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Biomedical subjects

C Saltini

Publications and source records attributed to C Saltini.

At least 55 records · Page 3Linked to original sources
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

Activation of alveolar macrophages in asymptomatic HIV-infected individuals.

After the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection during the progression of this immune dysfunction, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system, during the asymptomatic phase of HIV infection. Compared to normals, in HIV-infected individuals the class II MHC molecules DR, DQ, and DP were all expressed more frequently and in greater cell surface density on AM (p < 0.03, all comparisons), and there was increased spontaneous release of superoxide anion (O2-.) by AM (p < 0.002). To gain insight into whether the activation of the AM was an inherent property of the cells or dependent on the in vivo milieu, AM were evaluated after 24 h in culture for O2-. release. In contrast to the findings in fresh AM, after 24 h in culture, O2-. release by HIV AM was not different from normals (p > 0.7), suggesting that these AM had been activated in vivo. To assess whether IFN-gamma could be mediating these effects, mRNA levels of the IP-10 gene (a gene specifically induced by increased concentrations of IFN-gamma) were quantified in AM. Strikingly, the IP-10 gene was expressed only in AM of HIV-seropositive individuals, suggesting the AM had been exposed to IFN-gamma in vivo. Overall, these observations are consistent with the concept that the HIV-seropositive state is associated with activation of AM, in part due to local exposure to IFN-gamma.

Adult↗
PubMed1993

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↗
PubMed1993

Mycobacterial antigen complex A60-specific T-cell repertoire during the course of pulmonary tuberculosis.

The Mycobacterium bovis antigen complex A60 is known to be immunodominant in tuberculosis and to have a protective effect against experimental infection in vitro and in vivo. To identify immunodominant and possibly protective antigens in pulmonary tuberculosis, the T-cell repertoire directed to nitrocellulose-bound fractions of A60 antigen was analyzed in active tuberculosis patients during the course of the infection and after recovery. The results show that patients infected with Mycobacterium tuberculosis acquired complete A60-T-cell reactivity only in the late phases of infection. At disease onset, patients with active tuberculosis were characterized by (i) T-cell unresponsiveness to most A60 fractions, (ii) high tumor necrosis factor alpha production, and (iii) low gamma interferon (IFN-gamma) release. Several weeks after chemotherapy, the unresponsive state disappeared and the following reverse situation was observed: (i) high blastogenic response to almost all A60 fractions, (ii) low tumor necrosis factor alpha release, and (iii) high IFN-gamma production. In addition, 60% of these patients significantly responded against seven A60 fractions (61 to 58, 56 to 53, 49 to 46, 46 to 44, 35 to 33, 33 to 30, and 30 to 28 kDa), indicating that they included immunodominant antigens. Furthermore, only the fractions within the molecular mass ranges of 56 to 44 and 35 to 28 kDa induced IFN-gamma synthesis. One year after complete recovery from infection, more than 60% of past-active tuberculosis subjects had memory T cells specific for the immunodominant fractions of 61 to 58, 56 to 53, 49 to 46, and 33 to 30 kDa. Since the same fractions induced the strongest IFN-gamma production, known to exhibit antimycobacterial effects, it is suggested that these may represent the inducers of a protective immune response.

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

T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor.

Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T-cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the alpha beta receptor, the most abundant type of TCR. The surface density of T-cell surface alpha beta TCR expression was evaluated by flow cytometry with an anti-alpha beta antibody and TCR beta-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface alpha beta TCR expression and increased beta-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of alpha beta TCR compared with their autologous blood T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1991

Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung.

In the context of the central role of the alveolar macrophage in host defense of the respiratory epithelial surface, and the ability of IFN-gamma to activate mononuclear phagocytes, we have evaluated strategies to use rIFN-gamma to activate human alveolar macrophages in vivo. To accomplish this, rIFN-gamma was administered to nonsmoking normals, the amounts of IFN-gamma quantified in serum and respiratory epithelial lining fluid (ELF) and the status of IFN-gamma related activation of blood monocytes and alveolar macrophages was evaluated by quantifying the expression of mRNA transcripts of IP-10, a gene induced specifically by IFN-gamma. Systemic administration (subcutaneous) of maximally tolerated amounts of rIFN-gamma (250 micrograms) was followed by detectable levels of IFN-gamma in serum but not ELF, the expression of IP-10 transcripts in blood monocytes but not alveolar macrophages, and multiple systemic adverse effects. To circumvent the inability of systemic administration to reach respiratory ELF and activate alveolar macrophages, rIFN-gamma (250-1,000 micrograms) was inhaled as an aerosol once daily for 3 d. Strikingly, while IFN-gamma was not detected in serum it was detectable in respiratory ELF in a dose-dependent fashion. Further, alveolar macrophages, but not blood monocytes, expressed IP-10 mRNA transcripts and, importantly, inhalation of aerosolized rIFN-gamma was not associated with local or systemic adverse effects. Thus, it is feasible to use rIFN-gamma to activate alveolar macrophages by targeting the cytokine directly to the lung. These data suggest a potential strategy for targeted cytokine therapy, without systemic side effects, to augment respiratory tract defenses in individuals at risk for or with lung infection.

