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Biomedical subjects

A Brun

Publications and source records attributed to A Brun.

At least 55 records · Page 3Linked to original sources
PubMed1997

Whole-body hyperthermia and ADPRT inhibition in experimental treatment of brain tumors.

Malignant primary brain tumors have hitherto been incurable. One reason for this may be the migrating tumor cells that spread into the surrounding normal brain, creating the basis for inevitable recurrences. Therefore, local therapy may have a temporary effect, but for a cure, the treatment must reach all the tumor cells. Whole-body hyperthermia (WBH) is such a general treatment, which we have studied in a rat glioma model. Cells of the RG2 rat glioma cell line were inoculated in the right caudate nucleus of Fischer-344 rats, which were then either controls or treated with WBH, induced by a radiant heat device for 4-5 sessions of 30 min at body temperature 42 degrees C (rectal), and/or nicotinamide (NAM), an effective radiosensitizer in animal tumor models and an inhibitor of ADPRT (poly adenosine diphosphate ribosyl transferase), a chromatin-bound enzyme suggested to be important in the DNA repair system. We have shown that WBH 42 degrees C alone, or in combination with NAM, has no effect upon tumor growth if a larger number of RG2 cells (5,000) are inoculated. If only 1,000 cells are inoculated, a significant inhibitory effect (p < 0.05) is observed on tumor growth as compared to the untreated control animals. Thus, WBH is feasible, and in some circumstances effective, in a rat glioma model. WBH in combination with other therapies influencing cell metabolism may be of value in future postoperative treatment of human malignant brain tumors.

Animals↗
PubMed1997

Clinical characteristics of a chromosome 17-linked rapidly progressive familial frontotemporal dementia.

OBJECTIVE: To describe symptoms, signs, neuroimaging results, and neuropathologic findings in patients from a family with chromosome 17q21-linked autosomal dominant frontotemporal dementia. DESIGN: Multiple case report with genetic investigations. SUBJECTS: The disease was observed in a Swedish family and documented in 3 generations. Four siblings are described in this article. RESULTS: A rapidly progressive dementia with genetic linkage to chromosome 17q21 was observed. The mean age of onset was 51 years and the average duration of disease to death was 3 years. Two patients started with speech disturbances leading to a progressive, nonfluent aphasia, 1 patient had onset symptoms of leg apraxia and akinesia and muscular rigidity, and in 1 patient reckless driving was the first symptom. Loss of spontaneous speech developed later in all patients and emotional bluntness in 3 of the patients. Cerebral perfusion was decreased in the frontal areas in all patients. In the person with apraxia as the onset symptom, the cerebral blood flow was also diminished in the left hemisphere, where a slight atrophy was detected on magnetic resonance imaging scans. At the postmortem examination, slight gliosis of the parietal lobes was observed in this patient. In all patients there was a frontocentral degeneration of the cortex with discrete microvacuolation and gliosis. CONCLUSION: Clinical features of frontotemporal dementia, parkinsonism, an early age of onset, a rapid disease progression, and variable onset symptoms were seen in these patients. Two other clinically distinct diseases, dementia with pallido-ponto-nigral degeneration and a disinhibition-dementia-parkinsonism-amyotrophy complex, have recently been mapped to chromosome 17q21. In the family described in this article, genetic linkage was detected to the same region, suggesting the possibility that these diseases may originate from pathogenic mutations in the same gene.

Chromosomes, Human, Pair 17↗
PubMed1997

Hippocampal pyramidal cell disarray correlates negatively to cell number: implications for the pathogenesis of schizophrenia.

Brains from patients with therapy-refractory schizophrenia were examined with respect to pyramidal cell disarray in the hippocampus, a finding reported in some studies, but not confirmed in others. A significantly higher number of disarrayed cells was seen in the brains of the schizophrenic patients in all subfields of the Cornu Ammonis (CA) investigated. Compared with controls the schizophrenic patients also had significantly fewer pyramidal cells in the observed areas of CA1-CA3, but not in CA4. There were no signs of gliosis. Finally, there was a significant negative correlation between the number of disarrayed cells and the total number of pyramidal cells in CA1-3 in the group of probands and controls taken together, a finding interpreted as lending support to the idea of a prenatal migratory disturbance in the pathogenesis of schizophrenic syndromes.

