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Biomedical subjects

C J Sindic

Publications and source records attributed to C J Sindic.

At least 19 recordsLinked to original sources

Progressive multifocal leukoencephalopathy: simultaneous detection of JCV DNA and anti-JCV antibodies in the cerebrospinal fluid.

We report on a case of biopsy-proven progressive multifocal leukoencephalopathy (PML) in a patient without obvious immunodeficiency. Analysis of the cerebrospinal fluid revealed the simultaneous presence of JC virus DNA and of locally produced, anti-JC virus antibodies. The intrathecal humoral immune response increased throughout the course of the disease, whereas the detection of the JC genome became ultimately negative in spite of the continuous extension of the lesions with fatal outcome.

Aged↗

Expression of costimulatory molecules and cytokines in CSF and peripheral blood mononuclear cells from multiple sclerosis patients.

We amplified the mRNA for cytokines in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients and 21 other neurological patients, using the reverse transcription polymerase chain reaction (RT-PCR). Radioactive hybridization of the amplified DNA allowed quantitation of mRNA levels. Expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 mRNA was elevated in CSF cells from MS patients. IFN-gamma and IL-10 mRNA levels were higher in MS patients than in other inflammatory neurological diseases. mRNA coding for transforming growth factor (TGF)-beta was detectable in the majority of cases, with higher expression in CSF cells of MS and other inflammatory neurological diseases than in noninflammatory controls, and higher expression in PBMC of MS patients than in all other cases. In many MS patients both proinflammatory and immunoregulatory cytokine messages were detected in the CSF compartment without correlation with the clinical activity of the disease. In contrast, mRNA for the costimulatory molecule B7.1 was only detected in the CSF cells of some MS patients, who showed clinical signs of acute relapse at the time of the spinal tap.

Cytokines↗

Sequestrum-like appearance of a multiple sclerosis brain lesion on serial magnetic resonance images.

Using serial magnetic resonance imaging, we monitored an unique lesion of the brain in a 15-year-old girl with clinically definite and laboratory-supported remitting-relapsing multiple sclerosis. During initial phases of the disease course, cystic necrosis around the plaque was observed. Later, remyelination of the central core of the lesion was speculated, as similarities in signal intensity between the core and the normal appearing white matter were partially recovered both on the T1- and the T2-weighted images.

Adolescent↗

B7-1 (CD80), B7-2 (CD86), interleukin-12 and transforming growth factor-beta mRNA expression in CSF and peripheral blood mononuclear cells from multiple sclerosis patients.

Costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are differently involved in T cell stimulation. In chronic experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), B7-1 was preferentially involved in pathophysiology of relapses. We used reverse transcription polymerase chain reaction (RT-PCR) to amplify the mRNA coding for these molecules in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC) from 18 MS patients and 21 other neurological patients. In CSF cells of MS cases, B7-1 mRNA was only detected in some patients who showed clinical signs of acute relapse at the time of the spinal tap, while B7-2 mRNA was widely detectable without difference between active or stable MS and controls. mRNA coding for transforming growth factor-beta (TGF-beta) was detectable in the majority of cases, with higher expression in CSF cells of MS and other inflammatory neurological diseases (OIND) than in noninflammatory controls, and higher expression in PBMC of MS patients than in all other cases. Finally, mRNA coding for interleukin (IL)-12p40 was only detected in a very few number of MS and inflammatory cases. These findings were related to previous detection of other cytokines in the same cases, showing relationships in CSF cells between high expression of B7-1, IL-12p40 and TNF-alpha.

Actins↗

Intrathecal synthesis of virus-specific oligoclonal IgG, and of free kappa and free lambda oligoclonal bands in acute monosymptomatic optic neuritis. Comparison with brain MRI.

Twenty-seven patients with acute monosymptomatic optic neuritis were randomly selected from a population-based cohort of patients extensively screened for known etiologies of ON. Paired serum and CSF obtained median 20 days from onset were examined for oligoclonal IgG, free kappa and free lambda chains, and virus-specific oligoclonal IgG antibodies by an affinity-mediated capillary blot technique. CSF-restricted oligoclonal IgG bands, free kappa and free lambda chain bands were observed in 17, 15 and nine patients, respectively. In addition, 16 patients showed a polyspecific intrathecal synthesis of oligoclonal IgG antibodies against one or more viruses (12 measles, nine varicella zoster, six rubella, six mumps) compared to all the 18 examined patients with definite multiple sclerosis (P = 0.0014). The presence of virus-specific oligoclonal IgG was significantly related to the results of oligoclonal IgG (P = 0.0034), free kappa chain bands (P = 0.0020), and brain MRI abnormalities (P = 0.0402). At 1 year follow-up five patients had developed clinically definite multiple sclerosis; all had virus-specific oligoclonal IgG antibodies, oligoclonal IgG and abnormal MRI at onset.

