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Biomedical subjects

F Lolli

Publications and source records attributed to F Lolli.

At least 37 records · Page 2Linked to original sources

Cytokine pattern in the cerebrospinal fluid from patients with GBS and CIDP.

Macrophage-colony stimulating factor (M-CSF) and, less frequently, IL-1 beta and IL-6 were detected in the cerebrospinal fluid (SF) from Guillain-Barré syndrome (GBS) patients. IL-1 alpha, IL-2, IL-10, TNF alpha, and IFN gamma were not found. Detectable cytokine levels were not observed in chronic inflammatory demyelinating polyneuropathy (CIDP) SF nor in any of the sera studied. These findings suggest a prominent intrathecal activation of cells of the monocyte/macrophage lineage (Mø) in GBS, and further support the hypothesis of a crucial role for Mø in GBS immunopathology.

Cytokines↗

Intrathecal synthesis of interleukin-10 (IL-10) in viral and inflammatory diseases of the central nervous system.

The intrathecal synthesis of interleukin 10 (IL-10) was investigated in 120 paired cerebrospinal fluid (CSF) and serum specimens from patients with various inflammatory and non-inflammatory diseases of the central nervous system (CNS). IL-10 was not demonstrated in the sera, but detectable levels were found in the CSF from: patients with acute viral ("aseptic") meningitis, but only within 48-72 h of symptom onset; human immunodeficiency virus type 1 (HIV)-infected patients with HIV-related encephalitis/leukoencephalopathy or cryptococcal meningitis; a patient with primary B cell lymphoma of the CNS, and a patient with encephalomeningeal sarcoidosis (in whom IL-10 was demonstrated in all CSF collected over a period of 6-months). In chronic meningeal infections/inflammations, IL-10 seems to be continuously produced within the CSF. Our findings suggest that IL-10, a cytokine which exerts many immunosuppressive actions, may play different immunomodulatory roles in CNS diseases; in particular, its intrathecal synthesis may explain why some infectious and inflammatory meningeal diseases may have slow development and chronic evolution.

AIDS Dementia Complex↗

HIV antigen-reactive T cells detected by antigen-induced interferon gamma secretion.

The T cell repertoire to human immunodeficiency virus (HIV) was studied in HIV-infected patients of different clinical stages by the detection and enumeration of cells that secreted interferon gamma (IFN-gamma) in short-term cultures of blood mononuclear cells after stimulation in vitro with the HIV recombinant antigens pB1, p121, p24-15, gp160bac, and the HIV V3 loop peptide. T cell reactivities to cytomegalovirus (CMV) and Mycobacterium tuberculosis-purified protein derivative (PPD) were examined in parallel. Among 29 patients with HIV infection, 48% had blood cells recognizing one or more of the five HIV antigens. The mean numbers of HIV antigen-reactive T cells varied between 1/approximately 6000 blood cells for pB1 and 1/approximately 20,000 cells for p24-15. None of the five HIV antigens studied was identified as an immunodominant T cell epitope in HIV infection. T cells from 20% of the patients responded to all five HIV antigens in parallel, but the antigen preferentially recognized varied from patient to patient. Those with more advanced disease had a tendency to lower numbers of HIV antigen-reactive T cells. Most HIV-infected patients had both CMV- and PPD-reactive T cells, but numbers were significantly lower in more advanced disease. It should be possible to adopt the present method to evaluate fine specificities of the T cell repertoire to other antigens and to study the involvement of other cytokines besides IFN-gamma, for example, the Th2 cell-related cytokine interleukin 4.

Adult↗

Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function.

Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 +/- 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 +/- 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l +/- 0.11 vs. 0.21 g/l +/- 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml +/- 1.45 vs. 2.85 mg/100 ml +/- 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 +/- 0.0027 vs. 0.0058 +/- 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 +/- 0.0028 vs. 0.0059 +/- 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations.

Aged↗

Antibodies specific for the lipid-bound form of myelin basic protein during experimental autoimmune encephalomyelitis.

