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Biomedical subjects

T Asai

Publications and source records attributed to T Asai.

At least 163 records · Page 9Linked to original sources

Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis: involvement of T cells in the development of tissue outgrowth.

BACKGROUND: The aim of this study was to analyze cellular and cytokine interactions governing the development of synovial tissue outgrowth in patients with rheumatoid arthritis (RA). METHODS: A single-cell suspension of dissociated synovial tissues of RA patients was cultured for a long period to develop tissue outgrowth. The resulting tissue outgrowth was characterized by immunohistochemical staining and ELISA. RESULTS: The tissue outgrowth developed in vitro included various cell types, such as macrophage-like synovial cells, fibroblast-like synovial cells and lymphocytes. Even after prolonged cultivation, synovial cells devoid of infiltrating T lymphocytes did not form tissue outgrowth. The outgrowth contained CD3+ cells, LeuM3 (CD14)+ cells and HLA-DR+ cells. The T cells expressed lymphocyte function-associated antigen (LFA)-1 and CD2, and the synovial cells expressed intracellular adhesion molecule (ICAM)-1 and LFA-3, suggesting possible interactions via LFA-1/ICAM-1 and CD2/LFA-3. Production of T-cell derived IFN-gamma and IL-17 and synovial-cell-derived fibroblast growth factor (FGF)-1 and IL-15 was confirmed in the tissue outgrowth as well as in RA synovial tissue. These cell types stimulate each other by secreting cytokines, leading to the secretion of proinflammatory cytokines and matrix metalloproteinase (MMP)-1 by the tissue outgrowth and proliferation of both lymphocytes and synovial cells. CONCLUSION: This study emphasizes the importance of cellular interactions between T cells and synovial cells, via adhesion molecules and the secretion of cytokines with stimulatory activity towards other cell types, for the hyperactivity of RA synovial cells.

Arthritis, Rheumatoid↗

Delayed onset of pulmonary hypertension associated with an appetite suppressant, mazindol: a case report.

The use of the appetite suppressant agents aminorex and fenfluramine derivatives has been reported as a risk factor for the development of pulmonary hypertension. A 29-year-old female developed pulmonary hypertension suspected to be due to an amphetamine-like appetite suppressant agent, mazindol ((+/-)-5-(p-chlorophenyl)-2,5-dihydro-3H-imidazo [2,1-a] isoindol-5-ol). She was admitted to Sapporo Medical University Hospital with dyspnea due to severe pulmonary hypertension. Twelve months prior to admission, she had taken mazindol continuously for a period of 10 weeks. As yet, her pulmonary hypertension has not completely improved. This is the first reported case of mazindol-associated pulmonary hypertension, which developed after a long latent interval, and it suggests that mazindol is also a risk factor for the development of pulmonary hypertension, making long-term follow-up necessary for patients taking this anorectic agent.

Adult↗

Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.

Adult↗

Genetic determinants of plasma triglyceride levels in (OLETF x BN) x OLETF backcross rats.

Altered lipid metabolism is closely associated with diabetes in humans, although predisposing genetic factors that affect hyperlipidemia have not yet been clarified. Our previously established OLETF strain is an obese rat model of type II diabetes, exhibiting hypertriglycemia as well as hyperinsulinemia, hyperglycemia, insulin resistance, and abundant abdominal fat. To identify genetic factors responsible for dyslipidemic phenotypes in OLETF rats, we performed a whole-genome scan using 293 male (OLETF x BN) x OLETF backcross rats. Our analysis identified two significant quantitative trait loci (QTLs), on rat chromosomes 1 and 8, that are related to fasting triglyceride levels. The chromosome 1 QTL colocalized with Dmo1 (diabetes mellitus, OLETF type 1), a locus previously shown to associate strongly with both fat levels and body weight. The other significant QTL localizes to the chromosome 8 marker D8Mit2, in a region where several apo-lipoprotein genes are clustered.

Animals↗

Characterization of the gene encoding serine acetyltransferase, a regulated enzyme of cysteine biosynthesis from the protist parasites Entamoeba histolytica and Entamoeba dispar. Regulation and possible function of the cysteine biosynthetic pathway in Entamoeba.

