Cyclosporine reversibly inhibits natural killer-cell activity.
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Biomedical subjects
Publications and source records attributed to M Tumbarello.
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Lymphokine-activated killer (LAK) activity was analyzed in 31 human immune deficiency virus 1 (HIV-1)-infected patients. It was found to be reduced in all groups of patients, being more pronounced in those with acquired immune deficiency syndrome (AIDS) and AIDS-related complex compared to HIV-1-seropositive, asymptomatic individuals. Only high doses of interleukin-2 were able to restore LAK activity comparable to that of normal controls. In addition, HIV-1 gp41 synthetic peptide sequences 735-752 and 846-860 were able to significantly inhibit normal LAK activity at all the effector:target ratios tested. HIV-1-positive serum and the supernatant fluids from cultured peripheral-blood mononuclear cells from HIV-1-infected patients had the same inhibitory effect on normal LAK activity. These data provide evidence that (1) LAK activity appears to be impaired during the course of HIV-1 infection and (2) HIV-1-positive serum and HIV-1 components could exert a profound inhibition of this functional activity.
Immunological studies on 12 patients with culture-proven frequently recurrent herpes simplex genitalis were performed. All the patients were evaluated at three time intervals, initially without lesions and/or within 24 hr of lesion onset (acute illness); Days 5-7 from onset and after healing (convalescence); and between recurrences (quiescence). During the first 24 hr of lesions there was a decreased number of helper (CD4+) and an increased number of suppressor/cytotoxic (CD8+) cells with a resultant decrease in the CD4/CD8 ratio. An increased proportion of CD8+ cells coexpressing the CD11 marker (suppressor cells) was noted and correlated with a low proliferative response to HSV-2 antigens. Both the NK cells (CD16+) and the NK cell activity versus HSV-2-infected targets and the K562 cell line were decreased. Five to seven days after onset the number of CD8+ cells remained increased, although the expression of CD11 marker was decreased, indicating that the majority of CD8+ cells were cytotoxic (i.e., CD8+CD11-). At this time, the lymphoproliferative response to HSV-2 antigens and NK cell activity increased, correlating both with the number of CD16+ cells and with the expression of HLA-DR on this subset. In the interval between two recurrences, no significant alteration in any of the above immunological parameters was observed.
Because of the variety of problems connected with the AIDS epidemic, there is an urgent need for qualified information and counselling. In June 1987, The Italian Ministry of Health established a hot-line, acting within the National AIDS Operational Centre. Through the analysis of more than 39,000 calls received during the first year of activity, a clear outline has been obtained of the emotional impact of the disease on Italian public opinion, and of the problems raised. 67% of callers belong to 20-39 age group; the male/female ratio is 2:1. Interesting correlations have been found between the content of the questions and the sex, age, and type of caller. The vast majority of questions concerning basic concepts and notions about HIV infections are asked by no-risk-related subjects. During the first year, the percentage of questions asked by subjects actually at risk increased, and the questions themselves have become more specific.
The Italian AIDS hot-line has recently completed its first two operational years. Established as an emergency service, it was initially overloaded with calls, under the emotional impact of a new disease. As the average number of calls settled to around a hundred per day, a wider approach aimed at the concerns raised by callers has been possible. A particular effort has been made to handle psychological and social aspects of HIV infections. A large proportion of the questions analyzed (62,500) deal with doubts about transmission (30%), reliability of diagnostic tests (15%), and handling individual situations. Some categories of callers, such as drug users, parents or relatives of HIV-infected people, and seropositives often require experienced telephone counselling. HIV-positive callers follow the proportional distribution of AIDS cases in Italy: intravenous drug users forming the majority, followed by homosexuals and finally heterosexual subjects (reaching 10%, a value in accordance with trend projections). The demand for advice has increased over time, together with an evident refinement of question content.
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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 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).
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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.
