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Biomedical subjects

M L Phillips

Publications and source records attributed to M L Phillips.

At least 37 records · Page 2Linked to original sources
PubMed2000

Towards a functional neuroanatomy of self processing: effects of faces and words.

We studied the neural correlates of self vs. non-self judgements using functional magnetic resonance imaging (fMRI). Individually tailored faces and personality trait words were used as stimuli in three experiments (exp.). In the first two experiments, brain activation was measured while subjects viewed morphed versions of either their own (self face exp.) or their partner's face (partner's face exp.), alternating in blocks with presentation of an unknown face. In the self face exp. right limbic areas (hippocampal formation, insula, anterior cingulate), the right middle temporal lobe, left inferior parietal and left prefrontal regions showed signal changes. In the partner's face exp., only the right insula was activated. In the third exp., subjects made decisions about psychological trait adjectives previously categorized as describing their own attributes. Activation was present in the precuneus, the left parietal lobe, left insula/inferior frontal gyrus and the left anterior cingulate. A reaction time advantage was present when subjects responded to self-relevant words. The main area with signal changes during self-reference processing, regardless of the type of stimulus, was the left fusiform gyrus. The self-relevant stimuli engaged to a differential extent long term and working memory, semantic and emotional processes. We suggest that regions activated by these stimuli are engaged in self-processing.

Adult↗
PubMed2000

Perception of threat in schizophrenics with persecutory delusions: an investigation using visual scan paths.

BACKGROUND: Cognitive theories of persecutory delusions in schizophrenia include increased attention to threat and reduced re-appraisal of information during decision-making. METHODS: We employed visual scan path measurements, an 'on-line' marker of attention, in schizophrenic patients with persecutory delusions (N = 19), negative symptom- and medication-matched patients with non-persecutory delusions (N = 8), and normal controls (N = 18). Stimuli comprised black-and-white photographs of social scenes rated as depicting either neutral, ambiguous or overtly threatening activity. Foreground areas containing salient information with regard to the overall scene were rated independently as either threatening or non-threatening in both the overtly threatening and ambiguous scenes; all foreground areas were rated as non-threatening in the neutral scene. RESULTS: For the ambiguous scene only, schizophrenics with persecutory delusions directed gaze to less threatening areas, and, for all three scenes, demonstrated reduced re-appraisal of information compared with both control groups. All subjects showed similar viewing strategies for the overtly threatening and neutral scenes. CONCLUSIONS: These findings suggest abnormal information gathering and evaluation in schizophrenics, specifically related to the presence of persecutory delusions. In particular, the results point to biased processing of contextual information in an ambiguous setting in these patients, and perhaps perception of threat in inappropriate places.

Adult↗
PubMed2000

A differential neural response in obsessive-compulsive disorder patients with washing compared with checking symptoms to disgust.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) have symptoms that predominantly concern washing (washers) or checking (checkers), or both. Functional neuroimaging has been used to identify the neural correlates of the urge to ritualize but has not distinguished between washing and checking symptoms in OCD. We used functional magnetic resonance imaging to compare the neural response to emotive pictures in washers and checkers. METHODS: In one of two 5-minute experiments, washers (N = 7), checkers (N = 7) and age-matched normal controls (N = 14) were scanned while viewing alternating blocks of normally disgusting (rated as disgusting by all subjects) and neutral pictures. In the other experiment, all patients and a normal subgroup (N = 8) viewed alternating blocks of washer-relevant (rated as more disgusting by washers than normal controls or checkers) and neutral pictures. RESULTS: In all subjects, normally disgusting pictures activated visual regions implicated in perception of aversive stimuli and the insula, important in disgust perception. Only in washers were similar regions activated by washer-relevant pictures. In checkers, these pictures activated fronto-striatal regions associated with the urge to ritualize in OCD. Normal controls were more similar in neural response to checkers than washers to these pictures. Both normal controls and checkers had frontal regions activated significantly more by washer-relevant than normally disgusting pictures, and had these regions activated significantly more than washers by washer-relevant pictures. CONCLUSIONS: We demonstrate a differential neural response to washer-relevant disgust in washers and checkers: only washers demonstrate a neural response to washer-relevant disgust associated with emotion perception rather than attention to non-emotive visual detail.

