Search PubMed⌕ Search

Biomedical subjects

M Melis

Publications and source records attributed to M Melis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Clozapine does activate nigrostriatal dopamine neurons in unanesthetized rats.

Antipsychotic drugs are traditionally classified as typical or atypical on the basis of their property to cause or not to cause extrapyramidal side-effects. A widely accepted selectivity for the mesolimbic, vs. the nigrostriatal, dopaminergic system is postulated to underlie the existence of fewer or no extrapyramidal side-effects during treatment with atypical neuroleptics. In order to verify this hypothesis we examined the effect of acute clozapine on nigrostriatal dopaminergic neurons recorded from non-anaesthetised and from chloral hydrate-anaesthetised rats. Extracellular single-unit recording coupled with antidromic activation from the neostriatum was used. Intravenous administration of cumulative doses of clozapine (1.25-10 mg/kg) increased the firing rate of nigrostriatal dopaminergic neurons in non-anaesthetised rats, but failed to significantly modify the activity of the same units under chloral hydrate anesthesia. These results indicate that acute clozapine activates nigrostriatal dopamine cells in non-anaesthetised rats and cast doubts about a direct link between the lack of significant extrapyramidal side-effects and the selectivity of atypical neuroleptics, such as clozapine, for the mesolimbic dopamine system.

Analysis of Variance↗
PubMed1998

Mesolimbic dopaminergic decline after cannabinoid withdrawal.

The mesolimbic dopamine system has recently been implicated in the long-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamine neurons are involved in the neurobiologic mechanisms underlying withdrawal from chronic cannabinoid exposure. Rats were treated chronically with the major psychoactive ingredient of hashish and marijuana, Delta9-tetrahydrocannabinol (Delta9-THC). Administration of the cannabinoid antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome, whereas abrupt Delta9-THC suspension failed to produce overt signs of abstinence. In contrast, both groups showed a reduction in dopamine cells activity as indicated by extracellular single unit recordings from antidromically identified meso-accumbens dopamine neurons. The administration of Delta9-THC to spontaneously withdrawn rats restored neuronal activity. Conversely, SR 141716A produced a further decrease of spontaneous activity in cannabinoid-treated although it was ineffective in control rats. These data indicate that withdrawal from chronic cannabinoid administration is associated with reduced dopaminergic transmission in the limbic system, similar to that observed with other addictive drugs; these changes in neuronal plasticity may play a role in drug craving and relapse into drug addiction.

Animals↗
PubMed1998

Haloperidol does not produce dopamine cell depolarization-block in paralyzed, unanesthetized rats.

A widely accepted theory postulates that chronic treatment with neuroleptics causes, in rats, the depolarization block of the majority of midbrain dopamine (DA) neurons. However, we reported that such treatment fails to reduce the number of spontaneously active DA neurons when the neuronal sampling is performed in the d-tubocurarine-paralyzed instead of chloral-hydrate anesthetized preparation. The present experiments were aimed at verifying whether the negative results might be due to the use of d-tubocurarine as paralyzing agent. Rats were chronically treated with haloperidol (0.5 mg kg-1 i.p., daily) for 3 to 4 weeks. Two to three hours after the last injection, the number of spontaneously active DA neurons in the ventral tegmental area (VTA) were sampled, and their discharging characteristics analyzed, both in animals under chloral hydrate anesthesia and in rats immobilized either with d-tubocurarine, gallamine or succinylcholine. The results indicate that chronic treatment with haloperidol reduced the number of spontaneously active VTA-DA neurons by about 65% in animals under chloral hydrate anesthesia, but failed to modify the number of spontaneously firing DA neurons in rats immobilized with d-tubocurarine, gallamine or succinylcholine. The results indicate that the depolarization block of DA neurons does not occur in the paralyzed preparation and raise doubts about the presence of this phenomenon in the intact non- anesthetized unrestrained animal.

Animals↗
PubMed1998

Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors.

