Expression of the alpha 5 beta 1 fibronectin receptor on T lymphocytes of patients with HIV-1 infection.

AIMS: To evaluate the expression of the alpha 5 beta 1 integrin fibronectin receptor (FNR), which mediates several processes, including phagocytosis, cell motility and the immune response, on T lymphocytes of patients with HIV-1 infection. METHODS: T lymphocytes were incubated with monoclonal antibody directed against FNR and then with monoclonal antibodies, conjugated with phycoerythrin, directed against CD3, CD4 and CD8 positive cells. Expression of FNR on CD3, CD4 and CD8 positive cells was analysed using flow cytometry. RESULTS: Normal expression of FNR was observed on CD3 positive cells from asymptomatic HIV positive patients and those with AIDS. Increased expression of FNR was observed on CD8 positive cells from asymptomatic HIV positive patients and on CD4 positive cells from patients with AIDS. Increased FNR expression was observed on CD4 positive cells from patients with AIDS, particularly those with opportunistic infections caused by Pneumocystis carinii, Mycobacterium sp, Toxoplasma gondii, and Cryptococcus neoformans. CONCLUSION: Increased expression of FNR on CD8 and CD4 positive cells in asymptomatic HIV positive patients and those with AIDS, respectively, may be an epiphenomenon correlated with lymphocyte activation by HIV-1 or opportunistic infection, Further study is required to determine whether upregulation of FNR expression has a direct role in the pathogenesis of AIDS.

Cerebrospinal fluid concentration of fibronectin in patients with HIV-1 infection and central nervous system disorders.

AIMS: To evaluate the fibronectin concentrations in the cerebrospinal fluid of HIV-1 infected patients with central nervous system disorders. METHODS: Fibronectin was determined by an immunoturbidimetric assay in 41 HIV-1 infected patients with AIDS dementia complex, progressive multifocal leucoencephalopathy, and opportunistic infections. RESULTS: A significant decrease in fibronectin concentrations in the cerebrospinal fluid of patients with AIDS and dementia complex and progressive multifocal leucoencephalopathy was observed, as well as in those with opportunistic infections of the central nervous system (p < 0.0001). In particular, a significant decrease in fibronectin concentration in cerebrospinal fluid was observed in patients with cerebral toxoplasmosis and cryptococcal meningitis (p < 0.0001). CONCLUSIONS: Because fibronectin can bind to several viruses, fungi, and protozoa, it is conceivable to suppose that the consumption of fibronectin in the cerebrospinal fluid of patients with neurological disorders may be related to the binding of fibronectin to HIV itself, or to viral proteins, or to organisms responsible for opportunistic infections.

Circulating fibronectin and fibronectin receptor in children with pertussis.

AIM: To determine concentrations of fibronectin and fibronectin receptor in children with pertussis. METHODS: Concentrations of circulating fibronectin and serum fibronectin receptor were detected in eight children affected by pertussis, eight children with acute upper or lower respiratory tract infections, and in 14 healthy control children. The single radial immunodiffusion technique and a solid phase enzyme immunoassay were used to detect circulating serum concentrations of fibronectin and fibronectin receptor. RESULTS: On admission, a significant decrease in fibronectin was detected in children with pertussis (p = 0.0006). Significant and decreased concentrations of fibronectin were also observed in children with upper or lower respiratory tract infections (p = 0.0002). On the other hand, serum fibronectin receptor concentrations were significantly increased in patients with pertussis, whereas patients with upper or lower respiratory tract infections had normal circulating fibronectin receptor concentrations. CONCLUSIONS: Fibronectin deficiency in children with pertussis may be related to diffusion and deposition of this protein in bronchial and alveolar spaces to limit infection, while increased fibronectin receptor concentrations are probably the expression of T cell activation and cell-mediated immunity during Bordetella pertussis infection.

Serum concentrations of nitrite in patients with HIV-1 infection.

