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Biomedical subjects

M Hofer

Publications and source records attributed to M Hofer.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Functional imaging of the brain using low dose gadolinium-DTPA and Turbo-FLASH sequences].

A method for measuring regional blood volume and flow is described based on the reduced relaxation time following intravenous injection of Gd-DTPA. The optimal Gd dose and other parameters were first determined using turbo-flash sequences and a dilution phantom. A single maximum was found for a Gd-DTPA concentration of 4 mmol/l. Taking account of normal heart/time volumes and in order to stay below this arterial value Gd-DTPA was injected as a bolus at the rate of 1 mmol/sec. From the phantom measurements there appears to be a functional connection between measured signal intensity and Gd concentration. The method was applied to 15 patients with cerebral tumours, using altogether 26 perfusion examinations. The results from 4 patients are given as examples; in these, blood volume and flow were calculated for each pixel in a 128 x 128 matrix. It was found that the Gd-DTPA injected is sufficient to be shown with certainty in the grey and white matter and that this is able to demonstrate pathological changes in a functional manner. Comparison with Gd-DTPA doses such as are used for morphological imaging (typically, 10 mmol corresponding to 0.1 mmol/kg body weight) has shown that doses above 1.6 mmol may lead to distortion of the concentration curves.

Aged↗
PubMed1993

[The selective arterial and venous MR angiography of intracranial arteriovenous malformations].

This study evaluates the usefulness of MR angiography (MRA) in analysing cerebral arterial blood supply and venous drainage in patients with intracranial arteriovenous malformations (AVM). Selective MRA of the carotid, middle cerebral or vertebrobasilar territories was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective, non-selective arterial, as well as venous MRA in 13 consecutive patients were compared with the findings at intraarterial angiography, the latter serving as the "gold standard". Sensitivity in identifying major feeding arteries was 100%. Determination of the absolute and relative AVM sizes at selective MRA corresponded with IAA. The mean difference was 17.6 and 3.9% respectively. Both display of superficial and deep venous drainage was provided by 2-dimensional venous MRA. The authors conclude that selective MRA of cerebral arteries as used here is a powerful non-invasive method to demonstrate blood supply by single feeding vessels in intracranial malformations. 2D venous MRA permits an accurate evaluation of the venous drainage pattern.

Adult↗
PubMed1993

[Quantification of extracranial carotid stenosis. Magnetic resonance angiography and Doppler sonography versus intra-arterial angiography].

UNLABELLED: To assess various non-invasive techniques for quantifying internal carotid artery CA stenosis, per cent luminal diameter reduction on intraarterial angiograms (IAA) was measured in 63 patients with ICA stenosis or occlusion. These data were compared with independent measurements based on MR-angiography, continuous-wave (cw) Doppler ultrasonography, systolic peak flow velocity and colour Doppler assisted duplex imaging. Correlations with IAA were equally strong for MR angiography, cw Doppler and colour Doppler analysis (0.95; 0.92; 0.92). Positive predictive values for > or = 70% ICA stenosis were lower and negative predictive values were higher for cw Doppler (0.85; 0.92) and colour duplex analysis (0.81; 0.94) than for MR angiography (0.86; 0.88). Statistical analysis showed non-linear correlations between percentage of lumen diameter narrowing and the length of the zone of signal intensity loss (0.72) and maximum systolic peak flow velocity (0.77). CONCLUSION: Several non-invasive methods do compare with IAA in identifying and quantifying high-grade ICA stenosis and may suffice for decisions on treatment.

Adult↗
PubMed1993

[The hemodynamics and anatomy of the circle of Willis. The technic and clinical value of selective MR angiography].

This study evaluates the usefulness of MR angiography in analysing the individual collateral flow dynamics and anatomy of the circle of Willis in 56 patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar area was performed by means of presaturation up to the brain-supplying arteries at the level of the middle neck (angled presaturation slabs). Results obtained with selective and non-selective MRA in 56 consecutive patients were compared with the findings at transcranial Doppler ultrasonography and arterial angiography. Ischaemic cerebral infarctions were classified by computerized tomography and correlated with the results of collateral flow analysis: Sensitivity of selective MRA in detecting intracranial collateral flow via anterior or posterior communicating artery was 96 and 97%, respectively; sensitivity in depicting extracranial transorbital flow was lower (71%). Non-selective MRA was 100% sensitive in detecting a non-filling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Slow flow infarctions occurred more frequently in patients with transorbital and posterior-to-anterior collateral flow than in patients with collateral flow via anterior communicating artery.

Angiography↗
PubMed1993

Evaluation of the biological effects of police radar RAMER 7F.

