Search PubMed⌕ Search

Biomedical subjects

R O'Connor

Publications and source records attributed to R O'Connor.

At least 19 recordsLinked to original sources
PubMed2002

Methods for generation of monoclonal antibodies to the very small drug hapten, 5-benzimidazolecarboxylic acid.

Drug-specific monoclonal antibodies (MAbs) were produced against the very small drug hapten (162.15 Da), 5-benzimidazolecarboxylic acid, an analogue of 2-(4-Thiazolyl)benzimidazole (TBZ) but lacking the thiol group. TBZ is widely used as a broad-spectrum anthelmintic in various animal species and humans and also as a food preservative and agricultural fungicide. The anti-5-benzimidazolecarboxylic acid antibodies produced have potential use for extraction and/or detection of protein-bound residue forms of TBZ. Three in vivo immunisation regimes (with combinations of two related small drug haptens and two different adjuvants/carrier molecules) and an in vitro immunisation procedure using a combination of three related unconjugated small drug haptens were investigated. Specificity for the hapten immunogen/s was initially determined using two different ELISA procedures. BIACORE analysis, in conjunction with drug binding inhibition studies, was used to confirm the specificity of a small number of selected clones. In vivo immunisation with a drug molecule conjugated to a lipopeptide/T-cell epitope, which acts both as a carrier molecule and an adjuvant was the most useful of the methods tested for the production of specific MAbs to a typically very small hapten with low immunogenic properties.

Animals↗
PubMed2002

Structure-activity relationship of indomethacin analogues for MRP-1, COX-1 and COX-2 inhibition. identification of novel chemotherapeutic drug resistance modulators.

We report the screening of analogues of indomethacin to investigate the structure-activity relationship (SAR) of indomethacin-mediated multidrug resistance associated protein-1 (MRP-1) inhibition. By examining the activities of compounds with minor variations of the parent structure, we were able to separate MRP-1, glutathione-S-transferase (GST), cyclooxygenase (COX)-1 and COX-2 inhibitory activities. Combination cytotoxicity assays were utilised to identify agents which possess synergistic potential in MRP-1-expressing cell lines. MRP-1 Inside Out Vesicles (IOVs) were utilised to demonstrate the ability of the indomethacin analogues to inhibit the pump directly. Most of the indomethacin analogues active as MRP-1 inhibitors were poor GST inhibitors when compared with the GST-inhibitory activity of indomethacin. Two of the MRP-1 inhibitory analogues were found to have no COX-1 inhibitory activity and low COX-2 inhibitory activity, suggesting potentially reduced clinical toxicity. One MRP-1 inhibitory indomethacin analogue was also found to have low COX-1 inhibitory activity, but significant COX-2 inhibitory activity, making this analogue again interesting in terms of low potential toxicity, but with the possibility of direct inhibitory effects on tumour growth.

Cyclooxygenase 1↗
PubMed2002

A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study.

We evaluated relapse in patients with stable, chronic schizophrenia over a 1-year period; inpatients were randomized to ziprasidone 40 mg/day (n = 72), 80 mg/day (n = 68), 160 mg/day (n = 67) or placebo (n = 71). The probability of relapse (Kaplan-Meier) at 1 year was significantly lower in the ziprasidone 40, 80, and 160 mg/day groups (43%, 35% and 36%, respectively) compared to placebo (77%; P = 0.002, P < 0.001 and P < 0.001, respectively). In those patients who remained on treatment for at least 6 months, only 9% subsequently relapsed on ziprasidone compared to 42% on placebo (P = 0.001). All three doses of ziprasidone were significantly superior to placebo on Positive and Negative Syndrome Scale (PANSS) efficacy variables (all P < 0.05). Ziprasidone was associated with a significantly greater mean improvement in the PANSS negative symptom subscale compared to placebo (P < 0.05). Discontinuation due to adverse events was similar with ziprasidone and placebo. Ziprasidone treatment was indistinguishable from placebo in assessments of movement disorders and was not associated with weight gain or cardiovascular abnormalities. These results demonstrate that ziprasidone was effective in reducing the frequency of relapse and was associated with long-term improvement in negative symptoms. Ziprasidone was well tolerated in this population of patients with chronic, stable schizophrenia.

