John McGregor - Academia.edu (original) (raw)

Papers by John McGregor

Research paper thumbnail of Use of Microarrays and Immunohistochemistry to Investigate Accelerated Atherosclerosis in Human Graft Coronary Artery Disease

Atherosclerosis Supplements, 2008

Research paper thumbnail of Identification of genes involved in acute rejection following heart transplantation in a murine model: use of cDNA arrays

Journal of the American College of Cardiology, 2002

SRI and TDI at mid-ventricle in systole peak systolic value Control (n=34) No-CHF (n=28) CHF (n=26)

Research paper thumbnail of Acute rejection in human heart transplantation: Identification and characterization of two important markers (MIP-1β and VE-cadherin)

Journal of the American College of Cardiology, 2003

NYHA classes in patients with left ventricular dysfunction after MI. Trandolapril resulted in sig... more NYHA classes in patients with left ventricular dysfunction after MI. Trandolapril resulted in significantly lower furosemide consumption. expression of TlMPs is unchanged while expression of MMPP and 9 is increased. Therapy with ER-MET does not influence TlMPs but reduces expression of MMPP and 9, a finding consistent with reduced RIF following chronic therapy with the ER-MET.

Research paper thumbnail of 1051-129 Use of quantitative reverse transcriptase-polymerase chain reaction for validation of macrophage inflammatory protein-1β and vascular endothelium-cadherin as important markers of acute rejection after heart transplantation

Journal of the American College of Cardiology, 2004

S-Cardiac Function and Heart Failure 175A Cardiac Function and Heart Failure for providing mechan... more S-Cardiac Function and Heart Failure 175A Cardiac Function and Heart Failure for providing mechanical support to the failing heart in these settings. Methods: We retrospectively reviewed all patients who received a Thoratec Single-Lead-Vented-Electric LVAD at our institution between August 1990 and February 2003. Twentyfive patients with viral myocarditis were identified. Twenty-five patients whose primary indication for LVAD was coronary artery disease (CAD) were randomly selected from the same database to serve as a control group. Variables analyzed included patient demographics, duration of LVAD support, preoperative white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) values, percent explanted, success rate of bridge to transplantation, and post-transplant survival rates. Results: The VM group was younger than (35.88+/-16.43 years vs. 58.88+/-4.30 years) (p<0.01) and consisted of a greater proportion of female patients than (36% vs. 8%) (p=0.02) the CAD group. Duration of LVAD support, preoperative WBC and ESR values, and percent explanted were similar between the two groups. Bridge success rates and post-transplant survival rates were also comparable (64% transplanted in VM, 60% transplanted in CAD (p=0.86); 1-and 5-year post-transplant survival rates of 86.67% and 72.80% in VM, 71.43% and 62.50% in CAD, respectively (p=0.34)). Conclusions: These findings suggest that despite the variable clinical course of VM and the potential to rapidly progress to end-stage heart failure, LVAD implantation in these patients yields outcomes similar to those receiving LVADs for CAD. Device support permits decompression of the dilated ventricle, facilitating myocardial recovery and the likelihood of bridging successfully to transplant or explant.

Research paper thumbnail of T-cadherin expression in cardiac allograft vasculopathy: Bench to bedside translational investigation

The Journal of Heart and Lung Transplantation, 2010

BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term surv... more BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR). METHODS: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries. RESULTS: 1829, 2582 and 1925 genes (fold changes Ͼ2 or Ͻ2 and p values Ͻ0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries. CONCLUSIONS: T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.

Research paper thumbnail of Identification of MIP-1β and VE-Cadherin as important markers of acute rejection following human heart transplantation

The Journal of Heart and Lung Transplantation, 2003

Research paper thumbnail of CD36 N-terminal cytoplasmic domain is not required for the internalization of oxidized low-density lipoprotein

Bioscience Reports, 2008

The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the ar... more The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent ‘foam cell’ formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present study has addressed the function of the CD36 N-terminal cytoplasmic domain in the binding and internalization of OxLDL. A selection of CD36 N-terminal cytoplasmic domain mutants were generated and stably expressed in HEK-293 (human embryonic kidney) cells. The capacity of three mutants [CD36_C3/7-A (CD36-C3A/C7A), CD36_D4/R5-A (CD36-D4A/R5A) and CD36_nCPD− (CD36 lacking the N-terminal cytoplasmic domain)] to bind and endocytose OxLDL was then studied using immunofluorescence microscopy and quantitative fluorimetry. Each of the CD36 constructs was expressed at differing levels at the cell surface, as measured by flow cytometry and Western blotting. Following incubation with DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine per...

