Increased permeability of the blood-brain barrier induced by magnetic and electromagnetic fields.
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Animals↗
Biomedical subjects
A Brun
Publications and source records attributed to A Brun.
A novel mutation in the beta-protein coding region of the amyloid beta-protein precursor (APP) gene.
A novel mutation, a C to T transition at base pair 2124 in exon 17 of the amyloid beta-protein precursor (APP) gene, has been identified by direct sequencing of amplified DNA from two Alzheimer's disease (AD) patients. A simple oligonucleotide-hybridization procedure was developed to allow population studies of this DNA variation. The mutation, which is silent at the protein level, was present in 2 out of 12 investigated AD patients, in 1 out of 60 non-AD patients and in 1 out of 30 healthy individuals. The mutation can be used as a new marker for linkage studies involving the APP gene, although more comprehensive population studies are required to determine the status of the mutation as a possible risk factor for the development of AD.
Alzheimer Disease↗
Effect of lesioning of medullary catecholamine neurons or the median eminence on the development of cerebral vasospasm in the squirrel monkey.
Injections of blood into the interpeduncular fossa and cisterna magna in the squirrel monkey produce an angiographically demonstrable, biphasic cerebral vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at six days after the subarachnoid haemorrhage (SAH). Selective lesioning of the A2 nucleus in the medulla oblongata or the median eminence in the hypothalamus prior to the SAH prevents the development of both the acute and late cerebral vasospasm. The present data indicate that the A2 nucleus and the median eminence participate in the development of vasospasm in the squirrel monkey.
Animals↗
Characterization of p30, a highly antigenic membrane and secreted protein of African swine fever virus.
We have identified and characterized a 30-kDa phosphoprotein (p30) of African Swine Fever Virus (ASFV) that is synthesized, membrane localized, and released into the culture medium at early times after infection. Sequence analysis of the p30 open reading frame predicts a highly antigenic protein with putative phosphorylation, glycosylation, and membrane attachment sites.
African Swine Fever Virus↗
Cell culture propagation modifies the African swine fever virus replication phenotype in macrophages and generates viral subpopulations differing in protein p54.
We have detected 86 African swine fever (ASF) virus-induced proteins in infected pig macrophages by two-dimensional electrophoresis. No differences among protein patterns of wild-type viruses could be observed by this methodology. However, during cell culture adaptation and propagation we have characterized changes in the molecular weight of the ASF virus specified protein p54, which show direct correlation with both size and number of viral subpopulation variants generated during cell culture propagation. Passages in culture appear to select for viral subpopulations that specify p54 proteins with higher molecular weights than the wild-type virus. The virus propagation in cell culture also affected its replication phenotype in pig macrophages decreasing the viral titers in these cells between passage 44 and 81. Nevertheless, the changes observed in p54 did not imply differences in biological properties, such as infectivity, virulence or host cell range among viral clones isolated, each one specifying for only one p54 form with different molecular weight. This protein becomes then a valuable quantification marker to follow evolution and generation of ASF virus diversity in vitro.
African Swine Fever↗
Metoclopramide as a sensitizer of 1,3-bis(2-chloroethyl)-1-nitrosourea treatment of brain tumors in the rat.
RG2 glioma-like cells grown in in vitro culture can be inoculated into rat brains using stereotactic surgical procedures to produce tumors with a diameter of 12-16 mm2 in 20-21 days. This system has been used to evaluate if metoclopramide (MCA) could sensitize the tumor toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU alone (15 mg/kg, intravenously), and MCA alone (2 mg/kg, intraperitoneally), and these drug treatments in combination, were administered so that BCNU alone was given as a single dose on day 3 after inoculation of the RG2 cells, MCA alone was given on day 3 at 0 and 3 h followed by five or six treatments per week beginning 24 h after the 3 h dose, and BCNU plus MCA were given according to the combined schedule where the first MCA treatment was scheduled 30 min prior to the BCNU infusion. The design of this study required the drug treated animals to be matched to untreated animals (controls) at the time of inoculation of the RG2 cells. Under these experimental conditions, BCNU alone and MCA alone had no effect on tumor growth, whereas BCNU plus MCA significantly retarded brain tumor growth. The normal tissue toxicity induced by BCNU treatment, evaluated by measurement of body weight and survival, was not potentiated by the combination of BCNU plus MCA. These data extend the previous findings of MCA as a radio- and chemosensitizer to include the sensitization of another cytotoxic agent (BCNU) and of another type of tumor (malignant glioma).
Animals↗
Frontal lobe degeneration of non-Alzheimer type.
