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M Romano

Publications and source records attributed to M Romano.

At least 199 records · Page 11Linked to original sources
PubMed1997

Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment.

IL-6-/- mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6-/- leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC). EC express only the gp130 signal transducing chain and not the subunit-specific IL-6R and are therefore unresponsive to IL-6. However, EC are responsive to a combination of IL-6 and soluble IL-6R as measured by the activation of STAT3, chemokine expression, and augmentation of ICAM-1. Activation by IL-6-IL-6R complexes was inhibited by an IL-6 receptor antagonist and potentiated by a superagonist. Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.

Animals↗
PubMed1997

Effects of Ajoene on lymphocyte and macrophage membrane-dependent functions.

Ajoene, (E, Z) -4, 5, 9-trithiadeca-1, 6, 11-triene 9 oxide, is a compound originally isolated from ethanolic extracts of garlic that impairs platelet aggregation by inhibiting the functional exposure of platelet integrins GPIIb/IIIa. In vitro, Ajoene is toxic for several tumoral cell lines, and exert an antiproliferative effect on T. cruzi and murine malaria parasites. Here we show that Ajoene strongly inhibited the proliferation induced in human lymphocytes by the mitogens phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and anti-CD3, and the capping formation induced in B lymphocytes by anti-IgM antibodies. On macrophages, Ajoene was also found to partially inhibit the lypopolysaccharide-induced production of Tumor Necrosis Factor (TNF), and to decrease the phagocytic activity of thioglycolate-elicited mouse peritoneal macrophages for IgG-opsonized, human erythrocytes. Ajoene also partially prevented the lytic effect of human and rabbit TNF on Actinomycin D-treated WEHI 164 cells. These results strongly suggest that Ajoene is a potent modulator of membrane-dependent functions of immune cells.

Animals↗
PubMed1997

Ambulatory monitoring of left ventricular function: walk and bicycle exercise in congestive heart failure.

UNLABELLED: The aim of this study was to assess changes in left ventricular (LV) function during 6-min walk test and cardiopulmonary exercise by continuous radionuclide monitoring in patients with congestive heart failure (CHF). METHODS: Seventeen patients with CHF and 10 normal subjects underwent monitoring of LV function (Vest) during 6-min walk test and during bicycle exercise with combined analysis of pulmonary gas exchange. During cardiopulmonary exercise, all parameters of LV function were measured at rest, at the anaerobic threshold (AT) and at peak oxygen uptake (peak VO2). RESULTS: In the normal subjects, during the walk test, heart rate (HR), ejection fraction (EF), end-diastolic volume (EDV), cardiac output (CO) and stroke volume (SV) significantly increased from rest to peak (all p < 0.001), while end-systolic volume (ESV) significantly decreased from rest to peak (p < 0.001). In patients with CHF, during the walk test, HR, EDV, ESV and CO significantly increased from rest to peak (p < 0.001), EF significantly decreased from rest to peak (p < 0.001) and SV did not show significant change. During cardiopulmonary exercise, normal subjects showed a significant increase in HR and CO, from rest to AT and from AT to the peak VO2 (p < 0.001). EF, EDV and SV significantly increased from rest to AT (p < 0.001), with no significant change from AT to peak VO2. ESV decreased from rest to AT (p < 0.001), showing no significant change from AT to peak VO2. In patients with CHF, HR, CO, ESV and EDV increased significantly from rest to AT (p < 0.001) and from AT to peak VO2 (p < 0.001). EF and SV did not show significant changes from rest to AT, showing a significant decrease from AT to peak VO2 (p < 0.001). CONCLUSION: Vest can be used to evaluate cardiac responses during 6-min walk test and cardiopulmonary exercise in patients with CHF. In such patients, significant impairment of LV function is already present during submaximal physical exercise becoming more evident during the anaerobic phases of bicycle exercise.

Case-Control Studies↗
PubMed1997

Serum interleukin 6 concentrations in chronic hepatitis C patients before and after interferon-alpha treatment.

