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Background: beta-Trace protein (Btp) has been proposed as a valuable marker of cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin (B-2Tr) determination. However, there is still controversy about the appropriate cut-offs to be used (range 0.35-6 mg/L). The aim of the study was to evaluate cut-offs of Btp determination for detection CSF leakage. Further, we assessed whether the Btp secretion to serum ratio (Btp-sec/ser-ratio) would add diagnostic value., Methods: Prospective study in patients with suspected CSF leakage. Quantitative determination of Btp in secretion and serum (Dade-Behring) and qualitative measurement of B-2-Tr in secretion and serum. Results were assessed in view of clinical data. Cut-offs and diagnostic characteristics were determined by ROC analysis., Results: A total of 176 samples were assessed originating from 105 patients. In 43 samples CSF leakage could be confirmed. Sensitivity of B-2-Tr was 84%, specificity amounted to 100%. The area under the curve (AUC) for Btp-measurement in secretion was 0.98. At a cut-off of 0.68 mg/L, sensitivity was 100% and specificity 91%. At a cut-off of 1.11 mg/L, the specificity was 100% with a sensitivity of 93%. The Btp-sec/ser-ratio has an AUC of 0.99. Combining a 0.68 mg/L cut-off in secretion with a Btp-sec/ser-ratio cut-off of 4.9 reveals a sensitivity of 99% and a specificity of 100%., Conclusions: Btp is a rapid and accurate marker for the presence of CSF leakage. Combining measurement of Btp in secretion together with determination of the Btp-sec/ser-ratio enhances the diagnostic characteristics of the Btp assay. Determination of Btp in both serum and secretion is thus recommended.

Objectives: In animal models and in vitro studies leptomeninges have been shown to be the origin of neurotrophic substances that support the survival and growth of neuronal cells. Because dementia is associated with neuronal loss, we investigated whether leptomeningeal dysfunction may be involved in the pathogenesis of dementia disorders., Methods: We analysed the cerebrospinal fluid (CSF) concentrations of the leptomeningeal derived beta trace protein, beta2 microglobulin, and cystatin C., Results: There was a statistically significant difference of the CSF beta trace protein levels among different groups. Patients with idiopathic normal pressure hydrocephalus (NPH) (17.5 (SD 4.3) mg/l) showed significantly lower CSF beta trace protein levels than patients with Alzheimer's disease (23.8 (6.2) mg/l), depression (24.2 (7.3) mg/l), and normal controls (25.3 (4.9) mg/l). To patients with vascular dementia (20.1 (5.6) mg/l) and frontotemporal dementia (21.9 (7.0) mg/l), the difference was not significant. There was no significant difference regarding the CSF and serum concentrations of beta2 microglobulin or cystatin C among the different groups., Conclusions: We conclude that leptomeningeal dysfunction may be involved in certain types of dementia such as NPH and that reduced CSF beta trace protein levels in patients with NPH may aid in differentiating this difficult to diagnose disorder from other syndromes such as Alzheimer's disease.

Fever is an important part of the host defense response, yet fever can be detrimental if it is uncontrolled. We provide the first evidence that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), can attenuate the febrile response to lipopolysaccharide (LPS) in rats via an action on the brain. Furthermore, we show that PPARgamma is expressed in the hypothalamus, an important locus in the brain for fever generation. In addition, 15d-PGJ2 and its synthesizing enzyme (PGD2 synthase) were present in rat cerebrospinal fluid, and their levels were enhanced in response to systemic injection of LPS. The antipyretic effect of 15d-PGJ2 was associated with reduction in LPS-stimulated cyclooxygenase-2 expression in the hypothalamus but not in p44/p42 mitogen-activated protein kinase phosphorylation or in the expression of the PPARgamma. Thus it is likely that there is a parallel induction of an endogenous prostanoid pathway in the brain capable of limiting deleterious actions of the proinflammatory prostaglandin E2-dependent pathway.

