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Biomedical subjects

M Nardi

Publications and source records attributed to M Nardi.

At least 127 records · Page 7Linked to original sources
PubMed1993

Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus-type 1-immune thrombocytopenic purpura patients.

Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti-idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet-monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/- 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1-ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype-matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cloning and sequencing of pepC, a cysteine aminopeptidase gene from Lactococcus lactis subsp. cremoris AM2.

A gene coding for an aminopeptidase (PepC) from Lactococcus lactis subsp. cremoris AM2 was cloned by complementation of an Escherichia coli mutant lacking aminopeptidase activity. The nucleotide sequence was determined. A portion of the predicted amino acid sequence of PepC (436 amino acids) showed strong homology to the active site of cysteine proteases. No signal sequence was found, indicating an intracellular location of the enzyme.

Amino Acid Sequence↗
PubMed1993

[Stress and ischemic heart disease].

The role of mental stress in ischemic heart disease is two-fold: as a risk factor of coronary artery disease and as a trigger of acute ischemic attacks in patients with established coronary atherosclerosis. The role of stress as a risk factor is still controversial. Data regarding the relationship between occupational factors and development of coronary atherosclerosis have not been confirmed. A type personality, above all when anger and hostility traits are present, seems to be a predisposing factor for the development of coronary artery disease. These data however, were not confirmed in study groups including patients with a higher prevalence of other, more important, risk factors. Stress can have an important role as a trigger of acute ischemic attacks. This is indirectly shown by the circadian distribution of the main manifestations of ischemic heart disease (sudden death, myocardial infarct, ST segment depression). In fact, their incidence is significantly higher in the morning hours, after awakening, when mental stress is higher. In the laboratory setting, mental stress can induce myocardial ischemia in a variable percentage of patients (0 to 80%). Prevalence of mental stress-induced myocardial ischemia varies depending on the stressor used, the patients group and, above all, the diagnostic tool. Ischemic episodes induced by mental stress, in fact, are generally silent and less severe and extensive than those elicited by exercise stress testing. It is therefore often necessary to use methods, such as myocardial scintigraphy, with higher sensitivity for the detection of myocardial ischemia in comparison with ECG. Patients with mental stress-induced myocardial ischemia tend to present higher scores on measures of aggressivity, anger and hostility. These psychological features are related to a hightened cardiovascular reactivity with a brisk and greater increase in heart rate and blood pressure after exposure to stress. It would be therefore useful to identify patients with such a behaviour by psychological assessment and/or analysis of sympatho-vagal balance by analysis of heart rate variability. The mechanism by which mental stress can induce myocardial ischemia is represented by an increase in myocardial oxygen demand, through the increased heart rate and blood pressure, probably associated with an increase in coronary vascular resistance. This last phenomenon is likely caused by small coronary vessel constriction mediated by alpha-adrenergic activation and by a reduced EDRF release by the damaged endothelium.

Acute Disease↗
PubMed1993

[The acute and 24-hour modifications to the atrial natriuretic factor in patients who have undergone mitral valvuloplasty. The hemodynamic and echocardiographic correlations].

BACKGROUND: The recent introduction of percutaneous transvenous mitral valvuloplasty (PTMV) for the treatment of mitral stenosis (MS) has provided a unique human model for the study of short-term changes in ANF secretion before and after a reduction in left atrial pressure. This study was designed to investigate the effect of a short-term reduction in left atrial pressure and volume, as determined by echocardiographic study, on ANF and other neurohumoral factor plasma levels (renin and aldosterone). MATERIALS AND METHODS: 10 patients in III FC NYHA, with normal sinus rhythm and MS underwent PTMV. Hemodynamic parameters were measured immediately before and after (20-30 minutes) PTMV. Plasma levels of ANF, aldosterone and plasma renin activity (PRA) were obtained before (24 h) and after (2 h and 24 h) valvuloplasty; echocardiographic left atrial size before (24 h) and 24 h after PTMV. RESULTS: Immediately after PTMV mean left atrial (LA) pressure decreased from 22.3 +/- 6.8 mmHg to 10.0 +/- 2.4 mmHg (p < 0.01); mitral valve area (MVA) increased from 0.99 +/- 0.28 cm2 to 2.17 +/- 0.26 cm2 (p < 0.01). 24 hours after PTMV on echocardiography, LA systolic volume decreased from 59.5 +/- 16.9 cm3 to 42.3 +/- 8.3 cm3 (p < 0.01), LA diastolic volume from 82.6 +/- 15.8 cm3 to 66.5 +/- 12.6 cm3 (p < 0.01), and LA diameter from 48.1 +/- 7.5 mm to 39.2 +/- 4.4 mm (p < 0.01). ANF plasma levels before PTMV were 64.0 +/- 36.9 fmol/ml; 2 and 24 hours after PTMV they fell to 34.2 +/- 21.6 fmol/ml (p < 0.01) and to 20.3 +/- 21.0 fmol/ml (p < 0.01), respectively. PRA values were 15.7 +/- 13.2 ng/ml/h before PTMV; 2 and 24 hours after PTMV they increased to 17.5 +/- 23.2 ng/ml/h (NS) and to 22.3 +/- 16.8 ng/ml/h (p < 0.01). The aldosterone plasma levels were 43.2 +/- 27.9 ng/dl before PTMV and 47.3 +/- 35.8 ng/dl (NS) and 45.3 +/- 28.0 ng/dl (NS) 2 and 24 hours after PTMV. CONCLUSIONS: These results indicate that LA "de-stretching" due to the MVA increase and LA pressure decrease, leads to an abrupt reduction of ANF secretion. According to other studies, PRA increases immediately after PTMV, with a further increase 24 hours after PTMV.