IFN-alpha represents the treatment of choice in chronic hepatitis C. It acts directly on the cells infected by the virus and indirectly via the cytokine network. We studied the behavior of interleukin 6 (IL-6), a cytokine that is particularly active in the liver and considered an index of liver inflammation and necrosis, in order to evaluate the relationships between IFN-alpha administration and serum levels of this cytokine. Our study series was composed of 60 patients (32 males, 28 females, mean age 53.03 +/- 12.7 years) affected by chronic hepatitis C and 24 healthy controls (14 males, 13 females, mean age 45.8 +/- 5.9 years). We determined serum IL-6 concentrations before and after 3,000,000 IU of IFN-alpha t.i.w./6 months in the former and compared them with levels observed in the controls. Pre- and post-treatment serum IL-6 levels were higher in chronic hepatitis patients and correlated with HAI score and HCV RNA prior to treatment. Diversely, this correlation was less significant after completion of the treatment. Furthermore, IL-6 concentrations depended on the type of response to treatment, i.e. they decreased in complete responders, while increased in partial and non-responders. Our data indicate that IL-6 concentrations, before treatment, are expression of viral-induced inflammation and that, after treatment, may be increased by the action of IFN-alpha treatment.

Adult↗
PubMed1996

Activation of human monocytes and the acute monocytic leukemia cell line (THP-1) by lipoxins involves unique signaling pathways for lipoxin A4 versus lipoxin B4: evidence for differential Ca2+ mobilization.

Lipoxins are bioactive eicosanoids that are generated during multicellular events such as inflammation, thrombosis, and atherosclerosis. They have selective actions on peripheral blood cells, in that previous results indicate that lipoxin A4 (LXA4) and lipoxin B4 (LXB4) inhibit neutrophil migration while they are both potent stimuli of peripheral blood monocyte (PBM) chemotaxis and adherence. Here, we report the impact of lipoxins on levels of free cytosolic calcium ([Ca2+]i) in PBM and THP-1 cells (acute monocytic leukemia cells) as well as on the functional responses of these cells. LXA4, but not LXB4, induced a concentration-dependent increase in [Ca2+]i in monocytes that was half-maximal at approximately 200 nM. Prior exposure of the cells to EGTA reduced the LXA4-induced increase in [Ca2+]i by approximately 50 to 60%, indicating the contribution of both intracellular mobilization and external influx in LXA4 Ca2+ regulation. A leukotriene B4 receptor antagonist, ONO 4057, did not significantly alter LXA4-induced [Ca2+]i, while it inhibited the action of leukotriene B4. LXA4 also induced a rise in [Ca2+]i in the monocytic leukemia cell line (time to reach maximum = 15.1 +/- 0.87 s), and both LXA4 and LXB4 stimulated a concentration-dependent THP-1 cell adherence to laminin with concentrations as low as 10(-10)M. In contrast to the findings with LXA4, exposure of THP-1 or PBM to LXB4 was not accompanied by mobilization of intracellular Ca2+. Although both LXA4 and LXB4 stimulate adherence of PBM, they did not evoke superoxide anion generation by these cells, nor did they affect the rate of acidification of extracellular medium by monocytes, as monitored using a microphysiometer. Together, these results indicate that an increase in [Ca2+]i is a component of the signal transduction events following monocyte interaction with LXA4, but not LXB4, and that both LXA4 and LXB4 are potent and selective agonists for THP-1 cells and PBM. Moreover, they suggest that LX display a unique profile of actions with mononuclear cells compared with other known agonists of monocytes, and that LX can direct monocyte-mediated events.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Constitutive insulin-like growth factor-II expression interferes with the enterocyte-like differentiation of CaCo-2 cells.

In this study we have examined the role of insulin-like growth factor-II (IGF-II) in the differentiation of the CaCo-2 human colon carcinoma cell line. We have shown previously that IGF-II is an autocrine growth factor for CaCo-2 cells. IGF-II expression is high in proliferating, undifferentiated CaCo-2 cells and markedly decreases when cells become confluent and start to differentiate. To evaluate whether differentiation of CaCo-2 cells depends on an IGF-II related pathway, we treated cells with a blocking antibody to the IGF-I receptor that mediates most IGF-II biological effects. Treatment of preconfluent CaCo-2 cells with this antibody decreased by 40% autonomous cell proliferation and induced differentiation as shown by an increase in sucrase isomaltase activity and apolipoprotein A-I (apoA-I) mRNA levels. To examine the significance of autocrine IGF-II production in CaCo-2 cell differentiation, we generated stable CaCo-2 cell lines that constitutively express rat IGF-II under the control of a Rous sarcoma virus promoter. Sustained expression of IGF-II resulted in: (a) increased proliferative rate; (b) high IGF-I receptor number, even after reaching confluence; (c) increased capability of anchorage-independent growth; (d) inhibition of the expression of apoA-I and SI mRNAs. Analysis of several independent IGF-II-transfected clones showed an inverse correlation between IGF-II mRNA levels and expression of the differentiation markers, the cells expressing the higher levels of the transfected IGF-II being the less differentiated ones. Our data suggest that perturbation of IGF-II-mediated cell proliferation interferes with the enterocyte-like differentiation pathway of CaCo-2 cells.

