Effects of unilateral and bilateral carotid baroreflex stimulation on cardiac and neural sympathetic discharge oscillatory patterns.

Background: Left and right carotid baroreflex afferents participate in generating the spontaneous variability of heart rate (HR), arterial pressure (AP), and muscle sympathetic nerve activity (MSNA), but the relative contribution of each side is unclear. Pathophysiological conditions unilaterally affecting carotid baroreceptor function might result in abnormal changes of HR, AP, and MSNA variability, thus markedly affecting prognosis. We tested the hypothesis that unilateral carotid baroreceptor perturbation might differentially affect HR, AP, and MSNA variability compared with stimulation of the opposite side.

Cowpea mosaic virus-based chimaeras. Effects of inserted peptides on the phenotype, host range, and transmissibility of the modified viruses.

Expression of foreign peptides on the surface of cowpea mosaic virus particles leads to the creation of chimaeras with a variety of phenotypes and yields. Two factors were shown to be particularly significant in determining the properties of a given chimaera: the length of the inserted sequence and its isoelectric point. The deleterious effect of high isoelectric point on the ability of chimeras to produce a systemic infection occurs irrespective of the site of insertion of the peptide.

Inhibition of telomerase activity by geldanamycin and 17-allylamino, 17-demethoxygeldanamycin in human melanoma cells.

As it has been demonstrated that the heat shock protein 90 (HSP90) is required for the assembly and activation of telomerase in human cells, we investigated the effect exerted by the ansamycin antibiotics geldanamycin (GA) and 17-allylamino,17-demethoxygeldanamycin (17-AAG), two well-known inhibitors of the HSP90 chaperone function, on telomerase activity in JR8 human melanoma cells. Using an antibody to HSP90, we precipitated the telomerase activity associated with the molecular chaperone. The results of TRAP (telomeric repeat amplification protocol) experiments carried out on HSP90 immunoprecipitates showed that exposure to 100 ng/ml GA and 17-AAG induced a significant (P < 0.

Perspectives in melanoma treatment with signal transduction.

Data from all parts of the world show a rising incidence of cutaneous malignant melanoma. The latter is one of the most difficult malignancies to treat. Early stage melanoma is curable but once metastatic it is almost uniformly fatal.

Inorganic mercury changes the fate of murine CNS stem cells.

Stem cells isolated from the central nervous system of both embryonic and adult mice can generate neurons and glia through the activation of different patterns of differentiation in dependence of exposure to appropriate epigenetic signals. On the other hand, environmental conditions might affect the proliferation, migration, and differentiation of these cells. We report here, for the first time, that inorganic mercury affects the proliferative and differentiative capacity of adult neuronal stem cells (ANSCs).

Lack of dendritic cell mobilization into the peripheral blood of cancer patients following standard- or high-dose chemotherapy plus granulocyte-colony stimulating factor.

Background: Dendritic cells (DC), the most specialized antigen-presenting cells, can be detected in the peripheral blood (PB) and divided into two subsets of populations, DC1 and DC2, endowed with different functions. The aim of this study was to evaluate the effect on DC release and on their subsets of three regimens utilized to mobilize CD34+ cells into the PB in cancer patients and in normal CD34+ cell donors.

Patients And Methods: The mobilizing sequences were: standard-dose epirubicin+taxol+granulocyte-colony-stimulating factor (G-CSF; 15 patients with advanced breast cancer), high-dose cyclophosphamide (CTX)+G-CSF (10 patients with breast cancer patients and 7 with non-Hodgkin's lymphoma, NHL), and G-CSF alone (5 normal donors of CD34+ cells for allogeneic transplantation).

Cowpea mosaic virus: from the presentation of antigenic peptides to the display of active biomaterials.

The potential of cowpea mosaic virus (CPMV), a plant icosahedral virus, for the presentation of foreign peptides and proteins is reported. The most prominent feature at the virus surface is a region of the smaller of the two coat proteins (S) which has been extensively used for the insertion of foreign peptides. Given the availability of the three-dimensional structure of the native virus and the amenability of foreign peptide-expressing CPMV chimeras to crystallisation, immunological data can be correlated with the conformational state of the foreign insert.

A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris).

The macrocyclic lathyrane polyester Euphorbia factor L10 (1a) has been obtained from the seeds of the caper spurge (E. lathyris). The interaction of L10 (1a) and its acetyl derivative (1b) with P-glycoprotein, a multidrug transporter overexpressed in cancer cells and responsible for resistance to chemotherapy, was investigated.

Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone.

Besides acting complexly on both normal and tumor cells, transforming growth factor-beta (TGF-beta) can determine the nature of the response to the antigen, strongly inhibiting the differentiation of naive CD4+ T-cells toward a T helper-1 (Th-1) phenotype; in a number of experimental models, TGF-beta also appeared to be a potent immunosuppressant factor. TGF-beta was shown to be released by some human malignant mesothelioma (MMe) cells, which affects the immune response to this tumor. Thus, for a better understanding of the role of TGF-beta in the immune response to MMe cells, we evaluated the production of a Th-1 cytokine (IFN-gamma) and of a Th-2 cytokine (IL-4), following Purified Protein Derivative (PPD) recall antigen presentation by human MMe cells to a class-II major histocompatibility complex (MHC-II)-matched PPD clone (PPD clone).

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM).

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

Objective: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis.

Design: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting.

Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity?

