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Biomedical subjects

Alexandru C Stan

Publications and source records attributed to Alexandru C Stan.

6 recordsLinked to original sources
PubMed2005

Efficacy of clonal deletion vs. anergy of self-reactive CD4 T-cells for the prevention and reversal of autoimmune diabetes.

The self-reactive CD4 T-cells play an essential role in triggering and sustaining organ-specific autoimmune diseases. Silencing or elimination of these cells can prevent and reverse an autoimmune process. We have previously showed that a single dose-administration of a soluble dimeric MHC II-peptide chimera (DEF) in double-transgenic mice delayed the onset autoimmune diabetes, and restored the euglycemia in already diabetic mice for a period of 1 week. DEF dimer protection relied on induction of anergy of diabetogenic CD4 T-cells in spleen, and stimulation of IL-10-secreting T regulatory type 1 cells in pancreas. Herein, we show that an octameric form of DEF has doubled the period of protection and reversal of disease by clonal deletion of diabetogenic CD4 T-cells in both the thymic and peripheral compartments. Deletion occurred by activation-induced cell death subsequent to repartitioning and signaling of FAS-FADD apoptotic module in the plasma membrane lipid rafts. Our previous and present data indicated first, that DEF valence translates into various effects on the antigen-specific CD4 T-cells, i.e., Th2 immune deviation, anergy, and apoptosis. Second, the present findings argue for a better efficacy of clonal deletion than anergy of diabetogenic CD4 T-cells for the protection and reversal of autoimmune diabetes.

Animals↗
PubMed2004

Supracallosal longitudinal fiber bundle: heterotopic cingulum, dorsal fornix or Probst bundle?

A thick longitudinal fiber bundle found within the dorsal corpus callosum in two unrelated adults (in a micrencephalic female patient and incidentally in another male patient) is considered to be a congenital aberrant cingulum. Agenesis or apparent hypoplasia of the indusium griseum of the limbic-cingular system as an accompanying finding in the present cases may support this hypothesis. The dorsal fornix and Probst bundle are discussed in terms of differential diagnosis, although there was no further support for this possibility. The hyperplastic dorsocallosal gray substance is excluded.

Adult↗
PubMed2002

Expression of JC virus agnoprotein in progressive multifocal leukoencephalopathy brain.

To examine the function of JC virus (JCV) agnoprotein, we examined the brains of cases of progressive multifocal leukoencephalopathy (PML), which is caused by JCV infection, using a newly generated antibody. The antibody reacted with 8 kDa protein specific for JCV agnoprotein by Western blotting. In vitro analyses showed that JCV capsid protein VP1 and large T antigen (T-Ag) were localized in the nuclei, but that agnoprotein was mainly detected in the cytoplasm of JCV-infected cells with an occasional nuclear staining. In the PML brain, an immunoreactive signal for agnoprotein was distributed in the perinuclear areas and cytoplasmic processes with occasional punctate staining in demyelinating lesions as well as adjacent myelinated areas. Agnoprotein presented mostly in the infected oligodendrocytes and partly in the astrocytes. Using double immunostaining, agnoprotein was seen to be expressed in the cytoplasmic processes of the cells, the nuclei of which were labeled with VP1 and T-Ag, where virus particles existed. Thus, JCV agnoprotein was mostly expressed in the infected oligodendrocytes and mainly localized in the cytoplasmic processes apart from virus particles in the demyelinated lesions.

Adult↗
PubMed2002

Halofuginone inhibition of COL1A2 promoter activity via a c-Jun-dependent mechanism.

OBJECTIVE: The naturally occurring compound halofuginone has been shown to antagonize collagen synthesis by fibroblasts both in vitro and in vivo. We previously demonstrated that this inhibitory property was related to the ability of halofuginone to disrupt transforming growth factor beta signal transduction. The present study further analyzed the ability of halofuginone to affect transcription factors that can regulate type I collagen gene expression by examining its effect on c-Jun, the negative regulator of collagen gene transcription. METHODS: The phosphorylation state of c-Jun in the presence of halofuginone was examined via direct Western blotting, and the transcriptional activity of the activator protein 1 (AP-1) binding element via electrophoretic mobility shift assay and luciferase reporter assay. We determined whether the effect of halofuginone on collagen synthesis was dependent on the presence of c-Jun by ectopic expression of a wild-type or dominant-negative c-Jun construct in the presence of halofuginone and assaying alpha2(I) collagen promoter strength via luciferase reporter assay. The effect of halofuginone on alpha2(I) collagen message levels in fibroblasts when wild-type or dominant-negative c-Jun was overexpressed was determined. We also determined whether halofuginone had an effect on the phosphorylation state of c-Jun in the skin of TSK/+ mice via immunohistochemistry. RESULTS: Treatment of fibroblasts with 10(-8)M halofuginone enhanced basal and mitogen-mediated phosphorylation of c-Jun in culture. This elevated phosphorylation of c-Jun correlated with enhanced DNA binding and transcriptional activation of an AP-1 complex consisting of c-Jun and Fos but lacking the c-Jun antagonist JunB. Overexpression of c-Jun enhanced in a dose-dependent manner the ability of halofuginone to inhibit the activity of a luciferase reporter construct under control of the -3200-bp to +54-bp COL1A2 promoter, whereas the expression of a dominant-negative c-Jun construct abolished this effect. Northern blotting showed that overexpression of c-Jun enhanced the ability of halofuginone to reduce collagen alpha2(I) messenger RNA levels in fibroblasts, whereas expression of the dominant-negative c-Jun abolished this effect. Topical administration of a halofuginone-containing cream for 20 days to TSK mice, which spontaneously develop dermal fibrosis, greatly increased the phosphorylated form of c-Jun in the skin; this was followed by a decrease in skin thickness and type I collagen messenger RNA expression. CONCLUSION: Our findings illustrate the powerful down-regulatory property of c-Jun toward type I collagen and establish that halofuginone exerts its effect on collagen synthesis in a c-Jun-dependent manner.

Administration, Topical↗
PubMed2002

De novo development of a cavernous malformation of the brain: significance of factors with paracrine and endocrine activity: case report.

OBJECTIVE AND IMPORTANCE: De novo development of cavernous malformations is poorly documented in the literature. CLINICAL PRESENTATION: We report the case of a 37-year old woman with de novo growth of a cavernous malformation of the brain. The patient presented with a 12-month history of nonspecific headaches and paresthesias after two pregnancies. After computed tomographic scanning of the cranium, a cavernous malformation located parieto-occipitally within the right brain hemisphere was diagnosed. Control magnetic resonance imaging scans obtained 12 years earlier did not reveal a similar lesion. INTERVENTION: Surgery was performed, and the specimen was analyzed histopathologically. CONCLUSION: Immunohistochemistry demonstrated lack of expression of pituitary hormones as well as of androgen, estrogen, and progesterone hormone receptors. However, strong expression of both basic fibroblast growth factor and CD44 was detected in surrounding tissue, and expression of CD44 was noted within the matrix of the cavernous malformation.

Adult↗