Interleukin-2 reconstitutes natural killer activity in transplant recipients.
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Biomedical subjects
Publications and source records attributed to L Ortona.
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In the decade 1977-1986 the total number of cases of brucellosis recorded in Italy was 25,165. The reported cases probably reflect only a minority of the total number of the effective cases due to lack of reporting. The epidemiological and clinical features of 62 cases of brucellosis, observed by the authors are reported as a sample of the total number of cases.
The relationship between cerebrospinal fluid (CSF) markers of HIV infection and the spectrum of neurological manifestations were studied in 15 AIDS patients (13 with and 2 without confirmed neurological disorders). We demonstrated the presence of intrathecally synthesized anti-HIV antibodies. Antibodies to HIV envelope proteins were present in all patients but those to HIV core proteins in 9/13 cases only. HIV antigen and HIV p24 antigen were present in 6/14 and 4/12 cases respectively. HIV was not isolated from 6 samples of CSF. We have demonstrated that CSF markers of HIV infection were present in all AIDS patients, with or without neurological manifestations. Moreover HIV p24 antigen seems to be a very reliable marker of HIV infection.
The inhibitory effect on normal natural killer (NK) cell activity of two synthetic peptides corresponding to amino acid sequences 735-752 and 846-860, respectively, as deduced from the amino acid sequences of HTLV-IIIB gp160, was assessed. Sequences 735-752 and 846-860 correspond to regions located within the HIV transmembrane gp41, the carboxy terminus of HIV gp160. These two synthetic peptides have been shown previously to suppress the mitogen- and alloantigen-induced normal human lymphocyte blastogenic responses. Peptides 735-752 and 846-860 conjugated to protein carriers exerted a significant inhibition on the normal NK cell activity assayed against K562 tumor target cells in an in vitro 51Cr-release cytoltoxicity assay. At variance, control peptides similarly conjugated had no effect on NK activity. Addition of exogenous recombinant human interleukin-2 (IL-2) resulted in a partial restoration of the suppression of NK cell activity exerted by both peptides. Binding experiments indicated that peptides 735-752 and 846-860 did not affect the formation of effector cell-target cell conjugates, suggesting inhibitory effect(s) subsequent to the formation of the lytic complex as one potential mechanism of the observed NK suppression. These results suggest that peptides 735-752 and 846-860 homologous to sequences within the HIV transmembrane gp41 may play an important role in the pathogenesis of the defective NK cell activity observed in patients with acquired immunodeficiency syndrome (AIDS).
An ELISA assay was designed to detect the presence of parasite related antigens associated with circulating immune complexes in patients affected by urinary schistosomiasis. The assay makes use of bovine conglutinin as the immune complex recognition unit and of human anti-Schistosoma antibody as the antigen recognition unit. Using this method we showed that 10 of 15 (67%) patients with a positive polyethylene glycol assay had circulating immune complexes in which parasite antigens could be detected.
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A chronic coinfection with CMV, EBV etc. has been described in patients with HIV infection; recently a coinfection with other retroviruses has been described too. We have looked for the presence of antibodies to HTLV-I (anti HTLV-I) and to HIV-2 (anti HIV-2) in 135 HIV infected (HIV-positive) subjects living in Rome. They were 100 i.v. drug addicts, 24 homo/bisexuals, 4 partners of HIV-positive patients, 5 polytransfused and 2 without any known risk factor; 32 of them had a full-blown AIDS, 52 had ARC and 51 were symptom-free. Anti HIV, anti HTLV-I and anti HIV-2 were detected with ELISA method and confirmed by Western Blot (W.B.) technique. Antibodies to HTLV-I were found in 14 cases (10.4%) and antibodies to HIV-2 in 12 cases (8.9%). The contemporary presence of anti HIV, anti HTLV-I and anti HIV-2 was not found in any subjects. Our data fail to show a clear relationship among the coinfection with different retroviruses and the various risk factors for HIV infection and the HIV-related clinical picture (AIDS, ARC, etc.).
