Showing papers by "Kumamoto University published in 1996"
TL;DR: It is strongly suggested that defects in TRKA cause CIPA and that the NGF–TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans.
Abstract: Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is an autosomal-recessive disorder characterized by recurrent episodes of unexplained fever, anhidrosis (absence of sweating) and absence of reaction to noxious stimuli, self-mutilating behaviour and mental retardation. The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. Mice lacking the gene for TrkA, a receptor tyrosine kinase for NGF, share dramatic phenotypic features of CIPA, including loss of responses to painful stimuli, although anhidrosis is not apparent in these animals. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analysed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice- and missense-mutation in the tyrosine kinase domain in these three patients. Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF-TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans. These results also implicate genes encoding other TRK and neurotrophin family members as candidates for developmental defect(s) of the nervous system.
589 citations
TL;DR: It is concluded that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.
Abstract: The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2) Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice
492 citations
TL;DR: It is clear that a CML-protein adduct is a major immunological epitope in AGE structures, but there still exist other major epitope(s) expressed commonly in A GE-proteins.
Abstract: Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329−7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE−proteins indicated that Ne-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML−protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to ∼8 mol/mol of protein. Further e...
436 citations
TL;DR: In this paper, a linear relationship between bandgap and band edge was obtained for almost all the semiconductor oxides and it was pointed out that a bandgap energy higher than about 2.46 eV is necessary for water photolysis without bias voltage.
426 citations
TL;DR: There is a deficiency in endothelial NO activity in spasm arteries, which leads to the supersensitivity of the artery to the vasodilator effect of nitroglycerin and to the Vasoconstrictor effect of acetylcholine in patients with CSA, which plays an important role in the pathogenesis of coronary spasm.
Abstract: Background Coronary spasm can be induced by acetylcholine, serotonin, ergonovine, or histamine, all of which cause vasodilation when the endothelium is intact by releasing nitric oxide (NO). Coronary spasm is promptly relieved by nitroglycerin, which vasodilates through its conversion to NO. It is thus possible that NO release may be deficient in the spasm arteries in patients with coronary spastic angina (CSA). The aim of this study was to determine whether NO release is deficient in coronary arteries of patients with CSA. Methods and ResultsNG-monomethyl-l-arginine (L-NMMA), an inhibitor of NO synthase, was infused into coronary arteries in 21 patients with coronary spastic angina (CSA) and in 28 control patients. Coronary spasm was induced by intracoronary injection of acetylcholine and was documented angiographically in all patients with CSA. L-NMMA dose-dependently decreased basal luminal diameter of coronary arteries in control patients, whereas it had no effect on basal diameter of the spasm arteri...
370 citations
TL;DR: The generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase) gene suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain.
Abstract: Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.
364 citations
TL;DR: It is shown that mouse embryonic fibroblasts lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest and that two tumour-suppressor transcription factors converge functionally to regulate the cell cycle through the activation of a common target genes.
Abstract: Normally growing cells promptly cease DNA synthesis when exposed to genotoxic stresses, such as radiation, and this cell-cycle arrest prevents the accumulation of mutations. The transcription factor interferon regulatory factor (IRF)-1 is essential for the regulation of the interferon system, inhibits cell growth, and manifests tumour-suppressor activities. Here we show that mouse embryonic fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1 and p53 are independent of one another. Furthermore, we show that transcriptional induction of the gene encoding p21 (WAF1, CIP1), a cell-cycle inhibitor, by gamma-irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is activated, either directly or indirectly, by both in a transient cotransfection assay. These two tumour-suppressor transcription factors therefore converge functionally to regulate the cell cycle through the activation of a common target gene.
339 citations
TL;DR: Heterogeneity inthe immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS suggests the presence of two etiologically distinct diseases in Asians.
Abstract: The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic resonance images of the brain and spinal cord were studied in 57 Japanese patients with multiple sclerosis (MS). Twenty-three patients clinically displayed selective involvement of the optic nerve and spinal cord and were classified as having Asian-type MS. The other 34 patients had disseminated central nervous system involvement and were classified as having Western-type MS. Patients with Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but more gadolinium-enhanced spinal cord lesions than did patients with Western-type MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101 allele were associated with Western-type MS (41.2%), but not with either Asian-type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS thus suggests the presence of two etiologically distinct diseases in Asians.
297 citations
Journal Article•
TL;DR: Electrogene therapy, which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.
Abstract: A novel method for high-efficiency and region-controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cells 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoat-tractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in the tumor tissue. This method, “electrogene therapy,” which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.
