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Biomedical subjects

I Ferrari

Publications and source records attributed to I Ferrari.

At least 19 recordsLinked to original sources
PubMed2000

Interactions between red blood cells and a lethal, partly quaternized tertiary polyamine.

Partially quaternized poly[thio-1-(N,N-diethyl-aminomethyl) ethylene]s, Q-P(TDAE)(x) with x indicating the percentage of quaternized subunits, have been proposed as potential carriers for drugs insoluble in water. However these cationic polyelectrolytes form emboli upon intravenous administration. In order to study the mechanism, Q-P(TDAE)(11) was incubated in vitro with red blood cells (RBCs) suspended in various aqueous media such as autologous plasma, autologous serum, albumin dissolved in phosphate buffer, plasma-serum mixtures and Tris buffer. The deformability of the RBC membrane studied by viscometry was not affected by the polycation. Q-P(TDAE)(11)-induced hemagglutination was studied by optical microscopy. It depended on the polymer concentration and on the presence of plasma proteins. As ghosts were formed in some cases, hemolysis was investigated by measuring potassium and hemoglobin released from RBCs. Fibrinogen and serum proteins, except albumin, protected RBCs from hemolysis. Moreover the order of addition of the suspension components modulated dramatically the Q-P(TDAE)(11)-induced hemolysis. Addition of Q-P(TDAE)(11) to whole blood caused hemolysis whereas addition of the polymer to plasma prior to contact with RBCs did not affect the cell integrity. In contrast, addition of the polymer to RBCs suspended in albumin solution caused greater hemolysis than the addition to whole blood, and the contact between Q-P(TDAE)(11) and albumin prior to RBC addition still enhanced cell lysis. Two conclusions can be drawn from these observations: (i) Q-P(TDAE)(11) induces both hemagglutination, probably through electrostatic interaction, and hemolysis, because Q-P(TDAE)(11) disrupted the RBC lipid bilayer; (ii) proteins can decrease or increase the deleterious effects of Q-P(TDAE)(11) on RBCs.

Blood Proteins↗
PubMed1998

Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens.

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.

Amino Acid Sequence↗
PubMed1998

Costello syndrome in two Brazilian children.

The increasing number of children with Costello syndrome described world wide has helped in delineating further the characteristic features of this condition. We report here two children, seen in the Genetic Division of the Brasilia University Hospital, showing the main features of the syndrome: "coarse" face, redundant skin on the feet and hands, hyperextensible hand and finger joints, curly hair, growth and psychomotor retardation, and feeding problems. In addition, one of the patients developed hydrocephalus during the evolution of the disease, making the third published patient with this complication. We discuss the appropriateness of serial brain imaging studies in Costello syndrome in light of the relative frequency of central nervous system malformations.

Brazil↗
PubMed1997

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus.

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.

Amino Acid Sequence↗
PubMed1997

Detection of micronuclei in peripheral erythrocytes of Cyprinus carpio exposed to metallic mercury.

Cyprinus carpio fish (carp), exposed to elemental or metallic mercury (Hg0) at concentrations of 2.0, 20.0, and 200.0 mg per liter of water, were kept in concrete tanks for 159 days. Ten fish were used for each concentration level. Thirteen samples of peripheral blood were collected from each animal through gill puncture, 12 during the first 90 days of the experiment, and the last one at the end of the experiment. The micronucleus test (MNT) was designed to study dose and time yield effects of mercury after indirect exposure in vivo. The results indicated that for a concentration of 2.0 mg Hg0/l, there was no significant increase in frequency of micronuclei (MN), but at higher concentrations (20.0 and 200.0 mg Hg0/l) there was a significant increase in MN frequencies. This effect was higher after 31 days of exposure, followed by slight stabilization and gradual decrease.

Animals↗
PubMed1996

Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease.

