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We have identified for the first time an energy‐time dispersion of precipitating electron flux in a pulsating aurora patch, ranging from 6.7 to 580 keV, through simultaneous in‐situ observations of sub‐relativistic electrons of microburst precipitations and lower‐energy electrons using the Loss through Auroral Microburst Pulsation sounding rocket launched from the Poker Flat Research Range in Alaska. Our observations reveal that precipitating electrons with energies of 180–320 keV were observed first, followed by 250–580 keV electrons 0–30 ms later, and finally, after 500–1,000 ms, 6.7–14.6 keV electrons were observed. The identified energy‐time dispersion is consistent with the theoretical estimation that the relativistic electron microbursts are a high‐energy tail of pulsating aurora electrons, which are caused by chorus waves propagating along the field line. Microbursts, which are bursts of high energy electrons, and pulsating auroras, which periodically blink and caused by the precipitation of low energy electrons, are observed in the Earth's polar ionosphere. The detection time differences of the electrons associated with microbursts and pulsating auroras were detected by a sounding rocket. A possible mechanism for the generation of these precipitations is the interaction of electrons with a particular type of wave, known as “chorus,” which propagates along geomagnetic lines. The observed energy‐time dispersion of the precipitating electrons is quantitatively consistent with theories of electron precipitation based on this interaction. A sounding rocket observed simultaneously precipitating sub‐relativistic electron microbursts and pulsating auroral electrons250–580 keV electron precipitations were detected 0–30 ms after 180–320 keV electron precipitations in a single auroral patchThe energy dispersion of observed electrons is consistent with the theory that they are due to chorus waves propagating to higher latitudes A sounding rocket observed simultaneously precipitating sub‐relativistic electron microbursts and pulsating auroral electrons 250–580 keV electron precipitations were detected 0–30 ms after 180–320 keV electron precipitations in a single auroral patch The energy dispersion of observed electrons is consistent with the theory that they are due to chorus waves propagating to higher latitudes

Myositis is rarely associated with Behcet's disease. We report such a case with characteristic magnetic resonance imaging (MRI) findings, and review the literature. CASE REPORT A 29 year old man [...]

We investigated the electrochemical oxidation of highly oriented pyrolytic graphite (HOPG) in sulphuric acid solution under applying alternative potential pulses to elucidate the oxidation mechanism of carbon support of Pt/C catalyst under dynamic operation of polymer electrolyte fuel cells (PEFCs). After the potential pulse test between 0.6 and 1.0 V for 15 h, the capacitance of HOPG was increased and pits were found on the oxidised surface. With increase in the lower potential limit to 0.8 V, the increasing rate of capacitance was almost equal to that after holding at 1.0 V for 15 h, which suggests that carbon oxidation reaction could be accelerated in PEFCs by continual variation of the cell voltage. After the potential pulse test between 0.2 and 1.0 V, it was clarified that alcohol and carbonyl groups were accumulated on the surface of HOPG. The oxidation mechanism of HOPG under potential pulse condition was described.

