PubMed Health⌕ Search

Biomedical subjects

L Richeldi

Publications and source records attributed to L Richeldi.

30 records · Page 2Linked to original sources
PubMed1998

Immunogenetic basis of environmental lung disease: lessons from the berylliosis model.

The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.

Animals↗
PubMed1997

Interaction of genetic and exposure factors in the prevalence of berylliosis.

Prevalence of berylliosis, a lung disorder driven by the activation of beryllium-specific T cells, is associated with a major histocompatibility complex (MHC) class II marker (HLA-DPB1Glu69) and with the type of industrial exposure. We evaluated the interaction between marker and exposure in a beryllium-exposed population in which the prevalence of berylliosis was associated with machining beryllium. The presence of the marker was associated with higher prevalence (HLA-DPB1Glu69-positive machinists 25%; HLA-DPB1Glu69-negative machinists 3.2%, P = 0.05) and predicted berylliosis independent of machining history (odds ratios 11.8 and 10.1). The study shows that in berylliosis the carrier status of a genetic susceptibility factor adds to the effect of process-related risk factors.

Adult↗
PubMed1997

Serological markers predicting tuberculosis in human immunodeficiency virus-infected patients.

SETTING: Human immunodeficiency virus (HIV)-positive patients retrospectively identified at the Hospital of Bari, Italy, with diagnosis of tuberculosis (TB) (n = 30) or non-tuberculous pneumonia (n = 29). Serum samples drawn at the time of diagnosis and one year before. Anti-purified protein derivative (PPD) and anti-diacyltrehalose (DAT) serum antibodies quantified by ELISA assay. OBJECTIVE: Since TB patients with HIV infection may present with elevated serum antibodies against Mycobacterium tuberculosis, we hypothesized that TB-specific antibody markers might predict TB in these subjects. DESIGN: A retrospective study was designed to assess the presence of M. tuberculosis-specific antibodies in HIV-positive patients developing TB. RESULTS: Of 30 HIV-positive TB patients, 24 (80%) had anti-PPD or anti-DAT antibodies at the time of TB diagnosis, and 20 (67%) one year before. In a sub-population of 16 of the 30 HIV-positive subjects, positivity for anti-PPD or anti-DAT antibodies one year before TB diagnosis was higher (11/16, 69%) than for the PPD skin test (4/16, 25%, P < 0.01). Antibody tests were specific for TB since positivity rates were lower both in patients with non-tuberculous pneumonia (P < 0.01) and in those with M. avium infection (P < 0.05). CONCLUSION: Antibody markers may predict TB in HIV-positive subjects, including those with negative PPD skin test.

AIDS-Related Opportunistic Infections↗
PubMed1995

Molecular diagnosis of tuberculosis.

Rapid and sensitive tools for the diagnosis of tuberculosis are needed, due to the increased incidence of tuberculosis epidemics and the length of time required by classical diagnostic tests, especially among human immunodeficiency virus (HIV)-infected patients. In this context, the recent advances in cloning and characterization of M. tuberculosis genes has allowed the application of basic molecular biology techniques to the examination of clinical samples, such as sputum and bronchoalveolar lavage (BAL), for the molecular diagnosis of tuberculous infection. By using the polymerase chain reaction (PCR) for the amplification of mycobacterial nucleic acids and nonradiometric revelation techniques, the time required for the identification of mycobacteria has been considerably shortened (24-48 h), in comparison to the time required by microbiological tests. When PCR technique is performed by experienced laboratory personnel using controlled protocols, false-negative (caused primarily by endogenous polymerase inhibitors) and false-positive results (due to contamination) can generally be avoided, achieving sensitivity and specificity close to 100%. In the clinical practice, the use of molecular testing for the diagnosis of tuberculosis, in combination with "classic" diagnostic tools, can greatly enhance the diagnostic ability of pulmonary clinicians, particularly in paucibacillary infections and in patients with atypical presentation, such as immunodeficient individuals.

