Soluble CD30 and lymphocyte activation gene-3 (CD223), as potential serological markers of T helper-type cytokine response induced by acellular pertussis vaccine.

T cell responses are involved in vaccine-induced immunity to pertussis but no easy-to-monitor, serological markers are available to assess these responses. The lymphocyte activation gene-3 (CD223) molecule is present on, and released by, activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with Th2 immune responses. Starting from the recent knowledge of the cytokine profile induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria-tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The correlation of the two proteins with specific antibody and T cell responses was assessed. The main findings are: i) sCD223 and sCD30 levels are inversely related, suggesting that the two markers are the expression of different and counter-regulated T-cell responses; ii) sCD30 level correlated with induction of T cell proliferation to pertussis vaccine antigens and antibody response to pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate markers to assess the induction of Th-type responses in vaccine recipients.

Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients.

The ability of a mannoprotein antigen from Candida albicans (MP) or interleukin-2 (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression and by protein secretion. The subjects studied were all responsive to both MP and IL-2, as assayed by lymphoproliferation of PBMC cultures. In control subjects, MP and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expression, but only MP was able to induce considerable levels of IL-6 and IL-2 mRNA expression. In MP-activated PBMC from glioma subjects, a highly defective IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA expression, was observed. This impairment was paralleled by a decreased accumulation of IL-6 and IL-2 mRNA. The pattern of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects. Coherently, in PBMC cultures from glioma patients, there was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of IFN-gamma compared with healthy controls. No or very low levels of IL-4, IL-10, and TGF-beta 2 mRNA expression were detected in PBMC cultures of both glioma and control populations, irrespective of the activation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Human ballistic arm abduction movements: effects of L-dopa treatment in Parkinson's disease.

In patients with Parkinson's disease who had never previously been treated with any antiparkinsonism drug, we studied the effects of L-dopa on ballistic arm abduction movement in a step-tracking task. L-Dopa treatment increased the mean velocity of the initial movement towards the target without loss of accuracy and with improved motor performance under open-loop conditions. Performance also improved in motor tasks with expected perturbation. EMG patterns of arm abduction movements showed abnormal features in untreated patients and improved after L-dopa treatment.

Interleukin-6 production by U373 MG, a human astrocytoma cell line: different pathways involved in substance P and lipopolysaccharide activation.

Substance P (SP) and lipopolysaccharide (LPS) stimulated interleukin-6 (IL-6) gene expression, as well as IL-6 protein secretion in the human astrocytoma cell line U373 MG. Staurosporine, an inhibitor of protein kinase C (PKC), entirely blocked SP- but not LPS-induced IL-6 release. In addition, the down regulation of PKC inhibited the SP response and only marginally altered LPS activation. Differently from SP, LPS-induced IL-6 release was markedly reduced by W7, a calmodulin antagonist. Moreover, SP interacted in a synergistic manner with LPS. Thus, neural (SP) and bacterial (LPS) mediators stimulate U373 MG IL-6 release via distinct, though not antagonistic, activation pathways.

Cell-mediated and antibody responses to Bordetella pertussis antigens in children vaccinated with acellular or whole-cell pertussis vaccines. The Progetto Pertosse-CMI Working Group.

