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Biomedical subjects

A Lazzarin

Publications and source records attributed to A Lazzarin.

At least 289 records · Page 16Linked to original sources

Rapid killing of actinomycin D-treated tumor cells by human monocytes. II. Cytotoxicity is independent of secretion of reactive oxygen intermediates and is suppressed by protease inhibitors.

Pretreatment with Actinomycin D (ActD, 1 microgram/ml for 3 hr) rendered WEHI 164 tumor cells susceptible to killing by human monocytes in a 6-hr 51Cr release assay. The present study was designed to elucidate the role of reactive oxygen intermediates (ROI) and of proteolytic enzymes in this reactivity. ActD-treated WEHI 164 cells did not trigger any measurable release of O-2 or H2O2 from monocytes. Monocytes exposed to phorbol-12-myristate-13-acetate, which enhanced release of ROI, did not show augmented killing of ActD-treated tumor cells. Scavengers of oxygen metabolites (catalase, superoxide dismutase, gluthatione, and mannitol), which inhibited ROI-mediated PMA-induced monocyte cytotoxicity against erythrocytes, did not affect monocyte killing of ActD-treated WEHI 164 cells. Enzymatically generated ROI with xanthine/xanthine-oxidase glucose/glucose-oxidase did not show preferential killing of ActD-treated WEHI 164 cells. Two patients with chronic granulomatous disease had normal levels of monocyte cytotoxicity against ActD-treated tumor cells. To determine the possible role of proteolytic enzymes in mediating this reactivity, we studied various antiproteases. Organophosphorous agents (DFP and PMSF), chloromethyl-ketone derivatives of tosylamino acids (TLCK and TPCK), Actinomyces products (pepstatin and chymostatin), and the synthetic protease substrate TAME inhibited monocyte-mediated cytotoxicity against ActD-treated WEHI 164 cells. The macromolecular protease inhibitors alpha-1 antitrypsin, bovine pancreatic trypsin inhibitor (BPTI), soybean trypsin inhibitor, and the synthetic protease substrate ATEE had little effect on monocyte cytotoxicity. When monocytes were preincubated with drugs for 1 hr and washed, TLCK, TPCK, and PMSF inhibited cytolysis, whereas the less effective chymostatin and TAME and the inactive BPTI had no effect under these conditions. Inhibition by preincubation with TLCK, PMSF, and TPCK was completely reversed after 6 hr of culture. Supernatants of monocyte cultures had lytic activity against ActD-treated WEHI 164 but not against untreated cells. Antiproteases inhibited the lytic activity of monocyte supernatants. These results strongly suggest that ROI do not play a critical role in monocyte-mediated rapid killing of drug-treated tumor cells, and that proteolytic enzymes are involved in this reactivity.

Adolescent↗

Immunological status in heroin addicts: effects of methadone maintenance treatment.

In opiate addicts specific and unspecific immune responses were examined, before and after methadone treatment. Anomalous immune responses were characterized by compromised cellular immunity (functional deficits of polymorphonuclear leukocytes and T-lymphocytes) in association with efficient production of antibodies. After methadone treatment an elevation of leukocyte functions was noted. The presence of elevated titres of circulating immune complexes observed in all the patients tested could bring about a functional exhaustion of neutrophils. The defects of cellular immunity can be considered important risk factors in the pathogenesis of infectious diseases in addicts.

Adolescent↗

Prolonged course and relapses of acute type A hepatitis.

Sixty-nine consecutive patients with acute type A hepatitis were followed-up to establish the natural history of the disease. Illicit drug abusers were not included in this study. 19% (13/69) of the patients at 6th month, and 6% (4/69) at 12th month showed aminotransferase (ALT) values at least two folds the upper levels. The histological examinations performed in 5 of these cases suggest that persistence of abnormal ALT levels may be related to a misdiagnosed chronic liver disease preexisting the acute type A hepatitis. Three of the 69 patients had a relapsing hepatitis with two peaks of serum ALT 6-8 weeks apart. The illness resolved uneventfully in all these patients. The exclusion of exposure to liver toxins such as alcohol or drugs, as well as other known hepatitis virus infection in these cases, suggests that the two distinct episodes of hepatitis could be the result of the sequential infection of hepatitis A and non-A, non-B viruses.

Acute Disease↗

Polymorphonuclear leucocyte function during acute viral hepatitis.

Polymorphonuclear (PMN) phagocytosis was tested in three groups of 12 patients (non drug-addicts) hospitalized for acute A, B and non-A, non-B hepatitis. The same test was performed in 12 parenteral drug-addicts (P.D.A.) with non-A, non-B hepatitis, in 12 P.D.A. with type B hepatitis and in 30 P.D.A. without evidence of acute hepatitis. Percent of phagocytosis was evaluated at time of admission to hospital, at discharge and three months after the acute episode. A statistically significant reduction of phagocytosis was present in each of the non-addicts group at time of admission to hospital. At the discharge this reduction was confirmed for type B and non-A, non-B hepatitis, whereas an improvement was noted for type A hepatitis. Control tests carried out 3 months later evidenced that also in patients affected with type B and non-A, non-B hepatitis the percentages of phagocytosis had reached almost normal values. An increased percent of phagocytosis resulted from incubation of patients' PMN with normal human serum. Among drug-addicts the percentages of phagocytosis do not differ from the data recorded in non-addicts patients during the acute stage of the disease. However, three months after the acute episode, a deficit of phagocytic activity was still present in drug-addicts. These data would support the hypothesis that a serum factor impairing the PMN phagocytosis in acute hepatitis is present. Circulating immune complexes were found in the same sera. They might play an important role in inhibitory effect on neutrophils phagocytic activity.