NK activity and cells with NK phenotype (CD16+) were studied in 21 patients with HIV infection. In particular 8 patients with full-blown AIDS, 6 with AIDS related complex (ARC), 7 asymptomatic seropositive for anti-HIV antibodies were evaluated. Six subjects seronegative for anti-HIV antibodies from groups at risk for HIV infection were evaluated as well. NK activity was significantly reduced in AIDS and ARC patients but normal in asymptomatic seropositive subjects and in seronegative subjects at risk. NK cells (CD16+) were normal in AIDS patients, and in asymptomatic seropositive subjects, increased in ARC patients and in the subjects at risk. No statistical correlation was evident between the NK activity and the number of CD16+ cells in individual patients. The percentage of CD16+ cells coexpressing the HLA-DR marker i.e. CD16+ HLADR+ cells was significantly elevated only in ARC patients, and normal in the others. NK activity is the first line of defense against an invading virus and plays an important role in the immune surveillance of neoplasms. Therefore the reduced NK activity in AIDS and ARC patients can be consistent with the development of viral infections and unusual neoplasms frequently observed in such patients. The lack of correlation between defective NK activity and normal or increased number of cells with NK phenotype seems to indicate the existence of a more profound alteration in the function of NK cells rather than a simple numeric variation.
Reported are the results of a study on the incidence of nosocomial surgical infections in ten wards of the university hospital A. Gemelli, Rome. One thousand, five hundred five patients were studied and the overall incidence of surgical infections was 8.7%. Factors that influenced infection rates included age, immunosuppressive diseases, and immunosuppressive therapy. We assessed the inutility of antibiotic prophylaxis in clean operations and its usefulness in clean operations with insertion of prostheses or other devices. The importance of the duration of preoperative hospitalization and of the length of the operation were also noted. The most frequent etiological agents proved to be Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. The average hospital stay for patients with surgical infection was more than double that of patients with no infection (25.7 days v 11.7 days).
Using the automated hematologic analyzer Technicon H6000, which classifies leukocytes by their size and peroxidase activity, the authors have observed in nine patients with full-blown acquired immune deficiency syndrome (AIDS) a consistent increase in peroxidase content of circulating neutrophils. The increase in peroxidase activity was homogeneous in three patients (P less than 0.05). The most striking finding, however, was the occurrence of single abnormal neutrophils with peroxidase activity higher than the major neutrophil population (i.e., HPX [high peroxidase] cells). The importance of this phenomenon was correlated with the clinical status, higher HPX values being found in patients with more advanced disease. These instrumental observations were associated with the morphologic finding of atypical neutrophils, much larger than normal, with irregular nuclei and abundant cytoplasm filled with peroxidase-positive granulations. Such cells represent, in the authors' experience, the most common expression of dysgranulopoiesis in AIDS.
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Ninety-two microbiologically documented staphylococcal infections were treated with cefamandole in an open comparative study on the clinical efficacy of this cephalosporin in the therapy of infections caused by both methicillin-susceptible and methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp. The majority of the episodes (86 of 92) were treated with cefamandole alone, and six were treated with cefamandole in association with other antibiotics. In the evaluable S. aureus infections, 34 of 46 (73.9%) due to methicillin-susceptible strains and 12 of 16 (75%) due to methicillin-resistant strains responded to therapy. In particular, among the patients infected by methicillin-susceptible S. aureus 6 of 9 cases of septicemia, 0 of 2 cases of endocarditis, 2 of 2 cases of pneumonia, 2 of 3 osteoarticular infections, 8 of 12 cases of peritonitis in patients with chronic renal failure in continuous ambulatory peritoneal dialysis (CAPD), 13 of 15 skin-soft tissue infections, and 3 of 3 urinary tract infections responded to therapy. Among those due to methicillin-resistant strains, cure was achieved in 2 of 4 cases of septicemia, 0 of 1 case of endocarditis, 9 of 10 skin-soft tissue infections, and 1 of 1 urinary tract infection. In the evaluable infections caused by coagulase-negative staphylococci, 9 of 11 (81.8%) due to methicillin-susceptible and 15 of 17 (88.2%) due to methicillin-resistant strains responded to therapy. In particular, among patients infected by methicillin-susceptible, coagulase-negative staphylococci, 4 of 4 cases of septicemia, 0 of 1 case of endocarditis, 1 of 1 case of pneumonia, 1 of 1 case of peritonitis in CAPD, 2 of 3 infections of skin-soft tissue, and 1 of 1 urinary tract infection responded to therapy. Among patients infected by methicillin-resistant, coagulase-negative staphylococci were cured 5 of 6 cases os septicemia, 6 of 6 cases of peritonitis (in CAPD), 4 of 4 infections of skin-soft tissue, and 0 of 1 urinary tract infection.