Apolipoprotein A-I↗
PubMed1996

Influence of digitalis on left ventricular functional response to exercise in congestive heart failure.

This was a double-blind, placebo-controlled, crossover study designed to determine the influence of digitalis treatment on left ventricular (LV) response to physical exercise in patients with congestive heart failure (CHF). In 10 patients with CHF (ejection fraction 29 +/- 2%), LV function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed during control conditions and after a 3-week treatment with digoxin (0.25 mg/day orally) or placebo. Ten normal volunteers matched for sex and age constituted the control group. In normals, exercise ejection fraction and end-diastolic volume increased (both p <0.001), while end-systolic volume decreased progressively (p <0.001). In control conditions, patients with CHF had a sharp increase in heart rate during exercise, while ejection fraction did not change; both end-diastolic and end-systolic volumes increased significantly (both p <0.001) during exercise. During digoxin treatment, heart rate response to exercise recorded in patients with CHF was comparable to that recorded in normal subjects. In addition, a significant increase in ejection fraction during exercise was detected (P <0.001), and the increase in end-systolic volume was significantly smaller than that observed in control conditions (p <0.05). When patients received placebo, the responses of LV function to exercise were comparable to those observed in control conditions. These findings demonstrate that digitalis has a favorable influence on LV functional adaptation to exercise in CHF.

Adult↗
PubMed1996

Activation of fetal promoters of insulinlike growth factors II gene in hepatitis C virus-related chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Increased prevalence of hepatitis C virus (HCV) infection has been found in patients with hepatocellular carcinoma (HCC). The expression of insulinlike growth factor II (IGF-II) has been linked to hepatocarcinogenesis in the experimental animal and in humans. Since reactivation of fetal IGF-II transcripts has been observed in human HCC, we have analyzed the levels of adult P1 and fetal P3 and P4 IGF-II promoter-derived transcripts in the liver of patients with HCV-related chronic active hepatitis (CAH), cirrhosis, and HCC by means of a semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) assay. Transcripts derived from adult P1 promoter were increasingly expressed from normals to patients with CAH and cirrhosis, but were undetectable in the tumorous area of 5 of 7 HCC patients and present at low levels in the nontumorous area of all HCC patients. Transcripts derived from fetal P3 promoter were not detectable in normal subjects, while they were expressed abundantly in most CAH and all cirrhotic patients. Transcripts from fetal P4 promoter were detected at high levels in 3 of 9 CAH patients and in the majority of cirrhotic patients. Increased expression of fetal promoter-derived transcripts was also found in the liver of HCC patients, although levels were lower than in cirrhosis. Also, the activity of fetal P3 and P4 promoters was higher in the nontumorous than in the tumorous area of the liver of HCC patients. The expression of IGF-II transcripts was correlated with the rate of cell mitotic activity by measuring the expression of the proliferating cell nuclear antigen (PCNA) gene. PCNA messenger RNA (mRNA) levels progressively increased from normals to CAH and to cirrhotic patients, and persisted at a high level in the tumorous and in the nontumorous area of HCC subjects, thus showing that the increase of IGF-II transcripts in CAH and cirrhosis is accompanied by an activation of cell mitosis in these samples. These data suggest that the activation of IGF-II gene expression from adult and fetal promoters may play a role in premalignant proliferation observed in HCV-related chronic liver disease.

Adult↗
PubMed1996

A Simple, Reproducible Animal Model of Arterial Occlusion with Mixed Thrombus.