Actins↗
PubMed1990

Biased accumulation of T lymphocytes with "memory"-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung.

Expression of alternatively spliced products of the CD45 leukocyte common antigen gene identifies two populations of blood T cells: "naive" T cells (containing CD45R-IV mRNA transcripts, CD45 220, 205 kD surface proteins detected with antibody 2H4) that respond poorly to recall antigens, and "memory" T cells (containing CD45R-0 mRNA transcripts, expressing CD45 180 kD protein, detected with antibody UCHL1) that respond promptly to recall antigens. While blood contains approximately equal numbers of "naive" and "memory" T cells, it is known that UCHL1+ "memory" T cells accumulate at sites of chronic inflammation. To test the concept that "memory" T cells are a feature of the T lymphocyte populations present in tissues chronically exposed to antigens in normals as well as in individuals with chronic inflammation, we evaluated T lymphocytes obtained from blood and the epithelial surface of the lower respiratory tract of normal individuals for the expression of specific CD45 surface protein isoforms and corresponding mRNA transcripts. Flow cytometric analysis of CD45 220, 205, and 180 kD surface proteins demonstrated that lung T cells of normals are dominated by UCHL1+ "memory" cells (86 +/- 2%) while autologous blood T cells have equal proportions of "memory" UCHL1+ and "naive" 2H4+ T cells. In addition, polymerase chain reaction analysis of CD45 mRNA transcripts revealed that the lung cells expressed CD45R-0 mRNA transcripts but 17-fold fewer CD45R-IV mRNA transcripts than autologous blood T cells (p less than 0.01). The pattern of lung T cells being dominated by CD45R-0 mRNA+, UCHL1+ "memory" T cells was also observed in individuals with chronic beryllium disease, an example of a chronic inflammatory disease in which antigen-specific T cells accumulate on the pulmonary epithelial surface. Like the normals, the lung T cells of the beryllium disease patients were dominated by CD45R-0 mRNA transcript+, UCHL1+, T cells. However, on a quantitative basis, the beryllium patients contained far greater numbers of T cells, i.e., the T cell populations on the surface of the normal and inflamed lung are similar in character ("memory" T cells) but differ in numbers (there are far more in the chronic inflammatory state). Thus, T cell populations on the epithelial surface of the normal lung likely reflect the chronic exposure to a diverse set of antigens, with a pattern that is qualitatively similar to that observed among T cells accumulating in response to a single antigen.

Adult↗
PubMed1989

Systemic glutathione deficiency in symptom-free HIV-seropositive individuals.

To find out whether systemic glutathione deficiency is associated with human immunodeficiency virus (HIV) infection, thus contributing to the immunodeficiency state, glutathione concentrations in venous plasma and lung epithelial lining fluid (ELF) of symptom-free HIV-seropositive and normal individuals were measured. Total and reduced glutathione concentrations in the plasma of the HIV-infected subjects were about 30% of those in the normal individuals. Concentrations of these substances in the ELF of HIV-infected subjects were about 60% of those in the controls. There was no correlation between ELF and plasma concentrations of total or reduced glutathione. Since glutathione enhances immune function, glutathione deficiency may contribute to the progressive immune dysfunction of HIV infection.

Adult↗
PubMed1989

Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells.

