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C Prince

Publications and source records attributed to C Prince.

At least 19 recordsLinked to original sources
PubMed2007

A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.

Amino Acid Sequence↗
PubMed1999

Spinal cord axonal loss in multiple sclerosis: a post-mortem study.

There is increasing interest in the contribution that axonal damage may make to clinical disability in multiple sclerosis (MS). The present study reports a post-mortem examination of the area occupied by the lateral white matter columns of the spinal cord and nerve fibre density in the corticospinal tracts at C3 and T2 in 23 males and 20 females with MS, who lacked plaques at these levels, and in 31 controls who, although most had had some neurological disease, showed no sign of cervical or spinal cord thoracic disease. The lateral column cross-sectional area, measured by low power image analysis of the outlined lateral columns, was reduced in MS by 17% at C3 and 21% at T2 in males and by 13% at C3 and 18% at T2 in females. These reductions were significant at both levels in males (P<0.004 at C3 and P<0.009 at T2 ) but only at T2 in females (P<0. 03). The nerve fibre density, measured by automatic image analysis of x200 microscopic fields in the region occupied by the crossed pyramidal tracts, was reduced by 41% at C3 and 42% at T2 in males and by 19% at both C3 and T2 in females. These reductions were likewise significant at both levels in males (P<0.003 and P<0.000 at C3 and T2, respectively) and T2 only in females (P<0.045). In MS, nerve fibre density was significantly lower at C3 (P<0.004) and T2 (P<0.000) in males than females. No differences were seen in these parameters between males and females in controls. The reductions in total nerve fibre densities were entirely accounted for by reductions in small nerve fibres (cross sectional area less than 5 microm2 ). No significant reductions were seen in large fibre (cross sectional area 5 microm2 or more) densities. It is concluded that substantial axonal loss and spinal cord lateral column white matter atrophy occur at C3 and T2 in MS, and that these changes can be detected in some patients from early in the course of the disease.

Adult↗
PubMed1998

Osteopontin stimulates a subpopulation of quiescent human prostate epithelial cells with high proliferative potential to divide in vitro.

BACKGROUND: Osteopontin (OPN) is a secreted extracellular matrix (ECM) protein found in bone, as well as associated with epithelial cells. The main objective of these studies was to test in vitro the hypothesis that interaction with OPN stimulates proliferation of a quiescent subpopulation of prostate epithelial cells with high proliferative potential. METHODS: To simulate conditions that restrict proliferation and inhibit terminal differentiation of basal cells in vivo, control cultures grew on substrate coated with collagen (CO) or fibronectin (FN), in medium containing low levels of growth factors. RESULTS: Under growth-restricting conditions, most prostate epithelial cells with high proliferative potential, seeded in control secondary cultures, were quiescent within the time frame of the studies, as indicated by the small number of large colonies in these cultures. Growing prostate epithelial cells (PR) under the same growth-restricting conditions, but on substrate coated with OPN instead of CO or FN, stimulated proliferation of a subpopulation of single cells with high proliferative ability as indicated by: 1) dose-dependent increase in the percentage of single cells incorporating bromodeoxyuridine, i.e., proliferating PR; and 2) subsequent dose-dependent increase in the percentage of large colonies. The OPN effect was not merely due to preferential attachment to OPN, because PR attachment to OPN, CO, or FN was identical. PR attachment to OPN was inhibited in the presence of GRGDTP or an antibody against the integrin subunit alphav, but not in the presence of an RGES peptide or a nonspecific IgG. CONCLUSIONS: Integrin-mediated OPN/PR interaction stimulates proliferation of a quiescent subpopulation of prostate epithelial cells with high proliferative potential, possibly stem cells.

Cell Adhesion↗
PubMed1998

Cyclosporin A has low potency as a calcineurin inhibitor in cells expressing high levels of P-glycoprotein.