294 citations
TL;DR: It is concluded that the particle-laden cells in the hepatic lymph are recently produced immature DC that manifest a temporary phagocytic activity for intravascular particles during or after the terminal division and that the phagocytetic activity is downregulated at a migratory stage when they translocate from the sinusoidal area to the hepatatic lymph.
Abstract: Initiation of an adoptive immune response against pathogenic organisms, such as bacteria and fungi, may involve phagocytic activity of dendritic cells (DC) or their immature precursors as a prelude to antigen processing and presentation. After intravenous injection of rats with particulate matter, particle-laden cells were detected in the peripheral hepatic lymph. Since it has been known there is a constant efflux of DC from nonlymphoid organs into the draining peripheral lymph, we examined whether these particle-laden cells belonged to the DC or macrophage lineage. The majority of particle-laden cells in lymph showed immature monocyte-like cytology, and the amount of ingested particles was small relative to typical macrophages. We identified these particle-laden cells as DC based on a number of established criteria: (a) they had a phenotype characteristic of rat DC, that is, major histocompatibility complex class Ihigh+ and IIhigh+, intercellular adhesion molecule 1+ and 80% positive with the rat DC-specific mAb OX62; (b) they showed strong stimulating capacity in primary allogeneic mixed leukocyte reaction; (c) in vitro, they had little phagocytic activity; and (d) the kinetics of translocation was similar to that of lymph DC in that they migrated to the thymus-dependent area of the regional nodes. Furthermore, bromodeoxyuridine feeding studies revealed that most of the particle-laden DC were recently produced by the terminal division of precursor cells, at least 45% of them being <5.5 d old. The particle-laden DC, defined as OX62+ latex-laden cells, were first found in the sinusoidal area of the liver, in the liver perfusate, and in spleen cell suspensions, suggesting that the site of particle capture was mainly in the blood marginating pool. It is concluded that the particle-laden cells in the hepatic lymph are recently produced immature DC that manifest a temporary phagocytic activity for intravascular particles during or after the terminal division and that the phagocytic activity is downregulated at a migratory stage when they translocate from the sinusoidal area to the hepatic lymph.
269 citations
TL;DR: The results suggest that the mechanism of APC inhibition of LPS-induced pulmonary vascular injury was independent of its anticoagulant activity and was related to its ability to inhibit accumulation of leukocytes.
TL;DR: A direct relationship between p53 expression and loss of viability in CNS neurons is demonstrated using adenovirus-mediated transduction to promote neuronal cell death even in the absence of excitotoxin.
Abstract: A role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. These findings were recently extended with the demonstration that mice deficient in p53 ("knock-out" mice) exhibit almost complete protection from seizure-induced brain injury, whereas wild-type mice display significant neuronal cell loss in the hippocampus and other brain regions. Because the p53 knock-out mice used in the latter study expressed a global p53 deficiency in all cell types, it was not possible to conclude that protection was conferred by the exclusive absence of p53 in neurons. Therefore, in the present study, we determined whether p53 expression in isolated neurons is directly coupled to a loss of viability associated with excitotoxic challenge. Primary cultures of hippocampal or cortical neurons were derived from animals containing p53 (+/+, +/-) or those deficient in p53 (-/-). p53-Deficient neurons appeared identical to wild-type neurons with respect to morphology, neurofilament expression, and resting levels of intracellular calcium. Neurons containing at least one copy of p53 were severely damaged by exposure to kainic acid or glutamate. Cell damage was assessed by direct cell counting and by nuclear morphology after propidium iodide staining of DNA. In contrast, neurons deficient in p53 (-/-) exhibited little or no damage in response to excitotoxin treatment. Despite their divergent outcomes, p53 (+/+) and p53 (-/-) neurons demonstrated similar sustained elevations in intracellular calcium levels triggered by glutamate exposure. Restoring p53 expression to p53-deficient neurons, using adenovirus-mediated transduction, was sufficient to promote neuronal cell death even in the absence of excitotoxin. These results demonstrate a direct relationship between p53 expression and loss of viability in CNS neurons.
TL;DR: Breath-hold HASTE-MRCP with a phased-array multicoil consistently allows for high-quality images of both normal and diseased pancreaticobiliary tracts.
Abstract: Images of breath-hold MR cholangiopancreatography (MRCP) using HASTE (half-Fourier acquisition single-shot turbo spin-echo) sequences were taken in healthy volunteers. The technique was then evaluated as a noninvasive alternative to direct cholangiopancreatography in patients with pancreaticobiliary diseases.Forty healthy volunteers and 56 patients with various pancreaticobiliary diseases were examined by MRCP using HASTE with 128 echo train lengths on a 1.5-T MR unit. A body phased-array coll was used for data collection. Imaging times were 2 sec for the single-slice technique with a 20-mm slice thickness and 18 sec for sequential acquisition by the multislice technique with a 5-mm slice thickness (effective TE, 87 msec). We used the healthy volunteers to determine our ability to detect normal structures. The results obtained by HASTE for both patient groups were correlated with imaging by percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography.In all healthy volunteer...
