy and thoracotomy groups had equivalent duration of chest tube drainage (thoracoscopy 38 +/- 28 hours, thoracotomy 31 +/- 26 hours; p = 0.47) and length of hospital stay (thoracoscopy 77 +/- 82 hours, thoracotomy 69 +/- 55 hours; p = 0.72). Definitive pathologic diagnoses were made in all patients. CONCLUSIONS: There is no clinical or statistical difference in outcomes for thoracoscopic and thoracotomy approaches. Both thoracoscopy and thoracotomy are acceptable procedures for diagnostic lung biopsy in diffuse interstitial lung disease.

Biopsy↗
PubMed2000

Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer.

BACKGROUND: Microvessel density, an indirect measure of angiogenesis, has been shown to be an independent prognostic marker in many solid tumours including non-small cell lung cancer (NSCLC). Platelets transport and release angiogenic growth factors. Platelets are increasingly likely to adhere to tumour microvessels due to raised expression of platelet-binding proteins and stasis in blood-flow. Increased vascular permeability in tumour microvessels facilitates platelet extravasation into the extracellular matrix. Adherence and extravasation both lead to platelet activation and release of growth factors capable of instigating the angiogenic process. METHODS: A total of 181 patients were identified who underwent resection of stage I-IIIa NSCLC with a post-operative survival >60 days. Patients were followed-up for a minimum of 24 months. Sections from the tumour periphery were stained for the endothelial marker CD34 (Novocastra NCL-END) using standard ABC immunohistochemistry. Chalkley counting was used to assess microvessel density. RESULTS: A pre-operative platelet count greater than the median and above the normal range (>400) was associated with a poor outcome (P=0.01 and P=0.04, respectively). Tumours with an above median and high Chalkley count (upper tertile) had a worse prognosis (P=0.007 and P=0.0006, respectively). There was no association between platelet count and Chalkley count. CONCLUSIONS: Platelet and microvessel counts are both potential prognostic markers for NSCLC. The role of platelets in the angiogenic process needs to be further investigated.

Adult↗
PubMed2000

Angiogenesis and non-small cell lung cancer.

Lung cancer is the commonest cause of cancer death in the western world. Recent evidence suggests that angiogenesis is related to poor prognosis in many solid tumours including non-small cell lung cancer. Angiogenesis is controlled by a complex interaction between growth and apoptotic factors, proteases and adhesion molecules. The angiogenic process may prove a target for novel therapies such as matrix metalloproteinase inhibitors, growth factor antisense RNA, growth factor receptor antagonists and naturally occurring antiangiogenic peptides. These agents may be used alone or in combination with traditional chemotherapy, radiotherapy and surgery.

Angiogenesis Inhibitors↗
PubMed2000

Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

Aged↗
PubMed2000

Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer.

High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1-3, N0-2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P= 0.009 and P= 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r= 0.21; P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P < 0.02) and microvessel density (P < 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC.

Adenocarcinoma↗
PubMed2000

Induced sputum: validity of fluid-phase IL-5 measurement.

BACKGROUND: IL-5 measurement in the fluid phase of induced sputum is considered to be important in the assessment of asthma, but the validity of these measurements is uncertain. OBJECTIVE: We investigated the validity of sputum IL-5 measurements through a series of spiking experiments and examined the effect of dithiothreitol (DTT) on these measurements. METHODS: Induced sputum from 26 asthmatic subjects was spiked with IL-5 and processed, and the percentage of recovery was measured by means of immunoassay. In 6 of the 26 samples the effect of adding albumin to the processing fluids was studied. In 3 separate samples radiolabeled IL-5 was added, and the recovery measured by means of gamma counting and immunoassay were compared. In addition, the effect of DTT on the immunoassay was examined. RESULTS: The mean +/- SD recovery of spiked IL-5 was 26.1% +/- 14.6% measured by means of immunoassay; adding albumin increased the recovery to 47.7% +/- 8.0% (P <.001). The mean recovery measured by means of gamma counting was 84.8% +/- 5.7% (P <.001); adding albumin had no effect on recovery. DTT had no significant effect on IL-5 measurement. CONCLUSION: The validity of IL-5 measurement by means of current methods is poor. The discrepancy in recovery as measured by gamma counting compared with immunoassay suggests that there is a problem with the recognition of IL-5 epitopes by immunoassay in induced sputum. This cannot be attributed to DTT but may be due to other interfering substances present in sputum, such as sputum proteases, soluble receptors, or autoantibodies.

Dithiothreitol↗