Aged↗
PubMed1997

High level expression of the major antigenic African swine fever virus proteins p54 and p30 in baculovirus and their potential use as diagnostic reagents.

At present, the eradication of African swine fever (ASF) in affected countries is based only on an efficient diagnosis program because of the absence of an available vaccine. The highly antigenic ASF virus proteins p54 and p30, encoded by genes E183L and CP204L respectively, were expressed in baculovirus for diagnostic purposes. A sequence comparison analysis of these genes from different field virus strains which are geographically diverse and isolated in different years, revealed that both genes are completely conserved among the isolates. Partially purified baculovirus-expressed proteins were used in ELISA and Western blot for ASF antibody detection in sera from experimentally inoculated pigs and field sera from ASF innaparent carriers. These comparative analyses showed that p54 presents better reactivity than p30 in Western blot. However, recombinant p30 was more efficient for antibody detection by ELISA, improving the discrimination between positive and negative sera by this technique. These data suggest the convenience of using p30 as ELISA antigen, while p54 should be the selected antigen for ASF virus antibody detection by Western blot. The combined use of both antigens for serodiagnosis of ASF disease will improve the sensitivity of innaparent carriers detection, facilitating also the interpretation of the tests, and eliminating the use of ASF virus in antigen production.

African Swine Fever↗
PubMed1997

The Drosophila cytochrome P450 gene Cyp6a2: structure, localization, heterologous expression, and induction by phenobarbital.

The cytochrome P450 gene Cyp6a2 from Drosophila melanogaster is located on the right arm of chromosome 2 at position 43A1-2 and comprises two exons separated by a 69-bp intron. Phenobarbital treatment of flies leads to a rapid increase in the level of CYP6A2 mRNA and to an increased production of the CYP6A2 protein. DNA from the Cyp6a2 promoter region was functional when linked to a luciferase reporter gene and transfected into D. melanogaster Schneider cells. Moreover, a dose-dependent induction of luciferase activity by phenobarbital indicated that elements necessary for phenobarbital induction are located within 428 bp of the translation start site. Heterologous expression of the CYP6A2 protein in lepidopteran cells infected with a Cyp6a2-recombinant baculovirus was observed by Western blotting of cell lysates and by spectral characterization of the reduced-CO complex of the P450. The CYP6A2 protein produced in this system metabolized aldrin and heptachlor to their epoxides and metabolized the insecticide diazinon by desulfuration to diazoxon and by oxidative ester cleavage to 2-isopropyl-4-methyl-6-hydroxypyrimidine. Metabolism in lysates of cells infected with recombinant baculovirus was greatly enhanced by the addition of purified housefly NADPH cytochrome P450 reductase and cytochrome b5. These results show that CYP6A2 catalyzes the metabolism of organophosphorus insecticides and they implicate Cyp6a2 overexpression in metabolic resistance. The Cyp6a2 gene appears to be a suitable model for a genetic analysis of the phenobarbital induction process.

Aldrin↗
PubMed1997

Cytochrome P-450 field insecticide tolerance and development of laboratory resistance in grape vine populations of Drosophila melanogaster (Diptera: Drosophilidae).

Studies were conducted between 1993 and 1996 using 3 natural grape vine populations, 1 susceptible laboratory strain, and 1 resistant selected strain of Drosophila melanogaster L. In vitro monooxygenase activity (ethoxycoumarine-O-deethylation) (ECOD) was recorded from microsomal fractions of all strains. Results varied over a 6-fold range between susceptible laboratory Canton and resistant selected RDDT strains and over a 2-fold range between the Canton strain and natural populations of flies. Few significant variations of ECOD activity were detected among the natural populations despite many insecticide treatments, but activities were significantly correlated with toxicological tolerance to 5 of the 15 insecticides (deltamethrin, fipronil, chlorpyriphos ethyl, DDT, and diazinon). Moreover, immunoblotting responses of microsomal protein encoded by Cyp6A2 showed that the levels of expression were quantitatively correlated with toxicological tolerance to almost the same group of insecticides (deltamethrin, fipronil, chlorpyriphos ethyl, DDT, fenvalerate, and fenthion). However, the level of CYP6A2 expression in some natural strains (still weakly resistant) was almost comparable with one of the resistant strains. In vivo monooxygenase activity recorded in individual abdomens of flies showed that frequency distributions of ECOD activity in natural populations overlapped those of the resistant and laboratory strains, which were much narrower. Substantial and fast frequency changes (of the narrowness) that obtained in laboratory were related to either the time of rearing of 1 of the natural populations or selecting this population with an insecticide that has a toxicology correlated with both of the monooxygenase signs measured. Perspectives on using the CYP6A2 expression and ECOD activity for detecting a resistance mechanism by cytochrome P450 in field populations are discussed.