In the locality of Colle (Cantabrian Zone, NW Spain), the upper part of the Valporquero Shale Formation (Emsian, La Vid Group) contains an interval of shales and marlstones (barren, greenish-grey shales and fossiliferous, greenish-grey or reddish shales/marlstones) with beds and packages of homogeneous and cross-bedded skeletal limestones. Metre-scale mud mounds and coral biostromes occur encased in the fossiliferous reddish and greenish-grey shale/marlstones, respectively, with the coral biostromes overlying conspicuous skeletal limestone bodies. These rocks were deposited on a carbonate ramp, ranging from above storm wave base for the cross-bedded skeletal limestones to below the storm wave base for the remaining deposits, organic buildups included. The vertical stacking of these facies and the occurrence of the two types of buildups are interpreted to reflect the interplay among several (possibly 4th and 5th) orders of relative sea-level variations, during a 3rd-order highstand. Coral biostromes occur in early 5th-order transgressive system tracts developed within late 4th-order highstand, and are interpreted to have thrived on a stable granular substrate (skeletal limestones) in non-turbid waters, being later aborted by the onset of muddy sedimentation. Biostrome features suggest that they developed under environmental conditions essentially different from those related to the sedimentation of their granular substrate. Mud mounds occur in 5th-order transgressive and early highstand system tracts tied to early 4th-order sea-level rise. Field relationships suggest that mud mounds grew coevally with muddy sedimentation, with high-frequency variations in carbonate vs.terrigenous mud sedimentation influencing their development.In the locality of Colle (Cantabrian Zone, NW Spain), the upper part of the Valporquero Shale Formation (Emsian, La Vid Group) contains an interval of shales and marlstones (barren, greenish-grey shales and fossiliferous, greenish-grey or reddish shales/marlstones) with beds and packages of homogeneous and cross-bedded skeletal limestones. Metre-scale mud mounds and coral biostromes occur encased in the fossiliferous reddish and greenish-grey shale/marlstones, respectively, with the coral biostromes overlying conspicuous skeletal limestone bodies. These rocks were deposited on a carbonate ramp, ranging from above storm wave base for the cross-bedded skeletal limestones to below the storm wave base for the remaining deposits, organic buildups included. The vertical stacking of these facies and the occurrence of the two types of buildups are interpreted to reflect the interplay among several (possibly 4th and 5th) orders of relative sea-level variations, during a 3rd-order highstand. Coral biostromes occur in early 5th-order transgressive system tracts developed within late 4th-order highstand, and are interpreted to have thrived on a stable granular substrate (skeletal limestones) in non-turbid waters, being later aborted by the onset of muddy sedimentation. Biostrome features suggest that they developed under environmental conditions essentially different from those related to the sedimentation of their granular substrate. Mud mounds occur in 5th-order transgressive and early highstand system tracts tied to early 4th-order sea-level rise. Field relationships suggest that mud mounds grew coevally with muddy sedimentation, with high-frequency variations in carbonate vs.terrigenous mud sedimentation influencing their development.

Bacterial translocation/Acute radiation syndrome/Endotoxin/G-CSF/OK-432 Acute radiation induces bacterial translocation from the gut, followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterial translocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterial translocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation.

Abstract: A 68-year-old woman with early rheumatoid arthritis (RA) was admitted to the hospital because of tender and swollen knee joints. We performed a targeted synovial biopsy under arthroscopy to examine the histopathological characteristics 1 month after clinical onset. The synovia showed the typical histopathology of RA. Although the inflammatory changes were predominantly limited to the surface area of the synovia, associated with neovascularization and cell infiltrates composed mainly of T cells, plasma cells, and macrophages, lesions with fibrin deposition, mesenchymoid transformation and/or immature lymphoid follicles were also observed in part, indicating that this case was in the progression phase of RA. What we regularly call "early" might be "too late" even if it is within 1 month of clinical onset.

Background Bleomycin (BLM), a well known anti-cancer drug, often causes acute lung injury and fibrosis by mechanisms that are not well understood. It is suspected that some proteases and active oxygen species generated from inflammatory cells cause the lung injury and subsequent lung fibrosis. It was therefore hypothesised that inhibition of adhesion of inflammatory cells to the endothelium might prevent these developments. Methods BLM (100 mg/kg) was injected into the tail veins of ICR mice to evaluate the induction of E-selectin, an adhesion molecule known to induce neutrophil attachment on endothelial cells. E-selectin mRNA induction was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The myeloperoxidase (MPO) activities in the lung tissues of BLM treated and control mice were compared to evaluate neutrophil infiltration. Pathological changes in the lungs of soluble E-selectin transgenic mice (TG) and their TG negative (non-TG) littermates after BLM treatment were also compared. Serum samples of TG mice and non-TG mice were tested for their ability to block the binding of sialyl Lewis ^x to recombinant E-selectin in vitro. Results E-selectin mRNA was maximally induced at six hours after BLM treatment in the ICR mice. The soluble form of E-selectin which can competitively inhibit the binding of sialylated antigens on inflammatory cells to E- and P-selectins on the endothelium was detected in the serum of TG mice. BLM induced lung fibrosis occurred in non-TG mice but not in TG mice. This result confirms the finding that the serum of TG mice inhibits the binding of sialyl Lewis ^x to E-selectin in vitro. Conclusion E-selectin plays an essential role in BLM induced lung fibrosis through the induction of neutrophil and other inflammatory cell accumulation, and soluble E-selectin may be of use in the prophylactic treatment of lung fibrosis.