Lipocalin-type prostaglandin D synthase (PGDS) is considered to be mainly produced in the leptomeninges and secreted into cerebrospinal fluid (CSF). We found PGDS levels in CSF of patients with normal pressure hydrocephalus (NPH) (8.99+/-2.59 microg/ml, mean+/-S.D., n=14) to be significantly lower than levels in a control (15.29+/-5.17, n=14, P<0.0001) and other dementia group (19.14+/-4.34, n=7, P=0.0003). Thus, PGDS level in CSF is a useful marker for the differential diagnosis of NPH from other diseases with dementia.

Background: Liquorrhea caused by cerebrospinal fluid fistula may lead to meningitis and should be treated surgically. The diagnostic approach and the surgery may be difficult and improvements are needed., Material and Methods: We present two cases of liquorrhea. A review of the diagnostic and surgical methods is given., Results: In both cases the diagnosis was confirmed by detection of beta-trace protein. In one case the surgery was complicated. This patient had a cerebrospinal fluid fistula from the sphenoid sinus. In a third operation, performed with sodium fluorescein dying, the fistula was closed., Interpretation: Rhinorrhea and meningitis are unspecific signs of a possible cerebrospinal fluid fistula. Beta-trace protein is recommended as a diagnostic marker, because this protein has the highest positive predictive value for the presence of cerebrospinal fluid. High-resolution CT scans are the most helpful imaging technique for determining the leakage site, but this is not conclusive in all cases. Using sodium fluorescein may give better outcomes of surgical interventions.

Objective: Cerebrospinal fluid (CSF) fistulas need to be reliably diagnosed for the optimal management. Recently, in preference to beta2-transferrin, another CSF protein, beta-trace protein (betaTP), is similarly used with a new method for CSF diagnosis. This study evaluates the sensitive interpretation and limits of this new betaTP test for use in routine CSF fistula diagnosis., Methods: Nephelometric detection of betaTP has been made in nasal secretion, serum, and CSF samples from healthy individuals as well as patients with reduced glomerular filtration rate and with bacterial meningitis. Additionally, 53 patients with suspected CSF rhinorrhea are also analyzed., Results: The betaTP test can also be used to reliably diagnose CSF rhinorrhea even slightly better than the beta2-transferrin test. It should not be used for patients with renal insufficiency and bacterial meningitis as they substantially increase serum and decrease CSF betaTP values, respectively., Conclusion: Quantitative measurement of betaTP is a noninvasive, highly sensitive, quick, and inexpensive method that can be used for the detection of CSF rhinorrhea in nasal secretions. However, in cases where there is doubt about the interpretation, the results should be proved with beta2-transferrin test or sodium-fluorescein test.

Objective: Beta-trace protein concentrations in cerebrospinal fluid (CSF), serum and nasal secretions are investigated with a new quantitative, immunonephelometric assay., Results: The mean beta-trace concentration of normal lumbar CSF (18.4 mg/l) and normal serum (0.59 mg/l), from n = 132 control patients, were 10% higher than reported earlier for smaller control groups. The reference range of beta-trace protein in nasal secretions is very low (median: 0.016 mg/l, range <0.003-0.12 mg/l, for n = 29 controls). Clinically confirmed cases of CSF rhinorhea (n = 20) showed beta-trace concentrations between 0.36 and 53.6 mg/l, with a median of 2.4 mg/l. We propose a cut-off value of 0.35 mg/l above which a CSF contamination in the secretion is plausible. A clinically confirmed CSF otorhea had a value of 1.75 mg/l., Conclusion: This new beta-trace protein assay offers a fast, sensitive and reliable routine method to detect a CSF rhinorhea or otorhea.

beta-trace protein is an immunological marker for the detection of cerebrospinal fluid leakage to the nose or ear. Analysis of beta-trace protein via a nephelometric assay is a valuable test for the identification of cerebrospinal fluid in rhinorrhea or otorrhea.

