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Biomedical subjects

L Rakic

Publications and source records attributed to L Rakic.

At least 19 recordsLinked to original sources
PubMed2006

Induced resistance in the human non small cell lung carcinoma (NCI-H460) cell line in vitro by anticancer drugs.

Exposure of human non-small cell lung cancer cells (NCI-H460) to gradually increasing concentrations of doxorubicin resulted in the appearance of a new cell line (NCI-H460/R) that was resistant to doxorubicin (96.2-fold) and cross-resistant to etoposide, paclitaxel, vinblastine and epirubicin. Slight cross-resistance to two MDR-unrelated drugs 8-Cl-cAMP and sulfinosine was observed. Flow cytometry analysis showed that the accumulation of doxorubicin in the resistant cells was 88.4% lower than in the parental cells. Also, verapamil significantly decreased the efflux rate in NCI-H460 and NCI-H460/R cells, whereas curcumin inhibited the efflux in NCI-H460 cells only. Gene expression data confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells. In contrast, mrp1 and lrp expression was unaffected by the doxorubicin resistance. Further work should develop a rationale for a novel treatment of NSCLC with appropriate modulators of resistance aimed at improving the outcome of the acquired drug resistance.

Antineoplastic Agents↗
PubMed2005

Pattern of glial fibrillary acidic protein expression following kainate-induced cerebellar lesion in rats.

In the present study glial fibrillary acidic protein (GFAP) expression was assessed following intravermian injection of kainic acid (KA) or physiological saline to adult rat cerebellum. After 2- to 30-day recovery period, free-floating sections cut with a microtome were obtained and were proccessed for immunocytochemistry against GFAP. Injection of both kainate and physiological saline elicited significant astrogliotic reaction, i.e. in the area around the lesion thick GFAP-positive Bergmann fibers with typical orientation appeared in the molecular and hypertrophied astrocytes abundantly appeared in the granular layer. However, following kainate intoxication lesion was not surrounded by typical demarcation glial scar during 30-day recovery period in contrast to the appearance of usual glial scar in the group injected with physiological saline, as early as 7-day postlesion. Preserved spatial organization of Bergmann fibers and the absence of typical demarcating glial scar after kainate-induced cerebellar lesion suggest distinct pattern of astrogliosis that presents an interesting model system to study the importance of glial scar in the recovery after ischemic brain insults.

Animals↗
PubMed2004

Spatio-temporal changes in neurofilament proteins immunoreactivity following kainate-induced cerebellar lesion in rats.

1. Spatio-temporal changes in phosphorylated (pNFP) and nonphosphorylated (npNFP) neurofilament proteins were assessed immunocytochemicaly in adult rat cerebellum, 2-30 days following unilateral injection of kainic acid (KA) or physiological saline (s.c.). 2. Analysis of the staining intensity and pattern demonstrated that injection of both KA and physiological saline elicited significant and long-lasting increase of pNFP and npNFP immunoreactivity, at the ipsilateral, and to lesser extent at the contralateral side of lesion. 3. Kainate intoxication induced abundant expression of pNFP and npNFP in cerebellar white matter, as well as in all layers of perilesioned cortex. Higher pNFP expression was evidenced in the Purkinje cell layer, particularly at cell bodies, initial segments, and proximal dendrites, which normally do not contain pNFP. In addition, synaptophysin immunocytochemistry was used as a marker of synaptogenesis and plasticity. 4. Spatio-temporal pattern of NFP and synaptophysin expression suggests that perilesioned cortex undergoes dynamic changes following brain demage and possess a reparative capacity to abridge the consequences of brain trauma.

Animals↗
PubMed2001

Differential effects of amphetamine and phencyclidine on the expression of growth-associated protein GAP-43.

The purpose of the present study was to test changes in the expression of growth-associated protein (GAP-43) after chronic treatment with two different psychotomimetic drugs: amphetamine and phencyclidine. Rats were treated chronically for 7 days (twice daily) with 5 mg/kg of amphetamine and phencyclidine and sacrificed after 2, 5 or 7 days of treatment, and following 7, 14 or 21 days of recovery after full treatment (7 days). Separate groups of rats were treated on the same regiment with haloperidol, and control group was treated with vehicle. To determine the effects of different psychotomimetic drugs on the expression of GAP-43 we have used Northern blotting and quantitative in situ hybridization. Treatment with amphetamine induced decrease of GAP-43 mRNA expression, that was detected also during recovery period, up to 14 days after the last day of 7 days treatments. On the contrary, PCP induced increase of GAP-43 mRNA expression, that was detectable from the first days of treatment until 21 days after the last day of treatment. Treatment with haloperidol did not produce significant changes in GAP-43 mRNA expression. It can be suggested that GAP-43 upregulation upon phencyclidine treatment occurs as a result of functional activation of pathways able to participate in remodeling, while amphetamine showed neurotoxic effect, decreasing expression of GAP-43 mRNA.

Amphetamine↗
PubMed2000

Breast cancer metastatic to the eyelids.

