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Biomedical subjects

L Dumitrescu

Publications and source records attributed to L Dumitrescu.

At least 19 recordsLinked to original sources

Single nucleotide polymorphism screening and association analysis--exclusion of integrin beta 7 and vitamin D receptor (chromosome 12q) as candidate genes for asthma.

BACKGROUND: The human genes coding for integrin beta 7 (ITGB7) and vitamin D receptor (VDR) are two of the several candidate genes for asthma and related phenotypes found in a promising candidate region on chromosome 12q that has been identified in multiple genomewide screens and candidate gene approaches. METHODS: All exons, including parts of the neighbouring introns, and the predicted promoter region of the ITGB7 gene were screened for common polymorphisms in 32 independent asthmatic and healthy probands, resulting in the detection of two single nucleotide polymorphisms (SNPs) unknown so far. In addition to these SNPs, five already described SNPs of the ITGB7 and one in the human VDR gene were analysed in a Caucasian sib pair study of 176 families with at least two affected children, using matrix assisted laser desorption/ionization time of flight mass spectrometry. All confirmed SNPs were tested for linkage/association with asthma and related traits (total serum IgE level, eosinophil cell count and slope of the dose-response curve after bronchial challenge). RESULTS: Two new variations in the ITGB7 gene were identified. The coding SNP in exon 4 causes a substitution of the amino acid GLU by VAL, whereas the other variation is non-coding (intron 3). None of the eight analysed SNPs, of either the ITGB7 or the VDR genes, showed significant linkage/association with asthma or related phenotypes in the family study. CONCLUSIONS: These findings indicate that neither the human ITGB7 nor the VDR gene seem to be associated with the pathogenesis of asthma or the expression of related allergic phenotypes such as eosinophilia and changes in total IgE level.

Adolescent↗

The heat shock response reduces myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in mice.

The stress response (SR) can block inflammatory gene expression by preventing activation of transcription factor nuclear factor-kappa B (NF-kappaB). As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases, we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis (EAE). EAE was actively induced in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide. Whole body hyperthermia was used to induce a heat shock response (HSR) in immunized mice 2 days after the booster MOG(35-55) peptide injection. The HSR reduced the incidence of EAE by 70%, delayed disease onset by 6 days, and attenuated disease severity. The HSR attenuated leukocyte infiltration into CNS assessed by quantitation of perivascular infiltrates, and by reduced staining for CD4 and CD25 immunopositive T-cells. T-cell activation, assessed by the production of interferon gamma (IFNgamma) in response to MOG(35-55), was also decreased by the HSR. The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE, including the early increase in RANTES (regulated on activation of normal T-cell expressed and secreted) expression, and the later expression of the inducible form of nitric oxide synthase. The early activation of transcription factor NF-kappaB was also blocked by the HSR. The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases.

Animals↗

Temporal, regional, and cell-specific changes of iNOS expression after intrastriatal microinjection of interferon gamma and bacterial lipopolysaccharide.

Here we study expression of the inducible isoform of nitric oxide synthases after intrastriatal microinjection of interferon-gamma and bacterial lipopolysaccharide in the rat at different time points to detect time- and localisation-dependent changes of iNOS expression. Three different areas in the striatum and the corpus callosum were evaluated. Antibodies against the glial fibrillary acidic protein and the microglia/brain macrophage epitope ED1 were used to detect colocalization of inducible nitric oxide synthase with astrocytes or activated microglia/brain macrophages, respectively. Inducible nitric oxide synthase-positive cells occurred first in intravascular and perivascular cells at 4 h. Perivascular and parenchymal inducible nitric oxide synthase expression increased up to 24 h in the striatum, whereas in the corpus callosum inducible nitric oxide synthase expression was maximal after 16 h. Inducible nitric oxide synthase was still present in perivascular cells 7 days after immunostimulation. At all time points, inducible nitric oxide synthase was predominantly detected in ED1-positive microglia/brain. Nitrotyrosine immunohistochemistry was performed to detect NO-mediated nitration of proteins at all time points. Nitrotyrosine-positive neurons and microglial cells were detected from 24 h until 7 days after immunostimulation and were absent in controls. Detailed knowledge of the changes in the time course and cellular source of inducible nitric oxide synthase expression following brain immunostimulation provide a basis for establishing treatment strategies and windows of therapeutic intervention during neuroinflammation.