Chronic beryllium disease is characterized by the accumulation of helper/inducer T cells, macrophages, and granulomas in the lungs. To evaluate the hypothesis that the proliferation of CD4+ (helper/inducer) T cells in the lungs of patients with this disorder is maintained by local activation of beryllium-specific T-cell clones, we studied T cells obtained from peripheral blood and by bronchoalveolar lavage in eight patients and five healthy controls. The proliferation of T cells in response to beryllium in vitro was confined to the CD4+ T cells from the patients and was dependent on the presentation of antigen in the presence of both major histocompatibility complex class II antigens and functional interleukin-2 receptors. T cells from the patients' lungs had a significantly greater response to beryllium than did T cells from their peripheral blood (stimulation index, 103 vs. 5; P less than 0.01). Lines and clones of cells developed from T cells from the patients' lungs showed dose-dependent proliferation in response to beryllium but did not respond to recall antigens or to other metals. Although all beryllium-specific T-cell clones were CD4+ and none were CD8+ (suppressor/cytotoxic), all beryllium-specific clones studied had different rearrangements of T-cell antigen receptors, suggesting that the response to beryllium involved T cells with diverse specificities for beryllium. We conclude that in patients with chronic beryllium disease, beryllium acts as a class II-restricted antigen, stimulating local proliferation and accumulation in the lung of beryllium-specific CD4+ (helper/inducer) T cells. Hence, chronic beryllium disease is a hypersensitivity disease in which beryllium is the specific antigen.

Adult↗
PubMed1989

Expression of HLA class II genes in alveolar macrophages of patients with sarcoidosis.

Sarcoidosis is characterized by the accumulation of activated helper/inducer T-cells and macrophages at sites of disease. The accumulation of these T-cells may be related to the ability of sarcoid alveolar macrophages to present antigen and stimulate lymphocyte proliferation in an exaggerated fashion. In the context that HLA Class II gene (HLA-DR, DQ, and DP) expression is essential to the interaction of lymphocytes with antigen-presenting cells such as macrophages, we have evaluated the hypothesis that the expression of Class II genes may be up-regulated in sarcoid alveolar macrophages. Northern blot and dot blot analysis with 32P-labeled cDNA probes for HLA-DR, DQ, and DP genes revealed that both normal and sarcoid alveolar macrophages contain Class II mRNA transcripts, but that the levels in sarcoid and normal alveolar macrophages are similar (p greater than 0.3, all comparisons). Furthermore, evaluation of surface expression of Class II molecules with monoclonal antibodies and flow cytometry analysis demonstrated that alveolar macrophages of both patients with sarcoidosis and normal subjects express all three Class II molecules, DR, DQ, and DP, but there were no significant differences between sarcoid patients and normal subjects in the proportions of macrophages expressing these surface molecules. However, there was a significantly higher surface density of Class II molecules on sarcoid alveolar macrophages (p less than 0.05, all comparisons sarcoid to normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Clinical enhancement of post-periodontal surgical therapy by a 0.12% chlorhexidine gluconate mouthrinse.

Previous studies have demonstrated the potential beneficial effects of post-surgical rinsing with 0.2% chlorhexidine. In the present investigation a new chlorhexidine formulation (Peridex) (CHx) and concentration (0.12%) was evaluated clinically to determine if similar effects could be detected from the use of the new product and treatment regimen. A double blind, randomized, placebo-controlled study was carried out in 40 patients during a 6 week period. Patients who had moderate periodontitis (AAP Class III) received osseous periodontal surgery in one quadrant. Each surgical site received periodontal dressing and patients were given a placebo or CHx mouthrinse to be used twice each day. Compared to placebo, CHx significantly reduced plaque at all examinations (54.4% reduction over placebo at 6 weeks, P less than 0.05). Visible plaque (PlI greater than 2) in the CHx group was reduced by 99% over the placebo group at 6 weeks and at 4 weeks post-surgical, gingival inflammation scores were significantly lower in the CHx group (17% reduction over the placebo at 4 weeks, P less than 0.05). Gingival bleeding scores (GI greater than 2) were significantly lower in the CHx group at 4 and 6 weeks (41% and 40% reduction over the placebo group, P less than 0.05). Probing pocket depth and attachment level changes were not significantly different between both groups. Epithelialization rates and pain assessment demonstrated consistently better results in the CHx group, although differences were not statistically significant. Use of 0.12% chlorhexidine immediately following periodontal surgery, for 6 weeks, has been shown to be a clinically effective adjunct providing enhancement of the post-surgical management of periodontal surgical patients.

Chlorhexidine↗
PubMed1989

Effect of 0.12% chlorhexidine on bacterial recolonization following periodontal surgery.

