Showing papers by "Kumamoto University published in 1990"

The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene

Abstract: Mice homozygous for the recessive mutation osteopetrosis (op) on chromosome 3 have a restricted capacity for bone remodelling, and are severely deficient in mature macrophages and osteoclasts. Both cell populations originate from a common haemopoietic progenitor. As op/op mice are not cured by transplants of normal bone marrow cells, the defects in op/op mice may be associated with an abnormal haematopoietic microenvironment rather than with an intrinsic defect in haematopoietic progenitors. To investigate the molecular and biochemical basis of the defects caused by the op mutation, we established primary fibroblast cell lines from op/op mice and tested the ability of these cell lines to support the proliferation of macrophage progenitors. We show that op/op fibroblasts are defective in production of functional macrophage colony-stimulating factor (M-CSF), although its messenger RNA (Csfm mRNA) is present at normal levels. This defect in M-CSF production and the recent mapping of the Csfm structural gene near op on chromosome 3 suggest that op is a mutation within the Csfm gene itself. We have sequenced Csfm complementary DNA prepared from op/op fibroblasts and found a single base pair insertion in the coding region of the Csfm gene that generates a stop codon 21 base pairs downstream. Thus, the op mutation is within the Csfm coding region and we conclude that the pathological changes in this mutant result from the absence of M-CSF.

Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms

Abstract: Two cell lines have been established from insulinomas obtained by targeted expression of the simian virus 40 T antigen gene in transgenic mice. These cell lines, designated MIN6 and MIN7, produce insulin and T antigen and have morphological characteristics of pancreatic beta cells. MIN6 cells exhibit glucose-inducible insulin secretion comparable with cultured normal mouse islet cells, whereas MIN7 cells do not. Both cell lines produce liver-type glucose transporter (GT) mRNA at high level. Brain-type GT mRNA is also present at considerable level in MIN7 cells, but is barely detectable in MIN6 cells, suggesting that exclusive expression of the liver-type GT is related to glucose-inducible insulin secretion. MIN6 cells do not express either major histocompatibility (MHC) class I or class II antigens on the cell surface. However, treatment with interferon-gamma induces high levels of MHC class I antigens, and a combination of interferon-gamma and tumor necrosis factor-alpha induces a MHC class II antigen on the cell surface. These results emphasize that the MIN6 cell line retains physiological characteristics of normal beta cells. The MIN6 cell line will be especially useful to analyze the molecular mechanisms by which beta cells regulate insulin secretion in response to extracellular glucose concentrations. We discuss a possible role of GT isoforms in glucose sensing by beta cells.

Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Possible role of early coronary atherosclerosis.

Abstract: We examined the response of left coronary arteries to intracoronary injection of acetylcholine (ACh) 50 micrograms in 74 patients by measuring the diameter changes with a videodensitometric analysis system. Patients with angiographically normal coronary arteries were subdivided into a younger group of 26 patients (age, 9-29 years) and an older group of 23 patients (age, 31-68 years). In the younger group, the diameter at the distal segment of the left anterior descending artery (LAD) and at the proximal, middle, and distal segments of the left circumflex artery (LCx) increased significantly (16.7 +/- 19.3%, p less than 0.01, for LAD and 8.0 +/- 18.8%, p less than 0.05; 11.0 +/- 16.1%, p less than 0.01; and 19.8 +/- 17.5%, p less than 0.01, for LCx segments, respectively) in response to ACh. In the older group, on the other hand, the diameter at the proximal and middle segments of LAD and LCx decreased significantly (-20.8 +/- 16.9%, p less than 0.01; and -17.9 +/- 28.4%, p less than 0.01, for LAD segments and -14.6 +/- 17.4%, p less than 0.01; and -11.3 +/- 21.4%, p less than 0.05, for LCx segments, respectively). The dilator response to ACh in the younger group was significantly greater in the distal segment than in the proximal segment in both LAD and LCx (p less than 0.01 for LAD and p less than 0.05 for LCx). The constrictor response to ACh in the older group was significantly greater in the proximal than the distal segment in both LAD and LCx (p less than 0.05 for LAD and LCx, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute lung injury from mechanical ventilation at moderately high airway pressures.

