Search PubMed⌕ Search

Biomedical subjects

C M Brown

Publications and source records attributed to C M Brown.

At least 73 records · Page 4Linked to original sources

Cerebrospinal fluid free choline in movement disorders of paediatric onset.

We measured free choline in cerebrospinal fluid (CSF) of 78 patients with movement disorders of paediatric onset and various controls as a putative index of central phospholipid metabolism. Most of the disorders studied were myoclonic disorders, such as progressive myoclonus epilepsy, the opsoclonus-myoclonus syndrome, and essential myoclonus, but other movement disorders, interictal seizure disorders, and different neurological and nonneurological disorders were also included. There were no significant differences in CSF choline concentrations in myoclonic disorders or other movement disorders compared with controls. The CSF choline levels were lowest in children with seizure disorders including progressive myoclonus epilepsy. In progressive myoclonus epilepsy, the CSF choline values resembled other epileptic disorders rather than other myoclonic disorders. When all the data were analysed collectively, no significant relation of CSF choline was found to patient age, gender, aliquot of CSF measured, or the length of time the sample was stored at -70 degrees C. Separate analyses of data from children and adults showed a trend toward a biphasic relation between patient age and CSF choline which could be pursued in developmental studies of normal subjects. Reduced CSF choline may indicate increased choline incorporation into brain phospholipids, disturbances of choline metabolism, decreased choline release, or non-neural factors.

Acetylcholine↗

Acute amino acid loads that deplete brain serotonin fail to alter behavior.

Acute depletion of brain serotonin (5-HT) can be induced in both rats and humans by giving an amino acid load deficient in tryptophan (TRY). Because this treatment is relatively easy to administer and short-acting, it seems well suited for studying mood and/or behavioral changes linked to aberrant 5-HT functioning in humans. To investigate the ability of a TRY-deficient amino acid load to induce behavioral changes in animals, this study measured performance on an operant schedule of differential reinforcement of low rates of responding (DRL), locomotor activity in both novel and familiar environments, and paw-lick latencies on a hot-plate. All of these measures have been found previously to be altered by impairments of the brain 5-HT system. Adult male Sprague-Dawley rats were administered by gavage an amino acid load lacking TRY, an amino acid load containing TRY, or distilled water. Three hours later, behavioral tests were conducted. Although 5-HT levels were decreased in the hippocampus (-23.3%) and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in the striatum (-35.1%) and hippocampus (-38.5%), there were no effects of the TRY-deficient load on any of the behavioral tests. Because reliable mood-altering effects have been reported in human subjects using this method, their behavioral counterparts may be too subtle to observe in animals. Alternatively, effects observed in humans may reflect nonserotonergically mediated consequences of such tryptophan deficient amino acid loads and/or preexisting abnormalities of 5-HT or other systems in such people.

Amino Acids↗

Neuropeptide Y-induced operant responding for sucrose is not mediated by dopamine.

Neuropeptide Y (NPY) induces feeding in previously satiated animals after injection into the hypothalamus, especially the perifornical region (PFH). NPY also appears to have rewarding properties as evidenced by its ability to produce a conditioned place preference following injection into the nucleus accumbens (N.Acc), an effect ostensibly mediated by mesolimbic dopamine (DA). Since the progressive-ratio (PR) operant schedule has also been used to assess an organism's motivation to respond for rewarding stimuli, we tested the possibility that NPY increases PR responding for sucrose pellets. Adult male rats were injected with NPY (0-235 pmol) bilaterally through cannulae aimed to terminate in the PFH. This produced a dose-dependent increase in the total number of responses made and the number of reinforcers earned. The DA receptor blocker, alpha-flupenthixol (FLU)(0-0.2 mg/kg intraperitoneally), attenuated both NPY(156 pmol)-induced and drug-free PR responding while having no effect on NPY(156 pmol)-induced free-feeding. FLU injected directly into the N.Acc (0-5 microg) also failed to reduce sucrose free-feeding. These results suggest that distinct reward mechanisms are activated during PFH NPY-induced feeding vs. PR responding, since FLU disrupted the latter but not the former.

Animals↗

Getah virus infection of Indian horses.

