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Biomedical subjects

K J Murphy

Publications and source records attributed to K J Murphy.

At least 19 recordsLinked to original sources
PubMed2002

Psychological adjustment to familial-genetic risk assessment for ovarian cancer: predictors of nonadherence to surveillance recommendations.

OBJECTIVE: To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance. METHODS: Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12-18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment. RESULTS: Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (chi2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (chi2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk. CONCLUSIONS: These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.

Adult↗
PubMed2002

Pooling of echographic contrast agents during transcranial Doppler sonography: a sign in favor of slow-flowing giant saccular aneurysms.

Transcranial Doppler (TCD) sonography is a new imaging technique allowing for non-invasive evaluation of the intracranial vascular anatomy and cerebral hemodynamics. The recent introduction of echographic contrast agents has significantly increased the sensitivity of TCD for the diagnosis of intracranial vascular lesions. We report a case of giant AComA aneurysm, undetected by color and power TCD, which became visible after echographic contrast administration as a delayed and persistent area of contrast enhancement. Knowledge of atypical or contrast-specific lesion appearances will become important if contrast-enhanced TCD is to be used routinely in the diagnosis of intracranial aneurysms.

Contrast Media↗
PubMed2001

Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7.

Adenosine Triphosphatases↗
PubMed2001

Anti-ischemic and cognition-enhancing properties of NNC-711, a gamma-aminobutyric acid reuptake inhibitor.

NNC-711 [1-(2-((diphenylmethylene)amino)oxy)ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride], a gamma-aminobutyric acid (GABA) reuptake inhibitor with anticonvulsant activity, was investigated with respect to its cognition-enhancing and neuroprotective potency. In the rat, administration of NNC-711 immediately prior to training prevented amnesia for a passive avoidance task induced by the acetylcholine receptor antagonist scopolamine. NNC-711 was also effective in protecting against ischemia-induced death of CA1 pyramidal neurons in a model of bilateral common carotid artery occlusion in the gerbil. In addition to a neuroprotective activity, NNC-711 exhibited significant cognition-enhancing actions. Daily administration of NNC-711, immediately prior to a spatial learning task, significantly reduced escape latencies in the water maze paradigm in both mature (postnatal day 80) and aged (28 months) rats. All of the above actions exhibited a bell-shaped response with an optimal dose of 0.5-1.0 mg/kg. These investigations with NNC-711 and previous clinical observations on the structurally related anticonvulsant tiagabine confirm the potential of GABA reuptake inhibitors as anti-amnesia and cognition-enhancing agents.

Amnesia↗
PubMed2001

Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy.

PURPOSE: The purpose of this study was to examine the relationship between overall survival and prognostic factors in carcinoma of the cervix treated with radiation therapy. A clinicopathologic study was performed on 24 patients. METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor biopsies were stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53. Clinical factors such as stage, grade, tumor size, pre- and post-treatment hemoglobin level, and radiotherapy dose were also evaluated. RESULTS: Median follow-up was 75 months for living patients. The only immunohistochemical or clinical factor that was associated with improved survival was decreased COX-2 distribution staining. High COX-2 distribution staining was associated with decreased overall survival (p = 0.021) and decreased disease-free survival (p = 0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall survival rates for tumors with low vs. high COX-2 distribution values were 75% and 35%, respectively. COX-2 staining intensity was found to correlate positively with tumor size (p = 0.022). CONCLUSION: These findings indicate that increased expression of COX-2 portends a diminished survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early-response gene involved in angiogenesis and inducible by different stimuli, these data may indicate opportunity to intervene with specific inhibitors of COX-2 in carcinoma of the cervix.

Adenocarcinoma↗
PubMed2001

Anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé: an angiographic study.

We studied the anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé in 57 consecutive angiograms. Patients with pathology in intracranial venous structures or with inadequate image quality of the venous system were excluded. Arachnoid granulations were found in 12 of the 57 patients (21.1%), always at the junction of the vein of Labbé and the transverse sinus; the vein of Labbé was present in 55 patients (96.5%), most often without associated arachnoid granulations; the latter, however, were not observed in the absence of a vein of Labbé. This study confirms the close, constant anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé. This observation may help to differentiate arachnoid granulations from pathologic conditions involving the transverse sinus such as dural sinus thrombosis. The constant character of this relationship suggests a developmental role of afferent veins in the formation of arachnoid granulations.

Arachnoid↗
PubMed2001

In vitro evaluation of the effectiveness of distal protection in the prevention of cerebral thromboembolism during carotid stent placement.