The enteric protist parasites Entamoeba histolytica and Entamoeba dispar possess a cysteine biosynthetic pathway, unlike their mammalian host, and are capable of de novo production of L-cysteine. We cloned and characterized cDNAs that encode the regulated enzyme serine acetyltransferase (SAT) in this pathway from these amoebae by genetic complementation of a cysteine-auxotrophic Escherichia coli strain with the amoebic cDNA libraries. The deduced amino acid sequences of the amoebic SATs exhibited, within the most conserved region, 36-52% identities with the bacterial and plant SATs. The amoebic SATs contain a unique insertion of eight amino acids, also found in the corresponding region of a plasmid-encoded SAT from Synechococcus sp., which showed the highest overall identities to the amoebic SATs. Phylogenetic reconstruction also revealed a close kinship of the amoebic SATs with cyanobacterial SATs. Biochemical characterization of the recombinant E. histolytica SAT revealed several enzymatic features that distinguished the amoebic enzyme from the bacterial and plant enzymes: 1) inhibition by L-cysteine in a competitive manner with L-serine; 2) inhibition by L-cystine; and 3) no association with cysteine synthase. Genetically engineered amoeba strains that overproduced cysteine synthase and SAT were created. The cysteine synthase-overproducing amoebae had a higher level of cysteine synthase activity and total thiol content and revealed increased resistance to hydrogen peroxide. These results indicate that the cysteine biosynthetic pathway plays an important role in antioxidative defense of these enteric parasites.

Acetyltransferases↗

Elevated serum haptoglobin in pigs infected with porcine reproductive and respiratory syndrome virus.

We examined the two acute phase proteins, alpha (alpha)-1 acid glycoprotein (AGP) and haptoglobin (HP), in serum of pigs following experimental porcine reproductive and respiratory syndrome (PRRS) virus infection. Increased levels of serum HP, but not AGP, were observed from 7 to 21 days post-inoculation in the infected pigs. Furthermore, serum IL-6 increased in the infected pigs, but TNF-alpha did not. The increase of serum IL-6 in pigs following PRRS virus infection may induce production of HP. Also, in the field investigation, serum HP in pigs was dramatically increased after exposure to the PRRS virus.

Acute-Phase Proteins↗

Enhancement of translation by the downstream box does not involve base pairing of mRNA with the penultimate stem sequence of 16S rRNA.

The downstream box (DB) is a sequence element that enhances translation of several bacterial and phage mRNAs. It has been proposed that the DB enhances translation by base pairing transiently to bases 1469-1483 of 16S rRNA, the so-called anti-DB, during the initiation phase of translation. We have tested this model of enhancer action by constructing mutations in the anti-DB that alter its mRNA base-pairing potential and examining expression of a variety of DB-containing mRNAs in strains expressing the mutant anti-DB 16S rRNA. We found that the rRNA mutant was viable and that expression of all tested DB-containing mRNAs was completely unaffected by radical alterations in the proposed anti-DB. These findings lead us to conclude that enhancement of translation by the DB does not involve mRNA-rRNA base pairing.

Bacterial Proteins↗

Sec-dependent pathway and DeltapH-dependent pathway do not share a common translocation pore in thylakoidal protein transport.

Thylakoidal proteins of plant chloroplasts are transported to thylakoids via several different pathways, including the DeltapH-dependent and the Sec-dependent pathways. In this study, we asked if these two pathways utilize a common translocation pore. A fusion protein consisting of a 23-kDa subunit of the oxygen evolving complex and Escherichia coli biotin carboxyl carrier protein was biotinylated in E. coli cells and purified. When incubated with isolated pea thylakoids in the absence of avidin, the purified fusion protein was imported into the thylakoids via the DeltapH-dependent pathway. However in the presence of avidin, the fusion protein became lodged in the thylakoid membranes, with its N terminus reaching the thylakoidal lumen, while its C-terminal segment complexed with avidin exposed on the thylakoidal surface. The translocation intermediate of the fusion protein inhibited the import of authentic 23-kDa subunit, suggesting that it occupies a putative translocation pore for the DeltapH-dependent pathway. However the intermediate did not block import of the 33-kDa subunit of the oxygen evolving complex, which is a substrate for the Sec-dependent pathway. These results provide evidence against the possibility of a common translocation pore shared by the Sec-dependent pathway and the DeltapH-dependent pathway.

Acetyl-CoA Carboxylase↗

Nigral degeneration following striato-pallidal lesion in tissue type plasminogen activator deficient mice.

Tissue type plasminogen activator (tPA) has been suggested as a key factor in excitotoxic neuronal death in the hippocampus. Transneuronal degeneration of the substantia nigra pars reticulata (SNR) neurons after striato-pallidal lesions is attributable to excess excitatory glutamatergic inputs into the SNR following inhibitory GABAergic deafferentation and tPA may contribute to the mechanism of transneuronal degeneration of the SNR. To examine this possibility, we studied pathological changes in the SNR following striato-pallidal lesions produced by electrocoagulation in tPA-deficient mice. There was no difference in the degree of SNR degeneration, or in microglial activation and proliferation in the degenerating SNR of tPA-deficient and control mice. Our results indicate that tPA does not contribute to transneuronal degeneration in the SNR following striato-pallidal lesions in mice.

