Interleukin-6 (IL-6) is known as a proinflammatory cytokine involved in immune response, inflammation, and hematopoiesis. Inhibitory effects of anti-inflammatory drugs on IL-6 bioactivity using IL-6-dependent hybridoma have been evaluated. Three out of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) showed IC₅₀ values of less than 100 μM, which were in the order of oxyphenylbutazone hydrate (IC₅₀=7.5 μM)>meclofenamic acid sodium salt (31.9 μM)>sulindac (74.9 μM). Steroidal anti-inflammatory drugs (SAIDs) exhibited significant inhibitory effects at 100 μM on the IL-6 bioactivity, and their inhibitory potencies were in the order of budesonide (IC₅₀=2.2 μM)>hydrocortisone 21-hemisuccinate (6.7 μM), prednisolone (7.5 μM), betamethasone (10.9 μM)>dexamethasone (18.9 μM) and triamcinolone acetonide (24.1 μM). The results would provide an additional mechanism by which anti-inflammatory drugs display their anti-inflammatory and immunosuppressive effects at higher concentrations.

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Arachnoid granulation is a protrusion of the arachnoid membrane into the cranial sinus, and is thought to play an essential role in the cerebrospinal fluid (CSF) absorption. Because the cells covering the apex region of the arachnoid granulation have different morphological features compared to the ordinary endothelial cells lining of the cranial sinus lumen, it has been expected these covering endothelial cells perform some specific function in the CSF absorption mechanism. However, little is known about functional differences between the covering endothelium of the arachnoid granulation and the ordinary sinus endothelium. In the present study, the characteristics of the covering cells located at the apex of arachnoid granulations of human, monkey and dog brain were examined by histochemical and immunohistochemical methods. The endothelial cells lining the cranial sinus lumen generally expressed such proteins as von Willebrand factor (vWF), CD31 and glycoproteins containing GS-1 or LE-1 lectin reacting sugar residue which are endothelial cell markers. However, the endothelial cells specifically located at the apex of arachnoid granulations failed to show vWF immunoreactivity, whereas the other endothelial markers were positive in each species we examined. Double staining of vWF antibody with other markers has clearly demonstrated that the endothelial cells on the apex region of arachnoid granulations exhibit no expression of vWF whereas cells lining the lateral region of arachnoid granulations and the luminal surface of ordinary cranial sinuses showed co-localization of these markers. The structural and histochemical differences between endothelial cells located at the apex region of arachnoid granulations and those of the sinus wall may reflect functional differences.

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The arachnoid granulations or villi are not always present in lower mammals and even in human late prenatal fetus. They grow in number and size with advanced age, and thus it seems appropriate to regard them as safety-valves for the cerebrospinal fluid (CSF) to be prevented from its hypertension accompanied by the age and by the increasing volume of the brain. Using 2 macaque monkeys and 12 rats, and by means of scanning and transmission elecron microscopies, tracer experiments with horseradish peroxidase, elastic staining of thin sections, and freeze-substitution of rapidly frozen brains, evidences are presented to show that the drainage sites of the CSF in the brain are the sites being devoid of the bloodbrain barrier, that is, the subfornical organ at the root of the choroid plexus of lateral ventricle, the pineal body at the root of the choroid plexus of third ventricle, and the area postrema at the root of the choroid plexus of fourth ventricle, and also the hypophysis and its vicinity, and the choroid plexus itself.

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The stable isotopic composition of carbon in graphites from various localities is in general informative for the genesis of graphite. A differentiation between the origin from carbonates, igneous or biogenic carbon can be established by stable carbon isotope determinations in many cases. On the other hand, it is indispensable to know the influence of various events causing shift of the isotopic ratio. After discussion of origin and stable isotopic composition of graphites, five typical case studies are presented.