OBJECTIVE: To examine induction and persistence of cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens in infants receiving antipertussis vaccines. DESIGN AND SETTING: A randomized, blinded study of 142 children receiving acellular pertussis vaccines combined with diphtheria-tetanus toxoids (DTaP) (DTaP manufactured by SmithKline Beecham [DTaP-SB], Rixensart, Belgium, and DTaP manufactured by Chiron Biocin [DTaP-CB], Siena, Italy), or a whole-cell pertussis vaccine (DTwP) (Connaught Laboratories Inc, Swiftwater, Pa), or a diphtheria-tetanus (DT) (Chiron Biocine) only vaccine. Three doses of each vaccine were given at 2, 4, and 6 months of age, and CMI and antibody responses were evaluated before and at 1 and 14 months after vaccination. METHODS AND MAIN OUTCOME MEASURES: Cell-mediated immunity was assessed by proliferation of peripheral blood mononuclear cells stimulated in vitro by B pertussis antigens (pertussis toxin, filamentous hemagglutinin, and pertactin). Antibody titers against pertussis toxin, filamentous hemagglutinin, and pertactin were determined by a standardized enzyme-linked immunosorbent assay. RESULTS: A CMI-positive response to at least 1 B pertussis antigen at 1 or both postvaccination assays was detected in 46%, 55%, and 83% of DTwP, DTaP-SB, and DTaP-CB vaccine recipients, respectively. Frequency of CMI response to individual antigens ranged from less than 4.9% against pertussis toxin in DTwP recipients to 52% against pertactin in DTaP-CB recipients. The postvaccination responses measured at 14 months equalled, or had increased frequency or intensity, that of the 1-month postvaccination responses. Elevated antibody titers against the 3 antigens were present in all DTaP recipients 1 month after vaccination and were higher in CMI-positive children than in CMI-negative children. They fell, however, to low, if not negligible, levels 14 months after vaccination. CONCLUSIONS: Acellular pertussis vaccines were better inducers of CMI response than the whole-cell vaccine, particularly against pertussis toxin. Once acquired, CMI persisted, in contrast with the rapid antibody decline. Thus, CMI responses could be a useful adjunct to serology in the evaluation of pertussis vaccine immunogenicity and a better correlate of long-term immunity to B pertussis than antibody titers.

Induction of a specific antibody response to Bordetella pertussis antigens in cultures of human peripheral blood mononuclear cells.

The role of specific antibodies in protective immunity to Bordetella pertussis has not yet been clearly defined. In the present work, the induction of a specific antibody response to B. pertussis in cultures of human peripheral blood mononuclear cells (PBMC) was investigated, on the assumption that the capacity of circulating lymphocytes to mount a specific response in vitro may provide a useful parameter for the evaluation of protective immunity. When PBMC from normal adult donors were cultured with a heat-inactivated B. pertussis whole-cell suspension, cells secreting antibodies to pertussis toxin, pertactin and filamentous haemagglutinin were generated consistently. The antibody response peaked between days 7 and 11 of culture and the antibodies produced were exclusively of the IgM class.

Mannoproteins from Candida albicans elicit a Th-type-1 cytokine profile in human Candida specific long-term T cell cultures.

Since T lymphocytes are active producers of regulatory cytokines, long-term T cell cultures (LTTC) specific for a major mannoproteic antigen (MP) of Candida albicans from peripheral blood mononuclear cells (PBMC) of healthy donors were generated and their cytokine profile studied. LTTC consisted of an expanded CD3CD4 T-helper (Th) populations, with a high proportion of CD45R0 T memory cells. Stimulation of LTTC by MP induced a Th-1 type cytokine profile, as indicated by the presence of IFN-gamma and the absence of IL-5 (both as mRNA and protein) in cell cultures and supernatants. These results suggest a predominant Th1 response elicited by C. albicans mannoprotein antigen in human PBMC.

A macrophage derived blastogenic factor -MBF- induces cytokines and cytotoxic effectors in human peripheral blood mononuclear cells.

A soluble macrophage-derived blastogenic factor, previously reported as MBF, is secreted from macrophages activated with galactose oxidase. It was previously shown that MBF is able to induce IFN-gamma production and proliferation of T lymphocytes. In this study we found that MBF is able to induce in human peripheral blood mononuclear cells (PBMC) production of interleukin 1 (IL-1) beta, interleukin 2 (IL-2) and tumor necrosis factor (TNF) alpha and generation of MHC-unrestricted cytotoxic activity. The induction of killer cells is likely to rely on IFN-gamma production in that in PBMC treated with a monoclonal antibody (Mab) against IFN-gamma, the MBF induced cytotoxic activity was drastically reduced. A comparison of MBF induced cytotoxic effectors with those induced by IL-2 showed that both cytotoxic effectors pertain to NK lineage, in that they were CD3- and CD16+. On the contrary, the precursors of MBF and IL-2 induced killer cells were different; MBF cytotoxic precursor cells were highly sensitive to L-Leucine methyl ester (Leu-OME), a drug able to eliminate monocytes and NK cells, whereas IL-2 cytotoxic precursors were unaffected by this drug.