Due to the frequent use of intrapleural interleukin-2 (IL-2) to treat pleural effusions from malignant mesothelioma (MMe), we measured nitric oxide (NO) end product nitrite (NO(2)(-)) in pleural effusions of 12 MMe patients with chronic or chronic-relapsing pleurisy. Through high performance liquid chromatography analysis, NO(2)(-) was found in the initial pleural fluid sample of all patients (156.25 pmol ml(-1)), and increased significantly following IL-2 intrapleural instillation, both at 24 (589.

Transcription and alternative splicing of telomerase reverse transcriptase in benign and malignant breast tumours and in adjacent mammary glandular tissues: implications for telomerase activity.

Telomerase activity was determined in 15 breast cancers, 24 benign breast lesions, and 36 breast tissues adjacent to benign or malignant tumours. A positive TRAP (telomeric repeat amplification protocol) signal was detected in 67% of carcinomas and 29% of benign tumours. In five of ten cases, non-invaded breast tissues adjacent to telomerase-positive carcinomas also displayed telomerase activity.

Decrease of TGF-beta1 plasma levels and increase of nitric oxide synthase activity in leukocytes as potential biomarkers of Alzheimer's disease.

A variety of inflammatory proteins have been identified in brains of Alzheimer's disease (AD) patients, including inflammatory cytokines, acute phase proteins and complement components. In the present paper we have investigated the levels of circulating inflammatory mediators as potential biomarkers of this disease, concentrating mostly on transforming growth factor beta (TGF-beta1) in plasma and on nitric oxide synthase (NOS) activity in leukocytes. Plasma and leukocytes were isolated from 48 sporadic AD and 23 healthy control subjects of same age and sex.

Higher levels of melanin and inhibition of cdk2 activity in primary human melanoma cells WM115 overexpressing nPKCdelta.

Many studies have attempted to define the state of differentiation of melanoma cells and to correlate it with other critical parameters of malignancy such as the tumorigenic and metastatic nature of the cells. In the present paper we focused on the possible relationships between the novel protein kinase C isoform nPKCdelta, melanin synthesis and proliferative capacity in a primary human melanoma cell line WM115. Cells were transfected to produce overexpression of this isoform and the effects on melanin synthesis, cyclin-E dependent kinase (cdk2) activity and cyclin E expression were studied.

Impact of topotecan-based chemotherapy on the immune system of advanced ovarian cancer patients: an immunophenotypic study.

The effects of topotecan-based chemotherapy (CT) on peripheral blood lymphocyte (PBL) subsets were evaluated in ovarian cancer patients. Fourteen patients with epithelial ovarian cancer, at the diagnosis or relapsed after platinum-based CT, were treated with: a) topotecan in association with carboplatin and taxanes as first line CT; b) topotecan alone or c) topotecan in association with carboplatin both as second line of treatment after platinum. The phenotype of PBL was determined before starting treatment and immediately before each CT course by flow cytometric analysis.

Weekly taxanes in metastatic breast cancer (review).

Metastatic breast cancer is still considered an incurable and difficult to treat disease, even if several classes of antineoplastic agents have shown various levels of activity in these patients. Taxanes are the most effective drugs in breast cancer, together with the anthracyclines, but they have several important side-effects with standard administration schedules. The weekly administration of both paclitaxel and docetaxel, respectively at 80-100 mg/m2/week and 35-40 mg/m2/week, is feasible and it has an efficacy level at least comparable with the standard 21-day administration.

Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure.

Background: Premature ovarian failure (POF) is a secondary hypergonadotrophic amenorrhoea affecting 1-3% of females, whose aetiology is almost unknown. However, inhibin alpha gene (INHalpha) has recently been indicated as candidate in POF pathogenesis.

Methods: We analysed patients affected by POF (n = 157) for the missense mutation (769G-->A transition) in the exon 2 of the INHalpha gene.

Differential localisation of nPKC delta during cell cycle progression.

nPKC delta is a phospholipid-dependent and calcium-independent PKC isoform, whose over expression in BL6T murine melanoma cells, modifies their proliferative and metastatic potential in vivo. We focus here on the possible relationship between the subcellular localisation of nPKC delta and distinct phase of the cell cycle. Our findings show a dynamic localisation of nPKC delta in dependence of the phase of the cell cycle.

Determination of free and total (free plus protein-bound) melatonin in plasma and cerebrospinal fluid by high-performance liquid chromatography with fluorescence detection.

A simple, sensitive and accurate method for the estimation of free and total (free plus protein-bound) melatonin (MLT) in human plasma and cerebrospinal fluid (CSF) is described. Via Chem-Elut cartridges, free and total MLT (the latter obtained after a deproteinization step) were quantified in dichloromethane-extracted samples and analyzed in one chromatographic run by high-performance liquid chromatography (HPLC) with fluorimetric detection. The column used was an Extrasil ODS-2 (3 microm, 150 x 4.

The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor.

The aim of this study was to evaluate whether the presence of simian virus-40 (SV40) is associated with increased release of vascular endothelial growth factor (VEGF) in human malignant mesothelioma (MM) cells. We studied nine cell lines derived from pleural effusion (PE) of patients with MM, and three different cultures of normal human mesothelial cells (NHMC) derived from pleural fluid of patients with congestive heart failure. NHMC were transfected with full length SV40 (NHMC-FL) or large T antigen (NHMC Tag) DNAs.

Slow breathing increases arterial baroreflex sensitivity in patients with chronic heart failure.

Background: It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction.

Methods And Results: We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in 81 patients with stable (2 weeks) CHF (age, 58+/-1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15]) and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from 9.