Gonadal mosaicism in hereditary angioedema.
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Amino Acid Substitution↗
Biomedical subjects
R Perricone
Publications and source records attributed to R Perricone.
Coagulation factor XI and venous thrombosis.
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Antiphospholipid Syndrome↗
Impaired human ovarian follicular fluid complement function in hereditary angioedema.
We sought and detected functionally active complement in human ovarian follicular fluid obtained during the peri-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity, alternative pathway activity and C1 inhibitor function were present with values within the normal serum range. Active complement in follicular fluid is relevant for the function of the enzymatic multifactorial mechanism of ovulation. The presence in hereditary angioedema patients of both complement (C1 inhibitor deficiency and chronically consumed complement) and ovarian abnormalities (cystic ovaries), led us to study complement function in the follicular fluid of women of reproductive age affected with hereditary angioedema. In contrast to healthy women, hereditary angioedema patients showed dramatically reduced classical pathway activity and undetectable functional and antigenic C1 inhibitor. C4 was very low, while C3 and B were slightly reduced or within the normal serum range. This complement profile was also detected in patients' sera. Since hereditary angioedema patients often show cystic ovaries (polycystic or multifollicular), the presence of multifollicular ovaries in the two patients studied, along with complement dysfunction, may be relevant. These findings, as well as the normalisation of the ovaries found by us in hereditary angioedema patients and in the patients reported here who were undergoing danazol treatment, and the increase in C1 inhibitor and the improvement of clinical symptoms, suggest a further link between complement and ovarian function.
Adult↗
High-dose intravenous immunoglobulin treatment activates complement in vivo.
Several complement modulating effects of high-dose intravenous immunoglobulins (IVIG) have been proposed from in vitro studies and experimental animal models. However, the in vivo effects of IVIG on plasma complement in humans are yet not known. We have investigated the in vivo effects of IVIG on complement in seven women with unexplained recurrent spontaneous abortion who were without evidence of autoimmune disease. Samples were obtained before and after the very first infusion of IVIG. There was a marked increase in immunoglobulin G (IgG) from (median and range) 12.4 (9.4-15.9) to 26.8 (22.4-30.0) g/l but no change in immunoglobulin A (IgA) or immunoglobulin M (IgM). A significantly increased complement activation was demonstrated using neoepitope-specific enzyme immunoassays to the activation products C3bc (median increased from 9.8 to 31.2 AU/ml), Bb (0.66-1.66 g/ml), C5a (10.5-12.7 ng/ml), and TCC (0.81-2.19 AU/ml) (P = 0.015 for all). There were no changes in antigenic concentrations of individual complement components or regulators (C1q, C4, C3, C1-inhibitor, C4b-binding protein) and no decrease in complement haemolytic activity (classical and alternative CH50), which were all within the normal range. The classical pathway activation products C1rs/C1-inhibitor complexes, C4bc and C4d were elevated in all patients before IVIG treatment and did not change significantly during treatment. In conclusion, IVIG induced a significant activation of complement in vivo.
Abortion, Habitual↗
Comparative activity of idarubicin and idarubicinol in combination with cyclosporin A in multidrug-resistant leukemia cells.
4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good cytotoxic activity in vitro against tumor cell lines displaying the multidrug-resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol (2HIDA) and, in this form, seems to exert its antitumoral activity in vivo. Recent studies have shown that 2HIDA has tumoricidal activity similar to that of the parent drug when tested in vitro in sensitive neoplastic cells. In this work we compared in vitro the effects of IDA and 2HIDA used alone and in combination with 2 microM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R and in their sensitive parent cell lines FLC and K562. IDA and 2HIDA showed the same cytotoxic activity in sensitive cells. After 1 h of exposure of cells to each anthracycline, we observed that the cellular uptake of IDA and 2HIDA was also similar. In resistant cells, 2HIDA was 3-4 times less active than IDA. We observed that the intracellular uptake of 2HIDA was lower than that of IDA, and this may be correlated with a greater ability of P-glycoprotein to expel 2HIDA as opposed to IDA. Indeed, when MDR cells were exposed to IDA and 2HIDA in combination with 2 microM CyA, the cytotoxic effect of these anthracyclines was the same, and it was similar to that observed in sensitive cells. These data confirm the utility of the combination of IDA and an MDR-reversing agent in hematological malignancies displaying the MDR phenotype.
