Biomedical subjects

C Tortorella

Publications and source records attributed to C Tortorella.

At least 55 records · Page 3Linked to original sources

PubMed1999

Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.

OBJECTIVE: To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. METHODS: T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. RESULTS: MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. CONCLUSIONS: Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.

Adult↗

PubMed1999

Guanylin: a novel regulatory peptide possibly involved in the control of Ca2+-dependent agonist-stimulated aldosterone secretion in rats.

Guanylin is a 15-amino acid peptide, which activates guanylate cyclase (GC) and plays a major role in the regulation of water and electrolyte secretion by intestinal mucosa. The expression of guanylin prohormone has been recently demonstrated in the rat adrenal gland, and this prompted us to investigate whether guanylin, like other peptides secreted by adrenal medulla, affects the function of the adrenal cortex. Autoradiography demonstrated the presence of [125I]guanylin binding sites in the zona glomerulosa (ZG), but not zona fasciculata-reticularis. Guanylin did not change either basal or ACTH-stimulated steroid secretion of dispersed rat adrenocortical cells, but concentration-dependently (from 10(-10) M to 10(-8) M) inhibited aldosterone response of ZG (capsular) cells to both angiotensin-II (ANG-II) and K+. Guanylin (10(-8) M) blocked the aldosterone secretagogue effect of the Ca2+-channel activator BAYK-8644, and the Ca2+-ionophore ionomycin counteracted the inhibitory action of this peptide on the secretory responses of capsular cells to ANG-II and K+. As expected, guanylin did not affect cyclic-AMP release by capsular cells, but evoked a sizeable increase in cyclic-GMP production. Both the inhibitor of GMP synthase decoyinine and the GC-inhibitor LY-83583, although suppressing cyclic-GMP release, did not affect guanylin-evoked inhibition of K+-stimulated aldosterone secretion. Collectively, these findings allow us to conclude that guanylin: i) inhibits aldosterone secretion of rat ZG cells by interfering with the agonist-induced activation of voltage-gated Ca2+-channels, the stimulation of guanylate cyclase conceivably playing a negligible role; and ii) could be included in that group of regulatory peptides, secreted by medullary chromaffin cells, which are able to counteract an exceedingly high aldosterone secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1998

Prognostic value of proton magnetic resonance spectroscopy in ischemic stroke.

OBJECTIVE: To determine the correlation between metabolite concentrations and clinical outcome during the acute or subacute phase of ischemic stroke by using single-voxel localized proton magnetic resonance spectroscopy (1H-MRS). SETTING: A university hospital neurologic department. PATIENTS AND METHODS: Combined single-voxel 1H-MRS and magnetic resonance imaging were performed on 26 patients with a recent ischemic stroke (on 8 patients during the first 24 hours after the stroke and on 18 during the first week). For all patients, the signals from N-acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were compared with those on the contralateral side as peak area ratios. The data for 1H-MRS were related to scores on the Scandinavian Stroke Scale and the Barthel Index at a 6-month clinical follow-up. RESULTS: The signals from N-acetylaspartate, choline-containing compounds, and creatine-phosphocreatine were significantly reduced in all infarcted areas (P<.001, P<.001, and P=.003, respectively, Wilcoxon signed rank test). A lactate signal was present in 19 patients. The statistical analysis showed a significant positive correlation between N-acetylaspartate signals and Scandinavian Stroke Scale scores and between reduction of N-acetylaspartate signals and Barthel Index scores (Spearman rank correlation test). Patients in whom lactate was present had Scandinavian Stroke Scale scores significantly lower than patients in the group without lactate (Mann-Whitney U test). CONCLUSION: Single-voxel 1H-MRS performed during the acute or subacute phase of ischemic stroke may provide prognostic information.

Adult↗

PubMed1998

Spontaneous and Fas-induced apoptotic cell death in aged neutrophils.