Adolescent↗
PubMed2002

Identification of an IGF-1R kinase regulatory phosphatase using the fission yeast Schizosaccharomyces pombe and a GFP tagged IGF-1R in mammalian cells.

AIMS: To study the regulation of type 1 insulin like growth factor receptor (IGF-1R) tyrosine kinase activity using the fission yeast Schizosaccharomyces pombe and a green fluorescent protein (GFP) tagged, full length IGF-1R. METHODS: The beta chain of the IGF-1R (betawt) was expressed under inducible conditions in the fission yeast S. pombe. Western blot analysis with antiphosphotyrosine antibodies was used to assess the kinase activity of betawt. A GFP tagged IGF-1R (GFP-IGF-1R) was constructed to study the tyrosine kinase activity of the full length IGF-1R. The signalling capabilities of GFP-IGF-1R in response to IGF-1 stimulation were investigated in transiently transfected fibroblasts. Immunofluorescent staining for cellular phosphotyrosine content was used to assess the localisation and tyrosine kinase activity of GFP-IGF-1R. RESULTS: The betawt protein displayed functional tyrosine kinase activity in S pombe and phosphorylated endogenous yeast proteins. In response to IGF-1 stimulation, the GFP-IGF-1R became autophosphorylated and also activated the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways. Tyrosine phosphorylation and kinase activity of the GFP-IGF-1R could be visualised by immunofluorescence with antiphosphotyrosine antibodies. Coexpression of a mammalian tyrosine phosphatase PTP1B with betawt completely inhibited this tyrosine kinase activity in yeast and also reduced the tyrosine phosphorylation in COS cells transfected with the GFP-IGF-1R. CONCLUSIONS: Schizosaccharomyces pombe can be used to analyse the tyrosine kinase activity of the IGF-1R beta chain and its regulation by tyrosine phosphatases. In addition, the regulation of IGF-1R tyrosine kinase activity can be studied using a GFP tagged IGF-1R. Using both of these methods, IGF-1R kinase activity was shown to be inhibited by the protein tyrosine phosphatase, PTP1B.

Animals↗
PubMed2001

Transient activation of Jun N-terminal kinases and protection from apoptosis by the insulin-like growth factor I receptor can be suppressed by dicumarol.

The insulin-like growth factor I receptor (IGF-IR) activated by its ligands insulin-like growth factor (IGF)-I or IGF-II mediates suppression of apoptosis and contributes to tumorigenesis and cell growth. Here we investigated the activation of the stress-activated protein kinases including Jun N-terminal Kinases and p38 MAPK by IGF-I in interleukin-3-dependent FL5.12 lymphocytic cells that overexpress the IGF-IR (FL5.12/WT). We have shown previously that IGF-I protects these cells from apoptosis induced by interleukin-3 withdrawal but does not promote proliferation. IGF-I induced a rapid and transient activation of JNK that peaked at 40 min that was paralleled by a transient and robust phosphorylation of c-Jun. p38 was constitutively phosphorylated in FL5.12/WT cells. Activation of the JNK pathway by IGF-I occurred in the presence of phosphatidylinositol 3-kinase inhibitors and could be enhanced by anisomycin. Analysis of a series of FL5.12 cells expressing mutated IGF-IRs and analysis of 32D/IGF-IR cells showed that neither the C terminus of the receptor nor IRS-1 and IRS-2 were required for JNK activation, although tyrosine 950 was essential for full activation. The JNK inhibitor dicumarol suppressed IGF-I-mediated activation of JNK and phosphorylation of c-Jun but did not affect p38 and IkappaB phosphorylation or activation of AKT. IGF-I-mediated protection from apoptosis in FL5.12/WT cells was completely suppressed by dicumarol and partially suppressed by a p38 inhibitor. In the breast carcinoma cell line MCF-7, treatment with dicumarol also induced apoptosis. These data indicate that transient activation of JNK by IGF-I is mediated by signals that are distinct from those leading to phosphatidylinositol 3-kinase and AKT activation. The data further suggest that the SAPK pathways contribute to suppression of apoptosis by the IGF-IR.