Adult↗
PubMed1992

Functional activity of protein C in newborn infants. A report of a study and a review of the literature.

Protein C is lower in newborn infants than in adults. There are conflicting reports regarding functional activity and the presence of des-gamma carboxylated species in the newborn. We have compared protein C activity and antigenic level in newborn infants and found the activity: antigen ratio to be lower than in adults (0.69 versus 1.0). We discuss this finding in relation to the previously published reports.

Adult↗
PubMed1992

Development of a monoclonal antibody capable of differentiating platelet PLA1/PLA1, PLA1/PLA2 and PLA2/PLA2 genotypes.

A monoclonal antibody, LK-4, has been developed which distinguishes platelet PLA1/PLA1, PLA1/PLA2 and PLA2/PLA2 genotypes on platelet glycoprotein GPIIIa of Triton-solubilized platelet extracts. An ELISA assay has been developed which traps GPIIIa with Concanavalin A, enriching the platelet extract for the PLA antigens. A second monoclonal antibody, DEK-10, which reacts equally with GPIIIa of PLA1/PLA1 and PLA2/PLA2 platelet extracts is employed as an internal standard to correct for individual differences in GPIIIa content, GPIIIa extracted by Triton X-100 and GPIIIa trapped with Concanavalin A. This ELISA assay clearly differentiated 11 different PLA1/PLA1 subjects from eight PLA2/PLA2 women with a history of neonatal alloimmune thrombocytopenia as well as six unrelated obligate heterozygotes and should be useful in evaluating the PLA genotype of pregnant women and their families.

Alleles↗
PubMed1992

Autoimmune anti-HIV-1gp120 antibody with antiidiotype-like activity in sera and immune complexes of HIV-1-related immunologic thrombocytopenia.

Autoimmune antiidiotype-like antibody (Ab2) directed against anti-HIV-1gp120 (Ab1) was found in high titer in the sera of 10 consecutive homosexual and 11 narcotic addict HIV-1-related immunologic thrombocytopenia (HIV-1-ITP) patients, was barely detectable in 10 nonthrombocytopenic HIV-1 sero-positive individuals, and was not detectable in 5 normal subjects by use of a solid-phase RIA. Reactivity of autologous Ab2 for Ab1 was 4-120-fold greater than Ab2 for homologous Ab1. Affinity-purified Ab2 did not block the binding of affinity-purified Ab1 to its HIV-1gp120 epitopes on immunoblot, indicating the absence of "internal image" antiidiotype. Both Ab1 and Ab2 are precipitable from sera with polyethylene glycol (PEG) and present in a macromolecular complex that is excluded by gel filtration on G200 and contains IgG, IgM, C3, and the anti-F(ab')2 antiidiotype-like complex. PEG-precipitable complexes bind to platelets in a saturation-dependent manner. Neither affinity-purified Ab1 nor Ab2 binds to platelets. However, the combination of Ab1 and Ab2 (preincubated for 2 h at 22 degrees C) binds to platelets in a saturation-dependent manner at an optimum ratio range of 10-20:1. Ab2 reactivity correlates with serum PEG-precipitable immune complex level (r = 0.91; P less than 0.001) and with thrombocytopenia (r = 0.89; P less than 0.001). We suggest that the anti-HIV-1gp120 antiidiotype-like complex contributes to the markedly elevated platelet Ig and C3 level of HIV-1-ITP patients and propose that this may contribute to their thrombocytopenia.