AIMS: To measure circulating concentrations of nitrite in patients with HIV-1 infection. METHODS: Nitrite concentrations were measured using the Griess reaction adapted to microtitre plates in the serum of 10 asymptomatic HIV-1 positive patients, 33 patients with AIDS with cerebral disorders, 17 patients with AIDS with pulmonary involvement, and in eight patients with AIDS with other disorders. Nitrite concentrations were also measured in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF) of patients with AIDS with pulmonary involvement and cerebral disorders, respectively. RESULTS: Increased serum concentrations of nitrite were observed in patients with pulmonary involvement, and in particular in serum and in BAL samples of patients with interstitial pneumonia (36.2 (26.2) mumol/l and 0.3 (0.4) mumol/l, respectively). Increased serum concentrations of nitrite were also noted in patients with retinitis caused by infection with cytomegalovirus. Serum nitrite concentrations were also raised in patients with cerebral toxoplasmosis, whereas normal serum concentrations were found in patients with HIV-1 encephalopathy and cryptococcal meningitis. Nitrite concentrations in CSF were not raised in patients with cerebral disorders. CONCLUSIONS: These results suggest that production of nitrite in patients with AIDS with concomitant opportunistic infections may be part of the host defense against opportunistic organisms.

In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis.

Nitric oxide (NO) exhibits potent antimicrobial activity in vitro. The function of NO in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the production of NO in vitro from murine peritoneal and alveolar macrophages, and murine macrophage cell line (J774A.1) stimulated with Bordetella pertussis or pertussis toxin (PT). In addition, we determined circulating levels of NO in the sera and bronchoalveolar lavage (BAL) fluids of mice infected intranasally with B. pertussis. The results of this study showed that in vitro murine peritoneal macrophages induce production of NO in response to B. pertussis and PT. In addition, murine macrophage cell line, J774A.1 also induces NO production after stimulation with B. pertussis. NO production was also detected in alveolar macrophages from mice infected intranasally with B. pertussis. Finally, a significant increment of circulating levels of NO was noted, in the sera but not in the BAL fluids, of mice infected intranasally with B. pertussis.

Effects of recombinant human gamma interferon on intracellular survival of Bordetella pertussis in human phagocytic cells.

Several studies have demonstrated that Bordetella pertussis has the ability to enter and survive intracellularly within human polymorphonuclear leukocytes (PMNL) and human monocytes/macrophages. The effects of human recombinant gamma interferon (IFN-gamma) on the survival of B. pertussis in PMNL and human monocytes, and on the oxidative burst activity of PMNL and human monocytes in response to B. pertussis were assessed in this study. IFN-gamma partially increased intracellular killing of phagocytosed B. pertussis in human monocytes, as determined by an orange acridine-crystal violet assay. In contrast, IFN-gamma did not enhance intracellular killing of B. pertussis in PMNL. No significant increase of superoxide production was noted in human monocytes in response to B. pertussis when stimulated with various concentrations of IFN-gamma. The partial increase of B. pertussis killing by IFN-gamma within monocytes, together with poor production of superoxide may explain how B. pertussis can survive within human phagocytic cells, and thus cause a more prolonged course of the disease.

Interaction of human plasma fibronectin with viral proteins of human immunodeficiency virus.

Fibronectin (FN) is present in soluble and matrix forms in various body fluids and tissues, and has been shown to bind to several pathogens, including viruses. The interaction of FN with viral proteins of human immunodeficiency virus (HIV-1) was investigated by immunofluorescence technique using a cell line chronically infected with HIV-1 (H9-V). The results of this study showed that FN binds to HIV-1 infected cells, especially at FN concentration of 5 micrograms/ml. In addition, FN-pentapeptide has shown the ability to bind to HIV-1 infected cells. On the other hand, preincubation with antibodies against FN abolished the binding of FN to HIV-1 infected cells. Finally, FN has shown to bind to HIV-1 glycoproteins, including gp41 and gp120. In contrast, no binding to HIV-1 core proteins, including p15 and p24, was noted. We suggest that FN, in binding HIV-1 particles, may reduce viremia and thus may be involved in the clearance of viral proteins from the cells.