TL;DR: A model for binding site I is elaborated in which novel nomenclatures, region Ia, Ib, and Ic are proposed for the acenocoumarol, DNSA and n-butyl p-ABE binding regions, respectively.
TL;DR: The results suggest that the patterns of endoderm gene expression during EB development reflect the order found during mouse development in vivo, and EB formation may serve as an in vitro system to study the differentiation process.
TL;DR: The high frequency of this defective virus in the aggressive form of ATL suggests that it may be caused by the genetic instability of HTLV-I provirus, and cells with this defectiveirus are selected because they escape from immune surveillance systems.
TL;DR: Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high incidence in the southwestern region, and the retrovirus, human T-lymphotropic virus type I (HTLV-I), is found to be the causative agent.
Abstract: Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high incidence in the southwestern region. The retrovirus, human T-lymphotropic virus type I (HTLV-I), is found to be the causative agent of ATL. In ATL-endemic areas, the rate of HTLV-I carriers is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumor cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes: the acute, chronic, smoldering, and lymphoma types. Chemotherapy is not effective; the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, or from man to woman, or by blood transfusion.
TL;DR: Arginase II mRNA was coinduced with nitric oxide synthase mRNA in murine macrophage‐like RAW 264.7 cells by lipopolysaccharide and enhanced by dexamethasone and dibutyryl cAMP, and was prevented by interferon‐γ.
TL;DR: The distinct differentiation pathways of monocyte/macrophage, resident macrophages, other macrophage subpopulations, and Macrophage‐related cells are reviewed together with the heterogeneity of macrophAGE precursor cells.
Abstract: Macrophages are a heterogeneous population differing In their site of location, morphology and function. They develop from hematopoletic stem cells originating In both fetal and bone marrow hematopolesls. In yolk sac and early hepatic hematopoiesls, primitive/fetal macrophages develop from hematopoletic stem cells, bypassing the stage of monocytic cells (monoblasts, promonocytes and monocytes), possess proliferatlve capacity and differentiate into resident macrophages in tissues in late ontogeny. Monocytic cells develop In hepatic hematopolesis after the development of primitive/ fetal macrophages, then move into the bone marrow in late ontogeny, forming a monocyte-derived macrophage population in tissues. Like monocytes, the monocyte-derived macrophages have no proliferative potential and are short-lived, whereas the resident macrophages are long-lived in tissue, possess proliferatlve capacity and can be sustained by self-renewal. In adult life, the bone marrow releases macrophage precursors (immature myeloid cells) and monocytes into peripheral blood, but normally not monoblasts or promono-cyts. The myeloid precursor cells migrate into tissues and differentiate into resident macrophages or related cells in situ due to macrophage differentiation or growth factors, such as M-CSF and GM-CSF, produced in situ and/or supplied Immorally. Monocytes, however, migrate into tissues in response to inflammatory stimuli and differentiate Into exudate macrophages. The distinct differentiation pathways of monocyte/macrophages, resident macrophages, other macrophage subpopulations, and macrophage-related cells are reviewed together with the heterogeneity of macrophage precursor cells.
TL;DR: In this article, the extraction rate of oil from freeze-dried ginger root with supercritical carbon dioxide was measured as a function of CO2 flow rate, particle size, temperature, and pressure.
Abstract: The extraction rate of oil from freeze-dried ginger root with supercritical carbon dioxide was measured as a function of CO2 flow rate, particle size, temperature, and pressure. The extraction curv...
TL;DR: MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system.
Abstract: Methylmercury (MeHg) penetrates the placental barrier to affect developing fetuses in the uterus. However, the mechanism of placental MeHg transport is not well defined. To clarify the MeHg transport system that functions in the placenta, pregnant rats were intravenously administered MeHg on day 18 of gestation. The fetal blood was collected from the umbilical cord at 30 and 60 min after the administration, and its mercury concentration was measured. MeHg was found to be rapidly transported to the fetal blood in a time- and dose-dependent manner, and predominantly distributed in the blood cells there. MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system. The suppression by methionine was not so marked as by phenylalanine. Since methionine administration caused a rapid increase of the cysteine, which functioned as a predominant carrier in MeHg transport, in the maternal plasma, newly synthesized cysteine seemed to accelerate the mercury uptake. Accordingly, the acceleration by the extra cysteine would compensate partly the competitive effect of methionine as a neutral amino acid.