The results of a study on the incidence of nosocomial infections in a 1800 bed University hospital are reported. The study, carried out over a 9 months period, included: continuous microbiological surveillance, and a clinical and epidemiological survey. On the basis of the microbiological data collected and analyzed by a computer data system, developed and employed for the control of nosocomial infections, a weekly bed-to-bed survey was carried out by the staff of the Institute of Infectious Diseases. Among 2777 suspected nosocomial infections, as revealed by microbiological monitoring, 701 were confirmed after the bed-to-bed survey. The nosocomial infection rate was 6.75 per 100 discharges. It was higher in the surgical than in the medical wards (7.3 and 6 per 100 discharges, respectively). Nosocomial urinary tract infections were the most frequent (74.2%). The urinary infection rate was higher in the surgical than in the medical wards (5.3 and 4.6 per 100 discharges, respectively). Escherichia coli (19.4%), Pseudomonas aeruginosa (19.3%), Proteus spp. (18.4%) were the pathogens most frequently associated with nosocomial infections. They were followed by Klebsiella pneumoniae (7.8%) and Staphylococcus aureus (6.5%) in frequency. Among the risk factors, involved in nosocomial infections, the importance of catheterization was confirmed: among our patients with nosocomial urinary tract infections, 73.4% and 79.5%--in the medical and surgical wards, respectively--underwent urological instrumentation, mainly catheterization. An analogous and more detailed study is now in progress and will be extended in the next years.
During acute viral hepatitis, we observed a significant decrease in OKT4/OKT8 ratio with a significant increase in the OKT8 positive subset in acute type B and non-A-non-B hepatitis. This altered ratio persisted in type B for a long time until HBsAg antibody became detectable, while it soon returned to normal in type A and non-A-non-B hepatitis. In the majority of acute hepatitis the altered ratio is because of an increase and not to a decrease in the whole T cell population, as described in chronic HBV infection. The number of HNK-1 positive cells remained raised during the recovery phase of type B and non-A-non-B hepatitis, a finding consistent with the hypothesis that NK cells play a role in the host defence against B and non-A-non-B virus infections. Serum beta 2-microglobulin concentrations were increased only in acute hepatitis B and non-A-non-B where immunological mechanisms are suspected to be involved, and showed a good correlation with the population of activated OKIa positive cells.
Type A, type B and type non-A, non-B hepatitis patients were followed up. Several parameters were checked at ten day intervals. Circulating immune complexes (CIC) were detected in a large percentage of patients by using the PEG test and an assay that makes use of bovine conglutinin (K) as recognition unit, and an enzymatically labelled immune complex as the probe. The decrease in the mean level of CIC in the patients correlated with the decrease in serum transaminases and bilirubinaemia in type A and type B hepatitis. Although the pattern of the mean values of the two assays was similar for type A and type B hepatitis, when the two CIC assays were compared for each patient, no significant correlation was found. In light of these and previous results, the necessity for performing CIC monitoring with more than one assay is also discussed.