Abstract: We have explored adverse pulmonary effects of mechanical ventilation at a peak inspiratory pressure of 30 cmH2O in paralyzed and anesthetized healthy sheep. A control group of eight sheep (group A) was mechanically ventilated with 40% oxygen at a tidal volume of 10 ml/kg, a frequency of 15 breaths/min, a peak inspiratory pressure less than 18 cmH2O, and a positive end-expiratory pressure of 3-5 cmH2O. During the ensuing 48 h, there were no measurable deleterious changes in lung function or arterial blood gases. Another 19 sheep were ventilated with 40% oxygen at a peak inspiratory pressure of 30 cmH2O under a different set of conditions and were randomly assigned to two groups. In group B, the respiratory rate was kept near 4 breaths/min to keep arterial PCO2 in the normal range; in group C, the frequency was kept near 15 breaths/min by including a variable dead space in the ventilator circuit to keep arterial PCO2 near baseline values. There was a progressive deterioration in total static lung compliance, functional residual capacity, and arterial blood gases. After some hours, there were abnormal chest roentgenographic changes. At time of death we found severe pulmonary atelectasis, increased wet lung weight, and an increase in the minimum surface tension of saline lung lavage fluid.

Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice.

Abstract: We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.

Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.

Abstract: Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.

Molecular cloning and expression of the murine interleukin-5 receptor.

Abstract: Murine interleukin-5 (IL-5) is known to play an essential role in Ig production of B cells and proliferation and differentiation of eosinophils. Here, we have isolated cDNA clones encoding a murine IL-5 receptor by expression screening of a library prepared from a murine IL-5 dependent early B cell line. A cDNA library was expressed in COS7 cells and screened by panning with the use of anti-IL-5 receptor monoclonal antibodies. The deduced amino acid sequence analysis demonstrates that the receptor is a glycoprotein of 415 amino acids (Mr 45,284), including an N-terminal hydrophobic region (17 amino acids), a glycosylated extracellular domain (322 amino acids), a single transmembrane segment (22 amino acids) and a cytoplasmic tail (54 amino acids). COS7 cells transfected with the cDNA expressed a 60 kd protein that bound IL-5 with a single class of affinity (KD = 2-10 nM). FDC-P1 cells transfected with the cDNA for murine IL-5 receptor showed the expression of IL-5 binding sites with both low (KD = 6 nM) and high affinity (KD = 30 pM) and acquired responsiveness to IL-5 for proliferation, although parental FDC-P1 cells did not show any detectable IL-5 binding. In addition, several cDNA clones encoding soluble forms of the IL-5 receptor were isolated. Northern blot analysis showed that two species of mRNAs (5.0 kb and 5.8 kb) were detected in cell lines that display binding sites for murine IL-5. Homology search for the amino acid sequence of the IL-5 receptor reveals that the IL-5 receptor contains a common motif of a cytokine receptor family that is recently identified.

Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice

Abstract: Insulin-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting beta-cells leading to overt diabetes. The best model for the disease is the non-obese diabetic (NOD) mouse. Two unusual features of the class II major histocompatibility complex (MHC) of the NOD mouse are the absence of I-E and the presence of unique I-A molecules (I-ANOD), in which aspartic acid at position 57 of the beta-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse. Here we report that the expression of I-Ak (A alpha kA beta k) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A beta-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A beta-chain from aspartic acid to serine is not sufficient for the development of the disease.

Holocene glacial rebound and sea-level change in NW Europe

Abstract: SUMMARY Observations of Late Pleistocene and Holocene sea-level change relative to the crust exhibit very considerable variations across NW Europe in consequence of the response of the Earth’s crust to the deglaciation of Fennoscandia and of the water added to the oceans from the melting of all Late Pleistocene ice sheets. Inversion of sea-level observations from a site near the centre of the Fennoscandian ice sheet and from three sites located beyond the margin of the ice sheet at the time of maximum glaciation yield a range of plausible models for the Earth’s response and for the ice models. Further constraints on this range of models is placed by a comparison of observed sea-levels with predicted values at other sites near the former ice sheet margins. The resulting mantle parameters are: upper mantle viscosity (3-5) X 10’’ Pa s; lower mantle viscosity (2-7) X loz1 Pa s; lithospheric thickness 100150 km. These values represent effective parameters that describe the response of the Earth to surface loading of short to intermediate wavelengths on a time-scale of 104yr. The lower mantle viscosity is poorly constrained but the marked increase from upper to lower mantle is a characteristic of all plausible solutions. The inversion places a constraint on the total volume of ice in the Fennoscandian ice sheet such that the equivalent sea-level rise from this contribution is about 13-14 m. A less well-determined constraint of about 10 m equivalent sea-level rise is suggested for the Barents-Kara ice sheet. The inversion also indicates that a small amount of melt-water, from ice sheets far away from Europe, continued to be added into the oceans during Late Holocene time so as to raise the equivalent sea-level by about 3 m during the past 6000 yr, consistent with similar inversions of data from sites in the Australian and Pacific regions.

Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules.

Abstract: Growth of early B precursor cells was investigated in vitro by using rIL-7 and IL-7-defective stromal cell line PA6 as separate growth signals. B cell development proceeds through three sequential stages different from the growth signal requirement. The cells in the first stage require PA6 alone for the proliferation, and differentiate into the second stage, which requires both PA6 and IL-7 for its growth. When IL-7 is available for the cells in the second stage, they proliferate extensively on the PA6 layer, and some acquire the ability to proliferate in response to IL-7 alone. This sequential change of growth signal requirement, however, does not proceed autonomously along the time schedule. The possibility that it is primarily directed by the result of Ig gene rearrangement is considered. This mode of growth control may explain why only functional B cells are selected in the error-prone process of Ig gene rearrangement during B lineage differentiation.

Structures of human genes coding for cytokine LD78 and their expression.

Abstract: LD78 is a member of a newly identified superfamily of small inducible proteins involved in inflammatory responses, wound healing, and tumorigenesis. Southern blot analysis of the EcoRI-digested human genomic DNAs, using previously isolated LD78 cDNA as a probe, showed that in each individual there are 4.2- and 4.8-kilobase-pair (kb) fragments and that some have an additional 6.5-kb fragment. The 4.2-kb fragment contained genomic DNA sequences corresponding to the LD78 cDNA and was named the LD78 alpha gene. The 4.8-kb fragment contained similar sequences, showing 94% homology to the LD78 alpha gene, and was named the LD78 beta gene. The LD78 alpha gene was present in a single or a few copies per haploid genome, whereas the copy number of the LD78 beta gene and of the 6.5-kb fragment hybridizable to LD78 cDNA varied among the samples tested. Treatment of human myeloid cell lines HL-60 and U937 with phorbol 12-myristate 13-acetate (PMA) increased within 2 h cellular levels of the RNA hybridizable to LD78 cDNA. The human glioma cell line U105MG and primary culture of human fibroblasts also expressed the hybridizable RNA in response to PMA. Addition of cycloheximide had no apparent effect on this response in U937 cells and inhibited the response in fibroblasts, whereas it stimulated the response in HL-60 and U105MG cells. mRNA phenotyping experiments revealed that the LD78 alpha and LD78 beta genes were both transcribed in PMA-stimulated U937 cells.

Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

Abstract: Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors.

Distribution of IL-5 receptor-positive B cells. Expression of IL-5 receptor on Ly-1(CD5)+ B cells.

Abstract: mAb to murine IL-5R were prepared by means of fusion between mouse myeloma cells and spleen cells from a rat immunized with membrane-enriched fractions of IL-5-dependent early B cell line (T88-M). Two mAb (H7 and T21) were selected for their competitive inhibition of receptor binding by 35S-labeled IL-5 and of IL-5 biologic activities. The number of binding sites recognized by the mAb on different cell lines correlated with IL-5 responsiveness. Most surface IgM+ peritoneal B cells were H7+ and more than 70% were also Ly-1(CD5)dull+, and responded to IL-5 for polyclonal IgM production in a high frequency. A significant proportion of splenic B cells reacted with these mAb, although lower number (one-log less) than peritoneal B cells and a small proportion of H7dull+ splenic B cells seems to be Ly-1(CD5)dull+, 1 of 200 splenic B cells responded to IL-5 for IgM production. These results suggest that IL-5R+ B cells may consist of a subpopulation of B cells. Intriguingly, lymphoid populations of bone marrow cells were stained with H7 and T21, whereas myeloid populations were brightly stained with only T21. Finally, both H7 and T21 mAb specifically precipitated a protein of a Mr 60,000 from 125I-labeled cell lysates of IL-5R+ T88-M cells. The IL-5R with similar size (Mr 55,000 to 60,000) was precipitated from the cell lysates of peritoneal B cells. T21 mAb but not H7 mAb precipitated a protein of a Mr 110,000 from the cell lysates of bone marrow cells.