Adult↗

Data on cytokine mRNA expression in CSF and peripheral blood mononuclear cells from MS patients as detected by PCR.

Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the mRNA coding for different cytokines in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients as compared with 21 other neurological patients. mRNA levels were quantitated by radioactive hybridization of the PCR products. Expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA was elevated in CSF cells of MS patients. In many MS patients, both proinflammatory and immunoregulatory cytokine messages were detected in the CSF compartment. Such immune reactivity of CSF cells, as opposed to PBMC, was not associated with higher clinical activity of the disease. Expression of the B7.1 accessory molecule mRNA was similarly investigated. In the CSF, it was detected only in some clinically active MS cases and in other inflammatory diseases.

Case-Control Studies↗

Clinical relevance of the determination of anti-GQ1b antibodies in Miller Fisher and Guillain-Barré syndromes.

Anti-GQ1b antibodies were assayed by an enzyme-linked immunosorbent assay in sera from patients with non-neurological disorders (N = 20), and with various neurological disorders (N = 59), including nine cases of Miller Fisher syndrome, 16 cases of Guillain-Barré syndrome and one case of acute post-infectious ophthalmoparesis. Such antibodies were found in most cases (8 out of 9) of Miller Fisher syndrome, and at very high titres, in one case of Guillain-Barré syndrome characterised by an initial ophthalmoparesis, and in the case of isolated post-infectious ophthalmoparesis. The latter was characterised by a long-lasting occurrence of these antibodies. Anti-GQ1b antibodies are specific for an immune-mediated neuropathy of the cranial, especially oculomotor, nerves.

Autoantibodies↗

The detection of intrathecal synthesis of anti-herpes simplex IgG antibodies: comparison between an antigen-mediated immunoblotting technique and antibody index calculations. European Union Concerted Action on Virus Meningitis and Encephalitis.

The detection of intrathecal antibody synthesis was compared by the calculation of antibody indices (AI) derived from ELISA techniques with the detection of virus-specific oligoclonal IgGs by an antigen-mediated capillary blot technique. Twenty-seven paired serum and cerebrospinal fluid (CSF) samples were examined from 15 immunocompetent patients with herpes simplex virus encephalitis (HSE) diagnosed by PCR on early CSF samples. These techniques were also applied to paired samples from 20 multiple sclerosis (MS) patients, 10 patients with other inflammatory neurological diseases and 10 patients with non inflammatory neurological disorders. There was a good correlation between the results obtained by AI and those obtained by immunoblotting, especially in HSE (2 discordant results out of 27). Discrepancies were more frequent (25%) in MS patients where a "polyspecific" reaction characterized by low affinity antibodies is known to occur. Some of the discrepancies could, in part, be due to serological cross-reaction with varicella zoster virus.

Adolescent↗

Community-acquired Serratia marcescens meningitis.

Serratia marcescens is an unusual cause of community-acquired meningitis in adults. We report a case of S. marcescens meningitis occurring 29 years after a head injury and preceded by 3 years of intermittent nasal discharge of cerebrospinal fluid (CSF). One month before admission, the patient had received treatment with cefadroxil. This case illustrates the risk of Gram-negative bacillary meningitis in patients with a CSF leak when they are treated with antibiotics. When patients have a chronic clear nasal discharge, one should look for a past medical history of head injury before prescribing antibiotics. In the presence of a fistula, any antibiotherapy may lead to the selection of resistant organisms which may be difficult to treat. Due to the high risk of meningitis and the fact that spontaneous closure in delayed CSF rhinorrhoea is unlikely, surgical repair of any associated fistulae is mandatory.

Anti-Bacterial Agents↗

Detection of CSF-specific oligoclonal antibodies to recombinant JC virus VP1 in patients with progressive multifocal leukoencephalopathy.