This paper presents results of experiments on the effects of electromagnetic radiation in the millimeter range (frequency 34.0 +/- 0.1 GHz, power density 20 muW/cm2) emitted by a police radar device. Considering the physical properties of the radiation in millimeter range (skin effects), the experiments were carried out on hairless mice. The main physiological parameters tested were body mass, body temperature, peripheral blood, and mass and cellularity of several important organs. Critical organs, the skin, and cornea were examined by electron microscopy. Differentiation ability of hematopoietic cells, progenitors of granulocytes and macrophages, and DNA synthesis in the cornea were compared in irradiated and nonirradiated animals. None of the parameters tested was affected to an extent that would indicate the start of a pathological process or the risk of damage to genetic material.

Animals↗
PubMed1993

Noradrenaline reduces cardiovascular effects of the combined dipyridamole and AMP administration but preserves radioprotective effects of these drugs on hematopoiesis in mice.

Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.

Adenosine Monophosphate↗
PubMed1993

Hyporesponsiveness of murine myeloid progenitor cells to glucan following its repeated administration.

A moderate marrow granulocytic hyperplasia developed after 4 injections of glucan (soluble derivative carboxymethylglucan) administered to mice at 3-4-day intervals. However, when evaluating the response of the marrow granulocyte-macrophage colony-forming cells (GM-CFC) to the fifth glucan injection given in the repetitive treatment schedule, the development of hyporesponsiveness of these cells was found, contrary to the stimulatory action of a single glucan injection. In addition, the prompt increase in serum granulocyte-macrophage colony-stimulating activity occurring after a single glucan injection, and proposed to upregulate myelopoiesis, was absent in mice treated with glucan repeatedly. A joint administration of glucan with diclofenac, an inhibitor of prostaglandin synthesis, was able to enhance the GM-CFC response to a single glucan injection, probably due to the removal of the downregulation action of prostaglandins on these progenitor cells. However, a repeated administration of diclofenac with glucan did not reduce substantially the development of GM-CFC hyporesponsiveness. Thus, the results suggest that the GM-CFC hyporesponsiveness or tolerance to repeated glucan injections was induced by weakening the mechanisms of positive control mediated by the serum colony-stimulating activity.

Adjuvants, Immunologic↗
PubMed1993

Elevation of extracellular adenosine induces radioprotective effects in mice.

The radioprotective effectiveness of the elevation of extracellular adenosine induced in mice by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, a soluble adenosine pro-drug, was evaluated. Based on survival studies, endogenous hemopoietic spleen colony formation, and the postirradiation behavior of bone marrow granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the combined administration of dipyridamole and AMP protects mice when given either 15 or 60 min before irradiation. It could be deduced that the radioprotective action is induced by at least two independent mechanisms: (1) protection by hypoxia as a result of the effect of the treatment on the cardiovascular system, and (2) and enhanced regeneration of the hemopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hemopoietic stem cells. Both of these protective mechanisms, which are able to increase the regeneration of hemopoiesis, seemed to be effective in enhancing the survival of mice given single radiation exposures, with a dose reduction factor for the LD50/30 of 1.11. The protective efficiency of the mechanisms enhancing the postirradiation recovery of hemopoiesis was also evident in experiments evaluating the survival of mice subjected to fractionated irradiation and a repeated administration of the protective agents.

Adenosine↗
PubMed1992

Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis.

An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation.

Animals↗
PubMed1992

CFU-S and haematopoietic microenvironment in mice after fractionated irradiation. A study on spleen colonies.

The paper is aimed at evaluating the quantity and quality of the haematopoietic stem cells, CFU-S, in the bone marrow and the functional effectiveness of the haematopoietic microenvironment of the spleen in two time intervals after repeated exposure of mice to doses of 0.5 Gy gamma-rays once a week (total doses of 12 and 24 Gy). After irradiation, bone marrow was cross-transplanted between fractionatedly irradiated and control mice. The parameter evaluated were numbers of spleen colonies classified into size categories. The data obtained provide evidence for a significant damage to the CFU-S, concerning both their number and proliferation ability, after both total doses used. The functional effectiveness of the haematopoietic microenvironment of the spleen was impaired only in bone marrow recipients receiving a transplant after having been exposed to a total dose of 24 Gy; this dose combined with subsequent pre-transplantation irradiation resulted in a marked suppression of cell production within the spleen colonies formed from a normal bone marrow on the spleens of fractionatedly irradiated mice.

Animals↗
PubMed1992

Enhancement of hematopoietic recovery in gamma-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin production, and glucan, a macrophage activator.