Background: Current animal models of thrombotic arterial occlusion are complex and difficult to perform. A more simplified model of thrombotic occlusion with angiographic endpoints and mixed thrombotic composition would be useful to assess the effectiveness of new therapeutic modalities. Methods and results: Femoral arteries in 38 New Zealand White rabbits were cannulated. The animal protocol involved denudation of one iliac artery by stripping with progressively increasing balloon size, followed by inflow arterial occlusion and the addition of thrombin. Cineangiography was performed at baseline and 10 minutes after the procedure to assess TIMI blood flow. Baseline angiography revealed normal TIMI 3 flow in all arteries. A successful angiographic endpoint of TIMI 0 or TIMI 1 blood flow was achieved in only 6 or 46% of 13 rabbits with initial use of the protocol, but was successful in 25 or 100% of a consecutive series of rabbits after the initial or repeat use of the protocol. Importantly, histologic analysis of thrombus revealed a mixture of platelets, erythrocytes, and fibrin. The mean injury index of the internal elastic lamina (IEL) was 40.7 +/- 35.16%. No correlation was found between TIMI flow change and intact IEL (R = -0.068, p > 0.5). Total procedure time was about 1 hour. Conclusion: This simple and reproducible animal model of arterial occlusion provided a mixed thrombus that is comparable to human thrombus and thus may be useful to assess thrombolytic agents or new coronary interventional devices.

Journal Article↗
PubMed1996

Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas.

To evaluate the possibility of preoperatively obtaining an index of aggressiveness for intracranial meningiomas, we prospectively studied 22 patients with computed tomographic or magnetic resonance imaging evidence of meningeal tumour, using single-photon emission tomography (SPET) of the brain and thallium-201 (201Tl). On a brain-dedicated SPET scanner, a rapid acquisition protocol with early, short scans was started simultaneously with the intravenous administration of 111 MBq 201Tl, covering the initial intratumoral distribution of the tracer. Twenty minutes post injection, a delayed SPET scan was also obtained. On the reconstructed and attenuation-corrected images we calculated the 201Tl concentration in tumour and normal contralateral brain tissue, and compared intratumoral tracer concentration in the initial and the final part of the rapid acquisition protocol. Benign and malignant meningiomas were classified as such based on histological examination. In malignant lesions, the ratio of the 201Tl concentration at 2-4 min post injection to that at 14-16 min was found to be significantly higher than in non-aggressive neoplasms (mean+/-1 SD: 1.14+/-0.31 and 0.56+/-0.13, respectively, P <0.01). Conversely, in the delayed scan, most lesions showed high tracer concentration, and the two groups could not be distinguished. In addition, three recurrent meningiomas displayed the same imaging behaviour as the malignant group, i.e. had similar 201Tl concentration values at 2-4 and at 14-16 min. Our findings suggest that the comparative assessment of intratumoral 201Tl concentration at 2-4 and at 14-16 min post injection could provide a fast, simple method to differentiate preoperatively intracranial meningiomas with different biological behaviour.

Female↗
PubMed1996

Histamine H2-receptor antagonists stimulate proliferation but not migration of human gastric mucosal cells in vitro.

Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to test the hypothesis that the H2 blockers roxatidine and ranitidine might stimulate migration and proliferation of gastric mucous cells derived from a human well-differentiated gastric adenocarcinoma cell line (MKN 28 cells) in vitro, in conditions independent of systemic factors and of acid inhibition. Confluent monolayers of MKN 28 cells were wounded with a razor blade and were then incubated with roxatidine or ranitidine. The number of cells migrating to the damaged area was determined 24 hr later. Cell proliferation was assessed by means of [3H] thymidine uptake and cell counts after incubation with roxatidine or ranitidine. Neither H2 antagonist significantly stimulated cell migration. On the other hand, cell proliferation was dose-dependently and significantly enhanced by incubation with roxatidine and ranitidine. Exogenous administration of TGF-alpha significantly stimulated MKN 28 cell division. However, incubation with roxatidine or ranitidine did not increase the steady-state mRNA expression of TGF-alpha or EGFR as assessed by northern blot analysis. Based on these in vitro findings, we postulate that the ulcer healing effect of these H2 antagonists in vivo might be due in part to stimulation of gastric mucosal cell proliferation.

Adenocarcinoma↗
PubMed1996

Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats.