AIDS-Related Opportunistic Infections↗
PubMed1993

HLA-DPB1 glutamate 69: a genetic marker of beryllium disease.

Chronic beryllium disease (CBD) is a lung disorder related to beryllium exposure and is characterized by the accumulation in the lung of beryllium-specific CD4+ major histocompatibility complex (MHC) class II-restricted T lymphocytes. Evaluation of MHC class II genes in 33 CBD cases and 44 controls has shown a negative association with HLA-DPB1*0401 (P < 0.001) and a positive association with HLA-DPB1*0201 (P < 0.05) alleles, which differ at residues 36, 55 to 56, and 69 of the beta 1 chain. Among CBD cases, 97 percent expressed the HLA-DPB1*0201-associated glutamic acid (unaffected population, 30 percent; P < 0.001) at residue 69, a position involved in susceptibility to autoimmune disorders. This suggests that HLA-DP has a role in conferring susceptibility and that residue 69 of HLA-DPB1 could be used in risk assessment for CBD.

Adult↗
PubMed1993

Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis.

The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.

Adult↗
PubMed1992

[Mycobacterium tuberculosis. From the gene to the diagnosis].

Pulmonary tuberculosis still in on the list of the world major health problems. Tuberculosis has not been eradicated yet, from developing countries. Furthermore, its incidence is increasing in the industrialized world, due to the human immunodeficiency virus (HIV) epidemic. In this regard, atypical clinical presentation of tuberculosis in individuals who have a deficient immune system, such as those at risk of tuberculosis because of HIV infection, makes the diagnostic process more difficult. Tuberculosis cases are often diagnosed later in HIV individuals compared to non-HIV individuals. The ensuing greater risk of contagion thus requires rapid and sensitive diagnostic protocols. In this context, several biotechnological tools have been developed that can be applied to the diagnosis of tuberculosis. M. tuberculosis genes have been cloned, monoclonal antibodies against pure proteins have been produced, thus enabling researchers to generate molecular and biochemical probes. As a consequence, DNA hybridization and DNA amplification techniques have been applied to the detection of mycobacteria, and ELISA kits of high sensitivity are been already made available. In regard to the latter, it is likely that monospecific and highly sensitive immunoassays will be developed that are directed against "active disease" immunodominant antigens. It may thus be expected that future new technologies will supplement the traditional tools for the diagnosis of tuberculosis and rapid diagnosis protocols will be available to chest clinicians in a foreseeable future.

Antibodies, Bacterial↗
PubMed1988

Activities of human alveolar macrophages (HAMs). Note 1: Observations on phagocytosis and bacterial killing in the presence of miocamycin.

We studied the activity of human alveolar macrophages (HAMs) obtained by bronchoalveolar lavage (BAL) from human lungs. In particular, we studied in vitro phagocytosis and bacterial killing in basal conditions and in the presence of miocamycin (MOM), a macrolide antibiotic. At a dose of 600 mg every 12 hours, MOM concentrations in the serum were 2.60 micrograms/ml 1 hour after administration and 0.75 microgram/ml 8 h after. The antibiotic cannot be assayed by the microbiological method in the acellular liquid of alveolar lavage. After penetrating the HAMs, it can be detected at a concentration of about 0.4 mcirograms/1.10(6) HAMs. MOM was able to penetrate HAM cytoplasm without altering their vitality. As a matter of fact, the Trypan blue exclusion dye test was not modified after long incubation in the presence of MOM. The HAMs, resuspended in a RPMI 1640 enriched medium, were able to phagocytize either live Staphylococci or inert Latex beads of 1 micron. MOM stimulated the HAM phagocytosis on both Staphylococci and Latex beads. The increase in Latex phagocytosis, a relatively inert substance on which MOM should not be active, is a confirmation of the antibiotic's directed stimulation of the HAMs. Finally, we have seen that the HAMs, which were noteworthy in killing the phagocytized bacteria, were stimulated by MOM after only 30 minutes of contact with the antibiotic.

Anti-Bacterial Agents↗