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Biomedical subjects

S Barbieri

Publications and source records attributed to S Barbieri.

At least 55 records · Page 3Linked to original sources

T cell-derived IL-3 induces the production of IL-4 by non-B, non-T cells to amplify the Th2-cytokine response to a non-parasite antigen in Schistosoma mansoni-infected mice.

We describe a novel amplification mechanism underlying the increased early IL-4 production observed in Schistosoma mansoni-infected mice in response to a non-parasite Ag, sperm whale myoglobin (SwMb). Earlier studies have shown that splenic Fc epsilon R+ non-B, non-T (NBNT) cells from schistosome-infected mice secrete IL-4 after stimulation with parasite Ag. We now demonstrate that purified NBNT cells from SwMb-immunized S. mansoni-infected mice do not respond directly to SwMb, but produce IL-4 in response to IL-3. Accordingly, we show that the early SwMb-specific IL-4 response of spleen cells (SC) from immunized infected mice is dependent on IL-3 and on CD4+ T cells. Thus, most of the early SwMb-induced IL-4 from SC of infected mice appears to be produced by NBNT cells triggered by IL-3 synthesized by SwMb-specific CD4+ T cells. IL-3-induced IL-4 production was also observed in purified NBNT cells from immunized uninfected mice, but the frequency and/or IL-4-producing capacity of splenic IL-3-responsive cells was found to be 8 to 16 times higher in immunized infected animals. IL-4 production by purified CD4+ cells from immunized infected mice was also seen after SwMb stimulation, but this response showed slower kinetics than those of total SC, was IL-3-independent, and on average threefold greater than that by CD4+ cells from immunized uninfected controls. Thus, increased SwMb-induced IL-4 production in immunized S. mansoni-infected mice results from direct synthesis by CD4+ T cells, as well as their stimulation via IL-3 of an expanded population of NBNT cells. The latter pathway may serve as an amplification loop for Th2-cytokine responses.

Animals↗

Anti-GD1a ganglioside antibodies in peripheral motor syndromes.

High titers of anti-GD1a antibodies have been found in patients with Guillain-Barre syndrome or motor neuropathy. To determine the possible diagnostic relevance of these antibodies, we measured serum anti-GD1a IgG and IgM antibodies by enzyme-linked immunosorbent assay in 195 patients with different motor syndromes and in 335 control subjects. Moderately high antibody titers (1/1,280-1/5,120) were occasionally found in patients with chronic inflammatory demyelinating polyneuropathy (5%), multifocal motor neuropathy (18%), lower motor neuron disease (3.8%), or amyotrophic lateral sclerosis (1.8%) and in immunological control subjects (1.2%), while titers of 1/20,480 or higher were only found in 2 patients with Guillain-Barre syndrome (IgG in both) and 2 with motor neuropathy and IgM lambda monoclonal gammopathy improving with immunotherapy. In both motor neuropathy patients and the Guillain-Barre syndrome patient who were retested during recovery, anti-GD1a titers decreased concomitantly with clinical improvement. High anti-GD1a antibody titers may be found in several motor syndromes but only markedly increased anti-GD1a titers are strictly associated with potentially treatable dysimmune neuropathies.

Aged↗

Evidence for a subclinical involvement of the central nervous system in mild or moderate chronic respiratory insufficiency.

Nineteen patients with mild or moderate chronic respiratory insufficiency, mean age, 63.3 y., have been investigated with pulmonary function tests, clinical examination and somatosensory (SEPs), visual (VEPs) and brainstem auditory (BAEPs) evoked potentials. Nineteen age and sex matched subjects acted as controls. None of the subjects had conditions known to affect the central nervous system (CNS). SEP N20 latency was significantly prolonged in 7 out of 19 patients and its mean value in the patients' group was significantly higher (21.02 vs 19.49 msec p < 0.001). VEP P100 latency was prolonged in the patients' group in 16/38 and 15/38 eyes with spatial frequencies of 30' and 15' of arc respectively. The P100 mean value was also significantly prolonged in the patients' group for both eyes and spatial frequencies (108.08 vs 101.87 msec p < 0.001 and 115.82 vs 107.63 msec p < 0.001 for spatial frequencies of 30' and 15' respectively). No significant difference was evident with BAEPs The data seem to support the hypothesis of a subclinical involvement of CNS in these cases, with preferential damage to the newer phylogenetic structures.