Research paper thumbnail of IL-2 Transmembrane Constructs

Research paper thumbnail of Brain Tumor Imaging and Surgical Management

Topics in Magnetic Resonance Imaging, 2006

ABSTRACT

Research paper thumbnail of Identification of a Domain (155–183) on CD36 Implicated in the Phagocytosis of Apoptotic Neutrophils

Journal of Biological Chemistry, Jun 28, 1996

Clearance of apoptotic neutrophils by macrophages is a crucial event following the resolution of ... more Clearance of apoptotic neutrophils by macrophages is a crucial event following the resolution of acute inflammation. CD36, together with ␣ v ␤ 3, has been identified as one of the adhesion molecules on the surface of macrophages implicated in the clearance of polymorphonuclear leukocytes. The domain on CD36 implicated in the phagocytosis of aged neutrophils remains to be elucidated. In this study, COS cells transfected with human CD36 cDNA had a significantly higher capacity to phagocytose human apoptotic neutrophils compared with murine CD36 cDNA. Moreover, monoclonal antibodies 10/5 or OKM5 (epitopes identified on amino acids 155-183) but not monoclonal antibody 13/10 (epitope identified on amino acids 30 -76) inhibited phagocytosis of apoptotic neutrophils by COS cells transfected by human CD36. Swapping the human CD36 155-183 domain from human to murine CD36 (human-murine CD36 chimera) imparted to murine CD36-transfected COS cells an increased capacity to phagocytose apoptotic neutrophils. Conversely, when the murine domain 155-183 was inserted in human CD36, a decreased phagocytic capacity was observed. In addition, a synthetic peptide (155-169) but not its scrambled form significantly inhibited phagocytosis. These results identify for the first time a functional domain encompassing amino acids 155-183 on human CD36 implicated in the recognition and phagocytosis of apoptotic neutrophils.

Research paper thumbnail of Il-2 transmembrane construct

Research paper thumbnail of Testing the polymorphic interactions between classes

... Robert McDaniel John D. McGregor Department of Computer Science Cl emson Uni versi ty Cl emso... more ... Robert McDaniel John D. McGregor Department of Computer Science Cl emson Uni versi ty Cl emson, SC29634-1906 johnmc@cs ... reducing the testing e ort introduced by these combined features of the object-oriented paradigm, a polymorphic message pass is de ned in terms ...

Research paper thumbnail of An Open Boundary Condition for Models of Thermals

Journal of the Atmospheric Sciences, Mar 1, 1976

Numerical models of thermals usually introduce a closed box within which convection occurs. A bou... more Numerical models of thermals usually introduce a closed box within which convection occurs. A boundary condition which allows inflow and outflow through the edges of the computational domain is discussed. The results of numerical experiments using this boundary condition are then compared and contrasted with those obtained when a rigid boundary is assumed. It is found that the flow development is especially sensitive to the choice of the upper boundary condition even before warm fluid reaches the top of the computational domain.

Research paper thumbnail of Omeprazole is not cytotoxic to colorectal cancer cells in vitro

Research paper thumbnail of 6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

Journal of Biomedicine and Biotechnology, Feb 1, 2006

Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular di... more Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5) overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain), two recently described motifs (Osa Homology Domain), and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH) rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL) rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth.

Research paper thumbnail of Laser-assisted laparoscopic excision of liver cyst

Research paper thumbnail of Cancer of the proximal colon after a "normal" colonoscopy

