Role of donor passenger leukocytes on the induction of tolerance in rat liver transplantation.
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Animals↗
Biomedical subjects
S Goto
Publications and source records attributed to S Goto.
Morphologic changes in the elastic fibers of the temporomandibular joint after experimental disc perforation in the rabbit.
PURPOSE: Elastic fibers in the attachment regions of the temporomandibular joint (TMJ) are considered important in the movements of the disc during jaw motion. This study was designed to determine whether there are change in the elastic fibers of the TMJ when the disc is perforated for a long period. MATERIALS AND METHODS: Each TMJ of five rabbits was surgically exposed, and a mediolateral perforation was made in the center of the articulating region of the disc with a scalpel. Five untreated and three sham-operated rabbits were used as controls. The TMJs were removed after 10 months and processed for histochemical demonstration of elastic fibers. RESULTS: Osteoarthritic changes and a significant decrease in number of the elastic fibers in the anterior-inferior attachment and posterior-inferior attachment of the TMJ disc were observed after disc perforation. Conversely, elastic fibers appeared in the fibrous tissue on the resorbed bone of the articular eminence. CONCLUSIONS: Experimental disc perforation changes the distribution and density of the elastic fiber in the TMJ as well as causes osteoarthritis. A knowledge of these facts may improve our understanding of perforation of the disc.
Animals↗
Cadherin-8 protein expression in gray matter structures and nerve fibers of the neonatal and adult mouse brain.
The topological distribution of mouse cadherin-8 protein in the neonatal and adult mouse brain was studied immunohistochemically using a rabbit antiserum. Cadherin-8 expression was restricted to several areas in neonatal brains constituting particular neural circuits, i.e. the limbic system, the basal ganglia-thalamocortical circuit, and the cerebellum and related nuclei. In addition, the nerve fibers linking some of the cadherin-8-positive areas, i.e. the habenulo-interpeduncular tract, decussation of the dorsal tegmentum, the medial longitudinal fasciculus, transverse pontine fibers, the brachium conjunctivum and the inferior cerebellar peduncle were cadherin-8 positive, as were the spinal tract of the trigeminal nerve, oculomotor nerve, facial nerve and trigeminal nerve. Cadherin-8 expression also showed a patch-like distribution in the intermediate gray layer of the superior colliculus, resembling acetylcholinesterase-rich patches in allocation. Segmentally organized cadherin-8-positive areas were found in the neonatal cerebellar Purkinje cell layer. Some nuclei and fibers in the brainstem and cerebellum, expressing cadherin-8 at neonatal stages, were also stained in the adult mouse brain. These findings suggest that cadherin-8 is involved in the formation of particular neural circuits by connecting areas expressing this molecule with positive nerve fibers, and indicate its possible implication in subdivisional organization in the superior colliculus and cerebellum.
Animals↗
Electromyography during chewing movement in patients with anterior disc displacement of the temporomandibular joint.
The purpose of this study was to investigate the value of electromyography in patients with anterior disc displacement (ADD) of the temporomandibular joint (TMJ). Electromyography (EMG) during chewing movement was evaluated in 48 women with unilateral ADD of the TMJ (21 patients with ADD with reduction and 27 with ADD without reduction). As a control group, 31 women without TMJ dysfunction were evaluated. The duration of contraction, latency, cycle time, and integrated value on the EMG were measured in the patients and controls. There were significant differences between the patients and controls in the duration of contraction, cycle time, and integrated value. However, there were no differences in any measurements between the two subgroup patients. EMG appeared to be a method of documenting that masticatory function was impaired in patients with ADD.
Adolescent↗
A transient increase in endogeneous erythropoietin levels after paediatric liver transplantation.
We investigated whether liver transplantation affects endogeneous erythropoietin (EPO) synthesis. Serum EPO levels were measured before transplantation and during the peri-transplant period in ten consecutive paediatric patients who had received a liver allograft without recombinant EPO therapy. All patients were anaemic on post-operative day 1 (POD 1); however, the haemoglobin levels of three patients gradually increased and required phlebotomy on POD 5-9. The serum levels of EPO in all patients were within the normal range before surgery, but six of the ten patients had a transient increased level of EPO at 1248 h after transplantation. A transient increase of endogeneous EPO following paediatric liver transplantation may be associated with extramedullary erythropoiesis in human liver grafts.
Child↗
Antigen presenting cells and chimerism.
