Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis.

We described previously that multiple sclerosis (MS) patients with oligoclonal IgM against myelin lipids (M+) develop an aggressive disease. Our aim was to assess possible mechanisms regulating the production of these antibodies. We studied B cell subsets in 180 patients with MS, and 69 with other neurological diseases.

CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis.

Oligoclonal IgG bands (OCGB) are characteristic of multiple sclerosis (MS). Most patients show OCGB exclusively in cerebrospinal fluid (CSF). Others have serum bands with additional ones in CSF.

Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment.

Background And Purpose: Interferon beta and Glatiramer acetate are safe immunomodulatory treatments (IT) for multiple sclerosis (MS), but not always effective. New drugs are available, although they show more side-effects and unknown long-term safety profile. Anti-lipid oligoclonal IgM bands (OCMB) distinguish MS patients with early aggressive course.

Antiviral activity of lauryl gallate against animal viruses.

Background: Antiviral compounds are needed in the control of many animal and human diseases.

Methods: We analysed the effect of the antitumoural drug lauryl gallate on the infectivity of the African swine fever virus among other DNA (herpes simplex and vaccinia) and RNA (influenza, porcine transmissible gastroenteritis and Sindbis) viruses, paying attention to its effect on the viability of the corresponding host cells.

Results: Viral production was strongly inhibited in different cell lines at non-toxic concentrations of the drug (1-10 microM), reducing the titres 3->5 log units depending on the multiplicity of infection.

Influence of oligoclonal IgM specificity in multiple sclerosis disease course.

Oligoclonal IgM bands (OCMB) against myelin lipids predict an aggressive multiple sclerosis (MS) course. However, the clinical significance of OCMB without lipid specificity, present in other MS patients, remains unknown. We describe here a characterization of these antibodies and study their role in MS progression.

Accuracy of CSF and MRI criteria for dissemination in space in the diagnosis of multiple sclerosis.

Demonstration of lesion dissemination in space (DIS) and time (DIT) is necessary for the diagnosis of multiple sclerosis (MS) in clinically isolated syndromes (CIS). The McDonald criteria accepted two methods to demonstrate DIS. The fulfillment of at least three of four MRI Barkhof criteria (MRI-BC) or, alternatively, the finding of at least two MRI lesions on T2-weighted images (T2 lesions) plus the presence of oligoclonal IgG bands (OCGB) in cerebrospinal fluid (CSF).

Inhibition of proliferation and induction of apoptosis in human breast cancer cells by lauryl gallate.

Lauryl gallate is an antioxidant food additive showing low toxicity to normal cells. Here, its antiproliferative effect has been studied on three human breast cancer cell lines: estrogen-dependent, wild-type p53, MCF7; estrogen-independent, non-functional p53, MDA-MB-231 and MCF7 ADR, which overexpresses P-glycoprotein (P-gp) and displays a multidrug-resistant phenotype. Lauryl gallate inhibited proliferation and induced cell cycle alterations in all three cell lines without altering P-gp functionality in the drug-resistant cells.

Clinically isolated syndromes: a new oligoclonal band test accurately predicts conversion to MS.

Background: Patients with a clinically isolated demyelinating syndrome (CIS) are at risk of developing a second attack, thus converting into clinically definite multiple sclerosis (CDMS). Therefore, an accurate prognostic marker for that conversion might allow early treatment. Brain MRI and oligoclonal IgG band (OCGB) detection are the most frequent paraclinical tests used in MS diagnosis.

Early differential diagnosis of multiple sclerosis using a new oligoclonal band test.

Background: Intrathecal IgG synthesis (ITGS), in conjunction with magnetic resonance imaging, can help in the early diagnosis of multiple sclerosis (MS). Recently, we developed a new oligoclonal IgG band (OCGB) test for ITGS detection that is more sensitive and easier to interpret than previously described methods.

Objective: To assess the accuracy of a new OCGB detection test in the diagnosis of MS.

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS.

Oligoclonal IgM bands restricted to cerebrospinal fluid are an unfavorable prognostic marker in MS, the most common demyelinating disease of the CNS. We have attempted to identify the B cell subpopulation responsible for oligoclonal IgM secretion and the specificity of these bands. In addition, we explored the relationship between specificity and disease evolution.

