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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 73 records · Page 4Linked to original sources
PubMed1997

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. CONCLUSIONS: These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Adult↗
PubMed1997

A controlled family study of late-onset non-affective psychosis (late paraphrenia).

BACKGROUND: The relationship between those schizophrenia-like conditions that have their onset in late life and early-onset schizophrenia is unclear. Very few family history studies of patients with late-onset psychosis have been reported, and it is not known whether their relatives have an increased risk of psychosis. METHOD: Information was collected on the psychiatric morbidity of 269 first-degree relatives of patients with schizophrenia or delusional disorder with an onset after the age of 60 (late paraphrenia), and 272 first-degree relatives of healthy elderly control subjects, using a research diagnostic instrument. RESULTS: With a narrow age range (15-50 years) at risk, the estimated lifetime risk of schizophrenia was 1.3% in the relatives of both cases and controls. With a wider age range (15-90 years) at risk, estimated lifetime risk of schizophrenia was 2.3% for the relatives of cases and 2.2% for the relatives of controls. However, depression was significantly more common among the relatives of cases than controls. CONCLUSIONS: Those schizophrenia-like psychoses with onset in late life are not genetically associated with schizophrenia.

Adult↗
PubMed1996

Modulation of auditory and visual cortex by selective attention is modality-dependent.

Using functional magnetic resonance imaging (fMRI), we investigated whether the response of auditory and visual cortex was modulated by attending selectively to either heard or seen numbers presented simultaneously. Alternating attention between modalities modulated fMRI signal within the corresponding sensory cortex. This study provides evidence that attention acts locally during early auditory cognitive sensory processing, and that modulation of auditory and visual sensory cortex by attention is modality-dependent.

Adult↗
PubMed1996

A direct demonstration of functional specialization within motion-related visual and auditory cortex of the human brain.

BACKGROUND: Physiological studies of the macaque brain have shown that there is a large expanse of visual cortex, the V5 complex, which is specialized for visual motion, and that several areas within V5 are specialized for different kinds of visual motion. In continuing work on motion-related visual cortex, we wished to chart the specialized visual motion areas in the human brain and to determine their anatomical relationship. Human subjects viewed different motion displays, and the cortical location of the increased activity produced by each stimulus was recorded. The technique of functional magnetic resonance imaging (fMRI) was used, in order to image the same subjects repeatedly. RESULTS: We found that each of the three motion stimuli activated specific parts of the V5 complex. These sites of activation overlap with V5 and, to a smaller extent, with each other. Unexpectedly, the three motion stimuli also activated neighbouring, but nonoverlapping, regions of auditory cortex that are normally activated by the perception of speech. CONCLUSIONS: The three sites of activation produced by the visual motion stimuli occupy adjacent territories within the V5 complex. Components of the V5 complex are specifically connected to regions within auditory cortex.

Auditory Cortex↗
PubMed1996

Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1.

Adherence of mature Plasmodium falciparum parasitized erythrocytes (PRBCs) to microvascular endothelium contributes directly to acute malaria pathology. We affinity purified molecules from detergent extracts of surface-radioiodinated PRBCs using several endothelial cell receptors known to support PRBC adherence, including CD36, thrombospondin (TSP), and intercellular adhesion molecule 1 (ICAM-1). All three host receptors affinity purified P. falciparum erythrocyte membrane protein 1 (PfEMP1), a very large malarial protein expressed on the surface of adherent PRBCs. Binding of PfEMP1 to particular host cell receptors correlated with the binding phenotype of the PRBCs from which PfEMP1 was extracted. Preadsorption of PRBC extracts with anti-PfEMP1 antibodies, CD36, or TSP markedly reduced PfEMP1 binding to CD36 or TSP. Mild trypsinization of intact PRBCs of P. falciparum strains shown to express antigenically different PfEMP1 released different (125)I-labeled tryptic fragments of PfEMP1 that bound specifically to CD36 and TSP. In clone C5 and strain MC, these activities resided on different tryptic fragments, but a single tryptic fragment from clone ItG-ICAM bound to both CD36 and TSP. Hence, the CD36- and TSP-binding domains are distinct entities located on a single PfEMP1 molecule. PfEMP1, the malarial variant antigen on infected erythrocytes, is therefore a receptor for CD36, TSP, and ICAM-1. A therapeutic approach to block or reverse adherence of PRBCs to host cell receptors can now be pursued with the identification of PfEMP1 as a malarial receptor for PRBC adherence to host proteins.