Metastases to the eyelids are rare. They may appear as diffuse swellings, nodules or ulcerations. Most often they correspond to the dissemination of a breast adenocarcinoma. An 83 year old woman is reported with mammary adenocarcinoma metastasizing to the eyelids.

Adenocarcinoma↗
PubMed1999

Correlation between triplet repeat expansion and computed tomography measures of caudate nuclei atrophy in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, progressive disorder characterized by choreic movements, cognitive decline, and psychiatric manifestations. Eleven patients with HD were retrospectively selected from a larger group of 42 patients based on the similar, early onset of the disease (between 21 and 30 years) and the same duration of HD at the moment of computed tomography (CT) examination (5 years). A significant correlation between the number of CAG trinucleotides and the bicaudate index or the frontal horn index, two indices of caudate atrophy, was found in this group of patients. Our results, although in a small number of patients, suggest that the striatal degeneration, assessed by CT measures, is primarily regulated by the size of expanded CAG repeats.

Adult↗
PubMed1999

Simultaneous reactivation of herpes simplex virus and varicella-zoster virus in a patient with idiopathic thrombocytopenic purpura.

Simultaneous reactivation of distinct Herpesviridae with development of clinical manifestations is exceptional. We report a 48-year-old woman suffering from idiopathic thrombocytopenic purpura. As the disease remained refractory to corticosteroids, immunoglobulins and splenectomy, a cure of vinblastine was administered. An atypical stomatitis developed few days later. Immunohistochemistry on a Tzanck smear and a biopsy evidenced a Herpes simplex virus type 1 (HSV-1) infection. The patient presented simultaneously a single necrotic lesion on the abdomen. Immunohistochemistry on a skin biopsy revealed the presence of the varicella-zoster virus (VZV) gE, gB and IE63 proteins. Intravenous aciclovir was initiated. The present case of simultaneous clinical infections by HSV-I and VZV underlines the importance of complementary viral identification testing in the event of unusual clinical presentations.

Abdomen↗
PubMed1999

[Cutaneous melanomas, a spectrum of emerging cancers in women of Wallonia. Outlook by the Mosan Study Group of Pigmented Neoplasms].

The Mosan Study Group of Pigmented Neoplasms was founded about 15 years ago. It has collected more than 20,000 cutaneous malignancies including melanomas and basal and squamous cell carcinomas. The incidence of these cancers is on the rise in Wallonia. In particular, malignant melanomas represent a spectrum of emerging cancers characterized by a proteiform biological outcome. They mostly affect young women. The major risk factor appears to be iterative and unwise ultraviolet exposures. The prevention of melanomas is basically founded on such a dogma and accordingly relies on sunscreens. However, controversies about their beneficial effects are rife and fueled by axiomas and contradictory sophisms. At the exception of surgery, the therapeutic options for the diverse types of melanomas do not yet fulfill the scope of evidence-based medicine.

Carcinoma, Squamous Cell↗
PubMed1999

Kikuchi-Fujimoto lymphadenitis with cutaneous involvement.

We report a case of Kikuchi-Fujimoto disease with cutaneous involvement in a European man. In contrast, the disease is most prevalent in women of Asian descent. The condition is probably under-recognized when histology is not used to identify lymphadenitis of protracted course. Skin lesions may mimic clinically other unrelated disorders including lymphomas and immune or infectious dermatoses. Histology of skin lesions may bring a clue to the diagnosis when apoptotic plasmacytoid monocytes are recognized. The relationship between Kikuchi-Fujimoto disease and lupus erythematous remains a matter of debate.

Apoptosis↗
PubMed1999

Proliferation of spleen cells in culture stimulated by 7-thia-8-oxoguanosine: evidence that both B- and T-cells are the targets of its action.

7-thia-8-oxoguanosine (immunosine) is a nucleoside analog showing efficient antiviral activity in rodent models as a consequence of enhancement of the immune response. However, little is known about the mechanisms of its action. In this work the effect of immunosine on proliferation of mouse and rat splenocytes in culture was studied. It was found that the compound stimulated proliferation of lymphocytes in a dose-dependent manner without any additional stimuli. The effect is predominantly mediated by interleukin-2 (IL-2) as judged by increased IL-2 production, upregulation of IL-2 receptor alpha (IL-2R alpha) expression and by significant inhibition (60-75%) of cell proliferation by anti-IL-2R alpha monoclonal antibodies (mAbs). Immunosine also stimulated proliferation both of T- and B-cells purified by immunomagnetic sorting. The response of B-cells was much higher than that of T-cells. The stimulatory effect of immunosine on both lymphocyte subpopulations was further increased by the addition of enriched splenic antigen-presenting cells or purified dendritic cells. Proliferation of purified T-cells to immunosine was also significantly potentiated by an anti-alpha beta T-cell receptor mAb (R 73). All these data suggest that T-, B- and accessory cells in splenic cultures are the targets of immunosine action.

Adjuvants, Immunologic↗
PubMed1998

[Cholinergic receptors in early (pre-nervous) sea urchin embryos].