Antibiotics, Antineoplastic↗
[The use of hyperimmune anti-cytomegalovirus immunoglobulins in HIV infection].
Cytomegalovirus (CMV) is one of the most frequent opportunistic agents that affects HIV positive subjects. The prophylaxis and treatment of cytomegalovirus infection in HIV positive subjects represent difficult and controversial problems. In this study we evaluated efficacy of anti-CMV immunoglobulins (derived from plasma with a high titer of CMV anti-bodies) in primary and in secondary prophylaxis for CMV disease in adults with severe immunodeficiency caused by HIV infection. For primary prophylaxis, in 22 patients with CD4 < 200/mmc enrolled to receive a monthly infusion of intravenous immunoglobulins (IVIG) at 200 mg/kg we observed prophylactic effect for the prevention of CMV and bacterial infections. Concerning secondary prophylaxis, 7 patients with CMV manifestation treated after remission with anti-CMV IVIG at 200 mg/kg every two weeks, had a low frequency of relapse and a good clinical outcome. Because their tolerability, anti-CMV immunoglobulins are an interesting option particularly for the prevention of CMV and bacterial infection in HIV-positive adults in advanced stages of disease.
AIDS-Related Opportunistic Infections↗
Normal fetal growth in women with antiphospholipid syndrome treated with high-dose intravenous immunoglobulin (IVIG).
Antiphospholipid antibodies are associated with fetal distress and fetal death. Although different therapeutic regimens have been used, the incidence of fetal growth retardation varies between 30 and 60 per cent of reported cases. We report the evolution of fetal growth in patients with antiphospholipid antibody syndrome treated with high-dose intravenous immunoglobulins (IVIG). Fourteen patients with a history of recurrent spontaneous abortion and immunological diagnosis of antiphospholipid syndrome were followed longitudinally. Intravenous immunoglobulin at a dose of 0.5 g/kg body weight for two consecutive days was started from the fifth week of pregnancy and repeated every 4 weeks until the 33rd week of gestation. Fetal biometry was evaluated longitudinally from the appearance of the gestational sac at 4 weekly intervals. In the period between 26 and 34 weeks, the frequency of evaluation was increased to every 14 days. Data obtained were compared with a control group of 70 fetuses with uneventful pregnancies matched for gestational age. Neonatal weight is shown in relation to the centiles for the normal population. One patient out of 14 (7.1 per cent) developed gestational hypertension and abruptio placentae. No other pregnancy complications were seen. No proteinuria was found. The mean maternal age was 31.2 +/- 3.8 years. Median birth weight was 3433 g +/- 287. The median centile of the birth weight was 65.3 +/- 18.6. Mean gestational age at delivery was 1.3 weeks. No fetal or neonatal growth retardation was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Abortion, Habitual↗
Complement activation and sensitizing antibodies in Lyme borreliosis. A microbial adherence immobilization assay for Borrelia burgdorferi (MAIA-BB).
A report is presented about the capability of complement to directly clump Borrelia burgdorferi. The new phenomenon which has been termed "microbial adherence", is either antibody-independent or requires the presence of "sensitizing" antibodies depending the strains tested. Microbial adherence is associated with immobilization and killing of borrelias. A microbial adherence immobilization assay for B. burgdorferi (MAIA-BB) was developed to detect sensitizing antibodies in patients with Lyme borreliosis and in B. burgdorferi-infected animals.
Animals↗
Angiotensin-converting enzyme activator from purified human neutrophils.
An endogenous ACE activator has been revealed. Neutrophil-enriched human leucocyte preparations released in isotonic media a relatively thermostable factor, capable of increasing the angiotensin-converting enzyme activity 1.6-2.0-fold. Activator would not pass through a 30 kDa cutoff membrane. Data on the presence of the activator in vivo were obtained in studies of protein-free serum fractions of patients with a hereditary CI-esterase inhibitor deficiency. It was suggested that the neutrophil-released ACE activator could have a role in the modulation of the inflammatory response.
