Search PubMed⌕ Search

Biomedical subjects

H Morris

Publications and source records attributed to H Morris.

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

Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.

PURPOSE: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N-methyl-D-aspartate (NMDA) receptor (NR) 2A/B coassembled with NR1 subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes. METHODS: The histopathological, morphological, and immunocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from subdural grids. The NMDA antibodies identified subunits NR1 (splicing variants 1a, 1b, 2a, and 2b) and NR2A/B. RESULTS: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity. CONCLUSION: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.

Adolescent↗
PubMed2000

The preclinical pharmacological profile of WAY-132983, a potent M1 preferring agonist.

Muscarinic M1 preferring agonists may improve cognitive deficits associated with Alzheimer's disease. Side effect assessment of the M1 preferring agonist WAY-132983 showed significant salivation (10 mg/kg i.p. or p.o.) and produced dose-dependent hypothermia after i. p. or p.o. administration. WAY-132983 significantly reduced scopolamine (0.3 mg/kg i.p.)-induced hyperswimming in mice. Cognitive assessment in rats used pretrained animals in a forced choice, 1-h delayed nonmatch-to-sample radial arm maze task. WAY-132983 (0.3 mg/kg i.p) significantly reduced scopolamine (0.3 mg/kg s.c.)-induced errors. Oral WAY-132983 attenuated scopolamine-induced errors; that is, errors produced after combining scopolamine and WAY-132983 (to 3 mg/kg p.o.) were not significantly increased compared with those of vehicle-treated control animals, whereas errors after scopolamine were significantly higher than those of control animals. With the use of miniosmotic pumps, 0.03 mg/kg/day (s.c.) WAY-132983 significantly reduced AF64A (3 nmol/3 microliter/lateral ventricle)-induced errors. Verification of AF64A cholinotoxicity showed significantly lower choline acetyltransferase activity in the hippocampi of AF64A-treated animals, with no significant changes in the striatal or frontal cortex. Cognitive assessment in primates involved the use of pretrained aged animals in a visual delayed match-to-sample procedure. Oral WAY-132983 significantly increased the number of correct responses during short and long delay interval testing. These effects were also apparent 24 h after administration. WAY-132983 exhibited cognitive benefit at doses lower than those producing undesirable effects; therefore, WAY-132983 is a potential candidate for improving the cognitive status of patients with Alzheimer's disease.

Animals↗
PubMed1999

Synthesis and SAR of adatanserin: novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT(1A) and 5-HT(2) activity as potential anxiolytic and antidepressant agents.

Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT(1A) receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT(1A) receptors (K(i) = 8 nM) and acceptable selectivity versus D(2) receptors (K(i) = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylamide, demonstrated high affinity for 5-HT(1A) binding sites (K(i) = 1 nM for both) and moderate affinity for 5-HT(2) receptors (K(i) = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT(1A) agonist activity in vivo in rat serotonin syndrome and 5-HT(2) antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT(1A) partial agonist and 5-HT(2) antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

Animals↗
PubMed1999

Molecular cloning and demonstration of an aminopeptidase activity in a filarial nematode glycoprotein.

ES-62 is an abundant phosphorylcholine-containing secreted glycoprotein of the filarial nematode Acanthocheilonema viteae. Using an antiserum directed against the parasite molecule, 3 cDNAs of size, approximately 1.5-1.6 kbp were isolated from an A. viteae expression library. Sequence analysis in combination with N-terminal amino acid sequencing of purified ES-62 revealed that each clone contained a full-length cDNA for ES-62 corresponding to 474 amino acid residues but differed in their 5' and 3' untranslated regions. Characterisation of the 5' end of ES-62 mRNA using 5' rapid amplification of cDNA ends showed that it coded for a signal sequence. Several tryptic peptides were independently sequenced using quadruple-time-of-flight mass spectrometry and used to confirm the cDNA sequence. The mature protein was found to contain three potential N-linked glycosylation sites. Comparison of the derived amino acid sequence of ES-62 with the SwissProt database identified a sequence (between amino acid residues approximately 250 and 350 of mature ES-62) with significant similarity to several bacterial/fungal aminopeptidases. Incubation of ES-62 with leucine-7-amino-4-methylcoumarin as substrate confirmed that ES-62 possessed aminopeptidase activity.