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Cranial meninges of humans were studied by electron microscopy after fixation in situ and histochemical demonstration of nicotinamide-adenine dinucleotide diaphorase within mitochondria.
There was an intimate fusion between the innermost portion of the dura mater (dural border cells) and the outermost portion of the arachnoid (arachnoid barrier layer). Cranial meninges did not contain a true subdural space, when specimens were well prepared with spatial relationships preserved. If cleavage had occurred during preparation, the subdural space was artificially formed by the separation of dural border cells, because the latter showed a paucity of intercellular contacts and weak collagenous reinforcements.
The arachnoid barrier layer was a squamous layer of elongated cells with numerous tonofilaments, desmosomes and tight junctions. There was a lining of junctional devices between the innermost two cell layers. There was a number of extracellular lacunae, being separated by interdigitations and containing collagen fibrils, elastins, granular material and matrix vesicles with or without psammoma bodies. The mitochondrial enzymes of this layer showed negative activity in intact specimens, but a positive one in cleaved dural border cells and arachnoid trabecular cells. An incomplete basement membrane covered the innermost aspect of this layer.
The arachnoid trabecular cells generally had electron-lucent cytoplasm with a few tonofilaments. The cells beneath the arachnoid barrier layer had oval nuclei and wide cytoplasm containing numerous mitochondria. This layer was anchored by flattened or button-shaped pedicles, otherwise these cells formed an epithelial cluster. The cells lying within the subarachnoid space had elongated nuclei and cytoplasmic projections. The arachnoid trabeculae consisted of both a network of arachnoid trabecular cells and interwoven collagen fibrils. Alternating with these cells were numerous resting macrophages.

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Plasmodium berghei NK65を, BALB/cならびにBALB/c nu/nuマウスに感染させて寿命を比較すると, 胸腺のないnu/nuマウスの方が長生きした。しかしながらPlasmodium berghei 17Xの感染実験では, 寿命に差はなかった。寿命の差は, 血中のparasite数によるのではなくて, hostのIL-2の産生能ならびにキラーT細胞の誘導能の差によることが判明した。
さらに寿命は, 抗マラリア抗体価とも血中の免疫複合体値とも相関しなかった。感染後いずれのマウスも, T細胞機能は一般に低下したが, NK細胞活性は上昇した。

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Neurovirulence of in vivo-passed wild measles virus and that of the cell-associated SSPE virus were compared by intracerebral inoculation into monkeys. The wild measles virus was found to lack neurovirulence without producing neurological signs or significant histological changes in the brains, whereas the virus was confirmed to preserve the properties characteristic of the wild virus. In contrast, inoculation of the SSPE virus induced rapid onset of neurological signs with mild but definite histological changes including degeneration of nerve cells. The fact that SSPE virus exhibited neurovirulence in monkeys indicated importance of the current assay system for neurovirulence of measles vaccine by intracerebral inoculation into monkeys.

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Arachnid granulations are not always present in lower mammals and primate newborns. In order to visualize the route for the cerebrospinal fluid (CSF) to drain into the venous system, horseradish peroxidase (HRP) was injected into the lateral ventricle or cisterna cerebellomedullaris of the mouse and rat.
From 30 to 60min after the commencing of a slow infusion for 15-30min of 0.05-0.1ml solution containing 10-20mg HRP, the mouse, whose skull had been exposed, was dropped into cold acetone at dry ice temperature; other animals were fixed by perfusion with aldehyde solution. The frozen head was dissected in a cryostat kept at -18°C to remove the skull, but leave the dura mater and the falx cerebri. The brain with meninges was cut into 30-45μm sagittal sections in the cryostat, and processed for peroxidase reaction. The perfusion-fixed brains were used for scanning electron microscopy and for electron microscope observation of the tracer.
The reaction product was found within fenestrated venous capillaries of the choroid plexus. The route for the HRP in the CSF to drain into the sinus rectus via the vena chorioidea and vena cerebri magna was directly visualized in the mouse.

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The antibody response to the recombinant protein, R32tet32, which contained the repetitive sequence (NANP)_n of Plasmodium falciparum CSP was determined in C57BL/6 mice during the course of nonlethal infection with Plasmodium yoelii 17X. Marked suppression of the IgG antibody response to R32tet32 occurred when mice were immunized at peak parasitemia (on day 16). In vitro antibody responses of spleen cells from acutely infected mice to R32tet32 were similarly suppressed. Stimulation of normal spleen cells cultured for 5 days with 100 ng/ml of R32tet32 gave an optimal IgG antibody response, but spleen cells from infected mice obtained at peak parasitemia failed to respond to a broad range of antigen concentrations. Cocultivation studies employing enriched lymphocyte populations from infected and uninfected C57BL/6 mice indicated that both T and B cells from infected mice were defective in their response to R32tet32. The response to the repetitive region was restored by the addition of recombinant mouse interleukin-2 (IL-2) at a dose of 50 U/ml to cultures of spleen cells from infected mice.