Bioscience Trends, Aug 1, 2009

In common with other diagnostic tests, colonoscopy has a false negative rate which is infrequentl... more In common with other diagnostic tests, colonoscopy has a false negative rate which is infrequently assessed. The available literature suggests that lesion miss rate is higher for proximal colonic tumors. A total of 367 patients were diagnosed with cancer of the colon and rectum over a period of 2 years. Ninety-two of these patients had tumors proximal to the splenic flexure. Their 5-year pre-diagnosis colonoscopic exposure was analyzed. The primary end-point of this study was to confirm the false negative colonoscopy rate in patients subsequently diagnosed with cancer of the proximal colon. The secondary endpoint was to assess the effects of diagnostic delay on tumor stage and presentation. In the group of patients with proximal colon cancer (n = 92) we identified 10 patients (11%) who, as a result of incomplete (2 cases) or falsely negative (8 cases) colonoscopies, suffered a median diagnostic delay of 17 months (range 3-60). At diagnosis, 4 of these patients had Dukes' D caecal cancer, 4 had Dukes' C caecal cancer and 2 had Dukes' B transverse colon cancer; 3 presented with perforated tumours and 1 with intestinal obstruction. In this small subgroup of patients therefore 40% presented with emergency complications compared to 8% in the rest of the group with proximal cancers (p < 0.01). Missed cancers are more likely to present with complications. This study highlights the importance of recognition of an incomplete examination and the adverse impact of missed diagnosis on subsequent presentation.

Research paper thumbnail of Effect of the Surgeon's Speciality Interest on the Type of Resection Performed for Colorectal Cancer

Dis Colon Rectum, 1994

PURPOSE: The aim of this study was to examine the type of resection performed for colorectal canc... more PURPOSE: The aim of this study was to examine the type of resection performed for colorectal cancer by surgeons with a colorectal interest and compare this with the type of resection performed by surgeons with other specialty interests. METHODS: One hundred sixteen patients had curative surgery performed for primary colorectal cancer over a one-year period by ten surgeons with four different specialty interests. RESULTS: Surgeons with an interest in colorectal cancer resected twice as much colon (280 mm vs. 130 ram; P > 0.0001, Mann-Whitney Utest) and were more likely to remove adjacent clinically involved organs (15 percent vs. 0 percenO for left-sided colon and rectal cancers compared with surgeons with vascular or transplant interests. Surgeons with an interest in gastroenterology performed a resection that was intermediate between the colorectal and other specialty groups for left-sided cancers. Distal resection margins were significantly greater (55 mm vs. 20 mm; P > 0.001) for sigmoid cancers in the colorectal group, but were similar in all groups for rectal cancer. Resection lengths and margins for right-sided cancers were similar in all groups, although the number of lymph nodes retrieved from the mesentry was greater in the colorectal group (13 vs. 7.5; P = 0.08). CONCLUSION: This study shows a wide variability in the type of resection performed for colorectal cancer and illustrates the need for clinical trials to evaluate the effect of such variability on patient outcome. [Key words: Curative surgery; Colorectal cancer; Surgeon's specialty interest; Resection lengths; Resection margins] Reinbach DH, McGregor JR, Murray GD, O'Dwyer PJ. Effect of the surgeon's specialty interest on the type of resection performed for eolorectal cancer. Dis Colon Rectum 1994; 37:1020-1023.

Research paper thumbnail of Measurements of landscape-scale fluxes of carbon dioxide in the Peruvian Amazon by vertical profiling

Vertical profiles of carbon dioxide were measured within and above the atmospheric boundary layer... more Vertical profiles of carbon dioxide were measured within and above the atmospheric boundary layer at a tropical forest site in the Peruvian Amazon during July 1996 using a tethered balloon sampling platform. Flask samples were collected within and above the mixed layer and analyzed off-site for carbon dioxide by nondispersive infrared spectrophotometry. Ozone and temperature vertical profiles were used to determine the boundary layer heights and growth rates. The mean values for methane, carbon monoxide, hydrogen, carbon-13, and oxygen-18 ratios were determined within and above the mixed layer. Daytime carbon dioxide flux values were calculated using the budget method. Nocturnal fluxes were estimated by integrating the carbon dioxide mixing ratios as a function of height from the ground to the inversion layer and dividing the total accumulated carbon dioxide by the time since sunset. The daytime carbon dioxide flux of-13 + 2 •tmol C m '2 s '• and the nocturnal flux of +5.0 + 1.0 •tmol C m '2 s '• are in good agreement with previous studies in the Brazilian Amazon. phere and the higher deposition rate of nitrogen and other minerals [Gifford, 1994; Eamus and Jarvis, 1989; McMurtrie et al., 1992; McGuire et al., 1995]. On the other hand, their continued destruction through deforestation and biomass burning is a significant short-term carbon dioxide source that ultimately decreases the forest's potential as a carbon sink [Auclair and Bedford, 1993; Vloedbeld and Leeroans, 1993; Brown et al., 1993].