Animals↗
PubMed1997

Patterns of azathioprine metabolites in neutrophils, lymphocytes, reticulocytes, and erythrocytes: relevance to toxicity and monitoring in recipients of renal allografts.

Monitoring of azathioprine (AZA) therapy by the measurement of 6-thioguanine nucleotides (6-TGN) concentrations in red blood cells (RBC) may improve safety and ensure optimal immunosuppressive effects of AZA in organ transplantation. The authors explored the rationale for such monitoring by measuring thiopurine metabolites in peripheral blood cell types that are more relevant to the effects and kinetics of AZA and its active metabolites. Neutrophil granulocytes were isolated by density gradient centrifugation, and CD4+ lymphocytes and reticulocytes by using specific immunomagnetic beads. In neutrophils, 6-TGN concentrations had median measurements 31 times higher than in RBCs. In contrast to the high methylated mercaptopurine (me-MP) concentrations in RBCs, these metabolites were not detected in the neutrophils. Thiopurine metabolite levels were lower than the analytic limit of detection in all the CD4+ samples. The concentrations of 6-TGN and me-MPs were lower in reticulocytes than in RBCs in general, indicating that thiopurine metabolites are taken up by RBCs in the circulation. This study's findings, that 6-TGN concentrations are very high in neutrophils, whereas me-MPs are undetectable, many explain the specific neutropenic adverse effect of AZA. The results also add support to monitoring AZA through measurements of 6-TGN and me-MPs in RBCs.

Aged↗
PubMed1997

Evaluation of malignancy in ring enhancing brain lesions on CT by thallium-201 SPECT.

OBJECTIVE: To investigate patients with cystic enhancing lesions on CT and to determine whether thallium-201 (201Tl) SPECT adds to further preoperative information in differential diagnosis between gliomas and abscesses. METHODS: Twenty one patients with cystic ring enhancing CT findings were studied and uptake indices were compared with CT enhancement volumes, histopathology, and survival times. RESULTS: Fourteen high grade gliomas, three low grade gliomas, and four abscesses were found. Uptake was higher in the highly malignant glioma group (median thallium index (TI)=2.1), than in the low grade glioma group (median TI=1.4) or among the abscesses (median TI=1.6). Overlapping indices were found between high and low malignant cystic gliomas as well as between either one of the glioma groups and the infectious lesions, and there were no significant differences between groups. There was a level at the value 2, where TI > or = 2 correlated with tumour diagnosis. One low grade tumour had an extremely high index and a very high enhancement volume. Indices correlated significantly with CT enhancement volumes (P=0.005). There was no significant correlation between Tl indices and patient survival times among the high grade gliomas. One patient with a highly malignant tumour but low Tl uptake < 2, had a survival > five years. CONCLUSIONS: It is concluded that high 201Tl uptake in enhancing cystic lesions is an indicator of highly malignant glioma. However, the differentiation between the high malignant gliomas and abscesses or low malignant gliomas by 201TL SPECT is only partial with an overlap between these groups.

Adult↗
PubMed1997

Structural nerve changes at wrist level in workers exposed to vibration.