Acute Disease↗

Brachial paresis complicating acute non-A, non-B hepatitis.

We report a case of right arm paresis in a parenteral drug addict suffering from acute non-A, non-B hepatitis. His hepatic and neurological symptoms developed together with high level of circulating immune complexes, complement activation, and false VDRL positivity. Immunological abnormalities normalized with the resolution of acute hepatitis and improvement of paresis. These results suggest that neurological dysfunctions may complicate non-A, non-B hepatitis. Moreover, we postulate an immune-mediated mechanism for neuropathy, via a neuropathic activity of circulating immune complexes.

Acute Disease↗

Polymorphonuclear leucocytes functions from premature infants after prevention of respiratory distress syndrome with betamethasone and ambroxol.

An increase in the infection rate both in mother and newborn after antenatal administration of corticosteroids for prevention of RDS has been shown. The aim of this study was to compare PMN functions in two groups of premature infants whose mothers had received betamethasone or ambroxol for prevention of RDS. Blood samples were collected within the first four days of life from 40 newborns. Thirteen infants received antenatal administration of 6 mg of betamethasone acetate and 6 mg sodium phosphate i.m., which was repeated 24 hours later. Twelve received antenatal administration of ambroxol, 1 g i.v. every day for 5 days. Fifteen did not receive any antenatal treatment. Mean gestational age and mean birth weight was not significantly different between the betamethasone group (33 +/- 3.1 weeks and 2080 +/- 567 g) and the ambroxol group (32.9 +/- 3.4 weeks and 2164 +/- 793 g). Phagocytosis and killing ability was significantly lower in the betamethasone group in comparison to the ambroxol group (21.3% +/- 2.2 rather than 48.4% +/- 15; p 0.01 and 11.4% +/- 1.7 rather than 20.5% +/- 6.1; p 0.01 respectively). Immunoglobulin or complement levels were not significantly different in the three groups.

Ambroxol↗

[Generalized and persistent lymphadenopathy in drug addicts: clinical and epidemiological aspects].

Persistent unexplained lymphadenopathy with intermittent fever, weight loss, night sweats and malaise was observed in the period from March 1983 to April 1984 in 66 intravenous drug addicts living in Milan. A high percent of these subjects showed cellular immunity alterations, with significant decrease of total lymphocyte count (p less than 0.001) and of OKT4+ cells (percent and absolute number) (p less than 0.001) OKT8+ cells were augmented in percent, but not in absolute count. OKT4/OKT8 cell ratio were inverted, with significant reduction versus the healthy controls (p less than 0.001). IgG mean concentrations were significantly higher than the normal (p less than 0.001). Anergy or hypoergy to recall skin testing were evidenced in 58/66 patients. Cases of persistent unexplained lymphadenopathy associated with abnormalities of cellular immunity are considered as a possible prodrom of AIDS and were frequently observed in high risk populations. The occurrence of this clinical syndrome in a urban area may be premonitory of further progression to the epidemic. It will be necessary to assess whether this clinical and immunological picture will result in some of these patients in full blown acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Preliminary clinical experiences with the use of immunomodulators in burns.

The remarkable progress achieved in control of infections in burned patients has significantly increased survival rates. Nevertheless, septic complications are still the leading cause of death in these patients. The immunologic disturbances present after severe burns certainly play a key role in susceptibility to infection, and in particular the impairments of the phagocytic system warrant major investigative efforts in order to increase host defenses. Determination of phagocytic and microbicidal capacity of neutrophils from burned patients evidenced a marked functional impairment of these cells. The alterations recorded were partly due to intrinsic (cellular) defects, and partly to extrinsic (serum) defects. Indeed, opsonic factors are known to be reduced in these patients, but also phagocytosis-inhibiting factors such as immunocomplexes have been detected in the patients we have studied. Administration of the immunomodulating agents methysoprinol and timostimoline were found to be effective in partially restoring neutrophil function. Rational immunotherapy in burned patients will consist of replacement of humoral mediators, clearance of inhibitory factors and stimulation of the cellular effectors of immunity.

Adjuvants, Immunologic↗

Humoral immune responses in human loaiasis.

Some immunological parameters in three white patients who contracted loaiasis in endemic areas are reported. Microfilariae count in peripheral blood was elevated in one patient, discrete in another while in the third no microfilariae were detected. Serum IgE levels were elevated in two patients and normal in one of them. High eosinophils percentage (greater than 30%) and high titres of specific anti-filarial antibodies were detected in all patients. C3 and C4 levels fell between the normal values and C3PA was low in one patient. No circulating immune complexes were demonstrated. Two patients showed high anticomplementary activity. Our results are in accord with the possibility of a suppression mechanism in immune response in patients with high microfilaremia. Clinical features of loaiasis could be related to a type 1 (reaginic) reaction.

Adolescent↗