Aged↗

n-Hexane-induced parkinsonism: pathogenetic hypotheses.

n-Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by-products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n-hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease.

Air Pollutants, Occupational↗

Peripheral neuropathy in IgM monoclonal gammopathy and Wäldenstrom's macroglobulinemia: a frequent complication in elderly males with low MAG-reactive serum monoclonal component.

Peripheral neuropathy (PN) is a frequent complication during primary macroglobulinemia (PM), whose immunological genesis has been suggested by various authors. This study involved 65 PM patients (44 men and 21 women aged 35-78), diagnostically divided into MGUS (31 cases), and indolent (IWM, 24 cases) or symptomatic (WM, 10 cases) Waldenstrom macroglobulinemia groups. All patients underwent neurological examination, including electrodiagnostic evaluation and the determination of the serum titre of antimyelin-associated glycoprotein (MAG). An evaluation was made of the prevalence of PN and its correlation with a series of hematological variables. The prevalence of PN was 31.6%: of those with PN, 73.1% manifested both clinical and electrophysiological signs of PN, primarily of the demyelinating type. Significant correlations emerged between the presence of PN and sex (M vs. F P = 0.0001), advanced age (P = 0.049), low MC levels (P = 0.025), high anti-MAG titres (P = 0.001) and high Hb levels (P = 0.001). No significant correlation with the diagnostic definition of PM was found, although the majority of cases with (particularly demyelinating) PN were MGUS or IWM. At multivariate analysis, the presence of PN significantly correlated with sex (P = 0.0001), age (P = 0.019), and anti-MAG titre (P = 0.001). Ten of the 26 PN cases showed no MAG reactivity. Significant correlations between PN and low serum MC levels/high MAG reactivity support the hypothesis of the antibody-mediated origin of many PN, and that the presence of PN depends on the characteristics of the proliferating pathological B clone, rather than on the tumor burden of the form of macroglobulinemia. Clinically, our data reconfirm the frequency of PN during PM and indicate simple clinicohematological variables useful for identifying patients at high neuropathic risk.

Adult↗

Fc epsilon receptor-positive cells are a major source of antigen-induced interleukin-4 in spleens of mice infected with Schistosoma mansoni.

When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fc epsilon receptor (Fc epsilon R)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 x 10(3) cells). FACS analysis revealed that these Fc epsilon R+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of Fc epsilon R+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts.

Animals↗

High-dose intravenous immunoglobulin therapy in multifocal motor neuropathy.

We treated five consecutive patients with multifocal motor neuropathy (MMN) with high-dose intravenous immunoglobulin (IVIg). Four patients had increased levels of anti-asialo-GM1 IgM and two of anti-GM1 IgM as well; one patient had no reactivity. We treated them twice with 0.4 g/kg IVIg for 5 consecutive days at a 2-month interval, followed by maintenance infusions up to 6 to 12 months. All patients with high anti-asialo-GM1 had a consistent clinical improvement starting 3 to 10 days after the first IVIg course; in one patient, recovery was complete and persistent for 12 months without additional treatment, while in three patients, improvement only lasted 20 to 30 days. There was a similar improvement in these patients after the second course of IVIg which was maintained by periodic 2-day IVIg infusions. Clinical improvement in these patients was associated with a reduction of conduction block in most, but not all, motor nerves, while antibody titers were not consistently modified by treatment. There was no clinical or electrophysiologic improvement in the patient without antiglycolipid activity after 6 months of IVIg. IVIg may be a safe and effective therapy for MMN.