Adolescent↗
PubMed2000

An examination of hypervigilance for external threat in individuals with generalized anxiety disorder and individuals with persecutory delusions using visual scan paths.

One account of generalized anxiety disorder (GAD) is that it results from hypervigilance, manifest as excessive scanning of the external environment and preferential attention to threat. However, for individuals with GAD, there has been no direct study of scanning, and evidence for preferential attention to threat has only been found for threat-words. We therefore devised a new measure of hypervigilance. Visual scan paths were recorded of individuals with GAD (N = 12) and people without a psychiatric illness (N = 12) viewing complex pictures that varied in threat content. People with persecutory beliefs (N = 11) also participated in the study to test the hypothesis that anxiety, via such hypervigilant cognitive processes, may contribute to the maintenance of delusions. Compared with the control group, the anxious individuals were not found either to scan excessively for or to look at threat. The anxiety group was therefore not hypervigilant for external threat, which is inconsistent with the hypervigilance model. As a consequence, the hypothesis that anxiety maintains delusions was not tested. However, additional support was found for the hypothesis that people with delusions form rapid judgements on the basis of less data-gathering than control groups who are either anxious or have no psychiatric illness.

Adult↗
PubMed2000

Depersonalization in cyberspace.

We explored the possibility of carrying out clinical research on the Internet. To do so, we compared psychometric and demographic variables between two groups of sufferers of depersonalization disorder, one recruited via the Internet, the other from outpatients attending the Depersonalization Research Unit. No differences were found in demographics or features of depersonalization. Those seen in the clinic were, however, significantly more depressed. We then explored the answers to several questions posted on a depersonalization bulletin board by a second group of Internet users. Useful information on symptoms, precipitants, and treatment was gained. It is concluded that the Internet could become a valuable tool in clinical psychiatric research.

Adult↗
PubMed1999

A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

Adult↗
PubMed1999

Studying low-density lipoprotein-monoclonal antibody complexes using dynamic laser light scattering and analytical ultracentrifugation.

Monoclonal antibody complexes have proven very useful in the study of low-density lipoproteins (LDLs). Thus, complexes composed of two different monoclonal antibodies, selected from a panel of 11 different antibodies, and LDL have been employed to map apolipoprotein B (apoB) on the surface of the LDL. In this way, apoB was found to surround the LDL as a ribbon with a bow [Chatterton, J. E., et al. (1995) J. Lipid Res. 36, 2027-2037]. Moreover, monoclonal MB19, which recognizes a polymorphic site, has been employed to quantitate the two different allelic forms of apoB found on LDL in human sera, and in this way, we assessed the effect of most of the known common polymorphisms of this protein as well as detected the depletion of the normal allele product in two forms of familial defective apoB-100 [Chatterton, J. E., et al. (1995) Biochemistry 34, 9571-9580; Pullinger, C. R., et al. (1995) J. Clin. Invest. 95, 1225-1234]. In this paper, these studies have been extended by examining by dynamic light scattering and sedimentation velocity techniques the complexes formed with only one antibody, and complexes formed using two antibodies. Our data show that the largest complex formed with a single monoclonal antibody was that of an LDL dimer; no larger, nonspecific complexes were present. With two antibodies, a variety of complexes were seen. Thus, monoclonal antibodies MB47 and 4G3, which bound about 55 degrees apart, formed a very stable dimer. Monoclonal antibodies MB47 and 2D8, which bound 136 degrees apart, formed a very stable tetramer, with four LDLs held together in probably a circular structure with four monoclonal antibodies. Finally, monoclonal antibodies 2D8 and 1D1, which bound 86 degrees apart, probably formed a less stable LDL tetramer, held together by three to four monoclonal antibodies. A rationale for these structures is discussed, as well as the biological relevance of these complexes.

Animals↗
PubMed1999

Renaturation of recombinant Treponema pallidum rare outer membrane protein 1 into a trimeric, hydrophobic, and porin-active conformation.

