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Biomedical subjects

M Marini

Publications and source records attributed to M Marini.

At least 91 records · Page 5Linked to original sources
PubMed1997

The role of CD8+ Th2 lymphocytes in the development of smoking-related lung damage.

There is increasing evidence for the existence of different subsets of CD8+ T lymphocytes in humans, according to their cytokine secretion profile. Resistance or susceptibility to infections and the outcome of some inflammatory processes may depend on the lymphokine profile which predominates. We show one consequence of the switching of a host CD8+ T cell response from the Th1 effector function to the Th2 pattern in relation to the exposure to a common toxicant and its pathogenetic implications. Chronic obstructive bronchitis is a pulmonary disease characterized by airway inflammation with predominance of CD8+ T lymphocytes, mucus hypersecretion, repeated airway infections, and decline in lung function. Though smoking-related, it affects only a portion of smokers. The results of this study, comparing the functional characteristics of CD8+ T cell clones from smokers with the disease, unaffected smokers and healthy individuals, indicate that the smokers who have a predominance of CD8+ T lymphocytes of the Th2 phenotype may be predisposed to develop more severe smoking-induced lung damage, with chronic airway inflammation, repeated infections and persistent airflow obstruction.

Adult↗
PubMed1997

Eotaxin expression and eosinophilic inflammation in asthma.

Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils in the bronchial mucosa, and the mechanisms that cause the selective recruitment of these cells are areas of active investigation. In this study, we found increased expression of the eosinophil chemoattractant eotaxin in bronchial mucosa of asthmatic patients. The increase in number of cells expressing eotaxin mRNA correlated with the number of eosinophils in the bronchial tissue and with two major clinical and functional indices of disease severity, suggesting that eotaxin is involved in the recruitment of eosinophils and in eosinophil-induced tissue damage in asthma. Cell sources of eotaxin were bronchial epithelial cells, T lymphocytes, macrophages and eosinophils themselves. The use of drugs that interfere with eotaxin synthesis and function may represent a more specific approach in asthma treatment.

Asthma↗
PubMed1997

The allergen Der p1 induces NF-kappaB activation through interference with IkappaB alpha function in asthmatic bronchial epithelial cells.

Asthma is an inflammatory disease of the airways due to an interaction between genetic and environmental factors, and allergy represents the most important predisposing trait. Here, we investigated why and how the allergen most often implicated in the pathogenesis of asthma and other allergic diseases causes the expression of the genes for proinflammatory cytokines in airway epithelium. We found that Der p1 promotes activation of transcriptional factor NF-kappaB by interference with the function of its cytoplasmic inhibitor IkappaB alpha. This is the first report on the effect of an allergen on transcriptional factors. Our results improve the understanding of the mechanisms involved in allergic diseases and suggest potential therapeutic utility of NF-kappaB blockers.

Adult↗
PubMed1997

Ultrasound transmission velocity of the proximal phalanxes of the non-dominant hand in the study of osteoporosis.

The aim of our study was to evaluate a quantitative ultrasound technique for measuring bone tissue at the proximal phalanxes of the non-dominant hand. We correlated the mean value of the amplitude-dependent speed of sound (AD-SoS) measured at the distal metaphysis of the last four proximal phalanxes with age, months since menopause and bone mineral density (BMD) of the lumbar spine in 264 women. We further assessed the ability of the AD-SoS to discriminate between normal and osteoporotic subjects with documented vertebral fractures. We found a positive correlation between the AD-SoS and the lumbar spine BMD, whereas the AD-SoS negatively correlated with age and months since menopause. The AD-SoS showed a higher correlation with age changes and months since menopause than BMD. The AD-SoS was significantly higher in healthy females than in osteoporotic ones (p < 0.001). Multiple logistic regression analysis showed for age-adjusted values that AD-SoS decrease is significantly associated to the presence of fracture. Our results suggest that AD-SoS is valuable in assessing age and menopause related bone loss and is useful for diagnosing osteoporosis.

Absorptiometry, Photon↗
PubMed1997

Interindividual variability of enkephalin-degrading enzymes in human plasma.

The interindividual variability of the hydrolysis of leucine enkephalin, and of the formation of its hydrolysis by-products has been studied in human plasma. In agreement with known data, the data obtained indicate that Leu-enkephalin is degraded by several enzymes, belonging to three classes: aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases. The relative ratio of the substrate degraded by each enzyme class-as well as the expression of the single enzyme species within each class-appears to be individually determined. Interindividual variability observed seems controlled by two main factors: the pattern of enkephalin-degrading enzymes and, more notably, the low molecular weight plasma inhibitors. Both these factors appear to be partially specific of each donor. Possibly because of the composition of these factors, the hydrolysis pattern of the substrate is characteristic of each donor, and constant in blood obtained from successive drawings, at least within a relatively short period of time.