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Animals↗
Protective role of glutathione synthesis on radiation-induced DNA damage in rabbit brain.
1. Radiotherapy has attracted increasing interest in recent years. It is known that ionizing radiation induces oxygen radical injury, whereas oxidative stress by the radiation can cause cellular responses to defense cellular injury. In this study, the metabolism of antioxidants in response to ionizing radiation to the brain was studied in the brain using experimental rabbits. 2. Ionizing radiation to the hemicerebrum caused an increase in the levels of glutathione (GSH) and the activity of a GSH synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Ionizing radiation also induced DNA-damage estimated by the formation of 8-hydroxydeoxyguanosine. These changes were dependent on the radiation dose. 3. Previous intrathecal-administration of buthionine sulfoximine (100 microM), a specific inhibitor of gamma-GCS, increased DNA damage by radiation in the radiated hemicerebrum. That of S-methyl GSH, on the other hand, resulted in a significant reduction of DNA damage by radiation. 4. These results suggest that synthesis of GSH and Cu,Zn-SOD is responsive to ionizing radiation and this induction of antioxidants may play a role in reducing tissue damage in radiotherapy.
Animals↗
Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common form of human myelopathy caused by a compression of the spinal cord by ectopic ossification of spinal ligaments. To elucidate the genetic basis for OPLL, we have been studying the ttw (tiptoe walking; previously designated twy) mouse, a naturally occurring mutant which exhibits ossification of the spinal ligaments very similar to human OPLL (refs 3,4). Using a positional candidate-gene approach, we determined the ttw phenotype is caused by a nonsense mutation (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase. This enzyme regulates soft-tissue calcification and bone mineralization by producing inorganic pyrophosphate, a major inhibitor of calcification. The accelerated bone formation characteristic of ttw mice is likely to result from dysfunction of NPPS caused by predicted truncation of the gene product, resulting in the loss of more than one-third of the native protein. Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL.
Animals↗
Busulfan, cyclophosphamide and total body irradiation as conditioning for allogeneic bone marrow transplantation for acute and chronic myeloid leukemia.
Fifty patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) underwent allogeneic bone marrow transplantation between October 1988 and January 1997. Patients received 8 mg/kg of busulfan (BU) with 120 mg/kg of cyclophosphamide (CY) followed by 10 Gy of total body irradiation (TBI). Twenty consecutive patients with AML in first remission (n = 9) or CML, in chronic phase (n = 11) entered the study (group I). Thirty consecutive patients with advanced myeloid malignancies including AML (n = 19) and CML (n = 11) also entered the study (group II). The probability of leukemia-free survival at 5 years was 85% for group I patients and 50% for group II patients. Severe regimen-related toxicities occurred in 16% of patients (two in group I, six in group II). The most common sites affected by severe toxicities were lung (n = 6), liver (n = 2) and heart (n = 2). The relapse rate was higher for patients allografted in advanced stages of disease (O% at 5 years for group I and 28% for group II). These results suggest that BU + CY + TBI is a very effective conditioning regimen in patients with myeloid malignancies.
Adolescent↗
Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.
1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.
Animals↗
Nicardipine normalizes elevated levels of antioxidant activity in response to xanthine oxidase-induced oxidative stress in hypertensive rat heart.
It has been reported that the production of oxygen radicals mediated by xanthine oxidase (XO) is stimulated in hypertensive cardiovascular endothelium, suggesting involvement of oxidative stress in pathogenesis of hypertension. In this study we estimated the effect of nicardipine, a calcium blocker, on the oxidative stress and antioxidant activities in left ventricles from spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP). The activity of XO increased 3.5-fold in SHR and 6.2-fold in SHRSP compared to that in normal controls (WKY). Interestingly, the levels of glutathione (GSH) and the activity of its synthesizing enzyme (gamma-glutamylcysteine synthetase, gamma-GCS) elevated concomitantly in SHR and SHRSP: the level of GSH increased 1.2-fold in SHR and 1.3-fold in SHRSP. The activity of gamma-GCS was elevated 1.5-fold in SHR and 2.4-fold in SHRSP, accompanying an increase in the expression of its mRNA. Treatment of these rats with nicardipine, for 4 weeks improved blood pressure, from 176 +/- 10 to 140 +/- 8 mmHg in SHR, and from 201 +/- 11 to 167 +/- 5 mmHg in SHRSP, respectively, and decreased wet weight of heart, levels of GSH, and the activities of XO and gamma-GCS. Nicardipine reduced the expression of gamma-GCS mRNA. Collectively, these results suggest that reactive oxygen species produced by XO in hypertensive rat heart cause induction of the expression of gamma-GCS and nicardipine plays a role in reducing the oxidative stress in hypertensive heart.
