Biomedical subjects

T A Martin

Publications and source records attributed to T A Martin.

At least 19 recordsLinked to original sources

PubMed2006

The influence of CD44v3-v10 on adhesion, invasion and MMP-14 expression in prostate cancer cells.

The expression of certain CD44 variants has been linked with metastasis and tumour progression. In particular, high molecular weight forms of CD44 show restricted expression in tumours and may correlate with tumour development and metastasis. In this study, we examined the expression of CD44 variants in prostate cancer cell lines: the invasive PC-3 and DU-145, low invasive LNCaP, and two non-invasive prostate epithelial cell lines. PC-3 prostate cancer cells were transfected with a high molecular weight CD44 variant isoform, CD44v3-v10, isolated from non-invasive prostate epithelial cell lines. These transfected cells (PC-NIVO) were assessed using in vitro invasion, tumour-endothelial, growth, and migration assays. The expression of MMP-14 was examined using SDS-PAGE and Western blot analysis. Transfected PC-3 cells (PC-NIVO) were found to be less adherent to endothelial cells and had significantly reduced invasiveness compared to wild-type PC-3 or control cells. In addition, tumour cell adhesion to endothelial cells and invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. Further investigation revealed a reduction in the expression of MMP-14 in PC-NIVO cells, but not in PC-3 or control cells. In conclusion, non-invasive prostate epithelial cells express a high molecular weight CD44 isoform, CD44v3-v10, which may counteract the standard isoform function of CD44 by reducing adhesion and invasion of endothelium by prostate tumour cells through negation of the MMP-14 function.

Cell Adhesion↗

PubMed2005

National character does not reflect mean personality trait levels in 49 cultures.

Most people hold beliefs about personality characteristics typical of members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth," or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity.

Adolescent↗

PubMed2005

The Coxsackie-adenovirus receptor has elevated expression in human breast cancer.

The Coxsackie-adenovirus receptor (CAR) is the primary site for adenovirus attachment during infection and has been used as a delivery mechanism for gene therapies. However, the expression profile of the receptor in cancer, particularly in clinical breast cancer, is poorly reported. This study evaluated the expression of CAR in human breast cancers. Frozen sections from breast cancer primary tumours (matched tumour n=114 and background n=30) were immunostained with CAR antibody. RNA was reverse transcribed and analysed by quantitative-PCR (Q-PCR). Levels of CAR were analysed against the clinical background, with a median follow-up of 72 months. Staining intensity of CAR was increased within tumour sections compared to background tissue. Q-PCR revealed significantly elevated levels of CAR transcript in breast tumours (32 313+/-7067 mean+/-SE vs. background tissue 11 483+/-7069, P=0.023). CAR expression also increased with grade of tumour. Patients who had tumour metastases also showed elevated levels of CAR expression (metastasis: 61 940+/-22 749 vs. alive and well 29 655+/-8149), however those with local recurrences had reduced levels of CAR. Ductal carcinomas expressed lower levels of CAR compared to tumours of other types. Tumours with nodal involvement were also associated with higher levels of CAR (node positive 2320 median vs. node negative 1077.5). Levels of CAR were significantly correlated with long-term survival over a period of 6 years (P=0.004, univariate analysis). We conclude that CAR expression is elevated in primary breast cancers. This may have a bearing on its use as means of delivery for gene therapy and suggests that further work is necessary to understand this complex molecule.

Adenoviridae↗

PubMed2005

Assessing microvessels and angiogenesis in human breast cancer, using VE-cadherin.

AIMS: Vascular endothelial (VE)-cadherin, also known as cadherin-5 and CD144, is an adhesion molecule uniquely expressed in endothelial cells. We hypothesized that VE-cadherin may be a useful marker for assessing microvessels and angiogenesis in human breast cancer and sought to determine whether a correlation exists between levels of VE-cadherin, angiogenic markers factor VIII and platelet endothelial cell adhesion molecule (PECAM)-1 and patient outcome in breast cancer. METHODS AND RESULTS: Frozen sections from breast cancer primary tumours (tumour n = 114, background n = 30) were immunostained with VE-cadherin, factor VIII and PECAM-1 antibodies and microvessel number was assessed. RNA was reverse transcribed and analysed by quantitative polymerase chain reaction (Q-PCR). VE-cadherin immunostaining showed a significant difference in microvessel number in tumour compared with background. There was no significant difference in the number of microvessels stained with PECAM-1 or factor VIII; there was increased staining of other structures within the sample and higher general background staining. Q-PCR revealed elevated levels of VE-cadherin and PECAM-1 in tumour samples compared with background tissue and in patients with a poor prognosis, as determined by the Nottingham Prognostic Index. There was no difference in levels with factor VIII. Both VE-cadherin and PECAM-1 had significantly reduced expression in lobular compared with ductal carcinomas: there was no difference with factor VIII. CONCLUSION: Higher levels of angiogenic marker molecules in breast cancer may have an association with poor prognosis in patients. Moreover, VE-cadherin appears to be a preferable marker for such analysis.