The aims of the present work are twofold: first, to confirm the condition for obtaining gold–yellow TiN films without bias application; second, to examine the quantitative relationship between the colorimetric properties and electrical resistivity of these films. For the first aim, TiN films were prepared by DC reactive sputtering under a no-bias condition in the facing targets sputtering (FTS) apparatus, in which discharge is maintained even at a low gas pressure of less than 0.3 Pa. For the second aim, the color of the films was evaluated by means of the chromaticity coordinates, xand y, and the luminance factor Y, which is an index of the brightness based on a CIE standard colorimetric system. Gold–yellow TiN films having low resistivity were obtained, and a study of their electrical and colorimetric properties has provided the following conclusions. (i) The colorimetry of the films is affected by both the mixing ratio and total gas pressure. In particular, the brightness (the luminance factor) Yvaried greatly with a change in total gas pressure. (ii) Even without bias application, a gold-colored TiN film with higher brightness Yhas been obtained by deposition at an appropriate mixing ratio of N2/Ar and also under lower total gas pressure (ρ=0.31 μΩ m and Y=49 for the films deposited at 0.15 Pa). (iii) As the total gas pressure was increased, the column size, the surface roughness and oxygen content showed a clear increase. Thus, the films deposited under an atmosphere higher than 0.15 Pa had higher resistivity and lower brightness. (iv) Based on our results, the quantitative relationship between the resistivity and brightness of the TiN films is shown by the relation of ρ=775Y−2.

Pseudobinary (Ti1−xAlx)N films were synthesized by a new inductively combined rf-plasma assisted planar magnetron sputtering method. From X-ray diffraction measurement, the deposited (Ti1−xAlx)N films were identified as having the B1 structure up to 50mol% Al (x=0.5). In the range from x=0.6 to x=0.7, two phases with the B1 and B4 structures were observed. These results suggest that the critical composition for the phase change from B1 to B4 structure is located between 50mol% Al and 60mol% Al. The critical composition decided experimentally shows a discrepancy with the theoretically predicted value (65mol% Al), which may arise from a somewhat high substrate temperature (450°C) in this study. Oxidation resistance increases with increasing the Al content in the (Ti1−xAlx)N films up to 70mol% Al, irrespective of coexistence of the B1 and B4 phases in the (Ti1−xAlx)N films with x=0.6 and x=0.7, while both the hardness and Young's modulus show a maximum value, respectively. Thus, it is indicated that the existence of the (Ti1−xAlx)N films with the B1 structure is quite effective for improving the oxidation resistance, and the appearance of the B4 phase in the pseudobinary nitride films degrades mechanical properties such as the hardness and Young's modulus.

The effect of oxygen addition to TiN was investigated by producing oxynitride films with the arc ion plating method. These titanium oxynitride films were identified to be NaCl(B1) structure by XRD measurements with θ-20 and glancing angle methods. By increasing the content of oxygen in the deposited films, the preferential orientation of the films changed from the <111direction to the <200direction, and the existence of titanium ions with a higher valence, such as Ti3+and Ti4+as well as divalent titanium, in the deposited films was indicated by the change of Ti2pphotoelectron spectra. From the result on Vickers hardness, it was also indicated that suitable addition of oxygen to TiN is preferable to improve the hardness of the TiN films.