Acquired Immunodeficiency Syndrome↗
PubMed1992

CT arthrography and arthroscopy in chronic glenohumeral joint instability.

The authors evaluate the value of CT arthrography in glenohumeral joint instability. A study was conducted on a group of 16 patients with recurrent dislocation of the shoulder. All patients underwent CT arthrography and arthroscopy. The diagnostic accuracy of CT arthrography was rated for different types of lesions on the basis of arthroscopic confirmation of its findings. Our results, which include a statistical analysis, showed a diagnostic accuracy of 97.3% in Bankart lesions and 100% in Hill-Sachs lesions and loose bodies. Dilation of the subscapular bursa and injury of the glenoid labrum-IGHL complex were often identified, while chondritis and synovitis were less frequently diagnosed. The authors therefore conclude that CT arthrography may be considered an extremely reliable diagnostic test for obtaining an overall picture of injuries due to instability. Arthroscopy, on the other hand, should be reserved for cases in which surgery may be performed in the same stage as diagnosis.

Adult↗
PubMed1992

Thrombocytopenia in children infected with human immunodeficiency virus: long-term follow-up and therapeutic considerations.

Among 180 children infected with human immunodeficiency virus (HIV-1), 14 (8%) developed thrombocytopenia during the course of the disease and have been followed for an average period of 18.8 months. Eight of 14 patients had clinical signs of bleeding. Increased levels of anti-platelet IgG antibodies were detected in 86% of patients tested and did not correlate with severity of disease. Eight patients were treated initially with intravenous immunoglobulins (IVIG) and responded with a transient increase in the platelet count of at least 30 x 10(9)/L. Sustained remission could not be achieved in the patients treated with IVIG alone. Corticosteroids were used in 6 patients who became refractory to IVIG and resulted in sustained remission in only one patient. Spontaneous remission of thrombocytopenia occurred in one patient. Ten patients were treated with zidovudine (ZVD) for a period of 3-20 months. Sustained improvement in the platelet counts occurred in only three of the children treated with ZVD.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A 13-mer peptide straddling the leucine33/proline33 polymorphism in glycoprotein IIIa does not define the PLA1 epitope.

We confirm the recent report (J Clin Invest 83:1778, 1989) of a polymorphism at amino acid 33 of platelet GPIIIa associated with the PLA1/PLA2 phenotype by using the polymerase chain reaction on cDNA derived from platelet RNA, using the base-pair primers 105-129 and 452-428. Platelet cDNA from three PLA2-homozygous individuals, when digested with Nci I, gave two bands of 256 bp and 91 bp, whereas eight PLA1 cDNAs gave a single band of 347 bp. Two 13-mer amino acid peptides straddling the amino acid polymorphism: SDEALP (L/P) GSPRCD were synthesized for epitope studies. Two mouse polyclonal antibodies were raised: one against the PLA1-associated peptide, the other against the PLA2 peptide. Both antibodies react with either peptide, as well as with both PLA1 and PLA2 platelets. The PLA1 peptide did not block the binding of two different human anti-PLA1 antibodies to the 100-Kd GPIIIa band on immunoblot of platelet extracts; neither did it block the binding of the same antibodies to PLA1-platelet extracts in an enzyme-linked immunosorbent assay. Further studies were performed on the PLA1 epitope following subtilisin digestion of purified GPIIIa. A 55-Kd fragment was obtained that retained the PLA1 epitope as well as the first 13 N-terminal amino acids of GPIIIa. Reduction of the 55-Kd fragment resulted in loss of the PLA1 epitope with production of a 67-Kd, 21-Kd, and 10-Kd band on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The 55-Kd band does not react with LK-2, a monoclonal antibody versus GPIIIa that inhibits adenosine diphosphate, collagen, epinephrine, and thrombin-induced aggregation. Thus, the PLA1 epitope is conformation-induced, resides on an N-terminal 55-Kd fragment composed of two or more peptides held together by -SH bonds, and is not required for platelet aggregation.

Amino Acid Sequence↗
PubMed1991

Micronuclei in lymphocytes of young patients under antileukemic therapy.