Agonists of nicotinic acetylcholine receptors (nAChR) nicotine and 1-acetyl-4-methylpiperazine do not act on the early sea urchin embryogenesis but evoke calcium shock in both oocytes and early embryos under certain conditions. Many nAChR ligands protect both oocytes and embryos against this shock. There seem to exist putative nAChR on the cell surface of the early sea urchin oocytes and early embryos. Pre-nervous acetylcholine seems to be functionally coupled via these receptors with the second messengers, endogenous activators of the protein kinase C.

Acetylcholine↗
PubMed1998

[Skin microcirculation, adherence molecules and inflammatory dermatoses].

Skin is a peculiar organ with regard to its microcirculation. The dermal vasculature is enriched with abundant anastomoses. It forms a single compartment where blood can be pulsed in any direction without always following an arteriolovenular gradient. Under various pro-inflammatory stimuli, endothelial cells express diverse adhesion molecules whose specificity leads to the intradermal collection of specific leukocytic lineages. Such basic mechanism is at the origin of all inflammatory dermatoses. It is possible and even probable that some antihistamines, flavonoids and antiseptics modulate in a beneficial way the expression of some adhesion molecules.

Anti-Infective Agents, Local↗
PubMed1997

Enhanced serum response element binding activity correlates with down-regulation of c-fos mRNA expression in the rat brain following repeated cortical lesions.

Repeated lesions of rat cerebral cortex result in transient peaks in the level of the c-fos transcript, but after the second lesion, this peak is substantially diminished. Using this lesion paradigm, we have analyzed the participation of the c-fos promoter elements SRE and DSE in the regulation of c-fos transcription. Following a single lesion, SRE/DSE binding activity peaked at 2 h, subsequent to the maximal levels of c-fos mRNA and parallel to the peak of c-Fos protein. After a second lesion (reinduction), 4 h following the initial lesion, SRE/DSE binding activity peaked after only 30 min and was significantly higher than following the first lesion. Once again, this peak occurred after the peak of c-fos mRNA expression and parallel with the second peak of c-Fos protein expression. These results suggested that the SRE and DSE promoter elements participated in the induction and down-regulation of c-fos transcription in vivo and suggested the possible involvement of Fos protein in its own regulation. The ability of Fos/Fra proteins to participate in a transcriptional complex was confirmed in gel-shift experiments with an AP-1 element, and the biphasic trend of binding activity was observed. Supershift experiments were performed to directly determine whether Fos protein was participating in SRE and/or DSE transcriptional complexes. No alterations in the position or intensity of the shifted band were observed using Fos/Fra antiserum suggesting that Fos/Fra proteins could be involved in c-fos down-regulation through mechanisms other than direct participation in the SRE/DSE transcription complex.

Animals↗
PubMed1997

Optimization of in situ hybridization histochemistry for localization of GAP-43 mRNA in fetal brain during human development.

In situ hybridization histochemistry has proven to be an important tool for cellular and molecular studies in neurobiology. The method basically involves the anatomic localization of labeled RNA or DNA molecules that hybridize with complementary target RNA or DNA sequence in the cell. In regard to gene expression, in situ hybridization allows the study of specific mRNA level and distribution between various cell types, or of comparative levels of mRNA throughout development. Major advantages of in situ hybridization are: (a) specific mRNAs can be detected in heterogeneous cell populations where only one of multiple sets of cells present may be transcribing the mRNA of interest; (b) it allows the maximal use of rare tissues that may be in short supply (clinical biopsies, embryos, cultured cells); (c) the location of the mRNA can be identified on conventional microscopic sections without the necessity of electron microscopy; and (d) identification of specific gene without metabolic incorporation of radiolabeled precursor into the endogenous protein in the cells. Because of these advantages, we decided to utilize this approach for specific studies involving the expression and distribution of GAP-43 (growth-associated protein 43) mRNA in early human development. The method we employed for in situ hybridization is basically a modification of the many original protocols developed by others and can be easily applied to many studies of cellular gene expression in the human nervous system.

Autoradiography↗
PubMed1996

GAP-43 mRNA expression in early development of human nervous system.

The temporal and spatial distribution of GAP-43 mRNA in early human development, from 6 to 23 gestational weeks (g.w.), was examined by in situ hybridization histochemistry. GAP-43 mRNA was expressed as early as 6 g.w. in all regions of developing nervous system, the spinal cord, brainstem, cerebellum, diencephalic and telencephalic regions. Although the pronounced level of expression persisted during the entire examined period, the intensity of expression varied along the spatial axis over time. Analysis at the cellular level revealed that early on in development (6 g.w.) GAP-43 mRNA was expressed in the entire neuroblast population. With the onset of differentiation, at 13-23 g.w., GAP-43 mRNA expression had switched to the neurons that are in the process outgrowth. The highest level of GAP-43 mRNA expression was localized in the regions consisting of differentiating neurons, such as the cortical plate and intermediate zone of the telencephalic wall, and several delineated subcortical and thalamic nuclei. The spatial and temporal pattern of GAP-43 mRNA expression obtained suggests a possible dual role of GAP-43 in the development of the human nervous system: in the embryonic brain it could be involved in fundamental processes underlying cell proliferation; in the fetal brain its expression is specifically correlated with differentiation and the outgrowth of axons.

Cell Differentiation↗