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Biomedical subjects

G Angarano

Publications and source records attributed to G Angarano.

At least 109 records · Page 6Linked to original sources

Early abnormalities of the antibody response against Mycobacterium tuberculosis in human immunodeficiency virus infection.

Among human immunodeficiency virus (HIV)-infected persons, those who react against purified protein derivative (PPD) have higher risk of tuberculosis. Since PPD testing has limited predictive power in HIV-positive populations, new markers of antituberculous immunity were sought by analyzing antibodies to Mycobacterium tuberculosis antigens (PPD and its fraction A60) in 102 HIV-positive subjects, some PPD-positive and some PPD-negative, and in 23 HIV-positive tuberculosis patients. ELISA and Western blotting were used. Forty HIV-negative healthy subjects and 40 HIV-negative tuberculosis patients were evaluated as controls. While all those HIV-negative and PPD-positive had IgG antibodies recognizing the 38-, 28-, and 19-kDa M. tuberculosis antigens, only 26% of those HIV-positive and PPD-positive (all with < 400 CD4+ cells/mm3) and none of the HIV-positive tuberculosis patients recognized them, indicating that the lack of IgG against those antigens, in the presence of a specific IgM response, is a marker of immunodeficiency.

Adolescent↗

Correlation between seroreactivity to HIV-1 V3 loop peptides and male-to-female heterosexual transmission.

OBJECTIVE: To evaluate the correlation between seroreactivity to peptides corresponding to the V3 loop of the major envelope glycoprotein from different HIV-1 strains and the risk of heterosexual HIV-1 transmission. METHODS: Sera from 39 infected individuals (16 transmitters and 23 non-transmitters) were tested for reactivity against synthetic peptides representing sequences of the V3 loop apex from HIV-1 strains MN, SC, WMJ2, RF and IIIB. RESULTS: A skewed distribution in seroreactivity to RF and IIIB peptides was observed between the two groups: reactivity was more prevalent in sera from non-transmitting than from transmitting individuals. Reactivity to the MN, SC and WMJ2 peptides was very frequent and there were no differences between the two groups. CONCLUSION: These data suggest that antibodies reactive with a larger set of V3 apex peptides (i.e., cross-reactive antibodies) could play a role in the prevention of heterosexual transmission.

Amino Acid Sequence↗

Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection.

Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFN alpha 2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFN alpha 2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2-8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.

Alanine Transaminase↗

Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

CD4-Positive T-Lymphocytes↗

Preliminary data on the establishment of permanent cell lines continuously producing HIV-1: factors affecting the transmissibility and adaptability of "wild" HIV-1 isolates.

This study examines some technical aspects of the transmission to and permanent adaptability in continuous cell lines of wild HIV-1 isolates. Three cell systems (the lymphocytic cell lines Molt-3 and H-9 and the monocytoid cell line U-937) and two transmission protocols (cell to cell and cell-free) were used. Two different replicative behaviours were observed among isolates efficiently transmitted: a) transmissibility but not adaptability (consisting in a limited length of viral replication); aa) transmissibility and adaptability (consisting in a stable and long term virus production). The second type of replication was confined to viruses from patients with severe immunodeficiency. Technical and viral factors can affect the rate of transmissibility and adaptability: the modality of infection (cell to cell transmission appeared to be the most efficient) and the tropism of the virus (some viruses could infect only one T cell line).

Adaptation, Physiological↗

A simple method to detect HIV-1 protein specificity of IgG intrathecal synthesis in HIV-1 infection.

There is currently no simple method to detect the antigen specificity of anti-HIV-1 IgG intrathecal synthesis (IS). Fifty-seven pairs of serum and corresponding CSF from 29 HIV-1 seropositive patients were adjusted to an identical concentration of total IgG and tested by a commercial HIV-1 Western Blot (WB) assay. IgG IS to a given HIV-1 protein was demonstrated when the corresponding band was present in CSF but absent or significantly less represented in serum. A total anti-HIV-1 IS was defined as the presence of an IS to one or more HIV-1 antigens. Our WB analysis of CSF and serum, compared with conventional mathematical formulas, showed a higher sensitivity in demonstrating anti-HIV-1 IgG IS. Moreover, the method disclosed which HIV-1 proteins represent the target of IgG IS. This procedure is easy to perform and therefore may represent a valuable tool to study central nervous system (CNS) involvement by HIV-1 during different stages of infection.