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Carbon and oxygen isotopic compositions of graphite and coexisting carbonate were determined for the regional metamorphic areas of Kurobegawa, Toyama Pref. and Kamioka, Gifu Pref. as well as the contact metamorphic aureoles of Kasuga, Gifu Pref., Ikeno, Aichi Pref., Ikenojizo, Kyoto Pref., and Ugakei, Mie Pref. in central Japan. In graphite bearing crystalline limestones, carbonate-graphite pairs are considered to have been in carbon isotopic equilibrium during various metamorphisms. In the contact metamorphic aureoles of the Kasuga area, the carbon isotopic geothermometry gives a temperature similar to that estimated from the mineral assemblages. There is a local variation of carbon isotopic temperatures from 470 to 740°C within one hundred meters from the igneous contact in the Kasuga area. This would be attributed to the heterogeneity of the metamorphic temperatures near the igneous contact. On the other hand, in the regional metamorphic terrane of the Kurobegawa area, the carbon isotopic fractionation between graphite and coexisting carbonate is almost constant for gray limestone. This would show that the metamorphic temperature is constant during metamorphism within an area of at least a few square kilometers. In the polymetamorphic terrane of a part of the Kurobegawa area, the carbon isotopic temperature represents the maximum temperature of the late stage of a progressive metamorphism. In the Kamioka area, the isotopic geothermometry gives a temperature higher than 810°C, which is far above the metamorphic temperature expected from mineral assemblages. This high grade metamorphism would have occurred at an early stage of the Hida polymetamorphism.

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The range of Eurasian Coot Fulica atra in Japan has expanded gradually since the 1980s, and the numbers of coot wintering at several sites in Japan have increased. In this paper, we summarize the trends in coot numbers wintering in Japan and mainland East Asia. In Japan, wintering numbers of coot have increased in most regions, except in northern Chiba Prefecture. The increase began in the late 1990s or around 2000 at several water bodies in the Kanto, Chubu, Kinki and Chugoku regions of Honshu. It also increased in the mid-2000s at several water bodies in the Tohoku, Kanto, Chubu, and Kinki regions of Honshu, and perhaps also on the island of Kyushu. In China, huge numbers of coot overwintered at several sites in the lower Yangtze floodplain (e.g., Poyang Lake, Dongting Lake) and along the Jiangsu Coast near the Yangtze River mouth (e.g., Yancheng Nature Reserve, Hongze Hu Lake) during the 1990s. However, during the 2000s, no sites in China held more than 10,000 wintering coot. The number of coot wintering in coastal south China has also decreased. In South Korea, the number of wintering coot has increased especially since the mid-2000s. The increases in the populations of wintering coot in central and western Japan and in South Korea seem to be mainly as a result of changes in coot populations and/or habitats outside Japan. We suggest two possible causes: the breeding population of coot on the East Asian mainland may have increased, or some coot that used to overwinter in China may have begun wintering in Japan and South Korea.

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小型ピロプラズマ病の新しい検出法としてTheileria sergentiメロゾイトの組み換えDNAプローブを作出し, ハイブリダイゼーションによる赤内型メロゾイトの検出を試みた. T. sergentiの遺伝子ライブラリーはpUC-18ベクターを用いて作出し, コロニーハイブリダイゼーションとサザンハイブリダイゼーションでスクリーニングしT. sergentiに特異的なクローン8個を得た. そのうち2個のクローンのインサートを精製し³²P-dCTPあるいはビオチン-11-dUTPで標識しプローブとして用いた. ドット・ブロットハイブリダイゼーションで, 精製したT. sergentiのDNAを用いた場合, ³²P標識プローブは15pg (約1,200個のメロゾイトに相当), ビオチン標識プローブでは125pg (約10,000個のメロゾイトに相当) を検出できた. T. sergenti感染赤血球を用いた場合のメロゾイトの検出限界は, ³²P標識プローブで8,000個, ビオチン標識プローブで16,000個であった.