Amino Acid Sequence↗
PubMed1999

5HT antagonists attenuate MK801-impaired radial arm maze performance in rats.

Glutamatergic hypofunction occurs in Alzheimer's disease (AD). MK801, a noncompetitive blocker of glutamate N-methyl-D-aspartate receptors, was used to disrupt the cognitive performance of rats trained on a delayed nonmatching to sample radial maze task. Drugs which act by blocking serotonin (5-HT) receptors were evaluated for their ability to reduce the cognitive impairment produced by MK801. Specifically, WAY-100635, a selective 5-HT1A receptor antagonist, buspirone, a 5-HT1A partial agonist, ritanserin, a 5-HT2 antagonist, and ondansetron, a 5-HT3 antagonist, were assessed. In addition, the muscarinic agonist arecoline was evaluated for its potential cognitive benefit in this model. It was found that WAY-100635 significantly reduced the cognitive impairment induced by MK801. Treatment with single doses of ritanserin, ondansetron, or arecoline in combination with MK801 did not result in a cognitive impairment, indicating that these drugs attenuated the MK801 impairment. The combination of buspirone and MK801 resulted in an inability of the animals to complete the task. These results suggest that interactions between 5-HT and glutamate may mediate the beneficial effects of reducing cognitive impairment and that 5-HT antagonists, especially selective 5-HT1A antagonists, may be useful in treating AD. Further, it is indicated that the MK801 model of cognitive impairment may add to the armamentarium of tools available to predict treatment efficacy in AD.

Alzheimer Disease↗
PubMed1999

Use of corticosteroids to suppress drug toxicity in complicated tuberculosis.

Four cases of tuberculosis complicated by allergic or toxic reactions to antibiotic treatment are presented. In each, it was considered essential to suppress the reactions in order to give effective chemotherapy. This was achieved by using prednisolone generally in a dose of 40 mg/day or less during the continuation phase of therapy. Reactions to essential treatment are an important indication for corticosteroid treatment in tuberculosis.

Adult↗
PubMed1999

Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects.

Oral glucose is a potent stimulant of glucagon-like peptide-1 (GLP-1) secretion. The effect of oral fructose on GLP-1 secretion in humans is unknown. The aims of this study were to determine (i) whether oral fructose stimulates GLP-1 secretion and (ii) the comparative effects of oral glucose and fructose on appetite. On 3 separate days, 8 fasting healthy males received, in single-blind randomized order (i) 75 g glucose, (ii) 75 fructose, or (iii) 75 g glucose followed by 75 g fructose I h later. Venous glucose, insulin and GLP-1 were measured. Appetite was assessed by visual analog questionnaires and intake of a buffet meal. Whereas glucose and fructose both increased plasma glucose, insulin and GLP-1 (P < 0.000)] for all), the response to glucose was much greater (P < 0.005 for all). There was no increase in plasma GLP-1 when fructose was given after glucose. There was no difference in food intake after oral glucose or fructose. We conclude that oral fructose (75 g) stimulates GLP-1 (and insulin) secretion, but the response is less than that to 75 g glucose. These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation.

Adult↗
PubMed1999

Clinical genetics of familial progressive supranuclear palsy.

Recent studies have shown that progressive supranuclear palsy (PSP) could be inherited, but the pattern of inheritance and the spectrum of the clinical findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology in four probands, with familial PSP. Pathological diagnosis was confirmed according to recently reported internationally agreed criteria. The spectrum of the clinical phenotypes in these families was variable including 34 typical cases of PSP (12 probands plus 22 secondary cases), three patients with postural tremor, three with dementia, one with parkinsonism, two with tremor, dystonia, gaze palsy and tics, and one with gait disturbance. The presence of affected members in at least two generations in eight of the families and the absence of consanguinity suggests autosomal dominant transmission with incomplete penetrance. We conclude that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic expression of the disease.

Adult↗
PubMed1999

Periictal diffusion-weighted imaging in a case of lesional epilepsy.

PURPOSE: Diffusion-weighted MR imaging (DWI) has been used for the early diagnosis of acute ischemic lesions in humans and in animal models of focal status epilepticus. We hypothesized that DWI may be a sensitive, noninvasive tool for the localization of the epileptogenic area during the periictal period. METHODS: A periictal DWI study was performed on a 35-year-old patient during focal status epilepticus with repetitive prolonged focal motor seizures originating from a lesion in the right frontal lobe. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: On DWI, a single area of signal increase (decrease in ADC) was found in the region of focal electrocorticographic seizures that was mapped intraoperatively. CONCLUSIONS: Ictal/postictal DWI may be a useful technique for seizure localization in patients with lesional epilepsy.