Cyclosporin A (CsA) is a widely-used immunosuppressant drug whose therapeutic and toxic actions are mediated through inhibition of calcineurin (CN), a calcium- and calmodulin-dependent phosphatase. Inhibition of CN by CsA requires drug binding to its protein cofactor in the inhibition, cyclophilin. Because cyclophilin is a high affinity target for CsA it is expected that this protein can act as a reservoir for the drug in the cell and may be able to inhibit cellular efflux of CsA. P-glycoprotein (P-gp) is known to increase the rate of CsA efflux from CsA loaded cells but it is not clear if the P-gp drug efflux pump can compete effectively with cyclophilin at therapeutically relevant concentrations of CsA. To test the hypothesis that increased expression of P-gp confers protection against CsA-dependent inhibition of CN phosphatase activity, KB-V cells expressing varying levels of P-gp were analyzed to determine the potency of CsA as a CN inhibitor. When intact cells were treated with CsA, a positive correlation was observed between P-gp expression and resistance to CsA-dependent inhibition of CN: the IC50 is approximately 20-fold higher in the multidrug resistant epidermal carcinoma cell line, KB-V, which expresses P-gp at a high level than in the parental, KB, cell line expressing very low levels of P-gp. The resistance displayed by KB-V cells is abrogated by co-administration of the P-gp inhibitor verapamil, whereas verapamil has no effect on CsA potency in control KB cells. In cell lysates from KB-V cells with different amounts of P-gp CsA exhibits equivalent potency, indicating that the difference in sensitivity to CsA among the cell types requires maintenance of cell integrity. These observations support the view that resistance to CN inhibition by CsA occurs in cells with moderately elevated P-gp activity. Therefore, P-gp activity appears to be an important determinant of CsA cellular specificity for both therapeutic and toxic effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Four cases of amitraz poisoning in humans.

Only 7 cases of human poisoning with amitraz have been previously published and most of them are poorly documented. Four additional cases are now reported. The symptoms observed were remarkably similar in all cases: all patients experienced drowsiness; 3 presented with bradycardia, miosis and/or hyperglycemia; 2 developed hypotension and/or vomiting. These symptoms are compared to those observed in previous human or animal poisoning. Alpha 2-adrenoceptor stimulation could explain the clinical and laboratory features in most cases.

Adult↗
PubMed1995

Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not colonic Crohn's disease.

Immune mechanisms, possibly involving cell-surface molecules such as CD44, have been invoked to explain the pathogenesis of inflammatory bowel disease. We used monoclonal antibodies against epitopes encoded within the variable region of CD44 to investigate CD44 isoform expression in colon, small intestine, and liver in patients with various intestinal disorders and in controls. Biopsy samples from patients with ulcerative colitis showed significantly increased epithelial expression of CD44 isoforms containing the v6 and v3 epitopes, detected with antibodies 2F10 and 3G5, respectively. CD44v6 was detected on colonic crypt epithelial cells in 23 of 25 ulcerative colitis samples compared with 3 of 18 colonic Crohn's disease samples (p = 3.0 x 10(-6); odds ratio 57.5 [95% CI 6.83-702]) and 3 of 52 controls (22 normal colon, 10 infective colitis, 2 radiation colitis, and 18 colonic Crohn's disease; p < 1 x 10(-8); odds ratio 199 [25.5-2294]). No significant expression of CD44v6, CD44v3, or CD44v8/9 was found in samples of normal proximal colon from 4 patients with distal ulcerative colitis, whereas samples from the affected area showed staining for CD44v6 and CD44v3. No expression of CD44 variants was found in 15 samples of normal small intestine, 11 small-bowel pouchitis, 8 coeliac disease, 3 small-bowel Crohn's disease, 6 normal liver, 6 primary biliary cirrhosis, or 9 primary sclerosing cholangitis. The high intensity of CD44v6 and v3 epitope expression on crypt epithelial cells in ulcerative colitis suggests that CD44 isoforms may have an important role in ulcerative colitis. Their detection could have diagnostic potential in differentiating ulcerative colitis from other forms of colonic inflammation including Crohn's disease.

Antibodies, Monoclonal↗
PubMed1995

Enhancing transfer of training: using role-play to foster teamwork in the cockpit.