It has been proposed that prostaglandin (PG) D(2) induces physiological sleep in mammals by acting on sleep centers located in the anterior hypothalamus. In fetal sheep, definitive rapid-eye-movement and non-rapid-eye-movement sleep states appear at approximately 125 d gestation (term is approximately 147 d). In adult animals, PGD synthase (PGDS) (functionally and structurally homologous to beta-trace protein) is secreted into CSF with a circadian pattern, with the highest concentrations present during sleep. In this study we show that PGDS/beta-trace protein is present in fetal sheep CSF at 125 and 135 d gestation but not at 90 d gestation. SeCl(4), a specific inhibitor of PGDS, was given to unanesthetized fetal sheep (130-140 d gestation) by intracerebroventricular infusion at a dose of 25, 100, 500, or 1000 pmol/min for 4 hr. Artificial CSF was infused in control experiments. Arousal behavior, defined as the presence of nuchal muscle electromyogram activity, electro-ocular activity, and breathing movements during low-amplitude electrocortical activity, increased from 3.8 +/- 1 min/hr to 6.6 +/- 0.5 and 7.0 +/- 0.3 min/hr at doses of 100 and 500 pmol/min, respectively (p < 0.05). SeCl(4) at 25 and 1000 pmol/min had no significant effect on arousal activity. Infusion of PGD(2) at 500 pmol/min intracerebroventricularly for 4 hr decreased the incidence of arousal from 3.8 +/- 0.5 min/hr to 0.7 +/- 0.3 min/hr (p < 0.05). When 500 pmol/min PGD(2) was infused immediately after a 4 hr infusion of SeCl(4) (500 pmol/min), the SeCl(4)-induced increase in arousal behavior was abolished. Together, the presence of PGDS/beta-trace protein in fetal CSF in late gestation and the effects of SeCl(4) in increasing the incidence of arousal-like behavior suggest that PGD(2) has a role in the induction and maintenance of prenatal sleep.

Objective: beta-Trace protein (beta-TP) is an immunological marker for the detection of cerebrospinal fluid traces. The aim of the study was to evaluate the predictive values of a new research assay for beta-TP., Methods: A total of 154 specimens from patients with otorrhea or rhinorrhea were investigated for cerebrospinal fluid (CSF) by use of a laser-nephelometric assay for beta-TP. Samples were obtained between January 1994 and November 2000. A sample was reported to be positive for CSF when the beta-TP concentration was more than 6 mg/L. Case evaluations were performed retrospectively and tabulated for indication, clinical course, additional investigations, surgical procedure, and follow-up., Results: beta-TP was detected in 16 specimens; 138 samples were negative for beta-TP with a value less than 3 mg/L. One sample was suggestive of CSF traces at 4.6 mg/L. In correlation with the clinical course, the intraoperative findings, intraoperative visualization with sodium fluorescein, high-resolution computed tomography of the paranasal sinuses or the petrous bone, computed tomographic cisternography, magnetic resonance imaging, and radionuclide cisternography, there was no false-positive result. On four occasions, false-negative results occurred, with an overall accuracy of 0.974. The beta-TP test had a negative predictive value of 0.971 and a positive predictive value of 1., Conclusion: Analysis of betas-TP via the nephelometric assay is a valuable and reliable test in cranial base surgery for the identification of CSF.

Charge microheterogeneity of the beta-trace protein (beta-TP = lipocalin-type prostaglandin D synthase) in the cerebrospinal fluid (CSF) of patients with various neurological disorders was analyzed by capillary isoelectric focusing (CIEF). Under the conditions employed, beta-TP in the low-molecular-weight protein fraction of CSF was separated into at least four isoforms with different p/ values. An isoform with the pl value of 4.6-4.8 was usually the most abundant. The total beta-TP level in the CSF was determined by enzyme-linked immunosorbent assay (ELISA) to be elevated in patients recovering from organic damage to the CNS and those with pathological brain atrophy. Changes in the total beta-TP level in the CSF were occasionally accompanied by those in its charge microheterogeneity, as revealed by CIEF. Such quantitative and qualitative changes in beta-TP in human CSF indicated changes in its pathophysiological roles in association with various neurological disorders.