Antibody Specificity↗

Zidovudine prophylaxis after accidental exposure to HIV: the Italian experience. The Italian Study Group on Occupational Risk of HIV Infection.

OBJECTIVES: To evaluate the use of zidovudine prophylaxis in HIV-exposed health-care workers (HCW) in Italy and to determine its short-term toxicity. DESIGN: Longitudinal, open study with retrospective and prospective collection of data. SETTING: All Italian clinical centres that care for HIV-infected patients and are licensed by the Ministry of Health to dispense zidovudine and 30 hospitals participating in the Italian Multicentre Study on Occupational Risk of HIV Infection. STUDY POPULATION: HCW and other individuals who accepted zidovudine prophylaxis after accidental exposure to HIV. RESULTS: Data were collected for 224 HIV-exposed individuals until 30 June 1991. An increase in zidovudine prophylaxis was observed. All but 10 subjects received 1000-1250 mg zidovudine per day. Anaemia (five cases), neutropenia (one case) and an increase in serum alanine aminotransferase levels (two cases) were the only haematochemical side-effects observed; none of the subjects ceased prophylaxis because of side-effects. More than 50% of subjects had constitutional reactions; as a result, prophylaxis was stopped by 29 patients. These adverse effects began within 10 days of prophylaxis; all resolved after prophylaxis was stopped. No HIV-antibody seroconversions were observed after a mean follow-up of 8 months. CONCLUSIONS: Zidovudine prophylaxis has become a feature of the management of occupational exposures to HIV in health-care settings; short-term toxicity is mild, dose-related and reversible. Further studies are needed to assess the risk of long-term sequelae.

Administration, Oral↗

HIV-1 isolation from small amounts of whole blood: a technical evaluation.

We have evaluated a simple and sensitive culture technique for isolation of Human Immunodeficiency Virus Type-1 (HIV-1) from small amounts of whole blood. Data shown in the paper demonstrate that: 1) cell cultures from small amounts of heparinized whole blood (HWB) allow a high isolation rate in infected subjects at all stages of diseases; 2) among asymptomatic subjects the HIV-1 isolation rate is increased in cell cultures from HWB, with respect to cell cultures from peripheral blood mononuclear cells; 3) cultural results from HWB are not influenced by the presence of detectable serum p24 antigen, but a good correlation was found with the titre of anti p24 antibodies in serum; 4) continuous cell lines (such as Molt-3 cells) instead of peripheral blood mononuclear cells can be used, obtaining good results, for HIV-1 isolation from HWB; 5) frozen samples of HWB can be used in cell cultures for HIV-1 isolation; 6) the type of anticoagulant (Heparin or EDTA) used for the collection of blood does not influence viral replication in cell cultures from whole blood; 7) viral isolation from HWB is highly sensitive; amounts so small as five microliters of whole blood are sufficient, in some cases, to obtain viral replication in cell cultures; 8) the minimal dose of HWB sufficient to infect cell cultures (HWB M.D.I.) varied among different patients. Although this work failed to establish a correlation between this parameter and the clinical and immunological status of patients, it is conceivable that HWB M.D.I. could give information about viral load in blood and have a prognostic significance; 9) the HWB M.D.I. rise in patients treated with Zidovudine, suggesting that this method could be employed in the virological evaluation of trials with antiretroviral drugs.

Acquired Immunodeficiency Syndrome↗

Lack of HBV and HDV replicative activity in HBsAg-positive intravenous drug addicts with immune deficiency due to HIV.

The effects of HIV infection on HBV and HDV replication and liver damage were evaluated by comparing the findings from 48 anti-HIV-positive HBsAg chronic carriers with those from 22 matched anti-HIV-negative subjects. The state of HBV/HDV infection was also related to the degree of immunodeficiency of the anti-HIV-positive patients. Most patients were intravenous drug addicts (IVDA) (84.2%); male homosexuals represented only a small proportion (7.1%). Serum HBV-DNA was detected more frequently in anti-HIV-negative than in anti-HIV-positive patients (50% vs. 35%) despite evidence of HDV replication in the anti-HIV-negative group (P = 0.02). Seroconversion from ongoing to inactive HBV infection occurred in 45% of anti-HIV-negative patients as well as in 23% of anti-HIV-positive patients (P = ns). The difference in severity of liver damage between the two groups was not statistically significant (P = 0.84). Furthermore, in the anti-HIV-positive subjects, HBV and/or HDV activity was detected in 63% of patients with mild immunodeficiency (CDC groups II and III with a total CD4 count greater than 400/mm3) and also in 75% of ARC-AIDS patients (CDC groups IV A-IV C) (P = ns). Severe hepatic disease occurred in subjects with CD4 counts above or below 400/mm3 (13 vs. 6, respectively). In conclusion, the data do not demonstrate that HBV or HDV infections are modified by HIV. The epidemiological background of the patients investigated and the extensive spread of hepatitis viruses in Italy before the appearance of HIV may account for the lack of relationship between HIV and HBV/HDV infections.

