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Volume 115 (2000)
- Issue 6 Pages 323-
- Issue 5 Pages 271-
- Issue 4 Pages 185-
- Issue 3 Pages 123-
- Issue 2 Pages 67-
- Issue 1 Pages 5-
Volume 115, Issue 4
Displaying 1-8 of 8 articles from this issue
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Katsuko MORIGIWA, Yutaka FUKUDA, Masayuki YAMASHITA2000 Volume 115 Issue 4 Pages 185-192
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSMicroglia, the resident macrophages in the central nervous system (CNS), are rapidly activated upon trauma or ischemic injury, releasing cytokines and undertaking tissue repair. Recent studies have indicated that CNS immune cells express ionotropic P2X and metabotropic P2Y purinoceptors and undergo functional changes in response to extracellular ATP. Non-stimulated cultured rat retinal microglia expressed metabotropic P2U(P2Y2, P2Y4) and ionotropic P2Z (P2X7) purinoceptors equally, whereas in LPS-stimulated microglia, P2Z and its Ca2+ response became dominant. Upon hypoxia (1% oxygen) activation, the P2U response became dominant, and proliferation was induced possibly via intracellular Ca2+ mobilization and/or capacitative Ca2+ entry. TNF-α and IL-1β were released in both LPS- and hypoxia-activated states, enhanced by the P2Z agonist BzATP and suppressed by the antagonist oATP, indicating P2Z involvement in their release. P2Z activation was simultaneously anti-mitotic and induced apoptosis of microglia. Release of cytokines may be induced via Ca2+ influx and activation of NFAT, NF-κB or p44/42 and p38 MAP kinases, switching off the mitotic signal transduction pathway and triggering the apoptotic cascade at the same time.View full abstractDownload PDF (9157K) -
Masabumi MINAMI, Masamichi SATOH2000 Volume 115 Issue 4 Pages 193-200
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSChemokines constitute a large and still growing family of structurally-related small (8-10 kDa) cytokines that have chemotactic activity for leukocytes. Recently, some receptors for chemokines were reported to be used as a co-receptor by HIV at infection. In addition to their well-established role in inflammatory response and recently-reported role as a co-receptor for HIV, recent data suggest that chemokines and their receptors physiologically and pathologically play crucial roles as the mediators for intercellular communication among the cells intrinsic to and recruited into the brain; i.e., neurons, astrocytes, microglia, endotherial cells and leukocytes. Some chemokines such as SDF-1 and fractalkine are constitutively produced in the brain, implicating that they have an important role in maintenance of CNS homeostasis or determination of the patterning of neurons and or glial cells in developing brain and normal adult brain. Chemokines such as MCP-1, MIP-1α and CINC were shown to be induced by various neuroinflammatory stimuli, suggesting that they are involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, stroke and AIDS dementia syndrome. Chemokines and their receptors are potential targets for therapeutic intervention in neurodegenerative diseases.View full abstractDownload PDF (8321K) -
Hiroshi TAKAGI2000 Volume 115 Issue 4 Pages 201-207
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSHippocampal long-term potentiation (LTP) is one of the best-studied models of learning and memory at the molecular level. In the hippocampal CA1 region, at least three different LTPs were reported: early phase LTP (E-LTP), late phase LTP (L-LTP) and anoxic LTP (A-LTP). E-LTP is induced by the activation of postsynaptically silent synapses. Unlike the E-LTP, L-LTP is dependent on protein synthesis and may be due to an increase in the number of sites of synapse. Unlike the E- and L-LTP, A-LTP is induced by presynaptic K+ channel modulations and is a crucial trigger for neuronal cell death. Interleukin-1β (IL-1β), which is produced under the anoxic conditions, plays an important role in A-LTP induction, and brain-derived neurotrophic factor (BDNF) plays a crucial role in L-LTP induction. IL-1β antagonist and, or BDNF improve the cerebral anoxia-induced inhibition of E-LTP. These results suggested that the new synaptic sites, products of the BDNF induced L-LTP, will play an important role in synaptic plasticity (ex. E-LTP) instead of the synaptic sites of death neurons (induced by A-LTP). The neuronal cytokine system regulates these LTP expressions co-operatively and may play a crucial role to keep the brain system in the steady-state condition.View full abstractDownload PDF (7591K) -
Tetsuro HORI2000 Volume 115 Issue 4 Pages 209-218
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe brain and the immune system communicate with each other by sharing signal molecules and receptor mechanisms. While the brain may modulate the immunity by controlling the endocrine system and the innervations on the lymphoid organs, the immune system signals the brain via multiple channels mainly using cytokines as signal substances and thereby produces a wide spectrum of acute phase responses such as fever, anorexia, activation of hypothalamic-pituitary-adrenocortical axis and modulation of pain. This mini-review focuses on the issues (1) how the immune system transmits information to the brain and (2) how pro-inflammatory cytokines, interleukin-1 in particular, alter the activities of monoamines (catecholamines and serotonin) and some peptides (CRF, αMSH) for the manifestation of acute phase responses.View full abstractDownload PDF (11069K) -
Norimitsu MORIOKA, Atsuko INOUE, Yoshihiro NAKATA2000 Volume 115 Issue 4 Pages 219-227