In a longitudinal prospective study of dementias, several hundred cases have been examined from a clinical, brain imaging, neurochemical and neuropathological point of view. Frontal lobe degeneration of non-Alzheimer type (FLD) was the second most common primary degenerative dementia found in about 10% of the material. FLD has a consistent pathology and a characteristic clinical picture, which have been described by several independent research groups. The cortical degeneration mainly involves frontal or frontotemporal grey matter, without the circumscribed or knife-blade atrophy seen in Pick's disease. The degeneration involves predominantly frontal areas, including the insula and cingulate gyrus in its anterior parts. The striate body is normal or only slightly altered. The pathological changes are non-specific, with neuronal loss, slight gliosis and spongiosis but none or few senile plaques, tangles, congophilic vessels or Pick cells. Pathological changes are in some respects similar to those in amyotrophic lateral sclerosis. FLD is a slowly progressive dementia with personality changes, lack of insight, disinhibition, stereotypy and later apathy. There is also progressive dynamic aphasia which ends in mutism and amimia. Memory, spatial ability and receptive language functions are comparatively spared. Psychotic symptoms, emotional reactions, hypochondriasis and a Klüver-Bucy-like syndrome are sometimes observed. Electroencephalography is normal, at least during the early stage, while functional brain imaging such as regional cerebral blood flow reflects the frontal pathology. It is possible to achieve early diagnosis and differentiation from Alzheimer's disease and cerebrovascular dementia by clinical examination with neuropsychological assessment supported by brain imaging, and in the future probably various biological markers. The aetiology is unknown but there is a positive family history for dementia of similar type in about 50% of post-mortem verified cases.
Cerebrovascular Circulation↗
A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4.
The authors undertook a controlled, prospective, randomized study of 171 patients with supratentorial astrocytoma grades 3 and/or 4 (classified according to Kernohan). All patients were given chemotherapy consisting of procarbazine, vincristine, and lomustine (CCNU) (PVC). Half of the patients received whole-brain irradiation (RT) to a dose of 5800 cGy in the tumor-bearing hemisphere and 5000 cGy in the contralateral hemisphere. After diagnosis of progressive tumor growth, patients received individual treatment. The endpoint of the study was time to progression, but cases were followed until the patients died. Median time to progression (MTP) for the whole randomized population was 21 weeks. Median survival time (MST) was 53 weeks; 18% of patients survived for 2 years or longer. Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP (81 weeks) and MST (124 weeks) than all other patients. For patients less than 50 years of age treated with PVC alone, MTP was 21 weeks and MST was 66 weeks. For patients more than 50 years of age treated with PVC plus RT, MTP was 23 weeks and MST was 51 weeks; in the PVC group, MTP was 17 weeks and MST was 39 weeks. Age, Karnofsky index, areas of Grade 2, and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses. Patients less than 50 years of age treated with PVC plus RT had significantly longer survival (P = 0.037) when correcting for these factors in a multi-variate analysis.
Adult↗
Trisomy 7 and sex chromosome loss need not be representative of tumor parenchyma cells in malignant glioma.
We describe the cytogenetic findings in short-term cultures from 40 malignant gliomas, all of which had at least one clone with a simple numerical chromosome aberration. More than one aberrant clone was found in 17 tumors. The most frequent changes were loss of a gonosome (sole aberration in 38 clones), trisomy 7 (sole aberration in four clones), and combinations thereof (the aberrations +7 and -X or -Y were found together as the only changes in four clones). Clones with solitary trisomies for other autosomes--3, 5, 6, and 18--were seen in five tumors. Clones with structural rearrangements were found in nine tumors. The bands most commonly involved were lp36, 7p22, 9p22, 17p13, and 19q13. An extra copy of chromosome 7 was seen as part of a structurally abnormal clone in five tumors. In one case, trisomy 7 and even tetrasomy 7 were found in clones with simple numerical changes, but not in the clone with structural rearrangements. Likewise, the clonal loss of a gonosome was in six tumors, with structural abnormalities not present in the structurally aberrant clones; on the other hand, in two clones with structural aberrations a sex chromosome had been lost. The combined findings indicate that loss of a sex chromosome and trisomy 7 should not be seen as tumor-specific aberrations in gliomas. Instead, both glioma parenchyma cells and nonneoplastic cells in brain tumors may have a propensity to acquire extra copies of chromosome 7 and to lose gonosomes.
Aneuploidy↗
Monoaminergic dysfunction in Sjögren-Larsson syndrome.