An ultrasensitive method for the detection of oligoclonal IgG bands.

We have developed an ultrasensitive isoelectrofocusing (IEF) method for the detection of oligoclonal (OGC) IgG bands in cerebrospinal fluid (CSF) and sera. In this procedure, double antibody and peroxidase immunodetection have been substituted by a single antibody labelled with alkaline phosphatase. Alkaline phosphatase immunodetection not only improves tenfold the sensitivity of the assay but also gives a sharper pattern resolution making the interpretation easier and increases the specificity of this technique.

Tumoricidal activity of lauryl gallate towards chemically induced skin tumours in mice.

Lauryl gallate (antioxidant food additive E-312) prevents the formation of dimethylbenzanthracene-induced skin tumours in mice, and kills, selectively, tumoral cells on established tumours. This results in total remission, after topical application of the compound on the tumoral mass, without affecting the surrounding tissue.

Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis.

Intrathecal IgM synthesis (ITMS) predicts a worse evolution in the first stages of multiple sclerosis (MS). The aim of this study was the follow-up of a group of relapsing-remitting MS patients for a longer time to evaluate whether the ITMS implies a poor prognosis. Oligoclonal IgM bands were performed in 29 MS patients followed up from 5 to 16 years.

Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS.

Background: The authors have recently described that intrathecal IgM synthesis (ITMS) correlates with a higher disability in patients with clinically definite MS (CDMS).

Objective: To follow-up a group of patients with MS in the initial stages of the disease to evaluate if the presence of ITMS correlates with a worse evolution.

Methods: Oligoclonal IgM bands were performed in 22 patients with MS with a mean of 1.

Lauryl gallate inhibits the activity of protein tyrosine kinase c-Src purified from human platelets.

The inhibitory effect of gallic acid (3,4,5-trihydroxybenzoic acid), and its ester derivatives methyl, propyl, octyl and lauryl has been tested on the tyrosine kinase activity of affinity purified c-Src from human platelets, using the artificial substrate Poly (Glu,Na,Tyr) 4:1. When tested as inhibitor of the autophosphorylation of the enzyme and the phosphorylation of the protein tyrosine phosphatase SHP-1 by c-Src, lauryl gallate was found to be a more potent inhibitor than other widely used protein tyrosine kinase (PTK) inhibitors such as genistein and herbimycin A. However, lauryl gallate did not inhibit the activity of the serine threonine kinases protein kinase A (PKA) and casein kinase II (CKII) from rat brain.

SHP-1 expression in peripheral T cells from patients with Sezary syndrome and in the T cell line HUT-78: implications in JAK3-mediated signaling.

SHP-1 is a key tyrosine phosphatase that acts as a negative regulator of signal transduction in lymphocytes, which has been found down-regulated in several T cell lines derived from human T cell malignancies. The standardization of a sensitive ELISA for the quantification of SHP-1 protein in peripheral T and B lymphocytes has enabled us to quantify the SHP-1 content of freshly isolated T cells from patients with Sezary syndrome and in the Sezary T cell line HUT-78. In all cases, a dramatic decrease in the content of this protein, when compared with the content in healthy volunteer controls, was observed.

Intrathecal IgM synthesis in neurologic diseases: relationship with disability in MS.

The authors studied the intrathecal IgM synthesis (ITMS) in paired sera and CSF samples from 65 patients with MS, 28 with CNS infection, 40 with other neurologic diseases and eight control subjects. ITMS was found in 30 patients with MS and in 20 with CNS infection, but not in patients with other neurologic diseases or in control subjects. In infectious samples, the ITMS is likely a primary response.

A sensitive and reproducible method for the detection of oligoclonal IgM bands.

We have developed a sensitive and specific isoelectrofocusing (IEF) method for the detection of oligoclonal (OGC) IgM in the cerebrospinal fluid (CSF) and sera. In this procedure, ampholytes, in the range pH 5-8, were used to improve the resolution, and serum was diluted in saline to avoid IgM precipitation. Samples were treated with 50 mM dithiothreitol (DTT) at pH 9.