On the hypothesis that myelin basic protein isolated with surrounding lipids may constitute an autoantigen in demyelinating diseases, we studied the antibody response to the lipid-free and lipid-bound form of myelin basic protein during the course of experimental autoimmune encephalomyelitis induced in rats with either form of protein. Immunization with the lipid-bound form of myelin basic protein induced high titres of antibodies directed to the protein, accompanied by no antibodies to cerebroside 30 days after immunization. Antibodies specifically directed to the lipid-bound form of myelin basic protein were revealed after removal of antibodies recognizing the delipidated myelin basic protein. Anti lipid-bound myelin basic protein antibodies could already be detected at day 10 post-immunization, reaching a maximum at day 20 post-immunization. Demonstrations of antibodies entirely specific for the lipid-bound form of myelin basic protein suggests that this molecule may present epitopes not to be found in its already extensively studied primary structure, possibly the result of conformational changes following lipid binding.

Animals↗

Acute spinal trauma: prognostic value of MRI appearances at 0.5 T.

Thirty-two patients with post-traumatic myelopathy were examined with a 0.5 T MRI system within 4 days of injury and the MRI findings analysed with respect to the immediate and residual functional deficit and (in 20 patients) the MRI appearances of the spinal cord in the chronic phase. In the acute phase a normal spinal cord was associated with only slight clinical deficit in four patients. Signal abnormalities in the spinal cord at the site of trauma were identified on T2-weighted spin-echo or T2*-weighted gradient-recalled echo images in 28 patients. The 12 most functionally impaired patients showed focal low signal suggestive of intramedullary haemorrhage: the other 16 had homogeneous high signal consistent with diffuse oedema. Swelling of the spinal cord and mild persistent cord compression following reduction were noted in 17 and 26 patients respectively. All patients were treated conservatively other than undergoing surgical decompression. Four died of complications. No patient with low signal in the spinal cord on initial MRI showed significant clinical improvement. Five whose spinal cord was hyperintense remained unchanged, whereas nine made a significant recovery, as did all patients with normal-appearing spinal cords. Cord compression on the initial examination was not relevant to clinical outcome. Intramedullary scars were identified at follow-up in 18 patients and were more extensive in those with haemorrhagic acute lesions. Haemorrhagic contusion of the spinal cord can be demonstrated in the acute phase with midfield MRI and is a valuable predictor of the functional outcome in patients with traumatic myelopathy.

Acute Disease↗

T and B cell responses to cytomegalovirus antigens in healthy blood donors and bone marrow transplant recipients.

We measured the production of interferon-gamma (IFN-gamma) from single T cells and the T cell proliferative response to different cytomegalovirus (CMV) antigens in healthy blood donors and bone marrow transplant recipients. The antigens consisted of a CMV nuclear antigen (CMV na) containing the pp65-kDa matrix protein and the immediate early antigens but lacking CMV glycoproteins, and an antigen comprising native CMV glycoproteins (CMV gp). We also measured the IgG antibodies to CMV na and CMV gp. The T cells reacted to CMV na in CMV seropositive blood donors both with the production of IFN-gamma and with proliferation, while bone marrow transplant recipients had a deficient T cell response. After stimulation with CMV gp, no T cell response could be observed in CMV seropositive subjects. IgG antibodies to CMV na coexisted in plasma with similar levels of antibodies to CMV gp.

Adolescent↗

Electrophysiological study of neurologically asymptomatic HIV1 seropositive patients.

EEGs, brainstem auditory evoked potentials (BAEPs) and auditory event-related potentials (ERPs) were recorded from 33 individuals infected with the human immunodeficiency virus, type 1 (HIV1+ patients: 13 CDC Class II or III; 20 Class IV). All were neurologically asymptomatic, non-demented, and had a past history of intravenous drug abuse. Sixteen age- and sex-matched normals and 10 HIV1- former drug addicts served as controls. Half of the HIV1+ and HIV1- subjects displayed mild EEG anomalies and, except for one HIV1+ patient, BAEPs were normal in both groups. ERPs were normal in all HIV1- subjects but anomalous (longer latencies of components P2, N2, P3; reduced amplitude of P3) in 9 HIV1+ patients (27%), the incidence of such anomalies being higher for Class IV than Class II/III patients. Auditory ERPs proved the most sensitive and specific of these electrophysiological procedures in detecting subclinical central nervous system involvement in HIV1 infection.