Oral administration of Shosaikoto(1.4g/kg) enhanced phagocytosis of casein-induced murine peritoneal macrophages and nitric oxide (NO) production of thioglycilate broth-induced murine peritoneal macrophages. To clarify the kind of compounds are responsible for this augmentation of macrophage function, ethanol-precipitation was carried out to produce two fractions: one of ethanol-precipitates (EP) and one ethanol-soluble (ES). The EP fraction consisted of polysaccharide and showed enhancement of phagocytosis and NO production comparable to Shosaikoto's. On the other hand, the ES fraction consisted of low molecular compounds and did not affect macrophage function. These results suggest a crude polysaccharide fraction plays an important role in Shosaikoto's macrophage activation.

Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alpha-3, G(o) alpha, Gs alpha, and G beta and myocardial levels of PTX-sensitive G proteins. Rats were treated by subcutaneous infusions, with osmotic minipumps, of 0.9% NaCl, isoprenaline (2.4 mg/kg/day), propranolol (9.9 mg/kg/day), or a combination thereof for 1, 2, 3, 4, or 8 days, and two groups were treated with NaCl or isoprenaline for 13 or 26 days. Additional groups of rats were treated with 0.24 or 0.07 mg/kg/day for 4 days to determine the dose dependency of the effects of isoprenaline. mRNA concentrations were determined by standardized slot blotting with 32P-labeled cDNA or cRNA probes. In isoprenaline-treated rats, mRNA levels of all members of the Gi alpha/G(o) alpha family increased gradually in parallel. The increase in Gi alpha-2, Gi alpha-3, and G(o) alpha mRNA levels reached significance on days 2-3, reached maximal values on days 3-4, and remained stable over the total time of treatment of up to 26 days. Compared with NaCl, maximal increases were 77% (Gi alpha-2; 16.4 versus 9.3 pg/micrograms), 58% (Gi alpha-3; 4.65 versus 2.95 pg/micrograms), and 78% (G(o) alpha; 0.40 versus 0.22 pg/microgram). Gs alpha mRNA levels (about 30 pg/micrograms) and G beta mRNA levels remained unchanged. In isoprenaline-treated rats myocardial levels of PTX-sensitive G proteins increased by maximally 54%, compared with control. The time course differed slightly from the time course of mRNA up-regulation in the first 3 days of treatment and paralleled the increase in mRNA levels from day 4 on. Propranolol had no effect on G alpha mRNA or protein levels when given alone but abolished all effects of isoprenaline when given in combination. Isoprenaline at a dose of 0.24 mg/kg/day still induced an increase in Gi alpha-2 mRNA levels of 24%, without any effects on histopathology of the myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Shosaikoto, which is one of the Japanese and Chinese traditional herbal medicine mixtures, has several immunomodulating activities. Especially, Shosaikoto is a potent polyclonal B cell mitogen in vivoand in vitro. In order to characterize the active substances for mitogenic activity, Shosaikoto was fractionated by means of ethanol precipitation to give two fractions, called ethanol-precipitate (EP) fraction and ethanol-soluble (ES) fraction. The EP fraction consisted mainly of polysaccharides and showed significant mitogenic activity. The ES fraction consisted of low molecular compounds and did not show the activity in vitro. The EP fraction of hot water extracts of Glycyrrhizae Radixand Bupureuri Radixshowed the activities, and the ES fraction of a hot water extract of Glycyrrhizae Radixand all fractions of hot water extract of Scutellariae Radixshowed the cytotoxicity. These results suggested that the crude polysaccharide fractions could play an important role in the mitogenic activity by Shosaikoto.

