F. Sorice

Serum selenium concentration and disease progress in patients with HIV infection

The selenium concentration in the serum of 67 patients with HIV infection was measured to determine whether selenium deficiency occurred in the different stages of the disease. In the first stage of the study, patients were divided into four groups: symptom-free subjects, PGL (persistent generalized lymphadenopathy), ARC (AIDS related complex), and AIDS (acquired immunodeficiency syndrome). Selenium concentrations were normal in HIV antibody positive symptom-free subjects (1.18 +/- 0.27 mumol/L) and lower than normal in the other three groups (p less than 0.001). There was a significant correlation (p less than 0.001) between selenium levels and values of hemoglobin and erythrocyte sedimentation rate. Selenium deficiency was in no case associated with a lack of zinc in serum (also determined in all patients). In the second stage of the study, 12 patients were treated for a period of two months with low doses of selenium to assess whether such supplementation was able to restore their impaired immunological and hematological functions. The therapy increased serum selenium concentrations (from 0.77 +/- 0.23 to 1.44 +/- 0.41 mumol/L) and symptomatic improvements were noted. However, no changes were observed in the immunological and hematological parameters.

Cytomegalovirus encephalitis in two patients with AIDS receiving ganciclovir for cytomegalovirus retinitis

Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS.

High cerebrospinal fluid and serum levels of tumor necrosis factor-α in asymptomatic HIV-1 seropositive individuals. Correlation with interleukin-2 and soluble IL-2 receptor

The relationship between tumour necrosis factor-alpha (TNF-alpha) and the interleukin-2 (ILL-2) system in HIV-1 infection is important in understanding the dynamics of early immune response before the development of acquired immunodeficiency syndrome. Levels of TNF-alpha, IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured. High levels of TNF-alpha were detected in CSF of 17 (55%) and serum of 22 (71%) subjects, 15 (88%) of whom had elevated CSF IL-2 levels and 16 (94%) had high sIL-2R levels. Moreover, CSF levels of TNF-alpha significantly correlated with CSF levels of IL-2 and sIL-2R. TNF-alpha, IL-2 and sIL-2R seem to be released within the intrathecal compartment early in the course of HIV-1 infection. In view of the known cytotoxic effects of TNF-alpha, an early release may contribute to subsequent development of neurological complications.

The Effects of Substance P on Human Eosinophil Receptors and Functions

The undecapeptide substance P (SP), Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-LeuMet-NH,, was the first peptide found in both brain and gut. Release of SP from the peripheral terminals of sensory fibers is induced by nerve stimulation and various kinds of irritation of the tissues such as anoxia, heat irradiation, and The effects mediated by the release of SP by peripheral terminals are vasodilatation, histamine release, plasma extravasation, and contraction of smooth Overall, the SP-induced changes seem to function as a local defense mechanism. Many diseases in which sensory SP neurons have been postulated to contribute to the clinical manifestations (e.g., respiratory tract hyperreactivity, chronic inflammatory processes, urticaria) are characterized by an associated blood or tissue eosinophilia. No data are available on the relationship between SP and eosinophilic leukocytes, but previous observations have shown that SP can be considered a modulator of local immunologic responses. SP increases rH]thymidine and [3H]leucine uptake by T lymphocytes, phagocytosis of yeast particles by polymorphonuclear cells, H,O, production and chemotaxis of human leukocyte?-5 By using both radiolabeled or fluorescent conjugates of SP, specific receptors have been defined on a subset of T lymphocyte^.^ The results reported here show that in vitro SP significantly increases Fc IgG and Fc IgE receptor expression on the surface of human eosinophils and antibody (1gG)dependent cytotoxicity against nucleated target cells.

LDH Isoenzyme Distribution in Human Eosinophils

The lactate dehydrogenase (LDH) isoenzyme pattern has been determined in human eosinophils isolated from the peripheral blood of healthy donors and patients with parasitic diseases. Almost equal LDH1 and LDH5 values appear to be a characteristic of the eosinophils obtained from healthy subjects. Eosinophilic granulocytes which have been isolated from the peripheral blood of patients with eosinophilia due to parasitic infestations have reduced values of LDH5 accompanied by higher LDH1 as compared with eosinophils from healthy donors. Centrifugation of cells through multiple discontinuous gradients of polyvinylpyrrolidone-coated silica particles made it possible to isolate distinct eosinophil subpopulations of differing densities which showed differences in cell surface markers, K-cell activity and also LDH patterns. Analysis of the lactate dehydrogenase isoenzyme patterns showed that EAG+ and EAC+ eosinophilic leukocytes are characterized by very low values of LDH5.