IgG fractions of patients were screened for autoantibodies against the beta1- and beta2-adrenoceptors and the M2 acetylcholine receptor by enzyme immunoassays and surface plasmon resonance (SPR) using peptides corresponding to the second extracellular loop of these receptors. A high prevalence of anti-M2 acetylcholine receptor and, in decreasing order, of anti-beta1- and anti-beta2-adrenoceptor autoantibodies was shown. The enzyme immunoassays and the SPR studies on the anti-beta1 adrenoceptor and the M2 acetylcholine receptor autoantibodies were dependent on the ionic strength of the interaction buffer, suggesting the importance of electrostatic interactions in Ab recognition. IgG fractions showed chronotropic effects on neonatal rat cardiomyocytes in vitro. The positive chronotropic effect was enhanced in the presence of 1 microM of atropine, demonstrating a muscarinic stimulation by the IgG fractions in the presence of a beta-adrenergic stimulation, which was blocked by the use of 1 microM of the beta1-selective antagonist bisoprolol. The beta2-selective antagonist ICI 118,551 only partially inhibited the positive chronotropic effect induced by the IgG fractions, confirming the minor functional importance of autoantibodies against the beta2-adrenoceptor. Affinity-purified Abs confirmed that Abs against the beta1-adrenoceptors and the M2 muscarinic receptors exist together with an Ab population recognizing a cross-reactive epitope on both receptors. This epitope could be identified as a polyanionic stretch present in the second extracellular loop of both the beta1-adrenoceptor and the M2 acetylcholine receptor. This stretch corresponds to the previously determined cross-reactive epitope between the P0 ribosomal protein of Trypanosoma cruzi and the beta1-adrenoceptor.

Adrenergic beta-Antagonists↗
PubMed1995

Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

Amino Acid Sequence↗
PubMed1995

Endemic pemphigus foliaceus (fogo selvagem) in native Americans from Brazil.

BACKGROUND: Fogo selvagem (FS) is an autoimmune disease that is endemic in certain regions of Brazil and appears to be precipitated by an environmental factor. OBJECTIVE: Our purpose was to confirm the occurrence and prevalence of FS in a population of Xavante Indians living in an endemic region of central Brazil. METHODS: Clinical, anthropologic, and immunologic studies were carried out in patients and in normal inhabitants of the Pimentel Barbosa Indian Reservation, Mato Grosso, Brazil. RESULTS: FS was identified and confirmed in 10 patients from a patient pool of 295 with various skin diseases. The Xavante settlement has a total population of 746. Anti-desmoglein 1 autoantibodies were detected in all patients with FS and were absent from more than 300 serum samples collected from randomly selected unaffected persons. CONCLUSION: FS is strongly linked to outdoor activities and is largely restricted to immunogenetically predisposed persons. FS appears to have been endemic in certain regions of South America for several centuries.

Adolescent↗
PubMed1994

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Treatment of FIGO stage Ib cervical carcinoma with nodal involvement.

One hundred and eighty one patients with stage Ib cervical cancer underwent hysterectomy with pelvic lymphadenectomy. The overall incidence of lymph node metastases was 20%. Twenty seven (71%) patients with nodal involvement were treated by external radiotherapy (TCT) and 11 (29%) by both chemotherapy and radiotherapy (Lin. Acc.). The overall survival at 5 years was 80%; it was 43% for patients with positive nodes and 89% for patients without metastatic nodal disease. The 3 year survival of patients with positive nodes who underwent radiation therapy by TCT was 58%, while it was 72% for those treated by chemotherapy plus radiotherapy. We observed a recurrence in 23% of the cases, 52% in patients with positive nodes and 15% in those with negative nodes. The association chemo-radiotherapy in patients with metastatic lymph nodes seems to improve the survival and reduce the recurrence rate.

Adenocarcinoma↗
PubMed1993

Lymphocytes isolated from the peritoneal fluid of women with advanced ovarian carcinoma differ significantly from autologous peripheral blood lymphocytes.

The phenotypic and functional analysis of ovarian carcinoma-associated lymphocytes (OCAL), obtained from a group of patients with neoplastic carcinosis, reveals major differences between OCAL and peripheral blood lymphocytes (PBL). Virtually all of the OCAL belong to the T cell lineage, whereas both B and natural killer (NK) cells are virtually absent. NK activity is also significantly lower than that exerted by PBL. Following treatment with rIL-2, lymphokine-activated killer cell activity is poorly inducible in OCAL. In addition, in vitro stimulated OCAL produce low amounts of lymphokines. Clonal analyses reveal a low clonal efficiency, which indicates a severe proliferative defect. T cell clones obtained show peculiar features: the percentage of CD4 and CD8 clones varies greatly in the different samples. Both CD8 and a significant proportion of proliferating CD4+ clones are cytotoxic in a lectin-dependent cytolytic assay. These findings, together with the results obtained from comparative analyses of the peripheral blood of the same group of patients, demonstrate the unique characteristics of OCAL and should be considered in the preparation of protocols for the locoregional immunotherapy of ovarian carcinoma.