Epidemiology of psoriasis: case-control study in the province of Trentino (preliminary reports).

In the province of Trento a case-control study on the main environmental risk factors for psoriasis has been performed. No correlation has been demonstrated between the investigated factors and psoriasis, with the exception of familial predisposition.

[Clinico-statistical study on hydropinic and balneothermal therapy of psoriatic patients using the low mineral-content waters of the Comano springs]. / Indagine clinico-statistica sulla terapia idropinica e balneotermale con acqua oligominerale delle Terme di Comano in soggetti affetti da psoriasi.

The authors report the results obtained treating 39 subjects affected from psoriasis with hydropinic therapy and thermal balneo-therapy, using the thermal water of Comano. At the end of the treatment the results were rather bad with an inclusive reduction of 8.5% of the lesions as regards the initial data, but after 3-6 months an average per cent reduction of the lesions about 50% and in some cases quite a total regression of the psoriasis has been noted. No kind of collateral effects has been noted.

[Di George's syndrome with neutropenia in an adult patient]. / Sindrome di Di George con neutropenia in un paziente adulto.

The clinical data of a thirty-nine old inpatient woman are reported, whose main complaints were non-operable vulvo-vaginal condylomata, recurrent bacterial infections, complicated chickenpox and prominent lymphopenia. The peculiar facies get us to suggest the diagnosis of a case of the Di George syndrome in an adult patient. Was probably the associated neutropenia congenital and combined with immunodeficiency syndrome?

Organization of efferent extraspinal sympathetic pathways in Rana esculenta.

Origin and distribution of pre- and postsynaptic fibres in the sympathetic trunk of Rana esculenta (from ganglion 3 to ganglion 10) have been investigated by means of extracellular recordings. Two systems conducting efferent information appear to exist: 1) a system made of faster conducting fibres (B group pre- and postsynaptic fibres); presynaptic fibres originating from a very high monosegmental source (4th spinal root); postsynaptic fibres leave the sympathetic chain plurisegmentally (rami communicantes 5-10); 2) a system made of slower conducting fibres (C group pre- and postsynaptic fibres) originating plurisegmentally from spinal roots 5-8. Intracellular recordings have shown that: 1) integrative processes take place in the amphibian sympathetic trunk, as in the mammalian one, but are quantitatively lesser. Homonomous (B-B) and heteronomous (B-C) convergence has been observed in B neurons, and also the convergence of a collateral of a C postsynaptic axon on B neurons. 2) posthumous depolarizations are present: these are events modulating the activity of sympathetic neurons. In B neurons posthumous depolarization follows orthodromic responses, and a late posthumous depolarization can be seen in B and C neurons following either ortho- or antidromic stimulation.

[Age-related changes in some spatial-temporal parameters of ballistic movement in man]. / Osservazioni sulle variazioni indotte dall'età in alcuni parametri spazioi-temporali del movimento balistico nell'umo.

Age-related changes in spatio-temporal parameters of ballistic arm abduction movements were investigated in two groups of healthy volunteers: a group of younger subjects (aged 20-45 years) and a group of older subjects (aged 60-82 years). Arm abduction was performed in a step-tracking task. Older subjects exhibited longer reaction times, greater durations of the initial movement together with lower mean velocities. Accuracy, however, did not significantly differ from that of younger subjects. No differences were found both in the number and in the accuracy of "ballistic" movements, i.e. those completed within one mean reaction time or less. In motor tasks including slight expected perturbations during the movement, the motor performance of all tested subjects was not impaired. Furthermore, older subjects displayed a decrease in the duration of the initial movement and an increase of its mean velocity, without changes in accuracy; the increase of mean velocity became significant under visual closed-loop conditions. The results suggest that only some features of bradykinesia are age-related. Older subjects appear to retain a normal strategy for ballistic movement: the neural mechanisms controlling the generation of sufficient accelerative forces and of the appropriate timing for ballistic movements seem to be poorly activated rather than disrupted, since they may recover under specific circumstances.

