Macrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro.

Macrophages play important roles in host defense mechanisms. In the brain, besides microglial cells, meningeal macrophages are present. However, the pathobiological characteristics of meningeal macrophages in rats remain to be investigated. In normal meninx, immunohistochemically, macrophages reacting to CD163 (macrophage scavenger receptor) and major histocompatibility complex (MHC) class II-expressing cells (involving activated macrophages or dendritic cells) were sporadically seen without age-dependent changes. Injection of lipoplysaccharide (LPS) (5 microg; Escherichia coli) into the cerebrum increased the number of anti-CD68-positive macrophages (with greater phagocytic activity) in the meninx, with a peak at 12 h during observation period until 48 h; MHC class II-expressing cells showed a gradual increase in number from 3 h after injection; however, anti-CD163-positive macrophages did not show significant change. In in vitro studies, LPS (0, 0.02, 0.05, 0.5, 5, 50 and 100 microg/ml) was added to KMY-1 or KMY-2 cells, both of which had been established from a rat malignant meningioma. KMY-1 originally reacted to CD163, but LPS addition at 0.5 microg/ml and greater concentrations decreased the anti-CD163-positive cell number and instead increased the anti-CD68-positive cell number. LPS-treated KMY-2 increased the anti-CD163-positive cell number at 0.05 and 0.5 microg/ml. By RT-PCR methods, LPS (0, 0.5, 5, 50, and 100 microg/ml)-treated KMY-1 and KMY-2 showed an increase in mRNA of monocyte chemoattractant protein-1 (MCP-1, a chemokine), and LPS-treated KMY-2 increased mRNA of nerve growth factor (NGF, an immunological effecter). Collectively, under LPS treatment, macrophages with heterogeneous functions appear in rat meninx; rat meninx-forming cells may be involved in pathogenesis of meningeal inflammation by expressing different immunophenotypes and by producing regulatory proinflammatory factors such as MCP-1 and NGF.

Differential expression of peroxisome proliferator-activated receptor in histologically different human gastric cancer tissues.

Gastric cancer cell lines express peroxisome proliferator-activated receptor gamma (PPARgamma), and treatment with PPARgamma ligands suppresses growth of subgroup of these cell lines. However, expression and subcellular distribution of PPARgamma in human gastric cancer tissues is still unknown. Therefore, expression and subcellular localization of PPARgamma were examined among different histological types of gastric cancer tissues. Immunohistochemical staining for PPARgamma was performed using biopsy specimens of human gastric cancer of various histological types, gastric adenomas, and intestinal metaplasia. All samples of intestinal metaplasia and most samples of gastric tumors, except for signet ring cell carcinoma, expressed PPARgamma in the epithelial cells. Most samples of signet ring cell cancer lacked PPARgamma expression. All samples of intestinal metaplasia expressed PPARgamma only in the cytosol. For adenoma, 90% was positive for PPARgamma in cytosol, and 40% was positive in nuclei, for well-differentiated adenocarcinoma, 80% was positive in cytosol, and 20% was positive in nuclei. For moderately differentiated adenocarcinomas, 70% was positive for cytosol, and 80% was positive for nuclei; for poorly differentiated adenocarcinoma, 30% was positive in cytosol, and 70% was positive in nuclei. The frequency of samples with positive cytosolic staining decreased as the differentiation stage turned from intestinal metaplasia to adenoma, well-, moderately-, and poorly-differentiated cancers. Simultaneously, there was a tendency toward an increased frequency of samples with positive nuclear PPARgamma staining as the differentiation stage transformed from intestinal metaplasia to poorly-differentiated cancer. There was a striking difference in subcellular localization according to the differentiation levels of gastric dysplastic cells. The findings also supported an intestinal metaplasia-adenoma-well-differentiated gastric cancer sequence, and signet ring cell cancer was suggested to be of a different lineage from other types of gastric cancers.

Spatio-temporal patterns of pre- and postsynaptic inhibition induced by primary afferent activation in the trigeminal sensory nucleus in cats.

Spatio-temporal patterns of pre- and postsynaptic inhibition were studied in the trigeminal spinal nucleus oralis of cats by means of systematic electrical stimulation of the facial skin. Stimulation of the facial skin induced an EPSP-IPSP sequence in trigemino-thalamic relay cells (TRC). The IPSP was depressed by picrotoxin but was resistant to strychnine. The largest IPSP was evoked from the center of the excitatory area, where stimulation induced the largest EPSP and spike potentials at the lowest intensity in the same TRC. The amplitude of the IPSP decreased with increasing distance from the center in parallel with that of the EPSP. In the great majority of trigeminal primary afferent fibers, the largest primary afferent depolarization (PAD) was not evoked from the center of the excitatory area, where the threshold for spike generation was lowest, but from the adjacent points on the face. Spike activities in a trigeminal primary afferent fiber did not evoke any detectable PAD in itself. The duration of the PAD was definitely longer than the IPSP in TRC. However, the temporal distribution of the peak of PADs was very similar to that of the EPSP in TRC. Inhibition was evoked in glutamate-induced spike discharges of TRC by stimulation of the points on the face, which were located close to the center of the excitatory area of the TRC. However, the afferent inhibition of both spontaneous and peripherally induced spike discharges of TRC outlasted the postsynaptic inhibition. Thus, the late phase of the afferent inhibition is most probably due to presynaptic inhibition. Presynaptic inhibition, together with postsynaptic inhibition, would be involved also in the early phase of afferent inhibition through its mutual inhibitory organization.

Analysis of the circuitry responsible for primary afferent depolarization in the trigeminal spinal nucleus caudalis of cats.

Depth analysis was performed on the field potential evoked by stimulation of the infraorbital nerve in the trigeminal spinal nucleus caudalis and the subjacent lateral reticular formation of cats. It was shown by dye marking of the recording positions that each subnucleus of the nucleus caudalis (subnucleus marginalis, gelatinosus and magnocellularis) and the reticular formation could be differentiated from one another by the characteristics of the peripherally evoked field potentials. Responses of neurons were extracellularly recorded in the subnuclei gelatinosus and magnocellularis of the nucleus caudalis and in the reticular formation to stimulation of the trigeminal sensory branches (the frontal, infraorbital and lingual nerves), the nucleus ventralis posteromedialis of the thalamus and the cerebral cortex. The properties of the neurons were studied in relation to their thresholds, latencies, receptive fields (sensory branches effective for spike generation) and frequency-following capacities. These responses were then compared with properties of the PAD induced in the fibers terminating in the nucleus caudalis by similar peripheral and central stimulation. It was found that the neurons in the subnucleus magnocellularis were the most likely candidates for the interneurons mediating the peripherally evoked disynaptic PAD in the trigeminal nerve fibers terminating in the nucleus caudalis.