We have previously observed that while native Treponema pallidum rare outer membrane protein 1 (Tromp1) is hydrophobic and has porin activity, recombinant forms of Tromp1 do not possess these properties. In this study we show that these properties are determined by conformation and can be replicated by proper renaturation of recombinant Tromp1. Native Tromp1, but not the 47-kDa lipoprotein, extracted from whole organisms by using Triton X-114, was found to lose hydrophobicity after treatment in 8 M urea, indicating that Tromp1's hydrophobicity is conformation dependent. Native Tromp1 was purified from 0.1% Triton X-100 extracts of whole organisms by fast-performance liquid chromatography (FPLC) and shown to have porin activity in planar lipid bilayers. Cross-linking studies of purified native Tromp1 with an 11 A cross-linking agent showed oligomeric forms consistent with dimers and trimers. For renaturation studies of recombinant Tromp1 (rTromp1), a 31,109-Da signal-less construct was expressed in Escherichia coli and purified by FPLC. FPLC-purified rTromp1 was denatured in 8 M urea and then renatured in the presence of 0.5% Zwittergent 3,14 during dialysis to remove the urea. Renatured rTromp1 was passed through a Sephacryl S-300 gel exclusion column previously calibrated with known molecular weight standards. While all nonrenatured rTromp1 eluted from the column at approximately the position of the carbonic anhydrase protein standard (29 kDa), all renatured rTromp1 eluted at the position of the phosphorylase b protein standard (97 kDa), suggesting a trimeric conformation. Trimerization was confirmed by using an 11 A cross-linking agent which showed both dimers and trimers similar to that of native Tromp1. Triton X-114 phase separations showed that all of renatured rTromp1, but none of nonrenatured rTromp1, phase separated exclusively into the hydrophobic detergent phase, similar to native Tromp1. Circular dichroism of nonrenatured and renatured rTromp1 showed a marked loss in alpha-helical secondary structure of renatured rTromp1 compared to the nonrenatured form. Finally, renatured rTromp1, but not the nonrenatured form, showed porin activity in planar liquid bilayers. These results demonstrate that proper folding of rTromp1 results in a trimeric, hydrophobic, and porin-active conformation similar to that of the native protein.

Bacterial Proteins↗
PubMed1999

Selectin blockade reduces neutrophil interaction with platelets at the site of deep arterial injury by angioplasty in pigs.

The adhesion of neutrophils to damaged arterial surfaces is increased in the presence of platelets by a mechanism implicating platelet P-selectin. Such interactions may enhance thrombus formation and the vascular response to injury. In this study, we investigated the effects of a selectin blocker (CY-1503), an analogue of sialyl Lewisx, on platelet and neutrophil interactions after arterial injury produced by angioplasty in pigs.51Cr-platelet deposition and 111In-neutrophil adhesion were quantified on intact, mildly and deeply injured carotid arterial segments, produced by balloon dilation, in control (saline, n=8) and treated (CY-1503, 15 mg/kg IV, n=7) pigs. The hematological parameters, the aggregation of whole blood in response to adenosine diphosphate, and the activating clotting time, as well as the heart rate and mean arterial blood pressure, were similar among groups and were not influenced significantly by CY-1503. The level of platelet and neutrophil adhesion increased significantly with the severity of arterial injury but was not influenced by CY-1503 on intact and mildly injured arterial segments. However, at the site of deep arterial injury, CY-1503 treatment was associated with a 58% reduction (P<0.01) in neutrophil adhesion, from 446.7+/-72.6x10(3) neutrophils/cm2 in the control group to 186.8+/-38.7x10(3) neutrophils/cm2 in the CY-1503-treated group, whereas platelet deposition remained unchanged (43.4+/-15.6x10(6) platelets/cm2 versus 50.1+/-12.2x10(6) platelets/cm2 in the control group). In in vitro adhesion experiments, using isolated platelet and neutrophil suspensions, we found that CY-1503 interfered with the adhesion of neutrophils to damaged arterial surfaces only in the presence of platelets. In contact with thrombogenic arterial surfaces, adherent and activated platelets supports neutrophil adhesion at the site of deep injury by an adhesive interaction involving neutrophil sialyl Lewisx. The inhibitory effect of CY-1503 on neutrophil interaction with adherent platelets may be clinically relevant in patients undergoing percutaneous transluminal coronary angioplasty where platelet and neutrophil interactions may enhance the acute and chronic arterial response to injury.