On the basis of the strict analogies between polymorphonuclear cell (PMN) alterations in the aging and depressed functional capacities displayed by apoptotic PMN, we investigated the possible occurrence of age-associated changes in neutrophil apoptosis, either spontaneous or induced by Fas antigen (CD95) activation. In both cases, old subjects exhibited a time course kinetics of neutrophil apoptosis, as assessed by morphologic and quantitative DNA fragmentation analysis, which overlapped that observed in the young. These findings were confirmed by DNA ladder analysis, showing a progressive increase in DNA cleavage products in cells cultured in medium alone or added with agonistic anti-Fas IgM (CH-11) monoclonal antibodies (mAbs), after 12 and 6 hr of incubation, respectively. Aged purified neutrophils constitutively expressed CD95, at levels similar to those observed in the young. Moreover, although we failed to detect Fas ligand expression on PMN surface, treatment of cell cultures with antagonistic anti-Fas IgG1 (ZB4) mAbs determined a significant inhibition of spontaneous apoptosis in neutrophils from both groups of subjects, thus suggesting that the Fas/Fas ligand system is in fact involved in such an event. The results indicate that the overall intrinsic mechanisms regulating neutrophil cell death are not affected by age. Yet aged neutrophils showed a diminished capacity to be rescued by proinflammatory mediators, such as granulocyte-monocyte colony-stimulating factor, granulocyte colony-stimulating factor, and bacterial lipopolysaccharide, following Fas activation. This may hamper the accumulation of functionally active cells in inflammatory areas in vivo, thus contributing to the increased susceptibility of elderly individuals to life-threatening infections.

Aged↗

PubMed1998

Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis.

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF may negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover.

Apoptosis↗

PubMed1998

Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal brain lesions in patients infected with HIV.

OBJECTIVES: To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting metabolic changes in diffuse or focal lesions in the brain of patients infected with HIV. METHODS: Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative neurological controls were examined with a combined MRI and 1H-MRS technique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were acquired by single voxel, localised on focal lesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated. RESULTS: A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), suggesting neuronal or axonal damage independent of brain lesion aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) without between group differences. The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups (Fisher's test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher's test, p=0.00024). CONCLUSION: 1H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions. Nevertheless, the homogeneous metabolic pattern that characterises PML suggests the usefulness of 1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as HIV encephalopathies, from PML.

AIDS Dementia Complex↗

PubMed1998

Proadrenomedullin N-terminal 20 peptide inhibits aldosterone secretion of human adrenocortical and Conn's adenoma cells: comparison with adrenomedullin effect.

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two vasoactive peptides, which are highly expressed in human adrenal gland. Autoradiography showed the presence of abundant [125I]ADM and [125I]PAMP binding sites in both the outer cortex and medulla of human adrenals. ADM, but not PAMP binding was completely displaced by the specific CGRP1 receptor antagonist CGRP(8-37). ADM and PAMP concentration-dependently inhibited angiotensin-II (ANG-II)-stimulated, but not basal aldosterone secretion of dispersed human adrenocortical cells. PAMP was significantly more potent than ADM (IC50, 0.98 x 10(-11) vs. 3.16 x 10(-9) mol/L). CGRP(8-37) abolished the inhibitory action of ADM, without affecting that of PAMP. Qualitatively analogous findings were obtained using aldosteronoma dispersed cells. However, tumor cells were more sensitive than normal adrenocortical cells (IC50 were 1.32 x 10(12) and 1.51 x 10(-9) mol/L for PAMP and ADM, respectively). Moreover, PAMP was found to also depress basal aldosterone secretion (IC50, 4.27 x 10(-11) mol/L). Neither basal nor ANG-II-stimulated cortisol production by both normal and tumorous adrenocortical cells was altered by ADM or PAMP. Collectively, these findings confirm that ADM (CGRP1) and PAMP receptors are present in the human outer adrenal cortex and allow us to draw the following conclusions: 1) because of its potency, PAMP may a better candidate for being considered a physiological regulator of aldosterone secretion than ADM; and 2) under pathological conditions, both peptides may be capable of reversing overproduction of aldosterone.

Adenoma↗

PubMed1998

Proton magnetic resonance spectroscopy in primary blepharospasm.

Single-volume proton magnetic resonance spectroscopy, localized to basal ganglia, was carried out in 10 patients with primary blepharospasm (PB) to assess the levels of N-acetyl aspartate (NAA), creatine-phosphocreatine, and choline-containing compounds. NAA was reduced significantly in patients compared with control subjects. This result suggests a striatal neuronal loss in PB.

Aged↗

PubMed1998

Immunoresponsiveness in chronic hepatitis C patients: correlation between tissue and serum findings.

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.