Animals↗
LIGAND: chemical database for enzyme reactions.
MOTIVATION: The existing molecular biology databases focus on the sequence and structural aspects of biological macromolecules, i.e. DNAs, RNAs and proteins. However, in order to understand the functional aspects, it is essential to computerize the interaction of these molecules. Furthermore, living cells contain additional molecules, such as metabolic compounds and metal ions, that may also be considered as parts of the basic building blocks of life, but are not well organized in public databases. LIGAND chemical database is our attempt to solve these problems, at least for enzymatic reactions. RESULTS: LIGAND consists of two sections: ENZYME and COMPOUND. The ENZYME section is an extension of previous studies (Suyama et al. , Comput. Applic. Biosci., 9, 9-15, 1993), and it is a flat-file representation of 3303 enzymes and 2976 enzymatic reactions in the chemical equation format that can be parsed by machine. The COMPOUND section has been newly constructed for information on the nomenclature and chemical structures of compounds. It contains 5383 chemical compounds. Both ENZYME and COMPOUND entries contain rich cross-reference information, most of which is automatically generated by the DBGET/LinkDB system, thus providing the linkage between chemical and biological databases. LIGAND is updated daily, tightly coupled with the KEGG metabolic pathway database, and forms the basis for reconstruction and computation of pathways. AVAILABILITY: LIGAND can be accessed through the DBGET/LinkDB and KEGG systems in the Japanese GenomeNet database service via http://www.genome.ad.jp/. The flat-file format of the LIGAND database can be downloaded by anonymous FTP via ftp://kegg. genome.adjp/molecules/ligand/. CONTACT: goto@kuicr.kyoto-u.ac.jp; nishioka@scl.kyoto-u.ac.jp; kanehisa@kuicr.kyoto-u.ac.jp
Computational Biology↗
Hypocholesterolemic effects of the LDL receptor gene transcriptional upregulator CP-230821.
CP-230821 is a novel, potent LDL receptor gene transcriptional upregulator which decreases total plasma cholesterol level. Interestingly, this plasma LDL decrease does not alter hepatic lipid contents. A series of experiments was undertaken to study the molecular biology of this phenomenon. Twelve hours after CP-230821 treatment, the transcriptional activity and mRNA level of the LDL receptor gene in HepG2 cells were increased by 264% and 426%, respectively. Although treatment with the HMG-CoA reductase inhibitor compactin also increased LDL receptor gene transcription and mRNA, CP-230821 did not increase the level of HMG-CoA reductase gene transcription or mRNA. These results indicate that LDL receptor gene activity may play an important role in the decrease of plasma LDL level. These results further suggest that the LDL receptor gene and the HMG-CoA reductase gene are not strictly coordinately controlled.
Animals↗
Exchange of nucleoside monophosphate-binding domains in adenylate kinase and UMP/CMP kinase.
Two types of active chimeric enzymes have been constructed by genetic engineering of chicken cytosolic adenylate kinase (AK) and porcine brain UMP/CMP kinase (UCK): one, designated as UAU, carries an AMP-binding domain of AK in the remaining body of UCK; and the other, designated as AUA, carries a UMP/CMP-binding domain of UCK in the remaining body of AK. Steady-state kinetic analysis of these chimeric enzymes revealed that UAU is 4-fold more active for AMP, 40-fold less active for UMP, and 4-fold less active for CMP than the parental UCK, although AUA has considerably lowered reactivity for both AMP and UMP. Circular dichroism spectra of the two chimeric enzymes suggest that UAU and AUA have similar folding structures to UCK and AK, respectively. Furthermore, proton NMR measurements of the UCK and UAU proteins indicate that significant differences in proton signals are limited to the aromatic region, where an imidazole C2H signal assigned to His31 shows a downfield shift upon conversion of UCK to UAU, and the signals assigned to Tyr49 and Tyr56 in the UMP/CMP-binding domain disappear in UAU. In contrast, AUA has a Tm value about 11 degreesC lower than AK, whereas UAU and UCK have similar Tm values. These results together show that the substrate specificity of nucleoside monophosphate (NMP) kinases can be engineered by the domain exchange, even though the base moiety of NMP appears to be recognized cooperatively by both the NMP-binding domain and the MgATP-binding core domain.