An outbreak of disease, characterized by depression, anorexia, fever, limb oedema and lymphocytopenia, occurred on a farm for thoroughbreds in India in 1990. Twenty-six of the 88 horses on the farm were affected, predominantly adults. Signs were present in affected horses for 7-10 days, and the outbreak lasted 21 days. Seven of the 26 affected horses were tested for exposure to Getah virus using paired serum samples, acute and convalescent. Four of the 7 horses seroconverted to Getah virus, and the other three showed a 4-fold or greater rise in titre. The clinical and laboratory findings were similar, but not indentical, to those described in natural and experimental infections in Japanese horses. This is the first description of disease caused by Getah virus infection in horses outside Japan. In addition serum samples from 152 horses from 3 regions of India were evaluated for the presence of antibodies to Getah virus. The seroprevalence was found to be 17%, indicating exposure to the virus elsewhere in Indian horses.

Alphavirus↗

Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross-react with virus and cardiac myosin.

The laboratory-adapted K181 strain of murine cytomegalovirus (MCMV) induces both acute and chronic myocarditis, associated with autoantibodies to cardiac myosin, in susceptible BALB/c mice. However, the K181 MCMV strain has been maintained in the laboratory for many years and may not resemble naturally occurring strains of MCMV in its ability to induce myocarditis. Accordingly, six different isolates of MCMV from wild Mus domesticus were compared with K181 MCMV for their ability to induce myocarditis and autoantibodies to cardiac myosin in BALB/c mice. These isolates were shown to induce acute myocarditis similar to K181 MCMV, with associated focal and diffuse myocardial inflammation. However, the levels of myocarditis induced by the wild isolates during the chronic phase of the disease (days 32-56 post-infection) were low in contrast to the K181 strain. Interestingly, 30% of wild-trapped mice showed histological evidence of myocarditis and all were sero-positive to MCMV. Sera from BALB/c mice infected with wild MCMV isolates and from wild-trapped mice contained antibodies that cross-reacted with MCMV and cardiac myosin (S2 region). The cross-reactive region of MCMV was found to be a 50,000-55,000 MW viral polypeptide. These findings suggest that molecular mimicry may be involved in the pathogenesis of autoimmune myocarditis following infection with both laboratory and wild MCMV strains.

Acute Disease↗

An image correlation analysis of the distribution of clathrin associated adaptor protein (AP-2) at the plasma membrane.

Clathrin associated adaptor protein is involved in endocytosis at the plasma membrane (AP-2) and protein sorting at the Golgi membrane (AP-1). There is a great deal of information available on the structure, function and binding characteristics of AP-2, however, there is little quantitative data on the AP-2 distribution at the membrane. Image correlation spectroscopy is a technique which yields number counts from an autocorrelation analysis of intensity fluctuations within confocal microscopy images. Image correlation spectroscopy analysis of the indirect immunofluorescence from AP-2 at the plasma membrane of CV-1 cells shows that AP-2 is in a bimodal distribution consisting of large coated pit associated aggregates of approximately 60 AP-2 molecules, and smaller aggregates containing approximately 20 AP-2 molecules, which we propose are coated pit nucleation sites. Following hypertonic treatment 25% of the AP-2 molecules dissociate from the large AP-2 aggregates and form AP-2 dimers, leaving the remaining AP-2 as large aggregates with approximately 45 molecules. The smaller AP-2 aggregates completely dissociate forming AP-2 dimers. Dispersion of AP-2 with hypertonic treatment is not seen qualitatively because the number of large AP-2 aggregates is unchanged, the aggregates are just 25% smaller. Change in temperature from 37 degrees C to 4 degrees C has no affect on the number of AP-2 aggregates or the AP-2 distribution between the two populations. These data and estimates of the coated pit size suggest that coated pits cover approximately 0.9% of the cell membrane. Combination of image correlation spectroscopy analysis and measurements of the CV-1 cell surface area show that there are approximately 6x10(5) AP-2 molecules per CV-1 cell with approximately 2x10(5) AP-2 molecules within coated pit structures.

Adaptor Proteins, Vesicular Transport↗

Complementary use of the SciSearch database for improved biomedical information searching.

The use of at least two complementary online biomedical databases is generally considered critical for biomedical scientists seeking to keep fully abreast of recent research developments as well as to retrieve the highest number of relevant citations possible. Although the National Library of Medicine's MEDLINE is usually the database of choice, this paper illustrates the benefits of using another database, the Institute for Scientific Information's SciSearch, when conducting a biomedical information search. When a simple query about red wine consumption and coronary artery disease was posed simultaneously in both MEDLINE and SciSearch, a greater number of relevant citations were retrieved through SciSearch. This paper also provides suggestions for carrying out a comprehensive biomedical literature search in a rapid and efficient manner by using SciSearch in conjunction with MEDLINE.

Cost-Benefit Analysis↗

Partitioning of proteins into plasma membrane microdomains. Clustering of mutant influenza virus hemagglutinins into coated pits depends on the strength of the internalization signal.

