Macrophage-colony stimulating factor (M-CSF) in the cerebrospinal fluid.

In a series of 145 cases with neurological diseases, macrophage-colony stimulating factor (M-CSF) was detected in cerebrospinal fluid of patients with brain tumors, bacterial meningitis, and less frequently, AIDS-dementia complex. Granulocyte-colony stimulating factor (G-CSF) was found only in patients with bacterial meningitis; granulocyte-macrophage (GM)-CSF was never detected. These findings suggest that M-CSF may play an important intrathecal immunoregulatory role in neoplastic and infectious diseases of the central nervous system.

Dopamine (DA) and serotonin metabolic levels in the cerebrospinal fluid (CSF) in Alzheimer's presenile dementia under basic conditions and after stimulation with cerebral cortex phospholipids (BC-PL).

HVA and 5-HIAA levels in CSF were investigated in ten patients with presenile Alzheimer's dementia. As reported by others, CSF levels of dopamine and serotonin metabolism are lower in patients with presenile dementia than in normal controls of the same age. After lumbar puncture, the patients were treated with cerebral cortex phospholipids (200 mg i.v. daily). This produced a significant increase in CSF levels of HVA and 5-HIAA, as well as a reduction of serum PL. The data are interpreted as proving an active pharmacological action of cerebral cortex phospholipids on the various processes of the neurotransmitter substances in demential syndromes.

Immunological indices in presenile Alzheimer's disease.

Immunological indices, both T- and B-dependent, were studied in 11 patients affected by presenile Alzheimer's disease. The data obtained were compared with those from a group of normal adults of similar age and from a group of normal young subjects. Furthermore, antisera were produced in rabbits against Alzheimer's serum and compared to antisera against normal human serum. The following results were obtained: decrease of serum IgM levels; no monoclonal aspects or auto-antibodies were detected in our patients. The kappa/lambda ratio was also normal. The T cell system was functionally normaly, but with a slight decrease of the T cell number and with an increase of the Null lymphocytes. No specific serum proteins were found in the anti-Alzheimer antisera. The data are discussed in correlation to the possible genesis of senile plaques.

Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid.

Serum and cerebrospinal fluid (CSF) levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), and gamma-interferon (gamma-IFN) were measured in multiple sclerosis (MS) patients, human immunodeficiency virus type 1 (HIV-1)-infected patients and normal controls (NC). Increased levels of both IL-2 and sIL-2R were found in MS serum. Moreover, 11 of 50 MS patients showed detectable levels of IL-2 in the CSF. HIV-1-infected patients had increased levels of sIL-2R in serum and, less frequently, in the CSF. gamma-IFN was never detected in serum and CSF of all the patients studied. These findings confirm preliminary reports, further stress a systemic T-cell activation in MS, and support the hypothesis that an immunologic disorder exists in such patients.

Anti-gabaergic neuron autoantibodies in a patient with stiff-man syndrome and ataxia.

We describe a patient with autoimmune insulin-dependent diabetes whose original symptoms of trunk stiffness and rigidity of the abdomen were followed three years later by a pancerebellar syndrome. An autoantibody (autoAb) against GABAergic neurons was found in the patient's serum and cerebrospinal fluid (CSF); on Western blot, this autoAb recognized a 64-kDa antigen of cerebellar protein. The detection of this antibody in a case with ataxia suggests that a spectrum of different neurological diseases may be observed in patients harbouring anti-GABAergic neuron autoAb and supports the concept that factors other than autoAb contribute to the clinical presentation of these disorders.

Transferrin receptors in rat central nervous system. An immunocytochemical study.

Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical layers and in the brain stem where the reaction was most evident. Purkinje cells in the cerebellum and scattered neurons in the gray matter of the cervical spinal cord were weakly stained. Choroid plexus cells also reacted with the mab against TfR whereas oligodendrocytes in the cerebral white matter were faintly outlined by the mab. The presence of TfR on endothelial cells of brain capillaries was here confirmed.

Lead polyneuropathy of nonindustrial origin.

A case of a subacute, distal, symmetrical polyneuropathy in a housewife is reported. The fact that the polyneuropathy affected almost only the motor fibers led us to suspect an exogenous intoxication. Blood lead level and the urinary excretion of lead after intravenous EDTA very high. The blood lead levels were normal in the husband and children oif the patient. A glazed cup used only by the patient to keep tea with lemon juice was found to release toxic amounts of lead with acidic solutions. The manufacturer of the cup was not identified by the enquiring authorities and therefore almost certainly other lead-releasing cups are still in use. The importance of suspecting lead intoxication in individuals not professionally exposed is stressed.

