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PubMed1995

The role of the thalamus in functional neurosurgery.

The human thalamus has been the focus of much interest as a target organ for the stereotactic surgical modification of particularly pain and movement disorders. The sites receiving the greatest attention are portions of Vc, Vim, Vop, and the medial thalamus. As such procedures require physiologic corroboration of target site, a considerable literature has arisen concerned with electrical stimulation and microelectrode recordings within them. Not only do the physiologic observations accomplish the desired localization, but they also allow an insight into normal and pathologic thalamic physiology. Yet vast areas of the thalamus remain unstudied enigmas.

Brain Mapping↗

PubMed1997

Managing medical research data with a Web-Interfacing Repository Manager.

This paper describes the Web-Interfacing Repository Manager (WIRM), a perl toolkit for managing and deploying multimedia data, which is built entirely from free, platform-independent components. The WIRM consists of an object-relational API layered over a relational database, with built-in support for file management and CGI programming. The basic underlying data structure for all WIRM data is the repository object, a perl associative array whose values are bound to a row of a table in the relational database. Based on our experience implementing a target application (the Brain Mapper Console), we describe five stages through which a system passes as it evolves from a primitive file hierarchy to a full-fledged repository console.

Brain Mapping↗

PubMed1997

Monitoring proteolysis of recombinant human interferon-gamma during batch culture of Chinese hamster ovary cells.

Proteolytic cleavage of recombinant human interferon-gamma (IFN-gamma) expressed in Chinese hamster ovary (CHO) cells during batch fermentation has been monitored by mass spectrometric peptide mapping. IFN-gamma was purified from cell-free culture supernatant by immunoaffinity chromatography and cleaved by endoprotease Asp-N. Peptide fragments were resolved by reverse-phase HPLC and identified by a combination of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and automated N-terminal peptide sequencing. Using this approach, a peptide was identified as the C-terminal fragment of the IFN-gamma polypeptide. Analysis of this peptide by MS indicated that the recombinant IFN-gamma polypeptide secreted by CHO cells was truncated by at least ten amino acids, initially at Gln133-Met134. No full length (143 amino acids) polypeptide molecules were observed at any stages of the fermentation. Additional proteolytic cleavages at basic amino acids N-terminal of Gln133 occurred during the later stages of the culture resulting in a heterogeneous IFN-gamma polypeptide with "ragged" C-termini.

Amino Acid Sequence↗

PubMed1987

Adrenergic stimulation of the rat mesenteric vascular bed: a combined micro- and macrocirculatory study.

The sympathetic nervous system is one of the primary factors controlling vascular resistance. Vascular smooth muscle contraction by sympathetic stimulation is mediated primarily by alpha-adrenoceptors. In this study, we investigated the effects of different forms of adrenergic stimulation on simultaneously measured macro- and microcirculatory dynamics in the rat mesenteric vascular bed. Macrocirculatory effects were measured by means of registration of changes in mean arterial pressure (MAP) and blood flow feeding this tissue via a miniaturized Doppler flow probe around the superior mesenteric artery. Microvascular changes were measured at the level of A2 arterioles by means of intravital microscopic registration of arteriolar diameters and red blood cell velocity (RBC vel). Topical or intra-arterial application of noradrenaline caused a dose-dependent decrease in arteriolar diameter and RBC vel at doses that did not cause significant systemic effects. On the other hand, during intravenous application of noradrenaline or other vasopressor substances an increase in MAP and decrease in organ (Doppler) blood flow was not parallelled by a decrease in arteriolar diameter or RBC vel. In contrast, RBC vel increased in a dose-related manner, whereas arteriolar diameter only secondarily decreased to a small degree. Similar results were obtained when the sympathetic nervous system was activated by means of electrical stimulation of the posterior hypothalamus. These data indicate that adrenergic stimulation can elicit different vascular responses. The ultimate microvascular effect depends upon the way of stimulation or route of drug administration.

Animals↗

PubMed2005

Epitope mapping of monoclonal antibody 4C8 recognizing the protein huntingtin.