Role-plays serve a unique purpose in providing practice and feedback for aircrew team development training in the classroom. When compared with other training strategies, role-play provides targeted practice and feedback of specific behaviors at low cost, with the trade-off being the amount of fidelity it provides. This article presents guidelines for designing role-plays to elicit crew resource management (CRM) behaviors and providing feedback to trainees on their performance. Through careful design procedures, a role-play exercise can provide both targeted practice and feedback and serve a useful purpose in the overall training design of a CRM training program.

Accidents, Aviation↗
PubMed1995

Impact of automation on aircrew communication and decision-making performance.

Increasing levels of automation are being introduced into the cockpit. Yet, it is difficult to predict the impact of these automatic systems on other elements of flight, such as crew communication and the ability to arrive at an effective decision. This study attempted to clarify the relation among these variables. Forty-eight pilots were assigned to two-person crews and asked to fly a simulated mission in either automated or manual conditions using a low-fidelity simulator. The scenario was designed to require crewmembers to arrive at a collective decision based on information obtained about an evolving simulated disaster. The results indicated that the introduction of automation was not associated with better performance. However, several significant differences were observed in the communications of crews flying in the automated versus manual conditions. The results are discussed in terms of their implications for communications training for advanced technology aircraft.

Adult↗
PubMed1995

The measurement of team process.

The construct validity of measures of team process was evaluated using predictive, known groups and multitrait-multimethod (MTMM) validation strategies. Military air crews (N = 51) flew two simulated missions. Independent judges provided evaluations of the same six team process variables in both scenarios. An MTMM analysis of judges' ratings treating judges as a method variable showed good convergent and discriminant validity. Judges' mean ratings of the six process variables were correlated with mission effectiveness. Some process measures discriminated between student and instructor teams, thus showing discrimination between known groups. Conversely, an MTMM analysis of ratings treating scenarios as a method showed poor convergent validity. We concluded that important team process behaviors have been identified and can be rated validly but that multiple observations are necessary to assess characteristics of individual teams with any accuracy. The discussion includes implications for practice and future research.

Aircraft↗
PubMed1994

Human MCF activates monocytes to produce IL-1 but not TNF or CSF-1.

Monocyte cytotoxicity inducing factor (MCF) is a novel cytokine which was originally characterized by its ability to induce monocyte cytotoxicity against tumor targets. The present studies were undertaken to define the mechanisms of cytotoxicity. Since the cytotoxic state may be mediated, in part, by the secretion of monokines, MCF's effect on IL-1, TNF and CSF-1 were measured. MCF caused human peripheral blood monocytes to secrete large amounts of IL-1 but not TNF. In contrast monocytes produce CSF-1 in culture and this production was not enhanced by MCF. IL-1 neither appeared to directly lyse the target K562 nor was able to activate macrophages for cytotoxicity. However, IL-1 may be necessary for lysis of K562 by activated macrophages through its cytostatic effect on K562. MCF increased monocyte surface expression of DR-beta (when studied by fluorescent microfluorometry) and messenger RNA for DR-beta after 24 h in culture. These functional studies indicate that MCF is a cytokine with a distinct spectrum of biologic activities whose functions may be mediated by synthesis and secretion of IL-1.

Cytokines↗
PubMed1993

Successful limb salvage after recanalization of an occluded infrapopliteal artery utilizing a balloon expandable (Palmaz-Schatz) stent.

This case describes the first reported successful management of an infrapopliteal artery intimal dissection utilizing the Palmaz-Schatz balloon expandable stent. Stent deployment relieved the compromised blood flow caused by the intimal flap which could not be corrected by prolonged balloon inflation or removed with directional atherectomy, and averted any emergency surgical procedure.

Aged↗
PubMed1993

Stenting of a renal artery stenosis achieves better relief of the obstructive lesion than balloon angioplasty.