In human heart failureβ-adrenergic receptors are downregulated which contributes to the reduced responsiveness to positive inotropicβ-agonists in the diseased heart. The present study addressed the question whether the number ofβ-adrenergic receptors in the failing human heart is regulated at the level of the mRNA and whether the absolute steady-state levels of subtype-specific mRNAs mirror the expression of receptor-subtype proteins in human heart. In a collaborative effort, two different and independent methods, performed in two independent laboratories, reverse transcription followed by polymerase chain reaction (RT-PCR) and RNase protection assays, were used to determine the absolute steady-state levels ofβ1- andβ2-adrenergic receptor mRNAs in control (NF) and in failing human hearts. As determined by quantitative RT-PCR theβ1-mRNA was significantly reduced from 0.98 ±0.12 (n=10) to 0.49 ±0.11 pg /μg total RNA in dilated cardiomyopathy (dCMP,n=7) and to 0.40 ±0.11 pg /μg total RNA in ischemic cardiomyopathy (iCMP,n=8). The steady-state levels of mRNA specific forβ2-adrenergic receptors also tended to be decreased but without reaching significance (NF: 0.16 ±0.05, dCMP: 0.11 ±0.03, iCMP: 0.13 ±0.04 pg /μg total RNA). RNase protection assays revealed similar values.β1-mRNA was found to be significantly reduced from 1.22 ±0.22 in NF (n=10) to 0.63 ±0.14 pg /μg total RNA in dCMP (n=5) and to 0.52 ±0.1 pg /μg total RNA in iCMP (n=8). Theβ2-mRNA also tended to be lower in dCMP and in iCMP as compared to NF but again without reaching significance (NF: 0.14 ±0.02, dCMP: 0.099 ±0.02, iCMP 0.107 ±0.02 pg /μg total RNA). This is the first study to demonstrate in parallel by two different methods performed independently in two laboratories that the ratio ofβ1- andβ2-adrenergic receptor densities in the left ventricle of the normal human heart of about 80 /20 is closely related to the absolute steady state concentrations of their specific mRNA. In addition, the magnitude of the decrease in mRNA-levels ofβ1- andβ2-adrenergic receptors in the failing human heart closely correlates with the decrease of the respective receptor proteins. These data suggest that the predominant regulation ofβ-adrenergic receptors occurs at the mRNA level.

We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony- forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.

We studied the localization of T-cells and HLA-DR antigen-bearing (DR+) cells in rheumatoid synovitis by employing an improved two-color immunofluorescent staining (TCIF) technique. With this technique we have successfully identified DR+ activated T-cells in the inflammatory synovium. T-cells expressed HLA-DR antigen when they were in contact with DR+ antigen-presenting cells (APC). In addition, activated T-cells showed characteristic distribution within the synovium: they were found around high endothelial venules, within lymphoid follicles, and in hyperplastic synovial lining, suggesting their involvement in the development of rheumatoid synovial lesions via interaction with synovial DR+ APC lineage cells. These findings may contribute to better understanding of the role of activated T-cells in the histogenesis of rheumatoid synovitis, a typical chronic inflammatory lesion.

The preadipose cell line, PA6, can support long-term hemopoiesis. Frequency of the hemopoietic stem cells capable of sustaining hemopoiesis in cocultures of bone marrow cells and PA6 cells for 6 wk was 1/5.3 x 10(4) bone marrow cells. In the group of dishes into which bone marrow cells had been inoculated at 2.5 x 10(4) cells/dish, 3 of 19 dishes (16%) contained stem cells capable of reconstituting erythropoiesis of WBB6F1-W/Wv mice, indicating that PA6 cells can support the proliferation of primitive hemopoietic stem cells. When the cocultures were treated with an antagonistic anti-c-kit monoclonal antibody, ACK2, only a small number of day 12 spleen colony-forming units survived; and hemopoiesis was severely reduced. However, when the cocultures were continued with antibody-free medium, hemopoiesis dramatically recovered. To examine the proliferative properties of the ACK2-resistant stem cells, we developed a colony assay system by modifying our coculture system. Sequential observations of the development of individual colonies and their disappearance demonstrated that the stem cells having higher proliferative capacity preferentially survive the ACK2 treatment. Furthermore, cells of subclones of the PA6 clone that were incapable of supporting long-term hemopoiesis expressed mRNA for the c-kit ligand. These results suggest that a mechanism(s) other than that involving c-kit receptor and its ligand plays an important role in the survival and proliferation of primitive hemopoietic stem cells.