Adult↗
PubMed1997

Endothelin-1 induces bronchial myofibroblast differentiation.

Endothelin-1 may contribute to bronchial smooth muscle constriction and airway remodelling in asthma, where bronchial epithelial cells represent an important source of this peptide. We report here that asthmatic bronchial epithelial cells exposed to allergens in vitro induce the differentiation of airway fibroblasts into myofibroblasts, and that they do so through a granulocyte/macrophage colony-stimulating factor-mediated upregulation of endothelin-1 production. By this mechanism bronchial epithelial cells may participate in the genesis of bronchial subepithelial fibrosis, a process which contributes to airway narrowing in asthma.

Actins↗
PubMed1997

Effect of differentiation on the leucine enkephalin-degrading soluble enzymes released by the K562(S) cell line.

Leu-enkephalin hydrolysis kinetics were measured in the presence of soluble supernatants obtained from cultures of the K562(S) leukaemic cell line. Under these conditions, the substrate is degraded with formation of two distinct patterns of the hydrolysis by-products: in one pattern, similar amounts of Tyr and Tyr-Gly are formed; in the other, only Tyr-Gly can be measured. Kinetic data suggest that soluble proteolyses are released by these cells, and that either dipeptidylaminopeptidases alone, or both aminopeptidases and dipeptidylaminopeptidases are involved in substrate hydrolysis. This alternation of hydrolysis patterns appears consistent with existing data on the heterogeneity of K562 cells. In contrast with these results, chromatographic separation of the soluble enzymes indicates the release of all three classes of proteolyses known to hydrolyze enkephalins: aminopeptidases, dipeptidylaminopeptidases and dipeptidylcarboxypeptidases. In cells induced to differentiate by treatment with butyric acid, substrate hydrolysis is increased, and the pattern of the enzymes released is modified. In these cells, variations in both total proteolytic activity, and ratio between the three enzyme classes mentioned above are only minor, while the ratio between the different enzyme species within each class is greatly modified. Data obtained suggest that the expression of soluble enzymes is modified by differentiation. These data may also be interpreted as stressing the role of competition in controlling substrate hydrolysis by the multiple enzymes co-released by K562(S) cells.

Cell Differentiation↗
PubMed1997

Intraluminal leiomyosarcoma of the superior vena cava: a cause of superior vena cava syndrome.

Intraluminal tumours of the superior vena cavae (SVC) are extremely rare. We report a 75 year old male who suffered an acute syndrome of the SVC. The CT scan and phlebogram showed thrombosis of the right internal jugular, subclavian and innominate veins and the SVC. Fibrinolysis was started with 250.000 U, of urokinase and maintained for 72 hrs (75.000 U/h). A control phlebogram showed a great filling defect of the SVC which was enhanced in a postcontrast CT scan. An intraluminal leiomyosarcoma was diagnosed. A long and narrow pedunculated tumour was resected through a medial sternotomy and the SVC closed by direct suture without either a patch or a graft. The histopatholoy study confirmed the diagnosis. We cosider this protocol to be the procedure of choice for the diagnosis and treatment of the SVC syndrome since it can demonstrate any intraluminal or extramural aetiology.

Acute Disease↗
PubMed1997

A hemodynamic approach to clinical results in the TRAM flap after selective delay.

