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Biomedical subjects

D Maimone

Publications and source records attributed to D Maimone.

At least 19 recordsLinked to original sources
PubMed2006

Amyloid myopathy presenting with rhabdomyolysis: evidence of complement activation.

At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000-1200U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy.

Aged↗
PubMed2005

Possible increasing risk of multiple sclerosis in Catania, Sicily.

OBJECTIVE: To update prevalence and incidence rates of multiple sclerosis (MS) in Catania, Italy during 1990 to 1999 and evaluate their temporal profiles to assess a possible increase in the MS risk in our study population. METHODS: We studied the frequency of MS in Catania, Italy (population of 313,110 as reported in the 2001 census). The primary sources for the case ascertainment were the neurologic and motor-rehabilitation departments, the MS centers, the Italian MS Association, private neurologists, and family doctors. We considered as prevalent and incident cases all patients who satisfied Poser's criteria for clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS), and laboratory-supported probable MS (LSPMS). RESULTS: We found 288 subjects with MS who had onset of disease before December 31, 1999 (prevalence day) in a population of 313,110 inhabitants. The prevalence rate was 92.0/100,000 (95% CI 81.8 to 103.2) and was higher in women (102.4/100,000) than in men (80.4/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 years (208.2/100,000). From 1990 to 1999, 155 patients with MS had the clinical onset of the disease. The mean annual incidence was 4.7/100,000 (95% CI 4.0 to 5.5). Age-specific incidence showed a peak in the group aged 25 to 34 years (11.7/100,000). Mean annual incidence for 5-year intervals increased from 3.9/100,000 during 1990 to 1994 to 5.5/100,000 during 1995 to 1999. CONCLUSIONS: Prevalence and incidence rates of multiple sclerosis have further increased during the last decade.

Adolescent↗
PubMed2001

High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy.

Twenty years after a first survey, a follow-up study was performed on the prevalence of MS in Enna (Sicily), southern Italy. The prevalence of definite MS rose from 53 to 120.2 per 100,000 population. The incidence of definite MS for the period 1986 to 1995 was 5.7 per 100,000 per year. The innermost part of Sicily shows an elevated prevalence of MS, second only to Sardinia in the Mediterranean area.

Adolescent↗
PubMed2001

Pharmacogenomics of neurodegenerative diseases.

Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.

Alzheimer Disease↗
PubMed1997

IL-6 detection in multiple sclerosis brain.

By using a double-label immunohistochemistry technique, we demonstrated the presence of interleukin-6 (IL-6) in acute and chronic active plaques from the brain of six patients with multiple sclerosis (MS). IL-6 was mainly associated with astrocytes and rarely with macrophages or mononuclear infiltrating cells. The pattern of distribution for IL-6 immunoreactivity was similar to that of HLA-DR expression, but the two molecules almost never colocalized on the same cell. Our data indicate that in MS central nervous system IL-6 is predominantly located within resident glial cells which are concentrated at the sites of ongoing demyelination and immune activation. Although IL-6 exhibits several proinflammatory activities, indirect evidence suggests that the cytokine may also play an immunomodulatory role in inflammatory demyelinating disorders.

Adolescent↗
PubMed1997

Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.

We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.

Aged↗
PubMed1997

The potential role of hepatitis C virus in the pathogenesis of the neurological syndrome in chronic hepatitis C.

A 72-year-old man developed chronic sensory neuropathy (CSN) during chronic hepatitis C (HCV) infection. Neurological symptoms began one year after acute HCV hepatitis and slowly worsened over three years. No conventional cause for CSN was found. Circulating antinervous tissue antibodies (including anti-Hu) and inflammatory infiltrates in sural nerve biopsy specimens were absent. However, the presence of anti-HCV antibody and HCV-RNA in cerebrospinal fluid indicated that HCV had reached the intrathecal compartment, suggesting the direct viral involvement in the pathogenesis of CSN.

Aged↗
PubMed1995

Association of polyclonal anti-GM1 IgM and anti-neurofilament antibodies with CSF oligoclonal bands in a young with amyotrophic lateral sclerosis.

INTRODUCTION: The significance of the association of motor neuron syndromes with anti-GM1 antibodies remains unclear. We report the immunological study of a juvenile case of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Serum anti-Gm1 and anti-neurofilament antibodies were assayed by ELISA and western blotting and cerebrospinal fluid (CSF) isoelectrofocusing was performed. Immunocytochemical studies were carried out with the patient's serum and CSF on human brain and spinal cord sections. RESULTS: Serum polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands were detected. Furthermore, an in vitro production of anti-GM1 IgM was demonstrated. Immunocytochemical studies showed cytoplasm motor neuron immunostaining, due to both IgG and IgM, that substantially decreased after immunoabsorption of the serum with bovine neurofilament proteins but not with GM1-containing liposomes. No immunostaining was obtained with CSF. Immunosuppressive treatment with cyclophosphamide and two cycles of plasma exchanges lowered anti-GM1 antibody levels, but did not determine any clinical improvement. CONCLUSION: To our knowledge, this is the first report of ALS, associated with circulating levels and in vitro production of polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands. These findings suggest the occurrence in our patients of an autoimmune process that could be involved in the pathogenesis of ALS.