We have prepared monoclonal hapten-specific mouse IgG2b antibodies depleted of asparagine-linked carbohydrate chains by treating the hybridoma cells with tunicamycin. The carbohydrate-deficient antibodies behaved in an identical manner to the normal antibodies with regard to fine antigen-binding reactivity (a Fab fragment feature) and protein A binding capacity [a feature requiring integrity at the CH2 and CH3 domain-interaction regions in the constant region of the heavy chain (CH)]. However, they lost the ability to activate complement, to bind to Fc receptors on macrophages, and to induce antibody-dependent cellular cytotoxicity. Furthermore, antigen-antibody complexes produced from such carbohydrate-deficient antibodies failed to be eliminated rapidly from the circulation. We conclude that removal of carbohydrate chains from IgG molecules may have a profound and highly select impact on the biological activity to these antibodies.

Fas antigen (Fas) is a cell surface receptor molecule that mediates apoptosis-inducing signals into activated and/or autoreactive peripheral T and B cells by stimulation with Fas ligand or agonistic anti-Fas mAb. The i.p. administration of the hamster anti-mouse Fas mAb RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given another hamster anti-mouse Fas mAb Jo2 rapidly die of fulminant hepatitis with hemorrhage. Here, we report that MRL-gld/gld mice thoroughly recovered and/or were prevented from glomerulonephritis, arthritis, sialadenitis, vasculitis and lymphoadenopathy after receiving a single administration of the agonistic anti-mouse Fas mAb RK-8. The serum levels of autoantibodies were decreased after the administration. All the therapeutic effects of RK-8 persisted for >6 months. These findings suggest that the systemic administration of agonistic anti-Fas mAb without fulminant hepatitis-inducing activity is a useful therapeutic strategy for treating systemic autoimmune disease.

By screening a cDNA library constructed from aortic total RNA derived from Watanabe heritable hyperlipidemic (WHHL) rabbits by differential hybridization, we have obtained a cDNA encoding the kappa light chain of immunoglobulin. Northern blot analysis of total RNA prepared from aortas of WHHL and normal rabbits of various ages revealed that this light-chain mRNA accumulates gradually with age in aortas in WHHL rabbits. Northern blotting and in situ hybridization with an antisense oligonucleotide specific to rabbit immunoglobulin gamma heavy-chain mRNA also detected accumulation of this heavy-chain mRNA in advanced lesions of WHHL rabbit aortas. Moreover, immunohistochemical and electron microscopic analyses demonstrated the presence of plasma cells in the atherosclerotic lesions.

We examined the biological function of a nonstructural regulatory protein, NS1, of human parvovirus B19. Because of the cytotoxic activity of NS1, human hematopoietic cell lines, K562, Raji, and THP-1, were established as transfectants which produce the viral NS1 protein upon induction by using bacterial lactose repressor/operator system. NS1 was significantly produced in the three transfectant cells in an inducer dose- and time-dependent manner. Surprisingly, these three transfectants secreted an inflammatory cytokine, interleukin-6 (IL-6), in response to induction. However, no production of other related cytokines, IL-1beta, IL-8, or tumor necrosis factor alpha, was seen. Moreover, NS1-primed IL-6 induction was transiently demonstrated in primary human endothelial cells. Analysis with luciferase reporter plasmids carrying IL-6 promoter mutant fragments demonstrated that NS1 effect is mediated by a NF-kappaB binding site in the IL-6 promoter region, strongly implying that NS1 functions as a trans-acting transcriptional activator on the IL-6 promoter. Our novel finding, IL-6 induction by NS1, supports the possible relationship between parvovirus B19 infection and polyclonal activation of B cells in rheumatoid arthritis and indicates that NS1 protein may play a significant role in the pathogenesis of some B19-associated diseases by modulating the expression of host cellular genes.

