[Potentiation of the resistance to viral and bacterial infections after pidotimod administration in mice].
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Biomedical subjects
Publications and source records attributed to M Campa.
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An epidemiological investigation was carried out to evaluate the prevalence of Streptococcus mutans in a group of 134 adult patients. Markedly higher frequency of isolation was observed in caries-active subjects than in caries-inactive or caries-free subjects, indicating a significant association between the prevalence of the microorganism and the caries status. Moreover, the presence of the microorganism appeared to have a significant association with the extent of caries experience evaluated by the DMF score. These findings are in agreement with those reported previously for school children in other areas of Italy. Isolation of S. mutans was compared among patients groups with different caries activity in relation to culture times of dental plaque samples in a transport medium (Colorimetric Broth Medium). S. mutans was most frequently isolated from caries-active subjects when the medium was incubated for 48 h after inoculation with dental plaque samples.
Out of 1172 females recruited in a screening program for genital infections, 144 (12.28%) were cervical and/or urethral positive for Chlamydia trachomatis (Ct) by enzyme immunoassay (EIA). Patients positive for Ct showed no significant differences in terms of demography, sexual practices and clinical evidence as compared to a control group formed by Ct-negative females randomly selected. Historical data showed a higher frequency of previous pelvic inflammatory disease (PID) in patients as compared to controls. 11 of the 94 patients' partners tested were sperm positive for Ct. Of the 63 patients for whom therapeutic data were available, 38 were treated with josamycin, 16 with tetracycline and the others with different drugs. After treatment, EIA for Ct was negative for 92.1% of the patients treated with josamycin and for 68.7% of those treated with tetracycline. The results of this study confirm a high prevalence of asymptomatic Ct infection which may be correctly diagnosed by EIA performed on cervical and urethral samples. They also indicate that negative test results can be obtained by an appropriate antibiotic treatment.
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Adenosine deaminase, a purine metabolic enzyme, was studied in lymphoid tissues of the developing chicken in order to evaluate whether enzyme activity is related to development of the immune system in birds in the same way as for mammals, in which adenosine deaminase is essential for lymphocyte differentiation, especially for the T-cell lineage. Enzyme activity was assayed in thymocytes and bursal lymphocytes at different times during chicken development ranging from the 17th day of embryonic life up to the 50th day after hatching. Adenosine deaminase activity was significantly higher in the bursa than in the thymus, regardless of whether such an activity was expressed per mg protein or per 10(8) cells; moreover, no substantial difference in the relative levels of adenosine deaminase was observed in thymocytes at the various stages of thymus development studied. Significant changes in enzyme activity, however, were found in bursal lymphocytes in which different amounts of adenosine deaminase appeared to be related to definite stages of bursal development and to specific immunological responsiveness of B lymphocytes to intravenously injected antigens. Therefore, if adenosine deaminase does play a role in the functional maturation of the immune system in birds, such a role appears to be related to the differentiation of the B- rather than the T-cell lineage.
The skin penetration of roxithromycin was studied in 27 surgical patients treated with 300 mg orally followed by three oral doses of 150 mg 12-hourly. Peak plasma and skin concentrations of 7.9 +/- 1.2 mg/l and 31.3 +/- 3.7 mg/kg occurred 2.5 and 4 h after last dosing respectively. The plasma and skin half-lives were 7.7 and 6.0 h, and the mean plasma and skin area under the curve values were 64.3 mg/l.h and 155.3 mg/kg.h. Skin/plasma concentration ratios were 4.9 +/- 0.5, 9.7 +/- 1.2, 7.6 +/- 0.8 and 5.9 +/- 1.1, at 3, 4, 5 and 6 h after last dosing respectively. These results demonstrate that roxithromycin achieves high levels in human skin.
The peripheral blood lymphocyte response of patients with ankylosing spondylitis (AS) to several polyclonal B cell activators was investigated. No differences were found in the reactivity to pokeweed mitogen and protein A between patients and controls; in contrast, the peripheral blood lymphocyte response to Staphylococcus aureus strain Cowan I (SAC) was significantly higher in patients with AS than in controls. This responsiveness was not influenced either by the presence of the HLA-B27 antigen or by environmental factors or associated diseases, and it was higher in patients with active AS than in those with inactive disease. The percentage of circulating B cells was normal. The responses to T cell mitogens and the percentages of T cell subpopulations were similar in patients and in controls. The peripheral blood lymphocyte hyperactivity of patients with AS to SAC was associated with an increased in vitro production of immunoglobulins.