Adenylate Kinase↗
Reconstruction of amino acid biosynthesis pathways from the complete genome sequence.
The complete genome sequence of an organism contains information that has not been fully utilized in the current prediction methods of gene functions, which are based on piece-by-piece similarity searches of individual genes. We present here a method that utilizes a higher level information of molecular pathways to reconstruct a complete functional unit from a set of genes. Specifically, a genome-by-genome comparison is first made for identifying enzyme genes and assigning EC numbers, which is followed by the reconstruction of selected portions of the metabolic pathways by use of the reference biochemical knowledge. The completeness of the reconstructed pathway is an indicator of the correctness of the initial gene function assignment. This feature has become possible because of our efforts to computerize the current knowledge of metabolic pathways under the KEGG project. We found that the biosynthesis pathways of all 20 amino acids were completely reconstructed in Escherichia coli, Haemophilus influenzae, and Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as well, although it was necessary to assume wider substrate specificity for aspartate aminotransferases.
Amino Acids↗
[Impact of influenza epidemics and efficacy of vaccination among geriatric inpatients].
To determine the impact of influenza epidemics among geriatric inpatients and to monitor the clinical efficacy of influenza vaccination, the influenza infection rate in non-vaccinated inpatients was determined serologically and the incidence of febrile episodes and death were compared between the vaccinees and non-vaccinees hospitalized in the referred hospital from January through September, 1995. Three influenza subtypes, influenza A/H1N1, A/H3N2, and B, were endemic simultaneously from January to March in 1995. The pattern of incidence of febrile episodes varied for each ward. A total of 123 non-vaccinated inpatients were tested for elevation of serum hemagglutination inhibition titer to the three subtypes of influenza virus. Of these, 58 (47.2%) patients were infected with at least one of the influenza viruses during the epidemic of 1995. No patient with pre-existing HI titer over 128X was infected with any of three types of influenza, indicating that HI titer over 128X is the protective level. The febrile episode frequency was significantly higher in the non-vaccinees than in the vaccinees (49.6% vs. 32.6%), but it was quite comparable in the two groups after the influenza epidemic (34.9% vs. 35.8%). The number of observed deaths from January to September of 1995 was 4 (4.9%) in the vaccinee group and 12 (9.8%) in the non-vaccinee group. These results suggest that influenza epidemics have a striking impact on geriatric inpatients and that influenza vaccination has significant efficacy for the reduction of harmful events associated with influenza infection.
Aged↗
[Antibody response to a single injection of influenza vaccine among geriatric inpatients vaccinated annually].
To determine the efficacy of a single influenza vaccine administration in the elderly receiving annual influenza vaccination, antibody response to influenza vaccine was compared between once and twice injections in a geriatric cohort. Influenza vaccination had been done for 69 inpatients in the year prior to the study, and was administered twice for 34 of them and once for the other 35 during the study period. Influenza vaccine was injected twice to 77 inpatients who had not received influenza vaccine in the year prior to the study. Hemoagglutination inhibition (HI) antibody titer for influenza A/H1N1, A/H3N2, and B was measured before vaccination, after the first vaccination, after the second vaccination, and after the epidemic period, September 1995 to April 1996. HI antibody titer prior to vaccination was significantly higher in the patients who had received influenza vaccination the previous year. The influenza vaccine induced an increase in HI titer in almost all subjects, and the geometric mean of the HI titer after vaccination in the patients who received vaccine once was comparable to that of the patients injected vaccine twice. The number of patients with HI titers of over 128x increased, and the frequency ranged from 60.0% to 97.1% for the influenza viruses of the three subtypes. The frequency of HI titers over 128x was not significantly different among the three groups. The second vaccination did not increase the number of patients with HI titers over 128x when compared with the number after the first injection in the patients who had received influenza vaccine the previous year. These results suggest that prior vaccination does not diminish the antibody response to influenza vaccine in the elderly. The efficacy of a single influenza vaccination is comparable to that achieved by twice injections in the elderly receiving annual influenza vaccination.
Aged↗
Requiring higher doses of erythropoietin suggests pregnancy in hemodialysis patients.
BACKGROUND/AIMS: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. METHODS: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. RESULTS: The mean duration of HD was 6 years, the mean duration of the patients' marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. CONCLUSIONS: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.
Adult↗