A balloon-expandable (Palmaz-Schatz) stainless steel stent was utilized following balloon angioplasty (PTRA) to determine if the obstructive lesion, using quantitative methods (automated measuring the diameter stenosis, and transstenotic peak systolic and mean pressure gradients), was significantly further reduced or abolished. Hemodynamic transstenotic gradient and stenoses measurements were made during 21 renal artery stenting procedures; prior and following PTRA, and subsequent to stent deployment. The stent sizes placed in the renal arteries were 5 mm (19%), 6 mm (67%), and 7 mm (14%). The results were as follows: [table: see text] The balloon-expandable (Palmaz-Schatz) stent significantly further reduced, and in fact effectively abolished, the obstructive renal artery lesion in comparison to balloon angioplasty (PTRA). The stent's effectiveness with regard lesion recurrence, maintenance, and preservation of renal function; cure or improved management of hypertension; and survival will be determined by careful clinic follow-up.

Aged↗
PubMed1993

Alzheimer's disease is rare in Cree.

A community survey and subsequent clinical assessment of 192 Cree aged 65 years and over registered in two Reserves in Northern Manitoba identified only one case of probable Alzheimer's disease among eight cases of dementia, giving a prevalence of 0.5% for Alzheimer's disease and 4.2% for all dementias. This contrasted with an age-adjusted prevalence of 3.5% for Alzheimer's disease and 4.2% for all dementias in an age-stratified sample of 241 English-speaking residents of Winnipeg. Although it was not so for all dementias, the difference between the groups for prevalence of Alzheimer's disease was highly significant (p < .001). The age-specific patterns of all dementias in the two groups were significantly different, however (p = .0254).

Aged↗
PubMed1992

Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation.

In situ hybridisation has been used to detect mRNAs to the macrophage secretory products, lysozyme, interleukin 1 beta and tumour necrosis factor-alpha. Sections of paraformaldehyde fixed, frozen colonoscopic biopsies from patients with ulcerative colitis, Crohn's disease or normal controls were hybridised with specific radiolabelled probes and the signal detected by autoradiography. Lysozyme mRNA expression was more common in ulcerative colitis (22/27) and Crohn's disease (eight of eight) compared with controls (17/27). Positive cells were found mainly in the subepithelial region in normal colon, while in inflammatory bowel disease they also appeared in the deeper lamina propria. Immunocytochemistry in parallel sections showed that lysozyme mRNA was expressed only in macrophages or in metaplastic Paneth cells in longstanding inflammatory bowel disease. Tissue neutrophils did not express the lysozyme mRNA, though they have large stores of the protein. Tumour necrosis factor mRNA was detected in four of nine controls compared with 11/15 inflammatory bowel disease patients. For interleukin 1 beta, three of eight controls were positive compared with 10/13 with ulcerative colitis. The tumour necrosis factor signal was located mainly in the deeper lamina propria whereas the interleukin 1 beta was seen in subepithelial macrophages. These results confirm increased macrophage activation in inflammatory bowel disease and suggest functional heterogeneity within the intestinal macrophage population.

Adult↗
PubMed1992

Microscopic colitis: can it be qualitatively and quantitatively characterized?

This study reports the histological features helpful in diagnosing microscopic colitis. Rectal biopsy specimens from 14 patients with microscopic colitis, 14 with active ulcerative colitis and 14 without colonic inflammation were pooled and then assessed by three observers according to a predetermined protocol. Inter-observer agreement was good except for Paneth cell metaplasia and endocrine cell metaplasia. Compared with healthy tissue, microscopic colitis showed a significant (p less than 0.05) increase in chronic inflammatory cells and a depletion of goblet cells but these changes were less pronounced than those seen in ulcerative colitis (p less than 0.05). In contrast to ulcerative colitis, microscopic colitis was associated with a more marked infiltration with eosinophils and an increase in intra-epithelial lymphocytes. These results show that microscopic colitis can be distinguished both from normal colonic tissue and from ulcerative colitis.

Adolescent↗
PubMed1991

Mucosal characteristics of pelvic ileal pouches.

This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur.

Adenomatous Polyposis Coli↗