The anteroposterior distribution of monoamine and monoamine metabolite concentrations was determined in subcortical brain nuclei of two cases of Sjögren-Larsson syndrome (SLS) and was compared to two control cases. The brains were divided into halves and sectioned coronally. For biochemical analyses, caudate nucleus, putamen, globus pallidus, substantia nigra, nucleus accumbens, amygdala, and hippocampus were dissected macroscopically. Monoamine and its metabolites were determined by reverse-phase liquid chromatography with electrochemical detection. The other hemisphere was studied neuropathologically. The SLS cases revealed cell loss in substantia nigra and putamen and a widespread white-matter destruction. Biochemically, most pronounced alterations were seen in the dopamine system in putamen with severely reduced concentrations of dopamine (DA; 14% of control values) and the catabolic metabolites 3-methoxytyramine (3-MT; 9% of control values) and homovanillic acid (HVA; 20% of control values). In substantia nigra and the other striatal regions studied, a general decrease of 3-MT and HVA concentrations was observed in the SLS subjects compared to the controls, although the decrease was less pronounced than in putamen. Generally, somewhat reduced noradrenaline and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were seen in the SLS cases, whereas serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were increased compared to the controls in most regions studied. These data suggest a specific monoaminergic dysfunction in patients with SLS. The severe decline in the dopaminergic system in putamen suggests that supplementation of dopamine agonists may ameliorate the symptoms of SLS patients.
Biogenic Monoamines↗
Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria.
In erythropoietic protoporphyria, protoporphyrin overproduction occurs mainly in erythroid tissue. Protoporphyrin can be released from erythrocytes in the dark, but the release is greatly increased if the erythrocytes are exposed to small amounts of light. Protoporphyrin can be bound in plasma either to albumin or to low density or high density lipoprotein. The cutaneous symptoms in erythropoietic protoporphyria are primarily elicited by protoporphyrin-sensitized photodamage of endothelial cells due to the presence of protoporphyrin in lipid structures. Which structures are damaged first in endothelial cells is unknown. Endothelial cells probably accumulate protoporphyrin from albumin or lipoproteins present in the plasma. A direct transfer from the erythrocyte membrane to the endothelial cell membrane can also occur. The transfer processes are probably facilitated by light exposure. Degranulation of mast cells, invasion of neutrophils into interstitial tissue and complement activation seem to be of less importance than endothelial cell injury in the pathogenesis of erythropoietic protoporphyria. These processes may, however, participate in the final expression of the cutaneous symptoms. Uroporphyrin and coproporphyrin are hydrophilic and are probably unbound in plasma, although weak binding to plasma proteins cannot be excluded. In the hepatic porphyrias and in erythropoietic porphyria, the clinical symptoms are probably evoked by uroporphyrin and coproporphyrin present in the interstitial tissue. Very little is known about the primary targets of uroporphyrin and coproporphyrin photodamage in these disorders, but photodamage to intercellular structures probably represents the initial event. Activation of complement may contribute to the final expression of the cutaneous symptoms.
Endothelium, Vascular↗
Genetic characterization of a novel familial dementia.
Clinical and neuropathologic findings from a Danish family in which a dementing illness is segregating as an apparent autosomal dominant disorder were previously described (Gydesen et al. 1987). We present here genetic findings from this family in which linkage analysis has excluded Huntington's disease and chromosome 21-encoded Alzheimer's disease. None of the known prion mutations has been detected in affected individuals from this family. However, linkage analysis with the prion gene has been uninformative. This family probably represents a novel genetic dementia.
DNA Probes↗
A new method for isolation of reticulocytes: positive selection of human reticulocytes by immunomagnetic separation.
A method for isolating pure reticulocytes from leukocyte-depleted blood of normal persons is presented. The separation was achieved using an immunomagnetic technique. A monoclonal mouse antibody against human transferrin receptor was bound to magnetic beads conjugated with sheep antimouse antibody. The recovery of reticulocytes from peripheral blood was 15% to 42%. Blood used for isolation of reticulocytes could be stored for 4 days at 22 degrees C without altering the yield of reticulocytes. At 37 degrees C incubation, the reticulocytes matured rapidly and the transferrin receptor was found to have a half-life of 16 hours. The activity of several enzymes and the amount of creatine and hemoglobin A1C were measured both in the reticulocytes and peripheral blood. Of the enzymes, porphobilinogen deaminase had the best discriminatory power with a ratio of 8.8 between reticulocytes and peripheral red blood cells. The ratio for creatine was 16.7. The ability to isolate pure human reticulocytes, released after normal erythropoiesis, will offer new possibilities in the study of these cells.
Adult↗
[Porphyria variegata--the first case in Norway].
In Norway, the most common porphyrias are acute intermittent porphyria and porphyria cutanea tarda. We describe the first case of porphyria variegata in this country. The patient showed symptoms of the skin and had no abdominal discomfort. Her family was also evaluated and two other persons were found with suspected latent porphyria variegata. We discuss the main symptoms of this type of porphyria and the possibilities of treatment. We emphasize that examination of porphyrins in the feces of patients with porphyria variegata is essential for the diagnosis.