The depression of the granulomatous response to Mycobacterium bovis strain BCG in mice infected intravenously with 2 x 10(7) CFU of the microorganism turned out to be mediated by various types of cells arising at different times after infection. Anti-PPD B lymphocytes were found to play a major role at Day 1 after infection and to be no longer effective 4 days later. At this time the depression was mediated by anti-idiotype B lymphocytes, whereas T lymphocytes proved to be involved in later phases of the infectious process. These results show that B lymphocytes may be of critical importance in the regulation of cell-mediated immune reactions to this facultative intracellular parasite.
Tuberculosis is still a major health problem in almost all over the world. Thus, new directions in basic and applied research of tuberculosis are under investigation in several laboratories. In this paper, we provide recent data obtained in our laboratory with the recombinant DNA technology which allow a systematic survey of the microbial genome. Screening of the M. tuberculosis genomic DNA library in the phage lambda gt11 expression vector, using E. coli as surrogate host, has evidenced the possibility of producing recombinant M. tuberculosis proteins recognized by sera from tuberculosis patients and by specific monoclonal antibodies. Using this technology, we have isolated a recombinant protein (molecular weight 130 kilodaltons) which is identified by a murine monoclonal antibody recognizing a mycobacterial cell wall antigenic determinant present on a mycobacterial protein. This protein is only present on the mycobacterial species related to the tuberculosis complex (M. tuberculosis, M. bovis, M. africanum) and does not crossreact with nonpathogenic Mycobacteria. Since the immune response to mycobacterial infections is cell-mediated, the question arises about the use of M. tuberculosis-specific T lymphocytes to screen this gene bank. Thus, the recombinant mycobacterial protein isolated by antibodies has been then used to stimulate the proliferation of T lymphocytes from patients with tubercular pleuritis. This experiment indicates that the recombinant protein contains antigenic determinants recognized by T cells. Moreover, such protein is able to elicit delayed type hypersensitivity skin reaction in mice immunized or infected with M. tuberculosis and M. bovis. Finally, gene mapping and hybridization studies with native M. tuberculosis DNA confirme the mycobacterial nature of the recombinant DNA insert. Thus a good candidate for the prophylaxis and the immunodiagnosis of tuberculosis has been identified. The identification and selection of genes encoding antigenic determinants recognized by mycobacteria-specific T cells with protective functions will allow in the near future the construction by genetic engineering of recombinant vaccines effective in the control of this disease. This paper will briefly discuss the present strategy used in our laboratory to reach this goal.
Inflammatory disease such as prostatitis and prostatovesiculitis, can affect the fertility potential of the male population. In this study, the Authors tested the therapeutical efficacy of a second generation quinolone, enoxacin, in patients suffering from vesicular and/or prostatic inflammations. This drug has been shown to diffuse into the prostatic fluid, achieving therapeutical concentrations either in acute or chronic pathological conditions. Thirty infertile patients referring to our Andrology Center and showing seminal signs (leukocytes, abnormal sperm forms, chemical and physical alterations, etc) of genital tract inflammations were found to have positive sperm culture for enoxacin-sensitive strains. Further investigations (echotomography) showed that they were affected by prostatic and/or vesicular subacute chronic inflammations. The mean age was 32.2 (range 20-36) ys. All the patients discontinued any previous treatment for at least 90 days. Enoxacin was administered at the dose of 300 mg b.i.d. for two cycles of 10 days each, with intervals of 20 days. At the beginning and at the end of the treatment (days 0 and 60), semen analysis and culture were performed. A paired-T test was employed for the statistical evaluation of data. 26.6% of patients ad an altered fluidification before treatment. Only 10.0% of them showed the same sign after treatment. A condition of hyperviscosity was present in 50% and 16.6% of patients before and after treatment respectively. Likewise, an elevated number of leukocytes (greater than 10(6)/ml) occurred in the ejaculates of 43.3% of patients and in 23.3% after enoxacin treatment. Enoxacin treatment was efficacious in 89.2% of cases, in presence of either Gram positive or Gram negative bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Complete release of adenosine deaminase from mouse lymphocytes takes place when intact cells are stabilized by low-pH acetate buffer. Both the low pH and the acetate affect the enzyme extraction markedly. At pH 5.0 all the adenosine deaminase activity detectable in the whole cell homogenates is released into the acetate buffer in very few minutes, with a total amount of 2% protein being extracted. The complete extraction of the enzyme activity is never observed when, at pH 5.0, the acetate is replaced by glutamate, citrate, succinate or maleate and only 45% and 15% of the adenosine deaminase activity is extracted by the acetate at pH 6.0 and 7.0, respectively. The breakdown of adenosine by the enzyme activity extracted from the stabilized cells is due to deamination alone, since inosine is the only product of the catalyzed reaction and its formation is completely inhibited by coformycin, a selective inhibitor of adenosine deaminase. The enzyme extracted shows a specific activity 50-times higher than that found in the crude homogenates, and a substantial purification of the enzyme extracted is achieved by a single Sephadex G-100 gel filtration.