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSInterleukin-1 (IL-1) β is a proinflammatory cytokine that is produced by a large variety of cells, including macrophages, fibroblasts, mesangial cells and endothelial cells, and is believed to play important roles in the inflammatory responses, including hyperalgesia. Hyperalgesia is characterized by intensified pain with a reduced threshold to somatic stimulation, and it is involved in chronic inflammatory disease. Substance P (SP), an undecapeptide, has been shown to relay noxious signals as a neurotransmitter in primary afferent neurons. Thus it is expected that the change of neuropeptide activities in primary afferent neurons is attributed to inflammatory hyperalgesia by IL-1β. In our recent studies, IL-1β was found to stimulate SP release from cultured dorsal root ganglion cells via the cyclooxygenase system. These studies provide a new insight in the neural-immune intercommunication involved in the pain-regulation system observed in inflammation-induced hyperalgesia.View full abstractDownload PDF (9341K) -
Masako UCHIDA, Hajime NAKAHARA2000 Volume 115 Issue 4 Pages 229-235
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSA number of reports have characterized cetirizine as a potent histamine H1-receptor antagonist possessing inhibitory effects on eosinophil chemotaxis. In clinical pharmacological tests, cetirizine markedly reduced wheal and flare responses induced by histamines. The inhibition was fast onset, potent and long-lasting. A single clinical dose of cetirizine was more potent in inhibiting wheal response than other antihistamines such as terfenadine, loratadine, epinastine and ebastine. Cetirizine also inhibited eosinophil chemotaxis in vitro at a concentration easily attained after a clinical dose of 10 mg. Eosinophil infiltration into a site challenged with allergen in vivo was also inhibited. Potent antihistaminic effects of cetirizine afforded fast and strong relief from histamine-induced symptoms such as sneezing and rhinorrhoea in allergic rhinitis and itchy sensation in idiopathic chronic urticaria. Inhibitory effect of cetirizine on eosinophil chemotaxis may alleviate minimal persistent inflammation due to faintly but repeated intake of allergen. Such anti-inflammatory properties of cetirizine may be beneficial in reducing hypersensitivity to normalize the upper respiratory tract and eosinophil-related skin inflammation.View full abstractDownload PDF (7542K) -
Masao KATOH, Kouki HAYAMIZU2000 Volume 115 Issue 4 Pages 237-243
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTissue-type plasminogen activator (t-PA) is a potent thrombolytic agent that, owing to its strict fibrin specificity, is superior to urokinase and streptekinase. However, due to its extremely short half life (∼5 min), it is necessary to administer this drug by high-dosage infusion, increasing the possibility of systemic bleeding. We therefore considered it clinically desirable to create a thrombolytic agent with a prolonged plasma half life that can be administered by bolus injection. To this end, we created several genetically modified t-PA analogues and screened them for thrombolytic activity and in vivo pharmacokinetics. Of these, Pamiteplase (YM866) showed an improved plasma clearance profile without a reduction in fibrinolytic potency and fibrin specificity. In clinical studies on acute myocardial infarction (AMI), patients were injected with bolus Pamiteplase intravenously at dosages of 0.05, 0.1, or 0.2 mg 'kg-body weight. Angiographical examination of coronary artery showed that high incidence (70-76%) of reperfusion evaluated as TIMI grade II or III was achieved by the injection of 0.1 or 0.2 mg/kg of Pamiteplase. No anti-Pamiteplase antibodies have thus far been detected in the blood of patients. From these results, we conclude that it is of great clinical significance that Pamiteplase can be administered by single bolus injection to AMI patients.View full abstractDownload PDF (7240K) -
Michinao MIZUGAKI2000 Volume 115 Issue 4 Pages 244-250
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSProstaglandins (PGs), thromboxanes (TXs) and leukotrienes (LTs), named eicosanoids, are derived from polyunsaturated fatty acids such as arachidonic and eicosapentaenoic acids. Eicosanoids have various physiological actions, and they are closely associated with various pathological conditions. Quantitative analysis of eicosanoids production, therefore, may be useful as an index of pathological states and medical therapeutic effects. Quantitative methods require high sensitivity and selectivity because of the low concentration, short half-life time of their active compounds and coexistence of structurally similar interfering compouds. From this view point, gas chromatography/mass spectrometry (GC/MS) is one of the useful techniques for determination of eicosanoids. Using GC MS, we have developed determination methods for various eicosanoids and applied them to clinical studies. Although GC/MS is highly sensitive and selective, it often requires tedious and time-consuming derivatization and purification procedures. Liquid chromatography/mass spectrometry (LC/MS), on the other hand, is a simple and rapid determination method. LC/MS is sufficiently applicable to determination of prostanoids, and we previously established a new determination method for LTE4. In the present paper, I describe an advanced determination method for 11-dehydro TXB2, a stable urinary metabolite of TXA2, using liquid chromatography tandem mass spectrometry (LC/MS-MS).View full abstractDownload PDF (6762K)
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