Huntington's disease is a dominantly inherited, devastating neurodegenerative disorder, caused by a polyglutamine expansion (>37) in the N-terminal region of huntingtin, a protein of unknown function. In patients and normal individuals, N-terminal fragments of huntingtin are found, and the N-terminal fragments of mutant huntingtin are cytotoxic. The functions of wild-type huntingtin and the mechanisms underlying the toxic effects of mutant huntingtin are still ill defined. To get more insight into these topics, monoclonal antibodies (MAbs) are indispensable tools. Antibodies raised against the N-terminus are especially important. Among these, the 4C8 mouse MAb has been extensively used in various approaches. In this study, we have mapped the epitope of 4C8 to a 15-amino acid (aa) region spanning from aa 443 to 457 of the human protein, and found that mutation of three consecutive glutamic acids present in this region disrupts the recognition by 4C8. These results allow a more accurate interpretation of the results obtained by usage of the 4C8 antibody and broaden the utility of this antibody.

Amino Acid Sequence↗

PubMed1991

Persistent rat parvovirus infection in individually housed rats.

The duration of infection with rat virus (RV), an autonomous rodent parvovirus, was examined at multiple intervals over 6 months in rats inoculated by the oronasal route at 2 days of age or 4 weeks of age and individually housed after weaning to prevent cross-infection. Infectious virus was recovered by explant culture from 32 of 80 rats inoculated as pups and was detected as late as 6 months after inoculation. Rats inoculated as juveniles developed acute infection, but virus was not detected beyond 7 weeks after inoculation. Tissues from rats in both age groups were surveyed for RV DNA by Southern blotting using a double-stranded DNA probe made from a 1700 bp cloned fragment of RV spanning map units 0.19-0.52. Band patterns representative of acute infection (juvenile rats) were consistent with the replicating form of RV DNA, whereas patterns representative of persistent infection (rats inoculated as pups) were suggestive of defective or non-productive viral replication.

Aging↗

PubMed1996

Influence of activated charcoal on the disposition kinetics of methamphetamine enantiomers in the rat following intravenous dosing.

Methamphetamine (MAP) is a central nervous system stimulant that is widely abused by populations of several countries. There is no specific antidote for the treatment of an overdose. Activated charcoal administered orally has been used to enhance the systemic elimination of certain toxic substances via "gastrointestinal dialysis". The results of in vitro studies have shown that MAP can be rapidly adsorbed from solution by activated charcoal. We have evaluated the effect of a single oral dose of activated charcoal on the disposition kinetics of MAP following a short iv infusion. Male Sprague-Dawley rats were given an oral dose of activated charcoal (Actidose-aqua, 1 g/kg) 10 min before a short iv infusion of racemic MAP; whereas the control group was given an equivalent volume of water. Enantiomers of MAP and metabolites in serum and urine were analyzed by an enantiomer-specific method which employed HPLC and detection of a fluorescent derivative. There were no differences in any of the disposition parameters between the two groups. Within each group, the clearance (CLs) of l-MAP was greater than that of d-MAP. However, there were no differences in the steady-state volume of distribution (Vss). The CLs (mL/(min kg)) and Vss (L/kg) values for l- and d-MAP in the control group were (mean +/- SD): 55.8 +/- 20.4, 48.7 +/- 17.9, 2.64 +/- 1.16, and 2.90 +/- 1.36, respectively. The corresponding values in the charcoal-pretreated group were (mean +/- SD): 57.4 +/- 23.4, 51.1 +/- 20.7, 2.79 +/- 1.32, and 2.98 +/- 1.47. These results suggest that oral activated charcoal does not enhance the elimination of MAP from the body.

Animals↗

PubMed2001

Functional neuroimaging of cognition: state-of-the-art.

This paper presents a brief overview of functional neuroimaging studies of cognitive processes. A "publication profile" is identified for PET and fMRI studies of cognitive functions. It is shown that the number of publications has increased exponentially over the last ten years, and that a set of ten journals accounts for the vast majority of publications. It is argued that the field has moved from a state of explorative character to a state of high theoretical sophistication. With special reference to the contributions in this issue of Scandinavian Journal of Psychology, methodological, topical, regional, and clinical implications of cognitive neuroscientific studies are discussed.

Brain↗

PubMed2003

Assessment of the accuracy and safety of the different methods used in mapping the frontal sinus.