RATIONALE AND OBJECTIVES: The purpose of this in vitro study was to evaluate and quantify the benefit of the balloon protection device, to identify the most effective sequence of irrigation or flushing, and to determine the most effective catheter position to remove the maximum number of emboli or debris beneath the flow-arrest balloon. MATERIALS AND METHODS: Silicone models of the neurovasculature were attached to a systodiastolic pump. Stents were placed in carotid stenoses by using the distal flow protection technique. Embolic material was released within the stent. The effectiveness of different irrigation techniques was evaluated. RESULTS: Aspiration under the balloon through the guiding catheter with a 60-mL syringe followed by one power injection at 40 mL injected at 2 mL/sec will result in removal of about 98% of potential emboli from the internal carotid artery [corrected]. CONCLUSION: In vitro evaluation of the distal flow protection technique indicates that it should reduce stroke risk during carotid stent placement.

Carotid Stenosis↗
PubMed2001

Protein kinase C delta regulates neural cell adhesion molecule polysialylation state in the rat brain.

Polysialylation of neural cell adhesion molecule (NCAM PSA) modulates cell-cell homophilic binding and signalling during brain development and the remodelling of discrete brain regions in the adult. Following learning, a transient increase in the frequency of polysialylated neurones occurs in the dentate gyrus of the hippocampal formation, and this has been correlated with the selective retention and/or elimination of synapses that are transiently overproduced during memory consolidation. We now demonstrate that protein kinase C delta (PKCdelta) negatively regulates polysialyltransferase activity in the rat brain during development and also in the hippocampus during memory consolidation, where its down-regulation in the Golgi membrane fraction coincides with the transient increase in NCAM PSA expression. Decreased expression of PKCdelta was also observed in the hippocampus of rats reared in a complex environment and this directly contrasted the significant increase in frequency of hippocampal polysialylated neurones observed in these animals. These effects were isoform-specific as no change in total PKC enzyme activity was detected during memory consolidation and complex environment rearing had no effect on the hippocampal expression of PKCalpha, beta, gamma or epsilon. By sequential immunoprecipitation and immunoblot analysis, phosphorylation of polysialyltransferase protein(s) was (were) demonstrated to occur on both serine and tyrosine residues and this was associated with decreased enzyme activity. Moreover, a similar experimental approach revealed the degree of PKCdelta co-precipitation with polysialyltransferase protein(s) to be inversely correlated with polysialyltransferase activity. These findings support in vitro evidence indicating PKCdelta to regulate polysialyltransferase activity and NCAM polysialylation state.

Animals↗
PubMed2001

Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe.

2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16-85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.

Aging↗
PubMed2001

The modulations of NCAM polysialylation state that follow transient global ischemia are brief on neurons but enduring on glia.

To investigate the role of polysialylated neural cell adhesion molecule (NCAM PSA)-mediated plasticity after injury, we examined the temporal and spatial expression of NCAM PSA immunoreactivity in the medial temporal lobe following global ischemia. Male Mongolian gerbils were subjected to bilateral common carotid artery occlusion for 5 min and killed at increasing times post-occlusion. The well-characterized delayed CAl pyramidal cell death was observed 5-7 days post-occlusion. At post-occlusion days 1-2 there was a small but significant increase of NCAM PSA-positive hippocampal granule cells followed by an equally significant decrease at post-occlusion day 5. In contrast, a substantial increase in glial PSA expression was observed in all hippocampal regions at 1-7 days post-occlusion that was associated generally with stellate astroglia and specifically with the radial processes of glia traversing the granule cell layer of the dentate gyrus. Administration of the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-ben-zo(F)quinoxaline significantly blocked the ischemia-induced modulation of neuronal and glial NCAM PSA expression. Astroglial NCAM polysialylation became attenuated by 35 days post-occlusion except in the CAI area of cell death. The temporal and regional pattern of polysialylated NCAM expression in the ischemic gerbil hippocampus implicates this neuroplastic marker in mechanisms of neurotrophic-dependent repair/remodeling that ensue following transient interruption of blood flow.

Animals↗
PubMed2001

Elevated COX-2 expression in cervical carcinoma: reduced cause-specific survival and pelvic control.