Adult↗

Kinetics of the appearance of Fc epsilon RI-bearing cells in interleukin-3-dependent mouse bone marrow cultures: correlation with histamine content and mast cell maturation.

While it is known that mast cells arise from pluripotential hematopoietic cells and express their mature phenotypes in tissues, the sequence of events in maturation is incompletely understood. To study early mast cells, we sorted cells from interleukin-3 (IL-3)-dependent mouse bone marrow cultures on the basis of Fc epsilon RI and examined their morphology, histamine content, and growth characteristics. Flow cytometric analysis and sort showed that the Fc epsilon RI-bearing (Fc epsilon RI+) cells increased from 0% on day 0 to 90% by day 21 and that the total number of Fc epsilon RI+ cells increased from 0 at the start of culture to 3.75 x 10(5) cells by day 21 from an initial population of 1 x 10(5) cells. The dissociation rate of 125I-labeled IgE from early cultured cells resembled the dissociation rate of mouse IgE from mature murine mast cells. Mean fluorescence intensity increased over time, reflecting an increase in IgE receptor density. Fc epsilon RI+ cells were also positive for Fc gamma RII/III. Morphologic studies showed gradual acquisition of metachromatic granules in the Fc epsilon RI+ cells, which was paralleled by an increase in histamine content. Sorted Fc epsilon RI+ cells, when placed in liquid suspension culture, gave rise to pure mast cell populations. Fc epsilon RI+ cells sorted at day 3 and cultured in agarose with IL-3 gave rise to 4,800 small and 150 medium-size mast cell colony-forming units per 10(6) cells, while Fc epsilon RI- cells gave rise to 23 medium-size and 49 large mast cell colony-forming units per 10(6) cells. Fc epsilon RI+ cells grown in granulocyte-macrophage colony-stimulating factor (CSF) or macrophage-CSF did not give rise to colony-forming units. These results show that Fc epsilon RI+ cells have proliferative potential, but that there also is a population of mast cell progenitor cells that have not yet expressed Fc epsilon RI, and such individual progenitor cells have greater potential for proliferation than cells that express Fc epsilon RI.

Animals↗

Congenital myopathy with type 2A muscle fiber uniformity and smallness.

We describe a 12-year-old girl with congenital myopathy. ATPase histochemical reactions and immunocytochemical analysis of muscle fiber-type composition with monoclonal antibodies against slow, fast (2A and 2B) and fetal myosin demonstrate that this congenital disease is characterized by type 2A muscle fiber uniformity and smallness. This is an unusual feature for a congenital myopathy in which the fiber type predominance, when present, is confined to type I.

Biopsy↗

Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies.

In an unselected series of patients with monoclonal gammopathy of undetermined significance (MGUS) we found neuropathy in 2 of 34 patients with IgG (6%), 2 of 14 with IgA (14%), and 8 of 26 with IgM MGUS (31%). The neuropathy was subclinical in 6 patients (1 IgG, 1 IgA, and 4 IgM). Patients with IgG or IgA MGUS had a prominent motor impairment with electrophysiologic and morphologic findings suggestive of predominant axonal degeneration. No deposit of the M-protein in sural nerve and no reactivity of the M-protein with nerve was detected in these patients. Patients with IgM MGUS had a prominent sensory impairment with evidence of predominant demyelination. In 6 of these patients the M-protein reacted with the myelin-associated glycoprotein (MAG). The higher prevalence of neuropathy in patients with IgM MGUS may be related to the frequent reactivity of IgM M-proteins with MAG.

Adult↗

[Surgical emergency in thyroid disease: acute respiratory failure caused by tracheal obstruction].