The delay phenomenon in the transverse rectus abdominis myocutaneous (TRAM) flap was studied by means of a laser-Doppler flowmeter and an echo color-flow Doppler device. Twenty-eight patients who underwent breast reconstruction with a TRAM flap in our hospitals were analyzed. Eighteen of them underwent selective delay 1 month before the major surgical procedure, and of them, 15 completed the reconstructive procedure. Ten patients were used as a control group and underwent TRAM flap breast reconstruction without selective delay. Cutaneous blood flow in the TRAM flaps was measured in 20 patients with a laser-Doppler flowmeter, and measurements were taken before, during, and after the surgical procedure, following a standardized protocol, as in Tuominen's original scheme. Variations in the cutaneous blood flow in the standard TRAM flap (10 patients) confirmed data obtained from the literature, i.e., an increase when elevating the cutaneous and subcutaneous parts of the flap and a decrease when ligating the deep inferior and superficial epigastric vessels. Compared with the standard TRAM flap, blood flow in the delayed flaps (10 patients) seemed to be more stable, without falling under the baseline. When elevating the cutaneous and subcutaneous parts of the flap (phase 3), blood flow values reached 120.2 percent (SEM 46.8 percent) on the random side and 131.6 percent (p < 0.009, SEM 9.58 percent, standard deviation 30.3 percent) on the axial side. During phase 4 (cutting the rectus muscles), blood flow values reached 115.0 percent (SEM 40.5 percent) on the random side and 102.8 percent (SEM 1.2 percent, standard deviation 3.8 percent, p < 0.049) on the axial side. In order to obtain further hemodynamic data, 10 patients who underwent selective vascular delay 1 month prior to breast reconstruction with a delayed TRAM flap in our hospitals were then studied by means of an echo color-flow Doppler device. Two of these patients also had been studied with the laser-Doppler flowmeter. Superior epigastric artery diameter (in millimeters) and resistivity (expressed as Pourcelot's index) were measured before and after selective delay of the deep and superficial inferior epigastric vessels, following a standardized protocol. Measurements were taken with 7.5- and 10-MHz linear probes at a point located after the origin of the costomarginal artery. In every patient an increase in the superior epigastric artery diameter and a decrease in the resistivity index were observed, and this was statistically significant. In the nonirradiated patients, the increase in the average diameter of the superior epigastric artery was 98.1 percent, and the average resistivity index decrease was 14.1 percent. In the irradiated patients, the increase in the average diameter of the superior epigastric artery was 35.5 percent, and the average resistivity index decrease was 29.8 percent. In conclusion, laser-Doppler flowmeter evaluations show that cutaneous blood flow in the delayed flap is more constant and undergoes fewer variations than that in the standard TRAM flap. In addition, echo color-flow Doppler indicates that the basis for the increase in the vascular territory of the superior epigastric artery caused by the delay maneuver is an increase in the superior epigastric artery diameter, always accompanied by a decrease in the resistivity index. Two different mechanisms seem to us to be related to these modifications in the blood circulation. In the nonirradiated patients, superior epigastric artery dilation prevails, whereas in the irradiated patients, a decrease in the resistivity index is the dominant mechanism of compensation. These hemodynamic findings well support the decrease in flap necrosis reported in our series (standard TRAM: 30 percent; delayed TRAM: 7.1 percent).

Adult↗
PubMed1996

Apoptosis of human lymphocytes in the absence or presence of internucleosomal DNA cleavage.

Treatment of human peripheral blood lymphocytes with heat shock, ionising radiation, bleomycin, etoposide, or hydrogen peroxide induced morphological evidence of apoptosis that was associated with the appearance of 50 Kb double-stranded DNA fragments. The apoptotic response elicited by the above agents, with the exception of hydrogen peroxide, was also paralleled by the formation of internucleosomal DNA fragments. This effect of hydrogen peroxide, however, appeared to be confined to human lymphocytes, since apoptosis induced by the oxidant in U937 cells was in fact associated with DNA laddering.

Apoptosis↗
PubMed1996

Endothelin-1 induces increased fibronectin expression in human bronchial epithelial cells.

Endothelin-1 may be involved in the pathogenesis of asthma by causing bronchial smooth muscle constriction and airway remodelling. Bronchial epithelial cells represent an important source of endothelin-1 in this disease, and increased release of epithelial cell-derived endothelin-1 may contribute to the genesis of subepithelial fibrosis by promoting fibroblast proliferation and collagen production. In this study, we demonstrate that endothelin-1 upregulates fibronectin gene expression and fibronectin release in bronchial epithelial cells via an ETA receptor. Fibronectin is an important component of the extracellular matrix which is deposited in excess in the subepithelial area of asthmatic bronchial mucosa, and it represents a potent chemotactic factor for fibroblasts. Thus, endothelin-1 may induce subepithelial fibrosis both directly and by the autocrine mechanism reported here.

Blotting, Northern↗
PubMed1996

Comparison of ultrasound transmission velocity with computed metacarpal radiogrammetry and dual-photon absorptiometry.

The aim of our study was to evaluate the validity of a quantitative US technique for measuring the bone density of the proximal phalanges of the nondominant hand compared with computed metacarpal radiogrammetry and dual-photon absorptiometry (DPA) of the lumbar spine. Mean US bone velocity (UBV) correlated with mean metacarpal cortical index (MCI), with mean metacarpal bone density (MBD) and with bone mineral density (BMD) of the lumbar spine, whereas it was correlated negatively with age and menopause duration. The average UBV was significantly higher in premenopausal women than in postmenopausal women, and higher in normal lumbar DPA patients than in reduced lumbar DPA patients. We conclude that the US evaluation of the nondominant hand proximal phalanges may be a new alternative way for measuring bone mass in screening of osteoporosis.

Absorptiometry, Photon↗
PubMed1996

Role of enzymes and inhibitors in leu-enkephalin metabolism in rabbit and human plasma.