Clinical and immunological assessment in HIV+ subjects receiving inosine-pranobex. A randomised, multicentric study

Inosine-pranobex (methisoprinol, isoprinosine; INPX) is thep-acetamidobenzoic salt of N,N-dimethylamino-2-propanol and inosine in a 3:1 molar ratio. In early studies, INPX was found to partially inhibit human immunodeficiency virus (HIV) and to increase the immunocompetence of HIV-infected subjectsin vitro.We report the results of a randomised, multicentric clinical trial carried out on 553 HIV+ patients. 261 individuals were treated with INPX (two 500 mg tablets every 6 h for 3 months) and the remaining 292 constituted the untreated control group. INPX treatment was associated with a slightly improved clinical condition or with a trend in that direction, as compared to the untreated group. A preservation of the CD4/CD8 cell ratio values, a decrease in the CD8+ cells and an increase in the Leu 2–7+ cell number better than in the untreated individuals was also observed in the patients taking INPX. No serious or adverse effects of INPX have been observed.

Fractionation and characterization of hydatid fluid antigens with identification of an antigen similar to human serum albumin

Human and sheep hydatid fluids were separated by ultrafiltration, gel chromatography and immunoabsorption into several immunogenic fractions in which both parasite antigens and host substances were present. The immunological characterization of proteic antigens was carried out by immunodiffusion and immunoelectrophoresis with rabbit and ram antisera. A line of identity was observed between a human fraction (labelled as III) and a sheep fraction (labelled as 2B). Further evidence of the presence of a parasitic antigen in fraction III was given by its reaction against an antiserum from ram directed against sheep fraction 2B. The immunological characterization of fraction III indicated a close similarity between human serum albumin and parasitic antigens.

Tumour necrosis factor-α mediates blood—brain barrier damage in HIV-1 infection of the central nervous system

The pathogenesis of brain inflammation and damage by human immunodeficiency virus (HIV) infection is unclear. Because blood–brain barrier damage and impaired cerebral perfusion are common features of HIV-1 infection, we evaluated the role of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mediating disruption of the blood–brain barrier. Levels of TNF-α were more elevated in cerebrospinal fluid (CSF) than in serum of HIV-1 infected patients and were mainly detected in those patients who had neurologic involvement. Intrathecal TNF-α levels correlated with signs of blood–brain barrier damage, manifested by high CSF to serum albumin quotient, and with the degree of barrier impairment. In contrast, intrathecal IL-1β levels did not correlate with blood-brain barrier damage in HIV-1 infected patients. TNF-α seems to be related to active neural inflammation and to blood–brain barrier damage. The proinflammatory effects of TNF-α in the nervous system are dissociated from those of IL-1β.