Diagnostic and therapeutic approach to emergency due to acute and severe respiratory compromise by thyroid goiters with tracheal obstruction is discussed. Such an alarming condition was observed in 5 (2.3%) out of 215 mediastinal goiters operated between 1967-91. Retrospective and critical analysis of these cases pointed out that preventive removal of a large goiter is the best prophylaxis; first management is not surgical, although urgent features. Admission to intensive care center and endotracheal intubation allow an adequate interpretation of the pathologic condition and operative troubles and risks. Diagnostic investigations, effective and kept to a minimum (chest x-ray, tracheo-laryngoscopy, TAC), must be carried out without delaying thyroidectomy and prolonging intubation for days. The extraction of goiter is nearly always performable by the cervicotomic way. Whenever necessary endotracheal intubation obviates the need of tracheostomy for solving transient postoperative complications such as laryngeal oedema, local hematoma and recurrent nerves stupor.

Acute Disease↗

Purified Fc epsilon R+ bone marrow and splenic non-B, non-T cells are highly enriched in the capacity to produce IL-4 in response to immobilized IgE, IgG2a, or ionomycin.

Non-B, non-T cells from spleen and bone marrow cells produce IL-4 in response to cross-linkage of high affinity receptors for Fc epsilon R or Fc gamma RII, and to treatment with calcium ionophores. Cells bearing high affinity Fc epsilon R constituted 1 to 2% of non-B, non-T cells of spleen and of total bone marrow cells from naive donors. In mice whose immune systems had been polyclonally activated by injection with anti-IgD antibodies or had been infected with Nippostrongylus brasiliensis larvae, the frequency of Fc epsilon R+ cells in splenic non-B, non-T cells was also 1 to 2% but in bone marrow from anti-IgD-injected mice donors the frequency was approximately 5%. Cell sorting experiments revealed that all of the capacity to produce IL-4 in response to immobilized IgE or IgG2a or to ionomycin was found in the Fc epsilon R+ fraction. Among the Fc epsilon R+ spleen cells from naive donors, the frequency of IL-4-producing cells was 1/20 to 1/40 whereas in mice that had been injected with anti-IgD or infected with N. brasiliensis, the frequency of IL-4 producing cells in the Fc epsilon R+ population was approximately 1/5.

Animals↗

The natural history and results of surgery in 50 cases of syringomyelia.

In recent years, new neuroimaging techniques have revived interest in syringomyelia with respect to indications and results of surgery. Fifty patients, 36 of whom underwent surgery, have been reviewed. All patients but 3 underwent a new clinical assessment and 33 of them were also neurophysiologically investigated. In approximately one-third of the non-surgically treated patients the clinical course was benign. In 26 of the surgically treated patients an improvement was noted at the short-term assessment both for spasticity and pain, but in most of them it was not maintained in the medium term. Therefore, an accurate selection of the patients to be treated surgically is strongly recommended, particularly when the natural history of the disease is considered. Decompression of the posterior fossa seems to give the best results, yet no curative surgical treatment has been devised to date.

Adolescent↗

Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials.

We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing.

Aged↗

Murine B cells expressing Thy-1 after in vivo immunization selectively secrete IgE.

IL-4 induces Thy-1 expression and IgE secretion by LPS--and T cell-stimulated murine B cells in vitro. IFN-gamma inhibits both of these IL-4-mediated effects. IL-4 and IFN-gamma are often exclusively produced by different CD4+ T cell subsets. Injection of mice with a polyclonal goat anti-mouse IgD antibody (GaM delta) stimulates large increases in the serum concentration of IgE through the production of IL-4. Neutralization of endogenous IFN-gamma production in GaM delta-injected mice leads to further increases in serum IgE levels. We show that IL-4 and IFN-gamma, produced after GaM delta injection, respectively, stimulate and inhibit the number of splenic B cells expressing Thy-1 in vivo. Increased numbers of Thy-1-expressing B cells are observed concomitantly with the onset of enhanced IgE secretion. These Thy-1-expressing B cells are highly and selectively enriched for IgE-secreting cells.

Animals↗