Anisomycin↗
PubMed2001

Fast education: a comparison of teaching models for trauma sonography.

This study's objective was to evaluate the peritoneal dialysis and mannequin simulator models for the hands-on portion of a 4-h focused abdominal sonography for trauma (FAST) course. After an introductory lecture about trauma sonography and practice on normal models, trainees were assigned randomly to two groups. They practiced FAST on one of the two simulator models. After the didactic and hands-on portions of the seminar, FAST interpretation testing revealed mean scores of 82% and 78% for the peritoneal dialysis and mannequin simulator groups, respectively (p = 0.95). Post-course surveys demonstrated mean satisfaction scores for peritoneal dialysis and mannequin simulator models of 3.85 and 3.25, respectively, on a 4-point Likert scale (p = 0.317). A FAST educational seminar, which provides both didactic and hands-on instruction, can be completed in 4 h; the hands-on instruction phase can incorporate both normal models and abnormal simulation models, such as the peritoneal dialysis model and the multimedia mannequin simulator.

Emergency Medicine↗
PubMed2001

Can cardiac sonography and capnography be used independently and in combination to predict resuscitation outcomes?

OBJECTIVE: To measure the ability of cardiac sonography and capnography to predict survival of cardiac arrest patients in the emergency department (ED). METHODS: Nonconsecutive cardiac arrest patients prospectively underwent either cardiac ultrasonography alone or in conjunction with capnography during cardiopulmonary resuscitation at two community hospital EDs with emergency medicine residency programs. Cardiac ultrasonography was carried out using the subxiphoid view during pauses for central pulse evaluation and end-tidal carbon dioxide (ETCO(2)) levels were monitored by a mainstream capnograph. A post-resuscitation data collection form was completed by each of the participating clinicians in order to assess their impressions of the facility of performance and benefit of cardiac sonography during nontraumatic cardiac resuscitation. RESULTS: One hundred two patients were enrolled over a 12-month period. All patients underwent cardiac sonographic evaluation, ranging from one to five scans, during the cardiac resuscitation. Fifty-three patients also had capnography measurements recorded. The presence of sonographically identified cardiac activity at any point during the resuscitation was associated with survival to hospital admission, 11/41 or 27%, in contrast to those without cardiac activity, 2/61 or 3% (p < 0.001). Higher median ETCO(2) levels, 35 torr, were associated with improved chances of survival than the median ETCO(2) levels for nonsurvivors, 13.7 torr (p < 0.01). The multivariate logistic regression model, which evaluated the combination of cardiac ultrasonography and capnography, was able to correctly classify 92.4% of the subjects; however, of the two diagnostic tests, only capnography was a significant predictor of survival. The stepwise logistic regression model, summarized by the area under the receiver operator curve of 0.9, furthermore demonstrated that capnography is an outstanding predictor of survival. CONCLUSIONS: Both the sonographic detection of cardiac activity and ETCO(2) levels higher than 16 torr were significantly associated with survival from ED resuscitation; however, logistic regression analysis demonstrated that prediction of survival using capnography was not enhanced by the addition of cardiac sonography.

Capnography↗
PubMed2001

Emergency department evaluation of chest pain using exercise stress echocardiography.

OBJECTIVE: Patients with a low risk of coronary artery disease (CAD) presenting to the emergency department (ED) with chest pain pose a diagnostic dilemma because a small percentage will suffer an acute myocardial infarction (MI) and sudden death. The authors conducted this study to determine whether exercise stress echocardiography (ESE) could be used to further support the safe discharge of these low-risk patients. METHODS: A convenience sample of patients > or =30 years of age without a prior cardiac history who presented to an academic community hospital with chest pain, normal initial creatine kinase, and electrocardiography without ischemic changes underwent ESE within 6 +/- 1.7 hours (mean +/- SD). Abnormal ESE was defined as regional wall motion abnormality at rest or after exercise. The ED disposition and three- and six-month follow-up for cardiac events were recorded. This was a prospective observational cohort study. RESULTS: Of a total of 149 eligible patients, 145 completed the study. The mean age (+/-SD) was 47 +/- 9 years; 56% were male. No adverse events were noted during ESE. Seven patients (5%) had abnormal ESE (2 with rest wall motion abnormalities and 5 with exercise-induced wall motion abnormalities). Five of the seven underwent cardiac catheterization; three had CAD. All patients received telephone follow-up at three months and six months. Of the 138 patients with a normal ESE, all were free of cardiac events at three months. One patient had a non-Q-wave MI at six months (negative predictive value = 99.3%, 95% CI = 97.8% to 100%). CONCLUSIONS: Exercise stress echocardiography can be used to evaluate low-risk chest pain patients in the ED. Patients with a normal ESE may be considered for discharge with minimal risk of sequelae.

