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Biomedical subjects

O Picard

Publications and source records attributed to O Picard.

At least 37 records · Page 2Linked to original sources

Impairment of circulating lactoferrin in HIV-1 infection.

Levels of plasma lactoferrin are decreased in HIV-1-infected patients in relation to the progression of the disease. Plasma lactoferrin concentrations were determined using a specific and sensitive enzyme immunoassay. 97 plasma were studied (22 asymptomatic, 45 symptomatic patients compared to 30 healthy controls) and the results showed a highly significant decrease (p < 0.001) of the level of lactoferrin in HIV-1-infected patients (respectively 2.79 +/- 1.2 and 0.68 +/- 0.22 micrograms/ml) compared to controls (4.37 +/- 0.83 micrograms/ml). Since it is well established that plasma lactoferrin level could be influenced by the number of neutrophils, the experiments were reproduced in neutropenic patients who represent 10% of recruitment (6 among 45 symptomatic patients). The plasma from neutropenic symptomatic patients (neutrophils < or = 1,300/mm3) showed their mean lactoferrin level at 0.36 micrograms/ml still far above the normal values. In view of the different reported biological effects of lactoferrin that are of great importance in the non-specific defences, the real biological place of the lack of such a molecule could be one important component of the multifactorial nature of HIV-1 infection.

AIDS-Related Complex↗

A prospective evaluation of clinical criteria and polymerase chain reaction assay of cerebrospinal fluid for the diagnosis of cytomegalovirus-related neurological diseases during AIDS.

OBJECTIVE: To study the predictive value of clinical criteria and polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) for the diagnosis of cytomegalovirus (CMV)-related neurological disorders during AIDS. SETTING: Four infectious diseases departments in two tertiary referral teaching hospitals in Paris, France. DESIGN AND PARTICIPANTS: One-year prospective study involving 164 consecutive immunosuppressed HIV-seropositive patients undergoing lumbar puncture (LP). METHODS: A tentative diagnostic classification, based on strict operational criteria and PCR assay of CSF, was performed at the time of LP. At the end of the study, tentative diagnoses and PCR results were blindly and independently compared with the firm diagnoses, based on central nervous system histology, clinical outcome and/or viral culture of CSF. RESULTS: The tentative diagnosis showed CMV-related neurological disease in 38 patients, and CMV DNA was detected in 42. Among the 88 patients for whom a firm diagnosis was possible, 26 had a diagnosis of CMV-related neurological disease. The concordance between the tentative and firm diagnoses was 61%, with a kappa index of 0.40. In contrast, the sensitivity and specificity of PCR were respectively 92 and 94%, with positive and negative predictive values of 86 and 97%. The presence of CMV DNA in CSF was associated with an increased risk of death (P < 0.0001). CONCLUSIONS: Unlike clinical criteria, PCR detection of viral DNA in CSF can be used reliably for antemortem diagnosis of CMV-related neurological disease, a frequent complication of AIDS in this study. This rapid method should make a major impact on the management of these patients.

AIDS-Related Opportunistic Infections↗

Antiretroviral therapy for human immunodeficiency virus infection: hope and despair.

While considering AIDS as an infectious disease with a direct relation between the etiologic agent and the deep immunodeficiency, antiretroviral drugs created much hope. The only transient effect observed with AZT treatment may not be due only to resistance occurrence but to effects that AZT does not target. These effects seem to be related to cytokines secretion which major the immunodepression. Efficient treatment should restore a normal cytokines network.

Acquired Immunodeficiency Syndrome↗

Detection of CTL activity in PBMCS taken from HIV-ENV immunized individuals after in vitro viral infection.

The cellular immune response to the AIDS virus in healthy individuals immunized with HIV-1 antigens has not yet been entirely understood. Unlike HIV-1 infected patients where direct measurements of anti HIV-1 CTL activities can be readily performed with fresh peripheral blood mononuclear cells, uninfected volunteers immunized against HIV-1 antigens have fewer circulating CTL necessitating an in vitro activation in order to amplify the cytotoxic signal and make it measurable. This study presents experiments where specific CTLs are successfully obtained simply by in vitro infection of PBMCs from HIV-1 Envelope immunized individuals.

Acquired Immunodeficiency Syndrome↗

[Risk of nosocomial Pneumocystis carinii pneumonia in immunosuppressed patients non-infected by human immunodeficiency viruses].

We report four cases of Pneumocystis carinii pneumonia (PCP) in Human Immunodeficiency Virus (HIV)-seronegative patients. Two of them had been hospitalized for polymyositis treatment near AIDS patients, respectively 1 and 4 months before PCP. The two others suffered from localized cancer. Their evolution was complicated by respiratory distress and death in two of them. A telephone survey among 19 hospital units yielded nine cases of similar patients. They were only observed in wards caring for AIDS patients at the same time, thus raising the question of a possible nosocomial transmission of PCP between AIDS patients and immunocompromised HIV-seronegative patients. This adds to the growing concern for hospital-acquired infections, including resistant tuberculosis and other opportunistic pathogens. We propose some practical measures to limit this risk by simple means such as no-contact between at-risk populations, enhanced disinfection procedures of the rooms and masking of the coughing PCP patients.