Development, differentiation, and maturation of macrophages in the fetal mouse liver

Abstract: Primitive macrophages emerged in the sinusoidal lumen of the fetal mouse liver at 10 days of gestation before the initiation of hepatic hematopoiesis and matured into fetal macrophages. In the culture of cell suspensions from the fetal liver with LP3-conditioned medium, monocyte colonies were formed, but monocytopoiesis was poor in the early stage of hepatic hematopoiesis in vivo. In the culture of cell suspensions obtained from the fetal liver at 10 days of gestation on the monolayer of a mouse bone marrow stromal cell line, ST2, primitive/fetal macrophage colonies were formed before the development of monocyte/macrophage colonies and showed differentiation of primitive macrophages into fetal macrophages without passing through the stage of promonocytes and monocytes. At this time, the fetal cardiovascular system was connected with the vitelline vein just before the formation of the liver. With the progress of gestation, a monocytic cell series was observed to develop and form a monocyte/macrophage population. This was confirmed by in vitro studies with an LP3-conditioned medium and on a monolayer of ST2. Thus, it appears that there exist two different macrophage populations, a primitive/fetal macrophage population and a monocyte/macrophage population in hepatic hematopoiesis. It also appears that fetal macrophages are differentiated from primitive macrophages which are colonized into the fetal liver from the yolk sac or which develop in loco, presumably from hematopoietic stem cells.

Fuzzy multiple-input maximum and minimum circuits in current mode and their analyses using bounded-difference equations

Abstract: Multiple-input maximum and minimum circuits in current mode are proposed. The operation of these circuits is formulated using simultaneous bounded-difference equations. The exact analyses are performed by solving the bounded-difference equations. The accuracy of these circuits is better than the accuracy of binary tree realizations using two-input max/min circuits because no accumulation of errors occurs; furthermore, the operation speed is higher than the speed of the binary tree realization. The proposed circuits consist of only MOS transistors and are compatible with standard MOS fabrication processes. These circuits are useful building blocks for a real-time fuzzy controller and a fuzzy computer. >

Purified presequence binding factor (PBF) forms an import-competent complex with a purified mitochondrial precursor protein.

Abstract: In vitro mitochondrial import of the purified precursor form (pOTC) of rat ornithine carbamoyltransferase (OTC) is stimulated by a cytosolic factor(s) contained in rabbit reticulocyte lysate A protein factor that binds to pOTC but not to mature OTC and was named presequence binding factor or PBF, was purified 91,000-fold from the lysate by affinity chromatography using pOTC-bound Sepharose, DEAE-5PW HPLC and sucrose gradient centrifugation The purified PBF migrated as a single polypeptide of 50,000 daltons on SDS-PAGE On sucrose gradients, urea-denatured pOTC sedimented to the bottom, whereas PBF sedimented with an S20,w value of 55S When pOTC and PBF were centrifuged together, both polypeptides sedimented as a complex of 71S Formation of the pOTC-PBF complex was inhibited by micromolar concentrations of the synthetic presequence of pOTC and those of other mitochondrial precursor proteins The purified PBF markedly stimulated the import of purified or in vitro synthesized pOTC into the mitochondria PBF-stimulated pOTC import was further enhanced by a 70 kd heat shock protein (hsp 70) purified from yeast; the hsp70 alone had little effect Thus, PBF binds to the presequence portion of the precursors and may hold them in a transport-competent form in cooperation with hsp70

Rule-based stabilizer for multi-machine power system

Abstract: An application of the rule-based stabilizing control scheme to improve the overall stability of electric power systems is presented. Several simple rules are prepared for each generator in the system. The stabilizing signal for each generator is of the discrete type; it is renewed at every sampling time to control the generator excitation levels depending on the speed/acceleration state of the generator, using the measured speed deviation and the control rules. The efficiency of the proposed rule-based stabilizer is demonstrated by using a sample three-machine power system. >

Ca2+/calmodulin-dependent protein kinase II: localization in the interphase nucleus and the mitotic apparatus of mammalian cells.

Abstract: Indirect immunofluorescence was used to determine the distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in rat embryo fibroblast 3Y1 cells, rat C6 glioma cells, and human epidermoid carcinoma KB cells. During interphase at growing phase, CaM kinase II was localized diffusely in the cytoplasm and in the nucleus. In the nucleus, the enzyme was localized within the whole nuclear matrix in which the enzyme was specially concentrated in nucleoli. During mitosis, CaM kinase II was found to be a dynamic component of the mitotic apparatus, particularly present at microtubule-organizing centers. In metaphase and anaphase, CaM kinase II was observed at centrosomes and between the spindle poles. During telophase, CaM kinase II was condensed as a bright fluorescent dot at the midzone of the intercellular bridge between two daughter cells, while tubulin was found at each side of the midbody. Colchicine, a microtubule inhibitor, disorganized the tubulin- and CaM kinase II specific fluorescent structure of mitotic 3Y1 cells. In cold-treated cells, CaM kinase II was localized predominantly at centrosomes. The localization of CaM kinase II in the cell nucleus and the mitotic apparatus suggests that the enzyme may play a role in the cell cycle progression of mammalian cells.