TL;DR: TF belongs to the interferon receptor family and is one of the immediate early genes, suggesting that TF may participate in the regulation of cell growth, however, the correlation between the expression of TF and cell growth is still unclear.
Abstract: BACKGROUND
Tissue factor (TF), a cell surface receptor of factor VII/VIIa, was initially recognized as an initiator of the extrinsic coagulation pathway. TF has recently been found to be expressed highly in certain types of malignant tumors. In addition, TF belongs to the interferon receptor family and is one of the immediate early genes, suggesting that TF may participate in the regulation of cell growth. However, the correlation between the expression of TF and cell growth is still unclear.
METHODS
Expression of TF in 6 glioma cell lines and 44 glioma surgical specimens was studied by Northern blot analysis, Western blot analysis, immunohistochemistry, and in situ hybridization.
RESULTS
Northern blot analysis showed that glioma cells expressed minor novel transcripts of 3.3 kb and 1.6 kb, in addition to the transcripts of 2.2 kb and 3.1 kb that were previously reported. Western blot analysis revealed that the level of TF protein did not correlate with that of TF transcripts. Although immunohistochemical analysis of surgical specimens showed that all gliomas were positive for TF, it was interesting that 1 of 10 benign gliomas (10%) was positive for TF (malignancy Grade I–II), 12 of 14 anaplastic astrocytomas (86%) (malignancy grade III) and 19 of 20 glioblastomas (95%) (malignancy Grade IV) were moderately or strongly positive for TF. In situ hybridization showed the expression of TF mRNA in glioma cells.
CONCLUSIONS
TF is expressed in glioma and the level of expression correlates with the histologic grade of malignancy. Cancer 1996;77:1877-83.
TL;DR: The role of NO in solid tumor pathology was further investigated in animal tumor and a possible connection between nitric oxide (NO) and enhanced vascular permeability in solid tumors was reported.
Abstract: BACKGROUND. Rapid tumor growth is caused by angiogenesis factors, growth factors, etc. We previously reported a possible connection between nitric oxide (NO) and enhanced vascular permeability in solid tumor. In the present experiment, the role of NO in solid tumor pathology was further investigated in animal tumor. METHODS. To identify NO formed in solid tumor (AH136B) implanted in the feet of rats, electron paramagnetic resonance (EPR) spectroscopy was performed directly on the frozen tumor tissue at 110K by measuring endogenous nitrosyl iron-sulfur complexes, and by using exogenously added NO capturing agents, i.e., diethyldithiocarbamate (DETC)-Fe 2+ and N-(dithiocarboxy)sarcosine (DTCS)-Fe 2+ complexes. Induction of inducible isoform of nosymthase iNOS mRNA was examined with reverse transcriptase-polymerase chain reaction (RT-PCR) combined with Southern blot analysis. In addition, vascular permeability was assessed by measuring extravasation of 51 Cr-labeled bovine serum albumin in solid tumor. RESULTS. Strong EPR signals from NO adducts of DETC-Fe 2+ and DTCS-Fe 2+ as well as strong signals from NO-hemoglobin and dinitrosyl iron sulfur complex were generated by tumor. The signal height of NO-(DTCS) 2 -Fe 2+ observed in AH136B solid tumor was increased as the tumor gained up to 1.75 g. Induction of iNOS mRNA expression was confirmed by the above methods. Enhanced vascular permeability was suppressed by NOS inhibitors N ω -monomethyl-L-arginine or S-methylisothiourea sulfate and augmented with administration of L-arginine. CONCLUSIONS. Excessive NO production by iNOS in solid tumor was identified unequivocally by EPR spectroscopy. NO formed in solid tumor can be involved in enhanced vascular permeability and increased blood flow, and hence sustain tumor growth.
TL;DR: The results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophages growth factors in both fetal and adult life.
Abstract: In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.
TL;DR: In this article, the ages of molybdenites from eighteen ore deposits in Japan; fifteen vein-type, a skarn-type and a greisen-type; and a pegmatite-type deposit.
TL;DR: The results suggest that Mos is located upstream of MAPK in mouse oocytes as in Xenopus oocytes but is independent of MPF activity, and that Mos/MAPK is not necessary go GVBD and first polar body emission.