The present study was designed to determine if cannabinoids share with other drugs of abuse the ability to stimulate mesolimbic dopaminergic neurons and if this effect is mediated by cannabinoid receptors. To this end, the effects of the prototypical cannabinoid, delta9 tetrahydrocannabinol ¿(-)-trans-(6aR,10aR)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl- 3-pentyl-6H-dibenzo[b,d]pyran-1-ol¿, and the two highly potent synthetic cannabinoids, ¿(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl]pyrrolo[1,2,3-d e]-1,4-benzoxazin-6-yl, +(1-naphtalenyl)methanone¿ WIN 55,212-2 and ¿(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl )-cicloexan-1-ol¿ CP 55,940, on the spontaneous discharge rate of meso-accumbens dopamine (A10 dopamine) neurons were studied in rats. The intravenous administration of delta9-tetrahydrocannabinol, WIN 55,212-2 and CP 55,940 (0.0625-1.0 mg/kg) produced a dose-dependent increase in the spontaneous firing of A10 dopamine neurons both in non-anesthetized and anesthetized rats, with a maximal percent increase of 120, 187 and 155 in non-anesthetized and 33, 102 and 52, respectively, in anesthetized rats. The stimulant response to cannabinoids was suppressed by the specific cannabinoid receptor antagonist ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide¿ SR 141716A, indicating a cannabinoid receptor-mediated effect. These findings support the contention that cannabinoids regulate mesolimbic dopamine transmission and may help to explain the addictive properties of marijuana.

Action Potentials↗
PubMed1998

Transplacental transmission of human polyomavirus BK.

The presence of BK virus (BKV) and JC virus (JCV) in autopsy materials (placenta, brain, and kidney) of aborted fetuses was investigated by PCR using two sets of primers, specific for the regulatory region (RR) and for the capsid protein VP1, respectively. The RR of BKV was detected in 12 samples of placenta and brain and in nine samples of kidney obtained from 15 fetuses. Out of the 12 positive cases, four placentas, one brain, and three kidney samples also showed the presence of BKV DNA in the VP1 region. Of 12 placentas from a control group with a normal pregnancy outcome, the RR of BKV was detected in six samples, four of which were also positive for the VP1 region. None of the samples from either group was positive for the RR of JCV. In two cases, the nucleotide sequence of the BK RR demonstrated that the viruses isolated from maternal and fetal tissues showed a high homology with one another and had a characteristic deletion of the R63 box compared to the archetype strain. The results indicate that BKV may be transmitted vertically.

Abortion, Induced↗
PubMed1998

Oral focal mucinosis of the tongue.

Oral focal mucinosis (OFM) is an uncommon clinicopathological entity which is considered to be the oral counterpart of cutaneous focal mucinosis and cutaneous myxoid cyst. It is comprised of a clinically elevated mass with a histological feature of localised areas of myxomatous connective tissue. The present study adds a rare case of OFM of the tongue to the literature, and we present a review of the most characteristic oral myxomatous lesions.

Aged↗
PubMed1998

Increase in meso-prefrontal dopaminergic activity after stimulation of CB1 receptors by cannabinoids.

The intravenous administration of the psychoactive constituent of marijuana, delta9-tetrahydrocannabinol (delta9-THC) (62.5-1000 microg/kg), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 microg/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal dopaminergic neurons. In a restricted number of neurons (n=4), WIN administration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical activity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation of D1 dopamine receptors in the prefrontal cortex has been shown to impair working memory, the present results suggest that the negative effects of cannabinoids on cognitive processes might be related to the activation of dopaminergic transmission in the prefrontal cortex.

Action Potentials↗
PubMed1997

Chronic morphine and naltrexone fail to modify mu-opioid receptor mRNA levels in the rat brain.

Previous radioligand-binding studies have reported conflicting results concerning the effect of chronic morphine administration on the regulation of mu-opioid receptor (MOR) density. On the other hand, chronic administration of an opioid antagonist, such as naltrexone, has been shown to increase the density of the MOR. In order to determine if the changes in the MOR are associated with alterations in receptor mRNA levels, we investigated MOR gene expression following chronic treatment with morphine and/or naltrexone. MOR mRNA levels, determined by the ribonuclease protection assay (RPA), were unchanged with respect to control during chronic morphine treatment and morphine withdrawal in each of the analysed brain areas. Furthermore, chronic administration of naltrexone did not result in changes of MOR mRNA levels in rat striatum of naive and morphine-dependent rats, suggesting that the up-regulation of the MOR density, at least in this tissue, is not regulated at transcriptional level.

Animals↗
PubMed1997

Tenascin expression in elastotic cuffs of invasive ductal carcinoma of the breast.