[Spatial-temporal parameters of ballistic arm abduction in normal subjects and patients with Parkinson's disease]. / Parametri spazio-temporali dell'abduzione balistica del braccio in soggetti normali ed in pazienti con malattia di Parkinson.

Spatio-temporal parameters of ballistic arm abduction movements were studied in healthy control subjects and in patients with Parkinson's disease. Arm abduction was performed during a step-tracking task. Patients showed longer reaction times, slower mean velocities and lesser accuracy, with a marked tendency to undershooting. In patients, "ballistic" movements (taken as initial movements completed within a mean reaction time or less) were fewer and more inaccurate. Moreover, their motor performance was greatly impaired in motor tasks including slight expected perturbations during the movement: evident changes in velocity or even arrests, together with inability to overcome the obstacle were observed. The motor performance of all tested subjects did not differ significantly in visual open-loop conditions. The present results: i) support the hypothesis that Parkinsonism interferes with the generation of accurate ballistic actions and ii) contribute to the understanding of bradykinesia.

Differential release of an immunodominant 65 kDa mannoprotein antigen from yeast and mycelial forms of Candida albicans.

The release of mannoprotein (MP) antigen from Candida albicans grown at 28 degrees C (yeast form) or 37 degrees C (mycelial form), and the ability of each released material to stimulate a cell-mediated immune (CMI) response by human lymphocytes in vitro, were studied. Overall, the mycelial cells released more MP per unit of dry mass increase and the released material was relatively enriched with MP constituents of lower molecular mass with respect to the material released from yeast cells. Moreover, the mycelial MP contained a 65 kDa component (MP65) which was the largely predominant MP recognized by a rabbit anti-mycelium antiserum. When peripheral blood mononuclear cells from normal human subjects were stimulated in vitro with graded amounts of yeast or mycelial MP, the latter was about one order of magnitude more potent than the former in inducing lymphocyte proliferation. Following MP separation by gel permeation chromatography, an appreciable CMI response was stimulated only by the MP65-containing MP fractions, and to a degree apparently related to the amount of MP65 itself. Altogether, these data confirm our previous findings about the MP65 antigen as a major target of CMI response to C. albicans, and demonstrate that this antigen is released predominantly by the mycelial cells of the fungus in vitro.

Acellular vaccines induce cell-mediated immunity to Bordetella pertussis antigens in infants undergoing primary vaccination against pertussis.

The induction of cell-mediated immunity (CMI) to Bordetella pertussis antigens (whole, heat-inactivated bacterial cells [BPC], pertussis toxin [PT], filamentous haemagglutinin [FHA], pertactin [PRN]) was assessed by a lymphoproliferation assay in vitro in a cohort of children enrolled in a randomized clinical trial of pertussis vaccines efficacy in Italy. Four vaccination groups were compared: children receiving acellular pertussis (aP) vaccines from SmithKline Beecham (SB) or Chiron Biocine (CB) or whole-cell vaccine (wP) from Connaught, each combined with diphtheria and tetanus toxoids (DT), or a DT vaccine only. When the purified antigens were used, statistically significant differences in CMI responses were observed between pre- and post-vaccination samples. In particular, CMI responses to FHA and PRN were detected in the majority of both aP vaccines recipients, whereas DTwP-recipients were CMI-positive in a much lower proportion. Clear-cut differences in PT responses were detected between DTwP and DTaP vaccine recipients, in favour of the latter. These differences were maintained up to 24 months after completion of the primary vaccination schedule. Thus, CMI responses could be a useful adjunct to serology in studying the immune responses to pertussis vaccines.