Abstract: In Xenopus oocytes, Mos activates the mitogen-activated protein kinase (MAPK) signal transduction cascade and regulates meiosis. In mammalian oocytes, however, the functions of Mos are still unclear. In the present study, we used c-mos knockout mouse oocytes and examined the roles of Mos in mouse oocyte maturation and fertilization, including whether Mos controls MAPK and maturation promoting factor (MPF) activity. The kinetics of germinal vesicle breakdown (GVBD) and the first polar body emission were similar in wild-type, heterozygous mutant, and homozygous mutant mice. Activities of MPF were also not significantly different among the three genotypes until the first polar body emission. In contrast, MAPK activity in c-mos knockout oocytes did not significantly fluctuate throughout maturation, and the oocytes had abnormal diffused spindles and loosely condensed chromosomes, although a clear increase in MAPK activities was observed after GVBD in wild-type and heterozygous mutant oocytes that had normal spindles and chromosomes. After the first polar body emission, 38% of c-mos knockout oocytes formed a pronucleus instead of undergoing second meiosis, indicating the crucial role of Mos in MPF reactivation after first meiosis. When oocytes that reached second metaphase were fertilized or stimulated by ethanol, many c-mos knockout oocytes emitted a second polar body and progressed into third meiotic metaphase instead of interphase, although all fertilized or activated oocytes in the heterozygote progressed to interphase, indicating that Mos deletion leads to compensatory factors that might not be degraded after fertilization or parthenogenetic activation. These results suggest that Mos is located upstream of MAPK in mouse oocytes as in Xenopus oocytes but is independent of MPF activity, and that Mos/MAPK is not necessary for GVBD and first polar body emission. Our results also suggest that Mos plays a crucial role in normal spindle and chromosome morphology and the reactivation of MPF after first meiosis.
TL;DR: The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.
TL;DR: Arterial-phase helical CT of the liver after 4-ml/sec injection of contrast material significantly improves detection of hepatomas less than 3 cm in diameter when performed in addition to delayed scanning.
Abstract: Helical CT scanners allow multiple-phase sequential scans of the entire liver to be obtained during a single bolus injection of contrast material. The purpose of this study was to compare two injection protocols and to establish timing that would optimize detection of hepatomas less than 3 cm in diameter.Triple-phase helical CT of the liver was evaluated in 217 patients who had liver cirrhosis and were referred for known or suspected hepatomas. Proof of individual neoplasms was based on biopsy results, surgical findings, or findings of other imaging studies. Sixty percent nonionic contrast material, infused at 2 or 4 ml/sec, was followed by sequential arterial-phase, portal-venous phase, and equilibrium-phase helical scans of the liver. Aortic and hepatic enhancement curves were constructed by measuring CT attenuation. The CT attenuation values of individual tumor lesions were also measured. We compared the degree of enhancement of normal structures and tumors obtained with four scan protocols (injection ...
TL;DR: It is concluded that the C-terminal half of RNase E is not essential for viability but plays an important role for binding with PNPase, the multiprotein complex presumably cooperate for effective processing and turnover of specific substrates, such as mRNAs and other RNAs in vivo.
Abstract: We have isolated suppressor mutants that suppress temperature-sensitive colony formation and anucleate cell production of a mukB mutation. A linkage group (smbB) of the suppressor mutations is located in the rne/ams/hmp gene encoding the processing endoribonuclease RNase E. All of the rne (smbB) mutants code for truncated RNase E polypeptides lacking a carboxyl-terminal half. The amount of MukB protein was higher in these rne mutants than that in the rne+ strain. These rne mutants grew nearly normally in the mukB+ genetic background. The copy number of plasmid pBR322 in these rne mutants was lower than that in the rne+ isogenic strain. The results suggest that these rne mutations increase the half-lives of mukB mRNA and RNAI of pBR322, the antisense RNA regulating ColE1-type plasmid replication. We have demonstrated that the wild-type RNase E protein bound to polynucleotide phosphorylase (PNPase) but a truncated RNase E polypeptide lacking the C-terminal half did not. We conclude that the C-terminal half of RNase E is not essential for viability but plays an important role for binding with PNPase. RNase E and PNPase of the multiprotein complex presumably cooperate for effective processing and turnover of specific substrates, such as mRNAs and other RNAs in vivo.
TL;DR: In this paper, the shrinking core model was applied to the modeling of the extraction process and a quasi-steady-state solution without axial dispersion was derived, and the accuracy was discussed in comparison with the numerical solutions.
Abstract: Extraction or leaching of a solute from a solid material is a process involving mass transfer in the solid matrix. When the solute content in the solid material is sufficiently large as compared to the solubility in fluid phase, the process is similar to that of irreversible desorption. The shrinking-core model was applied to the modeling of the extraction process. The model including axial dispersion in the extraction column was solved numerically. Quasi-steady-state solution without axial dispersion was derived, and the accuracy was discussed in comparison with the numerical solutions. The model calculations gave a good agreement with the experimental extraction curve reported in literature.