We studied immunohistochemically one thousand one hundred and thirty-seven cases of primary invasive breast cancers (NST) and adjacent normal mammary glands for tenascin expression, and compared their elastic content to verify if a relationship exists between tenascin expression and elastosis. Periductal, perivascular and stromal elastosis were graded on a scale from 0 to 3 (absent to massive). All carcinomas showed tenascin expression and elastosis with various histological appearances. In the adjacent breast, teanscon was distributed around the normal ducts or with extasia and uctal hyperplasia without atypia. Digestion of the sections with elastase prior to staining resulted in a loss of the specific staining reactions in all areas where elastosis was present. Tenascin staining was observed in the mesenchyme closely surrounding the neoplastic ducts and the cancer cell nests. Stromal tenascin staining appeared stronger in those carcinomas that exhibited marked desmoplastic reactions. The highly differentiated tumours contained more elastosis in their tumour tissue than the poorly differentiated ones, whereas tenascin expression was stronger in poorly differentiated tumours than well differentiated tumours. A strong staining for tenascin was observed in the elastotic cuff. Tenascin staining did not disappear afterwards with elastase. We did not find a statistically significant correlation between tenascin expression, elastosis and prognostic factors such as size of the tumour, lymph node metastasis, tumour necrosis and age. In our study tenascin proved to be an additional element in elastotic areas even though the significance of an association between elastosis and tenascin is still unknown, as is that of elastosis itself.

Adult↗
PubMed1997

Dendritic cells with a potent accessory activity are present in human exudative malignant pleural effusions.

Dendritic cells are human leucocyte antigen (HLA)-DR positive accessory cells, that play a critical role in the development of cell-mediated immune reactions. Since the pleural space is frequently involved in cell-mediated immune reactions, we sought to isolate dendritic cells from pleural fluid. Pleural effusion mononuclear cells (PEMCs) were obtained by Ficoll centrifugation of exudative pleural effusions recovered from 19 patients with malignant pleurisy. After double-step adherence, firmly-adherent mononuclear cells (FAMs) and loosely-adherent mononuclear cells (LAMs) were recovered. The latter cells were centrifuged on a bovine plasma albumin gradient to obtain a loosely-adherent low density fraction. Nonadherent cells were rosetted with sheep red blood cells (SRBC) to obtain a nonadherent nonrosetting (NANR) cell fraction. Mitomycin C-treated PEMCs, NANRs, FAMs, and LAMs served as stimulatory cells in mixed leucocyte reaction experiments. 3H-thymidine incorporation by purified normal allogeneic blood T-lymphocytes was assessed as an index of accessory cell function. The phenotype of NANR, FAM and LAM cells was characterized using single and double stainings with a panel of monoclonal antibodies (MoAbs). Accessory cell (AC) activity (counts per minute (cpm) x 10(3)(+/-SE); 2.5 x 10(4) AC x well(-1) of LAM (148+/-24) and NANR (108.4+/-11.2) was greater than that observed for FAM (59.3+/-9.4) and for unfractioned PEMC (13.8+/-4.9). The FAM fraction was virtually entirely composed of CD68+ HLA-DR+ mononuclear phagocytes. NANR and LAM contained 51+/-12% and 65+/-6% HLA-DR+ cells, respectively, and most HLA-DR positive cells were negative for CD3, CD19, and CD68, markers for T-, B-lymphocytes and mononuclear phagocytes. Moreover, both NANR and LAM fractions contained significant numbers of cells bearing the RFD1 surface marker, expressed on dendritic cells. These results suggest that dendritic cells are present in exudative pleural effusions, and that they may be involved in the development of cell-mediated immune reactions in the pleural space.

Aged↗
PubMed1996

Pesticide residues in artichokes: effect of different head shape.

Residues of three pesticides (dimethoate, parathion, and pyrazophos) in two artichoke cultivars, Masedu and Spinoso sardo, were investigated. The amount of pesticides in artichokes was greatly affected by the head shape. In the case of the calix-shaped Masedu artichoke, the residues in whole heads at commercial ripening were on average about twice higher than those of the pagoda-shaped Spinoso sardo artichoke. In the heart this ratio was 4 to 42 times greater. Residue decay rates were very fast, mainly owing to the dilution effect due to head growth.