Cerebrospinal Fluid Antiganglioside Antibodies in Patients with AIDS

SummaryIn this study the presence of brain antiganglioside antibodies in the cerebrospinal fluid (CSF) of patients with HIV infection was analysed. CSF samples were collected from 45 patients with AIDS and from 45 anti-HIV negative subjects, 15 of whom presented aseptic meningitis. Nineteen AIDS patients had clinically well-documented encephalopathy. Thirteen of these patients had white matter lesions shown by magnetic resonance imaging (MRI). Both IgG and IgM antiganglioside antibodies were detected by immunostaining on thin layer chromatography plates in three CSF samples from AIDS patients with progressive encephalopathy with signs of a diffuse demyelination, as revealed by MRI. Two of these CSF samples reacted specifically with GM3, GM1 and GD1a and one with GD1a. In none of the HIV infected patients without demyelinating encephalopathy, but with opportunistic infections or cerebral lymphoma, nor in the anti-HIV negative control subjects were antiganglioside antibodies detected. No association with JCV DNA, CMV DNA, EBV DNA, detected by nested PCR, nor HIV antigen p24 was found. These findings show the presence of brain antiganglioside antibodies in the CSF of AIDS patients for the first time. However, the findings do not suggest relating the presence of these antibodies to HIV encephalopathy or particular viral agents, but indicate that the antibodies are detectable in subjects with progressive encephalopathy with a diffuse demyelination.ZusammenfassungDas Vorkommen von Antigangliosid-Antikörpern im Liquor cerebrospinalis wurde bei Patienten mit HIV-Infektion untersucht. Liquorproben wurden von 45 Patienten mit AIDS und von 45 anti-HIV-negativen Personen (davon 15 mit aseptischer Meningitis) entnommen. 19 der AIDS-Patienten hatten eine klinisch eindeutig dokumentierte Encephalopathie. Bei 13 dieser Patienten waren mit Kernspintomographie (MRI) Läsionen in der weißen Substanz nachzuweisen. Antigangliosid-Antikörper der IgG und IgM-Klassen wurden mit Immunstaining auf Dünnschichtchromatographie-Platten in drei Liquorproben von AIDS Patienten mit progressiver Encephalopathie mit den Zeichen einer diffusen Entmarkung, wie sie sich im MRI dargestellt hatten, entdeckt. Zwei dieser Liquorproben reagierten spezifisch mit GM3, GM1 und GD1a und eine mit GD1a. Anti-Gangliosidantikörper waren bei keinem der HIV-infizierten Patienten ohne demyelinisierende Encephalopathie aber mit opportunistischen Infektionen oder mit zerebralem Lymphom und auch bei keinem der anti-HIV negativen Kontrollpersonen nachzuweisen. Es fand sich keine Beziehung mit JCV DNA, CMV DNA oder EBV DNA, die mit Schachtel-PCR nachgewiesen wurden und auch nicht mit dem HIV-Antigen p24. Mit diesen Untersuchungen wird erstmal der Nachweis eines Vorkommens von Antigangliosid-Antikörpern im Liquor von AIDS-Patienten erbracht. Doch ist aus den Befunden keine Beziehung des Antikörpernachweises zur HIV-Encephalopathie oder definierten viralen Agentien abzuleiten. Vielmehr ist festzustellen, daß die Antikörper bei Personen mit progressiver Encephalopathie mit diffuser Demyelinisierung zu finden sind.In this study the presence of brain antiganglioside antibodies in the cerebrospinal fluid (CSF) of patients with HIV infection was analysed. CSF samples were collected from 45 patients with AIDS and from 45 anti-HIV negative subjects, 15 of whom presented aseptic meningitis. Nineteen AIDS patients had clinically well-documented encephalopathy. Thirteen of these patients had white matter lesions shown by magnetic resonance imaging (MRI). Both IgG and IgM antiganglioside antibodies were detected by immunostaining on thin layer chromatography plates in three CSF samples from AIDS patients with progressive encephalopathy with signs of a diffuse demyelination, as revealed by MRI. Two of these CSF samples reacted specifically with GM3, GM1 and GD1a and one with GD1a. In none of the HIV infected patients without demyelinating encephalopathy, but with opportunistic infections or cerebral lymphoma, nor in the anti-HIV negative control subjects were antiganglioside antibodies detected. No association with JCV DNA, CMV DNA, EBV DNA, detected by nested PCR, nor HIV antigen p24 was found. These findings show the presence of brain antiganglioside antibodies in the CSF of AIDS patients for the first time. However, the findings do not suggest relating the presence of these antibodies to HIV encephalopathy or particular viral agents, but indicate that the antibodies are detectable in subjects with progressive encephalopathy with a diffuse demyelination. Das Vorkommen von Antigangliosid-Antikörpern im Liquor cerebrospinalis wurde bei Patienten mit HIV-Infektion untersucht. Liquorproben wurden von 45 Patienten mit AIDS und von 45 anti-HIV-negativen Personen (davon 15 mit aseptischer Meningitis) entnommen. 19 der AIDS-Patienten hatten eine klinisch eindeutig dokumentierte Encephalopathie. Bei 13 dieser Patienten waren mit Kernspintomographie (MRI) Läsionen in der weißen Substanz nachzuweisen. Antigangliosid-Antikörper der IgG und IgM-Klassen wurden mit Immunstaining auf Dünnschichtchromatographie-Platten in drei Liquorproben von AIDS Patienten mit progressiver Encephalopathie mit den Zeichen einer diffusen Entmarkung, wie sie sich im MRI dargestellt hatten, entdeckt. Zwei dieser Liquorproben reagierten spezifisch mit GM3, GM1 und GD1a und eine mit GD1a. Anti-Gangliosidantikörper waren bei keinem der HIV-infizierten Patienten ohne demyelinisierende Encephalopathie aber mit opportunistischen Infektionen oder mit zerebralem Lymphom und auch bei keinem der anti-HIV negativen Kontrollpersonen nachzuweisen. Es fand sich keine Beziehung mit JCV DNA, CMV DNA oder EBV DNA, die mit Schachtel-PCR nachgewiesen wurden und auch nicht mit dem HIV-Antigen p24. Mit diesen Untersuchungen wird erstmal der Nachweis eines Vorkommens von Antigangliosid-Antikörpern im Liquor von AIDS-Patienten erbracht. Doch ist aus den Befunden keine Beziehung des Antikörpernachweises zur HIV-Encephalopathie oder definierten viralen Agentien abzuleiten. Vielmehr ist festzustellen, daß die Antikörper bei Personen mit progressiver Encephalopathie mit diffuser Demyelinisierung zu finden sind.

Intrathecal synthesis of interleukin-2 and soluble IL-2 receptor in asymptomatic HIV-1 seropositive individuals: Correlation with local production of specific IgM and IgG antibodies

The relationship between the interleukin-2 (IL-2) system and the humoral response against human immunodeficiency virus type-I (HIV-1) is important in understanding the immune reaction before the development of AIDS. Levels of IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured and correlated with levels of anti-1 IgG and IgM antibodies. High IL-2 levels were detected in the CSF of 20 (65%) subjects, 18 (90%) of whom had evidence of intrathecal synthesis of HIV-1-specific IgM antibodies. Similarly, IgG antibodies were detected in 10 subjects who had elevated IL-2 levels in the CSF. Moreover, intrathecal levels of IL-2 and sIL-2R correlated with intrathecal synthesis of both IgG and IgM antibodies. Local release of IL-2 seems to play an important role in the initiation of the antibody response against HIV-1 in early stages of infection and may be utilised in devising effective therapeutic strategies.