Objectives: To determine the sensitivity and specificity of a nephelometric beta-trace protein assay for the diagnosis of liquorrhoea., Methods: One hundred and forty clinical samples with suspected liquorrhoea were analysed by a newly developed nephelometric assay. An established electroimmunoassay served as a reference method. The sensitivity and specificity of the beta-trace nephelometric assay were calculated by a 2x2 contingency table for 10 different versions of a dichotomised nephelometric variable. In 52 patients (79 samples), the nephelometric findings were validated by referring to the clinical diagnosis based on the course of the disease, imaging techniques, and surgical inspection., Results: Given a specificity of 100%, a beta-trace protein concentration of 6 mg/l or higher in a sample indicated liquorrhoea with a sensitivity of 92% compared with the reference method and of 93% compared with the clinical evaluation. The relation between the electroimmunoassay and the nephelometric assay was highly significant (p<0.001)., Conclusions: The nephelometric beta-trace protein assay is a simple and rapid method for the detection of liquorrhoea with high sensitivity and specificity and may facilitate the diagnosis of fistulas leaking CSF.

Background: The recent theory of blood-cerebrospinal fluid (CSF) barrier function and dysfunction connects molecular flux and CSF flow rate. A reduced CSF flow rate is sufficient to account for the observed hyperbolic relation between different blood-derived protein concentrations in CSF in cases of a blood-CSF barrier dysfunction., Methods: The dynamics of brain-derived proteins in CSF are investigated with reference to the CSF flow rate measured by CSF/serum albumin concentration quotient., Results: Proteins from neurons or glial cells, tau protein, neuron-specific enolase, S-100 protein, all enter CSF primarily in the ventricular and cisternal space. Their concentration between normal ventricular and lumbar CSF is decreasing (in contrast to blood-derived proteins), and in the case of pathologically decreasing CSF flow rate, the concentration in lumbar CSF remains invariantly constant. Concentrations of the primarily leptomeningeal proteins, beta-trace protein and cystatin C, increase between normal ventricular and lumbar CSF, and in the case of pathologically decreased CSF flow rate they increase linearly in lumbar CSF (concentrations of blood-derived proteins increase non-linearly)., Conclusions: A satisfactory physiological explanation can now be given for the dynamics of proteins in CSF consisting of both brain- and blood-derived fractions (transthyretin, soluble intercellular adhesion molecule (s-ICAM)), as well as the disputed decrease of leptomeningeal protein concentrations (beta-trace protein, cystatin C) in cases of bacterial meningitis is also explained. The biophysical treatment of dynamics in the ventricular and lumbar CSF extends the new theory and shows that CSF flow rate is the most relevant parameter for understanding the pathological changes of both blood- and brain-derived proteins in CSF. The impact on diagnosis of neuro-degenerative diseases is discussed.

It was proposed that lipocalin type prostaglandin D synthase (L-PGD-S), a bifunctional protein both synthesizing PGD2 and transporting retinoids and other lipophilic ligands, could be involved in the development and the maturation of sperm. In the present study, the seminal plasma (SP) of 59 adult males was analyzed by standard WHO methods and immunoblotting, using a monospecific polyclonal antibody directed against L-PGD-S. Briefly, aliquots of SP (2.5 microl), were fractionated by polyacrylamide electrophoresis in the presence of sodium dodecyl sulfate, the blots were stained and densitometrically analyzed. To obtain quantitative data, the aliquot of SP was selected within the linear part of the dose/band intensity curve and a proper quality control was analyzed in all blots to normalize the intensity of the bands of different experiments. A significant reduction (p<0.05) of the L-PGD-S levels was observed in severe oligozoospermic patients compared to normozoospermic subjects and a significant correlation between L-PGD-S levels and sperm concentration was found, as reported by other authors. Further studies are warranted to evaluate the possible diagnostic and pharmacological applications of these observations.

