[Polysialylated NCAM in CSF, a marker for invasive medulloblastoma]. / La NCAM polysialylée du LCR, un marqueur des médulloblastomes invasifs.

We described a double-site enzyme-linked immunosorbent assay (ELISA) to measure polysialic acid neural cell adhesion molecule (PSA-NCAM) level in CSF. Immunocapture of PSA-bearing molecules is first effected by means of a monoclonal antibody (anti-MenB), directed against sialic acid polymers and adsorbed into plastic wells. Linked PSA-NCAM is then revealed by means of a second antibody, directed against an aminoacid sequence of NCAM and labelled with peroxydase. The lowest amount of PSA-NCAM detectable was estimated to be 0.11 microgram/l. This value was considered as the threshold for positivity. PSA-NCAM level was measured using this method in CSF from 29 patients with medulloblastoma. CSF had been collected at different times following tumor excision and stored at--80 degrees C. At the same times, cytological examination in CSF (medulloblastoma metastatic cells) and craniospinal imaging (tomographic scan or MRI) had been performed. PSA-NCAM was never detected in control CSF. For patients in remission, beyond the post-operative period of 1 or 2 months, 18 on 21 exhibited a PSA-NCAM level below the threshold value. For refractory patients, so classified according to the positivity of cytology and/or imaging, whatever the time after the tumor excision, PSA-NCAM was always positive (23/23), while either cytology or imaging were positive less frequently (16/23 for both). For relapses, PSA-NCAM was more frequently positive (6/7) than cytology and imaging (1/7 and 5/7, respectively). We concluded that PSA-NCAM positivity in CSF may be a reliable marker to detect the invasive or metastatic feature of medulloblastoma.

Changed transferrin sialylation in Parkinson's disease.

Variation in the sialylation pattern of transferrin was studied in serum and cerebrospinal fluid (CSF) of 90 patients with Parkinson's disease (PD), dementing and non-dementing, de novo and treated, and was compared with the variation observed in a group of 21 age-matched healthy controls. In serum and CSF of PD patients the proportional contribution of the different sialo-transferrins was independent of sex or dementia. However, a significant shift was found towards the more sialylated fractions for serum transferrin in both de novo and treated PD patients. This shift was not observed for CSF transferrin. The contribution of the tau-transferrin fraction, reduced in de novo PD patients, returns on treatment to the level observed for healthy controls. These observations may be important, as the degree of sialylation of transferrin in serum and CSF plays a role in the homeostasis of iron, and suggest that alterations in transferrin sialylation may play a role in the pathophysiology of PD.

Developmental changes of sialylation of soluble beta/A4 amyloid protein precursor derivatives in human cerebrospinal fluid.

Soluble beta/A4 amyloid protein precursor derivatives (APPs) in cerebrospinal fluid from infants, children, adults and aged individuals were treated with neuraminidase. In the samples from infants, reduction of molecular weight of APPs following neuraminidase treatment was significantly less than those from adults or aged individuals. Hyposialylation of beta/A4 amyloid protein precursor in infants may be relevant to a physiological role of this molecule in the development of the nervous system.

Changes in cerebrospinal fluid biotinidase activity in Staphylococcus aureus meningitis.

An early increase in activity of biotinidase in the cerebrospinal fluid (CSF) during the course of acute Staphylococcus aureus meningitis in a subject with subacute sclerosing panencephalitis (SSPE) is reported. A possible role of CSF biotinidase in the hydrolysis of specific opioid neuropeptides during acute inflammatory processes involving the CSF-central nervous system compartment is suggested.

Cerebrospinal fluid N-acetyl neuraminic acid estimation for early diagnosis and differentiation of bacterial meningitis.

Cerebrospinal fluid (CSF) analysis for free, bound and total N-Acetyl Neuraminic Acid (NANA) as well as serum NANA was done in 68 patients of bacterial meningitis, of which 37 cases were of pyrogenic meningitis and 31 of tuberculous meningitis. Ten patients were included in the control group. The free NANA levels were increased in only pyogenic meningitis, independent of protein levels but the bound form increased with the increase in CSF proteins. The increase of free NANA in CSF of pyogenic meningitis patients was not related to the cell count or sugar content in CSF or to the duration or severity of illness. This finding can be of great help in differentiating cases of pyogenic meningitis, particularly partially treated patients, who may have ambiguous pictures of CSF analysis, from the cases of tuberculous meningitis.

Cerebrospinal fluid free N-acetyl neuraminic acid levels--a diagnostic and prognostic test in meningitis.

Cerebrospinal fluid (CSF) free N-acetyl neuraminic acid (NANA) levels were estimated in 20 cases each of pyogenic and tubercular meningitis (TBM) and 10 controls. The levels of free NANA were significantly high (P less than 0.001) in pyogenic and partially treated pyogenic meningitis when compared to TBM. The CSF free NANA levels had direct correlation with severity of the disease, CSF sugar and protein levels in pyogenic meningitis. The CSF free NANA can even be a prognostic criterion in management of pyogenic meningitis. Higher the levels, poorer the prognosis.

[Clinical significance of sialic acid in the CSF; in relation to the malignancy and leptomeningeal dissemination].

We examined the level of sialic acid in cerebrospinal fluid (CSF) in 20 patients with brain tumor, and 5 patients with non-neoplastic disease of central nervous system. CSF concentration of sialic acid in the patients with malignant and semi-malignant or benign brain tumor was 5.26 +/- 2.39 mg/dl, and 1.82 +/- 1.61 mg/dl, respectively. In patients with non-neoplastic disease, it was 1.64 +/- 1.53 mg/dl. The difference between groups was statistically significant (p less than 0.005). In two patients with malignant brain tumor, the level of sialic acid was decreased by radiation therapy or intrathecal chemotherapy. In conclusion, CSF concentration of sialic acid was significant of diagnosis of brain tumor character of malignancy, and effect of therapy for CSF dissemination.