Adult↗
Cystic ovaries in women affected with hereditary angioedema.
Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic-pituitary) abnormality, including high plasma beta-endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (HANE) during attacks as well as during symptom-free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HANE who were not on oral contraceptives. We have found PCO in 5/13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.
Adolescent↗
Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma.
Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed.
Complement Activation↗
Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy.
A collaborative survey was carried out in Italy on a group of 59 subjects with a past history of meningococcal meningitis. The aim was to evaluate the prevalence of complement deficiencies, the serogroup of meningococci responsible for the disease and other possible immune abnormalities associated with the infection. Complement analysis allowed the detection of 10 cases (17%) with deficiencies of the terminal components, and in particular six cases of C8 beta, three of C7 and one of C6 defect. Half of the subjects with complement deficiencies had recurrences of meningitis and developed the infection at an older age in comparison with the control group with normal complement activity. The meningococcal C strain was the most diffuse (68%) and infected all the complement-deficient subjects. Evaluation of the antibody response to meningococcal capsular polysaccharides (PS) showed that only 42.5% of the individuals with group C had antibodies as opposed to 83% and 100% of the patients with meningitis due to group A and B, respectively. In all 59 subjects serum Ig as well as IgG subclasses were present, at normal levels for the age. Vaccination of seven out of the 24 subjects without detectable anti-meningococcal PS antibodies with the sole PS A+C induced a normal response in six of them, including a subject with complement defect. In the subject who did not respond to the antigen, the antibodies against the ubiquitous pneumococcal PS type 14 were also lacking, whereas anti-tetanus toxoid (TT) antibodies were normally present. From these data we may conclude the following: (1) the high prevalence (17%) of late complement components defect among survivors of meningococcal meningitis is also confirmed in the Italian population; (2) the serogroup C, responsible for the infections in all the cases with late complement components defect, is highly recirculating in Italy and apparently less immunogenic; (3) specific vaccination with meningococcal PS is a valid prophylaxis in subjects with lack of specific antibodies as well as in subjects with complement defect.
Adolescent↗
Pefloxacin in the antibacterial treatment of immunodepressed patients.
Pefloxacin 800 to 1200 mg daily was given for 3 to 20 days, orally or intravenously, to 84 immunocompromised patients. Five patients dropped out because of side effects and 2 for other causes. Treatment efficacy was evaluated in 77 patients, 43 men and 34 women, aged 18 to 80 years. Immunodepression resulted from malignancy in 46 patients, LAS/ARC or AIDS in 28, and from unknown causes in 3. Fifty-eight patients had documented infections (respiratory-tract infections 29, urinary-tract infections 13, septicemia 10, other 6) and 19 had a fever of unknown origin (FUO). Cure or significant improvement of symptoms was achieved in 81% of patients with documented infections and in 74% of patients with FUO. Side effects (mainly gastrointestinal disturbances and skin rash) occurred in 7 patients (8.2%), including dropouts. These results suggest that pefloxacin may be useful for the antibacterial treatment of immunodepressed patients.
Acquired Immunodeficiency Syndrome↗
Complement, complement activation and anaphylatoxins in human ovarian follicular fluid.
Functionally active complement was sought and detected in human follicular fluids obtained during the pre-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity and alternative pathway activity were present in nine fluids from four different donors with values within the normal serum range. The immunochemical analysis demonstrated the presence of complement factors from C1 to C9, of B and of C1 INH, H, I. Complement anaphylatoxins were found employing RIA techniques in amounts significantly higher than in human plasma, thus demonstrating that follicular fluid complement, at least during the pre-ovulatory period, is partially activated. A possible role for urokinase-like substances in such an activation was indicated by further in vitro experiments. The presence of active complement in follicular fluid can be relevant for the function of the enzymatic multi-factorial mechanism of ovulation.