A multicentric Italian investigation on legionnaires' disease is in course to clarify host factors as well as pathogen associated characteristics involved in the infection/disease. The main goal of the research plan is to account for some critical aspects concerning identification and prevention of legionellosis. To improve knowledge on factors associated with Legionella spp colonisation in hot waters, to detect cases and to characterize risk factors in subjects which develop pneumonia are specific objectives of the research programme. Preliminary results show that hot waters of houses and hotels are frequently contaminated (22.6% and 54.6%, respectively), mainly by L. pneumophila. Microbial concentrations were low in domestic waters (<1.000 ufc/l), but higher in samples from the hotels (geom. mean 1.85 x 10(3) ufc/l). Warming system, age of the plant, type of building were risk factors significantly associated with Legionella spp positivity. The active surveillance on patients affected by pneumonia with search for Legionella urinary antigen allowed the identification of 34 cases, 3 of which of nosocomial origin, corresponding to 4.2% of the screened pneumonia. After informed consent, 26 subjects were recruited for a case-control-study to clarify risk factors for the disease.
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We report the epidemiological data relative to meningococcal meningitis observed through a century, 1887-1986, in Italy. It is evident both from mortality and morbidity data that in Italy three epidemic peaks have occurred in 1915-1918, in 1939-1943 and in 1968-1972 respectively. The first two epidemic episodes are likely to be connected with the World Wars, the third one, recorded in other european and non european countries, probably reflects a pandemic recrudescence of the disease. The case fatality rate has shown periodic fluctuations connected with the epidemics and an average value of 10% until the sixties. Since then, the case fatality rate has stably decreased below that value. The seasonal distribution of the disease is similar both in the epidemic or non-epidemic period, with the higher incidence of cases between December and April and the lowest in August. There are no substantial differences in the regional distribution of the disease among the various regions of Italy. The distribution of cases, according to the different age-groups (0-14, 14-25, greater than 25 years old), indicates that the disease is more prevalent among the first group. However, in the last decade it is evident a trend of reduction among this group and a relative increase in other groups, in particular in subjects older than 25 years. In addition, meningococcal meningitis is prevalent among the males in the first two decades of life (less than 25 years old) while, afterward, there is an equal incidence both in males and females. The higher prevalence suggests a role of various close environmental contacts, such as the military service.(ABSTRACT TRUNCATED AT 250 WORDS)
Since 1982, 2911 adult AIDS cases have been officially reported in Italy up to December 31, 1988. The clinical presentation of all cases, reported to the Istituto Superiore di Sanità, Rome, and contained into the National AIDS Register, has been analyzed, with particular attention to opportunistic infections. 168 cases (mainly homosexual men) were found exclusively affected at diagnosis by Kaposi's Sarcoma (KS), while the other 2743 patients were affected by opportunistic infections and/or other pathologies. At diagnosis, 23.5% of patients had Pneumocystis carinii pneumonia (PCP), 32% esophageal or pulmonary candidiasis, and 7% cerebral toxoplasmosis. A decrease in frequency of Cytomegalovirus (CMV) diseases has been observed, as well as an increase of HIV encephalopathy from 1982 to 1988. The clinical picture of full-blown AIDS showed stability during the whole period of observation, with slight geographical variations.
BACKGROUND AND OBJECTIVE: Patients with hematological malignancies are at increased risk for developing bacteremia. No previous study has investigated the risk and prognostic indicators of bacteremia in such patients using a statistical approach. METHODS: A case-control study was performed in 106 patients with hematological malignancies (group A). Two hundred and twelve patients were included as controls and divided into two groups: 106 patients with hematological malignancy without bacteremia (group B) and 106 HIV-infected patients with bacteremia (group C). RESULTS: At univariate analysis, bacteremia risk factors in group A were: neutropenia for more than six days (p = 0.03 vs. group B), central venous catheter usage (p = 0.04) and absence of antibiotic prophylaxis (p = 0.03). At multivariate analysis, the use of CVC and neutropenia were independent bacteremia risk factors. The most frequent etiological agents were: Staphylococcus epidermidis and Pseudomonas aeruginosa. Comparing groups A and C, the distribution of Staphylococcus spp. was different, with S. epidermidis being prevalent in hematological patients only. As regards gram-negative organisms, it is of note that no episode of NT-Salmonella bacteremia was observed in group A, unlike group C, where they represent the second leading etiological agents. In group A, 14% of the patients died. Persistent neutropenia (p = 0.01) and the presence of relapsed neoplasm (p = 0.04) were prognostic indicators of bacteremia. INTERPRETATION AND CONCLUSIONS: Our findings suggest that bacteremia in patients with hematological malignancies strictly correlates with the intensity and length of neutropenia and CVC usage. Although we observed a low mortality rate, we stress that this clinical condition requires special attention from the physician, who must recognize and treat it promptly.