Angioplasty↗
PubMed1999

Assessment of medical personnel exposure to nitrogen oxides during inhaled nitric oxide treatment of neonatal and pediatric patients.

OBJECTIVE: This study was an assessment of potential exposures of medical personnel to nitrogen oxides during simulated and actual inhaled nitric oxide treatment of newborn and pediatric patients. DESIGN: Breathing zone exposures to nitric oxide (NO) and nitrogen dioxide (NO(2)) were monitored using data-logging personal dosimeters during simulated and actual administration of NO gas to patients in an intensive care setting. Sample. A total of 28 bedside nurses and 18 respiratory therapists were monitored during 6 different patient treatments. ANALYSIS: The highest measured concentrations of NO and NO(2) in the personal breathing zones of the nurses and respiratory therapists were peak readings (<1 minute in duration) of 6.7 parts per million (ppm) NO and 3.1 ppm NO(2). Exposures averaged throughout 15 minutes and throughout the work shift were below the limit of detection (0.8-ppm NO and 0.5-ppm NO(2)). CONCLUSION: Detectable exposures to NO and NO(2) were brief, infrequent, and well below Occupational Safety and Health Administration permissible exposure limits or any other exposure guideline, eg, American Conference of Governmental Hygienists Threshold Limit Values.

Administration, Inhalation↗
PubMed1999

An investigation into the perception of dominance from schematic faces: a study using the World-Wide Web.

The World-Wide Web (WWW) is considered to be a viable tool for scientific research, and several investigators have already made use of it in their studies. Although the WWW allows researchers to access a vast subject pool, questions of reliability and validity need to be addressed before it is incorporated into mainstream research. By replicating, on the Internet, an existing study (Keating, Mazur, & Segall, 1977) on the perception of schematic faces, we were able to conclude that experimental work carried out in this manner is not necessarily biased by the medium. One difference from previous work was the effect of a smiling versus a nonsmiling face on the perception of dominance, given an identical brow position for the two faces. This was replicated on a different occasion with different subjects, which may represent a shift in attitudes to this facial configuration since the original study was conducted. Young North American males were overrepresented in our sample, but comparison with other surveys indicates that the population sampled by the Internet is becoming more representative.

Facial Expression↗
PubMed1998

Neural responses to facial and vocal expressions of fear and disgust.

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus.

Adult↗
PubMed1998

Investigation of facial recognition memory and happy and sad facial expression perception: an fMRI study.

We investigated facial recognition memory (for previously unfamiliar faces) and facial expression perception with functional magnetic resonance imaging (fMRI). Eight healthy, right-handed volunteers participated. For the facial recognition task, subjects made a decision as to the familiarity of each of 50 faces (25 previously viewed; 25 novel). We detected signal increase in the right middle temporal gyrus and left prefrontal cortex during presentation of familiar faces, and in several brain regions, including bilateral posterior cingulate gyri, bilateral insulae and right middle occipital cortex during presentation of unfamiliar faces. Standard facial expressions of emotion were used as stimuli in two further tasks of facial expression perception. In the first task, subjects were presented with alternating happy and neutral faces; in the second task, subjects were presented with alternating sad and neutral faces. During presentation of happy facial expressions, we detected a signal increase predominantly in the left anterior cingulate gyrus, bilateral posterior cingulate gyri, medial frontal cortex and right supramarginal gyrus, brain regions previously implicated in visuospatial and emotion processing tasks. No brain regions showed increased signal intensity during presentation of sad facial expressions. These results provide evidence for a distinction between the neural correlates of facial recognition memory and perception of facial expression but, whilst highlighting the role of limbic structures in perception of happy facial expressions, do not allow the mapping of a distinct neural substrate for perception of sad facial expressions.

Adult↗
PubMed1998

Abnormal visual scan paths: a psychophysiological marker of delusions in schizophrenia.