The hydrolysis of leucine enkephalin by the proteolytic enzymes present in human and rabbit plasma has been studied by kinetic and chromatographic techniques. Data obtained indicate the existence of noticeable intraspecific differences in the kinetics of leu-enkephalin degradation, and of formation of its hydrolysis by-products. The separation of the enzymes active on the substrate and of the inhibitors active on these enzymes evidences the existence of a species specific distribution of both groups of substances. Yet, the dissimilar kinetics of the substrate hydrolysis and of formation of its hydrolysis by-products appear to arise more from diversities in the competition between the enzymes present in plasma and in the role of inhibitors than from the differences in the enkephalin-degrading enzymes. It is suggested that differences observed may be related to the existence of species specific populations of the information-carrying plasma peptides.

Animals↗
PubMed1996

Positive and negative immunomodulation by opioid peptides.

The data that follow review part of the existing evidence concerning the neuroimmune functions mediated by opioid peptides, with particular regard to dual immunomodulatory effects. Limited references to substances other than opioid peptides are included, mainly to emphasize the possible similarities in the mediation of neuroimmune interactions by different informational substances, while the interactions directed from the immune to the nervous system have deliberately been omitted.

Adjuvants, Immunologic↗
PubMed1996

Specificity of proteolysis inhibitors in rabbit plasma.

Hydrolysis and inhibition of hydrolysis of leucine enkephalin in Oryctolagus plasma were studied by kinetics and chromatographic techniques. By data obtained, in this species, enkephalins are degraded by the same enzymes active in other mammals: aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases. At variance with data obtained in other species, where enkephalins are hydrolyzed mostly by aminopeptidases, in Oryctolagus Leu-enkephalin hydrolysis is mainly due to dipeptidylcarboxypeptidases, whereas aminopeptidases contribution is the minimum of all three enzyme groups. Comparative analyses performed in the presence and in the absence of plasma inhibitors indicate that the ability of these substances to reduce substratum hydrolysis is very limited. On the contrary, the specific hydrolysis pattern evidenced appears to originate primarily from selective inhibition of the three groups of enzymes. Results obtained appear consistent with a role of plasma inhibitors in tuning hydrolysis to specific substrata, without appreciably modifying the amount of the substratum degraded.

Aminopeptidases↗
PubMed1996

Pathways of adenine nucleotide metabolism: degradation and resynthesis of IMP in ageing chicken heart.

The activities of enzymes involved in adenine nucleotide metabolism and the concentration of their metabolic products were studied in the hearts of chickens from birth to advanced age. In particular, in order to investigate the main mechanisms which contribute to ensure availability of adenine nucleotides during ageing of the heart, IMP concentration and the activities of enzymes involved in its turnover were studied. In newborn animals, AMP degradation, though limited in amount, was found to lead to the final products of purine metabolism. In fact, the activity of hypoxanthine phosphoribosyl-transferase (HPRT)-the salvage enzyme of IMP-was not detected. On the contrary, in young chickens, the low concentration of final products of purine metabolism, together with a remarkable activity of HPRT and a high concentration of IMP, indicates that metabolic flux converges on the salvage pathway. In adult chickens, an increase of purine catabolism was observed. This, together with an optimal concentration of endogenous adenine nucleotides, is indicative of a particularly high AMP metabolism. Finally, in chickens of advanced age, a reduced purine catabolism appeared to take place, thus contributing to the maintenance of the adenine nucleotide pool. In ageing heart, a major role of IMP turnover probably consists in the preservation of adenine nucleotides and in the recovery of high-energy phosphates.

Adenine Nucleotides↗
PubMed1996

Oxygen radicals induce stress proteins and tolerance to oxidative stress in human lymphocytes.

A set of eight proteins is induced in peripheral blood lymphocytes from normal donors by exposure to hydrogen peroxide or to xanthine oxidase plus hypoxanthine. Four of them (hsp90, hsp72 and proteins 65 and 50 kDa) are also expressed after heat shock, together with proteins 110, 100 and 38 kDa. Among proteins induced after oxidative stress is a 32 kDa protein-probably corresponding to heme oxygenase-1 (HO-1)- and a 27 kDa protein, both known to be induced by reactive oxygen species. Although ionizing radiation is known to generate a number of pro-oxidant intermediates, using our one-dimensional electrophoresis system we can detect no differences in the proteins synthesized after exposure to gamma-ray doses between 5 and 20 Gy as compared with control cells. Pre-exposure to a mild hyperthermia or to moderate oxidative stress significantly increases survival of lymphocytes challenged with high doses of reactive oxygen species, in conditions compatible with a protective rôle exerted by stress proteins. The increase in survival is accompanied by the maintenance of the proliferative capacity of the cells. The physiological rôle played by stress proteins in prevention and repair of damage and the relationships between stress protein induction, oxidative state, proliferation and mode of cell death are discussed.

Adult↗