Adult↗

PubMed1998

Modulation of cytoskeleton assembly capacity and oxidative response in aged neutrophils.

Several reports have emphasized that aged polymorphonuclear cells (PMN) exhibit an impairment of superoxide anion (O2-) generation when triggered with formyl-methionyl-leucine-phenylalanine (FMLP) in comparison to the younger counterpart. Since microfilaments and microtubules are involved in PMN-mediated functions, in a group of old donors we assessed the effects of either actin stabilizing and disrupting agents, i.e. phalloidin and cytochalasin B, or microtubule stabilization or disruption by taxol and colchicine, respectively, on FMLP-triggered neutrophil oxidative responsiveness. Results show that phalloidin treatment, at a concentration ranging from 10(-6) to 10(-8) M, gave rise to an inhibition of O2- release by aged PMN, while the same effect was seen in similarly treated young cells at a concentration of 10(-7) M only. On the contrary, cytochalasin B pretreatment led to an enhancement of O2- generation in both young and aged neutrophils, even if to a lower extent in the latter group. At the same time, taxol at 10(-8) M strength inhibited young cell responsiveness, while no effects were induced by colchicine treatment. Quite interestingly, elderly neutrophil function was negatively modulated by both microtubule affecting compounds. Altogether, these findings suggest the possible relevance of cytoskeletal affecting compounds in the modulation of FMLP-stimulated O2- release during senescence.

Actins↗

PubMed1997

Arginine-vasopressin stimulates CRH and ACTH release by rat adrenal medulla, acting via the V1 receptor subtype and a protein kinase C-dependent pathway.

Arginine-vasopressin (AVP) is a hypothalamic hormone that, like CRH, stimulates the pituitary release of ACTH, thereby activating adrenal glucocorticoid secretion. Evidence indicates that rat adrenal medulla contains a CRH-ACTH system duplicating that existing at the hypothalamo-pituitary level and involved in the paracrine stimulation of the cortex secretion. Therefore, we investigated by RIA the effect of AVP on the release of CRH and ACTH immunoreactivities (IR) by rat adrenal medulla in vitro. AVP concentration-dependently enhanced the release of both CRH-IR and ACTH-IR, and the effect was blocked by a selective antagonist of the V1 subtype of AVP receptors. The CRH receptor antagonist alpha-helical-CRH partially reversed AVP-evoked rise in ACTH-IR release, without altering either CRH response or basal secretions of CRH and ACTH. The specific inhibitors of protein kinase C Ro31-8220 and calphostin C abolished both CRH and ACTH responses to AVP. In conclusion, our present findings suggest that AVP stimulates intramedullary the CRH-ACTH system, acting via V1 receptors and activating protein kinase C.

Adrenal Medulla↗

PubMed1996

Enrichment of differentiated CD45RBdim,CD27- memory T cells in the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: To delineate in greater detail the phenotype of T cells that reside in the synovial tissue (ST) and synovial fluid (SF) of patients with rheumatoid arthritis (RA), in order to determine their precise differentiation status, and to determine whether the accumulation of these specific T cell subsets in these synovial compartments could be related to their capacity for transendothelial migration. METHODS: Lymphocytes from normal subjects or from the peripheral blood (PB), ST, and/or SF of RA patients were phenotypically analyzed by flow cytometry. Normal PB CD4+ T cells were also characterized using an in vitro assay of transendothelial migration. RESULTS: ST and SF were found to be enriched with memory (CD45RA-,CD45RO+,CD11abright,CD44bright and activated (CD69+) T cells. Moreover, ST and SF cells from RA patients were enriched in differentiated CD4+,CD45RBdim,CD27- T cells, a subset of mature memory T cells that develops after prolonged antigenic stimulation. In addition, PB of some RA patients contained an increased number of CD4+,CD45RBdim,CD27- T cells. The CD4+,CD11abright,CD44bright memory T cells, which included the CD45RBdim,CD27- more mature memory cells, exhibited an enhanced capacity for transendothelial migration that is likely to contribute to their enrichment in the rheumatoid synovium. CONCLUSION: RA patients manifest an increased number of mature memory T cells in the SF and ST, and some also have an increased number of these cells in PB that is likely to reflect chronic antigenic stimulation. The enrichment of these cells in the SF and ST reflects, in part, an enhanced capacity to migrate from the vascular space into inflamed tissue.