The role of the visual scan path as a psychophysiological marker of visual attention has been highlighted previously (Phillips and David, 1994). We investigated information processing in schizophrenic patients with severe delusions and again when the delusions were subsiding using visual scan path measurements. We aimed to demonstrate a specific deficit in processing human faces in deluded subjects by relating this to abnormal viewing strategies. Scan paths were measured in six deluded and five non-deluded schizophrenics (matched for medication and negative symptoms), and nine age-matched normal controls. Deluded subjects had abnormal scan paths in a recognition task, fixating non-feature areas significantly more than controls, but were equally accurate. Re-testing after improvement in delusional conviction revealed fewer group differences. The results suggest state-dependent abnormal information processing in schizophrenics when deluded, with reliance on less-salient visual information for decision-making.

Adult↗
PubMed1998

Transglutaminase-induced cross-linking between subdomain 2 of G-actin and the 636-642 lysine-rich loop of myosin subfragment 1.

G-actin was covalently cross-linked with S1 in a bacterial transglutaminase-catalyzed reaction. The cross-linking sites were identified with the help of fluorescent probes and limited proteolysis as the Gln-41 on the DNase I binding loop of subdomain 2 in G-actin and a lysine-rich loop (residues 636-642) on the S1 heavy chain. The same lysine-rich loop was cross-linked to another region of G-actin in a former study (Combeau, C., D. Didry, and M-F. Carlier. 1992. J. Biol. Chem. 267:14038-14046). This indicates the existence of more than one G-actin-S1 complex. In contrast to G-actin, no cross-linking was induced between F-actin and S1 by the transglutaminase reaction. This shows that in F-actin the inner part of the DNase I binding loop, where Gln-41 is located, is not accessible for S1. The cross-linked G-actin-S1 polymerized upon addition of 2 mM MgCl2 as indicated by electron microscopy and sedimentation experiments. The filaments obtained from the polymerization of cross-linked actin and S1 were much shorter than the control actin filaments. The ATPase activity of the cross-linked S1 was not activated by actin, whereas the K+ (EDTA)-activated ATPase activity of S1 was unaffected by the cross-linking. The cross-linking between G-actin and S1 was not influenced by the exchange of the tightly bound calcium to magnesium; however, it was inhibited by the exchange of the actin-bound ATP to ADP. This finding supports the view that the structure of the DNase binding loop in ADP-G-actin is somewhere between the structures of ATP-G-actin and F-actin.

Actins↗
PubMed1998

Effect of real-time teleradiology on the practice of the emergency department physician in a rural setting: initial experience.

RATIONALE AND OBJECTIVES: The authors' goal was to determine the feasibility and usefulness of online teleradiology consultation for emergency department physicians at a rural hospital. MATERIALS AND METHODS: Electronic linkage between the emergency department of Chatham County Regional Hospital (remote site) and the University of North Carolina Hospitals (host site) was established via a fiberoptic network. From October 1995 through September 1996, teleradiology consultation was initiated by an emergency department physician at the remote site and was provided online by host-site radiologists using a commercially available teleradiology system and a high-resolution digitizer. The turnaround time for each teleradiology consultation was calculated, and the effect of the consultation on diagnosis and treatment was assessed. The emergency department physicians scored their satisfaction and comfort levels with the system by using a scale of 1-7, with 7 representing the highest and 1 representing the lowest satisfaction and comfort. The online soft-copy interpretation was compared with a later interpretation of the original hard copy. RESULTS: A total of 123 separate studies comprising 460 radiographs were successfully transmitted in 90 discrete teleradiology events. The mean turnaround time for a teleradiology consultation was 1.3 hours. The teleradiology consultations led to changes in the emergency department physician's initial diagnosis in 27 of 90 cases (30%) and resulted in treatment changes in 23 of 90 cases (26%). The emergency department physicians reported an average satisfaction score of 5.4 and a comfort level of 5.6 with the teleradiology system. No major discrepancy between soft- and hard-copy interpretations was noted. CONCLUSION: Online real-time teleradiology consultation is feasible with available technology.

Adolescent↗