Bacterial plaque accumulation following periodontal surgery has been directly associated with delayed and altered surgical wound healing. Successful antimicrobial treatment following periodontal surgery depends upon the elimination and suppression of wound associated microorganisms. Highly effective antimicrobials should also prevent recolonization of periodontopathogens. In this investigation, the antimicrobial effect of a 0.12% chlorhexidine gluconate mouthrinse (Peridex) on bacterial recolonization after periodontal surgery was determined. A double-blind, randomized, placebo-controlled study was carried out on 40 patients for 6 weeks. Patients with moderate periodontitis (AAP Class III) underwent osseous periodontal flap surgery in one quadrant. Subgingival and marginal plaque samples from the surgery area were taken prior to surgery and 2 and 6 weeks postoperatively. General descriptive bacteriological cultural analysis and assays for specific microbial populations were carried out. During the 6 weeks of mouthrinse use, patients using chlorhexidine had significant reductions over placebo (P less than 0.05) in the number of total Gram-positive facultative cocci, streptococci (85.8%); Gram-positive facultative rods, primarily Actinomyces (91.7%); Capnocytophaga (97.6%) and Gram-negative anaerobic rods (94.5%). Few black pigmented Bacteroides or Actinobacillus actinomycetemcomitans were found prior to surgery or any time postoperatively. In the chlorhexidine group, 6 weeks post surgery, streptococci were the predominant bacterial group in the sampled plaque. Quantitatively, the distribution of bacteria, after 2 and 6 weeks of mouthrinse use, was consistent with a young, less mature plaque. A previous study demonstrated that this plaque was associated with clinical health.

Adult↗
PubMed1988

Sarcoidosis is not associated with a generalized defect in T cell suppressor function.

In pulmonary sarcoidosis, the marked expansion of CD4+ (helper/inducer) T cells in the alveolar structures of the lung is maintained by local IL-2 release by activated CD4+ HLA-DR+ T cells without concomitant expansion and activation of CD8+ (suppressor/cytotoxic) T cells, suggesting that sarcoid may be associated with a generalized abnormality of CD8+ T cells. Consistent with this concept, evaluation of the expression of the IL-2R on fresh lung T cells from individuals with active sarcoidosis demonstrated that 7 +/- 1% of sarcoid lung CD4+ T cells are spontaneously expressing the IL-2R compared with only 1 +/- 1% lung CD8+ T cells (p less than 0.01). However, stimulation of purified sarcoid blood CD8+ T cells with the anti-T3/TCR complex mAb OKT3 was followed by the normal expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). In addition, lung sarcoid CD8+ T cells responded to OKT3 similarly to normal lung CD8+ T cells and to autologous blood CD8+ T cells as regards expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). Finally, using CD4+ cells activated with allogenic Ag to induce, in coculture, fresh autologous CD8+ cells to suppress proliferation of fresh autologous CD4+ cells to the same Ag, sarcoid CD8+ T cells suppressed CD4+ cell proliferation in a normal fashion (p greater than 0.1). These results demonstrate that sarcoid CD8+ (suppressor/cytotoxic) T cells are competent to respond to a proliferation signal normally and can be induced to normally suppress CD4+ T cell proliferation to Ag, suggesting that the expansion of activated CD4+ T cells in pulmonary sarcoidosis is not due to a generalized abnormality of CD8+ T cells or of their suppressor T cell function.

Adult↗
PubMed1988

T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1.

T lymphocytes on the epithelial surface of the lower respiratory tract are thought to represent a relatively compartmentalized population of T cells that exchanges slowly with the blood. Since the lung is chronically burdened with antigens, "resident" T cells likely have a history of past activation. To evaluate this concept, we analyzed resident lung T cells for VLA-1 expression, which is indicative of a history of past stimulation. Lung lavage and blood T cells were evaluated in 13 normal nonsmokers using the monoclonal antibodies Leu4 (pan T cells), Leu3 (helper/inducer T cells), Leu2 (suppressor/cytotoxic T cells), TS2/7 (alpha 1 subunit of VLA-1), and A-1A5 (beta subunit of VLA-1) using immunofluorescence and immunoprecipitation. In contrast to normal blood T cells which did not express VLA-1, lung T cells expressed the 210-kDa alpha 1 and 130-kDa beta subunits of the VLA-1 complex, the same as blood T cells activated in culture for 3 weeks. Two-color immunofluorescence with Leu4 and TS2/7 showed that 19 +/- 6% of the lung T cells were VLA-1+, suggesting that a significant proportion of T lymphocytes on the alveolar epithelial surface are in a separate compartment from the VLA-1 blood cells. In sarcoidosis, a disease characterized by exaggerated numbers of active Leu3+ T cells in the lower respiratory tract, increased numbers of lung Leu3+ T cells expressing VLA-1 were present on the epithelial surface of the lung (P less than 0.05 compared to normals). These observations are consistent with compartmentalized, chronically stimulated T lymphocytes on the alveolar epithelial surface that exchange with the systemic immune system very slowly.

Antibodies, Monoclonal↗