Animals↗
PubMed1996

Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure.

OBJECTIVES: This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure. BACKGROUND: Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis. METHODS: The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2). RESULTS: Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05). CONCLUSIONS: Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Acute Disease↗
PubMed1996

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome.

Two subjects with narcoleptic syndrome and three healthy volunteers underwent functional magnetic resonance imaging during the simultaneous presentation of periodic auditory and visual stimuli both before and after administration of amphetamine. The effect of amphetamine in control subjects was a small reduction in the extent of sensory-induced activation. In the narcoleptic subjects, amphetamine led to an increase in the extent of induced activation within primary and association sensory cortex.

Acoustic Stimulation↗
PubMed1996

Biatrial appendage hypertrophy but not ventricular hypertrophy: a unique feature of canine pacing-induced heart failure.

BACKGROUND: The canine model of pacing-induced heart failure is characterized by an absence of ventricular hypertrophy despite severe hemodynamic stress and neurohormonal activation. Given the mode of ventricular pacing, hypertrophy might occur in the atrial appendage. METHODS AND RESULTS: Seventeen dogs underwent continuous right ventricular pacing for 3 weeks to severe heart failure. Twelve normal dogs served as control subjects. Pacing produced marked increases in both pulmonary capillary wedge pressure (7.6 +/- 1.8 mmHg at baseline to 32.6 +/- 7.5 mmHg at 3 weeks, P < .001) and right atrial pressure (6.5 +/- 1.8 to 15.1 +/- 2.4 mmHg, P < .001), marked increases in normalized left ventricular volume (3.0 +/- 0.5 to 4.6 +/- 0.5 mL/kg, P < .001) and left atrial volume (1.0 +/- 0.2 to 2.6 +/- 0.5 mL/kg, P < .001), but no change in left ventricular mass (2.3 +/- 0.4 to 2.6 +/- 0.5 g/kg, differences not significant), indicating no ventricular hypertrophy. Compared to the control dogs, total heart weight in the test animals was similar, but both the left appendage (0.18 +/- 0.04 vs 0.10 +/- 0.03 g/kg, P < .001) and right atrial appendage (0.15 +/- 0.03 vs 0.12 +/- 0.02 g/kg, P = .004) were much heavier than those of the control dogs. CONCLUSIONS: Rapid right ventricular pacing in the dog induces severe heart failure associated with a dichotomous response in the atrial appendage versus the ventricle. Aside from being a useful heart failure model that simulates the human condition, this unique feature may have physiologic implications in terms of atrial mechanical and endocrine functions and have applications for future studies into the mechanisms of cardiac remodeling and hypertrophy.

Animals↗
PubMed1996

A role for tumor necrosis factor-alpha in the increased mortality associated with Vibrio vulnificus infection in the presence of hepatic dysfunction.

OBJECTIVE: The present study was designed to evaluate whether pre-existing hepatic dysfunction (cirrhosis) leads to increased morbidity and mortality, in part through an inappropriate in vivo tumor necrosis factor-alpha response. SUMMARY BACKGROUND DATA: Vibrio vulnificus is the most commonly isolated member of the noncholera Vibrio sp., responsible for fulminant and frequently fatal septicemia. A strong clinical association exists between hepatic dysfunction and increased morbidity and mortality from Vibrio sp. infection. However, the underlying mechanism behind this association has not been fully delineated. METHODS: Cirrhosis was induced in C57BL/6 (15 to 20 g) mice using thrice-weekly injections of carbon tetrachloride (CCl4) for 7 weeks. Either a 7.0 to 9.5 X 10(7) (low dose) or a 0.8 to 1.2 X 10(9) colony-forming unit (high dose) of V. vulnificus was administered through a mini-laparotomy incision via transgastric puncture into both cirrhotic and control animals. RESULTS: Mortality in cirrhotic mice to low- and high-dose Vibrio infection was 88% (7/8) and 100% (8/8), respectively, whereas mortality in control animals was 0% (0/8) and 12% (1/8), respectively (p<0.01). Tumor necrosis factor-alpha mRNA could be detected by reverse transcriptase polymerase chain reaction in livers and lungs from infected animals 2 and 4 hours after Vibrio administration in both control and cirrhotic animals. Lung and liver tumor necrosis factor-alpha bioactivity, however, was significantly lower in cirrhotic animals infected with Vibrio when compared with controls. Serum tumor necrosis factor-alpha was only sporadically detected in both groups of Vibrio-infected animals. When cirrhotic mice challenged with a low dose of Vibrio sp. were pretreated with 1.0 mg/kg body weight of a novel tumor necrosis factor-alpha receptor immunoadhesin, the increased mortality was completely prevented. CONCLUSIONS: Cirrhotic mice show increased mortality to Vibrio infection, and this increased mortality is dependent on an in vivo tumor necrosis factor-alpha response.