Effects of interleukin-8 on suppression of human lymphocyte polarization and migration by anti-LFA-1 antibody.

We investigated the role of lymphocyte function-associated antigen 1 (LFA-1) in human T cell polarization and migration assay by using monoclonal antibody specific to beta chain (CD18) and alpha chain (CD11a). T cell polarization in response to fetal calf serum (FCS) and colchicine was suppressed by the addition of CD18 and CD11a antibodies. Furthermore, T cell migration in response to lymphocyte chemotactic factor (LCF) and casein was markedly depressed by the addition of CD18 and CD11a antibodies. Additional studies to evaluate effects of interleukin 8 (IL-8) on polarization and migration of T cells preincubated with CD18 or CD11a antibody showed that IL-8 restored the capability of migration of T cells, whereas did not restore polarization activity of such cells. These studies indicate that LFA-1 plays a role in the polarization and migration of T cells and that IL-8 may positively interfer with LFA-1-adhesion molecules.

A case of costochondral abscess due to Corynebacterium minutissimum in an HIV-infected patient.

Corynebacterium minutissimum, known as the causative agent of erythrasma, has recently been reported as a clinically significant pathogen in the immunocompromised host. We report for the first time the possible involvement of a multidrug-resistant C. minutissimum strain in a costochondral abscess occurring in an HIV-infected patient.

Immunological aspects of nitric oxide in HIV-1 infection.

Nitric oxide is produced in large amounts during host defense and immunological reactions and it is likely to have a role in non-specific immunity: nitric oxide exerts microbiostatic and microbicidal activity against a variety of pathogens, including protozoa, fungi, bacteria and some viruses. HIV-1 stimulates nitric oxide production by human macrophages and its production is increased in patients with HIV-1 infection. It is postulated that nitric oxide may play a part in modulating the immune response during HIV-1 infection. Nitric oxide produced by the HIV-1 infected monocytes/macrophages of lymph nodes, may adversely affect the survival of activated immune cells, including B and T lymphocytes and dendritic cells within their vicinity. It is suggested here that production of large amounts of nitric oxide by macrophages may lead to the inactivation of lymphocytes and thus to the induction of a persistent immunosuppression.

[Cardiomyopathy due to adriamycin: the possibility of its prevention. Monitoring by noninvasive technics]. / Cardiomiopatia da adriamicina: possibilità di prevenzione. Monitoraggio con tecniche non invasive.

To prevent delayed cardiomyopathy induced by adriamycin and subsequent severe congestive heart failure, a monitoring schedule with noninvasive techniques to measure cardiac performance (CPK-MB, electrocardiographic, systolic time intervals, echocardiography and quantitative radionuclide angiography) has been used. 15 patients, 33 to 65 years old, with metastatic breast carcinoma, previously treated with a polychemotherapy protocol not including adriamycin have been studied. Monitoring at 0 time allowed to exclude one patient with previous asymptomatic cardiomyopathy and to treat patients at risk with cardiovascular pathology, up to reach and even exceed the dosage of 550 mg/m2. Four of the treated patients showed positive findings of cardiomyopathy at different adriamycin dosage levels: 2 asymptomatic dilatative cardiomyopathies, 1 symptomatic and 1 with congestive heart failure remitted with medical therapy. No patient died because of cardiovascular complications. The results obtained show that of all noninvasive techniques used, only quantitative radionuclide angiocardiography allowed, when employed following an adequate monitoring schedule, to detect reliable findings of moderate and reversible cardiomyopathy thus indicating the appropriate time for drug discontinuation.