Adult↗
PubMed2001

Regulation of the effects of TGF-beta 1 by activation of latent TGF-beta 1 and differential expression of TGF-beta receptors (T beta R-I and T beta R-II) in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by subpleural fibrosis that progresses to involve all areas of the lung. The expression of transforming growth factor-beta1 (TGF-beta 1), a potent regulator of connective tissue synthesis, is increased in lung sections of patients with IPF. TGF-beta 1 is generally released in a biologically latent form (L-TGF-beta 1). Before being biologically active, TGF-beta must be converted to its active form and interact with both TGF-beta receptors type I and II (T beta R-I and T beta R-II). TGF-beta latency binding protein 1 (LTBP-1), which facilitates the release and activation of L-TGF-beta 1, is also important in the biology of TGF-beta 1. METHODS: Open lung biopsy samples from patients with IPF and normal controls were examined to localise T beta R-I, T beta R-II, and LTBP-1. Alveolar macrophages (AM) and bronchoalveolar lavage (BAL) fluid were examined using the CCL-64 bioassay to determine if TGF-beta is present in its active form in the lungs of patients with IPF. RESULTS: Immunoreactive L-TGF-beta 1 was present in all lung cells of patients with IPF except for fibroblasts in the subepithelial regions of honeycomb cysts. LTBP-1 was detected primarily in AM and epithelial cells lining honeycomb cysts in areas of advanced IPF. In normal lungs LTBP-1 immunoreactivity was observed in a few AM. AM from the upper and lower lobes of patients with IPF secreted 1.6 (0.6) fmol and 4.1 (1.9) fmol active TGF-beta, respectively, while AM from the lower lobes of control patients secreted no active TGF-beta (p< or =0.01 for TGF-beta in the conditioned media from AM obtained from the lower lobes of IPF patients v normal controls). The difference in percentage active TGF-beta secreted by AM from the lower lobes of patients with IPF and the lower lobes of control patients was significant (p< or =0.01), but the difference between the total TGF-beta secreted from these lobes was not significant. The difference in active TGF-beta in conditioned media of AM from the upper and lower lobes of patients with IPF was also not statistically significant. BAL fluid from the upper and lower lobes of patients with IPF contained 0.7 (0.2) fmol and 2.9 (1.2) fmol active TGF-beta, respectively (p< or =0.03). The percentage of active TGF-beta in the upper and lower lobes was 17.6 (1.0)% and 78.4 (1.6)%, respectively (p< or =0.03). In contrast, BAL fluid from control patients contained small amounts of L-TGF-beta. Using immunostaining, both T beta R-I and T beta R-II were present on all cells of normal lungs but T beta R-I was markedly reduced in most cells in areas of honeycomb cysts except for interstitial myofibroblasts in lungs of patients with IPF. TGF-beta 1 inhibits epithelial cell proliferation and a lack of T beta R-I expression by epithelial cells lining honeycomb cysts would facilitate repair of the alveoli by epithelial cell proliferation. However, the presence of both T beta Rs on fibroblasts is likely to result in a response to TGF-beta 1 for synthesis of connective tissue proteins. Our findings show that biologically active TGF-beta 1 is only present in the lungs of patients with IPF. In addition, the effects of TGF-beta 1 on cells may be further regulated by the expression of T beta Rs. CONCLUSION: Activation of L-TGF-beta 1 and the differential expression of T beta Rs may be important in the pathogenesis of remodelling and fibrosis in IPF.