OBJECTIVES: To analyse the character of morphological changes occurring in a well defined peripheral nerve in humans exposed to vibration from hand held tools. METHODS: Biopsies of the dorsal interosseus nerve just proximal to the wrist were taken from 10 men exposed to vibration and from 12 male age matched necropsy controls. The nerve was resected for pain relief either as the sole procedure or in conjunction with carpal tunnel release. All specimens were sectioned and examined by light microscopy in standard sections, thin epon sections, and teasing preparations. RESULTS: The combined results of the analyses showed pathological changes in all 10 patients dominated by breakdown of myelin and by interstitial and perineurial fibrosis. All but one of the 12 controls were normal. CONCLUSION: These findings often show severe nerve injury previously not described at this level. They indicate that demyelination may be the primary lesion in neuropathy induced by vibration followed by fibrosis associated with incomplete regeneration or with organisation of oedema. Vibration can induce structural changes in peripheral nerves just proximal to the wrist and such changes may constitute a structural component in carpal tunnel syndrome among people exposed to vibration. This may help to explain the poor results achieved by carpal tunnel release in these patients.

Adult↗
PubMed1997

Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias.

Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer's disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (+/- SD) was 5.4 +/- 4.5 and differed significantly among the groups (AD, 3.1 +/- 2.5; MID, 10.5 +/- 4.1; mixed, 7.7 +/- 4.3). Receiver-operator characteristic curves showed that the best cutoff was < or = 4 for AD and > or = 7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke (OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.

Brain Ischemia↗
PubMed1997

The Swedish Centenarian Study: a multidisciplinary study of five consecutive cohorts at the age of 100.

UNLABELLED: Centenarians born 1887-91, who lived in southern Sweden were asked to participate in this multidisciplinary study (N = 164). Of the survivors (N = 143), 70 percent agreed (N = 100). The purpose was to describe the population from physical, social, and psychological points of view; to characterize centenarians with various health conditions and diverse degrees of autonomy and life satisfaction; and to identify factors at 100 years that predict future survival. RESULTS: Eighty-two percent were women, 25 percent lived in their own home, 37 percent in old age homes, and 38 percent in nursing homes. Socioeconomic status showed a similar distribution compared to nationally representative data. Fifty-two percent managed activities of daily living with or without minor assistance. The incidence of severe diseases was low. In 39 percent a disorder of the circulatory system was found. Thirty-nine percent (women) and 11 percent (men) had had at least one hip fracture. Twenty percent had good hearing and good vision. Twenty-seven percent were demented according to DSM III-R criteria. Means on cognitive tests (word-list, digit-span, learning, and memory) were lower compared to seventy to eighty year old groups. The variation in performance was extremely widespread. Personality profiles (MMPI) indicated that the centenarians were more responsible, capable, easygoing and less prone to anxiety than the population in general. Extensive neuropathological investigation revealed no major diseases or large lesions but mild through multiple changes. RESULTS suggest that centenarians are a special group genetically. A causal structure model emphasized body constitution, marital status, cognition and blood pressure as particularly important determinants for survival after 100 years.

Aged↗
PubMed1996

African swine fever virus gene A179L, a viral homologue of bcl-2, protects cells from programmed cell death.

The African swine fever virus (ASFV) open reading frame A179L, which is similar to the human proto-oncogene bcl-2, has been cloned and expressed in vaccinia virus under control of the pEIL synthetic early/late promoter. The A179L gene product prevented cell death in HeLa and BSC-40 cells doubly infected with another recombinant vaccinia virus expressing the interferon-induced double-stranded RNA-activated protein kinase (p68 kinase), which activates a rapid cell death characteristic of apoptosis. This finding suggests that the A179L gene has a function similar to that of bcl-2 in preventing apoptosis and may play an important role during productive ASFV infection.

African Swine Fever Virus↗
PubMed1996

Inducibility of the Drosophila melanogaster cytochrome P450 gene, CYP6A2, by phenobarbital in insecticide susceptible or resistant strains.

The importance of cytochrome P450s in the biology of cells or organisms is clearly established. While numerous studies concern vertebrates, little is known about invertebrates cytochrome P450s. In this paper, we have focused on CYP6A2 gene expression in Drosophila melanogaster. We show the expression of this cytochrome P450 gene in the Canton(s) strain (wild type) to be under the control of phenobarbital. In adults treated with phenobarbital, this gene is transcribed in the midgut, the pericuticular fat bodies and the Malpighian tubules. The induction factor is 15. In the RDDTR strain of Drosophila melanogaster, which is resistant to the insecticide DDT, this gene is constitutively overexpressed in the same tissues (overexpression factor is 6 relative to untreated Canton(s) flies). Phenobarbital is not as effective on RDDTR (induction factor is 2.5 relative to untreated RDDTR flies) as on wild type strains.