Adult↗

Cine-MR imaging of aqueductal CSF flow in normal pressure hydrocephalus syndrome before and after CSF shunt.

Reproducibility of the aqueductal CSF signal intensity on a gradient echo cine-MR sequence exploiting through plane inflow enhancement was tested in 11 patients with normal or dilated ventricles. Seven patients with normal pressure hydrocephalus (NPH) syndrome were investigated with the sequence before and after CSF shunting. Two patients exhibiting central flow void within a hyperintense aqueductal CSF improved after surgery and the flow void disappeared after shunting. One patient with increased maximum and minimum aqueductal CSF signal as compared to 18 healthy controls also improved and the aqueductal CSF signal was considerably decreased after shunting. Three patients with aqueductal CSF values similar to those in the controls did not improve, notwithstanding their maximum aqueductal CSF signals decreasing slightly after shunting. No appreciable aqueductal CSF flow related enhancement consistent with non-communicating hydrocephalus was found in the last NPH patient who improved after surgery. Cine-MR with inflow technique yields a reproducible evaluation of flow-related aqueductal CSF signal changes which might help in identifying shunt responsive NPH patients. These are likely to be those with hyperdynamic aqueductal CSF or aqueductal obstruction.

Adolescent↗

Electrophysiologic study of HIV-1 + patients without signs of peripheral neuropathy.

HIV-1 seropositive patients have a high frequency of nervous system diseases, and asymptomatic abnormalities are frequently detected. We studied 124 neurologically asymptomatic HIV-1 seropositive subjects and 23 normal control subjects by nerve conduction studies. No alterations were detectable in the asymptomatic stages of infection (CDC groups II and III), while subclinical peripheral nervous system (PNS) impairment was detected in symptomatic HIV-1 stages (CDC group IV). Specifically, in CDC group IV we observed a reduction in the motor conduction velocity of the deep peroneal nerve and the median nerve, and a similar reduction of the sensory conduction velocity of the sural nerve. There were no differences of the amplitude and area of the muscular response or of the sensory nerve action potential. As our patients did not present clinical or laboratory evidence for a toxic-dismetabolic etiology, our data indicate a progressive myelin damage more directly related to HIV-1 infection. This subclinical finding may have importance for the progression of the disease in the PNS.

Action Potentials↗

Cerebrospinal fluid anti-cardiolipin antibodies in neurological diseases.

We studied, with sensitive ELISAs, the anti-cardiolipin antibodies of the G, A, and M classes in the cerebrospinal fluid (CSF) and serum of 179 neurological patients. The CSF and serum of 2 systemic lupus erythematosus (SLE) patients presented IgG anti-cardiolipin antibodies in corresponding levels. Anti-cardiolipin antibodies were produced within the central nervous system in neurosyphilis (A and M classes), in some patients affected by multiple sclerosis (G or M class), in two cases of Guillain-Barré syndrome (G and A classes), and in one AIDS patient (G class). The CSF anti-cardiolipin antibodies detected in our study suggest a local immune reaction against brain phospholipids in SLE and in human demyelinating disorders.

Antibodies↗

Intrathecal synthesis of free immunoglobulin light chains and IgM in initial multiple sclerosis.

We studied the intrathecal synthesis of free kappa, free lambda immunoglobulin light chains and of IgM in 33 consecutive patients with possible or probable MS at the time of their first diagnosis. Nineteen patients presented free kappa or lambda light chain bands in CSF after agarose isoelectric focusing, protein transfer to nitrocellulose and immunostaining with specific antisera. Nineteen patients had increased CSF levels of free kappa light chains as measured with a competitive ELISA. Fourteen had an increased IgM index, as evaluated with a sandwich ELISA. Twenty-six patients displayed CSF oligoclonal IgG bands in CSF and 25 had cerebral magnetic resonance imaging lesions suggestive of MS. The local production of free immunoglobulin light chains and IgM is often detected in the CSF of patients with early MS.

Adolescent↗

Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro.