Aged↗

Cytotoxic T lymphocytes specific for HIV-1 gp160 antigen and synthetic P18IIIB peptide in an HLA-A11-immunized individual.

Cytotoxic T cell determinants should be an important component of an anti-human immunodeficiency virus (HIV) vaccine. The epitopes of proteins can be defined with short synthetic peptides for class I-restricted CTLs. An immunodominant CTL epitope from the HIV-1 IIIB envelope protein gp160 comprising 15 amino acids (residues 315-329: RIQRGPGRAFVTIGK) (P18IIIB) has been identified that is recognized by class I MHC molecule H-2d-restricted murine CD8+ CTLs. We have investigated the epitope specificity of anti-HIV-1 CTLs in immunized individuals and we found that the CTL response was restricted by more than one class I MHC molecule, including HLA-A2 and HLA-A3. In the present work, we also show that the response against P18IIIB peptide is restricted by the HLA-A11 molecule in an individual immunized by vaccinia virus expressing gp160 protein. This peptide could thus be recognized in association with different HLA class I allotypes. This work has implications for vaccine strategies, using the P18 peptide.

Amino Acid Sequence↗

Antilactoferrin autoantibodies associated with HIV infection.

Sera from 85 HIV-infected patients were tested for the presence of antilactoferrin antibodies (anti-LF Abs) by specific ELISA. Fifty-seven sera were found positive, including sera from asymptomatic (18/28, 64.3%, mean O.D.: 0.27 +/- 0.05) and symptomatic patients (39/57, 68.4%, mean O.D.: 0.82 +/- 0.15). In the control group, only one out of 26 normal donors show any reactivity (mean O.D.: 0.06 +/- 0.01). None of the tested patients had clinical evidence of vasculitis, the previous reported antilactoferrin-associated pathology and if, in both groups, a similar frequency of anti-LF Abs was found, the autoantibody level was significantly higher among the symptomatic patients (p < 0.01). However, correlation was found neither with polymorphonuclear cell counts nor with the level of circulating lactoferrin. The characterization and the clinical significance of the autoantibodies are under investigation.

Acquired Immunodeficiency Syndrome↗

Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis.

CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1-infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression.

Acquired Immunodeficiency Syndrome↗

Envelope protein and p18(IIIB) peptide recognized by cytotoxic T lymphocytes from humans immunized with human immunodeficiency virus envelope.

Cytotoxic T cells are the main antigen-specific effector cells of the cellular immune system and MHC class I restricted cytotoxic T-lymphocyte (CTL) responses in mice, acting against the HIV-1 envelope protein, are known to be predominantly directed against an amino acid sequence in the third hypervariable domain. We have investigated the epitope specificity of anti-HIV-1 CTL in healthy human volunteers inoculated with a recombinant vaccinia expressing the HIV-1 gp160 envelope gene. Their isolated lymphocytes were stimulated in vitro with autologous HIV-1 infected cells. Our results show that immunization with recombinant virus is able to generate virus-specific CTLs to the HIV-1 gp160 envelope protein and to a 15-residue synthetic peptide corresponding to a highly variable region of the envelope p18(IIIB). The CTL response was restricted by class I MHC molecules HLA-A2 and A3 that commonly occur in the human population.

AIDS Vaccines↗

Striking similarities between HIV-1 Env protein and the apoptosis mediating cell surface antigen Fas. Role in the pathogenesis of AIDS.

We have designed a computer strategy in order to detect systematically peptidic sites with the potential of interfering with the immune regulatory processes. Applying this software to HIV-1 proteins has led us to unravel a few peptidic sites which could either act directly or be the targets of an auto-immune reaction during HIV-1 infection. We previously reported that the SLWDQ pentapeptide identity with a critical site of CD4 could trigger in HIV-1 infected individuals both an humoral and a cellular autoimmune reaction. In this study, we focused on surprising similitudes unravelled by our software Automat, between HIV-1/2 and another immunoregulatory molecule, the Fas protein which is also called the apoptosis-mediating cell-surface antigen.

Acquired Immunodeficiency Syndrome↗

An unusual case of mycosis fungoides presenting as sarcoidosis or granulomatous mycosis fungoides.

The authors describe a case of cutaneous and lymph node granulomas first reported as sarcoidosis. As skin sarcoidlike reactions disappeared, the development of typical histologic and immunopathologic features of cutaneous mycosis fungoides suggested granulomatous mycosis fungoides. This case illustrates the difficulties in differentiating true systemic sarcoidosis associated with mycosis fungoides from sarcoidlike reactions when extensive granulomas obscure the underlying cutaneous lymphoma. This report emphasizes the utility of immunohistochemical analysis to identify the early cutaneous T-lymphomatous infiltrate, initially admixed with epithelioid and giant cell granulomas. This technique also made it possible to characterize a Ki-1-positive anaplastic large-cell lymphoma when the transformation of mycosis fungoides into highly malignant lymphoma occurred in the lymph node.