Elevation of cerebrospinal fluid sialic acid concentration in children with central nervous system leukemia.

We studied sialic acid in the cerebrospinal fluid (CSF) of 52 children with leukemia and 51 children with non-leukemic diseases. The CSF sialic acid concentration in the children with central nervous system (CNS) leukemia was significantly higher than that in the children with acute lymphoblastic leukemia without CNS involvement, acute non-lymphocytic leukemia without CNS involvement, non-hemopoietic diseases, non-suppurative meningitis, epilepsy, and other neurologic diseases. Serial determinations revealed a rapid decline in the CSF sialic acid concentrations in the patients with CNS leukemia who responded well to the therapy and who were free from relapse of CNS leukemia. The simultaneously determined CSF beta 2 microglobulin concentration did not show any significant changes. These results suggest that the CSF sialic acid may be a good indicator of CNS leukemia.

Sialic acid in human serum and cerebrospinal fluid. Comparison of methods and reference values.

Sialic acid was estimated simultaneously by three methods: chemical determination based on Warren's method (Meth. Enzymol. 6, 463-464 (1963) with slight modifications, enzymatic measurement with a commercially available test kit, and high performance liquid chromatography (HPLC) according to Silver et al. (J. Chromatogr. 224, 381-388 (1981). These methods showed closely correlated (r greater than 0.930) results and displayed similar precision data. Interference studies demonstrated sufficient specificity for the chemical assay, which was 5-6 times more sensitive than the enzymatic test and hence chosen for the establishment of reference values. From 249 sera from healthy people between 16 and 63 years the 0.025-0.975-reference intervals were calculated to be 1.57-2.63 mmol/l for 127 men, and 1.69-2.64 mmol/l for 122 women with no significant dependence on age and sex. From 43 cerebrospinal fluids from healthy adults the respective values were 17.3-50.4 mumol/l. These data correspond to those of the literature. Some chemical assays employing thiobarbituric acid were compared. They proved reliable in contrast to the reaction of serum with 4-dimethylaminobenzaldehyde.

Evaluation of a fully mechanized enzymatic kinetic determination of sialic acid.

The enzymatic determination of sialic acid, commercially introduced recently as an end point method, has been considerably improved by the development of initial rate and peak rate modifications of the kinetic method, respectively, and adapted to a centrifugal analyser (Cobas Bio). The assay is completed within 3 min, takes 3 microliter sample volume and is reduced to a total reaction volume of 153 microliter. The costs per test thereby are lowered to about 10% of the original procedure. Within-run and day-to-day imprecisions (means = 0.81 g/l) are 2% and 3.9%, respectively; inaccuracy is between +1% and -2%. The detection limit is 0.012 g/l, i.e. about 3 times higher than that of the thiobarbituric acid method (0.0037 g/l) for sialic acid determination. The enzymatic-kinetic assay correlates well with the latter method (r = 0.973). There was no measurable interference by EDTA (less than 3 mg/l), bilirubin (less than 160 mumol/l), haemolysis (haemoglobin less than 5.25 g/l), or triglycerides (less than 3.50 g/l). The reference range (2.5th to 97.5th percentile) for sialic acid in sera of adults is 0.51 to 0.84 g/l (median 0.63 g/l) with no significant sex-related differences. The reference range for sialic acid in spontaneous urine samples is 0.01-0.13 g/l.

Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome.

Identical twin-sisters with evidence of a demyelinating disease showed multiple serum glycoprotein abnormalities. The association of a low serum iron level and a normal blood haemoglobin suggested an abnormality of transferrin too. This was confirmed by finding a sialic acid-deficiency of this glycoprotein in serum as well as in cerebrospinal fluid.

Total and lipid-bound sialic acid in the cerebrospinal fluid of patients with brain tumors.

Total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in the cerebrospinal fluid (CSF) from 63 patients with various neurological diseases. Of these, 27 had brain tumors: 20 had glioma, and 7 pituitary adenoma. TSA levels were significantly increased in the CSF of 18 of the 20 glioma patients (p less than 0.001), while in the adenoma patients were indistinguishable from the controls; with a 90 and 0% test sensitivity respectively. Conversely, the LSA concentrations were significantly elevated, both, in the glioma and pituitary adenoma patients (p less than 0.001), with a 68 and 100% test sensitivity respectively. These preliminary data suggest that measurement of TSA and LSA in the CSF should prove useful for the diagnosis of brain tumors and, perhaps, in the follow-up of patients undergoing treatment for brain tumors.

Markers in psychoses: studies from India.

Genetic considerations are important in studying the pathogenesis of the psychoses. There are few reports from India, however, which have pursued a "biological marker" approach to functional illness of this type. A review of such few studies as do exist is presented to add to contemporary knowledge in the area. Recommendations are also made for evolving newer research strategies.

[Cerebrospinal fluid chlorine-soluble proteins and lipoproteins in the differential diagnosis of cerebral infarct and brain tumor]. / Khlornorastvorimye belki i lipoproteidy likvora v differentsial'noi diagnostike tserebral'nogo infarkta i opukholi mozga.

Results of determining the chemical composition and the electrophoretic spectrum of chlorine-soluble proteins and lipoproteins in the cerebrospinal fluid of patients with cerebral infarctions and brain tumours are presented. The determinations showed non-identity of those proteins in the patients with the above diseases. The information obtained can be of value for solving a number of questions concerning the differential diagnosis, determination of the tumour character, as well as some other questions.