Antigens, CD↗

PubMed2002

Distribution and expression of CD44 isoforms and Ezrin during prostate cancer-endothelium interaction.

CD44 is a multifunctional cell surface adhesion molecule that has been implicated in tumour cell invasion and metastasis. Many cancer cell types as well as their metastases express high levels of CD44. Furthermore, the expression of certain CD44 variants has been linked with metastasis and tumour progression. It is known that ezrin, a member of the ERM family of proteins, can bind to CD44 and thus raises the possibility that it is involved in cell migration and metastasis. Therefore we examined the expression and distribution of CD44, its co-localisation and translocation with ezrin in prostate cancer cell lines as they interact with endothelial cells. Experimental results indicate prostate cancer cells express multiple CD44 isoforms that co-localise with ezrin in DU-145 and PC-3 prostate cancer cells. Treatment with hepatocyte growth factor (HGF/SF) resulted in up-regulation of CD44 and its co-translocation with ezrin during tumour-endothelial cell interactions. In addition, tumour cell adhesion to endothelial cells and their invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. It is concluded that CD44 and ezrin interact in endothelial cells and that they co-localise in the areas of tumour-endothelial contact. The CD44/ezrin complex plays a pivotal role in the capture and invasion of endothelial cells by prostate cancer cells.

Cytoskeletal Proteins↗

PubMed2001

Prism adaptation of reaching is dependent on the type of visual feedback of hand and target position.

The present study demonstrated that the magnitude of after-effect due to wedge prisms depends on the form of the visual feedback used to represent hand and target position in fast, targeted, transverse reaches. Trained human subjects made reaches with and without prisms in three visuomotor representations (VR): (1) the subject's actual hand and targets (Direct), (2) a real-time video broadcast of hand and targets (Video), or (3) abstract, computer-generated targets and a cursor representing hand position (Cursor). A significant after-effect occurred in each VR. However, the magnitude of the after-effect was significantly different among VRs: the magnitude was greatest in Direct, smaller in Video and smallest in Cursor. A significant after-effect (carryover) also occurred when a subject prism-adapted reaches in one VR and then removed the prisms and made initial reaches in another VR. Our data showed that when reaches were prism-adapted in Direct and then prisms were removed, there was a large carryover to initial reaches in Video or Cursor (D-->V and D-->C). In contrast, when prisms were worn in Video and removed for reaches in Direct (V-->D), there was a significantly smaller carryover than from both D-->V and D-->C. Finally, when prisms were worn in Cursor and removed for reaches in Direct (C-->D), there was very little detectable carryover. Our results suggest that adaptation is context-dependent and that the magnitude of carryover is dependent on the VR in which adaptation occurred. Interpretations of adaptations made in abstract training and experimental conditions may be greatly affected by this finding.

Adaptation, Physiological↗

PubMed2001

Matrix-bound fibroblasts regulate angiogenesis by modulation of VE-cadherin.

BACKGROUND: Vascular endothelial cadherin (VE-cadherin/cadherin-5) has previously been described as playing a specific role in angiogenesis due to its localisation at areas of intercellular contact, where it functions in maintenance of tubular architecture. Matrix-bound fibroblasts have been show to produce a number of factors that are important in inducing angiogenesis and to promote tubule-formation by human endothelial cells, an indicator of angiogenic potential. RESULTS: Tubule formation stimulated by fibroblast-derived growth factors can be prevented by the addition of monoclonal antibody to VE-cadherin. In addition, fibroblasts-derived growth factors are able to modulate the expression and hence the regulation of this endothelial cell specific cadherin. CONCLUSIONS: The change in VE-cadherin expression of human endothelial cells by fibroblast-derived growth factors may contribute to the regulation of angiogenesis.

