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Biomedical subjects

M J Berg

Publications and source records attributed to M J Berg.

At least 37 records · Page 2Linked to original sources
PubMed1997

Composition of white matter bovine brain coated vesicles: evidence that several components influence beta-amyloid peptide to form oligomers and aggregates in vitro.

Clathrin coated vesicles (CVs) purified from white matter of human or bovine brain contain amyloid precursor protein (APP), several C-terminal fragments encompassing the beta-amyloid domain (betaA), the alpha-secretase 11-12 kDa intermediate, ApoE and tau. The convergence of these components implicates CVs as potential sites for their interaction, yielding products linked to fibrillogenesis in Alzheimer's disease (AD). Analysis of components co-reactive with both anti-ApoE and betaA suggested presence of stable intravesicular conjugates. To evaluate these interactions in vitro, mixtures containing betaA(1-40), ApoE4 or E3 isoforms with and without lipid added as dymyristoyl phosphatidylcholine liposomes were co-incubated from 5 h to 7 days at 37 degrees C and analyzed on Western blots using a panel of antibodies recognizing betaA and ApoE. Data showed ApoE4 plus lipid induced betaA to form oligomers, conjugates and high Mr aggregates. The rates of formation for these products varied significantly with the ApoE isoform. E3 formed conjugates more rapidly, but these levels were exceeded by those of E4 at 7 days. ApoE4 plus lipid facilitated more rapid formation of higher Mr betaA aggregates which appeared in parallel with betaA oligomers containing up to seven molecules of betaA. Data suggest that the native ApoE, as found in CVs which contain lipid, can be an effective agent for promoting formation of betaA oligomers or other complexes that may be linked to formation of abnormal deposits in AD.

Amyloid beta-Peptides↗
PubMed1997

Tolerance to diazepam and changes in GABA(A) receptor subunit expression in rat neocortical areas.

Long-term treatment with diazepam, a full allosteric modulator of the GABA(A) receptor, results in tolerance to its anticonvulsant effects, whereas an equipotent treatment with the partial allosteric modulator imidazenil does not produce tolerance. Use of subunit-specific antibodies linked to gold particles allowed an immunocytochemical estimation of the expression density of the alpha1, alpha2, alpha3, alpha5, gamma(2L&S) and beta(2/3) subunits of the GABA(A) receptor in the frontoparietal motor and frontoparietal somatosensory cortices of rats that received long-term treatment with vehicle, diazepam (three times daily for 14 days, doses increasing from 17.6 to 70.4 micromol/kg), or imidazenil (three times daily for 14 days, doses increasing from 2.5 to 10.0 micromol/kg). In this study, tolerance to diazepam was associated with a selective decrease (37%) in the expression of the alpha1 subunit in layers III-IV of the frontoparietal motor cortex, and a concomitant increase in the expression of the alpha5 (150%), gamma(2L&S) and beta(2/3) subunits (48%); an increase in alpha5 subunits was measured in all cortical layers. In the frontoparietal somatosensory cortex, diazepam-tolerant rats had a 221% increase in the expression of alpha5 subunits in all cortical layers, as well as a 35% increase in the expression of alpha3 subunits restricted to layers V-VI. Western blot analysis substantiated that these diazepam-induced changes reflected the expression of full subunit molecules. Rats that received equipotent treatment with imidazenil did not become tolerant to its anticonvulsant properties, and did not show significant changes in the expression of any of the GABA(A) receptor subunits studied, with the exception of a small decrease in alpha2 subunits in cortical layers V-VI of the frontoparietal somatosensory cortex. The results of this study suggest that tolerance to benzodiazepines may be associated with select changes in subunit abundance, leading to the expression of different GABA(A) receptor subtypes in specific brain areas. These changes might be mediated by a unique homeostatic mechanism regulating the expression of GABA(A) receptor subtypes that maintain specific functional features of GABAergic function in cortical cell layers.

Animals↗
PubMed1997

A novel volumetric feature extraction technique with applications to MR images.

A semiautomated feature extraction algorithm is presented for the extraction and measurement of the hippocampus from volumetric magnetic resonance imaging (MRI) head scans. This algorithm makes use of elements of both deformable model and region growing techniques and allows incorporation of a priori operator knowledge of hippocampal location and shape. Experimental results indicate that the algorithm is able to estimate hippocampal volume and asymmetry with an accuracy which approaches that of laborious manual outlining techniques.

Algorithms↗
PubMed1995

Segmentation and feature extraction techniques, with applications to MRI head studies.