To examine the possibility that prostaglandin D synthase in CSF is involved in the brain responses to inflammation, we monitored the enzyme levels before and after administration of a bacterial endotoxin lipopolysaccharide (LPS) or proinflammatory cytokines. After an i.p. injection of LPS, the synthase levels began to rise within 1 day, peaked at 2 days and returned to the basal by 5 days after injection. The enzyme levels increased in a similar manner in response to tumor necrosis factor-alpha or interleukin (IL)-1 beta injected i.v. Centrally administered IL-1 beta had a similar effect. These findings support the hypothesis that PGD synthase in CSF participates in the brain responses to inflammation.

Beta-trace protein is a lipocalin that was recently identified as prostaglandin D synthase and represents a major constituent of human cerebrospinal fluid. Beta-trace protein, similar to beta 2-transferrin, has been used as an immunological marker for the detection of cerebrospinal fluid. Between 1982 and 1999, 130 specimens from 101 patients with suspected cerebrospinal fluid leaks of the anterior or lateral skull base have been investigated for beta-trace protein. The specimens were analyzed by one-dimensional immunoelectrophoresis using Laurrell's electroimmunoassay. In all, beta-trace protein could be detected in 57 specimens and was absent in 73. All case notes were studied retrospectively. In correlation with the clinical course and the findings of CT of the paranasal sinuses, high resolution CT of the petrous bones, CT cisternography, NMR, 111In-DTPA radionuclide cisternography, intraoperative findings, visualization of sodium-fluorescein stained cerebrospinal fluid using endoscopic blue light or testing for glucose, there was no false-positive result. A false-negative result occurred in two cases. These findings show that the beta-trace test has a sensitivity of 97.3% and a specificity of nearly 100%. Our findings show that analysis of beta-trace protein can be a valuable test for detecting CSF leakage and has certain advantages in comparison with the beta 2-transferrin assay.

Different mixtures from a serum pool and a cerebrospinal fluid (CSF) pool were used as models to study CSF contamination in secretions by determining two CSF specific proteins: beta-trace protein (beta-TP) and the asialo-transferrin (a-Tf) band which was detected by isoelectric focusing (IEF) with Tf specific immunofixation. Beta-TP and total Tf were measured immunonephelometrically. Secretion/serum ratios of beta-TP content > 2.0 indicated CSF contaminations with > or = 5% (v/v) CSF; this was confirmed by detecting the a-Tf band by IEF. Reliable a-Tf bands were only revealed with secretion/serum rations of Tf contents < 0.1, indicating an interference of major sialo-Tf fractions with the a-TF band detection in the sample. For CSF detection in rhinorrhea and otorrhea, complementary use of beta-TP assay and a-Tf assay is recommended. Preanalytically, dilution or concentration of the sample as well as denaturation of Tf and beta-TP should be prevented by optimizing sample collection.

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable clinical pictures. We report the delineation of a novel type of CDG identified in 2 children presenting with severe developmental delay, seizures, and dysmorphic features. We detected hypoglycosylation on serum transferrin and cerebrospinal fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene, 1 with a 274C>G transversion, the other with a 628delC deletion, were detected in both siblings. Complementation analysis using DPM1-null murine Thy1-deficient cells confirmed the detrimental effect of both mutations on the enzymatic activity. Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients. Because DPM1 deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this novel glycosylation defect was named CDG-Ie.