Adult↗
PubMed1994

Intrathecal synthesis of anti-myelin basic protein IgG in HIV-1+ patients.

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequently develop a broad spectrum of neurological syndromes, classified as HIV-1-associated cognitive/motor complex. Diffuse demyelination of hemispheric white matter is a commonly observed in HIV-1 infected brain, but the events leading to myelin destruction are still obscure. Since oligodendrocyte infection by HIV-1 is not proven as yet, myelin damage in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of autoimmune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients with HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-inflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1+ (16/25, 64%) than in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the search for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1+, in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti-MBP IgG levels was higher among HIV-1+ patients at stage II-III (4/4, 100%) or at stage IV B (7/9, 78%) than among those at stage IV C-IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP IgG may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possible demyelinating role of these antibodies remains to be demonstrated.

AIDS Dementia Complex↗
PubMed1993

T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis.

To investigate the function of peripheral blood monocytes in multiple sclerosis (MS), we measured the production of the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6), and the procoagulant, tissue factor (TF) in 17 patients with chronic progressive MS and 15 normal controls. Monocyte activity was tested under unstimulated, minimal endotoxin conditions and after culture with various stimuli, including Escherichia coli lipopolysaccharide (LPS), crude supernatant from anti-CD3-activated T cells, recombinant interleukin-2 (rIL-2), and recombinant interferon-gamma (rIFN-gamma). A higher number of MS patients than controls had circulating monocytes which spontaneously secreted IL-6 or contained detectable cell-associated IL-1 beta. Monocyte responses to LPS were comparable between the two groups; LPS caused production and secretion of all cytokines and TF in every MS patient and control. In contrast, crude T cell supernatants, rIL-2, and rIFN-gamma induced IL-1 beta release in a higher number of MS monocytes than that in controls, whereas the production and secretion of the other cytokines and TF activity were similar between the groups. We conclude that some MS patients have "primed" circulating monocytes, as shown by excessive spontaneous IL-6 release and intracellular IL-1 beta synthesis. Unstimulated MS monocytes, however, are not different from controls with respect to spontaneous secretion of small amounts of IL-1 beta and TNF alpha and expression of cell surface TF. Excessive IL-1 beta secretion by MS monocytes after stimulation with T-cell-derived lymphokines suggests dysregulation of T cell-monocyte interactions which may be most relevant in the central nervous system plaques where activated T cells are found.

Humans↗
PubMed1993

Serum and CSF anti-GM1 antibodies in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

High titers of antibodies directed against gangliosides, especially GM1, are found in the serum of patients with a variety of polyneuropathies, including those of the inflammatory type. We assayed anti-GM1 IgG and IgM levels in the serum and cerebrospinal fluid (CSF) of 23 patients with Guillain-Barré syndrome (GBS) and 10 with chronic inflammatory demyelinating polyneuropathy (CIDP) to investigate whether this immune response may also be localized within the intrathecal compartment and correlate with clinical parameters such as time interval since disease onset, disability score, preceding infectious episodes, and GM1 therapy. When compared to the control group, anti-GM1 IgG was increased in the serum of 39% of GBS and 10% of CIDP patients, whereas anti-GM1 IgM was elevated in 17% of GBS and none of the CIDP patients. In both patient groups, however, anti-GM1 antibody levels were more frequently elevated in CSF than paired sera: they belonged to the IgG class in 48% of GBS and 50% of CIDP patients, and to the IgM class in 48% of GBS and 55% of CIDP patients. In the GBS group, anti-GM1 IgM serum levels inversely correlated with time elapsed between sample collection and onset of disease (P < 0.05), whereas serum anti-GM1 IgG levels positively correlated with the loss of functional ability (P < 0.005). Increased anti-GM1 antibodies in GBS serum were not associated with clinical or serological evidence of infectious antecedents nor with previous GM1 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1993

Interleukin-6 levels in the cerebrospinal fluid and serum of patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.