Antigens, CD↗

PubMed2001

Throwing accuracy in the vertical direction during prism adaptation: not simply timing of ball release.

In a previous study, others have hypothesized that the variance in vertical errors that occurs while throwing at visual targets is caused by changes in any of three throw parameters: hand location in space, hand translational velocity, and hand orientation. From an analysis of skilled throwers, those authors concluded that vertical error is best correlated with variance in hand orientation, which in turn is related to the timing of ball release. We used a vertical prism adaptation paradigm to investigate which of these throwing parameters subjects use when adapting to external perturbation. Our subjects showed no correlation between hand position or hand translational velocity and ball impact height in normal, over-practiced throwing. However, video-based motion analysis showed that modifications both of position and speed of the hand play an important role when subjects are forced to compensate for a vertically shifting prism perturbation during a dart-like throw (these factors contribute approximately 30% of the adaptation). We concluded that, during adaptation, more degrees of freedom and more sources of potential error are modified to achieve the gaze-throw recalibration required to hit the target than are employed in this type of throw during normal conditions.

Adaptation, Physiological↗

PubMed2001

Tight junctions and their role in cancer metastasis.

Tight Junctions govern the permeability of endothelial and epithelial cells and are the most topical structures of these cell types. Tight junctions create an intercellular barrier and intramembrane diffusion fence. An important step in the formation of cancer metastases interaction and penetration of the vascular endothelium by dissociated cancer cells. Early studies demonstrated a correlation between the reduction of tight junctions and tumour differentiation and experimental evidence has emerged to place tight junctions in the frontline as the structure that cancer cells must overcome in order to metastasise. Changes in tight junction function are thus an early and key aspect in cancer metastasis. Further work is required to fully realise the potential that this structure has in cancer invasion and metastasis in order to develop new and novel therapies in the prevention of tumour metastasis.

Animals↗

PubMed2001

Hepatocyte growth factor modulates vascular endothelial-cadherin expression in human endothelial cells.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a cytokine exerting a wide range of biological functions on many cell types, including vascular endothelial cells. HGF/SF increases migration, motility, and dissociation of human umbilical vascular endothelial cells (HUVECs). This study demonstrated that such action of HGF/SF on HUVECs was achieved by regulation of the endothelial cell-specific cadherin, vascular endothelial (VE)-cadherin. HGF/SF induced a time-dependent reduction of VE-cadherin protein from HUVECs as shown by Western blotting and immunocytochemistry, accompanied by an increase in the migration of HUVECs. The change of VE-cadherin appeared at the mRNA level, as demonstrated by reverse transcription-PCR, with a decrease in the VE-cadherin signal. These results show, for the first time, that HGF/SF targets the endothelial cell-specific adhesion molecule VE-cadherin.

Animals↗

PubMed2001

A hammerhead ribozyme suppresses expression of hepatocyte growth factor/scatter factor receptor c-MET and reduces migration and invasiveness of breast cancer cells.

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF), via its receptor c-MET, has been implicated to play a pivotal role in breast cancer development and progression. This study examined a transgene-consisting of a combination of U1snRNA, hammerhead ribozyme, and antisense, designed to inhibit c-met expression-and its impact on the migration and in vitro invasion of breast cancer cells. EXPERIMENTAL DESIGN: A hammerhead ribozyme targeting human c-MET was cloned into a modified pZeoU1EcoSpe vector and transfected into breast cancer cells MDA MB 231 and MCF-7 by electroporation. Expression of MET mRNA and protein was determined. Migration and in vitro invasiveness of transfected cells were also analyzed. RESULTS: Breast cancer cells were transfected with the ribozyme-containing plasmids. Stable transfectants manifested an almost complete loss of MET mRNA and protein, as shown by reverse transcription-PCR, Northern blotting, and Western blotting, respectively, whereas the wild-type plasmid had no effects. Met-ribozyme transfected cells exhibited reduced migration and in vitro invasiveness through extracellular matrix (Matrigel), compared with the wild-type cells and cells transfected with empty plasmid. CONCLUSIONS: These data show that targeting c-MET by way of a hammerhead ribozyme encoding antisense to c-MET is an effective approach in reducing the invasiveness of breast cancer cells.

Base Sequence↗

PubMed2000

Neural tract tracing using Di-I: a review and a new method to make fast Di-I faster in human brain.

