Search

It has been reported that levels of neopterin are elevated in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, and that neopterin enhances cell death induced by H2O2 in mouse monocytes and macrophages. In the present study, we examined the relationship between the disappearance of inflammatory cells in the CSF of patients with bacterial meningitis and the effects of neopterin on cell death. We hypothesized that the rapid cell death of mononuclear leukocytes (MNs) and survival of polymorphonuclear leukocytes (PMNs) brought about by high levels of tumor necrosis factor-a TNF-a may be related to the pathophysiology of PMN predominance in the CSF of patients with bacterial meningitis. Peripheral blood leukocytes separated into two fractions (MNs and PMNs) were suspended in CSF samples from patients with bacterial meningitis, and the cell death rate was determined with MTT assay. The higher the CSF TNF-a level, the higher the MN mortality rate tended to be. In contrast, PMNs were able to survive high levels of TNF-a in the CSF. For control purposes, MNs and PMNs were also suspended in various conditioned media. The same association between TNF-a levels and MN mortality was observed, as was the survival of PMNs. The addition of neopterin enhanced the cytocidal effect of TNF. The present study suggests that neopterin is related to PMN predominance in the CSF of patients with bacterial meningitis via the effect of TNF-a on cell death.

'Gain' of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers (1-13) and is associated with poor prognosis (7,10,14). The well-characterized myelocytomatosis [...]

Cerebrospinal fluid (CSF) neopterin been previously reported in various diseases. In this study CSF neopterin, biopterin, and nitrite/nitrate (NOx) Contents were measured and the correlation between them in child patients with various kinds of neurological diseases were investigated. Changes in the CSF neopterin levels in patients with bacterial meningitis were similar to those previously reported for those with bacterial meningitis; on the 2th hospital day they were significantly higher than on admission, and on the 6th hospital day they were tapered. The CSF biopterin levels and CSF NOx content in patients with bacterial meningitis on admission were significantly higher than those with other categories and were decreased gradually. Although patients with high levels of CSF neopterin tended to have high CSF biopterin levels in any categories, there was no significant correlation between CSF neopterin and biopterin levels. The CSF biopterin and NOx levels in patients with convulsions were higher than those with aseptic meningitis. Since the neuro-protective or anticonvulsant role for NO was previously reported, high CSF biopterin and NOx levels in patients having epilepsy or febrile convulsions may be regarded as one of the endogenous mechanisms for recovery from an overexcitatory brain in patients with convulsive diseases.

CSF and serum levels of neopterin and several kinds of CSF cytokines were measured in child patients with non-pleocytotic CSF. The CSF neopterin levels with febrile convulsions (FCs) were 27.4±33.0 nmol/1 and the CSF neopterinlserum neopterin ratio (C/S ratio) with FCs was 2.07±2.06. The longer the FCs patients' convulsions lasted, the higher their CSF neopterin levels tended to be come. The CSF neopterin levels with FCs were significantly higher than in those with pyrexia without convulsions (6.5±2.5 nmol/L) or convulsions without pyrexia, including epilepsy (4.9±2.9 nmol/L). The C/S ratio was also higher in patients with FCs than in those with pyrexia without convulsions (0.31±0.17) or convulsions without pyrexia (0.82±0.50).In addition, there was a tendency for CSF IFN-γ levels to be higher in patients with FCs than in those with pyrexia without convulsions or convulsions without pyrexia. However, TNF-α and IL-1α were under measurable levels in cases of non-pi eocytotic CSF. The CSF neopterin levels in patients with exanthem subitum with FCs were higher than in those without FCs. It has been reported that there is a possibility of neopterin production by microglial cells. Our finding that CSF neopterin levels were elevated in patients with FCs, whose CSF had no pleocytosis, are consistent with the possibility of neopterin production by microglia. Our results further suggest that immune activation of microgrial cells is one of the mechanisms involved in the onset of FCs.

Cerebrospinal fluid (CSF) neopterin levels were measured in child patients with neurological diseases. CSF neopterin levels on admission were significantly higher in patients with bacterial meningitis than in those with aseptic meningitis or in those with non-pleocytotic CSF. CSF neopterin levels in patients with bacterial meningitis one day after admission were higher than those on admission and were markedly elevated with high levels of CSF IFN-γ and TNF-α. CSF neopterin levels in patients with bacterial meningitis one day after admission were related to the period of positive serum C-reactive protein. In patients with non-pleocytotic CSF, CSF neopterin and CSF IFN-y levels were higher in patients with febrile convulsion (FC) than in those with pyrexia only or convulsion (including epilepsy) only. These results suggest that elevation of CSF neopterin in bacterial meningitis results from monocytes/ macrophages costimulated with IFN-γ and TNF-α and that immunological activation in the central nervous system is one of the mechanisms of onset with FC.

The superficial zone (SZ) of articular cartilage is critical in maintaining tissue function and homeostasis and represents the site of the earliest changes in osteoarthritis. Mechanisms that regulate the unique phenotype of SZ chondrocytes and maintain SZ integrity are unknown. We recently demonstrated that expression of the chromatin protein high mobility group box (HMGB) protein 2 is restricted to the SZ in articular cartilage suggesting a transcriptional regulation involving HMGB2 in SZ. Here, we show that an interaction between HMGB2 and the Wnt/[beta]-catenin pathway regulates the maintenance of the SZ. We found that the Wnt/[beta]-catenin pathway is active specifically in the SZ in normal mouse knee joints and colocalizes with HMGB2. Both Wnt signaling and HMGB2 expression decrease with aging in mouse joints. Our molecular studies show that HMGB2 enhances the binding of Lef-1 to its target sequence and potentiates transcriptional activation of the Lef-1-[beta]-catenin complex. The HMG domain within HMGB2 is crucial for interaction with Lef-1, suggesting that both HMGB2 and HMGB1 may be involved in this function. Furthermore, conditional deletion of [beta]-catenin in cultured mouse chondrocytes induced apoptosis. These findings define a pathway where protein interactions of HMGB2 and Lef-1 enhance Wnt signaling and promote SZ chondrocyte survival. Loss of the HMGB2-Wnt signaling interaction is a new mechanism in aging-related cartilage pathology. aging | osteoarthritis | apoptosis | superficial zone