Bronchoalveolar Lavage Fluid↗
PubMed2001

Active treatment of depression.

Despite advances in medication and psychotherapeutic methods, most patients with depression are subject to frequent recurrences and lead damaged lives even when they do not meet criteria for an episode. This article suggests an active, directive, educational treatment approach for patients with depression, centered on two tools: 1. a Mood Journal, focusing on reestablishing the connection between the patients' mood changes and their external life; and 2. a series of "aphorisms" of depression, meant to be shared with patients early in treatment. These are assertions about the nature of depression and recovery from it, which help patients move toward taking an active role in questioning how the condition affects them.

Affect↗
PubMed2000

Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons.

Geniculate (gustatory) and trigeminal (somatosensory) afferents take different routes to the tongue during rat embryonic development. To learn more about the mechanisms controlling neurite outgrowth and axon guidance, we are studying the roles of diffusible factors. We previously profiled the in vitro sensitivity of trigeminal axons to neurotrophins and target-derived diffusible factors and now report on these properties for geniculate axons. GDNF, BDNF, and NT-4, but not NT-3 or NGF, stimulate geniculate axon outgrowth during the ages investigated, embryonic days 12-14. Sensitivity to effective neurotrophins is developmentally regulated and different from that of the trigeminal ganglion. In vitro coculture studies revealed that geniculate axons were repelled by branchial arch explants that were previously shown to be repellent to trigeminal axons (Rochlin and Farbman [1998] J Neurosci 18:6840-6852). In addition, some branchial arch explants and untransfected COS7 cells repelled geniculate but not trigeminal axons. Sema3A, a ligand for neuropilin-1, is effective in repelling geniculate and trigeminal axons, and antineuropilin-1, but not antineuropilin-2, completely blocks the repulsion by arch explants that repel axon outgrowth from both ganglia. Sema3A mRNA is concentrated in branchial arch epithelium at the appropriate time to mediate the repulsion. In Sema3A knockout mice, geniculate and trigeminal afferents explore medial regions of the immature tongue and surrounding territories not explored in heterozygotes, supporting our previous hypothesis that Sema3A-based repulsion mediates the early restriction of sensory afferents away from midline structures.

Animals↗
PubMed2000

A cell viability assay based on monitoring respiration by optical oxygen sensing.

A cell viability assay based on monitoring of the metabolic activity of living cells via their consumption of dissolved oxygen has been developed. It uses a microwell plate format and disposable phosphorescent sensor inserts incorporated into each sample. The wells are subsequently sealed from ambient oxygen using a layer of mineral oil, and periodically scanned from underneath with a simple fiber-optic phosphorescent phase detector. Thus, dissolved oxygen levels and time profiles of cell respiration can be determined noninvasively and compared to each other. The system was tested by monitoring the viability of the fission yeast Schizosaccharomyces pombe. In comparison with the conventional cell densitometry assay, the optical oxygen sensor method could reliably monitor lower numbers of cells (10(4)-10(5) vs 10(6)-10(7) cells/ml for densitometry), and accurately determine culture viability within 1 h. The assay was then applied to determine the viability of samples treated with toxic agents such as azide and in response to expression of a physiological inducer of cell death, the Bcl-2 family member Bak. The results obtained confirm that measurement of cell respiration by this assay can serve as a predictable, reliable, and fast method for high-throughput determination of cell viability and growth.

Biological Assay↗
PubMed2000

The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis.

Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.

Antibodies↗
PubMed2000

The effects of changes in housing on feeding and wheel running.

The experiments explored the effects on feeding when rats were moved between individual and paired housing. In Experiment 1, rats moved to paired housing showed a 3-day suppression in feeding (initially 23%) compared to chronically individual- or pair-housed rats. In Experiment 2, half of the rats from the two control groups of Experiment 1 were moved between individual and paired housing on alternate days. Only the rats moved to paired housing showed a feeding suppression (initially 40%), but the nature of the suppression differed from Experiment 1: it appeared that only one rat of each pair showed a feeding suppression. Experiment 3 examined simultaneous introduction of running wheels and moves to paired housing. The feeding suppression induced by the move to paired housing was more immediate and shorter lived than the wheel-induced suppression. Unlike wheel access, paired housing produced only a temporary suppression of body weight. These experiments suggest that the relatively simple manipulation of moving rats from individual to paired housing results in a temporary stress-induced decrease in feeding.