Clinical and experimental findings suggest that humoral factors, such as anti-peripheral nerve antibodies and cytokines, may be implicated in the immunopathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin-6 (IL-6) is a multifunctional cytokine that promotes immunoglobulin synthesis by B lymphocytes. Increased IL-6 release is associated with autoantibody production in a number of immune-mediated and neoplastic disorders. To investigate the possible involvement of abnormal IL-6 release in inflammatory polyneuropathies, we assayed IL-6 levels in the cerebrospinal fluid (CSF) and serum of 23 patients with acute GBS and seven with CIDP. We also studied 69 patients with other non-inflammatory neurological diseases (NIND), 25 with other inflammatory neurological diseases (IND), four with brain tumors (BT), and 15 normal donors (serum alone) as controls. We found detectable levels of IL-6 in the CSF of 57% of GBS, 43% of CIDP, 60% of IND, 75% of BT, and 4% of NIND. In GBS patients, no correlation was found between CSF IL-6 values and other laboratory or clinical parameters, such as CSF total protein, CSF albumin, CSF IgG, CSF/serum albumin ratio, functional disability score, and time elapsed from disease onset. Serum IL-6 levels were increased in six of 23 (26%) GBS, in one of 39 (3%) NIND, and in one of seven (14%) IND, but in none of the CIDP or BT patients. There was no correlation between serum and CSF IL-6 values, but cytokine levels in GBS sera correlated with time elapsed from clinical onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Norepinephrine and vasoactive intestinal peptide induce IL-6 secretion by astrocytes: synergism with IL-1 beta and TNF alpha.

Resident glial cells and invading inflammatory cells are responsible for cytokine production within the brain. Astrocytes are known to secrete a variety of cytokines upon stimulation with cytokines themselves, protein kinase C activators, bacterial or viral constituents. Astrocytes also have surface receptors for a wide number of neurotransmitters and neuropeptides and some of these substances affect astrocyte immune functions, such as major histocompatibility complex (MHC) class II antigen expression. To elucidate the activity of neuromediators on cytokine secretion by glial cells, we studied the secretion of interleukin-6 (IL-6) by cultured rat astrocytes after incubation with various neurotransmitters and neuropeptides. Norepinephrine (NE) and the beta-adrenergic agonist isoproterenol (IPT) induced IL-6 secretion in a dose-dependent fashion. NE effect was predominantly mediated by beta 2-adrenergic receptors with a minor contribution of alpha 1-adrenergic receptors. The induction of IL-6 release by dibutyryl-cAMP indicated that IL-6 secretion secondary to beta 2-adrenergic receptor activation probably occurs through cAMP signalling pathways. Vasoactive intestinal peptide (VIP) was the sole neuropeptide able to induce IL-6 secretion. NE and VIP promoted IL-6 mRNA synthesis and both substances synergized with interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) in inducing IL-6 release. Our findings provide further evidence that neurons modulate astrocyte cytokine production and thereby regulate central nervous system immune functions.

Animals↗
PubMed1993

Astrocyte cytolysis by MHC class II-specific mouse T cell clones.

The brain is "immunologically privileged," in part because class I and II MHC antigens are not normally present on glia or neurons. However, under certain conditions such as transplantation, glial cells express MHC proteins at levels sufficient for glia to become targets of immune responses. Cultured astrocytes expressing very low levels of MHC class I protein are killed efficiently by MHC class I antigen-specific CTL. Mouse brain allografts, however, are rejected by CD4+ T cells that are likely to be class II MHC-specific. The level of expression of MHC class II antigen needed to trigger specific killing of astrocytes by CD4+ T cells, independent of exogenous antigen, has not been studied. We examined the role of glial class II MHC in the lysis of cultured neonatal mouse astrocytes by an alloreactive murine CD4+ CTL alone. IFN-gamma induced functionally relevant increases in MHC class II antigen on target cells. Astrocytes were lysed by the CD4+ clone only when class II MHC antigens reached levels readily detectable by flow cytometry. MHC class II expression and lysis increased when astrocytes were coincubated with IFN-gamma and TNF-alpha. Conversely, lysis decreased when class II expression was downregulated by IFN-alpha/beta or dbcAMP. Cytolysis by CD4+ clones was blocked by antibodies to CD4 and LFA-1 on T cells, and to ICAM-1 and class II molecules on astrocytes. The role of LFA-1 in CD4+ cell-mediated lysis was greater than that of LFA-1/ICAM-1 in CD8+ T cell-mediated lysis. CD4+ cells may lyse activated astrocytes when the immune privilege of the brain is compromised as in transplantation, tumors, and inflammatory diseases.

Animals↗
PubMed1992

Cytokines in the vitreous of patients with proliferative diabetic retinopathy.

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.

Adult↗
PubMed1992

Two brothers with a variant of hereditary sensory neuropathy.

We report two brothers with the clinical symptoms and neuropathological findings of hereditary sensory and autonomic neuropathy (HSAN) type IV but with normal sweating function and absence of recurrent fever. We propose that our patients may have a lower degree of expression of the genetic defect underlying HSAN type IV or that they represent a separate genetic entity.

Adolescent↗