Research paper thumbnail of IL-2 transmembrane construct

Research paper thumbnail of Use of Microarrays and Immunohistochemistry to Investigate Accelerated Atherosclerosis in Human Graft Coronary Artery Disease

Atherosclerosis Supplements, 2008

Research paper thumbnail of Identification of genes involved in acute rejection following heart transplantation in a murine model: use of cDNA arrays

Journal of the American College of Cardiology, 2002

SRI and TDI at mid-ventricle in systole peak systolic value Control (n=34) No-CHF (n=28) CHF (n=26)

Research paper thumbnail of Acute rejection in human heart transplantation: Identification and characterization of two important markers (MIP-1β and VE-cadherin)

Journal of the American College of Cardiology, 2003

NYHA classes in patients with left ventricular dysfunction after MI. Trandolapril resulted in sig... more NYHA classes in patients with left ventricular dysfunction after MI. Trandolapril resulted in significantly lower furosemide consumption. expression of TlMPs is unchanged while expression of MMPP and 9 is increased. Therapy with ER-MET does not influence TlMPs but reduces expression of MMPP and 9, a finding consistent with reduced RIF following chronic therapy with the ER-MET.

Research paper thumbnail of 1051-129 Use of quantitative reverse transcriptase-polymerase chain reaction for validation of macrophage inflammatory protein-1β and vascular endothelium-cadherin as important markers of acute rejection after heart transplantation

Journal of the American College of Cardiology, 2004

S-Cardiac Function and Heart Failure 175A Cardiac Function and Heart Failure for providing mechan... more S-Cardiac Function and Heart Failure 175A Cardiac Function and Heart Failure for providing mechanical support to the failing heart in these settings. Methods: We retrospectively reviewed all patients who received a Thoratec Single-Lead-Vented-Electric LVAD at our institution between August 1990 and February 2003. Twentyfive patients with viral myocarditis were identified. Twenty-five patients whose primary indication for LVAD was coronary artery disease (CAD) were randomly selected from the same database to serve as a control group. Variables analyzed included patient demographics, duration of LVAD support, preoperative white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) values, percent explanted, success rate of bridge to transplantation, and post-transplant survival rates. Results: The VM group was younger than (35.88+/-16.43 years vs. 58.88+/-4.30 years) (p<0.01) and consisted of a greater proportion of female patients than (36% vs. 8%) (p=0.02) the CAD group. Duration of LVAD support, preoperative WBC and ESR values, and percent explanted were similar between the two groups. Bridge success rates and post-transplant survival rates were also comparable (64% transplanted in VM, 60% transplanted in CAD (p=0.86); 1-and 5-year post-transplant survival rates of 86.67% and 72.80% in VM, 71.43% and 62.50% in CAD, respectively (p=0.34)). Conclusions: These findings suggest that despite the variable clinical course of VM and the potential to rapidly progress to end-stage heart failure, LVAD implantation in these patients yields outcomes similar to those receiving LVADs for CAD. Device support permits decompression of the dilated ventricle, facilitating myocardial recovery and the likelihood of bridging successfully to transplant or explant.

Research paper thumbnail of T-cadherin expression in cardiac allograft vasculopathy: Bench to bedside translational investigation

The Journal of Heart and Lung Transplantation, 2010

BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term surv... more BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR). METHODS: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries. RESULTS: 1829, 2582 and 1925 genes (fold changes Ͼ2 or Ͻ2 and p values Ͻ0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries. CONCLUSIONS: T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.

Research paper thumbnail of Identification of MIP-1β and VE-Cadherin as important markers of acute rejection following human heart transplantation

The Journal of Heart and Lung Transplantation, 2003

Research paper thumbnail of CD36 N-terminal cytoplasmic domain is not required for the internalization of oxidized low-density lipoprotein

Bioscience Reports, 2008

The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the ar... more The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent ‘foam cell’ formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present study has addressed the function of the CD36 N-terminal cytoplasmic domain in the binding and internalization of OxLDL. A selection of CD36 N-terminal cytoplasmic domain mutants were generated and stably expressed in HEK-293 (human embryonic kidney) cells. The capacity of three mutants [CD36_C3/7-A (CD36-C3A/C7A), CD36_D4/R5-A (CD36-D4A/R5A) and CD36_nCPD− (CD36 lacking the N-terminal cytoplasmic domain)] to bind and endocytose OxLDL was then studied using immunofluorescence microscopy and quantitative fluorimetry. Each of the CD36 constructs was expressed at differing levels at the cell surface, as measured by flow cytometry and Western blotting. Following incubation with DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine per...