Animals↗
PubMed1996

Breaking and entering: host penetration by the fungal rice blast pathogen Magnaporthe grisea.

Fungal plant pathogens have evolved diverse mechanisms for penetrating into host plant tissue, ranging from entry through natural plant openings to various mechanisms of direct penetration through the outer surface. The filamentous fungus Magnaporthe grisea can cause disease on many species of the grass (Poaceae) family. The disease on rice, Rice Blast, is of enormous economic importance and biological interest. The mechanism used by this pathogen for breaching the formidable host surface barriers has been studied cytologically and genetically as a model for plant pathology, and represents a remarkably sophisticated achievement of nature. The single-celled appressorium of M. grisea acts as a vessel for the generation and application of perhaps the highest turgor pressures known. The fungus requires and utilizes melanin-derived, osmotically generated pressures estimated at 80 bars to drive an actin-rich cellular protuberance through the surface of a rice leaf or plastic coverslip.

Ascomycota↗
PubMed1996

Cross-reactive epitope among proteins in Plasmodium falciparum Maurer's clefts and primate leukocytes and platelets.

Erythrocytes infected with malaria parasites often contain membranous vesicles that are presumed to facilitate macromolecule traffic between the parasite and erythrocyte membranes. One such vesicle network, called Maurer's clefts, is expressed in Plasmodium falciparum-infected erythrocytes and contains a 50-kD polypeptide. Using a monoclonal antibody reactive with this polypeptide, we show that hepatic stages of P. falciparum express an epitope common to this blood-stage antigen. In addition, this epitope is cross-reactive with antigens expressed by primate leukocytes and platelets. Such epitopes may induce autoantibodies commonly seen in patients with malaria.

Animals↗
PubMed1996

Use of neural networks in brain SPECT to diagnose Alzheimer's disease.

UNLABELLED: The usefulness of artificial neural networks in the classification of 99mTc-HMPAO SPECT axial brain scans was investigated in a study group of Alzheimer's disease patients and age-matched normal subjects. METHODS: The cortical circumferential profiling (CCP) technique was used to extract information regarding patterns of cortical perfusion. Traditional analysis of the CCP data, taken from slices at the level of the basal ganglia, indicated significant perfusion deficits for Alzheimer's disease patients relative to normals, particularly in the left temporo-parietal and left posterior frontal areas of the cortex. The compressed profiles were then used to train a neural-network classifier, the performance of which was compared with that of a number of more traditional statistical (discriminant function) techniques and that of two expert viewers. RESULTS: The optimal classification performance of the neural network (ROC area = 0.91) was better than that of the alternative statistical techniques (max. ROC area = 0.85) and that of the expert viewers (max. ROC area = 0.79). CONCLUSION: The CCP produces perfusion profiles which are well suited to automated classification methods, particularly those employing neural networks. The technique has the potential for wide application.

Aged↗
PubMed1995

Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes.

Plasmodium falciparum-infected human erythrocytes evade host immunity by expression of a cell-surface variant antigen and receptors for adherence to endothelial cells. These properties have been ascribed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), an antigenically diverse malarial protein of 200-350 kDa on the surface of parasitized erythrocytes (PEs). We describe the cloning of two related PfEMP1 genes from the Malayan Camp (MC) parasite strain. Antibodies generated against recombinant protein fragments of the genes were specific for MC strain PfEMP1 protein. These antibodies reacted only with the surface of MC strain PEs and blocked adherence of these cells to CD36 but without effect on adherence to thrombospondin. Multiple forms of the PfEMP1 gene are apparent in MC parasites. The molecular basis for antigenic variation in malaria and adherence of infected erythrocytes to host cells can now be pursued.

Amino Acid Sequence↗
PubMed1995

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging.

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically "run" and "frozen" during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.

Echo-Planar Imaging↗