Study of antiphospholipid antibodies in patients treated with antiepileptic drugs.

Background: Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) are associated with a variety of clinical situations, including drug-intake, but their relationships with antiepileptic drugs have been scarcely investigated.

Objective: To determine the prevalence of antiphospholipid antibodies in patients treated with antiepileptic drugs and the associated risk of thrombotic events.

Patients And Methods: We performed the serologic study of thirty-six consecutively prospectively recruited epileptic patients treated with diverse antiepileptic drugs during 44.

Mechanistic aspects of the induction of apoptosis by lauryl gallate in the murine B-cell lymphoma line Wehi 231.

The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma line Wehi 231. This compound is able to inhibit protein tyrosine kinases (PTKs) in whole cells and in crude extracts with a better efficiency than other well-known PTK inhibitors such as herbimycin or genistein. Initial events triggered upon the incubation of cells with lauryl gallate in phosphate-buffered saline (up to 1 h) include the inhibition of tyrosine phosphorylation, discharge of the mitochondrial transmembrane potential, and induction of mRNA for Bcl-2.

Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells.

Tumoral lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) are long-lived cells in vivo, but they die rapidly by apoptosis in vitro. Here, it is reported that endothelial cells (ECs) inhibit the apoptosis of B-CLL cells, as determined by 4 different flow cytometric methods, and that this antiapoptotic effect is mediated mainly by soluble factor(s), as can be deduced from the following findings. First, EC-conditioned medium (ECCM) inhibited the apoptotic rate in B-CLL to approximately 50% of control.

The expression of integrins on activated T-cells in multiple sclerosis. Effect of intravenous methylprednisolone treatment.

We studied the effect of intravenous methylprednisolone (MP) on the expression of the integrins, LFA-1 and VLA-4, on activated blood T-lymphocytes in 17 patients with relapses of clinically definite relapsing-remitting MS. MP treatment did not induce changes in the expression of CD3, CD4, DR, LFA-1 or VLA-4 markers when measured in the total population of lymphocytes in MS patients in relation to treatment. Treatment influenced neither the LFA-1 nor VLA-4 positive cells within the CD3+ population.

Increased soluble serum HLA class I antigens in patients with lymphoma.

sHLA are soluble forms of class I histocompatibility antigens detected in human serum and cerebrospinal fluid. These molecules are secreted by B and T lymphocytes and the secretion increases dramatically upon mitogenic activation of these cells. sHLA was quantified by an ELISA sandwich method in sera from healthy blood donors, and from patients with Non Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD) both at diagnosis and at remission.

Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation.

The effect of gallic acid (3,4,5-trihydroxybenzoic acid) and its alkyl esters (methyl, propyl, octyl, and lauryl) has been studied on several tumoral and nontumoral cells. Three types of behavior have been observed; the first type is represented by the mouse B cell lymphoma Wehi 231 cell line in which death occurs according to the biochemical characteristics of classical apoptosis showing the DNA ladder fragmentation pattern. The second type is represented by the mouse fibroblast L929 cell line in which morphological characteristics such as cell shrinkage, chromatin condensation, and appearance of apoptotic bodies can be evidenced by microscopical observation.

Methimazole has no dose-related effect on the serum concentrations of soluble class I major histocompatibility complex antigens, soluble interleukin-2 receptor, and beta 2-microglobulin in patients with Graves' disease.

Soluble class I major histocompatibility antigens (sHLA), beta 2-microglobulin (beta 2-M), and soluble interleukin-2 receptor (sIL-2R), are secreted by B and T lymphocytes upon activation, and have been used as markers of immune activation in several diseases. Thirty-two Graves' disease patients were randomly assigned to three methimazole (MMI) regimens of treatment: (1) low-dose, starting with 45 mg/day, and lowering the dose thereafter to maintain normal serum thyroid hormones; (2) MMI 60 mg/day + levothyroxine, and (3) MMI 30 mg/day + levothyroxine. Serum sHLA, beta 2-M, sIL-2R, TSH receptor antibodies (TSH-R Ab), T3, and free T4 (fT4) were measured at diagnosis and at weeks 4, 12, and 24 (end of treatment).