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Biomedical subjects

H Hosseini

Publications and source records attributed to H Hosseini.

11 recordsLinked to original sources

Specific caspase pathways are activated in the two stages of cerebral infarction.

Necrosis and apoptosis have been initially identified as two exclusive pathways for cell death. In acute brain lesions, such as focal ischemia, this binary scheme is challenged by demonstrations of mixed morphological and biochemical characteristics of both apoptosis and necrosis in single cells. The resulting difficulty in defining the nature of cell death that is triggered by severe insults has dramatically impeded the development of therapeutic strategies. We show that in the early stages of cerebral infarction, neurons of the so-called "necrotic" core display a number of morphological, physiological, and biochemical features of early apoptosis, which include cytoplasmic and nuclear condensations and specific caspase activation cascades. Early activation cascades involve the death receptor pathway linked to caspase-8 and the caspase-1 pathway. They are not associated with alterations of mitochondrial respiration or activation of caspase-9. In contrast, pathways that are activated during the secondary expansion of the lesion in the penumbral area include caspase-9. In agreement with its downstream position in both mitochondria-dependent and -independent pathways, activation of caspase-3 displays a biphasic time course. We suggest that apoptosis is the first commitment to death after acute cerebral ischemia and that the final morphological features observed results from abortion of the process because of severe energy depletion in the core. In contrast, energy-dependent caspase activation cascades are observed in the penumbra in which apoptosis can fully develop because of residual blood supply.

Acute Disease↗

Protection against experimental autoimmune encephalomyelitis by a proteasome modulator.

The capacity of interferon beta to alter the course of multiple sclerosis has promoted a new therapeutic concept, based upon the modulation of the immune response rather than its suppression. As the proteasome plays a crucial role in the control of the inflammatory process and immune cell survival, targeting the proteasome appears as a novel approach for the prevention and treatment of inflammatory autoimmune diseases. We have previously shown that ritonavir, an HIV-1 protease inhibitor used in AIDS therapy, can modulate the proteasome function by inhibiting the chymotrypsin-like activity and enhancing the trypsin-like activity. We have, therefore, explored its therapeutic potential on experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis, in Lewis rats and SJL mice. Daily administration of ritonavir during autoimmune antigen stimulation prevented clinical symptoms of EAE in a dose- and time-dependent manner. This protection was accompanied by an inhibition of the mononuclear cell infiltration into the central nervous system usually observed in EAE. Despite a complete absence of clinical symptoms during first EAE induction, ritonavir-treated animals became resistant to further induction of EAE, suggesting an immune mechanism of protection. These results suggest that proteasome modulation using ritonavir or analogues may be of interest for patients with multiple sclerosis.

Animals↗

Regeneration of a transected peripheral nerve by transplantation of spinal cord encapsulated in a vein.

The objective was to investigate the regeneration of a transected peripheral nerve after transplantation of fragmented embryonic (E14-15) spinal cord cells which were encapsulated within a vein cavity. After 3 months transplantation, axonal regeneration was observed by staining with HE and antibody to neurofilament subtypes in six of 10 rats. In all six animals compound muscle action potentials to electrical stimulation could be recorded and indicated incomplete reinnervation of the fibular and tibial nerve, respectively. A chronic inflammation process around the transplant and a negative result of staining neurofilaments within the vein cavity and the transected nerve were found in animals lacking electrophysiological response to stimulation.

Action Potentials↗

[Contribution of immunohistochemistry and electron microscopy for the diagnosis of meningeal hemangiopericytomas. 15 case reports].

Meningeal hemangiopericytomas (HPC) are rare CNS tumors with a pour prognosis compared to meningiomas. In order to define diagnosis criteria, we performed an immunohistochemical and ultrastructural study in respectively 15 and 5 meningeal HPC. The following antibodies anti-KL1, EMA, vimentin, CD34, factor VIII, alpha-smooth actin, estrogen and progesteron receptors (RE, RP) were used in paraffin embedded sections whereas anti-NCAM and E-cadherin antibodies were used on frozen sections when available. We can differentiate meningeal HPC from meningioma because of a complete lack of immunostaining with epithelial markers as well as with NCAM antibody or RE and RP receptors. Besides a positivity with CD34 and alpha-smooth actin antibodies was always observed even focally in HPC. On the other hand, solitary fibrous tumor showed a strong and diffuse positivity with anti CD34 and anti-vimentin antibodies. Electron microscopy can be helpful in some instances showing membrane basal-like substance and absence of desmosomes.

Adult↗

Striatal dopaminergic denervation in pallidopyramidal disease demonstrated by positron emission tomography.

Pallidopyramidal disease is a rare disease of young patients in which they manifest a parkinsonian syndrome and pyramidal signs. Pallidopyramidal disease has been attributed to a degeneration of the pallidum and the pyramidal tract, although only 1 patient has been studied postmortem. In the present report, [18F]fluorodopa positron emission tomography in 2 patients showed a marked dopaminergic denervation of the striatum, suggesting that this disease corresponds more to a nigropallidopyramidal dysfunction.

Adolescent↗

Analyzing data from ordered categories.

Clinical investigations often involve data in the form of ordered categories--e.g., "worse," "unchanged," "improved," "much improved." Comparison of two groups when the data are of this kind should not be done by the chi-square test, which wastes information and is insensitive in this context. The Wilcoxon-Mann-Whitney test provides a proper analysis. Alternatively, scores may be assigned to the categories in order, and the t-test applied. We demonstrate both approaches here. Sometimes data in ordered categories are reduced to a two-by-two table by the collapsing of the high categories into one category and the low categories into another. This practice is inefficient; moreover, it entails avoidable subjectivity in the choice of the cutting point that defines the two super-categories. The Wilcoxon-Mann-Whitney procedure (or the t-test with use of ordered scores) is preferable. A survey of research articles in Volume 306 of the New England Journal of Medicine shows many instances of ordered-category data (about 20 per cent of the articles had such data) and no instance of analysis by the preferred methods presented here. We suggest that investigators who are unfamiliar with these methods should seek the assistance of a professional statistician when they must deal with such data.

Candidiasis, Oral↗