Chromatography, Gas↗
PubMed1996

ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells.

Intercellular adhesion molecule-1 (ICAM-1) expression by tumour cells may be involved in their interaction with defensive cells. In this study the surface ICAM-1 expression and soluble ICAM-1 (sICAM-1) production by five small cell lung cancer (SCLC) and five non-SCLC (NSCLC) cell lines was investigated. In addition, the effects of ICAM-1 upregulation by cytokines on the adhesion of lung cancer cells to allogeneic lymphokine-activated killer (LAK) cells and susceptibility to LAK cytotoxicity was also evaluated. ICAM-1 expression was assessed by flow cytometry. Soluble ICAM-1 release was measured by enzyme-linked immunosorbent assay (ELISA). Interaction with LAK cells was tested by adhesion and cytotoxicity assays. At baseline, SCLC lines did not express ICAM-1, while 4 of the 5 NSCLC lines expressed ICAM-1. ICAM-1 expression was induced by interferon-gamma (IFN-gamma) in 4 of the 5 SCLC lines and upregulated in 1 of the 5 NSCLC lines. ICAM-1 expression was induced by tumour necrosis factor-alpha (TNF-alpha) in 1 of the 5 SCLC lines (National Cancer Institute (NCI) H211), and upregulated in 2 of the 5 NSCLC lines (NCI H460 and NCI H838). Among the latter lines, one (NCI H838) released significant amounts of sICAM-1. Adhesion to LAK cells and susceptibility to LAK cytotoxicity were significantly higher in TNF-alpha-treated NCI H460 and NCI H211 cells, compared to untreated NCI H460 and NCI H211 cells. In contrast, no difference in adhesion to LAK cells and susceptibility to LAK cytotoxicity was detected between baseline and TNF-alpha-treated NCI H838 cells. Intercellular adhesion molecule-1 surface expression and soluble intercellular adhesion molecule-1 release may play an important role in interactions between lymphokine-activated killer cells and lung cancer cells.

Antineoplastic Agents↗
PubMed1996

Histiocytic necrotizing lymphadenitis (Kikuchi's disease).

We present a case report of a young asiatic women presenting Kikuchi's lymphadenitis, a suprahyoidea mass, pharyngitis, fever, weakness and lack of appetite. The clinical picture quickly improved after biopsy until complete remission within two months. Sierologic studies showed significant antibody titres revealing a previous EBV infection; they were also negative for Toxotest, HbsAg, HIV and serogroup 3 and 9 Yersinia Enterocolitica. Histological findings showed necrotic changes and large foci of infiltration in the cortex and/or paracortex. They consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid monocytes, neutrophils were absent. Immunohistochemistry revealed within the lesion T-Lymphocytes displaying a phenotype CD4+ while T-Lymphocytes CD8+ were observed in the paracortex and in the peripheral region of the lesion.

Adult↗
PubMed1995

Is there a role for adjuvant immunochemotherapy after radical nephrectomy in pT2-3N0M0 renal cell carcinoma?

Five-year overall survival after radical surgery in N0M0 renal cell carcinoma varies from 45-80% in pT2 to 35-50% in pT3 categories. In view of the alpha interferon and vinblastine combination which has shown some activity in advanced disease with increasing efficacy in limited metastatic invasion, we decided to explore the theoretical advantage of adjuvant chemo-immunotherapy in radically resected stage II, III renal cell carcinoma. A single-institution phase II study was undertaken to evaluate the efficacy and tolerability of alpha 2a-interferon (alpha 2a-INF) in combination with vinblastine in 30 patients with pT2-T3 N0M0 renal cell carcinoma (RCC). Thirty-two patients who received only radical nephrectomy and extended lymphadenectomy were analyzed and results were compared with the first group. Twenty-three of 30 (76.6%) patients in the first group are alive with no evidence of disease. The median follow-up for the 23 patients still alive was 67 months (range 60 to 72). Metastases were documented in 5 patients (16.6%) with a median interval to progression of 24 months. Four of them (13.6%) died of tumor. In the control group, 16 out of 32 patients (50%) are still alive, with a median follow-up for the patients still alive of 62 months (range 60 to 68). Fifteen patients developed distant metastases and 2 of them had a local recurrence. All of them (46.8%) died of tumor. Median progression interval was 24 months. After stratification by pathological grade, site, laterality and number of nodes found at lymphadenectomy there were no statistical differences in risk of progression or death in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Mononuclear cells in exudative malignant pleural effusions. Characterization of pleural phagocytic cells.