Adult↗
PubMed1999

A new epileptic seizure classification based exclusively on ictal semiology.

Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.

Electroencephalography↗
PubMed1999

Left ventricular opacification by intravenous contrast echocardiography.

BACKGROUND: The present study was undertaken in order to evaluate the efficacy of the intravenous administration of Albunex in obtaining left ventricular opacification and the relationship between left ventricular opacification and pulmonary pressures and cardiac function. METHODS: Fifty-two adult patients, mostly affected by ischemic heart disease, were enrolled in the study. In 37 of these patients, a complete right heart hemodynamic study was performed after Swan-Ganz catheterization. Albunex was administered in three randomized doses (0.10, 0.15 and 0.20 ml/kg) to all the patients. Left ventricular opacification was assessed both visually and using videodensitometric analysis. RESULTS: Left ventricular opacification was obtained in 93% of all the injections and an intermediate or strong opacification was obtained in 68%, while absent opacification was observed in 6% of the injections, irrespective of the contrast dose. An incremental opacification efficacy trend was observed from the lower to the higher dose, with an intermediate or strong opacification in 58 and in 77% of 0.10 and 0.20 ml/kg injections, respectively. Irrespective of the contrast dose, an enhancement of the endocardial borders was observed in 61% of the wall segments suboptimally visualized in basal conditions. The endocardial borders enhancement was obtained in 39 and in 79% of segments using the 0.10 and the 0.20 ml/kg doses, respectively. No statistically significant differences were observed between the videodensitometric parameters obtained using the three contrast doses. Finally, a significant relationship was observed between left ventricular opacification parameters and pulmonary pressures and left ventricular functional parameters, irrespective of the contrast doses considered. CONCLUSIONS: The results we obtained demonstrate the good overall efficacy of Albunex administered intravenously in order to obtain left ventricular opacification in a clinical population of cardiac patients. Moreover, they suggest that the dosage to be used clinically should preferably be at least 0.20 ml/kg, although no significant influence of contrast dosage on videodensitometric parameters has been observed. Finally, irrespective of the contrast dosage, the magnitude of left ventricular opacification appears to be influenced by the hemodynamic status of the patient.

Adult↗
PubMed1998

Semiological seizure classification.

We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows: a. Auras are ictal manifestations having sensory, psychosensory, and experiential symptoms. b. Autonomic seizures are seizures in which the main ictal manifestations are objectively documented autonomic alterations. c. "Dialeptic" seizures have as their main ictal manifestations an alteration of consciousness that is independent of ictal EEG manifestations. The new term "dialeptic" seizure has been coined to differentiate this concept from absence seizures (dialeptic seizures with a generalized ictal EEG) and complex partial seizures (dialeptic seizures with a focal ictal EEG). d. Motor seizures are characterized mainly by motor symptoms and are subclassified as simple or complex. Simple motor seizures are characterized by simple, unnatural movements that can be elicited by electrical stimulation of the primary and supplementary motor area (myoclonic, tonic, clonic and tonic-clonic, versive). Complex motor seizures are characterized by complex motor movements that resemble natural movements but that occur in an inappropriate setting ("automatisms"). e. Special seizures include seizures characterized by "negative" features (atonic, astatic, hypomotor, akinetic, and aphasic seizures). The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed.

Electroencephalography↗
PubMed1998

Upbeat nystagmus: clinicoanatomical correlation.

A patient is reported on with isolated upbeating nystagmus with a linear slow phase in whom a solitary lesion, probably inflammatory, was detected radiologically in the dorsal paramedian caudal medulla, encompassing the most caudal of the perihypoglossal nuclei, the nucleus intercalatus of Staderini. The conjunction of a vestibular pattern of nystagmus with this focal lesion runs contrary to a previous suggestion that the nucleus intercalatus may act as a neural integrator for vertical conjugate eye movements.

Adult↗
PubMed1998

Home care case management. Perspectives from the home front.