The use of Di-I in tract-tracing is briefly reviewed and a novel delayed-fixation approach to neural tract-tracing in the postmortem human adult brain is reported. Using the new approach, fast Di-I, a highly lipophilic fluorescent dye was injected into a particular region or nucleus and labelled tracts were followed for distances of some 20-40 mm. The procedure required approximately 36 h, yielding dye penetration rates of 1.0 mm/h or more. This contrasts with previous Di-I, silver impregnation, and horseradish peroxidase protocols, where the tracer penetration rate is typically 0.003 mm/h or less, and the distance traversed amounts to only a few mm even after months of incubation. The new method hinges on the simple consideration that aldehyde fixation, which is normally employed prior to administration of the marker, crosslinks membrane proteins and impedes dye diffusion. The short postmortem samples used in our protocol permit delaying fixation until after the dye has had time to penetrate, dramatically increasing the length and scope of neural circuits that can be traced. Using these methods, for example, we have confirmed the presence of an ipsilateral olivocerebellar climbing fiber projection in the human.

Animals↗

PubMed2000

Link between heart disease, cholesterol, and Alzheimer's disease: a review.

Increased prevalence of Alzheimer's disease-like beta-amyloid deposits in the neuropil and within neurons occurs in the brains of non-demented individuals with heart disease. Heart disease is a prevalent finding in Alzheimer's disease, and may be a forerunner to the dementing disorder. In the cholesterol-fed rabbit model of human coronary heart disease there is production and accumulation of beta-amyloid in the brain. This accumulation of beta-amyloid can be reversed by removing cholesterol from the rabbits' diet. In culture cells, a cholesterol challenge has been shown to increase production of beta-amyloid, and dramatic reductions of cholesterol produced by HMG Co-A reductase inhibitors decrease production of beta-amyloid. Increased beta-amyloid production is also produced by dietary cholesterol in a number of transgenic mouse models of Alzheimer's disease. Administration of HMG Co-A reductase inhibitors may block beta-amyloid production caused by dietary cholesterol in rabbits. Clinical trials testing the benefit of HMG Co-A reductase inhibitors in the treatment of Alzheimer's disease are underway.

Alzheimer Disease↗

PubMed1999

Hepatocyte growth factor/scatter factor decreases the expression of occludin and transendothelial resistance (TER) and increases paracellular permeability in human vascular endothelial cells.

Hepatocyte growth factor/scatter factor (HGF/SF), a multi function cytokine has been shown to regulate the expression of cell adhesion molecules in endothelial cells. In the current study, we examined the effects of HGF/SF on the function of tight junctions and the expression of occludin in these cells. Stimulation of human vascular endothelial cells with HGF/SF resulted in a concentration dependent increase in the paracellular permeability as measured using fluorescence labelled dextran but a decrease in the transendothelial cell resistance (TER) of the endothelial cells. Western blotting revealed that HGF/SF decreased the level of occludin in the cells, a primary tight junction forming protein. Immunofluorescence study indicated that shortly after treatment with HGF/SF there was a disturbance of the distribution of occludin and then a reduction in the staining of the molecule. It is concluded that HGF/SF decreases the expression of occludin, resulting in the functional change of tight junction.

Cell Line↗

PubMed1999

Regulation of angiogenesis and endothelial cell motility by matrix-bound fibroblasts.

This study sought to examine the effect of matrix-bound fibroblasts on angiogenesis and endothelial cell motility. Promotion of angiogenesis by matrix-bound fibroblasts was assessed using rat aortic ring and endothelial tube formation assays. Enhancement of human endothelial cell motility by matrix-bound fibroblasts was assessed using cytodex-2 bead and colloidal gold phagokinetic motility assays. Antibody to hepatocyte growth factor/scatter factor (HGF/SF) but not vascular endothelial growth factor (VEGf) decreased fibroblast-enhanced motility of endothelial cells. The promotion of tube formation by matrix-bound fibroblasts was neutralised with antibodies to HGF/SF and VEGf, both known promoters of angiogenesis. HGF/SF presence was detected by ELISA; whilst the presence of VEGf was detected by Western blotting. These data show that matrix-embedded fibroblasts regulate the motility of vascular endothelial cells and enhance angiogenesis, an effect partly attributed to production of angiogenesis-promoting cytokines HGF/SF and/or VEGf.