The aims of this study were to develop a methodology for the isolation of highly enriched mononuclear phagocyte populations from exudative malignant pleural effusions (EMPE) and to characterize the phenotype and functional properties of these cells. Pleural effusion mononuclear cells (PEMC) were isolated by Ficoll centrifugation of EMPE and transudative pleural effusions and allowed to adhere to plastic for 1 h to obtain a pleural effusion mononuclear adherent cell (PEMAC) fraction. Only 66.0 +/- 4.2 percent of PEMAC ingested latex particles, indicating that a significant proportion of PEMAC were not phagocytic cells. Latex-positive PEMAC had the morphologic appearance of macrophages and stained positive (97.3 +/- 4.3 percent) with the anti-CD68 monoclonal antibody (MoAb), specific for macrophages. Conversely, latex-negative PEMAC (34.0 +/- 4.1 percent of PEMAC) did not react with the anti-CD68 MoAb and stained with anti-CD3 (34.7 +/- 10.7 percent) and anticytokeratin (50.5 +/- 16.4 percent) MoAbs, indicating that T cells and mesothelial cells were present in the PEMAC fraction. To improve the purification of pleural macrophages, PEMAC were cultured for an additional 18 h and the cells that remained adherent after this period constituted the firmly adherent mononuclear cell (FAMC) fraction. Nearly 90 percent of FAMC ingested latex particles and were CD68-positive. Virtually all FAMC were CD3-negative and cytokeratin-negative. Similar percentages of FAMC from EMPE and transudative effusions expressed the monocyte-lineage markers CD11b and CD14, suggesting that the proportion of monocyte-like mononuclear phagocytes in the pleural space is not increased during local tumor-associated inflammatory responses. The FAMC from EMPE (1) expressed HLA-DR antigens, (2) released interleukin 1 (IL-1) beta and tumor necrosis factor (TNF) alpha, and (3) stimulated allogeneic T-lymphocyte proliferation. The results of this study suggest that pleural mononuclear phagocytes may be involved in tumor-associated inflammatory reactions in the pleural compartment by stimulating the proliferation of other inflammatory cells and by releasing inflammatory cytokines.

Aged↗
PubMed1994

Transitional papillary cell carcinoma of the ureter: a histological and ultrastructural study.

We report a case of transitional papillary carcinoma of the distal left ureter. The histological and ultrastructural features were seen and compared by SEM and TEM. Observations confirm the data of literature that the deep cells of neoplasm are a normal morphological finding while the superficial cells do not have the characteristics present in normal transitional cells. In addition, SEM shows small groups or single cells with "pleomorphic microvilli" on the cell surface. These, in ureter, confirm the studies of many authors who have observed these abnormalities in carcinomas of several organs like breast, colon, liver and mesothelium.

Aged↗
PubMed1993

Immunohistochemical detection of tissue-infiltrating lymphocytes in mild urothelial dysplasia.

The presence and distribution of immunocompetent cells in normal and dysplastic urothelium of the bladder were investigated in 3 patients. Using an indirect immunoperoxidase staining procedure, monoclonal antibodies reacting with B (Leu12+) and T (Leu4+) cells, cells of the suppressor/cytotoxic (Leu2a+), helper/inducer (Leu3a+) and natural killer (Leu7+) phenotypes, monocyte-macrophages (LeuM3+), and cells expressing interleukin-2 receptor and HLA-DR antigen (HLA-DR+) were tested in all specimens. The results confirmed the presence of a well ordered and compartmentalised distribution of immunocompetent cells in the normal mucosa far from dysplasia. There was an increased number of lymphocytes in the hyperplastic/dysplastic urothelium with associated Von Brunn's nests. Leu2a+ cells, HLA-DR expressing cells and monocyte-macrophages were present inside the epithelium, particularly within dysplasia and von Brunn's nests, but the Leu3a+/Leu2a+ ratio was not inverted (0.48 + 0.1 to 0.74 + 0.2). These findings reveal that in mild urothelial dysplasia with von Brunn's nests there is a spatial modification of the immunological barrier associated with the mucosa.

Adult↗