Animals↗
PubMed2000

Vasopressin pressor effects in critically ill children during evaluation for brain death and organ recovery.

BACKGROUND: Vasopressin (VP) shows promise as a pressor agent in animals and adult human cardiac arrest and resuscitation, but has not been studied for pressor effect in critically ill or arrested children. VP infusion is routine treatment for diabetes insipidus during brain death evaluation and organ recovery. We hypothesized that low dose VP infusion during organ recovery in critically ill children exerts a pressor effect, without major organ toxicity. METHODS: 34 VP-treated and 29 age-matched critically ill controls (C) < or =18 years were retrospectively reviewed during brain death evaluation and organ recovery. VP infusion protocol titrated VP dose clinically to urine output, with high variability. Pressor and inotrope management was titrated clinically to BP, cerebral perfusion and central venous pressures (when available) and peripheral perfusion with similar protocol targets for pre-load in VP and C groups. Outcome measures include dose, type and number of pressors and inotropes. Organ function was assessed at recovery and 48 h post-transplant by independent surgeon and transplant program organ function criteria. Analysis by Odds Ratio (OR), and chi-square. RESULTS: VP dose averaged 0.041+/-0.069 U/kg/h. Average baseline mean arterial pressure (MAP) before VP infusion was 79+/-17 mmHg VP and 76+/-14 mm Hg C (P=0.6). Subsequent average MAP were: 82+/-21 mmHgVP after VP infusion versus 71+/-16 mmHg C (P=0.01) and 80+/-14 mmHg VP versus 68+/-22 mmHg C (P=0.01). Ability to wean/stop pressors and inotropes was: dopamine (14/23) 42% VP versus (10/26) 38% C (P=0.75), dobutamine (4/7) 57% VP versus (0/6) 0% C (P=0.026), epinephrine (4/5) 80% VP versus (0/6) 0% C (P=0.006), norepinephrine/phenylephrine (4/4) 100% VP versus (2/5) 40% C (P=0. 057). Alpha agonist pressor dependence was successfully weaned from 7/9 (78%) VP versus 0/9 (0%) C: odds ratio=7.3, (P<0.01). There was no VP induced dysrhythmia, hypertension, anuria or toxicity reported. Good organ recovery function was not significantly different at recovery or 48 h post-transplant for kidney (79% VP versus 69% C, P=0.068), liver (87% VP versus 95% C, P=0.533), or heart (90% VP versus 71% C, P=0.11). CONCLUSIONS: Low dose vasopressin infusion exerts a pressor effect in critically ill children treated for diabetes insipidus during brain death and organ recovery. VP treated patients were 7.3 times more likely to wean from alpha agonists than comparably managed age matched controls, without adverse affect on transplant organ function. We speculate that further prospective assessment of VP safety and efficacy as a pressor adjunct for resuscitation of critically ill children is warranted.

Adolescent↗
PubMed2000

Regulation of survival signals from the insulin-like growth factor-I receptor.

Suppression of apoptosis by survival factors is important for the maintenance of normal tissue homoeostasis and the response to infection or injury. Survival factors such as insulin-like growth factor-I (IGF-I) initiate a signalling cascade that starts by tyrosine phosphorylation of substrates leading to the activation of serine kinases that modulate the activity of members of the Bcl-2 family, which regulates the apoptotic machinery in most cells. Tumour cells often have enhanced survival mechanisms due either to up-regulation of the IGF-I receptor and its ligands or to loss of function of a phosphatase (PTEN) that regulates part of this survival pathway. The C-terminus of the IGF-I receptor appears to be a regulatory domain for the anti-apoptotic activity of this receptor, and certain residues within the C-terminus are essential for this regulatory activity. Knowledge of the proteins and pathways, which interact with these C-terminal domains, should lead us to ways of modulating IGF-I-mediated survival in tumours.

Animals↗