To obtain a three-dimensional reconstruction of the hippocampus from a volumetric MRI head study, it is necessary to separate that structure not only from the surrounding white matter, but also from contiguous areas of gray matter--the amygdala and cerebral cortex. At present it is necessary for a physician to manually segment the hippocampus on each slice of the volume to obtain such a reconstruction. This process is time consuming, and is subject to inter- and intraoperator variation as well as large discontinuities between slices. We propose a novel technique, making use of a combination of gray scale and edge-detection algorithms and some a priori knowledge, by which a computer may make an unsupervised identification of a given structure through a series of contiguous images. This technique is applicable even if the structure includes so-called false contours or missing contours. Applications include three-dimensional reconstruction of difficult-to-segment regions of the brain, and volumetric measurements of structures from series of two-dimensional images.

Algorithms↗
PubMed1995

Folic acid improves phenytoin pharmacokinetics.

Phenytoin (PHT) therapy to control seizures decreases serum folate levels in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but also changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic acid is provided as a supplement has not been reported in women of child-bearing age. This study of six fertile women examined the interdependence of PHT and folic acid in a randomized crossover study of two treatments: treatment 1 consisted of 300 mg sodium PHT per day and treatment 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Dietary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0 +/- 18.6% (mean +/- standard deviation) and serum PHT concentration was in the low therapeutic range (43.92 +/- 14.52 mumol/L). During treatment 2, serum folate level increased 26.0 +/- 33.4%, and serum PHT level (39.04 +/- 14.16 mumol/L) was similar to that in treatment 1. Only one subject attained PHT steady state during treatment 1, but four subjects achieved steady state during treatment 2. Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.

Adult↗
PubMed1995

Ictal contralateral paresis in complex partial seizures.

Certain behaviors that occur during a complex partial seizure (CPS) are useful in lateralizing the side of seizure onset. In 5 (5.3%) of 94 consecutive patients with partial epilepsy, we observed ictal unilateral arm and hand paresis during 27 of 34 CPS. In all these seizures, this behavior occurred contralateral to an epileptogenic temporal lobe, as determined by video-EEG monitoring and surgical outcome. In 5 of the 27 seizures, an observer demonstrated that the paretic arm and hand were flaccid. None of these patients had postictal (Todd's) paralysis. In most of the seizures, the arm ipsilateral to seizure onset had simultaneous purposeful movements or automatisms, sometimes with awkward posturing. Ictal unilateral paresis is distinctly different from ictal dystonia or postictal paralysis and consistently lateralizes seizure onset to the contralateral temporal lobe. Recognition of this particular ictal behavior and comparison to other simultaneous behaviors can aid in the lateralization and possibly localization of the epileptogenic zone.

Behavior↗
PubMed1995

The transient syndrome of headache with neurologic deficits and CSF lymphocytosis.

We describe seven patients who experienced a transient syndrome consisting of headache with neurologic deficits and CSF lymphocytic pleocytosis. Thirty-three similar patients have been reported previously. All had from one to more than 20 episodes of a severe migrainous headache accompanied by a temporary neurologic deficit and lymphocytes in the CSF. Some patients had a preceding viral syndrome, increased intracranial pressure, elevated CSF protein, or focal EEG abnormalities. All stopped having episodes within 3 months. We present diagnostic criteria for this benign syndrome. Its cause remains unknown.

Adolescent↗
PubMed1994

Amyloid precursor protein is enriched in axolemma and periaxolemmal-myelin and associated clathrin-coated vesicles.