Adenocarcinoma↗
PubMed1993

Humoral autoimmune response in Chagas' disease: Trypanosoma cruzi ribosomal antigens as immunizing agents.

Molecular expression cloning techniques have revealed that patients with chronic Chagas' heart disease (cChHD) present a strong humoral response against the cloned C-terminal portions of the four Trypanosoma cruzi ribosomal P proteins TcP1, TcP2 alpha (TcP2b), TcP2 beta (TcPJL5), and TcP0. This protein family presents several features that may be important in the immunopathology of Chagas disease. Their exposed location on the ribosome, and the amplification of their parasite-specific, Ser free C-terminal domain, generate a strong anti-parasite P response that may induce anti-P autoimmunity. Evidences indicate that the serological pattern of the anti-P response from chagasic patients may be the consequence of a chronic immunization with T. cruzi ribosomal antigens.

Amino Acid Sequence↗
PubMed1991

Ifosfamide and etoposide salvage treatment in advanced ovarian cancer.

Twelve FIGO stage III-IV ovarian cancer patients progressing or relapsing after primary cisplatin-containing combination chemotherapy were treated with ifosfamide and etoposide. Only patients with clinically evaluable disease entered the trial. The 12 patients received a median number of 3 courses (range 1-6). No complete or partial response and two disease stabilizations were observed. Ten patients progressed on therapy. The combination of ifosfamide and etoposide does not appear to be an effective salvage treatment for advanced ovarian cancer.

Adult↗
PubMed1989

[Epilepsy in ring chromosome 14 syndrome].

A patient with ring 14 chromosome is reported. On the basis of this case and of a review of 28 cases published in the literature, the frequency of clinical signs and symptoms is determined, the constant and early incidence of epileptic seizures is emphasized and their characteristics are described. The associated congenital malformations are listed and their importance for karyotyping and consequent detection of new cases is emphasized.

Abnormalities, Multiple↗
PubMed1988

Clastogenic effect of the plant alkaloid ellipticine on bone marrow cells of Wistar rats and on human peripheral blood lymphocytes.

Ellipticine (EPC), a natural alkaloid extracted from Aspidosperma williansii (Apocynaceae), is known to have antitumor and cytotoxic activities on various types of tumors. This drug showed a strong clastogenic effect on bone marrow cells of Wistar rats treated in vivo (7.75-31.00 mg/kg body weight). EPC was also tested in vitro using the human peripheral blood lymphocyte system, at concentrations 100 times lower than those used in the in vivo test on rats, since the cytotoxic effect on lymphocytes was very strong. At the 2 highest concentrations used (7.75 X 10(-1) and 1.55 X 10(-1) micrograms/ml culture medium), EPC induced a statistically significant increase in the frequency of chromosome aberrations and sister-chromatid exchanges in lymphocytes. Based on data reported in the literature, we have tried to establish relationships between the clastogenic effect observed and the process of EPC intercalation into DNA and the formation of protein-associated DNA-strand breaks probably promoted by topoisomerase enzymes.

Alkaloids↗
PubMed1987

An evaluation of four methods for the detection of heterozygous cystinuria.

Heterozygotes for cystinuria (types II and III) may be detected on the basis of slight to moderate elevations in urinary cystine, lysine and sometimes arginine. This seems to be a common genetic trait, and there are indications of an increased risk of urinary stone disease. In order to test the sensitivity and reliability of the procedures normally used for screening and diagnosis of heterozygous cystinuria, we studied 32 heterozygotes previously diagnosed by ion-exchange chromatography of urinary amino acids, and 23 healthy individuals. A random urine sample from each subject was analysed using the cyanide-nitroprusside test, thin-layer amino acid chromatography, colorimetric estimations of cystine and lysine, and ion-exchange amino acid chromatography. Thin-layer chromatography provided the highest sensitivity. Thus the frequency of heterozygotes calculated in previous studies, based on screening by the cyanide-nitroprusside test, may be under-estimated. The colorimetric estimations of cystine and lysine provided low sensitivity as screening tests and, compared with the ion-exchange chromatography, were unreliable diagnostic methods.

Chromatography, Ion Exchange↗