Animals↗
PubMed1996

Erythropoietic protoporphyria: two populations of reticulocytes, with and without protoporphyrin.

Erythrocytes from patients with erythropoietic protoporphyria contain large amounts of protoporphyrin. The photosensitivity experienced by these patients is assumed to be due to a leakage of protoporphyrin from the erythrocytes and transfer to the skin, where protoporphyrin acts as a photosensitizer. The leakage of protoporphyrin from the erythrocytes has been offered as an explanation for the great variety in protoporphyrin content observed among erythrocytes in this disease. Based on density gradient separation of red cells, it has been concluded that all reticulocytes and young erythrocytes contain large amounts of protoporphyrin. From our results, density gradient centrifugation is not suitable for age separation of red cells from patients with erythropoietic protoporphyria. By developing a new method for isolation of reticulocytes and applying flow cytometry to determine protoporphyrin content in individual cells, it was observed that two populations of reticulocytes were present in patients with erythropoietic protoporphyria, one with and the other without protoporphyrin. The half-life of protoporphyrin in red cells was found to be 12-14 days, in contrast to 1-2 days described previously, suggesting a slower release of protoporphyrin from the red cells than previously anticipated.

Cell Separation↗
PubMed1996

Apoptosis: a mechanism of cell killing and lymphoid organ impairment during acute African swine fever virus infection.

Induction of programmed cell death has been described during infection with many different viruses. We have investigated the influence of African swine fever virus (ASFV) on apoptosis of different cell populations during in vitro and in vivo infection. We observed apoptosis in ASFV-infected monocyte/macrophage and peripheral blood mononuclear cell cultures. Apoptosis was demonstrated in these cells by DNA fragmentation, DNA staining and DNA-associated histone fraction detection assays. Flow cytometry analysis of infected cultures also showed morphological and functional alterations, including changes in the cell cycle and percentage of cell fractions stained with propidium iodide. After in vivo infection with three different virulent strains of ASFV, apoptosis of infected cells from the mononuclear phagocytic system and closely related elements from different tissues was observed. Additionally, infected pigs showed an intense degree of apoptosis of lymphocytes, which are not infected by the virus. In lymph nodes and other lymphoid organs, broad bands of apoptotic cells presented typical nuclear changes under light microscopy. The occurrence of DNA fragmentation was confirmed in these tissues using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling. These findings, together with the pathological observations in infected pigs of a depletion in cell populations in lymphoid organs, suggest that virus interference with programmed cell death plays a central role in pathogenesis of this disease, being responsible for lymphoid organ impairment in acute ASFV infection.

Acute Disease↗
PubMed1996

Fundamental pathological lesions in vascular dementia.

This review concerns the fundamental cerebral lesions in cases of vascular dementia. Extracerebral vascular alterations are dominated by atherosclerosis with or without thrombosis. In addition, occlusion of extracerebral arteries can be induced by thrombo-embolism and in rare cases by other vascular diseases, chiefly arteritis. Intracerebral microangiopathies are usually of arteriolosclerotic or hyalinotic types in which there is degeneration of smooth muscle cells of the media and deposition of components of extracellular matrix, chiefly collagens. Ageing, chronic hypertension, hyperlipidemias and diabetes are important factors inducing vascular lesions. The vascular lesions, often combined with systemic factors, may produce various ischemic and edematous alterations of the brain parenchyma. Occlusion and obliteration of arteries (macroangiopathy) are associated with large infarcts, whereas microangiopathy may cause lacunar infarcts and some forms of white matter degeneration. Cases of vascular dementia usually present many types of lesions in the brain parenchyma and its arterial supply. The extent and location of the injuries differ considerably from case to case. Location of the lesions, volume of destroyed tissue, multiplicity and bilateral occurrence are most important parameters underlying the clinical manifestations in vascular dementia. A strategic location of a small injury is in some cases of particular importance.

Aged↗