Humans↗
White matter changes in dementia of Alzheimer's type: the difference in vulnerability between cell compartments.
Structural white matter changes were found to be common in dementia of Alzheimer's type. A neuropathological investigation was undertaken in order to characterize and quantify these white matter changes. The tissue changes were compared with those in white matter in normal control cases and in complete white matter infarcts. Our results support the hypothesis that the white matter lesion seen in dementia of Alzheimer's type is due to incomplete infarction involving both axons and myelin and is a result of mild ischaemia. In mild ischaemia, the myelin compartment appears to be the most vulnerable. We have termed the lesion selective incomplete white matter infarction.
Aged↗
Erythropoietic protoporphyria: photodynamic transfer of protoporphyrin from intact erythrocytes to other cells.
Erythrocytes in patients with erythropoietic protoporphyria (EPP) contain large amounts of protoporphyrin and are regarded as the main source of protoporphyrin in this disease. Cells in the skin of EPP patients accumulate protoporphyrin released from the erythrocytes and upon sun exposure endothelial cells are photodamaged. In the present study a light-induced transfer of protoporphyrin directly from EPP erythrocytes to cultured cells is demonstrated. Erythrocytes were layered upon cultured cells and irradiated. The nearness of erythrocyte and cultured cell membranes potentiated the transfer of protoporphyrin between these cells. This transfer was rapid and preceded the release of protoporphyrin to proteins in the medium. Further irradiation of the protoporphyrin-enriched cultured cells, after removal of the erythrocytes, caused severe photodamage to the cells and survival was dependent on both the amount of protoporphyrin transferred and on the light fluence. Clinical observations and the results of this study indicate that light energy may be involved in two steps in the pathophysiology of EPP: (A) light-induced release of protoporphyrin from erythrocytes to endothelial cells and (B) photodynamic damage to protoporphyrin-enriched endothelial cells.
Cell Line↗
In situ hybridisation in herpetic lesions using a biotinylated DNA probe.
In situ hybridisation was performed with a biotinylated DNA probe for herpes simplex virus (HSV) using high temperature denaturation on formalin fixed, paraffin wax sections of lung, brain, ganglion and keratinising and non-keratinising squamous epithelia. Eosinophilic viral nuclear inclusions or characteristically moulded multiple nuclei with altered chromatin, which were present in two cases of HSV encephalitis and one case of viral pneumonitis, all showed complete hybridisation visualised by an alkaline phosphatase/nitroblue tetrazolium detector system. HSV encephalitis and trigeminal ganglionitis, which were confirmed serologically or clinicopathologically but lacked nuclear changes, also gave positive dense nuclear signal in neurons, glias and satellite cells. No staining was present in the ganglion cells in trigeminal zoster, the glia in progressive multifocal leucoencephalopathy, or in a variety of cells in a lung coinfected with cytomegalovirus. In 10 herpetic blisters of squamous epithelia, infected cells hybridised strongly, while morphologically similar herpes zoster lesions remained negative. In neural tissues non-hybridisation staining was most obtrusive in corpora amylacea and seemed to reflect nonspecific probe adherence. In squamous epithelium, major non-hybridisation staining was caused by probe and antibody possibly adhering to intracellular keratin. The HSV probe permits specific detection of virus in the absence of characteristic nuclear changes and allows varicella zoster virus to be differentiated from HSV, provided that the aforementioned problems with non-hybridisation staining are borne in mind.
Biotin↗
Colloid cysts of the third ventricle: correlation of MR and CT findings with histology and chemical analysis.
Eight patients with colloid cysts of the third ventricle were examined with CT and MR. In six, surgical resection was performed and the material was subjected to histologic evaluation; the concentrations of trace elements were determined by particle-induced X-ray emission. Stereotaxic aspiration was performed in two. The investigation showed that colloid cysts are often iso- or hypodense relative to brain on CT (5/8), but sometimes have a center of increased density. Increased density did not correlate with increased concentration of calcium or other metals but did correlate with high cholesterol content. Colloid cysts appear more heterogeneous on MR (6/8) than on CT (3/8), despite a homogeneous appearance at histology. High signal on short TR/TE sequences is correlated with a high cholesterol content. A marked shortening of the T2 relaxation time is often noticed in the central part of the cyst. Analysis of trace elements showed that this phenomenon is not related to the presence of metals with paramagnetic effects. Our analysis of the contents of colloid cysts does not support the theory that differing metallic concentrations are responsible for differences in MR signal intensity or CT density. We did find that increased CT density and high MR signal correlated with high cholesterol content.
Adult↗