Adult↗

Human cytomegalovirus (HCMV) late-mRNA detection in peripheral blood of AIDS patients: diagnostic value for HCMV disease compared with those of viral culture and HCMV DNA detection.

A reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect a human cytomegalovirus (HCMV) late mRNA in peripheral blood leukocytes (PBL) of 102 human immunodeficiency virus-infected individuals. The clinical value of this new technique for the diagnosis of acute HCMV disease was evaluated in comparison with viral culture and direct amplification of viral DNA (PCR). The sensitivity of the RT-PCR was slightly lower than that of the two other methods, but its specificity was 94%, compared to 55 and 32% for culture and PCR, respectively. Transcription of this late mRNA is linked to viral replication, and its detection in PBL confirms that these cells can support a complete viral cycle. The relationship between complete replicative cycles and HCMV disease makes RT-PCR a useful clinical tool.

AIDS-Related Opportunistic Infections↗

Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate.

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.

AIDS Vaccines↗

Cell-mediated immunity against HGP-30, a group-specific peptide of HIV p17 in individuals infected with the AIDS virus.

HGP-30, the synthetic peptide analogue and active component in an HIV-1 (human immunodeficiency virus, type 1) p 17 core-based experimental vaccine, has previously been shown to induce cytotoxic and helper T-lymphocyte responses. In order to further define the T-helper cell responses which are known to play a role in enhancing the immunological response to foreign antigens, we studied the response of individuals infected with HIV to HGP-30 at various stages of disease progression. We have investigated the proliferative cellular response of peripheral blood mononuclear cells (PBMCs) derived from individuals infected with HIV-1 to HGP-30. We have found a PBMC proliferative response to HGP-30 in 40% of the healthy seroconverted patients, in 35% of the CDC stage III patients and in 18% of the CDC stage IV patients. There was no correlation between the proliferative response to HGP-30 and other antigens such as HIV-like proteins or tetanus toxoid not to CD4 cell count. HLA-DR typing revealed the possible presentation of HGP-30 by several different class II molecules. Since these class II molecules occur frequently in the general population, HGP-30 appears to contain broadly reactive epitopes and thus is not restricted as are many peptide vaccines. Due to its broad reactivity and extreme conservation in many HIV-1 strains. HGP-30 is one of the promising candidates for inclusion as a subunit vaccine against HIV-1.

Acquired Immunodeficiency Syndrome↗

Rapid detection of cytomegalovirus DNA in cerebrospinal fluid of AIDS patients with neurologic disorders.

A polymerase chain reaction (PCR)-based method was used to detect cytomegalovirus (CMV) DNA in 82 cerebrospinal fluid (CSF) samples from 67 patients infected by human immunodeficiency virus (HIV). The test was positive for 14 patients, 8 of whom had CMV-related neurologic disease proven by viral culture of CSF or histologic examination. Encephalitis was the most frequent manifestation in patients with positive PCR results, but CMV DNA was also present in some patients with peripheral neuropathy or polyradiculomyelitis. All patients with proven CMV neurologic disease were positive by PCR. In contrast, viral culture was negative for 4 of the 8 patients and pathologic studies were available only for 5. The specificity of the PCR-based assay could not be assessed precisely because of the lack of a reference standard, but the results correlated well with clinical course and results of the other methods. These findings suggest that the PCR-based method may be a useful noninvasive tool for the rapid diagnosis of CMV-related neurologic disease.

AIDS-Related Opportunistic Infections↗

[Objective evaluation of sclerodermic skin using the slip-test. Results and validation with 30 patients and 60 controls].

The slip test is a non-invasive way to objectively evaluate the extent of scleroderma by measuring the "slipping" of the skin over an underlying bone. The results obtained in 30 scleroderma patients and 60 controls (178 tests due to multiple measurements) were analyzed to determine which test sites show a significant difference between patients and controls (Student's t-test) and which sites are the most discriminating for the diagnosis of the disease (multivariate analysis). Patient values were clearly distinct from those of controls. The best sites (defined by p < 0.05) were: the mandible, the second and first phalanges of the middle finger, the hands, the forearms, the epicondyles, the sternum, the iliac crests, the patellae, the tibias (the upper and lower fourths) and the feet; in all, 23 sites to which can be added the opening of the mouth (measurement of the maximal interlabial distance), which proved to be a reliable parameter. Multiple regression analysis yielded an equation that identified patients with scleroderma based on 4 variables (right forearm, right iliac crest, sternum and right rib). The slip test is thus the first reproducible quantitative test able to confirm and quantify clinical impressions in scleroderma. It is entirely able to objectively monitor the evolution of the disease under treatment. Nevertheless, complementary studies are needed to verify whether the slip test, which can be performed in 20 minutes during an office visit, can be used advantageously in the routine clinical evaluation of scleroderma.

Adult↗