The intrathecal synthesis of antibodies against recombinant VP1, the major structural protein of JC virus (JCV), was studied in 18 patients with progressive multifocal leukoencephalopathy (PML) and in 31 patients with various neurological disorders. Two methods were used, the calculation of an antibody specific index (ASI) on one hand and an antigen-driven immunoblotting for the detection of oligoclonal antibodies on the other. Most PML patients displayed an elevated (> 1.5) ASI (78%) and anti-VP1 oligoclonal antibodies restricted to the cerebrospinal fluid (55%). Only two other patients (one case each of multiple sclerosis and of neuroborreliosis) also showed an intrathecal synthesis of anti-VP1 oligoclonal antibodies, likely as a result of a 'polyspecific' reaction within the central nervous system.

Antibodies, Viral↗

Cytokine mRNA expression in CSF and peripheral blood mononuclear cells in multiple sclerosis: detection by RT-PCR without in vitro stimulation.

We amplified the mRNA for cytokines in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients and 21 other neurological patients, using reverse transcription polymerase chain reaction (RT-PCR). A radioactive hybridization of the amplified DNA allowed quantitation of mRNA levels. Expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 mRNA was elevated in CSF cells of MS patients. IFN-gamma and IL-10 mRNA levels were higher in MS patients than in other inflammatory neurological diseases. In many MS patients, both proinflammatory and immunoregulatory cytokine messages were detected in the CSF compartment. Such immune reactivity in CSF, as opposed to the peripheral compartment, did not correlate with the clinical activity of the disease.

Adult↗

Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a subacute viral infection of oligodendrocytes by JC virus occurring almost exclusively in immunocompromised patients. By use of partially purified recombinant VP1 as antigen, the IgG response was analyzed by a quantitative ELISA of paired cerebrospinal fluid (CSF) and serum samples. An intrathecal immune response to VP1, defined as an antibody-specificity index of CSF to serum antibody titers > or =1.5, was found in 76% of PML patients (47/62) but in only 3.2% of controls (5/155) (P < .001). Intra-blood-brain barrier synthesis of VP1-specific IgG antibodies is 76% sensitive and 96.8% specific for the diagnosis of PML. Furthermore, the excellent correlation (r = .985) between the plasma cell count in brain tissue and the humoral intrathecal immune response to VP1 in PML patients suggests a role for B cells in this disorder.

Adolescent↗

Multiple sclerosis and intrathecal IgA synthesis.

A clinically definite diagnosis of multiple sclerosis was done in a 61 year-old woman who displayed severe cerebellar and pyramidal tract involvement. Symptoms developed 5 years before with unsteadiness of gait and difficulties in walking. Diagnosis was supported by evoked potentials studies and magnetic resonance imaging. However, the cerebrospinal fluid (CSF) analysis was very unusual. CSF albumin and IgG concentrations were normal, as well as the IgG index. In contrast, the IgA level and the IgA index were markedly increased and the local synthesis of IgA was estimated at 31.36 mg/l. Reduction by dithiotreitol did not change the IgA level. On affinity immunoblots, oligoclonal IgA bands were not detected but oligoclonal IgG bands were present. The strong local production of IgA in this patient seems to be therefore polyclonal.

Dithioerythritol↗

Encephalitis in immunocompetent patients due to herpes simplex virus type 1 or 2: determination by polymerase chain reaction and detection of intrathecal virus-specific oligoclonal antibodies.

Serum and cerebrospinal fluid (CSF) of 13 patients have been examined to confirm and precise the diagnosis of herpes simplex virus encephalitis (HSVE). By amplifying the DNA with a nested polymerase chain reaction (PCR), we could demonstrate the herpetic origin of these cases of encephalitis. DNA of HSV type 1 or type 2 was directly identified and differentiated, by the use of both type-specific primes in the same reaction. The primer sequences were chosen in the glycoprotein D region for HSV type 1, and in the glycoprotein G region for HSV type 2. Only one case was due to the latter. In all but one cases, an immunoaffinity-mediated capillary blotting study was also performed. This technique showed the occurrence of oligoclonal CSF-specific IgG bands, while the antigen-driven immunoblotting demonstrated intrathecal production of oligoclonal anti HSV antibodies. In most of the cases, repeated CSF analysis allowed us to study the sequential detection of viral DNA and of intrathecal synthesis of virus-specific IgG in relation to the clinical course. All the patients were treated with acyclovir. In one case, a relapse was clinically suspected, but the PCR remained negative.

Adolescent↗