Focus groups were held with home care case managers in two cities in Canada which provided information on the role of the case manager, factors that influence decision making, recent changes that have taken place in case management, and the different and positive aspects of home care case management. Factors which influence decision making were grouped into organizational, client, family, other professionals, and case management factors. The differences in case managers' preparation and functions in the two sites are discussed. The difficult aspects of case management included making tough decisions related to client resources, and client, work life, and management issues. The positive aspects included the personal interaction with clients, the opportunity to follow through on services to clients, the diversity of case management work, and the opportunity for relatively independent professional practice.

Attitude of Health Personnel↗
PubMed1997

The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction.

Recombinant human procollagenase-3 and a C-terminal truncated form (Delta249-451 procollagenase-3) have been stably expressed in myeloma cells and purified. The truncated proenzyme could be processed by aminophenylmercuric acetate via a short-lived intermediate form (N-terminal Leu58) to the final active form (N-terminal Tyr85). The kinetics of activation were not affected by removal of the hemopexin-like C-terminal domain. The specific activities of both collagenase-3 and Delta249-451 collagenase-3 were found to be similar using two quenched fluorescent substrates, but Delta249-451 collagenase-3 failed to cleave native triple helical collagens (types I and II) into characteristic one- and three-quarter fragments. It was noted, however, that the beta1,2(I) chains of type I collagen were susceptible to Delta249-451 collagenase-3, which indicates that the catalytic domain displays telopeptidase activity, thereby generating alpha1,2(I) chains that are slightly shorter than those in native type I collagen. It can be concluded that the C-terminal domain is only essential for the triple helicase activity of collagenase-3. Binding of procollagenase-3 and active collagenase-3 to type I collagen is mediated by the C-terminal domain. Both collagenase-3 and Delta249-451 collagenase-3 hydrolyzed the large tenascin C isoform, fibronectin, recombinant fibronectin fragments, and type IV, IX, X, and XIV collagens; thus, these events were independent from C-terminal domain interactions. In contrast, the minor cartilage type XI collagen was resistant to cleavage. Kinetic analysis of the mechanism of inhibition of wild-type and Delta249-451 collagenase-3 by wild-type and mutant tissue inhibitors of metalloproteinase (TIMPs) revealed that the association rates for complex formation were influenced by both N- and C-terminal domain interactions. The C-terminal domain of wild-type collagenase-3 promoted increased association rates with the full-length inhibitors TIMP-1 and TIMP-3 and the hybrid N.TIMP-2/C.TIMP-1 by a factor of up to 33. In contrast, the association rates for complex formation with TIMP-2 and N.TIMP-1/C.TIMP-2 were only marginally affected by C-terminal domain interactions.

Amino Acid Sequence↗
PubMed1997

Analysis of the movement of line-like samples of variable length along the X-axis of a double TE104 and a single TE102 rectangular cavity

Movement of line-like samples with lengths from 5 to 50 mm along the x-axis of the double TE104 rectangular cavity has been analyzed. The observed dependencies of the EPR signal intensity versus sample position showed: (i) a sharp maximum for sample lengths from 5 to 20 mm; (ii) a plateau, over which the EPR signal intensity remained constant within experimental errors of 0.26-1.07%, for lengths from 30 to 40 mm; and (iii) a "sloping plateau," which could be approximated by the linear function (correlation, r = 0.98) for sample length 50 mm. Theoretical values of the experimentally observed dependencies of the intensity versus sample position were calculated using the modified sine-squared function and the correlation between observed and theoretically predicted dependencies is very good. The experimental dependence of the EPR signal intensity versus the sample length for samples situated at the same point in the cavity was nonlinear with a maximum for the 40-mm sample. The dependence of the EPR signal intensity upon the movement of a large cylindrical sample (o.d. 4 mm and length 100 mm) along the x-axis of the cavity was similar to that found for the 50-mm sample. However, an additional oscillating signal superimposed on the sloping plateau was observed. The presence of a large sample fixed in the complementary cavity of the double TE104 cavity caused an additional deformation of the signal intensity for a 30-mm sample which was moving in the first cavity. The primary effect was that the plateau was replaced by a region in which the intensity increased linearly with sample position, r = 0.99. Each of the above phenomena may be a source of significant errors in quantitative EPR spectroscopy. Cylindrical samples to be compared should be of identical length and internal diameter. Accurate and precise positioning of each sample in the microwave cavity is essential. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