Effect of protein C and activated protein C on coagulation and fibrinolysis in normal human subjects.

Abstract: Although protein C (PC) and activated protein C (APC) have been postulated to be useful for treating patients with thrombosis, their critical effect remains to be studied in human subjects. To examine whether purified PC or APC are useful for treating patients with thrombosis without showing any adverse effect, we studied effects on coagulation and fibrinolysis in normal human subjects. When highly purified human PC was administered intravenously to healthy subjects, plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously administered APC decreased with a half-life of 23 min as measured by prolongation of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the plasma half-life of APC when it was measured immunologically. These findings suggested that a significant fraction of the administered APC was rapidly inhibited by plasma inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting factor VIII (F-VIII) decreased transiently as measured by clotting assay. However, when determined by a chromogenic assay method in which 120-fold diluted plasma samples were used, plasma levels of F-VIII remained unchanged. Plasma levels of F-V did not decrease after APC administration. These findings suggested that prolongation of APTT and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator inhibitor in normal subject was not affected by administration of APC. Thus, PC or APC seems to function selectively at the site of thrombin-formation without lowering plasma levels of coagulation factors.

Hydrogen-alkali-metal-graphite ternary intercalation compounds

Abstract: Alkali-metal-graphite intercalation compounds (alkali-metal-GIC’s) absorb hydrogen in two ways: physisorption and chemisorption. Hydrogen uptake through the physisorption process occurs at low temperatures below about 200 K in higher stage alkali-metal-GIC’s, where hydrogen molecules are stabilized to form a two-dimensional condensed phase in the galleries of the graphite sheets. The concentration of absorbed hydrogen molecules is saturated at a rate of H2/alkali metal atom ∼2. The hydrogen physisorption shows a strong isotope effect and a swelling effect on c-axis lattice expansion. In the case of hydrogen uptake through the chemisorption process, dissociated hydrogen species are stabilized in the intercalate spaces. The activity of the chemisorption increases in the order Cs < Rb < K. The introduction of hydrogen generates a charge transfer from the host alkali metal GIC’s to the hydrogen since hydrogen has strong electron affinity. The hydrogenated potassium-GIC’s have intercalates consisting of K+-H−-K+ triple atomic layer sandwiches which are inserted between metallic graphite sheets. The inserted two-dimensional hydrogen layer is suggested to consist of H ions with a weakly metallic nature. The superconductivity of the hydrogenated potassium-GIC is also discussed in terms of the change in the electronic and lattice dynamical properties by hydrogen uptake. The hydrogen-absorption in alkali-metal-GIC’s is an interesting phenomenon in comparison with that in transition metal hydrides from the point of hydrogen storage. The hydrogen-alkali-metal-ternary GIC’s obtained from hydrogen absorption have novel electronic properties and lattice structures which provide attractive problems for GIC research. The studies of hydrogen-alkali-metal ternary GIC’s are reviewed in this article.

Fibrinopeptide A is released into the coronary circulation after coronary spasm.

Abstract: To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system.

Kupffer cell proliferation and glucan-induced granuloma formation in mice depleted of blood monocytes by strontium-89

Abstract: In mice with prolonged severe monocytopenia induced by selective irradiation of the bone marrow with the bone-seeking isotope 89Sr, the proliferative capacity of Kupffer cells was studied by immunohistochemistry with an anti-mouse macrophage monoclonal antibody, F4/80, ultrastructural peroxidase (PO) cytochemistry, and tritiated thymidine (3HTdR) autoradiography. The number and 3HTdR uptake of Kupffer cells were significantly increased in the splenectomized mice after severe monocytopenia had continued for more than 4 wk, and almost all the Kupffer cells showed a localization pattern of PO activity similar to that of resident macrophages in the liver of normal mice. In the glucan-induced granuloma formation in similar monocytopenic mice, Kupffer cells proliferated, conglomerated, and transformed into epithelioid cells, which fused together to become multinuclear giant cells. These results suggest that Kupffer cells are a self-renewing population by their own cell division and can participate actively in granulomatous inflammations in severely monocytopenic and intact mice.