Activation of T cells results in intracellular expression and secretion of cytokines such as interferon (IFN)-gamma. Here we have used three different assays for determination of IFN-gamma in tetanus toxoid- or mitogen-activated human T cell cultures. Two of these assays [intracytoplasmic immunofluorescence and enzyme-linked immuno spot assay (ELISPOT)] determined the expression and secretion of IFN-gamma at the single-cell level while the third assay enzyme-linked immunosorbent assay (ELISA) measured IFN-gamma secreted into the culture supernatant. Comparison of all three tests revealed a good correlation between the ELISPOT assay and the ELISA, whereas expression of intracellular IFN-gamma showed a qualitative but not a quantitative correlation with the latter. Both the immunospot assay and the immunofluorescence may be used to detect approximate numbers of specific T cells even when present at low frequencies. With the use of the immunospot assay antigen-specific T cells could be detected even in the absence of detectable IFN-gamma in the culture supernatants. However, the ELISA assay should be more convenient for screening large clinical material.

Antigens↗

Intrathecal synthesis of anti-HIV antibodies in AIDS patients.

We studied the production within the CNS of anti-HIV antibodies, of non-specific IgG, and the presence of HIV antigens in the serum and CSF of 28 HIV infected patients belonging to group IV in the Center for Disease Control classification. CSF and serum were diluted under optimal conditions to equalize their IgG content, to enable us to better interpret serum and CSF reactivity by means of Western blot and ELISA. Under these conditions, no patient displayed a limited immunological response profile in CSF as compared to serum. On the contrary, there was intrathecal synthesis (ITS) of anti HIV-antibodies in Western blot test in 21 patients for gp160 and ITS was demonstrable for env, gag, and pol products. ITS of anti-HIV antibodies occurred in 17 patients when measured by ELISA. ITS of non specific IgG and HIV-antigens in CSF were less frequent. A marked anti-HIV response is evident in the CSF-CNS compartment in the later phases of the HIV infection.

AIDS Dementia Complex↗

High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD.

We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy. Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA. Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices. This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage. Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS. Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy. Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.

Adult↗

Terminal component of complement C9 in CSF and plasma of patients with MS and aseptic meningitis.

A sensitive sandwich ELISA was applied to the measurement of the terminal component of complement C9 in CSF and plasma from 40 tension headache patients (reference group), 33 affected by clinically definite MS and 10 by aseptic meningitis. The levels of C9 in plasma were increased in aseptic meningitis. The determinations of CSF/plasma C9 ratio and C9 index, equal to (CSF C9/plasma C9): (CSF albumin/plasma albumin), thus accounting for changes of plasma C9 levels as well as damaged blood brain barrier, documented the existence of local consumption of C9 in aseptic meningitis. In contrast, only borderline alterations were evident in MS. The results indicate that local consumption of total C9 in CSF is an additional variable reflecting an acute inflammation within the CNS, but not demonstrable in MS, a chronic inflammatory CNS disorder.

Adolescent↗

Intrathecal synthesis of IgG, IgA, IgM and IgD in untreated multiple sclerosis and controls.

The intrathecal production (ITP) of the immunoglobulins (Ig) G, A, M and D was examined in untreated patients with multiple sclerosis (MS) and controls. Sensitive sandwich enzyme-linked immunosorbent assay systems were applied to the determination of IgA, IgM and IgD levels in the cerebrospinal fluid and plasma from a group of 61 consecutive MS patients (41 relapsing-remitting and 20 secondary chronic progressive MS). Age-related reference limits for all Ig variables were defined in a group of 57 patients with tension headache. ITP of IgG was demonstrated in 85% of the MS patients, ITP of IgA in 41%, of IgM in 44% and of IgD in 18%. Among 9 MS patients with normal IgG index, 3 displayed ITP of IgA, 3 of IgM and 1 of IgD. Plasma IgA was elevated in 20% and plasma IgM in 24% of the MS cases. No significant variation of Ig ITP was demonstrated in a different group of 27 untreated MS patients examined during exacerbation and remission. Among control patients with other inflammatory nervous system diseases, ITP of IgA, IgM and IgD was found more frequently, and of IgG in a smaller percentage compared with MS patients.

Adult↗