Search PubMed⌕ Search

Biomedical subjects

M Hommel

Publications and source records attributed to M Hommel.

At least 37 records · Page 2Linked to original sources

Restriction-fragment-length polymorphism analysis of small-subunit rRNA genes of Blastocystis hominis isolates from geographically diverse human hosts.

Genomic diversity among 14 isolates of Blastocystis hominis from 4 different geographic locations was examined by small-subunit rRNA (ssu rRNA) restriction-fragment-length polymorphisms (RFLP) using 5 different restriction endonucleases. On the basis of the observed RFLP patterns among the isolates, a total of 12 genotypes were identified, with 7 isolates exhibiting mixed RFLP genotypes. There was no correlation between B. hominis geographic origin and RFLP banding pattern or genotype.

Animals↗

Polar Plasmodium falciparum lipids induce lipogenesis in rat adipocytes in vitro.

Previous studies have shown that 'toxic malarial antigens' released by Plasmodium yoelii can induce hypoglycaemia in mice and act synergistically with insulin in stimulating lipogenesis in rat adipocytes in vitro. In this study, it was shown that similar bioactivity could be detected in Plasmodium falciparum culture supernatant, and the molecular basis of this activity was further investigated. Boiled spent culture medium from P. falciparum cultures ('BS-Pf') (exclusively released into the culture supernatant when schizonts rupture) acts in synergy with insulin to increase lipogenesis in a rat adipocyte assay by more than 250% (P < 0.001). Control preparations prepared from non-parasitized erythrocytes grown under similar conditions had no effect (P < 0.001). While contamination with mycoplasma has previously been shown to interfere with the interpretation of data obtained with other molecules thought to be released from P. falciparum in culture, including those inducing TNF-alpha and NO production by macrophages, such contamination was unequivocally ruled out here. BS-Pf alone did not stimulate the lipogenesis in short-term assays (less than 4 h), while long-term exposure of rat adipocytes to BS-Pf alone (12-24 h) caused a stimulation of lipogenesis at a level comparable to that observed with insulin. Furthermore, lipogenesis-inducing activity was also detected in the serum of squirrel monkeys infected with different species of malaria parasites (P. vivax, P. falciparum and P. brasilianum). Preliminary biochemical characterization showed that the biological activity was found in the solvent-extracted polar lipid fraction of boiled supernatant of P. falciparum cultures. All the different polar lipid fractions, collected from silica gel column chromatography, showed a comparable lipogenesis-inducing activity. Enzymatic treatment by phospholipase C of the lipid fraction, which co-migrated with the phosphatidylcholine standard, showed that the activity of the fraction was associated with the 1,2-diacylglycerol (1,2-DAG) moieties released from polar lipids. When this exogenous 1,2-DAG was added to the adipocyte cultures (short- and long-term cultures), it induced stimulation of lipogenesis in rat adipocytes, while no lipogenic activity was obtained from bacterial polar lipids and 1,2-DAG isolated from unparasitized erythrocytes. The importance of these findings is discussed with reference to other toxic malarial antigens and also to the potential role of these molecules in the induction of hypoglycaemia in the severe forms of malaria.

Adipocytes↗

Streptokinase in acute ischemic stroke: an individual patient data meta-analysis : The Thrombolysis in Acute Stroke Pooling Project.

BACKGROUND AND PURPOSE: Three major randomized controlled trials of streptokinase in acute ischemic stroke were curtailed because of safety concerns. The prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established to examine the aggregate data to identify factors influencing the effect of streptokinase. METHODS: Individual patient data from the Australian Streptokinase Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled. Multivariate modeling determined the interaction between treatment effect and delay from symptom onset to treatment, predicted baseline risk, age, concomitant aspirin or heparin use, and the presence of early CT signs on the outcomes of 10-day death, death and disability, or death alone at 3 or 6 months. RESULTS: Patients' records were pooled (total 1292 patients; streptokinase, n=653, no streptokinase n=639). The subgroup analysis of treatment effect according to delay from symptoms to inclusion shows only a trend toward a better treatment effect with shorter delay, which is not statistically significant for any outcome. Heavier patients in MAST-E may have had a lower (non significant) risk from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin increased the excess mortality rates in streptokinase-treated patients (17% without aspirin versus 91% with aspirin, P=0.005). The presence of early CT scan signs did not increase the detrimental effect of streptokinase. CONCLUSIONS: Few factors influenced the response to streptokinase. However, earlier administration, lower doses of streptokinase, and avoidance of concomitant aspirin should be considered if further streptokinase trials in acute stroke are planned.