As carbohydrate-deficient glycoprotein syndromes (CDGS) are multisystemic disorders with impaired central nervous function in nearly all cases, we tested isoforms of beta-trace protein (beta TP), a 'brain-type' glycosylated protein in cerebrospinal fluid (CSF) of nine patients with the characteristic CDGS type I pattern of serum transferrin. Whereas the serum transferrin pattern did not discriminate between the various subtypes of CDGS type I (CDGS type Ia, type Ic, and patients with unknown defect), beta TP isoforms of CDGS type Ia patients differed from that of the other CDGS type I patients. The percentage of abnormal beta TP isoforms correlated with the severity of the neurological symptoms. Furthermore, two patients are described, who illustrate that abnormal protein N-glycosylation can occur restricted to either the 'peripheral' serum or the central nervous system compartment. This is the first report presenting evidence for an N-glycosylation defect restricted to the brain. Testing beta TP isoforms is a useful tool to detect protein N-glycosylation disorders in the central nervous system.

In the pachymeninx (dura mater) from human spinal cord and brain, expression of mRNA for the beta-trace protein (beta-trace) was studied by in situ hybridization with digoxigenin-labeled cRNA probes. The localization of the protein was investigated using monoclonal and polyclonal antibodies, respectively. Very strong hybridization signals were observed in the fibroblasts of the pachymeninx. The results obtained by in situ hybridization were essentially confirmed by immunocytochemistry. By immunoblotting of proteins solubilized from the dura mater, strong immunoreactions were found with a polyclonal beta-trace antibody. Furthermore, beta-trace was quantified in human ventricular and lumbar cerebrospinal fluid (CSF) by use of an immunonephelometric assay. The beta-trace concentration in human lumbar CSF was elevated 11-fold as compared with ventricular CSF. Beta-trace determined in lumbar CSF most probably originates from fibroblasts of the pachymeninx. According to the bi- or probably multifunctional features of beta-trace, various sites of mRNA expression and protein synthesis exist in the human central nervous system (CNS). The major ones are the fibroblasts of the pachymeninx, and as previously shown, the epithelial layer of the choroid plexus., (Copyright 1999 Wiley-Liss, Inc.)

We measured the concentration of lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) and serum in patients 1, 3, 5, 7, 9, 11, 14 and 17 days after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms. The PGDS level in lumbar CSF increased about two-fold at day 3 (20.85 +/- 2.71 microg/ml, mean +/- SE) and at day 5 (25.24 +/- 3.76), as compared with the level at day 1 (11.25 +/- 1.07). The CSF level gradually decreased and returned to the day 1 level at day 17. The serum PGDS level was much lower than the CSF level (0.39 +/- 0.06 at day 1) and almost unchanged until day 17. The neuron-specific enolase level in CSF, as an index of brain damage, was maximum at day 1 (29.83 +/- 7.32 ng/ml) and decreased at day 3 and at day 5 (18.28 +/- 2.65 and 11.95 +/- 1.82, respectively). These results suggest that the transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.

Changes of glycosylation of cerebrospinal fluid proteins such as alpha2-macroglobulin, and prostaglandin D synthase were studied by lectin blotting, using concanavalinA, in multiple sclerosis (n = 42) and neuropathies (n = 20) in comparison to neurological controls (n = 22). The concanavalinA-reactivity of alpha2-macroglobulin, which was increased in the neuropathies but not in multiple sclerosis compared to controls, correlated with the total concanavalinA-reactivity in controls and neuropathies but not in multiple sclerosis, indicating that the protein could be abnormally glycosylated in the latter disease. Although the concentration and the concanavalinA-reactivity of prostaglandin D synthase were not significantly different in the three groups, the two parameters correlated only in neuropathies but not in controls or multiple sclerosis, probably due to the high heterogeneity of the protein. These changes deserve to be studied in further detail in view of their potential clinical applications.