Post-discharge recurrences of new-onset atrial fibrillation following cardiac surgery: impact of low-dose amiodarone and beta-blocker prophylaxis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent complication following cardiac surgery. It occurs mostly between the second and fourth postoperative days and often recurs within 30 days after surgery. While postoperative AF has been well analyzed, post-discharge recurrences of AF have not been clearly described even if they are reported as a frequent cause of re-hospitalization. METHODS: We followed up 185 patients for 10 +/- 5 months with the aim of characterizing the post-discharge recurrences of AF. All patients had recently undergone cardiac surgery complicated by AF and were in sinus rhythm at the time of admission to our Center. We also compared the efficacy of the main prophylactic regimens adopted in the referral Centers (amiodarone, beta-blockers, amiodarone plus beta-blockers) during the first postoperative month. RESULTS: In the first postoperative month AF recurred after discharge in 60 patients. The event rate was not different in patients treated with amiodarone and controls (47 vs 50%, p = NS), while it was significantly lower in patients taking beta-blockers either alone or associated with amiodarone (10 and 9% respectively, p = 0.002). At the end of follow up (10 +/- 5 months), AF persisted in 3 out of 176 study patients (1.7%). CONCLUSIONS: In patients undergoing cardiac surgery, post-discharge recurrences of AF are frequent during the first postoperative month and have a clinical relevance. Beta-blockers (not amiodarone) seem to be an effective prophylactic measure. The phenomenon tends to vanish in the long term, and a chronic prophylaxis is not justified.

Observations on the correlation between posture and jaw position: a pilot study.

The aim of this pilot study was twofold. The first was to show a method for having an objective and dynamic analysis of body posture, evaluating weight distribution and its connections with different mandibular positions. The second was to verify if a neuromuscularly stimulated occlusal position, called myocentric occlusal position, is associated with a positive or negative postural charge. For the second aim a group of 20 subjects (including both males and females), was chosen. Posture of each subject was analyzed in three different conditions: centric occlusion, rest position and myocentric position. To evaluate the dynamic of posture a platform capable of measuring the weight on the feet supporting points and the related variations during time of observation and the swinging of body barycenter was used. The data showed that there is an improvement in the position of the barycenter from the centric occlusion to the myocentric position. Such an improvement can't be observed from the intercuspal position to the rest position. The results of this pilot study are discussed.

[A single centre study about the effects of HFR on anemia]. / Studio monocentrico relativo agli effetti dell'emodiafiltrazione con reinfusione endogena (HFR) sull'anemia.

PURPOSE: Erythropoietin (EPO) deficiency, erythropoiesis inhibition and reduction in red blood cell survival are the main causes of anemia in endstage renal disease (ESRD). Hemodiafiltration (HDF) with on-line endogenous reinfusion eliminates backfiltration and uses an ultrapure dialysate and reinfusate. This technique should improve anemia correction by increasing uremic toxin removal and reducing inflammatory cytokine production. In this study, we evaluated the effects of HDF with on-line endogenous reinfusion on anemia correction. METHODS: This was a single-center, prospective and non-randomized study. We selected 12 patients on EPO therapy with steady haemoglobin (Hb) values; eight patients were treated with bicarbonate dialysis and four patients with on-line HDF. We switched them to HDF with on-line endogenous reinfusion for 6 months, changing the EPO dose when Hb levels were not within the 11-12 g/dL range. Biochemical data were measured every month. Results are expressed as means +/- m.s.e. Data were analyzed using the Student's t-test and analysis of variance for repeated measurements. A value p<0.05 was considered statistically significant. RESULTS: Patients maintained the same Hb, ferritin and dialytic efficiency throughout the study. The EPO supplementation was significantly higher in patients treated with bicarbonate dialysis (108 +/- 8 UI/kg/week as compared with patients treated with on-line HDF (36 +/- 5 UI/kg/week) during the 6 months before treatment by HDF with on-line endogenous reinfusion. In the last 6 months, we detected a reduction in EPO consumption, but not statistically significant, in the patients switched from bicarbonate dialysis to HDF with on-line endogenous reinfusion (83 +/- 6 UI/kg/week). CONCLUSIONS: The change from bicarbonate dialysis to HDF with on-line endogenous reinfusion caused a reduction in EPO supplementation and, consequently, a reduction in the cost of anemia therapy. It is necessary to increase the size of the study group and to prolong the observation period to possibly obtain statistical significances.