Arthritis, Rheumatoid↗

PubMed1996

Prognostic significance of metabolic changes detected by proton magnetic resonance spectroscopy in ischaemic stroke.

Proton magnetic resonance spectroscopy has proved to be useful for monitoring a number of metabolites in cerebral infarction. Combined magnetic resonance imaging and spectroscopy investigations were carried out in 14 patients with a recent ischaemic stroke (< 1 week); follow-up examinations were performed from day 28 to day 252 after stroke. The aim of this study was to assess the correlation between the changes of N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate and clinical evolution measured by the Scandinavian Neurological Scale (SNS). Initially the lactate magnetic resonance signal was present in all patients and the other metabolite contents were significantly reduced (P < 0.001; unpaired t-test) as compared with those on the contralateral side. Spearman's rank correlation test showed a positive correlation between the initial reduction of N-acetyl-aspartate content and the SNS (P < 0.05), and between the final N-acetyl-aspartate content and the SNS (P < 0.001). Our results suggest that serial examination in stroke patients may provide further prognostic information and encourage controlled clinical studies.

Adult↗

PubMed1996

Intra-adrenal 11 beta-hydroxysteroid dehydrogenase plays a role in the regulation of corticosteroid secretion: an in vitro study in the rat.

The expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) has been demonstrated in the adrenal glands, but until now little attention has been paid on its possible physiologic action. In-situ perfused rat adrenals released under basal conditions, in addition to mineralo- and glucocorticoids, notable amounts of 11-dehydrocorticosterone (DH-B), the inactive form to which corticosterone (the main glucocorticoid in rodents) is converted by 11 beta-HSD. The addition to the perfusion medium of glycyrrhetinic acid, a specific inhibitor of 11 beta-HSD, strongly reduced DH-B release and simultaneously evoked a moderate rise in both mineralo- and glucocorticoid output. The bolus administration of ACTH strikingly enhanced mineralo- and glucocorticoid secretion, but it significantly depressed DH-B release Rat adrenal microsome preparations possessed 11 beta-HSD activity, that was inhibited by glycyrrhetinic acid. Conversely, ACTH was without any apparent effect, a finding indicating that the in vivo observed ACTH-induced inhibition of adrenal 11 beta-HSD activity is mediated by an indirect mechanism whose elucidation requires further investigation. In conclusion, our present findings suggest that adrenal 11 beta-HSD plays a role in the regulation of steroid secretion in rats under both basal and stimulated conditions.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1996

High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques.

Proton magnetic spectroscopy (1H-MRS) investigation was performed on CSF samples of patients with neurological inflammatory diseases including 52 cases of multiple sclerosis (MS). 12 acute idiopathic polyneuropathies, 20 acute meningitides (10 viral and 10 bacterial). Spectra were compared with those acquired in 18 neurological controls. High CSF lactate levels were found in MS patients during clinical exacerbation of relapsing-remitting course (p = 0.036 vs neurological controls). In MS patients with MRI evidence of Gd-enhanced plaques CSF lactate was higher than in patients with MRI inactive plaques (p = 0.017). CSF lactate positivity correlated with number of CSF mononuclear cells in MS patients with clinical activity (p = 0.05) as well as in MS patients with MRI enhancement (p = 0.003). A comparative 1H-MRS investigation in vivo on localized demyelinating areas confirmed an elevated lactate signal in Gd-enhanced (61%) more frequently than in unenhanced (22%) plaques (p = 0.03). MS patients with high lactate signal in active plaques showed high lactate levels in CSF. Increased CSF lactate was found also in patients with acute meningitis and idiopathic polyneuropathy. These data suggest that changes in lactate levels may depend on anaerobic glycolytic metabolism in activated leukocytes during inflammatory diseases. A decrease of CSF formulate levels was found in MS patients during active and inactive clinical phase (p = 0.037, p=0.05 vs neurological controls respectively). Formate changes might be related to a disorder of choline-glycine cycle in MS. 1H-MRS in vivo showed significant increase of choline in acute plaques, whereas a decrease of N-acetyl aspartate was found in chronic plaques; these metabolites are undetectable in CSF. CSF glucose levels were lower in bacterial than in viral meningitis (p = 0.014) and in neurological controls (p = 0.05). These observations suggest that 1H-MRS may be able to detect CSF metabolic impairment in neurological inflammatory diseases. In MS some CSF findings reflect metabolic changes occurring in brain demyelinating areas, and they could be useful foe evaluation of disease activity in different stages of disease evolution.