The amyloid precursor protein (APP) is widely distributed within the CNS, where it is expressed in both neurons and glia. We have isolated axolemma and periaxolemmal-myelin from rat brain and have determined by Western blot that APPs, Mr 100-110 kDa, are major constituents of these membrane. Isolation of axolemma, periaxolemmal-myelin, and compact myelin show that while APP represents 1 and 0.6% of the proteins of these respective membranes, it is absent from compact myelin. These results indicate that APP transported down the axon is deposited at sites in the axolemma as well as the synapse, and that within the myelin complex, APP is targeted to the periaxolemmal domain. Both axolemma and periaxolemmal-myelin contained a 10.5 kDa APP peptide which, based on reactivity with anti-C-terminal APP antibodies but not with anti-N-terminal antibody, appears to be a membrane-associated C-terminal fragment. Western blots with antibodies to Alzheimer precursor-like proteins (APLP) indicate that APP immune reactivity is not a result of cross reactivity with APLPs. Isolation of axolemma from human autopsy material showed nearly identical results with a clear enrichment, relative to homogenate, of APP Mr 100-110 and the 10.5 kDa C-terminal peptide. The demonstration of APP in axolemma and periaxolemmal-myelin was replicated in membrane isolated from bovine brain. Bovine studies were extended to analysis of white matter clathrin-coated vesicles; these data show that coated vesicles isolated from white matter, under conditions that previous studies indicate are largely endocytic vesicles, contain levels of APP comparable to that found in axolemma and periaxolemmal-myelin. In addition, these vesicles contain cysteinyl and aspartyl proteases. Incubation of axolemma with cathepsin B at pH 6.0 caused a rapid loss in the immune reactivity of APP Mr 100-110 and Mr 10.5 when analyzed with antibodies to APP672-695. This appears to be the result of hydrolysis within the epitope and not proteolysis of APP or the C-terminal peptide, since no loss of reactivity was observed when analyzed with antibodies to sites more distal to the C-terminus. Thus, cathepsin B hydrolyses membrane bound APP close to the C-terminus and may be a useful tool for altering C-terminal APP function.

Amino Acid Sequence↗
PubMed1994

Hydrolysis of amyloid precursor protein-derived peptides by cysteine proteinases and extracts of rat brain clathrin-coated vesicles.

Amyloid precursor proteins (APPs) and C-terminal fragments were colocalized with cysteine proteinase-like enzymes in purified rat brain clathrin-coated vesicles. Vesicular extracts degraded beta A4(12-28), yielding a product profile similar to that of purified rat brain cathepsin B. Cathepsin B degraded this peptide sequentially, with initial cleavage occurring at Val18-Phe19 and Phe19-Phe20 followed by release of dipeptides. Enzyme also hydrolyzed beta A4(1-40) at Phe19-Phe20 bond but at lower rates, likely due to aggregate formation. An octapeptide analogue of the domain adjacent to beta A4 (N-Ac-Val-Lys-Met-Asp-Ala-Glu-Phe-NH2) was also hydrolyzed by brain cathepsins B and L, and metalloendopeptidase 24.11. Enzymes acted at multiple sites, but only 24.11 cleaved the Met-Asp bond, thus resembling a proposed beta-secretase. Data imply that clathrin-coated vesicles contain cysteine-like proteinases capable of initiating the processing of APP or its fragments.

Amino Acid Sequence↗
PubMed1994

Phenobarbital removal characteristics of three brands of activated charcoals: a system analysis approach.

The in vivo phenobarbital removal characteristics of three brands of activated charcoal (Actidose, Charcoaid, Superchar) were studied in normal volunteers using a system analysis approach. The subjects received a 200-mg dose of oral or intravenous phenobarbital followed by a single oral dose of 30 g of one of the three charcoals in a randomized crossover design. The relative merits of the three charcoals in enhancing the removal of oral and intravenous phenobarbital were assessed using a system analysis approach. The removal clearance, time to peak (tp), peak removal clearance (Rmax), percentage of dose removed (PCT infinity), and phenobarbital removal clearance (CLr) were calculated for the oral and intravenous treatments. Superchar had a pulse-like effect, with the shortest tp and the largest Rmax. Actidose and Charcoaid had similar effects, with Actidose inducing slightly greater phenobarbital removal. Superchar has the highest surface area and relative percentage of surface hydroxyl groups, whereas Actidose has the lowest surface area and relative percentage of surface hydroxyl groups of the three charcoals studied. Although correlations between the in vitro and the in vivo phenobarbital adsorption characteristics of the three charcoals may be difficult due to the presence of preservatives and palatibility enhancers in the commercial preparations, it appears that the in vivo effectiveness decreases as the surface area and the concentration of surface hydroxyl groups decrease. The proposed system analysis approach requires fewer assumptions than methods based on compartmental or physiologic approaches and has the advantage of describing the phenobarbital removal in a dynamic manner.

Absorption↗
PubMed1994

Stabilizing seizure disorders.

Scientific understanding of seizures and epilepsy is rapidly evolving. Recent advances in diagnosis, classification, and medical and surgical treatment have significantly altered our approach to patients with these conditions.

Adolescent↗
PubMed1992

Surface characterization of activated charcoal by X-ray photoelectron spectroscopy (XPS): correlation with phenobarbital adsorption data.

X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C-H, C-C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C-O), carbonyls (C = O), and carboxylic acids or esters (O-C = O). The C-O functional state contributed approximately 60-70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C-O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C-O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals.