Acute Disease↗

Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses.

Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30-45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5-6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76-80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro-propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.

Amino Acid Sequence↗

[Why hospitalize stroke patients in a specialized unit?].

A PUBLIC HEALTH CHALLENGE: Cerebral vascular events are the third most frequent cause of death in the adult population and the number one cause of disabilities, a public health challenge both in terms of health care service and health care expenditures. SPECIALIZED UNITS: Structured health care facilities, particularly specialized hospital units, can lower mortality, limit residual disability and reduce the need for long-term institutionalization. OUTLOOK: Specialized research and teaching units are paradigmatic of the impact of health care organization. The limited number of such specialized units in France raises important ethical considerations about effective access to health care. Functioning units could be a useful criteria for auditing quality of hospital facilities.

Adult↗

Hemorrhagic transformation in acute ischemic stroke. The MAST-E study. MAST-E Group.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is the most critical complication of thrombolytics in clinical trials in acute stroke. The aim of this study was to determine the rates and the predictors of HT in the Multicenter Acute Stroke Trial-Europe (MAST-E) study. METHODS: We performed a post hoc analysis of MAST-E data designed to assess the safety and efficacy of streptokinase administered intravenously within 6 hours of stroke onset. HT included all intracerebral hemorrhages and symptomatic hemorrhages (SHT) associated with clinical worsening. The predictors of HT and SHT were determined using multivariate modeling. RESULTS: Among the 310 patients included, 159 patients had HT and 37 SHT (97 and 33 in the streptokinase group and 62 and 4 in the placebo group, respectively). Patients with SHT had significantly more atrial fibrillation, diabetes mellitus, no heparin use, streptokinase treatment, and early CT signs. In the multivariate analysis, HT was predicted by early CT signs and streptokinase treatment. SHT was predicted by diabetes mellitus, early CT signs, streptokinase treatment, and the interaction between streptokinase treatment and decreased level of consciousness. Among the streptokinase-treated patients, the same predictors remained. CONCLUSIONS: The relative risks of HT after streptokinase were in the same range in MAST-E as in other streptokinase and tPA trials. Early CT signs were strong predictors of both HT and SHT, stressing that these patients are at high risk of bleeding. In our study, the predictors of HT and SHT were similar to those of tPA trials in acute stroke.

Acute Disease↗

[Ataxic hemiparesis due to lacunar infarct].

Ataxic hemiparesis is a syndrome in which pyramidal and cerebellar signs occur on the same side. Few authors have suggested that signs or symptoms can orientate toward a supratentorial or toward an infratentorial lesion. We have studied the risk factors and the clinical symptoms of 61 patients consecutively admitted for an ataxic hemiparesis due to a lacunar infarct diagnosed with MRI. The MRI was normal in 2 cases. A tandem lacunar infarct was found in 9 cases (pons and internal capsule in 5 cases, pons and corona radiata in 4 cases) and a clinico-radiological correlation was performed in 50 cases. The comparison of risk factors did not show any difference between the infratentorial (n = 10) and the supratentorial groups (n = 40) excepting for the history of coronary disease. The history of coronary disease was statistically more frequent in the infratentorial group. No difference was found for clinical findings between the 2 groups.

Aged↗

[Role of emergency cerebrovascular units in the network of care].

Stroke units can improve outcome after stroke as demonstrated by a meta-analysis which evidenced a reduction of the odds ratio for mortality (18 +/- 8 p. 100) and for poor outcome, death, or institutional care (25 +/- 10 p. 100), and death or dependancy (29 +/- 11 p. 100). Improved quality of life and shorter hospital stay have not been so clearly established. Stroke units are helpful in organizing acute neurology care. Moreover, stroke units are involved in teaching and research. Their development should be promoted in hospitals.