The SL/Ni strain of mice spontaneously develops a necrotizing polyarteritis (NPA) that is histologically quite similar to human polyarteritis nodosa. This NPA most frequently affected parametrial tissues and/or ovaries of females and small arterioles of the major salivary glands. Electron microscopic studies of early arterial lesions revealed massive budding of C-type particles from arterial smooth muscle cells just before or at the onset of arteritis. In addition, binding of mouse IgG and C3 to the plasma membrane of virus-producing smooth muscle cells was shown by immunoelectron microscopy. Antibody-bound muscle cells showed disintegration of their plasma membrane, but degeneration and necrosis of muscle cells were not associated with dense infiltration of neutrophils. SL/Ni mice had natural antibodies that bound specifically to a fibroblast cell line infected with an endogenous ecotropic murine leukemia virus (MuLV) recovered from a SL/Ni mouse. Most of the natural antibodies were cytotoxic in the presence of murine complement. Western blot immunoassays revealed that among 14 SL/Ni female mice tested, all of the 9 mice that were affected by arteritis had anti-gp70 antibodies, while the 3 anti-gp70- mice were not affected. The presence of anti-p30 or anti-p15 (anti-p12) antibodies, which were also detected in some SL/Ni mice, did not correlate with the development of arteritis. These results strongly support the hypothesis that NPA in SL/Ni mice is mediated by the lysis of arterial smooth muscle cells due to the deposition of cytotoxic natural antibodies directed to cell membrane-bound gp70 molecules of an endogenous ecotropic MuLV.

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.

Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and β-adrenoceptor agonists exert their positive inotropic effects by increasing Isivia the common mediator cAMP.

Zusammenfassung In isotonischen Unterstützungskontraktionen wurde der Einfluß von Aldadiene auf die Kontraktilität des isolierten Ventrikelmyokards untersucht. In Konzentrationen zwischen 0,1–100 µg/ml werden nichtsignifikante Zunahmen wesentlicher herzmechanischer Größen beobachtet. In Konzentrationen zwischen 500–2000 µg/ml sind signifikante Zunahmen der Muskelverkürzung, der Verkürzungs-und Erschlaffungsgeschwindigkeit sowie der Geschwindigkeit des isometrischen Spannungsanstieges zwischen 20–60% der Ausgangswerte nachweisbar. Simultan ermittelte Kraft-Geschwindigkeits-Beziehungen zeigen eine Rechtsverlagerung mit Zunahmen der isotonischen Verkürzungsgeschwindigkeit und der maximalen isometrischen Muskelspannung. Das Wirkungsmaximum ist nach etwa 3–4 min erreicht. Eine nach Abklingen der positiv inotropen Aldadienewirkung cinsetzende Reduktion der mechanischen Größen unter die entsprechenden Ausgangswerte läßt sich auf die Erhöhung der extracellulären Kaliumkonzentration zurückführen, die mit der Inkubation von Aldadiene verbunden ist. Unter der entsprechenden Natriumverbindung (Na-Aldadiene) ist diese späte Abnahme der Herzmechanik weitgehend aufgehoben. Die Befunde zeigen, daß Aldactone (Na-Aldadiene, K-Aldadiene) am isolierten Ventrikelmyokard positiv inotrop wirkt.

Superlattice fabrication is demonstrated by using SrCuO2+χand SrCoO2.5. Samples were prepared layer by layer with molecular beam epitaxy. The stacking of the each layer is investigated by x-ray diffraction. We succeeded in changing the B-site cations by every layer. However, the presence of two inequivalent cobalt oxide layers in SrCoO2.5strongly affects the structure of the superlattices.

Cyclooligomerization of the dihalobutadienes (I) or (V), catalyzed by zero‐valent nickel complexes such as Ni(PPh3)4generated by reduction of NiBr2(PPh3)2/PPh3 with Zn, gives the (4)‐ and (6)‐radialenes (II)‐(IV).