Animals↗

Intestinal absorption and permeability in human immunodeficiency virus-infected patients.

BACKGROUND: Impaired intestinal function could account for diarrhoea and weight loss, which are common features of advanced human immunodeficiency virus (HIV) infection. METHODS: We assessed intestinal permeability to lactulose and mannitol and absorption of D-xylose in 96 HIV-infected patients (group I: asymptomatic subjects (CDC-A); group II: symptomatic subjects (CDC-B or C) without body weight loss and/or diarrhoea; group III: 25 acquired immunodeficiency syndrome (AIDS) patients (CDC-C) with severe body weight loss and/or diarrhoea) and 10 healthy subjects as controls. RESULTS: An incremental decrease in urinary D-xylose recoveries was observed, with all groups statistically different from each other. Impaired intestinal permeability was only found in patients of group III (statistically different from all other groups). CONCLUSIONS: These findings suggest a loss of intestinal functional absorptive surface as HIV disease progresses. This process may be present at the early stage of infection. Impaired intestinal permeability is observed later in AIDS patients when digestive signs are present, particularly diarrhoea.

Adult↗

Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo.

Cytokines such as transforming growth factor-beta (TGF-beta) are thought to mediate escape from immune surveillance in human malignant glioma. Here, we report that ectopic expression of the small TGF-beta-binding proteoglycan, decorin, inhibits not only TGF-beta bioactivity but also TGF-beta 1 and TGF-beta 2 mRNA transcription and TGF-beta protein synthesis by human LN-18, LN-229, T98G and rat C6 glioma cells in vitro. Ectopic expression of decorin in C6 rat glioma cells results in strong inhibition of tumor formation in vivo. Decorin-expressing C6 gliomas grow initially but regress to very small residual tumors at 12 weeks after implantation whereas all control animals die or have to be killed within 4 weeks. Decorin-expressing tumors show a four-fold increase of infiltration by activated T cells and a 1.6-fold increase in total B and T cells. Chronic steroid-mediated immunosuppression abrogates the inhibitory effects of decorin gene transfer. We conclude that decorin-induced inhibition of TGF-beta release by glioma cells significantly enhances antiglioma immune responses in vivo. Clinical evaluation of decorin gene therapy for human malignant gliomas may be warranted.

Animals↗

The portals of entry of herpes simplex virus infections.

In the present paper different possible portals of entry into the body for Herpes simplex Virus are examined. The possibility to infect the cornea with HsV without a preceding scarification was established. Scanning microscopy clearly showed the lesions of the infected cornea and a parallelity between the concentration of the inoculum and the spread of lesions. The i.c., i.m. and i.p. portals of entry are compared as to their capacity to produce encephalitis. The titration of virus may also be realized in the animal experiment. The intragastric portal of entry could be clearly demonstrated. So it is possible to explain herpes encephalitis in human newborns from mothers infected with Herpes virus.

Animals↗

[Scanning electron-microscopic findings in orthoergically damaged skin surfaces of hairless mice (author's transl)].

Mechanic-chemically defined irritation of the skin surface of hairless mice regularly leads to macroscopically sub-visible changes of the horny layer. Scanning electron-microscopic analysis reveals extended regular horny layer dehiscences, as well as deeper dehiscence or trench formations in the area of irritation, as compared to normal skin. The damaged horny layer sample, presented respectively, depends-to a degree-upon type, intensity and duration of irritation. Hairless mice proved to be best suited at test animals for informative studies concerning cutaneous resistance to stress.

Animals↗

Side-effects of local anesthetics on the corneal epithelium of the rabbit eye.