The effects of diclofenac (inhibitor of prostaglandin production) and carboxymethylglucan (immunomodulator and an agent stimulating hematopoiesis), when given to mice 1 day before gamma-irradiation, were studied. Both of the agents were administered either alone or in combination. The investigations included the assessment of post-irradiation hematopoietic recovery in terms of bone marrow and spleen cellularity and endogenous spleen colony formation, as well as the determination of the survival of lethally irradiated mice. The results demonstrated at least additive radioprotective effects when mice were given diclofenac and carboxymethylglucan in combination. Experimental evidence provided by the increased 125iodo-deoxyuridine incorporation into the spleen and elevated hydroxyurea kill of endogenous spleen colony-forming units indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hematopoietic tissue. It is likely that the inhibition of prostaglandin production (diclofenac action) and the concomitant increased release of growth factors (glucan action) shift the regulatory balance towards the predominance of positive hematopoietic control.

Animals↗
PubMed1991

BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra.

Brain-derived neurotrophic factor (BDNF), present in minute amounts in the adult central nervous system, is a member of the nerve growth factor (NGF) family, which includes neurotrophin-3 (NT-3). NGF, BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most sympathetic neurons are responsive to NGF, but not to BDNF; NT-3 and BDNF, but not NGF, promote survival of sensory neurons of the nodose ganglion. BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. However, knowledge of their precise physiological role in development and maintenance of the nervous system neurons is still limited. The BDNF gene is expressed in many regions of the adult CNS, including the striatum. A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra.

Animals↗
PubMed1991

Aggregation behavior of lipid IVA in aqueous solutions at physiological pH. 1: Simple buffer solutions.

We have investigated the aggregation behaviour of lipid IVA (a bioactive precursor of lipid A and the lipid anchor of lipopolysaccharide) in aqueous solutions in the physiological pH range using dynamic light scattering, nuclear magnetic resonance, fluorescence, surface pressure, electron microscopy and force field simulation studies. The sonication of lipid IVA in PBS, Tris and Hepes produces vesicles which are stable in the concentration range of 10(-3) - 10(-7) M, possibly even at lower concentrations. The vesicle size is not sensitive to the nature of the buffer, only to the pH and to some extent to the ionic strength. The long time stability of the small unilamellar vesicles as well as the structureless 1H-NMR spectra might be attributed to a rigid surface structure. This structure is also supported by the simulation studies. We have tentatively proposed a coexistence of micelles and/or other aggregates with the bilayered vesicles at higher lipid concentrations in order to explain some of the experimental observations.

Buffers↗
PubMed1991

Hemopoiesis stimulating and radioprotective effects of carboxymethylglucan.

Carboxymethylglucan, a novel soluble derivative of beta-1,3-glucan, was found to enhance hemopoietic recovery in sublethally gamma-irradiated mice and to increase survival in lethally irradiated animals when given 24 hours prior to irradiation. Postirradiation treatment with carboxymethylglucan also induced favourable effects in terms of survival when used in combination with preirradiation cystamine administration.

Animals↗
PubMed1991

Ultrastructure of erythroblast mitochondria in mice treated with mixtures of radioprotectors.

Unirradiated mice were given i.p. a mixture of mexamine (20 mg/kg body weight) and AET (150 mg/kg body weight) or mexamine (20 mg/kg body weight) and cystamine (150 mg/kg body weight). Acute effects of these mixtures of radioprotective agents on the ultrastructure of basophilic and polychromatic bone marrow erythroblast mitochondria were studied. One hour after injecting mice with above-mentioned mixtures, statistically significant differences in the size of mitochondria were found between control mice and mice given a mixture of mexamine and cystamine. The differences in the number of dilated cristae per micron 2 of the mitochondrion area between control mice and both experimental groups given mixtures of radioprotective agents were also statistically significant. Thus it was proved that also mixtures of radioprotectors induced acute ultrastructural changes of mitochondria which were so far described only after treating mice with only one radioprotective agent.

5-Methoxytryptamine↗
PubMed1990

Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain.

Brain-derived neurotrophic factor (BDNF) is a protein that allows the survival of specific neuronal populations. This study reports on the distribution of the BDNF mRNA in the adult mouse brain, where the BDNF gene is strongly expressed, using quantitative Northern blot analysis and in situ hybridization. All brain regions examined were found to contain substantial amounts of BDNF mRNA, the highest levels being found in the hippocampus followed by the cerebral cortex. In the hippocampus, which is also the site of highest nerve growth factor (NGF) gene expression in the central nervous system (CNS), there is approximately 50-fold more BDNF mRNA than NGF mRNA. In other brain regions, such as the granule cell layer of the cerebellum, the differences between the levels of BDNF and NGF mRNAs are even more pronounced. The BDNF mRNA was localized by in situ hybridization in hippocampal neurons (pyramidal and granule cells). These data suggest that BDNF may play an important role in the CNS for a wide variety of adult neurons.

Amino Acid Sequence↗