Acute-phase proteins in Alzheimer's disease.

The main 'acute-phase proteins' were determined in serum of 20 patients with presenile Alzheimer's disease (AD) and compared with values in 18 age-matched healthy control subjects. Following parameters were evaluated: alpha 1-antitrypsin (alpha AT), haptoglobin (HPT), transferrin (TRF), acidic alpha 1-glycoprotein (A alpha G), ceruloplasmin (CER), alpha 2-macroglobulin (alpha MG), C-reactive protein (CRP), albumin (ALB), together with the immunoglobulins IgG, IgM and IgA, and some of the most significant factors of the classic (C3, C4) and alternative (properdin factor B) pathways of complement activation. The results showed a statistically significant increase in the levels of alpha AT (p less than 0.001), CER (p less than 0.001) and of all the complement factors studied (p less than 0.005). The levels of other acute-phase protein (HPT, TRF, A alpha G, alpha MG, CRP, ALB) and immunoglobulins (IgG, IgM, IgA) were similar in AD patients and normal controls. These results give rise the possibility that these elements indicate an altered immunoregulation compatible with chronic cell damage and/or chronic inflammation conditions. Moreover, the increased level of alpha AT can be related to the low production of interleukin-1 (IL-1) reported in AD, which supports the hypothesis of a relative derangement of the macrophage function in presenile AD patients.

[Down syndrome: immunological study in adults (author's transl)]. / Sindrome di Down: studio immunologico nei soggetti adulti.

The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome.

Circulating autoantibodies against central nervous system (CNS) antigens in neurological diseases.

A number of investigators have reported the detection of circulating autoantibodies directed against serum and cerebrospinal fluid (CSF) neuronal antigens in certain neurological clinical conditions. Using an immunohistochemical technique, we examined the sera and (when available) the CSF from 120 patients with several neurological disorders and 40 controls in order to analyze the incidence and specificity of the detection of these autoantibodies. Circulating autoantibodies were found in 3 patients with cerebellar degeneration and in 3 patients with stiff-man syndrome, and different staining patterns were revealed in the same disease. Our findings confirm the reported disease-specificity of the detection of these autoantibodies in biological fluids, suggesting that a standardized immunohistochemical technique could constitute an easy and reproducible diagnostic tool in selected neurological conditions. These procedures enable the identification of an immunological pathogenesis of the disease and, in some case, early cancer detection. When atypical staining patterns of staining are found at immunohistochemistry, Western blot characterization of the recognized neuronal antigens is recommended.

Growth factor (M-CSF) and antigenic properties of macrophages in meningioma.

In meningiomas, transformed meningeal cells can share morphological aspects (in hemangiopericytic meningioma) and antigenic properties (i.e.: HLA-DR antigens expression) with elements of the monocyte/macrophage lineage. In this report, we describe a case of a highly vascular meningioma where numerous tumor cells, studied with immunohistochemical methods, present phenotypic properties of macrophages. Moreover, the cerebrospinal fluid (CF) analysis disclosed, using a biological assay, a high level of a growth factor for monocytic elements, the Macrophages Colony Stimulating Factor (M-CSF). Our findings may confirm that transitional aspects between different mesenchymal cells could be present in meningiomas.

On the role of interleukin-2 (IL-2) in multiple sclerosis (MS). IL-2-mediated endothelial cell activation.

Increased serum levels of IL-2 and sIL-2R can be demonstrated in patients with active MS, a finding that strongly supports the hypothesis of a systemic T cell activation in such patients. However, IL-2 may play a crucial role in MS immunopathology by activating endothelial cells, as suggested by the vascular leak syndrome complicating hrIL-2 therapy. Early BBB impairment and focal perivascular edema that characterize MS lesions may be the effect of an IL-2-induced cytokine cascade.

Effect of high-dose steroid therapy on T-cell subpopulations. A longitudinal study in MS patients.

Lymphocyte subpopulations, T cell activation antigens, and serum levels of interleukin 2 (IL-2) and soluble IL-2 receptor (sIL2R), were studied in relapsing-remitting MS (RR-MS) patients before and after high-dose steroid therapy. Prior to therapy, a minority of patients showed increased HLA-DR antigen expression, and an increased number of CD16+ and CD19+ cells. Steroid treatment induced a significant increase in HLA-DR and CD19 expression, a significant reduction in CD16+, CD57+, and CD8+ CD57+ cells, and a slight, non-significant, decrease in IL-2 and sIL-2R levels and CD25 expression on CD4+ T lymphocytes.