Anaphylatoxins↗
Complement activation is associated with the presence of specific human immunodeficiency virus (HIV)-anti-HIV immune complexes in patients with acquired immunodeficiency syndrome-related complex or lymphoadenopathy syndrome.
The complement system was examined in a group of eight patients (six with lymphoadenopathy syndrome (LAS); two with acquired immunodeficiency syndrome (AIDS)-related complex (ARC], who were found to be human immunodeficiency virus (HIV)-positive, for the presence of specific HIV-anti-HIV complexes. A significant impairment of the classical and/or alternative pathway was found associated with the presence of cleavage fragments of C3 and/or B and a significant reduction in the complement factors studied. Ultracentrifugation fractions of serum samples obtained from one of the patients were assessed for the detection of specific HIV-anti-HIV (GP41-anti-GP41) complexes and were incubated with normal human serum to determine their complement activation capacity. A clear complement activation was found with the fraction in which a clear peak of HIV-anti-HIV (GP41-anti-GP41) immune complexes was present. The results demonstrate that specific immune complexes and complement activation are sometimes concomitantly present in patients with AIDS-related disease and that specific immune complexes may be one of the causal factors of the pathogenesis of complement activation in these patients. Possible consequences for the severe immune regulation with relevance to the dramatic failure in treating the virus effectively are discussed.
AIDS-Related Complex↗
[High-dose immunoglobulins in immune thrombocytopenic purpura].
Twenty-four patients with immune thrombocytopenic purpura (ITP) were treated with high doses of intravenous immunoglobulin (Ig). Increase in platelets was observed in all the patients. The maximum value was reached between the seventh and the twelfth day of treatment. The mean number of platelets was 18 x 10(9)/l before the treatment and 150 x 10(9)/l after the treatment. The effect was transient; in fact, a fall in the platelets was observed after 18 days of treatment. Our study confirms that high doses Ig is an effective treatment of ITP, but the high cost and the temporary effect limit its use only in those cases in which other treatments are ineffective or contraindicated.
Adult↗
Modulation of human concanavalin A-induced lymphocyte proliferative response by physiological concentrations of beta-endorphin.
The effects of physiological concentrations of beta-endorphin on the proliferative response to concanavalin A of human peripheral blood mononuclear cells from a large series of healthy donors are reported. These effects are also compared with those obtained employing beta-endorphin and phytohemagglutinin under the same experimental conditions. The donors (32), aged between 20 and 48 years, chosen among military personnel of the Italian Air Force, underwent clinical and laboratory investigations to exclude any detectable disturbance in their psychophysical fitness. Our results show that beta-endorphin is not mitogenic per se and is unable to modify the response of mononuclear cells to phytohemagglutinin irrespective of the concentration of opioid or mitogen used. beta-Endorphin is also unable to alter the PBMC response to low concentrations of concanavalin A, but significantly increases such a response when higher concentrations of concanavalin A and concentrations of beta-endorphin similar to those found in human plasma under physiological conditions are used. The effect is not reverted by naloxone, the specific opiate antagonist. When the activity of beta-endorphin on the mononuclear cell response to concanavalin A is examined at the single donor level, it is noted that some of the donors fail to show the opioid-dependent increase. The baseline levels of the response to concanavalin A of such subjects, compared to those of the donors whose response is augmented by the opioid, are significantly higher, thus demonstrating that beta-endorphin can selectively modulate concanavalin A-induced mitogenesis with a behavior depending on the individual characteristics of the donor's response. The process involves non-opioid cell receptors.
Adult↗
Primary gastrointestinal involvement in non-Hodgkin's lymphomas.
This paper reviews primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL). Every aspect of the topic is discussed though special attention is paid to histopathology and instrumental diagnosis as essential factors to stage the lymphoma and to determine an adequate therapy. Data from the most important works on the subject together with the results of our recent study of 40 primary GI-NHL are reported. Diverse findings by various authors are intentionally compared in a manner to present the work to the reader in the most critical way while trying to give an objective explanation of the different results on the basis of our own experience.
Adolescent↗