Journal Article↗

PubMed1999

Ceramic whisker reinforcement of dental resin composites.

Resin composites currently available are not suitable for use as large stress-bearing posterior restorations involving cusps due to their tendencies toward excessive fracture and wear. The glass fillers in composites provide only limited reinforcement because of the brittleness and low strength of glass. The aim of the present study was to reinforce dental resins with ceramic single-crystalline whiskers of elongated shapes that possess extremely high strength. A novel method was developed that consisted of fusing silicate glass particles onto the surfaces of individual whiskers for a two-fold benefit: (1) to facilitate silanization regardless of whisker composition; and (2) to enhance whisker retention in the matrix by providing rougher whisker surfaces. Silicon nitride whiskers, with an average diameter of 0.4 microm and length of 5 microm, were coated by the fusion of silica particles 0.04 microm in size to the whisker surface at temperatures ranging from 650 degrees C to 1000 degrees C. The coated whiskers were silanized and manually blended with resins by spatulation. Flexural, fracture toughness, and indentation tests were carried out for evaluation of the properties of the whisker-reinforced composites in comparison with conventional composites. A two-fold increase in strength and toughness was achieved in the whisker-reinforced composite, together with a substantially enhanced resistance to contact damage and microcracking. The highest flexural strength (195+/-8 MPa) and fracture toughness (2.1+/-0.3 MPa x m(1/2)) occurred in a composite reinforced with a whisker-silica mixture at whisker:silica mass ratio of 2:1 fused at 800 degrees C. To conclude, the strength, toughness, and contact damage resistance of dental resin composites can be substantially improved by reinforcement with fillers of ceramic whiskers fused with silica glass particles.

Ceramics↗

PubMed1999

Applicability of American College of Radiology appropriateness criteria in a general internal medicine clinic.

OBJECTIVE: The American College of Radiology (ACR) Appropriateness Criteria for Imaging and Treatment Decisions are intended to help radiologists and referring physicians use imaging procedures appropriately and cost-effectively, but these criteria have not undergone empirical testing. To assess how readily the ACR appropriateness criteria can be applied to clinical practice, we retrospectively examined their applicability in a general ambulatory care setting. MATERIALS AND METHODS: From all requests during an 8-month period for noninterventional CT, sonography, MR imaging, and nuclear medicine imaging procedures received from a general internal medicine clinic, we excluded cases for which relevant clinic notes were unavailable or incomplete. Three experienced radiologists classified cases by consensus, using data from radiology requests and clinic notes. Cases were classified as a "complete match" if the features matched a clinical condition and variant included in the ACR appropriateness criteria; as a "partial match" if the features matched a clinical condition but did not match all features of a variant; or as "unmatched." RESULTS: Of 316 cases, there were 202 complete matches (64%) and 37 partial matches (12%). Of the 77 unmatched cases (24%), 14 pertained to asymptomatic patients. CONCLUSION: The ACR appropriateness criteria could be applied to 76% of the imaging procedure requests that we received from a general internal medicine clinic. These results suggest that the ACR appropriateness criteria can be applied to diagnostic imaging in a general ambulatory-care setting.

Adult↗

PubMed1999

Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells.

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is known to act on cancer cells as well as endothelial cells and stimulate angiogenesis, thus playing an unwanted role in the development and progression of cancer. The current study examined the effects of a newly discovered HGF variant, NK4, on angiogenesis in vitro. Chemically generated NK4 (from recombinant human HGF/SF) was found to be able to inhibit HGF-induced activation (tyrosine phosphorylation) of the HGF/SF receptor cMET but was itself unable to activate cMET. Furthermore, NK4 was demonstrated to inhibit tubule formation from human umbilical vein endothelial cells that was induced by both HGF/SF and a HGF/SF-producing fibroblast (MRC5). Under the same settings, NK4 failed to increase tubular formation. NK4 had no effects on interleukin 8- and vascular endothelial growth factor-induced tubule formation. Using computer-assisted motion analysis, it was further shown that NK4 inhibited HGF-induced migration of human umbilical vein endothelial cells in a migration assay and in an endothelial wounding assay. These data show that NK4 is a complete antagonist to HGF. It inhibits HGF-induced endothelial movement and tubule formation. Thus, NK4 may have an important bearing on the control of cancer progression through its role in angiogenesis. Additional in vivo studies are warranted.

Cell Movement↗