Adolescent↗

PubMed1996

Effects of interferon-alpha treatment on neutrophil oxidative metabolism, lymphocyte proliferation and monocyte HLA class I antigen expression in patients with chronic hepatitis C.

Polymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month interferon alpha (IFN-alpha) treatment and divided into Responder ('R') and Nonresponder ('NR') subsets according to clinical outcome. Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between 'R' and 'NR' subsets: an elevated superoxide anion (O2-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen expression on CD14+ cells. IFN-alpha administration gave rise to a modulation of oxidative response in 'R' group only, since these individuals displayed an O2- release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-alpha therapy, even if it reached statistical significance in 'R' group only. Finally, a more marked difference between 'R' and 'NR' individuals was noted in terms of HLA class I antigen induction on CD14+ cells at the end of therapy, as a consequence of a reduced expression of these structures in 'NR' subjects. Altogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-alpha induced therapeutical effects in CH-C patients.

Adult↗

PubMed1996

Lipopolysaccharide-, granulocyte-monocyte colony stimulating factor and pentoxifylline-mediated effects on formyl-methionyl-leucine-phenylalanine-stimulated neutrophil respiratory burst in the elderly.

The impairment of superoxide anion (O2-) generation by aged polymorphonuclear cells (PMN) stimulated with formyl-methionyl-leucine-phenylalanine (FMLP) has been reported. In this work the effect of lipopolysaccharide (LPS), granulocyte-macrophage colony stimulating factor (GM-CSF) and pentoxifylline (POF) pretreatment on FMLP-triggered neutrophil oxidative metabolism in a group of healthy elderly individuals, was investigated. Results provide evidence that LPS and/or GM-CSF priming was able to enhance O2- production in old PMN, even if values were still lower than those observed in similarly-treated young cells. Moreover, even if the lag period was unaffected by inflammatory mediator treatment, the priming gave rise to a significant increase of maximum O2- release rate. On the contrary, POF pretreatment led to a significant decrease of oxidative responsiveness in either unprimed or primed PMN suspensions. These findings suggest the occurrence of different mechanisms in the imbalance of FMLP-activated neutrophil oxidative responsiveness during senescence. This may be of paramount significance for explaining the augmented frequency of severe infectious diseases with advancing age.

Aged↗

PubMed1995

Expression of CD45RB and CD27 identifies subsets of CD4+ memory T cells with different capacities to induce B cell differentiation.

The capacity of four subsets of CD4+ memory T cells, defined by expression of CD45RB and CD27, to provide help for B cells was examined. Larger amounts of Ig were induced by CD45RBdimCD27- cells compared with the CD45RBdimCD27+ population, whereas CD45RBbrightCD27+ or CD27- cells were poor inducers of Ig synthesis. Mitomycin C treatment, which prevents suppressive activity, markedly enhanced Ig production supported by each subset except for CD45RBbrightCD27- cells. Mitomycin C-treated CD45RBdim cells remained the most efficient inducers of Ig production, but no difference was detected between CD27+ and CD27- cells. The subsets also differed in their ability to proliferate and secrete cytokines, but these differences did not explain variations in the capacity to provide help for B cells. Both CD27- subsets exhibited decreased proliferation and uniquely secreted IL-4, with the CD45RBdimCD27- subset producing the greatest quantities of IL-4. No differences in IL-2 and IFN-gamma production were found. IL-10 secretion increased with the acquisition of the CD45RBdim phenotype and, within the CD45RBdim cells, with the loss of CD27. Staining for cytoplasmic cytokines indicated that individual populations of CD27-CD4+ helper T cells produced either IL-4 or IFN-gamma, whereas more than half of the IL-4 producers also synthesized IL-2. Finally, the different abilities of CD4+ memory T cell subsets to support B cell differentiation did not relate to variations in the expression of CD40 ligand. These results indicate that within the CD4+ memory T cell population an increase of helper activity associates with the shift from a CD45RBbright to a CD45RBdim phenotype. Within the CD45RBdim subset, the loss of CD27 is associated with a reduction of suppressive activity.

Adult↗