Internalization of membrane proteins involves their recruitment into plasma membrane clathrin-coated pits, with which they are thought to interact by binding to AP-2 adaptor protein complexes. To investigate the interactions of membrane proteins with coated pits at the cell surface, we applied image correlation spectroscopy to measure directly and quantitatively the clustering of influenza hemagglutinin (HA) protein mutants carrying specific cytoplasmic internalization signals. The HA system enables direct comparison between isolated internalization signals, because HA itself is excluded from coated pits. The studies presented here provide, for the first time, a direct quantitative measure for the degree of clustering of membrane proteins in coated pits at the cell surface. The degree of clustering depended on the strength of the internalization signal and on the integrity of the clathrin lattices and correlated with the internalization rates of the mutants. The clustering of the HA mutants fully correlated with their ability to co-precipitate alpha-adaptin from whole cells, the first such demonstration for a membrane protein that is not a member of the epidermal growth factor receptor family. Furthermore, both the clustering in coated pits and the co-precipitation with alpha-adaptin were dramatically reduced in the cold, suggesting that low temperature can interfere with the sorting of proteins into coated pits. In addition to the specific results reported here, the general applicability of the image correlation spectroscopy approach to study any process involving the clustering or oligomerization of membrane receptors at the cell surface is discussed.

Adaptor Protein Complex alpha Subunits↗

The translational signal database, TransTerm: more organisms, complete genomes.

TransTerm is a database of initiation and termination sequence contexts from more than 250 organisms listed in GenBank, including the four complete genomes:Haemophilus influenzae, Methanococcus jannaschii, Mycoplasma genitalium,and Saccharomyces cerevisiae. For the current release, more than 60 000 coding sequences were analysed. The tabulated data include initiation and termination contexts organised by species along with quantitative parameters about individual coding sequences (length, %GC, GC3, Nc and CAI). There are also tables of initiation- and termination-region nucleotide-frequencies, codon usage tables and summaries of stop signal usage. TransTerm is available on the World Wide Web at: http://biochem.otago.ac.nz:800/Transterm/homepage.h tml

Base Sequence↗

Electrophysiological evidence on the time course of semantic and phonological processes in speech production.

The temporal properties of semantic and phonological processes in speech production were investigated in a new experimental paradigm using movement-related brain potentials. The main experimental task was picture naming. In addition, a 2-choice reaction go/no-go procedure was included, involving a semantic and a phonological categorization of the picture name. Lateralized readiness potentials (LRPs) were derived to test whether semantic and phonological information activated motor processes at separate moments in time. An LRP was only observed on no-go trials when the semantic (not the phonological) decision determined the response hand. Varying the position of the critical phoneme in the picture name did not affect the onset of the LRP but rather influenced when the LRP began to differ on go and no-go trials and allowed the duration of phonological encoding of a word to be estimated. These results provide electrophysiological evidence for early semantic activation and later phonological encoding.

Adult↗

Lumbovertebral syndrome after repeat extradural blood patch.

We describe an obstetric patient who developed incapacitating headache after inadvertent dural tap and was treated with repeated blood patching. She subsequently developed severe lumbar back pain which, after exclusion of suspected extradural abscess, was treated successfully with simple analgesics and physiotherapy. Two possible explanations are offered to account for her symptoms. We compare this case with others in the literature.

Adult↗

Where to find nutritional science journals on the World Wide Web.

The World Wide Web (WWW) is a burgeoning information resource that can be utilized for current awareness and assistance in manuscript preparation and submission. The ever changing and expanding nature of the WWW allows it to provide up to the minute information, but this inherent changeability often makes information access difficult. To assist nutrition scientists in locating useful information about nutritional science journals on the WWW, this article critically reviews and describes the WWW sites for seventeen highly ranked nutrition and dietetics journals. Included in each annotation are the site's title, web address or Universal Resource Locator (URL), journal ranking and site authorship. Also listed is whether or not the site makes available the guidelines for authors, tables of contents, abstracts, online ordering, as well as information about the editorial board. This critical survey illustrates that the information on the web, regardless of its authority, is not of equal quality.

Computer Communication Networks↗

The development and evaluation of the hypertension temporal orientation (HTO) scale.