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The influence of cyclophosphamide (Cy) on the establishment and duration of the intestinal resistance against enteric infection with a mouse adenovirus, strain K87, was examined in inbred mice, strain DK1. When Cy (40mg/kg/day) was administered to mice for 17 days from the time of virus challenge, a clear prolongation of viral growth and a delayed appearance of neutralizing (NT) antibody in the intestinal wall as well as in the serum were observed. When Cy (40mg/kg/day, for 14 days) was administered after cessation of viral growth (4 to 6 weeks after virus challenge) and part of the mice were rechallenged with the virus, titers of NT antibody and immunoglobulins became significantly lower than those in control mice not treated with Cy, and regrowth of the virus was observed in eight out of twenty-five Cy-treated mice, regardless of the presence or absence of rechallenge. In this experiment, antibody titers in the intestinal contents of eight virus-positive mice were significantly lower than those of the remaining seventeen virus-negative mice. The time when the decrease of intestinal NT antibody was maximum coincided with the time of the maximal frequency of viral regrowth. It was discussed that these facts might present an evidence to support the idea that the intestinal resistance was acquired through local NT antibody belonging to IgA in the intestinal tract.

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10歳の気管支喘息患者の発作重積状態において著明な血小板増多 (80.2万/mm³) を認めた. 血小板数は発作の改善と共に減少した. トロンボエラストグラフでは凝固促進, 血小板増多のパターンであった. しかし, ADPを用いた血小板凝集能の検討では正常であった. そこで, 気管支喘息患者について, 発作時, 非発作時, 及び健康児の血小板数を検討したところ, それぞれ40.5±5.0万/mm³, 33.5±8.0万/mm³, 28.4±4.9万/mm³であり, 発作時に有意に高値を示した. 血小板増多は多くの喘息患者に認められ, その病態に何等かの関連をもつことが示唆された.

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To determine the functional significance of endoplasmic reticulum chaperones in hematopoietic cells, we analyzed the expression and post-translational modification of BiP/GRP78 and GRP94 as well as the cytoplasmic chaperones HSP70 and HSC70 during the differentiation of a mouse myeloid leukemia cell line, M1. The amounts of BiP/GRP78 and GRP94increased several-fold when M1 cells were induced to differentiate into macrophage-like cells by treatment with interleukin-6 (IL-6). Synthesis began to increase at 4 hr after IL-6 treatment. The phosphorylated form of BiP/GRP78 increased during the later stages of differentiation. These data suggested that the chaperone activity of BiP/GRP78 and GRP94 may be needed for differentiated macrophage-like cells or for the differentiation event itself, and that functionally different BiP/GRP78 accumulate during the differentiation of M1 cells.

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The induction of macrophage colony-stimulating factor (M-CSF) in monkey plasma following administration of FK 565 was observed within 2 h of injection peaked at 4 h, and remained high after 24 h. Interleukin-6 (IL-6) and M-CSF levels increased in monkeys treated with FK565, even at doses as low as 0.01 mg/kg. Granulocyte CSF (G-CSF) levels increased slightly following a dose of 1 mg/kg, but granulocyte macrophage CSF (GM-CSF) was not detected at any doses of FK565 studied. To examine the thrombopoietic activity of FK565 in vivo, single doses of drug (0.01, 0.1 or 1.0 mg/kg) were administered i.v. to cynomolgus monkeys or normal mice on day 0. The promotes platelet (PLT) count after FK565 injection decreased transiently on days 1 and 2, and then increased in a dose-dependent manner on day 5 and was still high on day 14. The experiment using anti-PLT antibody showed that the increased PLT count was not simply due to a rebound phenomenon after the transient decrease in PLT. The effect of i.v. FK565 was studied in mice myelosuppressed with a single dose of mitomycin C (MMC) (5.6 mg/kg). The fall in PLT count was suppressed on day 7 by 0.1 and 1.0 mg/kg FK565. Although intact cells or tissues are necessary for an increase in PLT following FK565 treatment, FK565 suppressed the impaired hematopoietic function seen after chemotherapy. FK565 is proposed as a drug to restore reduced neutrophil and platelet counts found in AIDS or cancer therapy.

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