The micronucleus test in peripheral blood lymphocytes was employed in the cytogenetic monitoring of children with acute lymphocytic leukemia (ALL), who had undergone chemotherapy and radiotherapy. Patients were treated with a variety of drugs, which included vincristine, methotrexate, daunomycin and prednisone; they also underwent cranial irradiation at the end of the first intensive phase of therapy. The first group under study consisted of 15 subjects on therapy, who showed a marked increase in micronucleated lymphocytes (mean: 19.96 +/- 12.96%) as a consequence of treatment compared with the control group (mean: 3.67 +/- 1.55%), while lower average values were obtained from 15 other subjects at the end of treatment (mean: 13.16 +/- 8.44%). A group of 6 patients was monitored during the entire period of therapy, namely at diagnosis, after 3 months of therapy, throughout maintenance therapy and at the end of it. The whole treatment lasted about 2 years. The results revealed a marked increase in basal micronucleus frequency, due to therapy: the micronucleated lymphocyte frequency remained significantly high throughout the treatment for almost all patients. These data clearly suggest the validity of the methodology in pointing out the role played by antileukemic agents in inducing somatic genetic damage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cloning and DNA sequence analysis of an X-prolyl dipeptidyl aminopeptidase gene from Lactococcus lactis subsp. lactis NCDO 763.

Lactococcus lactis subsp. lactis NCDO 763 (also designated ML3) possesses an X-prolyl dipeptidyl aminopeptidase (X-PDAP; EC 3.4.14.5). X-PDAP mutants were selected by an enzymatic plate assay on the basis of their inability to hydrolyze an L-phenylalanyl-L-proline-beta-naphthylamide substrate. A DNA bank from L. lactis subsp. lactis NCDO 763 was constructed in one of these X-PDAP mutants, and one clone in which the original X-PDAP phenotype was restored was detected by the enzymatic plate assay. The X-PDAP gene, designated pepXP, was further subcloned and sequenced. It codes for a protein containing 763 residues. Comparison of the amino-terminal sequence of the X-PDAP enzyme with the amino acid sequence deduced from the pepXP gene indicated that the enzyme is not subjected to posttranslational modification or exported via processing of a signal peptide. The pepXP gene from L. lactis subsp. lactis NCDO 763 in more than 99% homologous to the pepXP gene from L. lactis subsp. cremoris P8-2-47 described elsewhere (B. Mayo, J. Kok, K. Venema, W. Bockelmann, M. Teuber, H. Reinke, and G. Venema, Appl. Environ. Microbiol. 57:38-44, 1991) and is also conserved in other lactococcal strains.

Amino Acid Sequence↗
PubMed1991

Alizapride alone or alizapride-dexamethasone compared with metoclopramide-dexamethasone in patients at high risk of acute emesis after cisplatin. A randomized cross-over study.

Alizapride (ALZ) is a new benzamide derivative with promising antiemetic activity. In the present study, high-dose ALZ (16 mg/kg) alone or in combination with dexamethasone (DXM, 40 mg) was compared to a combination of DXM (40 mg) and metoclopramide (MCP, 4 mg/kg) in a randomized cross-over trial conducted on 21 out-patients at high emetic risk after moderate-dose cisplatin. All but 3 patients completed the planned cross-over trial for a total of 60 evaluable courses. The patients completed a self assessment questionnaire evaluating the severity and duration of both nausea and vomiting, the toxicity, as well as their subjective opinion of the antiemetic trial. At the dose and schedule employed, ALZ alone or in combination with DXM provided not only a significantly lower rate of complete protection against nausea and vomiting (0 and 4.8%) than MCP + DXM (28.6%) but was also less effective in reducing the number of vomiting episodes and the duration of the vomiting. In addition, the MCP - DXM regimen was the most frequently preferred. Except for one case of orthostatic hypotension following ALZ, benzamide-induced toxicity was mild, whereas that related to DXM was negligible. The results of this study suggest that high-dose ALZ gives no advantage compared to MCP in patients at high risk for emesis after moderate-dose cisplatin.

Acute Disease↗
PubMed1990

[Carcinoma of the male breast. Our experience].

A case series of 5 male patients afflicted with breast carcinoma is reported. The Authors describe symptomatology, diagnostic iter, principles of surgical treatment and results. Underlined is the wider surgical demolition in male breast cancer in comparison with females, even if natural history and biological conduct are comparable. This is because in male breast carcinoma the local and remote infiltration is more rapid than female for the less development of breast gland. Finally, indications for radiochemotherapy are comparable to female breast cancer.

Adult↗