Temporal orientation is a multidimensional concept that describes the perception of time among individuals. Time perception is structured by life experiences and can vary depending upon the particular context involved. Whether a person is past-, present- or future-oriented has been shown to influence his/her approach and reaction to health situations. Because the management of hypertension is based on achieving some future health state, hypertension provides a context in which an individual's time perspective may be particularly influential. One purpose of this study was to develop and evaluate a scale to measure temporal orientation that was specific to hypertension, namely the hypertension temporal orientation (HTO) scale. Data were collected via telephone interviews with 300 people who had been diagnosed by a physician as having hypertension. Principal components factor analysis revealed three dimensions of hypertension temporal orientation: (1) a nonexperiential domain; (2) an experiential disease domain; and (3) an experiential treatment domain with coefficient alpha estimates of 0.76, 0.66, and 0.63, respectively. The HTO scale was significantly discriminant of African Americans and whites on the experiential treatment domain whereby African Americans were more present-oriented regarding the daily management (or treatment) of hypertension as compared to whites. Additional evidence for the validity of the HTO scale was found with temporal orientation group comparisons on health perceptions. The findings provide early support for the reliability and validity of the HTO scale for measuring temporal orientation among people with hypertension.

Adult↗

TransTerm: a database of translational signals.

The TransTerm database of sequence contexts of stop and start codons has been expanded to include approximately 50% more species than last year's release. It now contains 148 organisms and >39 500 coding sequences; it is now available on the World Wide Web. The database includes: (i) initiation and termination sequence contexts organized by species; (ii) summary parameters about the individual sequences (sequence length, GC%, GC3, Nc, CAI) in addition to tables of base frequencies for each species' stop and start codon sequence context; (iii) species codon usage tables; and (iv) summary tables of stop signal frequency.

Animals↗

Masturbation prohibition in sex offenders: a crossover study.

Some self-help groups for individuals with aberrant sexual interests (e.g., Sexaholics Anonymous and Sex and Love Addicts Anonymous) maintain that a period of "sexual sobriety" is necessary for treatment. The hypothesis was tested that sexual urges during a 30-day period of voluntary abstinence from masturbation would be less frequent and intense than during a period when masturbation was not avoided. Outpatient pedophiles were randomly assigned to either refrain from masturbating or make no attempt to alter their masturbation frequency for a period of 30 days. All participants were crossed over to the other treatment condition at the start of the 2nd month. Sexual urges and behavior were measured using weekly self-reports. A repeated measures ANOVA failed to show a difference in reported intensity of sexual urges, F(7, 91) = 1.15, p = 0.34; masturbation urges, F(7, 91) = 1.73, p = 0.11; adult sex urges, F(7, 91) = 1.82, p = 0.09; or child sex urges, F(7, 91) = 1.58, p = 0.15, in Masturbation Allowed vs. Masturbation Not Allowed conditions. Of 17 participants, 3 (18%) were able to retain completely from masturbating for 1 month, 4 participants (25%) thought it was helpful not to masturbate; 1 participant (7%) thought therapists should recommend avoidance of masturbation. This study suggests that sexual sobriety from masturbation does not aid in the control of pedophilic fantasies. This may be because the technique is ineffective, or because so few participants are willing to engage in it.

Adult↗

The beta 1 sodium channel subunit modifies the interactions of neurotoxins and local anesthetics with the rat brain IIA alpha sodium channel in isolated membranes but not in intact cells.

Mammalian brain sodium channels consist of an alpha subunit and two smaller beta subunits. The role of the beta 1 subunit in modulating ligand interactions at these channels was examined using a cell line stably expressing human beta1 and rat brain IIA alpha subunits. Coexpression of the beta 1 subunit had no effect on the potencies of sodium channel blockers in inhibiting whole cell [3H]batrachotoxinin A benzoate ([3H]BTX) binding or veratridine-stimulated [14C]guanidinium influx. Coexpression of the beta 1 subunit also had no effect on the potencies of alpha scorpion toxin, brevetoxin, or RU 39568 in stimulating [14C]guanidinium influx. By contrast, coexpression of the beta 1 subunit had dramatic effects on ligand interactions in isolated membranes. In isolated membranes of cells expressing only the alpha subunit, the neurotoxins had no stimulatory effect on [3H]BTX binding and the potencies of local anesthetic-like channel inhibitors were 10-100-fold lower than those at native sodium channels. Whereas in membranes of cells coexpressing the beta 1 subunit, the neurotoxins increased [3H]BTX binding 30-fold and the potencies of the sodium channel inhibitors closely matched those found at native sodium channels. These findings indicate that the beta 1 subunit is not required for the binding of sodium channel activators or inhibitors but rather, that the beta 1 subunit may stabilize the alpha subunit in a functional conformation thereby allowing detection of these interactions in disrupted membranes.

Anesthetics, Local↗