Animals↗

TT virus in bone marrow transplant recipients.

TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT > 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.

Adolescent↗

An Escherichia coli strain with all chromosomal rRNA operons inactivated: complete exchange of rRNA genes between bacteria.

Current global phylogenies are built predominantly on rRNA sequences. However, an experimental system for studying the evolution of rRNA is not readily available, mainly because the rRNA genes are highly repeated in most experimental organisms. We have constructed an Escherichia coli strain in which all seven chromosomal rRNA operons are inactivated by deletions spanning the 16S and 23S coding regions. A single E. coli rRNA operon carried by a multicopy plasmid supplies 16S and 23S rRNA to the cell. By using this strain we have succeeded in creating microorganisms that contain only a foreign rRNA operon derived from either Salmonella typhimurium or Proteus vulgaris, microorganisms that have diverged from E. coli about 120-350 million years ago. We also were able to replace the E. coli rRNA operon with an E. coli/yeast hybrid one in which the GTPase center of E. coli 23S rRNA had been substituted by the corresponding domain from Saccharomyces cerevisiae. These results suggest that, contrary to common belief, coevolution of rRNA with many other components in the translational machinery may not completely preclude the horizontal transfer of rRNA genes.

Base Sequence↗

Evidence for neural regulation of inflammatory synovial cell functions by secreting calcitonin gene-related peptide and vasoactive intestinal peptide in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the possible involvement of the nervous system in the regulation of pathophysiologic responses in patients with rheumatoid arthritis (RA), we examined the expression of peripheral nerves containing the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in RA synovium and their effects on RA synovial cell functions. METHODS: The effects of CGRP and VIP on proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA (mRNA) expression by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. Expression of CGRP receptors (CGRPRs) and VIP receptors (VIPRs) on RA synovial cells was assessed by RT-PCR and radioreceptor assays. The functions of CGRPRs and VIPRs of the synovial cells were studied by using a CGRPR antagonist and a VIPR antagonist, respectively. RESULTS: CGRP and VIP inhibited the proliferation of, and the proinflammatory cytokine and MMP production by, RA synovial cells at the level of mRNA expression. Expression of CGRPR and VIPR on RA fibroblast-like synovial cells was confirmed by RT-PCR and radioreceptor assays. Functions of the neuropeptide receptors were inhibited by their receptor antagonists. CGRP and VIP inhibited nuclear translocation and phosphorylation of the transcription factor cAMP response element binding protein in RA synovial cells. CONCLUSION: CGRP and VIP inhibited excessive synovial cell functions, which suggests neural regulation of inflammatory responses in patients with RA and possible clinical application of the neuropeptides.

Adult↗

Awake tracheal intubation through the intubating laryngeal mask.

PURPOSE: To report successful awake insertion of the intubating laryngeal mask (Fastrach) and subsequent tracheal intubation through it, in a patient with predicted difficult tracheal intubation, due to limited mouth opening, and difficult ventilation through a facemask, due to a large mass at the corner of the mouth. CLINICAL FEATURES: A 53-yr-old woman with a large post-gangrenous mass on the right cheek to the angle of the mouth was scheduled for its resection. The right side of her face was damaged by a bomb attack followed by cancrum oris 50 yr ago. The distance between the incisors during maximum mouth opening was 2 cm and that between the gums on the right side < 1 cm. After preoxygenation and 50 micrograms fentanyl and 30 mg propofol i.v., propofol was infused at 2 mg.kg-1.hr-1. Lidocaine, 8%, was sprayed on the oropharynx. A #4 intubating laryngeal mask was inserted with a little difficulty. A fibrescope was passed through a 7.5-mm ID RAE tracheal tube, and the combination was easily passed through the laryngeal mask into the trachea. General ansthesia was then induced. Finally, the intubating laryngeal mask was removed, while the RAE tube was being stabilized using an uncuffed 6.0-mm ID tracheal tube. CONCLUSION: Awake tracheal intubation through the intubating laryngeal mask is a useful technique in patients with limited mouth opening in whom ventilation via a facemask is expected to be difficult.

Anesthetics, Intravenous↗

A subthreshold MOS circuit for the Lotka-Volterra neural network producing the winners-share-all solution.

An analog MOS circuit is proposed for implementing a Lotka-Volterra (LV) competitive neural network which produces winners-share-all solutions. The solutions give multiple winners receiving large inputs and are particularly useful for selecting a set of inputs through "decision by majority". We show that the LV network can easily be implemented using subthreshold MOS transistors. Results of extensive circuit simulations prove that the proposed circuit does exhibit a reliable selection compared with winner-take-all circuits, in the possible presence of device mismatches. These results pave a way to future implementation on a real device.

Journal Article↗