Emergency Medical Services↗

The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo.

The purpose of the present study was to evaluate in vivo the effect of a non competitive antagonist of the NMDA receptor, eliprodil, on the size of a focal ischaemic insult and on its temporal evolution in a rat model, using a spin-echo diffusion magnetic resonance imaging multislice technique. Rats were either injected with 1 mg/kg i.v. of eliprodil or with the vehicle only (placebo) 5 min after middle cerebral artery occlusion, or not injected (controls). Ten coronal slices were acquired every hour, up to 7 h after occlusion of the artery, and the volume of hyperintense signals was measured at each time point and for each animal. Diffusion magnetic resonance images revealed that the administration of eliprodil reduced significantly (by 50% or more) the volume of ischaemia, up to 7 h after occlusion, particularly in the cortex of the ipsilateral hemisphere. The results show the potential efficacy of eliprodil to reduce the cerebral ischaemic volume after arterial occlusion, thus confirming the interest of glutamate receptor antagonists in the treatment of ischaemia.

Animals↗

[Prevention of cerebral ischemic vascular accidents].

Application of all the measures for primary ischaemic stroke prevention is of major importance because they have a dramatic clinical effect. They are including the modification of lifestyle such as the level of physical activity, alimentation and cigarette smoking. Medications lowering blood pressure, serum cholesterol and glucose levels, and anticoagulants when atrial fibrillation is diagnosed are of proven efficacy. All these measures are also efficient in secondary prevention. Antiplatelets agents in case of atherothrombotic stroke and anticoagulants for cardioembolic stroke are of evident value. Evidence of efficacy of carotid surgery is clearly established for symptomatic tight stenosis. It could be expected that the application to a population of all these measures could result in a more than 50 percent decrease in incidence of ischaemic stroke.

Anticoagulants↗

Monoclonal antibodies against vascular endothelial antigens expressed in normal human brain.

A panel of monoclonal antibodies reactive with human-brain vessels was raised by immunizing BALB/c mice with homogenate of whole human brain, obtained from temporal lobectomies. Hybridoma supernates were screened by immunohistochemical methods on frozen sections of human brain, liver and spleen and 16 clones were isolated. The pattern of immunoreactivity varied with respect to the type of brain blood vessels predominantly labelled and to tissue specificity. Some antibodies cross-reacted with cow or squirrel monkey forebrain microvessels with an intensity equal to that shown by human brain. The immunoreactivity patterns reflected antigenic heterogeneity among different subsets of vascular endothelial cells in human brain.

Animals↗

IgG subclass recognition of Loa loa antigens and their correlation with clinical status in individuals from Gabon.

In endemic areas for Loa loa, a significant percentage of actively infected individuals have no circulating microfilariae, an observation which implies the existence of a stage-specific immune response. In an attempt to define the immunological basis of the amicrofilaraemic state, the reactivity of antigens from adult, microfilariae and infective larvae of L. loa was examined by Western blotting with individual serum samples from four clinically defined groups (high microfilaraemic, low microfilaraemic, amicrofilaraemic and endemic controls) using IgG subclass-specific reagents and IgE. In the adult parasite, a complex of antigens at 28-31 kDa was exclusively recognized by IgG1 from amicrofilaraemic individuals and, to a lesser extent, by IgG1 from endemic controls. However, this complex of antigens was recognized by IgG4 antibodies in serum samples from all individuals, including microfilaraemics. A microfilarial antigen of 21 kDa was recognized by IgG1 antibodies present in serum from amicrofilaraemic, endemic control and low microfilaraemic individuals. Persons with high levels of microfilariae did not recognise this antigen. In both the L3 and the microfilariae, a ladder antigen with increments of 15 kDa was the main target of IgG4 antibodies in amicrofilaraemic and microfilaraemic individuals. IgE antibodies recognized more antigens in the microfilarial stage than in the adult of L3. These results suggest that immunological differences between clinically defined groups are associated with the recognition of different antigens or epitopes.

Animals↗