BACKGROUND & AIMS: The mechanism by which gastric mucosa becomes more resistant to damage by repeated aspirin administration is not known. Transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) prevent drug-induced gastric injury. The aim of this study was to determine whether gastroduodenal tissue levels of TGF-alpha and EGF protein were altered during adaptation to aspirin-induced injury in monkeys and rats in vivo. METHODS: Animals were given aspirin daily for up to 28 days. Gross mucosal injury was assessed by computerized image analysis in rats and by endoscopy in monkeys. Mucosal concentrations of TGF-alpha and EGF were quantitated by radioimmunoassays from endoscopic biopsy samples in monkeys and from scraped mucosa in rats. RESULTS: Long-term administration of aspirin caused a significant increase in gastric and duodenal tissue levels of TGF-alpha in monkeys and rats; the increased levels of TGF-alpha significantly correlated with the decrease in aspirin-induced injury. No change in the gastroduodenal tissue levels of EGF was observed. Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats. CONCLUSIONS: Adaptation of the gastric mucosa to the damaging effect of aspirin is associated with a significant and specific increase in TGF-alpha protein in the gastroduodenum.

Adaptation, Physiological↗
PubMed1996

Effect of Helicobacter pylori on gastric epithelial cell migration and proliferation in vitro: role of VacA and CagA.

Helicobacter pylori infection is associated with inflammation of the gastric mucosa and with gastric mucosal damage. In this study, we sought to test the hypothesis that two H. pylori virulence factors (VacA and CagA) impair gastric epithelial cell migration and proliferation, the main processes involved in gastric mucosal healing in vivo. Human gastric epithelial cells (MKN 28) were incubated with undialyzed or dialyzed broth culture filtrates from wild-type H. pylori strains or isogenic mutants defective in production of VacA, CagA, or both products. We found that (i) VacA specifically inhibited cell proliferation without affecting cell migration, (ii) CagA exerted no effect on either cell migration or proliferation, and (iii) undialyzed H. pylori broth culture filtrates inhibited both cell migration and proliferation through a VacA- and CagA-independent mechanism. These findings demonstrate that, in addition to damaging the gastric mucosa, H. pylori products may also impair physiological processes required for mucosal repair.

Antigens, Bacterial↗
PubMed1996

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

Acetylcholine↗
PubMed1996

Significance of ammonia in the genesis of gastric epithelial lesions induced by Helicobacter pylori: an in vitro study with different bacterial strains and urea concentrations.

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain. The effect of VacA and ammonia was evaluated with and without addition of 10 mM urea, a physiological concentration for the human stomach, and with and without addition of 0.5 mg/ml acetohydroxamic and (AHA), an urease inhibitor. Our data show that: (1) both urease-positive H. pylori strains caused cell vacuolation in the absence of urea, the VacA-positive strain being approximatively twice as potent as the VacA-negative strain; (2) addition of urea to the culture medium caused an approximatively 3-fold increase in the vacuolating activity of both urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert any vacuolating effect, either in the presence or in the absence of urea; (4) the ratio between cell vacuolation induced by VacA-positive and VacA-negative strains was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and about 6 in the presence of AHA, either with or without urea added. The increment of vacuolation is likely due to an interaction between AHA and VacA. In conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when physiological levels of urea are present in the incubation medium. This finding suggests that all urease-positive H. pylori strains, both with and without VacA expression, should be considered as potentially cytotoxic for the human gastric mucosa, although VacA enhances the severity of cell damage.

Ammonia↗
PubMed1996

[Procollagen type I C-propeptide in kidney transplant recipients].

The excessive production of parathormone may persist or return after renal transplantation, so that latent hyperparathyroidism in time may lead to loss of bone mass and of the new kidney; a precocious diagnosis of this disease represents the best preventive measure. On a group of 50 successfully undergone kidney transplant patients (group A: 38 immunosuppression therapy with corticosteroids, azathioprine and cyclosporine A patients; group B: 12 immunosuppression therapy with azathioprine and ciclosporine A patients) we have evaluated also the most common markers of hyperparathyroidism, C-propeptide of procollagen of type I (PICP), that is a product of procollagen degradation and it represents in the serum a direct measure of osteoblastic bone activity. Our results showed alkaline phosphate, osteocalcin and PICP increase, which are index of osteoblastic activity and urinary collagen cross-links pyridinoline and deoxypyridinoline increase which are index of bone osteoclastic activity. The survey revealed a linear significant correlation only between PICP and pyridinoline and cross link deoxypyridinoline (p < 0.05). In this group of patients the only PICP could not have a diagnostic meaning. Owing to the particularly bone metabolism of our patients, that probably feel the effects of hyperparathyroidism of the pre-transplant period, PICP turns out insufficient to study the persistent or returned hyperparathyroidism.

Adult↗