Adsorption↗
PubMed1992

Parkinsonism treatment: Part III--Update.

OBJECTIVE: The purpose of this review is to update clinicians with recent advances in the management of parkinsonism, including drug therapy, transplantation, and diet. DATA SOURCES: Pertinent articles were obtained from an English-language literature search using MEDLINE (1970-1991), Index Medicus (1987-1991), Current Contents (1990), and bibliographic reviews of review articles. Index terms included parkinsonism, selegiline, pergolide, vitamin E, and transplantation. Fifty-five articles (representing 85 percent of the complete literature search) were selected by multiple reviewers for their contribution to the stated purpose. Emphasis was placed on double-blind, placebo-controlled, and randomized studies. Data from cited articles were examined by multiple reviewers for support of their stated hypothesis and were included as background for justification of major points in this article; critical studies were abstracted in more detail. RESULTS: New therapeutic measures have been added to the treatment of parkinsonism. Selegiline, a monoamine oxidase inhibitor type B, has shown beneficial results, especially in early stages. Pergolide, a dopamine agonist, may be an efficacious alternative to bromocriptine resistance or intolerable adverse effects. Vitamin E may have protective antioxidant properties, but very few clinical data are available. Fetal tissue transplantation needs continued research and remains very controversial. Diet modification may maximize the results of therapy with exogenous dopamine therapy. CONCLUSIONS: Clinicians should familiarize themselves with new alternatives for the management of parkinsonism in order to be reliable consultants for both professional and lay persons.

Antioxidants↗
PubMed1991

Brain cysteine proteinase inhibitors II: evidence that a 21-kDa papain-binding component resembles ras p21.

A 21-kDa protein extracted from rat or bovine brain at high pH was purified on alkylated-papain and shown to have dual ras-like and cysteine proteinase inhibitory (CPI) properties. This was demonstrated by its GTP-binding activity, cross-reactivity toward pan-reactive ras p21 monoclonal antibody, and inhibition of papain. The material eluted earlier than cystatins or kininogens on the alkylated papain-affinity column and was devoid of other CPIs based on immunoblot analysis. In a second procedure, ras p21s isolated from rat or bovine brain membranes by cholate extraction and purified by gel-permeation and hydrophobic interaction were shown to act also as potent CPIs, inhibiting rat brain cathepsin L, papain, or rat brain cathepsin B with Ki values of 3, 11, and 167 nM, respectively. This component cross-reacted with the monospecific anti-ras, but not with other anti-CPIs, and represented 3-4% of total GTP binding present in homogenates. The specific activity of the purified 21 kDa component was 4.7 nmol GTP-gamma-S bound per mg protein. The data support the notion that brain ras p21s constitute a separate group of CPIs and are available for regulating some aspects of brain protein turnover.

Amino Acid Sequence↗
PubMed1991

Model selection for the adsorption of phenobarbital by activated charcoal.

Activated charcoal is known to adsorb a wide variety of substances from solution, and several equations have been used to fit the resulting adsorption data. The determination of the correct model to fit phenobarbital adsorption onto activated charcoal was made using a calorimetric method. The differential heats of displacement of water by phenobarbital for four activated charcoals were determined and found to be linearly related to the amount of phenobarbital adsorbed. The activated charcoals studied had statistically similar heats of displacement. The linear relationship between heat evolved and the amount of phenobarbital adsorbed is consistent with the assumptions implicit in the Langmuir model.

Adsorption↗
PubMed1991

Differences in phenytoin biotransformation and susceptibility to congenital malformations: a review.

The clinical variability of teratogenic response to fetal drug exposure has been well documented. Metabolic differences in biotransformation have been shown to extend to multiple drugs and may involve many steps in drug metabolism with alterations of key intermediates. Although metabolic differences have been reported to be associated with complications of medication use, it has only recently been appreciated that such differences also may be associated in the unborn with the potential for the disruption of normal embryologic development and the production of congenital malformations. It has long been suspected that the teratogenicity of phenytoin may be mediated not only by the parent compound, but also by toxic intermediary metabolites that are produced during the biotransformation of the parent compound. Recent work elucidating differences in isoenzyme forms of cytochrome P-450 enzyme systems, glutathione, and microsomal epoxide hydrolase has provided increased interest in the multiple individual pharmacogenetic differences that may be significant factors affecting increased susceptibility to birth defects in individuals and families with fetal exposure to phenytoin.

Abnormalities, Drug-Induced↗