The purpose of this study was to correlate the level of cyclooxygenase-2 (COX-2) expression in carcinoma of the cervix with the clinical endpoints: local control, cause-specific survival, and patterns of failure in patients treated with radiotherapy. Formalin-fixed, paraffin-embedded tumor biopsies were stained for COX-2. Clinical factors such as stage, grade, tumor size, pre- and posttreatment hemoglobin level, and radiotherapy dose were also evaluated. Actuarial local control rates and cause-specific survival were determined according to the Kaplan-Meier method. COX-2 distribution staining was the only prognostic factor that was associated with local control and cause-specific survival. High COX-2 distribution staining was associated with decreased local control and decreased cause-specific survival by log rank comparison of Kaplan-Meier survival curves. The 5-year cause-specific survival rates for tumors with low versus high COX-2 distribution values were 90% and 22%, respectively (p = 0.0003). Actuarial pelvic control at 5 years was superior in patients with low COX-2 distribution staining (92%) compared with high staining (42%, p = 0.005). COX-2 staining intensity was found to correlate positively with tumor size (p = 0.02). These findings indicate that increased expression of COX-2 yields reduced pelvic control and cause-specific survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Previously, inhibition of COX-2 has been demonstrated to sensitize tumors to radiation without effect on normal tissue. Taken together, these data may support a novel therapeutic application of COX-2 inhibitors in the treatment of carcinoma of the cervix.

Cyclooxygenase 2↗
PubMed2001

Mechanical detachable platinum coil: report of the European phase II clinical trial in 60 patients.

PURPOSE: To determine the safety and reliability of the mechanical detachment system of a platinum coil (Detach-18) when used for neurovascular embolization. MATERIALS AND METHODS: Sixty patients (21 men, 39 women; age range, 26-75 years; mean age, 56.2 years) were treated in seven centers. Ease of introduction of the coil to the microcatheter, effect of coil passage on the microcatheter shape and stability during its delivery, retrievability of the coil before and after the transition zone passed beyond the microcatheter, detachment of the coil, and effect of coil rotation on the microcatheter stability were evaluated. The detachment system itself was evaluated for premature detachment, failure of the coil to detach, detachment time, number of turns, visibility of radiopaque markers, number of coils deployed per patient, and percentage of vessel occlusion obtained. A 0.015-inch-diameter regular coil and a 0.014-inch-diameter soft coil were used. RESULTS: A total of 1,061 coils were used; 1,009 were detached. The number of coils deployed ranged from four to 104 (mean, 17 coils). The coils passed easily through the microcatheter. The detachment maneuver occurred within 5-25 seconds, with five to 60 turns of the introducing wire. One premature coil detachment occurred without clinical sequela; 100% occlusion of the vessel lumen was achieved in 53 patients; 80%-90%, in four; and 70%-80%, in two. There were no device-related complications. CONCLUSION: The detachment system was safe and reliable. This is a useful system for coil embolization in neurovascular diseases.

Adult↗
PubMed2001

Role of the distal balloon protection technique in the prevention of cerebral embolic events during carotid stent placement.

BACKGROUND AND PURPOSE: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. METHODS: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. RESULTS: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017). CONCLUSIONS: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.

Angioplasty, Balloon↗
PubMed2001

Defining a molecularly normal colon.

As techniques evolve that allow molecular characterization of disease processes such as cancer, definition of "normal" at a molecular level becomes increasingly important. Increasingly large numbers of mutations are found at the genomic level, but whether all of those mutations contribute to the malignant state of a carcinoma cell is not clear. Without knowledge of what constitutes normality on the proteomic level in an organ or cell, we cannot determine what genomic changes are physiologically important. Traditionally, colon cancer is identified and classified by histological criteria. Margins of the colon are defined as "grossly uninvolved" when the histology is indistinguishable from that of normal (free from disease) colon. By using molecular pathology techniques and working backward from colon adenocarcinoma to hypoplastic polyps to presumably normal mucosa, we defined some of those protein differences. Our results may provide a molecular basis for identifying tumor formation and progression in situ.(J Histochem Cytochem 49:667-668, 2001)

Adenocarcinoma↗
PubMed2001

Vertebroplasty: a simple solution to a difficult problem.

Vertebroplasty is the percutaneous injection of bone cement into a symptomatic fractured vertebral body under fluoroscopic guidance. It is a safe and simple outpatient procedure. We discuss patient selection, the techniques, and the results based on our experience and that of our radiology colleagues.

Aged↗
PubMed2001

Vascular compression by a ventricular shunt catheter: clinical value of volume-rendered CT angiography.

One of the strongest advantages of CT angiography (CTA) lies in its unique ability to display simultaneously the anatomy of the vascular system and the topographic relationships existing between the vessels and the neighboring structures. The case we report, a 76-year-old man who underwent an intraventricular shunt placement complicated by a stroke, shows how this topographic assessment also provides important diagnostic information when vascular lesions resulting from an extrinsic compression mechanism are suspected.

Aged↗