Research paper thumbnail of IL-2 Transmembrane Constructs

Research paper thumbnail of Brain Tumor Imaging and Surgical Management

Topics in Magnetic Resonance Imaging, 2006

ABSTRACT

Research paper thumbnail of Identification of a Domain (155–183) on CD36 Implicated in the Phagocytosis of Apoptotic Neutrophils

Journal of Biological Chemistry, Jun 28, 1996

Clearance of apoptotic neutrophils by macrophages is a crucial event following the resolution of ... more Clearance of apoptotic neutrophils by macrophages is a crucial event following the resolution of acute inflammation. CD36, together with ␣ v ␤ 3, has been identified as one of the adhesion molecules on the surface of macrophages implicated in the clearance of polymorphonuclear leukocytes. The domain on CD36 implicated in the phagocytosis of aged neutrophils remains to be elucidated. In this study, COS cells transfected with human CD36 cDNA had a significantly higher capacity to phagocytose human apoptotic neutrophils compared with murine CD36 cDNA. Moreover, monoclonal antibodies 10/5 or OKM5 (epitopes identified on amino acids 155-183) but not monoclonal antibody 13/10 (epitope identified on amino acids 30 -76) inhibited phagocytosis of apoptotic neutrophils by COS cells transfected by human CD36. Swapping the human CD36 155-183 domain from human to murine CD36 (human-murine CD36 chimera) imparted to murine CD36-transfected COS cells an increased capacity to phagocytose apoptotic neutrophils. Conversely, when the murine domain 155-183 was inserted in human CD36, a decreased phagocytic capacity was observed. In addition, a synthetic peptide (155-169) but not its scrambled form significantly inhibited phagocytosis. These results identify for the first time a functional domain encompassing amino acids 155-183 on human CD36 implicated in the recognition and phagocytosis of apoptotic neutrophils.

Research paper thumbnail of Il-2 transmembrane construct

Research paper thumbnail of Testing the polymorphic interactions between classes

... Robert McDaniel John D. McGregor Department of Computer Science Cl emson Uni versi ty Cl emso... more ... Robert McDaniel John D. McGregor Department of Computer Science Cl emson Uni versi ty Cl emson, SC29634-1906 johnmc@cs ... reducing the testing e ort introduced by these combined features of the object-oriented paradigm, a polymorphic message pass is de ned in terms ...

Research paper thumbnail of An Open Boundary Condition for Models of Thermals

Journal of the Atmospheric Sciences, Mar 1, 1976

Numerical models of thermals usually introduce a closed box within which convection occurs. A bou... more Numerical models of thermals usually introduce a closed box within which convection occurs. A boundary condition which allows inflow and outflow through the edges of the computational domain is discussed. The results of numerical experiments using this boundary condition are then compared and contrasted with those obtained when a rigid boundary is assumed. It is found that the flow development is especially sensitive to the choice of the upper boundary condition even before warm fluid reaches the top of the computational domain.

Research paper thumbnail of Omeprazole is not cytotoxic to colorectal cancer cells in vitro

Research paper thumbnail of 6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

Journal of Biomedicine and Biotechnology, Feb 1, 2006

Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular di... more Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5) overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain), two recently described motifs (Osa Homology Domain), and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH) rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL) rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth.

Research paper thumbnail of Laser-assisted laparoscopic excision of liver cyst

Research paper thumbnail of Cancer of the proximal colon after a "normal" colonoscopy