Prostaglandin D synthetase (PGD-S; prostaglandin-H2 D-isomerase, EC 5,3,99,2), a 30 kDa glycoprotein also known as beta-trace protein that catalyzes the formation of prostaglandin D2 (PGD2) from PGH2, was purified to apparent homogeneity from human cerebrospinal fluid (CSF) using a two-step procedure involving HPLC on a Vydac C8 reversed-phase column and high performance electrophoresis chromatography (HPEC) using a 10% T SDS-polyacrylamide gel. The purity of PGD-S isolated from CSF was confirmed by silver stained SDS-polyacrylamide gel and direct protein microsequencing (NH2-APEAQVSVQPNFQ). A highly specific polyclonal antibody was prepared against this protein for immunoassay development. Using an ELISA, it was found that the concentration of PGD-S in CSF did not alter significantly in different pathological conditions of the central nervous system (CNS). These include dementia (n = 9), hydrocephalus (n = 4), neuropathy (n = 11), optic neuritis (n = 4), multiple sclerosis (n = 11), and demyelinating syndrome (n = 11), when compared to normal individuals (n = 12); however, the level of PGD-S in the CSF obtained from patients with brain tumor (n = 11), was reduced by as much as 2-fold when compared to control samples (n = 12) illustrating PGD-S is a potentially useful marker for brain tumor.

Prostaglandin D synthase (PGD synthase) or beta-trace protein is a major constituent of human cerebrospinal fluid (CSF) representing-3% of the total CSF protein. We have recently developed a highly specific immunofluorometric assay for PGD synthase, which enabled us to quantify the presence of PGD synthase in fluids and tissues not associated with the CNS. In this report we provide quantitative data of the presence of PGD synthase in CSF and serum from 302 subjects with various neurological diseases and symptoms. PGD synthase levels in CSF are approximately 35-fold higher than those of serum, with a median concentration of 11,299 micrograms/L. A statistically significant association of PGD synthase concentration in CSF was observed with both patient age and gender. There was no correlation between PGD synthase concentration in serum and patient age or gender. To evaluate the clinical utility of PGD synthase in diagnosing neurological diseases, the distribution pattern of PGD synthase in CSF and serum was examined for each neuropathology of 268 patients whose diagnosis was known. No statistical difference was observed between PGD synthase concentration in the CSF (129 cases) or the serum (94 cases) of multiple sclerosis afflicted subjects in comparison to all other patients studied. The distribution pattern was also not different for PGD synthase levels in CSF of patients with HIV/AIDS related neuropathies, viral meningitis and fibromyalgia. We conclude that PGD synthase measurement presents no clinical utility in diagnosing neurological disorders in adulthood. PGD synthase may have a physiological and/or pathological role in the developing brain and in neurodegenerative diseases.

Glutathione-independent prostaglandin D synthase (PGDS) is an enzyme responsible for biosynthesis of prostaglandin D2 in the CNS and is identical to a major cerebrospinal fluid protein, beta-trace. Although PGDS has been identified recently in rat leptomeninges, little information is available about human meninges or meningiomas. Here, we report PGDS to be expressed consistently in 10 human arachnoid and arachnoid villi and in 21 meningiomas by immunohistochemistry, Western blot, and reverse transcription (RT)-PCR analyses. In arachnoid, PGDS immunoreactivity was seen in arachnoid barrier cells but was negligible in arachnoid trabecula and pia mater. In contrast, in arachnoid villi, PGDS was seen in core arachnoid cells rather than in the cap cell cluster or arachnoid cell layer. Meningioma cells also showed intense immunoreactivity in the perinuclear region, and it was often concentrated within meningocytic whorls and around calcifying psammoma bodies. Immunoelectron microscopic data, when compared with the ultrastructure, showed that PGDS was localized at rough endoplasmatic reticulum of arachnoid and meningioma cells. Western blot showed a 29 kDa immunoreactive band indicating PGDS, but the extent of expression was variable from case to case, which was compatible with immunohistochemical data. RT-PCR revealed PGDS gene expression in all meningiomas studied, regardless of histological subtypes, and also in human arachnoid villi. Because human arachnoid and meningioma cells exclusively express PGDS, it can be considered their specific cell marker. These results show functional differences in various types of meningeal cells attributable to differences in PGDS expression.