INTRODUCTION: Frontal sinus obliteration continues to be the gold standard for frontal disease control and is often employed as a last resort of treatment after more conservative therapies fail. Different methods of sinus mapping have been previously reported and include (1) 6-foot Caldwell radiography, (2) sinus probing, and (3) sinus transillumination. Image-guided technology was recently introduced to clinical practice, but its utility in frontal sinus mapping has not been evaluated. OBJECTIVE: To assess the accuracy and safety of the previously reported methods of frontal sinus mapping and compare them with image-guided mapping. STUDY DESIGN: Five cadaveric heads were used. The four mapping methods were applied to each head along five different axes of the frontal bone: 0, 45, 90, 135, and 180 degrees. The true frontal sinus margin was ascertained. Measurements were made from the true sinus limits to the margin points estimated by the four frontal sinus mapping methods. RESULTS: The image-guided mapping method provided was the most accurate when compared with the other mapping methods (p < .01). The image-guided mapping method was also the least likely to overshoot the real margin compared with the other mapping methods (p < .001). The template method was the least accurate and least safe method. CONCLUSIONS: Image-guided mapping is the most accurate and safest method of mapping the frontal sinus margins.

Cadaver↗

PubMedDate not supplied

Circulatory response to laryngoscopy and tracheal intubation with or without prior oropharyngeal viscous lidocaine.

Oropharyngeal topical anesthesia with viscous lidocaine (25 ml of 2% as a "mouthwash and gargle" 10 min before laryngoscopy) attenuated the pressor but not heart rate (HR) response during laryngoscopy and tracheal intubation. Compared with control patients, mean arterial pressure (MAP) increased less in response to tracheal intubation (23 +/- 5 torr versus 39 +/- 4 torr, p less than 0.05) and returned toward awake levels sooner in patients receiving viscous lidocaine. MAP increased more than 40 torr in response to intubation in 6/20 patients treated with viscous lidocaine, while 12/20 control patients manifested this degree of blood pressure elevation. HR increased about 20 bpm (p less than 0.05) with or without viscous lidocaine. Arterial lidocaine concentrations were less than 0.5 microgram/ml after oropharyngeal anesthesia. Prior topical anesthesia of the oropharynx with viscous lidocaine should be considered when pressor responses during tracheal intubation would be particularly likely or hazardous.

Anesthesia, Local↗

PubMed2004

Mapping medical careers: questionnaire assessment of career preferences in medical school applicants and final-year students.

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers. METHODS: Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted. RESULTS: Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling.

Adolescent↗

PubMed1990

Cholinergic manipulation alters stimulus-evoked metabolic activity in cat somatosensory cortex.

The role of acetylcholine (ACh) in cerebral cortical activity has recently been reevaluated. It now seems clear that this neurotransmitter increases the magnitude of cortical responses. Although substantial information has been gathered regarding the role of ACh in sensory information processing, little is known about the participation of ACh in the organization of maps in the cerebral cortex. To address this issue, we used 2 methods to manipulate the supply of ACh in the somatosensory cortex of cats: 1) unilateral neurotoxic lesions of the basal forebrain and 2) unilateral topical applications of the cholinergic antagonist, atropine. For each experimental condition, the animal received an injection of 2-deoxyglucose (2DG) while identical somatic stimuli were delivered to the right and left forepaws. In the somatosensory cortex, the 2DG uptake most often occurred in the form of patches that extended from layer II to IV. When the patches were reconstructed into 2-dimensional maps of activity throughout the somatosensory cortex, they formed strips that ran in the rostrocaudal direction. The reconstructed maps revealed that the 2DG patterns in ACh-depleted and the normal cortex were similar in their overall topographic distribution. Depletion or antagonism of ACh, however, caused the stimulus-evoked metabolic label to be reduced in dimension and density. Measurements of background activity levels were obtained by using 1) cytochrome oxidase histochemistry or 2) metabolic activity values in regions of somatosensory cortex that were not specifically stimulated. This analysis indicated that background values in the ACh-depleted hemispheres were not different from those in the normal hemispheres. The absence of ACh therefore appears to reduce the cortical response to stimulation, while background activity values do not change. These observations indicate that ACh plays a significant role in the processing of sensory information and the organization of somatosensory cortical maps.

Acetylcholine↗

PubMed1999