Bioscience Trends, Aug 1, 2009

In common with other diagnostic tests, colonoscopy has a false negative rate which is infrequentl... more In common with other diagnostic tests, colonoscopy has a false negative rate which is infrequently assessed. The available literature suggests that lesion miss rate is higher for proximal colonic tumors. A total of 367 patients were diagnosed with cancer of the colon and rectum over a period of 2 years. Ninety-two of these patients had tumors proximal to the splenic flexure. Their 5-year pre-diagnosis colonoscopic exposure was analyzed. The primary end-point of this study was to confirm the false negative colonoscopy rate in patients subsequently diagnosed with cancer of the proximal colon. The secondary endpoint was to assess the effects of diagnostic delay on tumor stage and presentation. In the group of patients with proximal colon cancer (n = 92) we identified 10 patients (11%) who, as a result of incomplete (2 cases) or falsely negative (8 cases) colonoscopies, suffered a median diagnostic delay of 17 months (range 3-60). At diagnosis, 4 of these patients had Dukes' D caecal cancer, 4 had Dukes' C caecal cancer and 2 had Dukes' B transverse colon cancer; 3 presented with perforated tumours and 1 with intestinal obstruction. In this small subgroup of patients therefore 40% presented with emergency complications compared to 8% in the rest of the group with proximal cancers (p < 0.01). Missed cancers are more likely to present with complications. This study highlights the importance of recognition of an incomplete examination and the adverse impact of missed diagnosis on subsequent presentation.

Research paper thumbnail of Effect of the Surgeon's Speciality Interest on the Type of Resection Performed for Colorectal Cancer

Dis Colon Rectum, 1994

PURPOSE: The aim of this study was to examine the type of resection performed for colorectal canc... more PURPOSE: The aim of this study was to examine the type of resection performed for colorectal cancer by surgeons with a colorectal interest and compare this with the type of resection performed by surgeons with other specialty interests. METHODS: One hundred sixteen patients had curative surgery performed for primary colorectal cancer over a one-year period by ten surgeons with four different specialty interests. RESULTS: Surgeons with an interest in colorectal cancer resected twice as much colon (280 mm vs. 130 ram; P > 0.0001, Mann-Whitney Utest) and were more likely to remove adjacent clinically involved organs (15 percent vs. 0 percenO for left-sided colon and rectal cancers compared with surgeons with vascular or transplant interests. Surgeons with an interest in gastroenterology performed a resection that was intermediate between the colorectal and other specialty groups for left-sided cancers. Distal resection margins were significantly greater (55 mm vs. 20 mm; P > 0.001) for sigmoid cancers in the colorectal group, but were similar in all groups for rectal cancer. Resection lengths and margins for right-sided cancers were similar in all groups, although the number of lymph nodes retrieved from the mesentry was greater in the colorectal group (13 vs. 7.5; P = 0.08). CONCLUSION: This study shows a wide variability in the type of resection performed for colorectal cancer and illustrates the need for clinical trials to evaluate the effect of such variability on patient outcome. [Key words: Curative surgery; Colorectal cancer; Surgeon's specialty interest; Resection lengths; Resection margins] Reinbach DH, McGregor JR, Murray GD, O'Dwyer PJ. Effect of the surgeon's specialty interest on the type of resection performed for eolorectal cancer. Dis Colon Rectum 1994; 37:1020-1023.

Research paper thumbnail of Measurements of landscape-scale fluxes of carbon dioxide in the Peruvian Amazon by vertical profiling

Vertical profiles of carbon dioxide were measured within and above the atmospheric boundary layer... more Vertical profiles of carbon dioxide were measured within and above the atmospheric boundary layer at a tropical forest site in the Peruvian Amazon during July 1996 using a tethered balloon sampling platform. Flask samples were collected within and above the mixed layer and analyzed off-site for carbon dioxide by nondispersive infrared spectrophotometry. Ozone and temperature vertical profiles were used to determine the boundary layer heights and growth rates. The mean values for methane, carbon monoxide, hydrogen, carbon-13, and oxygen-18 ratios were determined within and above the mixed layer. Daytime carbon dioxide flux values were calculated using the budget method. Nocturnal fluxes were estimated by integrating the carbon dioxide mixing ratios as a function of height from the ground to the inversion layer and dividing the total accumulated carbon dioxide by the time since sunset. The daytime carbon dioxide flux of-13 + 2 •tmol C m '2 s '• and the nocturnal flux of +5.0 + 1.0 •tmol C m '2 s '• are in good agreement with previous studies in the Brazilian Amazon. phere and the higher deposition rate of nitrogen and other minerals [Gifford, 1994; Eamus and Jarvis, 1989; McMurtrie et al., 1992; McGuire et al., 1995]. On the other hand, their continued destruction through deforestation and biomass burning is a significant short-term carbon dioxide source that ultimately decreases the forest's potential as a carbon sink [Auclair and Bedford, 1993; Vloedbeld and Leeroans, 1993; Brown et al., 1993].

Research paper thumbnail of IL-2 transmembrane construct