Adult↗

[Analysis of the replication kinetics in primary culture of isolates of HIV-1 from infected patients in various stages of the disease].

The authors have studied the replicative kinetics and the induction of cytopathic effects of HIV-1 in primary co-cultures from infected subjects at various stages of the disease. Cultures from subjects with ARC or AIDS yielded HIV-1 replication more precociously and at higher levels compared to those from asymptomatic subjects; cytopathic effect "in vitro" were observed more frequently and earlier in cell cultures from ARC/AIDS subjects. Presented data indicate that the clinical and immunological deterioration during HIV-1 infection is related to viral replicative activity and suggest that the study of HIV-1 replicative kinetics in primary co-cultures may be helpful in predicting who will progress to AIDS.

AIDS-Related Complex↗

[Isolation of human immunodeficiency virus (HIV) from whole blood].

The authors describe a simple and sensitive technique for HIV isolation from small amounts of heparinized whole blood. This method demonstrated a high efficiency in detecting HIV at all stages of disease and appeared more sensitive with respect to viral isolation from peripheral blood mononuclear cells. Although further studies are needed to better understand the biological significance of a positive cultural result obtained by this method, HIV isolation from whole blood can be routinely employed, especially when small amounts of blood are available.

Acquired Immunodeficiency Syndrome↗

Different biological properties of paired HIV-1 isolates from peripheral blood mononuclear cells and cerebrospinal fluid.

Seven paired HIV-1 isolates from peripheral blood mononuclear cells (PMCs) and cerebrospinal fluid (CSF) of infected subjects at various stages of the disease were studied for their capacity to replicate in continuous cell lines (Molt-3 and U-937 cells) and to induce cytopathic effects "in vitro". Obtained results indicate that paired HIV-1 isolates from PMCs and CSF of the same patient can differ in their replicative activity "in vitro", suggesting that, at least in some cases, CSF isolates may represent a distinct subtype of HIV-1.

AIDS-Related Complex↗

Hepatitis B virus clearance from serum and liver after acute hepatitis delta virus superinfection in chronic HBsAg carriers.

Clinical, virological, and histological findings in four HBsAg chronic carriers who cleared HBV markers from both serum and liver following HDV superinfection are described. The patients were long-term HBsAg carriers and all were HBV-DNA/HBeAg positive. Liver biopsy, obtained from three of the patients between 5 and 15 months prior to HDV superinfection, showed chronic persistent hepatitis in two and chronic active hepatitis in one. During the follow-up of 9-19 months, the patients completely recovered from acute delta hepatitis with termination of HBsAg carriage and regression of the histological feature of chronic liver damage. These data demonstrate that sometimes HDV is able to induce a permanent inhibition of its helper virus. HDV superinfection probably enhances the immune clearance of infected cells during the replicative phase of chronic HBV infection.

Acute Disease↗

HIV-1 variability and progression to AIDS: a longitudinal study.

HIV-1 replicative activity and its relation to the clinical and immunological evolution of infection was studied in a group of 150 HIV-1 seropositive Italian i.v. drug abusers over a 1 year period. HIV-1 was isolated from 90 (60%) subjects; two groups of isolates were distinguished, according to replicative activity "in vitro" and ability to induce cytopathic effects in cell cultures, and were termed "rapid-high" and "slow-low" viruses, in agreement with other workers. Rapid-high viruses were recovered more frequently from patients with ARC/AIDS, while slow-low viruses seemed related to the asymptomatic period of infection. The replicative properties of HIV-1 seem to affect strongly the course of disease. In fact, an important CD4 cell decline occurred in asymptomatic subjects with rapid-high virus infection; asymptomatic subjects with negative viral cultures or with slow-low viruses showed no such decline. Asymptomatic subjects with negative viral cultures had no signs of disease during the observation period, while 9% with slow-low virus and 45% with rapid-high virus progressed to AIDS.

AIDS-Related Complex↗