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A simple method is described for achieving a good recovery and a partial purification of the membrane-bound 5'-nucleotidase (5'-N) from mouse lymphocytes. The experimental procedure is based upon plasma membrane isolation on polycationic beads and selective solubilization of the enzyme activity from bead-bound plasma membranes. With this method, more than 95% of the 5'-N activity detectable in the whole cell homogenates can be routinely recovered in a single fraction showing a 5'-N specific activity which is at least 60 times higher than that found in the crude homogenate. This method also provides a complete separation of 5'-N from the membrane-bound alkaline phosphatase (AP), as well as from any other interfering non-specific phosphatase. Since this method is rapid and highly reproducible even when small amounts of lymphocytes are available, it may be useful for detecting changes in 5'-N activity in the different T- and B-lymphocyte subpopulations.
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Mice infected subcutaneously with 2 X 10(7) CFU of Mycobacterium bovis strain BCG (BCG) were able to mount a specific DTH response, whereas mice infected intravenously with the same dose of microorganisms were not. The suppression turned out to be mediated by id+ anti-PPD B lymphocytes, which arose very early during the infectious process and induced anti-id B lymphocytes. These cells were found at Day 4 after infection and exerted their effect by activating antigen-specific suppressor T lymphocytes, which affected the efferent phase of the DTH response. These results clearly indicate that the activation of a complex immunosuppressive circuit represents a mechanism by which BCG may interfere with the host's immune response already during the very early phases of infection.
Lymphocyte subpopulations were evaluated in 31 patients affected by essential mixed cryoglobulinemia, using OKT3, OKT4, and OKT8 monoclonal antibodies in a cytotoxic assay. The patients with essential mixed cryoglobulinemia had a normal number of OKT3+ and OKT4+ cells but significantly lower values of OKT8+ cells compared to healthy controls. When the OKT4+/OKT8+ ratio was considered, patients could be subdivided into 3 main subgroups: 6 patients had a low OKT4+/OKT8+ ratio, 10 patients had a normal ratio, and 15 had a high ratio. This ratio did not correlate with age, sex, disease duration, low corticosteroid therapy or serological hallmarks of the disease. In contrast, purpura and liver involvement were more prevalent in patients with a normal or high OKT4+/OKT8+ ratio, while lung involvement was more prevalent in patients with a low ratio.
Staphylococcus aureus strain Cowan I, a strong polyclonal B-cell activator (PBA), inhibited contact sensitivity to oxazolone in mice when administered 24 hr before sensitization. This suppression was mediated by idiotype-positive (Id+) B lymphocytes, which arose very early during the sensitization process and induced anti-Id B cells. These cells were found at Day 3 of the sensitization process and exerted their effect by activating antigen-specific suppressor T lymphocytes, which affected the efferent phase of the immune response. S. aureus strain Wood 46, which lacks of the ability to act as a PBA, was unable to inhibit contact sensitivity. These results indicate that PBA may play an important role in the regulation of cell-mediated immune reactions.