The toxic side-effects of 0.4% Novesine and Chibro-Kerakain were investigated by scanning- and transmission electron microscopy in 15 rabbit corneae each in intervals of 3, 6, 10, 15 and 60 mins. The lesions following Kerakain were larger and occurred earlier. After 60 mins, the specimens after Novesine application showed an almost complete repair process, whereas after Kerakain the epithelial surface appeared to be functionally impaired.

Anesthetics, Local↗

[Herpes Simplex Keratitis under the Scanning lectron Microscope(author's transl)].

In 12 rabbits a dendritic keratitis could be provoked by applying a suspension of herpes viruses (Herpes virus hominis -- HVH type 1) onto their previously both uviolised and non-uviolised corneae. 4 days later ophthalmectomy was performed and the corneae were examined by the scanning electron microscope. Macroscopically, both in the uviolised eyes and the control eyes punctiform lesions of the corneae were observed. After short ray-treatment (3 min) no differences were present between the uviolised and non-uviolised eyes. At longer time of exposure (7--15 min), however, a more distinct alteration occurred in the uviolised eye. The scanning-electron-microscopical picture showed the dendritic lesions to be composed of numerous circular foci of 100 to 200 mu. There were no differences in the lesions of the uviolised and non-uviolised corneae. The fact that after ultraviolet ray-treatment a great part of the epithelial cells is sloughed off, but, nevertheless, the same dendritic lesions develop, contradicts the assumption of a morphological substrate of the epithelial cells being the inducing factor.

Animals↗

Scanning electron microscopy in ophthalmology.

In the context the technique of the scanning electron microscopy is described and the results are shown gained by the scanning electron microscope in ophthalmology. It is pointed out that questions specific to surface can be answered quicker and easier, if superificial microscopy together with the scanning electron microscope is used an additional source of information. Scanning electron optical pictures are very useful for ophthalmologic science.

Ciliary Body↗

[Pigment glaucoma. Scanning-electronmicroscopic findings. (author's transl)].

In case of a patient suffering from pigment glaucoma trabeculectomy was performed on both eyes. In one trabecular section the outer wall of Schlemm's canal, and in the other the trabecular framework were investigated by scanning-electronmicroscopy. The intertrabecular spaces were largely blocked by pigment granula, which, in some places, were stored in the clump cells of the iris. Even the outer wall of Schlemm's canal was dotted with pigment granula. The scanning-electronmicroscopic findings revealed the pigmental drainage blocking of the aqueous humour and explained the acute pressure rise in the pigment glaucoma with wide iridocorneal angle by an acute obstruction of the already largely blocked intertrabecular spaces.

Adult↗

Neurinomas of the trigeminal nerve.

Neurinomas of the trigeminal nerve are rare tumours. Six cases of a series of 8,894 intracranial tumours operated upon in the Neurosurgical Clinic of Bucharest are reported. The literature is reviewed. One hundred one other cases have been found. The signs and symptoms produced by these tumours, their slow development, the radiological and other diagnostic findings, the treatment and the prognosis are discussed.

Adult↗

Morphological study of rat thymus after tumoral, non-tumoral antigens and thiamine pyrophosphate administration.

The study was performed on 60 Wistar white rats sacrificed 24 hours and 7 days after administration of glycoprotein 8 (extracted from Jensen rat tumors), glycoprotein 5 (from normal rat blood), bovine albumin, tuberculin (PPD), and a complex of strychnine, picrotoxin and TPP administered alone or together with the above-mentioned antigens. In order to study thymus morphological changes, methods of quantitative morphology and current histological techniques were used. The thymus responds morphologically to the antigenic administration - (glycoprotein 8, bovine albumin and PPD) - by cortico-medullary ratio modification, expressed by decrease of cortical surface and increase of medullary one, thymocytes agglomeration in the perivascular sheaths and their deliverance in the blood flow. Under other conditions (strychnine, picrotoxin and TPP administration) thymus responds only by thymocytes agglomeration in the perivascular sheaths. Glycoprotein 5 does not induce any modifications in thymus structure.

Animals↗